chemotherapy , especially by intravenous administration , remains the primary modality of treatment for patients with leukemia , lymphoma , and other hematologic malignancies 1 , 2 , 3 . arac and other antineoplastic agents , when administered intravenously , require high doses to achieve their goal . for younger patients , such treatment works well , but older patients can not tolerate such intensive ( high dose ) chemotherapy . thus , more effective and less toxic therapies or new methods of treatment for older patients with aml ( acute myelogenous leukemia ) who are not eligible for a standard intensive induction therapy are needed . with this view in mind and not in keeping with past and present practices 4 such as intravenous and subcutaneous injection , we have designed a new method of targeted therapy that delivers chemotherapeutic agents directly into the marrow cavity , thus intensifying the effects of arac and thereby producing rapid destruction and elimination of the leukemic blast cells . chemotherapeutic agents , when given intravenously , are diluted multifold as they enter into the circulation and mix with approximately 5 l of circulating blood and as a result when they reach their target organ , particularly bone marrow , their effective concentration become much less than when they were injected intravenously . in addition , during their dispersion , they may also bind specifically or nonspecifically to proteins or other tissue components and become less effective . in addition , they may never reach the endosteal region and come in contact with the endosteal cells , according to some hypotheses , where leukemia originates 5 , 6 . furthermore , intramarrow injection not only delivers the active agent(s ) directly into the bone marrow , thus providing direct contact with multitude of leukemic blast cells , but also bathes the endosteum . admittedly , an injection of chemotherapeutic agents into the hip bones or sternum , can not directly affect other bone marrow sites , but agents released here are absorbed by venous sinusoids of this highly vascularized organ and ultimately reach distal bone marrow regions almost as effectively as by conventional ( intravenous ) methods of administration . thus , the overall effect achieved by intramarrow therapeusis is a more intimate association / contact of the anticancer drug(s ) with a large number of target cells and at a high concentration with potential enhancement of antineoplastic activity . the present technique of direct intramarrow injection / administration of chemotherapeutic agents has the potential advantage of overcoming many of the disadvantages associated with the conventional intravenous therapy . in addition , it may also circumvent some of the physiological barriers that a bloodborne molecule has to encounter before it reaches its target cell . furthermore , the total dose of arac used is much smaller than that used in standard 7 + 3 protocol . if indeed this or similar intraosseous treatment becomes successful , then in the future , aml patients can be treated on an outpatient basis , thus reducing the toxicity and cost of hospitalization . this study may also serve as the basis for treatment in both young and old newly diagnosed patients with aml . furthermore , this protocol may be exploited in the treatment of other hematologic malignancies such as multiple myeloma with bortezomib . the patient , a 76yearold white female , presented to the emergency room of hospital a with one month 's history of generalized weakness , diarrhea , frequency of micturition , and decreased appetite . the patient also stated that she was sleeping almost 20 h a day and felt extremely lethargic . her past medical history was significant for hypertension , diabetes mellitus , obesity , colitis , rectovaginal fistula , gerd , asthma , cellulitis , nephrolithiasis , copd , hiatal hernia , and atypical chest pain . on physical examination , the patient was noted to be anemic , but she was not in acute distress . laboratory investigations revealed white blood cell ( wbc ) 42.5  10/l , hemoglobin 7.3 g / dl with normal mean corpuscular volume ( mcv ) , and mean corpuscular hemoglobin ( mch ) and a platelet count of 31  10/l . the differential counts revealed 15% segmented forms , 5% bands , 60% blasts and 13% lymphocytes , and 7% nucleated red blood cells . the bone marrow aspirate revealed a highly cellular marrow ( 95% ) with 64.5% myeloblasts , 0.5% promyelocytes , 10% myelocytes , 5% metamyelocytes , 2% bands , 4% neutrophils , 1% monocytes , and 4% lymphocytes , 0% basophils , 0% eosinophils , 0% plasma cells , and 9% erythroid precursors . flow cytometry studies on the bone marrow aspirate sample revealed an abnormal blast cell population ( 58% of total events ) , which was  positive cd 117 ( partial ) , cd 33 , cd 13 ( dim ) , and cd 56 while negative for cd 34 , hladr , cd 10 , cd 19 , cd 20 , cd 22 , cd 14 , cd 64 , cd 1a , cd 2 , cd 3 , and cd 7 . only 14 metaphase spreads were available , which showed a normal female karyotype of 46 , xx . there was no evidence for either the flt3 it d or the codon 835/836 mutations . after providing informed consent , the patient was premedicated with 100 mg of hydrocortisone and 50 mg of benadryl intravenously half an hour before the intramarrow injection of arac . the first injection of arac ( 30 mg / m ) was given into the right posterior ilium . the subsequent intramarrow injections of arac ( 25 mg / m ) were given into the sternum ( each time a slightly different area of the sternum was chosen ) once daily for 5 days . the patient tolerated the treatment procedure well and without any untoward effects , particularly nausea and vomiting which commonly occurs during arac infusion . on the day of first intramarrow injection , three days following the start of the treatment , her wbc count fell to 30  10/l and blast cell counts fell to 20% . five days following the start of the treatment , her wbc count fell to 15  10/l and blast cell counts fell to 11% . at this stage , the patient thus showed a dramatic response to intramarrow injection of arac , particularly with respect to a rapid elimination of blast cells from the peripheral blood and perhaps also from the bone marrow . however , because of multiple comorbidities and socioeconomic condition , the patient 's family decided to discontinue her therapy and opted for hospice care . this circumstance precluded the opportunity to continue with our intramarrow injection therapy of arac as per planned protocol ( once daily for 57 days every 46 weeks ) as well as to obtain the followup bone marrow assessments . the optimal therapeutic approach for older ( age 60 years ) patients with aml is currently not known . in general , older aml patients have a poor prognosis and median overall survival rate is < 1 year 7 , 8 , 9 . new methods or newer agents with decreased toxicities and improved survival are needed to treat elderly patients with aml 10 , 11 , 12 , 13 . we have used a new method of intramarrow injection / administration of arac instead of the conventional intravenous or subcutaneous approach to induce remission in an elderly patient with aml . the approach of intramarrow injection / administration was chosen to provide a concentrated amount of chemotherapeutic agent ( in this case arac ) directly into the marrow cavity of posterior ilium and sternum so that a large number of leukemic cells could be exposed to the chemotherapeutic agent . in addition , it was also postulated that a proportion of the injected chemotherapeutic agent into the hip bones or sternum , would also be absorbed via venous sinusoids and ultimately reach the malignant cells in distal bone marrow regions thus providing an enhanced and overall antineoplastic activity . m on day 1 at the right posterior ilium and the subsequent intramarrow injections of arac ( 25 mg / m ) were given into the sternum once daily for 5 days ) was considerably smaller than the standard 7 + 3 protocol ( 100 mg / m / day for 7 days along with daunorubicin on days 13 ) . the schedule used for our patient is , in fact comparable to the lowdose ( 20 mg / m sc for 1014 days every 46 weeks ) arac protocol that is used for the treatment of elderly patients with aml 9 , 12 or relapsed or refractory aml patients 14 . the only difference between the lowdose arac treatment and our intraosseous protocol is that the latter provides direct contact of the leukemic cells with arac , thus affording a maximum killing effect of the leukemic cells . the small dose of arac used may also have reduced the toxicity of the drug particularly nausea and vomiting 15 . as the title implies , this is the first case in which we have used a new method ( intramarrow injection / administration ) of treating an elderly patient with aml . as a result , there are no biological studies assessing intramarrow injection of chemotherapeutic agents nor are there are any specific comparative studies between a standard arac approach and the schedule reported . although this is a single patient where intramarrow therapy with arac was used , this strategy seems to have worked in this particular case as evidenced by the fact that the leukemic blast cells were significantly reduced in number in the peripheral blood within days of starting the therapy . it is understood that a standardization of response criteria and treatment outcomes are required for the proper evaluation of treatment protocols for acute myeloid leukemia 16 . the brief and initial study of our patient , however , prevented this type of assessment .
key clinical messagewe have used intramarrow injection / administration of cytarabine ( arac ) instead of conventional intravenous approach to induce remission in an elderly patient with acute myelogenous leukemia . 
 we show for the first time that the intramarrow injection of chemotherapeutic agents such as arac can be used safely and effectively .