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#11 of 52
Velika Gorica, Croatia
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Melita Safran
Drawing - Color Pencils On Black Paper
This is one of my older drawings, made in 2002. Reminds me of my childhood
July 2nd, 2012
Viewed 574 Times - Last Visitor from New York, NY on 07/01/2015 at 11:42 PM
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More from Melita Safran
Montrose, CO - United States
Fantastically composed. Full of action and intrigue! Voted for this wonderful piece, David
Broomfield, CO - United States
Marysville, WA - United States
Melita.....this is wonderful. You have great talent. v
Portsmouth, NH - United States
Love your Unicorns! v
Jacksonville, fl - United States
Fantastic, great work. V/F/FB/T/G+/W promotions VAVO group
Kitchener, ON - Canada
Nice work! v
Union Dale, PA - United States
Melita I also voted for this painting ... E
Union Dale, PA - United States
Nice work Melita ... Elaine
Union Dale, PA - United States
Wonderful details in this Melita Voted � Elaine
Converse, TX - United States
Very nice! v
Bulli , Ne - Australia
I like this very much fv
Clarksboro, NJ - United States
Beautiful and playful fantasy piece. Love it! :v:
Stroud, Gl - United Kingdom
Beautiful. v
Galveston, TX - United States
Very lovely, looks surreal. Luv it! V/F
Calgary, AB - Canada
Simply beautiful work Melita !!!! v
Fullerton California, ca - United States
Nice drawing...v
Franklin Square, NY - United States
Melita, I saw this image on the promotional thread in the group, Vote and Vote Often while I putting some images up today and I could not believe the the detail and the realism of this image. The detail of the horses charging through the water is remarkable I feel like I can feel their movement and the water splashing around. Anytime you can get a viewer's feeling to feel that way you know you have created something special and you have. Great use of colors and not one detail left out. Fantastic drawing, Voted, Favorited and Promoted
Murphy, NC - United States
Very Nice!
Chicago, IL - United States
wonderful! v,f
Concho - Snowflake, AZ - United States
Thank you for v and f!
San Miguel, CA - United States
Great technique for the water! vf
Thank you Susan!
San Ramon, CA - United States
Voted Wow! I have to ditto Lianne Schneider! Oh my gosh your work is just stunning - absolutely outstanding each one! The sense of energy, the power of the horses, the motion...just amazing. And such beautiful detail...wonderful work!
Dear DJ Laughlin, you are so kind. Thank you for all your comments and votes. I'm glad you like my work :)
Velika Gorica, Do - Croatia
Thank you for your vote!
Rochester, Ne - United States
Beautiful work Melita!!! V
Whitewater, WI - United States
Very beautiful. Voted/faved.
Thank you Rachel!
Chicago, IL - United States
love this! v,s
Velika Gorica, Do - Croatia
Wow! Thank you all for your beautiful comments, promoting and returning for vote again!
Chicago, IL - United States
very nice! v
New Orleans, La - United States
like it so much I returned a few days later and voted again!
Orange Park, FL - United States
Back to promote on Facebook - personal page and fan page!
Orange Park, FL - United States
Awesome piece! v/f
Thank you Bob and Nancy!
Strykersville, NY - United States
Oh my gosh your work is just stunning - absolutely outstanding each one! The sense of energy, the power of the horses, the motion...just amazing. And such beautiful detail...wonderful work!
Thank you so much Lianne! It means a lot to me.
Velika Gorica, Do - Croatia
Thank you Glenn and Sonali for your kind comments!
North Brunswick, NJ - United States
Beautiful art work!
Hemet, CA - United States
Great execution! v
Velika Gorica, Do - Croatia
Thank you all for your comments and voting!
Pe�aflor - Chile
CONGRATULATIONS!! Featured on Female Artists - Creative Women!!! Absolutely fabulous artwork! Very well done!!!! Voted
Tarnow - Poland
Wow, wonderful image, Melita! v
New York, NY - United States
I agree with Carla. Beautiful piece Melita. v
Velika Gorica, Do - Croatia
Thank you Ana for featuring in Colored Pencil Art group!
Tallahassee, FL - United States
Love your technique of drawing on black paper! Works so well with this light subject matter, and gives lots of depth to your piece! V & P
Thank you so much Carla!
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Beverly Hills, CA (United States)
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Sheraton Xi'An Hotel
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Monks and Muslims in China
October 11, 2014
This morning we went to the Wild Goose Pagoda, a Tang Dynasty (618 to 907 AD) landmark. The seven-story pagoda was initially constructed in 652 AD to house sutra (documents written on palm leaves and sewn together with thread) brought back from India by the monk Xuan Zang, who later translated them into Chinese. …
Day 6
Today I was on my own because everyone was off to the Shaanxi history museum and spend some time with a local family but I went off to do some volunteer work that I have previously organised. I caught a taxi to a school just on the outskirts of the city. I got there at 7:45 and had a bit of a lecture on what I would be doing with the kids.
We …
Day 5
Today we started our journey at about 7am to go see the Terracotta Warriors. The Terracotta Army or the "Terracotta Warriors and Horses" is a collection of terracotta sculptures depicting the armies of Qin Shi Huang, the first Emperor of China. I was really excited to go see the Warriors. It took us an hour to get there, felt so much longer because …
Day 4
Today is our last day in Beijing before we head off. I had packed my bags and put them in the bus as we head off to the Summer Palace. The Summer Palace is a vast ensemble of lakes, gardens and palaces in Beijing, China. The Summer Palace is mainly dominated by Longevity Hill and the Kunming Lake. It covers an expanse of 2.9 square kilometres, …
Tang Dynasty Show!
Last night, the Tang Dynasty dinner show was simply amazing! We entered the theater and were in awe of the gorgeous d�cor. While we were eating there was a 12 piece ensemble of musicians playing traditional Chinese instruments with occasional singing. Our meal was in 6 courses and was all very tasty and interesting. We had some Chinese rice wine …

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Most of us are looking to eat healthier foods, but sometimes foods we think are low in sugar are not. According to a new report by Credit Suisse, you might be better off eating a doughnut than some of the stuff marketed as healthy.
9 surprising foods with more sugar than donuts
Published On: Mar 03 2014 08:45:03 AM EST Updated On: Mar 03 2014 09:01:12 AM EST
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Results 1 to 8 of 8
April 22nd, 2010 #1
WIP: Dragon&King drawings for animation
Screen from my animation....updates coming soon
Hide this ad by registering as a memberApril 22nd, 2010 #2
Here are my thougts about the picture.
It's quite hard to see what is going on, he is looking at something but what?
There is too much rimlight on the character imho, the crown and hair are lacking in shadows.
The background has some parts with a lot more contrast than in the foreground which aint really possible due to the atmposphere.
Keep up the good work! I am curious to see the rest of the animation.
Sorry for my crappy English
Looking for tips and tricks
April 22nd, 2010 #3
thank You. I`will keep in mind Your words. It must be "dream reality", with unnatural light, but your opinion is still important too me.
April 22nd, 2010 #4
you can't really give accurate feedback on an animation when all you have is a still image. animation is a medium of time and sequence. lets see some animation!
-start a revolution.
April 23rd, 2010 #5
i have animation in 9o precent done, but i must wait for permision to show it.....update coming soon.
Here , more frames from animation: http://michalogorek.wordpress.com/work-in-progress/
April 23rd, 2010 #6Registered User
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i like it, good concept to maybe put above the picture "King's reclamation" because thats what this picture tells me.
April 24th, 2010 #7
Here is fight scene...
April 26th, 2010 #8
another frame from my animation (duration 30 sec). Right now is finished, but i must wait for permission to publishing.


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ARTIST ROOMS Louise Bourgeois: A Woman Without Secrets : Talk and Tour
7 Aug 2014
Event times
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AboutAs part of our interpretation for ARTIST ROOMS Louise Bourgeois: A Woman Without Secrets, our young people?s group the Wonder Whys are producing their own gallery guide in response to the exhibition and its themes. Join them for a tour with a twist.
Have you been to this event? What do you think? Join the discussion here!
Remember, you can include links to your instagram pictures and to videos.


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Rebecca S. Allen Collection
Sept. 1988
Western Kentucky University Folklife ArchivesBowling Green, Kentucky, 42101-3576 USA
Collection is open for research. This collection and numerous other collections are accessible through a card catalog and print inventories at the Kentucky Building. Manuscripts and Folklife Archives collections do not circulate nor are they listed on the university's online library catalog. A valid I.D. is required to use the materials. Limited photocopying is done for patrons.
[Identification of item] Rebecca S. Allen Collection, Sept. 1988, FA 151,Library Special Collections, Western Kentucky University, Bowling Green.
1 folder. 2 items. 1 cassette tape.
History of Forest Park Baptist Church. Index, summary, transcription and cassette recording of interview with Edgar L. and Thelma Rose Mills, concerning the Forest Park Baptist Church in Bowling Green, Ky., September 12, 1988.
Copyright has not been assigned to the Western Kentucky University.
Hosted by the University of Kentucky
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Allergy ArmyJuly 1st, 2014
If you've got a case of the sniffles, consider adding onions and pineapple to your next meal. Quercetin, often sourced from yellow onions, is a commonly used natural antihistamine; its absorption into the body is increased when taken with bromelain, an enzyme found in pineapples that breaks up existing mucus and prevents more from developing.
Focus On: QuercetinJanuary 1st, 2013
What it is: Quercetin is a flavonoid found in fruits, vegetables, leaves, and grains. It is known to be one of the most active flavonoids.
[ Natural Sources ]
Red wine, onions, green tea, apples, berries, Ginkgo biloba, St. John's wort, and American elder are all great sources of quercetin.
[ Benefits ]What good does this most active flavonoid accomplish?
The Beauty Bar: QuercetinOctober 1st, 2010
Packed with anti-inflammatory polyphenols and carotenoids, quercetin offers superb free-radical protection and even cancer-preventing potential.By Jolene Hart
Phyto PowerDecember 1st, 2009
Chemical warfare isn't always a bad thing: Fruits and vegetables use their phytochemicals for protection as they grow, and once inside us, these same compounds have potent antioxidant and anticancer properties, says Michael Seidman, MD, director of wellness at the Henry Ford Health System's Center for Integrative Medicine in Detroit.By Matthew Kadey, RD


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Journal Sentinel business reporter Tom Daykin talks about commercial real estate and development.
Indoor soccer facility proposed for West Allis
Part of a multi-tenant light industrial building would be converted into an indoor soccer facility under a proposal pending before the West Allis Plan Commission.
Known as Strikers of Wisconsin, the facility would be used as indoor practice space for local soccer clubs. It would be within 4,600 square feet of a 21,600-square-foot building at 450 S. Curtis Road, according to a report by city planning staff.
The Plan Commission is to review the proposal at its Wednesday night meeting.
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Results 1 to 13 of 17
Thread: Droppity drop drop :)
November 21st, 2007 #1
Droppity drop drop :)
Been under the weather since Wednesday, and still fighting it off, but I had to get this pin-up done for my buddy's book called Clockwork Girl. Here's their site to those who'd like to get more familiarized with the characters [link]
Be sure to drink your Orange Juice, and plenty of water, gang. The flu ain't no joke.
Shot at 2007-11-20
And while I'm at it, here's some more stuff, too.
Hope y'all digs!
Shot at 2007-10-09
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Shot at 2007-11-21
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- SketchBook: -drop, drop it like it's hot->
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Last edited by cheeks-74; November 21st, 2007 at 04:36 AM.http://cheeks-74.deviantart.com/gallery/
it's not if you can't do it, but it's if you want to
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November 21st, 2007 #2King of Dragons
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Glad to see you back at it. Love all your work. Hope you feel weel. Peace!
November 21st, 2007 #3
Cheeks is back! hope you`ll feel better buddy.
excellent character work, fluid and dynamic poses you got here.
always liked your style, you know that...
I would like to see some of these more saturated, perhaps.
it works anyway, though.
keep it up.
We all pay for life with death, so everything in between should be free.
-Bill Hicks
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November 21st, 2007 #4
aw mann hope you get better real quick. my girls very ill with a gnarly cough, so i know how miserable you must feel (well, more like how miserable you would make your loved ones feel ). the picture of the pitcher is heaps dynamic, but then again i cant remember when your lines strayed from the dynamic. keep posting mate
November 21st, 2007 #5
I like so much your style and i ever Astonished abaut your capacity to give a Plasticityin a carachter movment!
November 21st, 2007 #6
I would give my left shoe to see your stuff animated with the same elegance and character as your images : )
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November 21st, 2007 #7
i liked your style, those players in motion are awesome.
November 21st, 2007 #8
Nice drop cheeks!
I could learn alot from your poses.
November 21st, 2007 #9Registered User
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everyone is commenting on your dynamic poses - and rightly so - but, beyond the obvious, BEAUTIFUL use of proportions, color and line. 'Grats on great work.
November 22nd, 2007 #10
i love how far you push wolvie. very few have the guts to really make him all their own. he looks like a barney rubble/wolvie mash up :P
-: [ sketchbook | sour.org ] :-
November 22nd, 2007 #11
Wow, the flu is everywhere! Even the Atlantic Ocean can't stop it..... Yep, I was also too late drinking orange juice.
Despite the flu you managed to made a great pin-up!!
The two main characters looked very familiar to me. I've probably seen them a while ago at the blog from Jose Lopez.... Yeah, that's it. He also made a great pin-up for Clockwork Girl. Both versions are different but very well executed.
Back to the work above: your sporty sketches are awesome!!
Hope you will soon be better.
May 11th, 2008 #12Registered User
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im crurious...what do you use for color.
May 11th, 2008 #13
Love the body language and energy in your work. The only bit I don't like is the hair on Wolverines arms - looks more like skin grafts to me.
my sketches here... http://conceptart.org/forums/showthread.php?t=92997
www.sevans.co.nz , for more images and to kill time.


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Hematopoietic Stem-Cell Transplantation for Solid Tumors of Childhood
Revision Date(s) 06/09/15; 06/09/14; 06/10/13; 06/12/12; 06/13/11; 06/08/10; 12/08/09; 06/10/08; 12/11/07; 11/14/06; 11/11/05; 12/14/04; 08/12/03; 06/17/03; 12/10/02; 12/21/00; 11/16/00
Autologous hematopoietic stem-cell transplantation may be considered medically necessary for:
Autologous hematopoietic stem-cell transplantation is considered investigational as initial treatment of low- or intermediate-risk neuroblastoma, initial treatment of low- or intermediate-risk Ewing's sarcoma, and for other solid tumors of childhood including, but not limited, to the following:
High-dose chemotherapy (with or without associated radiotherapy) and autologous stem-cell support may be considered medically necessary for treatment of recurrent Wilms tumor when employed as part of a randomized controlled clinical trial.
Tandem autologous hematopoietic stem-cell transplantation may be considered medically necessary for high-risk neuroblastoma when employed as part of a randomized controlled clinical trial.
Tandem autologous hematopoietic stem-cell transplantation is considered investigational for treatment of all other types of pediatric solid tumors except high-risk neuroblastoma, as noted above.
Allogeneic (myeloablative or nonmyeloablative) hematopoietic stem-cell transplantation is considered investigational for treatment of pediatric solid tumors.
Salvage allogeneic hematopoietic stem-cell transplantation for pediatric solid tumors that relapse after autologous transplant or fail to respond is considered investigational.
Placental and Umbilical Cord Blood as a Source of Stem Cells
This policy addresses peripheral neuroblastoma; those arising from the peripheral nervous system.
Hematopoietic stem-cell transplantation refers to any source of stem cells, i.e., autologous, allogeneic, syngeneic, or umbilical cord blood.
Relapse is defined as tumor recurrence after a prior complete response.
Primary refractory disease is defined as a tumor that does not achieve a complete remission after initial standard-dose chemotherapy.
Hematopoietic Stem-Cell Transplantation for Solid Tumors
Hematopoietic stem-cell transplantation (HSCT) refers to a procedure in which hematopoietic stem cells are infused to restore bone marrow function in cancer patients who receive bone-marrow-toxic doses of cytotoxic drugs, with or without whole body radiation therapy. Stem cells may be obtained from the transplant recipient (autologous HSCT) or can be harvested from a donor (allogeneic HSCT). Stem cells may be harvested from bone marrow, peripheral blood, or umbilical cord blood shortly after delivery of neonates.
Autologous HSCT takes advantage of the steep dose-response relationship observed with many chemotherapeutic agents and allows for escalation of chemotherapy doses above those limited by myeloablation. The use of allogeneic HSCT for solid tumors relies on a graft-versus-tumor effect. Allogeneic HSCT is uncommonly used in solid tumors and may be used if an autologous source cannot be cleared of tumor or cannot be harvested.
Solid Tumors of Childhood
Solid tumors of childhood are defined as those not arising from myeloid or lymphoid cells. Some of the most common solid tumors of childhood are neuroblastoma, Ewing's sarcoma/Ewing's sarcoma family of tumors (ESFT), Wilms tumor, rhabdomyosarcoma (RMS), osteosarcoma, and retinoblastoma.
The prognosis for pediatric solid tumors has improved over the last 2 decades, mostly due to the application of multiagent chemotherapy and improvements in local control therapy (including aggressive surgery and advancements in radiation therapy). (1)
However, patients with metastatic, refractory, or recurrent disease continue to have poor prognoses, and these "high-risk" patients are candidates for more aggressive therapy, including autologous HSCT, in an effort to improve event-free survival (EFS) and overall survival (OS).
Notes: Other solid tumors of childhood include germ cell tumors, which are considered separately in another medical policy. Solid tumors classified as embryonal tumors arising in the central nervous system (CNS) and tumors derived from glial cells (i.e., astrocytoma, oligodendroglioma, or glioblastoma multiforme) are also addressed in separate medical policies. Cord blood is discussed in greater detail in a separate medical policy. (See Related Policies)
Descriptions of the solid tumors of childhood that are addressed in this policy are as follows.
Peripheral Neuroblastoma
Neuroblastoma is the most common extracranial solid tumor of childhood, (2) with two-thirds of the cases presenting in children younger than 5 years of age. (3) These tumors originate where sympathetic nervous system tissue is present, within the adrenal medulla or paraspinal sympathetic ganglia. They are remarkable for their broad spectrum of clinical behavior, with some undergoing spontaneous regression, others differentiating into benign tumors, and still others progressing rapidly and resulting in patient death.
Patients with neuroblastoma are stratified into prognostic risk groups (low, intermediate, and high) that determine treatment plans. Risk variables include age at diagnosis, clinical stage of disease, tumor histology, and certain molecular characteristics, including the presence of the MYCN oncogene. Tumor histology is categorized as favorable or unfavorable, according to the degree of tumor differentiation, proportion of tumor stromal component, and index of cellular proliferation. (4) It is well established that MYCN amplification is associated with rapid tumor progression and a poor prognosis, (5) even in the setting of other coexisting favorable factors. Loss of heterozygosity (LOH) at chromosome arms 1p and 11q occurs frequently in neuroblastoma. (6) Although 1p LOH is associated with MYCN amplification, 11q is usually found in tumors without this abnormality. (6) Some recent studies have shown that 1p LOH and unbalanced 11q LOH are strongly associated with outcome in patients with neuroblastoma, (6) and both are independently predictive of worse progression-free survival (PFS) in patients with low- and intermediate-risk disease. Although the use of these LOH markers in assigning treatment in patients is evolving, they may prove useful to stratify treatment.
Clinical stage of disease is based on the International Neuroblastoma Staging System (INSS) as follows:
The low-risk group includes patients younger than 1 year of age with stage 1, 2, or 4S with favorable histopathologic findings and no MYCN oncogene amplification. High-risk neuroblastoma is characterized by an age older than 1 year, disseminated disease, MYCN oncogene amplification, and unfavorable histopathologic findings.
In general, most patients with low-stage disease have excellent outcomes with minimal therapy, and with INSS stage 1 disease, most patients can be treated by surgery alone. (2) Most infants, even with disseminated disease, have favorable outcomes with chemotherapy and surgery. (2) In contrast, most children older than 1 year with advanced-stage disease die due to progressive disease, despite intensive multimodality therapy, (2) and relapse remains common. Treatment of recurrent disease is determined by the risk group at the time of diagnosis and the extent of disease and age of the patient at recurrence.
Ewing's Sarcoma and the Ewing Family of Tumors
Ewing's sarcoma family of tumors (ESFT) encompasses a group of tumors that have in common some degree of neuroglial differentiation and a characteristic underlying molecular pathogenesis (chromosomal translocation). The translocation usually involves chromosome 22 and results in fusion of the EWS gene with one of the members of the ETS family of transcription factors, either FLI1 (90–95%) or ERG (5–10%). These fusion products function as oncogenic aberrant transcription factors. Detection of these fusions is considered to be specific for the ESFT and helps further validate the diagnosis. Included in ESFT are "classic" Ewing's sarcoma of bone, extraosseous Ewing's, peripheral primitive neuroectodermal tumor (pPNET), and Askin tumors (chest wall).
Most commonly diagnosed in adolescence, ESFT can be found in bone (most commonly) or soft tissue; however, the spectrum of ESFT has also been described in various organ systems. Ewing's is the second most common primary malignant bone tumor. The most common primary sites are the pelvic bones, the long bones of the lower extremities, and the bones of the chest wall.
Current therapy for Ewing's sarcoma favors induction chemotherapy, with local control consisting of surgery and/or radiation (dependent on tumor size and location), followed by adjuvant chemotherapy. Multiagent chemotherapy, surgery, and radiation therapy have improved the PFS in patients with localized disease to 60–70%. (7) The presence of metastatic disease is the most unfavorable prognostic feature, and the outcome for patients presenting with metastatic disease is poor, with 20–30% PFS. Other adverse prognostic factors that may categorize a patient as having "high-risk" Ewing's are tumor location (e.g., patients with pelvic primaries have worse outcomes), larger tumor size, and older age of the patient. However, "high-risk" Ewing's has not always been consistently defined in the literature. Thirty to forty percent of patients with ESFT experience disease recurrence and patients with recurrent disease have a 5-year EFS and OS rate of less than 10%. (8)
Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma of childhood, shows skeletal muscle differentiation. The most common primary sites are the head and neck (e.g., parameningeal, orbital, pharyngeal), genitourinary tract, and extremities. (9) Most children with RMS present with localized disease, and with conventional multimodal therapy, the cure rate in this group is 70–80%. (10) However, approximately 15% of children present with metastatic disease, and despite the introduction of new drugs and intensified treatment, the 5-year survival is 20–30% for this "high-risk" group. (10,11)
Wilms Tumor
Wilms tumor, the most common primary malignant renal tumor of childhood, is highly sensitive to chemotherapy and radiation, and current cure rates exceed 85%. (12) Ten to 15% of patients with favorable histology and 50% of patients with anaplastic tumors experience tumor progression or relapse. (12) Similar to newly diagnosed Wilms tumor, relapsed Wilms tumor is a heterogeneous disease, and current treatment strategies stratify intensity and scheduling of the treatment modalities based on prognostic features. For newly diagnosed disease, the most important prognostic features are stage and histology. Similar risk-adapted strategies are being attempted for the 15% of patients who experience relapse. Success rates after relapse range from 25–45%. For patients with adverse prognostic factors (histologically anaplastic tumors, relapse less than 6–12 months after nephrectomy, second or subsequent relapse, relapse within the radiation field, bone or brain metastases) event-free survival is less than 15%. (13) However, recent trials with high-dose chemotherapy (HDC) and autologous HSCT have reported 3- or 4-year OS rates from 60–73%. (14)
Osteosarcoma is a primary malignant bone tumor that is characterized by formation of bone or osteoid by the tumor cells. Osteosarcoma occurs predominantly in the appendicular skeleton of adolescents. In children and adolescents, more than 50% of these tumors arise from bones around the knee. The prognosis of localized osteosarcoma has greatly improved over the last 30 years, with OS rates increasing from 10% with surgery alone (usually amputation) to 70% with the introduction of neoadjuvant chemotherapy and limb-sparing surgery. (15) However, 30–40% of patients with non-metastatic osteosarcoma of the extremities experience recurrent disease, most commonly in the lungs. (15) Mean 5-year post-relapse survival rate is approximately 28%, with some groups having a 0% OS rate. Prognostic factors for recurrence include site and size of the primary tumor, presence of metastases at the time of diagnosis, resection adequacy, and tumor response to preoperative chemotherapy (measured as percent of tumor necrosis in the resection specimen). Overall EFS for patients with metastatic disease at diagnosis is about 20–30%. (16)
Retinoblastoma is the most common primary tumor of the eye in children. It may occur as a heritable (40%) or nonheritable (60%) tumor. (17) Cases may be unilateral or bilateral, with bilateral tumor almost always occurring in the heritable type. The type of treatment depends on the extent of disease. Retinoblastoma is usually confined to the eye, and with current therapy has at least a 90% cure rate. (17) However, once disease has spread beyond the eye, survival rates drop significantly; 5-year disease-free survival is reported to be less than 10% in those with extraocular disease, and stage 4b disease has been lethal in virtually all cases reported. (18) Extraocular disease may be localized to the soft tissues surrounding the eye, or to the optic nerve, extending beyond the margin of resection. Further extension may result in involvement of the brain and meninges, with subsequent seeding of the cerebrospinal fluid, as well as distant metastases to the lungs, bone, and bone marrow. Stage 4a disease is defined as distant metastatic disease not involving the central nervous system (CNS), and stage 4b is defined as metastatic disease to the CNS.
Medical policies are systematically developed guidelines that serve as a resource for Company staff when determining coverage for specific medical procedures, drugs or devices. Coverage for medical services is subject to the limits and conditions of the member benefit plan. Members and their providers should consult the member benefit booklet or contact a customer service representative to determine whether there are any benefit limitations applicable to this service or supply. This medical policy does not apply to Medicare Advantage.
The following considerations may supersede this policy:
The literature search for this policy was updated through May, 2014. Following is a summary of the literature.
Peripheral Neuroblastoma
Single Autologous HSCT
Three well-designed, randomized trials have been conducted using autologous hematopoietic stem-cell transplantation (HSCT) in the treatment of high-risk neuroblastoma.
In a study published in 1999, Matthay and colleagues (19) randomly assigned 129 children with high-risk neuroblastoma to a combination of myeloablative chemotherapy, total-body irradiation, and transplantation of autologous bone marrow and compared their outcomes to those of 150 children randomly assigned to intensive nonmyeloablative chemotherapy; both groups underwent a second randomization to receive subsequent 13-cis-retinoic acid (cis-RA) or no further therapy. The 3-year event-free survival (EFS) rate among patients assigned to transplantation was 43 +/- 6% versus 27 +/- 5% among those assigned to continuation chemotherapy (p=0.027). However, overall survival (OS) in the two groups was not significantly different, with 3-year estimates of 43% or 44% for those assigned to transplant or those to continued chemotherapy, respectively (p=0.87).
Long-term results from this same trial were reported after a median follow-up time of 7.7 years (range: 130 days to 12.8 years). (20) Five-year EFS for patients who underwent autologous transplant was 30% +/- 4% versus 19% +/- 3% for those who underwent nonmyeloablative chemotherapy (p=0.04). Five-year OS rates from the second randomization of patients who underwent both random assignments were 59% +/- 8% for autologous transplant/cis-RA, 41% +/- 7% for autologous transplant/no cis-RS, and, for nonmyeloablative chemotherapy, 38% +/- 7% and 36% +/- 7% with and without cis-RA. The authors concluded that myeloablative chemotherapy and autologous transplant results in a significantly better 5-year EFS and OS.
In a study published in 2005, Berthold and colleagues randomly assigned 295 patients with high-risk neuroblastoma to myeloablative therapy (melphalan, etoposide, and carboplatin) with autologous HSCT or to oral maintenance chemotherapy with cyclophosphamide. (21) The primary endpoint was EFS with secondary endpoints of OS and treatment-related deaths. Intention-to-treat analysis showed that the patients who received the myeloablative therapy had an increased 3-year EFS compared with the oral maintenance group (47% [95% confidence interval (CI): 38–55%] vs. 31% [95% CI: 23–39%]) but did not have significantly increased 3-year OS (62% [95% CI: 54–70%] vs. 53% [95% CI: 45–62%] p=0.0875). Two patients died from therapy-related complications during induction, no patients who received oral maintenance therapy died from treatment-related toxic effects, and 5 patients who received the myeloablative therapy died from acute complications related to the therapy.
In a study published in 2005, Pritchard and colleagues (22) reported the results of a randomized, multicenter study that involved 167 children with stage 3 or 4 neuroblastoma who were treated with standard induction chemotherapy and then underwent surgical resection of their tumor. Sixty-nine percent of the patients (n=90) who achieved complete or good partial response to the induction chemotherapy were eligible for randomization to HDC (melphalan) with autologous HSCT or no further treatment (NFT). Seventy-two percent (n=65) of the eligible children were randomly assigned, with 21 surviving at the time of the analysis (median follow-up 14.3 years). A significant difference in the 5-year EFS and OS was seen in children older than 1 year of age with stage 4 disease (n=48 children with stage 4; 5-year EFS 33% versus 17% in the melphalan versus NFT group p=0.01).
Tandem Autologous-Autologous and Allogeneic HSCT
Sung and colleagues retrospectively analyzed the efficacy of single versus tandem autologous HSCT in patients older than 1 year of age newly diagnosed with stage 4 neuroblastoma from 2000 to 2005 who were enrolled in the Korean Society of Pediatric Hematology-Oncology registry. (23) Patients were assigned to receive a single (n=70) or tandem (n=71) autologous HSCT at diagnosis; 57 and 59 patients underwent single and tandem transplantation as scheduled, respectively. Patient characteristics between the 2 groups were similar with the exception of a higher proportion of patients in the tandem group having bone metastases. Median follow-up was 56 months (range 24-88 months) from diagnosis. Transplant-related mortality occurred in 9 patients in the single transplant group and in 8 in the tandem group (2 after the first transplant and 6 after the second). The intent-to treat survival rate was 5-year EFS for single versus tandem 31.3% +/- 11.5% and 51.2% +/- 12.4%, respectively; p=0.03. When the survival analysis was confined to the patients who proceeded to transplant, the probability of relapse-free survival (RFS) after the first transplant was higher in the tandem group than the single group with borderline significance (59.1% +/- 13.5% vs. 41.6% +/- 14.5%; p=0.099). The difference became significant when the analysis was confined to patients who did not achieve a complete response (CR) prior to the first transplant (55.7% +/-17.0% vs. 0%; p=0.012). The authors concluded that tandem HSCT for high-risk neuroblastoma is superior to single HSCT in terms of survival, particularly in patients not in complete CR prior to the HSCT.
Ladenstein and colleagues reported on 28 years of experience for more than 4,000 transplants for primary (89%) and relapsed (11%) neuroblastoma in 27 European countries in the European Group for Blood and Marrow Transplantation registry. (24) Procedures included single autologous (n=2,895), tandem autologous (n=455) and allogeneic HSCT (n=71). The median age at the time of transplantation was 3.9 years (range 0.3-62 years), with 77 patients older than age 18 years. The median follow-up time from HSCT was 9 years. Transplant-related mortality (TRM) decreased over time in the registry for the patients who received autologous transplants only. The cumulative incidence of TRM was 4%, 6%, and 8%, respectively, at day 100, 1 year, and 5 years for the autologous group, but for the allogeneic group 13%, 16%, and 18%, respectively. Five-year OS for the autologous group (single and tandem) was 37% versus 25% in the allogeneic setting. Five-year OS for single versus tandem autologous HSCT was 38% versus 33%, respectively (p=0.105).
Kim and colleagues reported a retrospective analysis of 36 patients with high-risk (stage 3 or 4) neuroblastoma who underwent either a single autologous HSCT (n=27) or a tandem autologous HSCT (n=9) at Seoul National University Children's Hospital between 1996 and 2004. (25) Disease-free survival (DFS) of patients who underwent double HSCT was similar to that of patients who underwent a single autologous HSCT (p=0.5).
George and colleagues reported long-term survival data of high-risk neuroblastoma patients (n=82) treated with tandem autologous HSCT between 1994 and 2002. (26) Median age at diagnosis was 35 months (range 6 months to 18 years). Three- and 5-year OS were 74% (95% CI: 62-82%) and 64% (95% CI: 52-74%) respectively.
von Allmen and colleagues reported outcomes on 76 patients with previously untreated high-risk stage III/IV neuroblastoma treated with aggressive surgical resection with or without local radiation therapy followed by tandem autologous high-dose chemotherapy and stem-cell rescue. (27) Overall event-free survival (EFS) for the series was 56%.
Marcus and colleagues reported outcomes in 52 children with stage 4 or high-risk stage 3 neuroblastoma treated with induction chemotherapy, surgical resection of the tumor when feasible, local radiotherapy and consolidation with tandem autologous HSCT. (28) Radiotherapy was given if gross or microscopic residual disease was present prior to the myeloablative cycles (n=37). Of the 52 consecutively treated patients analyzed, 44 underwent both transplants, 6 underwent a single transplant, and 2 progressed during induction. The 3-year EFS was 63%, with a median follow-up of 29.5 months.
Kletzel and colleagues reported on the outcomes of 25 consecutive newly diagnosed high-risk neuroblastoma patients and one with recurrent disease, diagnosed between 1995 and 2000, and treated with triple-tandem autologous HSCT. (29) After stem-cell rescue, patients were treated with radiation to the primary site. Twenty-two of the 26 patients successfully completed induction therapy and were eligible for the triple-tandem consolidation high-dose therapy. Seventeen patients completed all 3 cycles of high-dose therapy and stem-cell rescue, 2 patients completed 2 cycles and 3 patients completed one cycle. There was one toxic death, and one patient died from complications of treatment for graft failure. Median follow-up was 38 months, and the 3-year EFS and survival rates were 57% ± 11% and 79% ±10%, respectively.
Grupp and colleagues reported the outcomes of a Phase II trial that involved 55 children with high-risk neuroblastoma who underwent tandem autologous HSCT. (30) Five patients completed the first HSCT course but did not complete the second. There were 4 toxic deaths. With a median follow-up of 24 months from diagnosis, 3-year EFS was 59%.
In summary, no studies that directly compared single autologous to tandem autologous HSCT for high-risk neuroblastoma have been published. Randomized trials that compared single autologous HSCT to conventional chemotherapy have reported EFS rates for the patients who underwent HSCT ranging from 43% to 47% at 3 years and 30% at 5 years. Case series on the use of tandem autologous for high-risk neuroblastoma have reported 3-year EFS rates ranging from 57% to 63%. A retrospective analysis of a registry of patients with newly diagnosed high-risk neuroblastoma reported 5-year EFS rates for single versus tandem autologous HSCT of 31% versus 51%, respectively (p=0.03).
National Cancer Institute (NCI) Clinical Trial Database (PDQ®)
A Phase III randomized, multicenter study of single versus tandem consolidation therapy in young patients with newly diagnosed high-risk neuroblastoma is active. (NCT00567567) Primary outcomes are EFS, response after induction therapy and incidence rate of local recurrence. Expected enrollment is 664 with an estimated trial completion date of December 2015.
Ewing's Sarcoma and the Ewing Family of Tumors
During the 1980s and 1990s, several small series, case reports, and a report from the European Bone Marrow Transplant Registry suggested that autologous HSCT could improve the outcome for patients with high-risk Ewing's sarcoma family of tumors (ESFT). (31) The original policy position on Ewing's was based on these studies/reports.
These aforementioned studies were characterized by small numbers of patients, and comparison of the studies was difficult for several reasons. Within each report, patients often received a variety of chemotherapeutic regimens, and many of the studies did not share the same patient eligibility criteria (and in some the definition of high risk included patients with criteria that did not result in inferior prognosis). In addition, some studies used autologous and others allogeneic HSCT.
Subsequently, in 2001, Meyers and colleagues (28) reported on a prospective study with autologous HSCT in 32 patients with newly diagnosed Ewing's sarcoma metastatic to bone and/or bone marrow. Induction therapy consisted of five cycles of cyclophosphamide-doxorubicin-vincristine, alternating with ifosfamide-etoposide. Twenty-three patients proceeded to the consolidation phase with melphalan, etoposide, total body irradiation (TBI), and autologous HSCT (of the 9 patients who did not proceed, 2 were secondary to toxicity and 4 to progressive disease). Three patients died during the high-dose phase. Two-year EFS for all eligible patients was 20% and 24% for the 29 patients who received the high-dose consolidation therapy. The study concluded that consolidation with high-dose chemotherapy (HDC), TBI, and autologous stem-cell support failed to improve the probability of EFS for this cohort of patients when compared with a similar group of patients treated with conventional therapy. The authors noted that their findings differed from some previous studies and noted that the previous studies suffered from heterogeneous patient populations. The authors concluded that future trials of autologous HSCT must be conducted prospectively, with identification of a group at high risk for failure and all patients entering the study at the same point in therapy.
Gardner and colleagues reported the results of 116 patients with Ewing's sarcoma who underwent autologous HSCT (80 as first-line therapy and 36 for recurrent disease) between 1989 and 2000. (29) Five-year probabilities of PFS in patients who received HSCT as first-line therapy were 49% (95% CI: 30–69%) for those with localized disease at diagnosis and 34% (95% CI: 22–47%) for those with metastatic disease at diagnosis. For the population with localized disease at diagnosis and recurrent disease, 5-year probability of PFS was 14% (95% CI: 3–30%). The authors concluded that PFS rates after autologous HSCT were comparable to rates seen in patients with similar disease characteristics treated with conventional therapy.
Results from one group of patients in the Euro-EWING 99 trial were reported by Ladenstein and colleagues for patients with primary disseminated multifocal Ewing Sarcoma (PDMES). (34) From 1999 to 2005, 281 patients with PDMES were enrolled in the Euro-EWING 99 R3 study; the Euro-EWING 99 Committee agreed to stop enrollment to this group and release the data. Median age was 16.2 years (range: 0.4-49 years). Patients with isolated lung metastases were not part of the analysis. The recommended treatment consisted of induction chemotherapy, HDC, and autologous HSCT and local treatment to the primary tumor (surgery and/or radiation or neither). Induction therapy was completed by 250 (89%) of patients. One-hundred sixty-nine (60%) of the patients proceeded to HSCT; reasons for not proceeding to HSCT included disease progression or other or unknown reasons. One patient died during induction therapy from sepsis. High-dose chemotherapy TRM consisted of 3 patients dying within the first 100 days after high-dose therapy-one from acute respiratory distress syndrome and 2 from severe veno-occlusive disease and septicemia; late deaths included 3 patients who died 1-1.5 years after high-dose therapy. After a median follow-up of 3.8 years, the estimated 3-year EFS and OS for all 281 patients was 27% +/- 3% and 34% +/- 4%, respectively. Individual risk factors were brought into a scoring model to predict outcome at diagnosis. The values of the score points were based on log-hazard ratios (HRs), and the factor with the smallest hazard ratio was assigned 1 point. One score point was attributed to the following risk factors: age older than 14 years, bone marrow metastases, 1 bone lesion and additional presence of lung metastases; 1.5 points were attributed to the risk factors of primary tumor volume equal to or greater than 200 mL and more than 1 bone lesion. This risk score allowed allocation of patients with PDMES at diagnosis to 3 risk groups with the following outcomes: group 1 (score ≤3; n=82) EFS of 50%, group 2 (score >3 but <5; n=102) EFS of 25%, and group 3 (score ≥5; n=70) EFS of 10% (p<0.0001). The authors concluded that this scoring system may facilitate risk-adapted treatment strategies.
2013 National Comprehensive Cancer Network (NCCN) Guidelines
NCCN guidelines state that the role of high-dose chemotherapy and stem-cell rescue in relapsed or progressive Ewing's sarcoma is yet to be determined in prospective randomized studies and makes no recommendations regarding its use in this disease setting. (Bone Cancer V.2.2013)
National Cancer Institute (NCI) Clinical Trial Database (PDQ®)
An active Phase III trial (NCT00987636) and will randomly assign patients with high-risk (localized disease and unfavorable tumor response or tumor volume >200 mL) or very high-risk (primary disseminated disease) Ewing's sarcoma to treatment with either autologous HSCT or standard chemotherapy. Primary outcome measure is EFS. Estimated enrollment is 1,383 and estimated trial completion date is March 2018.
Autologous HSCT has been evaluated in a limited number of patients with "high-risk" RMS (stage 4 or relapsed) in whom CR is achieved after standard induction therapy. Data are relatively scarce, due in part to the rarity of the condition.
McDowell and colleagues reported the results of the International Society of Paediatric Oncology (SIOP) study MMT-98, for pediatric patients from 48 centers with metastatic rhabdomyosarcoma (RMS), entered into the study from 1998 to 2005. (35) There were a total of 146 patients entered, aged 6 months to 18 years. The patients were risk-stratified and treated accordingly. One hundred and one patients were considered poor risk patients (PRG) if they were older than 10 years of age or had bone marrow or bone metastases. Planned therapy for the PRG was induction therapy, sequential HDC and peripheral blood autologous HSCT and finally, maintenance therapy. Seventy-nine of the 101 PRG patients (78.2%) underwent the high-dose therapy, after which 67.1% achieved a partial or complete response. Sixty-seven of the 101 PRG patients received local treatment: 37 radiation alone, 10 surgery alone and 20 both modalities. No treatment-related deaths were reported in the PRG. Three- and 5-year EFS for the PRG group was 16.5% and 14.9%, respectively and 3- and 5-year OS were 23.7% and 17.9%, respectively [HR: 2.46; 95% CI: 1.51-4.03; p<0.001).
Klingebiel and colleagues prospectively compared the efficacy of two HDC treatments followed by autologous stem-cell rescue versus an oral maintenance treatment (OMT) in 96 children with stage IV soft tissue sarcoma (88 of whom had rhabdomyosarcoma). (36) Five-year OS probability for the whole group was 0.52 +/- 0.14 for the patients who received OMT (n=51) and 0.27 +/- 0.13 for the transplant group (n=45; p=0.03). For the patients with rhabdomyosarcoma, 5-year OS probability was 0.52 +/- 0.16 with OMT versus 0.15 +/- 0.12 with transplant (p=0.001). The authors concluded that transplant has failed to improve prognosis in metastatic soft tissue sarcoma but that OMT could be a promising alternative.
Weigel and colleagues (37) reviewed and summarized published data on the role of autologous HSCT in the treatment of metastatic or recurrent rhabdomyosarcoma, which involved a total of 389 patients from 22 studies. Based on all of the data analyzing EFS and OS, they concluded that there was no significant advantage to undergoing this type of treatment.
Carli and colleagues (38) conducted a prospective nonrandomized study of 52 patients with metastatic RMS, who were in CR after induction therapy and subsequently received HDC ("megatherapy") and autologous HSCT and compared them to 44 patients who were in remission after induction therapy who subsequently received conventional chemotherapy. No significant differences existed between the two study groups (i.e., no differences in clinical characteristics, induction chemotherapy received, sites of primary tumor, histologic subtype, age, or presence/extent of metastases). Three-year EFS and OS were 29.7% and 40%, respectively, for the autologous HSCT group and 19.2% and 27.7%, respectively, for the group that received standard consolidation chemotherapy. The difference was not statistically significant (p=0.3 and 0.2 for EFS and OS, respectively). The median time after chemotherapy to relapse was 168 days for the autologous HSCT group and 104 days for the standard chemotherapy group (p=0.05). Therefore, although there was some delay to relapse, there was no clear survival benefit from using autologous HSCT compared to conventional chemotherapy.
National Cancer Institute (NCI) Clinical Trial Database (PDQ®)
No Phase III trials using HSCT for the treatment of rhabdomyosarcoma and assessing survival outcomes were identified.
Wilms Tumor
The evidence on the use of autologous HSCT for high-risk Wilms tumor consists of small series or case reports.
A meta-analysis reported on the efficacy of autologous HSCT in recurrent Wilms' tumor for articles published between 1984 and 2008 that reported survival data. (39) Six studies were included (12,14,40-43) for a total of 100 patients, and patient characteristics and treatment methods were similar across studies, although there was variation in the preparative regimens used. Patients were between the ages of 11 months and 16 years and had similar primary tumor stage, relapse location, and time to relapse across studies. The 4-year OS among the 100 patients was 54.1% (42.8-64.1%) and 4-year EFS based on 79 patients was 50.0% (37.9-60.9%). A multivariate analysis found that site of relapse and histology were important predictors for survival in that patients who did not have a lung-only relapse were at approximately 3 times the risk of death or recurrence than patients who relapsed in the lungs only (HR: 3.5 and 2.4, respectively), and the patients with unfavorable histology had approximately twice the risk of death compared to those with favorable histology. The authors compared the survival rates from these 6 studies in which the patients were treated with autologous HSCT to patients treated with conventional chemotherapy between 1995 and 2002. The authors found that, in general, the chemotherapy-treated patients had comparable or improved 4-year survival compared to the HSCT group; however, there was a suggestion that patients with lung-only stage 3 and 4 relapse may benefit from autologous HSCT with a 21.7% survival advantage over the chemotherapy patients (however, the ranges were very wide): 4-year OS for the stage 3 and 4 patients with lung only relapse treated with HSCT versus chemotherapy was 74.5% (51.7-87.7%) and 52.8% (29.7-71.5%), respectively.
National Cancer Institute (NCI) Clinical Trial Database (PDQ®)
A (NCT00025103) Phase II trial was launched to evaluate chemotherapy followed by surgery and radiation, with or without HSCT in patients with relapsed or refractory Wilms tumor or clear cell sarcoma of the kidney. The study design is interventional and uses 1 of 3 regimens (one of which includes HSCT) depending upon patient risk stratification. Primary outcome measures include unified treatment strategy, improvement of current survival rates, efficacy and toxicity and prognostic variables. Estimated enrollment is 75 (50 for HSCT and 25 for each of the non-HSCT regimens). Estimated final data collection date was November 2008, but the status is unknown, as no updates have been published since June, 2009.
Small series and case reports are available that examine the use of autologous HSCT in osteosarcoma. (44) Autologous HSCT has been successful in inducing short-lasting remissions but has not shown an increase in survival. (15)
2013 National Comprehensive Cancer Network (NCCN) Guidelines
NCCN states that the efficacy of HSCT in high-risk osteosarcoma patients has yet to be determined in prospective randomized studies and makes no recommendations regarding its use in this disease setting. (Bone Cancer V.3.2013)
Most studies of autologous HSCT for high-risk retinoblastoma have been very small series or case reports (45-50); however, the results have been promising in terms of prolonging DFS in these patients, particularly those without CNS involvement (stage 4a).
Dunkel and colleagues reported the outcomes of 15 consecutive patients with stage 4a metastatic retinoblastoma who presented between 1993 and 2006 and were treated with HDC and autologous HSCT. (51) Twelve patients had unilateral retinoblastoma, and 3 had bilateral disease. Metastatic disease was not detected at the time of diagnosis but became clinically evident at a median of 6 months (range: 1-82 months) post-enucleation. The patients had metastatic disease to bone marrow (n=14), bone (n=10), the orbit (n=9) and/or the liver (n=4). Two patients progressed prior to HSCT and died. Thirteen patients underwent HSCT, and 10 are retinoblastoma-free in first remission at a median follow-up of 103 months (range: 34-202 months). Three patients recurred 14-20 months post-diagnosis of metastatic disease, (2 in the CNS and 1 in the mandible), and all died of their disease. Five-year retinoblastoma-free and event-free survival were 67% (95% CI: 38-85%) and 59% (31-79%), respectively. Six of the 10 patients who survived received radiation therapy. Three patients developed secondary osteosarcoma at 4, 9, and 14 years after diagnosis of metastatic disease, 2 in previously irradiated fields and 1 in a non-irradiated field. The authors concluded that HSCT was curative for the majority of patients treated in their study with stage 4a retinoblastoma.
Dunkel and colleagues reported the outcomes of 8 patients diagnosed with stage 4b retinoblastoma between 2000 and 2006 treated with the intention of autologous HSCT. (18) Seven of the patients had leptomeningeal disease, and 1 had only direct extension to the CNS via the optic nerve. At the time of diagnosis of intra-ocular retinoblastoma, 3 patients already had stage 4b disease; the other 5 patients developed metastatic disease at a median of 12 months (range 3-69 months). Two patients progressed prior to HSCT, and 1 patient died of toxicity during induction chemotherapy. Of the 5 patients that underwent HSCT, 2 are event-free at 40 and 101 months. One of the event-free survivors received radiation therapy (external beam plus intrathecal radioimmunotherapy), and the other did not receive any form of radiation. Three patients had tumor recurrence at 3, 7, and 10 months post-HSCT. The authors concluded that HSCT may be beneficial for some patients with stage 4b retinoblastoma but that longer follow-up is necessary to determine whether it is curative in this population.
National Cancer Institute (NCI) Clinical Trial Database (PDQ®)
A single-arm, Phase III trial (COG ARET 0321, NCT00554788) is underway to estimate the proportion of children with extraocular retinoblastoma who achieve long-term EFS after autologous HSCT compared to historical controls. Expected enrollment is 60 patients. The estimated date of completion of the trial is February 2017.
Comparative Effectiveness Review
A comparative effectiveness review was conducted on the use of hematopoietic stem-cell transplantation in the pediatric population by the Blue Cross and Blue Shield Association Technology Evaluation Center for the Agency for Healthcare Research and Quality (AHRQ). (52) The following conclusions were offered:
The body of evidence on overall survival with single HSCT compared to conventional therapy for the treatment of high-risk rhabdomyosarcoma of mixed tumor type is insufficient to draw conclusions.
The body of evidence on overall survival with single HSCT compared to conventional therapy for the treatment of congenital alveolar rhabdomyosarcoma, cranial parameningeal rhabdomyosarcoma with metastasis, or the use of allogeneic transplantation for metastatic rhabdomyosarcoma was insufficient to draw conclusions.
The body of evidence on overall survival with single HSCT compared to conventional therapy for the treatment of trilateral retinoblastoma without CNS involvement was insufficient to draw conclusions.
Clinical Input Received through Physician Specialty Society and Academic Medical Centers
In response to requests, input was received from 3 academic medical centers and 2 Blue Distinction Centers for Transplants for review in April 2011. While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted. There was general agreement from all of the reviewers for most of the policy statements with the following exceptions. One of the reviewers considers autologous HSCT medically necessary for advanced stage retinoblastoma. One of the reviewers did not consider autologous HSCT for low- to intermediate-risk Ewing's sarcoma investigational, but did state that the results of the Euro-Ewing's phase III trial are awaited. Two reviewers agree with the policy statement that tandem autologous HSCT for pediatric solid tumors is investigational, two consider it medically necessary for high-risk neuroblastoma, and the fifth reviewer agrees that tandem autologous HSCT is considered investigational for pediatric solid tumors but also stated that it is considered standard for high-risk neuroblastoma at some centers.
Some transplant centers use tandem autologous HSCT as the preferred approach to the treatment of high-risk neuroblastoma.
A Phase III, randomized trial of single versus tandem autologous HSCT for high-risk neuroblastoma is currently underway.
Ewing's sarcoma family of tumors (ESFT)
Wilms tumor
Allogeneic HSCT
Very little evidence is available on the use of allogeneic HSCT for pediatric solid tumors, either upfront or as salvage therapy after a failed autologous HSCT. A large retrospective review of the use of allogeneic HSCT for high-risk neuroblastoma (24) failed to show a survival benefit over autologous HSCT and was associated with a higher risk of transplant-related mortality.
Blood derived hematopoietic progenitor cell harvesting for transplantation, per collection; allogeneic
Transplant preparation of hematopoietic progenitor cells; cryopreservation and storage
thawing of previously frozen harvest, without washing
thawing of previously frozen harvest, with washing
specific cell depletion with harvest, T cell depletion
tumor cell depletion
red blood cell removal
platelet depletion
plasma (volume) depletion
cell concentration in plasma, mononuclear, or buffy coat layer
Bone marrow; aspiration only
biopsy, needle or trocar
Bone marrow harvesting for transplantation
Bone marrow harvesting for transplantation; autologous
Bone marrow or blood-derived peripheral stem cell transplantation; allogenic
HLA typing; A, B, or C (e.g., A10, B7, B27), single antigen
A, B, or C, multiple antigens
DR/DQ, single antigen
HLA typing; DR/DQ, multiple antigens
lymphocyte culture, mixed (MLC)
Lymphocyte culture, primed (PLC)
Human leukocyte antigen (HLA) crossmatch, non-cytotoxic (e.g., using flow cytometry); first serum sample or dilution
Human leukocyte antigen (HLA) crossmatch, non-cytotoxic (e.g., using flow cytometry); each additional serum sample or sample dilution (List separately in addition to primary procedure)
Cord blood harvesting for transplantation, allogeneic
Cord blood derived stem cell transplantation, allogeneic
Bone marrow or blood-derived peripheral stem cell (peripheral or umbilical), allogeneic or autologous, harvesting, transplantation, and related complications; including: pheresis, cell preparation/storage; marrow ablative therapy; drugs, supplies, hospitalization without patient follow-up; medical/surgical, diagnostic, emergency and rehabilitation services; and the number of days of pre- and post-transplant care in the global definition
Add to Therapy Section - New Policy
Replace Policy - Additional minor changes recommended by Oncology Committee
Replace Policy - Policy reviewed; no criteria changes.
Replace Policy - Update CPT codes only.
Replace Policy - Policy updated; no criteria changes. Additional rationale language and references added.
Replace Policy - Policy renumbered from PR.8.01.111. No changes to dates.
Replace Policy - Scheduled review; codes updated; no criteria changes. Approved by OAP 10/29/04.
Replace Policy - Scheduled review; rationale and references updated; no change to policy statement. Recommended by OAP 10/27/05.
Disclaimer and Scope update - No other changes.
Replace Policy - Policy updated with literature search; no change in policy statement.
Replace Policy - Policy updated with literature review. Policy statement updated to include: High-dose chemotherapy and hematopoietic stem-cell support is considered investigational as initial treatment of low- or intermediate-risk neuroblastoma. Multiple cycle high-dose chemotherapy and hematopoietic stem-cell support (i.e., tandem or multiple transplants) is considered investigational for treatment of neuroblastoma. References added. Recommended and reviewed by OAP 11/15/07.
Codes Updated - CPT code 86817 deleted as directed by RPIW.
Replace Policy - Policy extensively consolidated and rewritten; updated with literature search. References also extensively revised; no changes to policy statements
Replace Policy - Policy updated with literature search; no change to the policy statement. Recommended and reviewed by OAP August 21, 2009. Code 86817 added back to the policy.
Code Update - New 2010 codes added.
Replace Policy - Policy updated with NCCN 2010 Guidelines. No change to policy statement. Reviewed and recommended by OAP Feb 2010.
Replace Policy - Policy presented to OAP for review May 12, 2011. Policy title changed to "Hematopoietic Stem-Cell Transplantation for Solid Tumors of Childhood" from "HDC with Hematopoietic Stem-Cell Support for Solid Tumors in Childhood." ICD-10 codes added to policy.
Code 38232 added.
CPT code 38204 was removed from the policy.
Replace Policy. Policy updated with literature search. Policy statement changed: Tandem autologous HSCT, previously considered investigational, may now be considered medically necessary for high risk neuroblastoma.
Update Coding Section – ICD-10 codes are now effective 10/01/2014.
Update Related Policies – Add 8.01.20-30, 8.01.514 and 8.01.520.
Reviewed and recommended by OAP, November 2012.
Update Related Policies, change title of policy 8.01.21.
Update Related Policies, change title of policy 8.01.30.
The following codes were removed from the policy, as they were not suspending and just informational: HCPCS J9000-J9999 and Q0083 – Q0085.
Replace policy. Policy updated with literature review; Rationale reorganized. References updated, added and renumbered. No change in policy statements.
Update Related Policies. Change title to policy 8.01.31.
Update Related Policies. Change title to policy 8.01.17.
Update Related Policies. Remove 8.01.31 as it was archived.
Update Related Policies. Change title to 8.01.21.
Update Related Policies. Change title to 8.01.30.
Update Related Policies. Remove 8.01.514 as it was deleted.
Update Related Policies. Delete 8.01.20 and replace with 8.01.529.
Annual Review. Policy updated with literature search. Policy statements changed. Retinoblastoma added to the list of conditions for which autologous HSCT is considered medically necessary; treatment of recurrent Wilms tumor with HDC or autologous HSCT and tandem autologous HSCT for high-risk neuroblastoma remain medically necessary, but now much be conducted as part of a clinical trial.
Update Related Policies. Remove 8.01.35, 8.01.42, 8.01.54, then add 8.01.530 and 8.01.532
Update Related Polices. Remove 8.01.23, 8.01.28 and 8.01.30.
Annual Review. Policy updated with literature review; no change in policy statements. Related Policies removed except 7.01.50. ICD-9 and ICD-10 codes removed; these were informational only.
Disclaimer: This medical policy is a guide in evaluating the medical necessity of a particular service or treatment. The Company adopts policies after careful review of published peer-reviewed scientific literature, national guidelines and local standards of practice. Since medical technology is constantly changing, the Company reserves the right to review and update policies as appropriate. Member contracts differ in their benefits. Always consult the member benefit booklet or contact a member service representative to determine coverage for a specific medical service or supply. CPT codes, descriptions and materials are copyrighted by the American Medical Association (AMA).


text:
Hello everyone - now i've got my model looking presentable with shorts I am looking towards starting with a T shirt for him.
I attach my viewport for your perusal, but I am already wondering how to get the seams for the arms to look and move correctly with the model.
I want to have s short sleeved shirt with a collar on it - maybe even a small cotton white hood on the back.
I want the sleeves to have a turnup on the end and a proper collar on the neck, opened for the top two buttons.
Buttons??? Oh dear - i've not even thought about those yet - later later…
I would like the shirt to have a check pattern - but have the material matching on the seams of the arms and torso.
BTW ignore the rendering on the manekin, the uv mapping to the texture has gone awol somewhere, but it's not important - he's just a model.
Should I shape the joint with the sleves straight or rounded/slanted or what? I don't want to have the figure looking square shouldered when I pose it.
Thanks in advance


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The Top 10 In Action Sports
01Brick By Brick: Camping Lego Style
02Booze and Bikes: 14 Tours That Let Combine Two of the Best Things in the World
03Who Needs Hollywood? These Incredible Videos Were All Filmed on the Simplest Cameras
04Sam Pilgrim vs. The World: The Champion Aiming To Reclaim His Crown In A New Era Of Biking
05Eccentric Adventures Episode 2: Britain's Most Brutal Illegal Event is All About Cheese
06A Journey Into Darkness: We Went Mountain Biking in the Abandoned Mines of Slovenia
07After the Apocalypse: Inside The World's Most Breathtaking Ghost Towns
08Debate: Let's Stop Hating On Parents Who Want To Raise Adventurous Kids
09Guns, Roses, And Eating Insects: Adventure Cycling in Vietnam
10From Intense Trails to Intensive Care: Dicing with Death In a Mountain Biking Paradise
Hyperlite Webb Boot by JD Webb
A Wakeboarding video by yournewbestfriend - 2,636 views
JD Webb's first pro model boot was designed to perfectly complement his freeride style. The Webb Boot interfaces with the System Binding allowing for a lightweight feel and maximum comfort. JD's new boot is built like nothing the wake industry has ever seen because of its true footwear construction. Beginning with a lightweight EVA outsole and TPR impact pods the JD Boot creates great cushioning under foot. Custom insoles with integrated arch support cradle the foot from maximum stability. Our exclusive Ultralon heat moldable liner material creates a custom fit and comfort throughout the boot. The Webb Boot also features a lower cut cuff and softer flexion to provide the broadest range of motion in the System line up.


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Hang tight!
Recipe by BAKER'S Chocolate
"Looking for the perfect dessert for a group of chocoholics? One serving of these indulgent molten cakes will hit the spot."
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4 (1 ounce) squares
BAKER'S Semi-Sweet Baking Chocolate
1/2 cup
1 cup
powdered sugar
egg yolks
6 tablespoons
1/2 cup
thawed COOL WHIP Whipped Topping
I have only eaten this on cruises before and of course thought it was way too difficult to make. SO NOT TRUE. This was so easy and delicious. I followed the recipe exactly except greased, buttered and dusted ramekins with a cocoa/sugar mix. Baked for 12 minutes. The cakes slid right out. The next time I will skip the whipped cream and just sprinkle wiht powedered sugar. I impressed myself. My husband is thrilled with the money he will save taking us on cruises to have this dessert.LOL. Thanks so much.
I think the bake time is way too long and the temp is too high. I made these twice, the first time I baked them 2 mins less than suggested and the middles didn't ooze and the edges were almost burnt. I did it again with the oven decreased to 350 and for 9mins. Better but still not quite. I am looking for something like Morton's Godiva chocolate cake. Maybe I will try again with some liqour added.
56 Ratings
This recipe is AWESOME! I always order this dessert if I see it on a restaurant menu. I made 12 cupcake sized cakes instead of 4 since they are so rich. Satisfies the chocolate craving!
I love it! I've had a hard time finding a good molten cake recipe and this one is delicious and easy. I add a dash of salt to it (to enhance the chocolate) and serve with ice cream instead of Cool Whip.
I tried this recipe using semi sweet chocolate chips in place of the semi sweet baker's chocolate; it doesn't work. The chocolate chips bake into the mix and the volcano doesn't erupt. However, my Aunt said that they were the best brownies ever.
Tried this for the first time tonight and used the recipe as stated with the exception of the Cool Whip. (I topped ours with a scoop of vanilla ice cream and chocolate sauce drizzles.) 13 minutes at 425 worked exactly right for me, but I did follow suggestions and first checked at 9 minutes. Thanks for such a great and easy recipe. My daughter said it was even better than Chili's! (Now THAT'S a compliment!)
Terrific taste, but I had to cook it only 10 minutes in order to still have a molten center. Easier than some other recipes I've tried (and chocolatier).
Okay, I had to give this 5 stars because I made so many mistakes with the recipe and it stilled turned out delicious! I am looking forward to making it again and actually following the recipe, I can't even imagine how good it will taste. So my mistakes -- I used unsweetened chocolate instead of semi-sweet (not bad if you don't like overly sweet desserts, I think I might try 2 oz. of each next time) and I completely left out the flour! The cakes came out as flat as can be but the taste was still yummy! I recommend following the recipe exactly.
French toast is such a perfect breakfast, light lunch, or even supper on these warm days.
Try one of our 100-plus cool cucumber salads.
Delicious recipes, party ideas, and cooking tips! Get a year of Allrecipes magazine for $7.99!


text:
Intel, PC makers broaden support for Chromebooks (Update)
Another wave of laptop computers running on Google's Chrome operating system will be hitting stores this summer in the latest challenge to Microsoft's dominant Windows franchise.
Another wave of laptop computers running on Google's Chrome operating system will be hitting stores this summer in the latest challenge to Microsoft's dominant Windows franchise.
An expensive mistake by Google could turn into a golden opportunity for China's Lenovo Group as it expands beyond its success in the personal computer industry.
Google is selling Motorola's smartphone business to Lenovo for $2.9 billion, a price that makes Google's biggest acquisition look like its most expensive mistake.
China's Lenovo Group is buying IBM's low-end server business for $2.3 billion, expanding a product line-up dominated by PCs, tablets and smartphones.
Two somber new reports show unprecedented declines in desktop and laptop sales during the first three months of the year—signs that the personal computer market may never fully recover from a new generation ...
Japanese and Chinese electronics firms NEC Corp. and Lenovo Group on Thursday announced they will form a personal computer joint venture in Japan, as they take on global giants such as Hewlett-Packard.
(AP) -- Lenovo Group expects wireless Internet products to account for up to 80 percent of its sales within five years as it pursues expansion in faster-growing emerging markets, CEO Yang Yuanqing said Friday.
(AP) -- The European Union on Monday published e-mail excerpts from computer makers and Intel Corp. to show that Intel pressured chip buyers into choosing Intel over rival Advanced Micro Devices Inc.
Lenovo Group said Tuesday its quarterly profit declined 5 percent, reflecting the computer maker's acquisition of the unprofitable Motorola mobile phone business.
Motorola unveiled three smartphone models on Monday for its return to China following a two-year absence from the most populous mobile phone market.
Shares in Lenovo dropped by five percent Thursday after the Chinese technology giant posted weaker than expected revenue figures, despite a 19 percent jump in quarterly net profit.
Lenovo Group announced the completion of its acquisition of Motorola Mobility from Google Inc. on Thursday in a move aimed at making the Chinese computer maker a global smartphone brand.
Lenovo Group has received U.S. and European approval to complete its acquisition of IBM Corp.'s low-end server business and plans to use it to grow faster outside its personal computer business, Lenovo's ...
Lenovo Group, the world's biggest personal computer maker, said Thursday its latest quarterly profit rose 23 percent on strong growth in sales of smartphones and other mobile devices.
Nearly 300 million smartphones were shipped in the second quarter of this year, up almost 25 percent from the same period last year, according to market research firm International Data Corp.


text: The number of emergency room visits involving energy drinks has doubled in recent years according to a new federal report. The Substance Abuse & Mental Health Services Administration (SAMHSA) says in a January drug abuse awareness newsletter that more than 20,000 patients including many teenagers visited their local ER in 2011 with "energy drink related" problems. Forty-two percent of those ...Read More »


text:
Tango Lighting specializes in chic, contemporary lighting and brings together a diverse collection of pieces designed in Europe. The Manhattan Wall Lamp is a sconce that adapts beautifully to just about any interior. An engraved, glossy opal glass panel diffuses a welcoming wash of light, and a gentle curve within the simple square metal frame makes it sleek and unobtrusive.
Hardwiring required; mounting hardware and canopy included.
This product has no reviews yet. Be the first to review this product. Write a review
Enjoy 10% off your first order*


text:
Gary Wilcock, managing director of Kerry Logistics Europe, passed away on June 21 after a short battle with cancer. He was 54.
Hong Kong
Hong Kong
Press Releases
Kalmar's Shanghai factory delivers its 1,000th reachstacker to Wing Wah Container Depot Co., Ltd., Hong Kong
23 Jun 2015
If Hong Kong was added to a table of China's top 20 container ports, it would slot in at number four both in terms of cumulative throughput this year and in May volumes, according to the Shanghai Shipping Exchange.
22 Jun 2015
Container terminals in Hong Kong have joined Maersk Line in calling for the territory's government to address competition law concerns that threaten to make the liner business illegal from next year.
15 Jun 2015
It seems nothing can stop the slide in Hong Kong container traffic as the port reported its 11th consecutive month of declining throughput growth in May with volumes falling 12.7 percent year-over-year.
11 Jun 2015
Most of Hong Kong's container shipping activity will be illegal from next year if the competition law due to be implemented by the government on Jan. 1 is enforced in its current form, said Maersk Line's chief executive of North Asia Tim Smith.
11 Jun 2015
The Hong Kong government this week said it would move forward with plans to expand container capacity at its Kwai Tsing Container Terminals. But move is unlikely to mollify critics who say the investment is too little too late to maintain the port's market share of Pearl River Delta traffic.
09 Jun 2015
Shanghai Pudong International Airport Cargo Terminal Ltd. (Pactl) continues to post record breaking throughput figures with May volumes rising 10.7 percent compared to the same month last year.
28 May 2015
Terminal operators and logistics industry executives in Hong Kong must have thrown up their hands in frustration during a welcome address by the city's Secretary for Transport and Housing Anthony Cheung at the inaugural Global Port Research Alliance conference held here recently.
17 May 2015
Container throughput at Hong Kong in April tumbled 11.7 percent year-over-year, the second month of double-digit declines, data from the government's Port Development Council showed.
15 May 2015
The U.S. West Coast labor dispute that choked California's ports for months may have been resolved but the effects continue to lift volumes at the world's largest air cargo carrier, Cathay Pacific.


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Nature | Christmas in Yellowstone | PBS
Duration: 50:24 (Full Program)
Program: Nature #2403
As snow falls and Christmas lights glow in Jackson Hole, a holiday season of a different sort settles in just beyond the town.Tags:
Nature | Trailer | Christmas in... (#2403)
Celebrate Christmas in Yellowstone. 00:32
Nature | Christmas in... (#2403)
Airs Wednesday, December 21, 2011 at 8:00 p.m. ET/PT. Check your local listings. 00:31
Nature | Inside the Yellowstone... (#2403)
Yellowstone visitors celebrate the holiday. 01:57
NATURE "Christmas in... (#2403)
This program re-airs Dec. 24. A red fox shows its ingenious method of catching rodents that it can hear - but not see... 02:04
NATURE | Christmas in... (#2403)
This program re-airs Dec. 23 on PBS (check local listings). Watch a grizzly bear deep in hibernation Join NATURE on... 02:09
NATURE | Bears of the Last... (#2815)
In the heart of the Gates of the Arctic National Park, Chris meditates on the importance of our national park system.... 01:12
Nature | Clash: Encounters of... (#2706)
Full Program: In Yellowstone National Park, two predators reign supreme: the grizzly bear and the wolf. 50:23
Nature | In the Valley of Wolves... (#2502)
Three years in the making, this is the dramatic saga of Yellowstone's Druid wolf pack, its turf wars with rival... 00:31
NATURE | Attenborough's Life...
In "Life on Camera," Sir David Attenborough revisits key places and events in his wildlife filmmaking career,... 00:33
NATURE | Attenborough's Life...
In "Understanding the Natural World," Sir David Attenborough shares his memories of the scientists and the... 00:32
NATURE | Attenborough's Life...
In "Our Fragile Planet," Sir David Attenborough reflects on the dramatic impact that human beings have had on the... 00:32
NATURE | An Original DUCKumentary... (#3004)
A look at all that's entailed in getting those duck feathers just right. "An Original DUCKumentary" premieres... 01:20
NATURE | An Original DUCKumentary... (#3004)
A newly hatched wood duckling jumps from her high-up tree nest to reach her calling mother. "An Original DUCKumentary"... 01:20
Nature | Animal Odd Couples | PBS (#3003)
Full Program: Love apparently knows no boundaries in the animal kingdom. 53:00
NATURE | Animal Odd Couples |... (#3003)
After being abandoned by her mother, a baby fawn, Pippin, was adopted by a Great Dane, Kate, and they have been best... 01:04
NATURE | Animal Odd Couples | The... (#3003)
Primatologist and evolutionary biologist Dr. Lauren Brent discusses her research on the social behavior of nonhuman... 01:41
NATURE | Animal Odd Couples | The... (#3003)
A 45-year-old female Aldabra tortoise was chosen by an unlikely suitor: a male Pacific Brant goose. An... 01:12
NATURE | Magic of the Snowy Owl... (#3002)
In the dim glow of the Arctic glow, the true majesty of the snowy owl can be seen in its frozen, white kingdom.... 01:05
NATURE | Magic of the Snowy Owl |... (#3002)
A snowy owl pair has made a nest out on the tundra. The much larger female is definitely sitting on eggs, and before... 01:28
- Watch more video from this program
Post Date: December 2, 2010


text:
Originally written on Pro Sports Daily | Last updated 10/30/12
Dallas Cowboys linebacker Sean Lee, previously declared out for the season, underwent surgery Tuesday on his right big toe. According to multiple media outlets, Lee expects to be fully healthy in time for the team's offseason training activities. Lee sustained a torn plantar plate in the toe during the Cowboys' 19-14 win over the Carolina Panthers on Oct. 21. The Dallas Morning News also reported that Lee injured the medial and lateral ligaments. "The whole point of getting the surgery (is) to correct it and not have injuries going forward," Lee said last week, according to the Morning News. "If I didn't correct it, it would be tough for me to even play this year, and it could lead to further issues, and I might not get back to where I was. Getting the surgery pretty much guarantees I'm not going to have issues going forward." Lee was the team's leader with 58 tackles when he went down for the season. He also had a forced fumble and an interception. The 26-year-old was in ...
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The Harbor Room Cancer Resource Center at Cambridge Medical Center will offer a free five-week series of gentle yoga instruction titled "Breathe, Stretch, Relax." The class will start on Wednesday, Oct. 3 and will be held on Wednesdays through October 31 (five sessions). The class runs 9 &...Read More
Cambridge Medical Center
Cambridge Medical Center will host an open house noon to 3 p.m. Sunday, Aug. 19 to celebrate the completion of its new Emergency Room (ER) and expanded Chemotherapy/IV therapy department. The new space opens for patient care on Sept. 6. Guests can get a behind the scenes look at the new $10.5 mill...Read More