precursor b - cell acute lymphoblastic leukemia accounts for 2% of all lymphoid neoplasms in the united states and occurs most frequently in childhood , but can also occur in adults with a median age of 39 years . we present a case of a 51-year - old caucasian female with the development of precursor b - cell acute lymphoblastic leukemia after suffering acute hepatitis a 4 weeks prior to her diagnosis . she presented with malaise for a month without spontaneous bruising / bleeding , infections , or b - symptoms , such as fevers , night sweats , or unintentional weight loss . nonspecific viral transformation of bone marrow has been discussed in the literature , but we specifically describe hepatitis a - induced adult - onset precursor b - cell acute lymphoblastic leukemia , which is the first reported case in the literature . classically , precursor acute lymphoblastic leukemia ( all ) is most commonly a childhood disease that is extremely responsive to chemotherapy ( 88% ) and has an excellent prognosis in most cases . all has known associations with radiation exposure , benzene , hair dyes , and down syndrome . in addition to these risk factors , adult - onset or atypical all may also be a complication of previous chemotherapy regimens . unlike its childhood counterpart , adult - onset all has an unfavorable response to chemotherapy ( 20 - 40% ) and has a poor prognosis . in the literature , there have been numerous references to a viral etiology involved in the pathophysiology and transformation of the bone marrow in children predisposing them to the development of all . however , there have not been any cases reported in the literature that were able to establish a causal relationship between all and a viral infection in a temporal manner . we report a case of acute hepatitis a - induced adult - onset precursor b - cell all , which is , to our knowledge , the first reported case in the literature . this paper reports a case where acute viral transformation of the bone marrow took place in a rather short time period . a 51-year - old caucasian female with a history of migraine headaches managed with topamax for the last year presented with increased malaise and fatigue when walking up a flight of stairs . several months prior , she had had normal laboratory studies and had been in great health . a day prior to her admission , she had been found to have severe anemia by her outpatient physician and was hospitalized for further evaluation . her physical assessment showed pallor and splenomegaly without any lymphadenopathy or bruises . computed tomography of the head , thorax , abdomen , and pelvis , checking for malignancy , was unremarkable except for splenomegaly . complete blood count at the time of admission showed pancytopenia with a hematocrit ( hct ) of 15% , a platelet count of 17,000 , a white blood cell count of 1.58 k / mm , with no indication of hemolysis or reticulocytosis . she was transfused with 5 units of blood during her hospital course , which increased her hct up to 24.7% , but was not an appropriate response . iu / l and an aspartate transferase level of 1,600 iu / l in the absence of hypotension , which warranted acute hepatitis serologies . hepatitis serologies were negative for hepatitis b and c antibody , but positive for hepatitis a igm antibody . further questioning after the identification of the positive hepatitis igm antibody revealed that the patient had experienced a bout of extreme diarrhea , nausea , vomiting , extreme malaise , and yellow - colored skin approximately a month prior to her admission . according to the laboratory findings and history , the patient had suffered acute hepatitis a approximately 1 month prior to her admission , from which she had recovered spontaneously without medical treatment . evaluation of her pancytopenia revealed a negative monospot test , but she was found to have high titers of epstein - barr virus ( ebv ) , antibody igg and ebv nuclear antigen antibody igg , which was consistent with an old or a convalescent phase of ebv infection and ruled out ebv as a cause of her pancytopenia . hepatitis a - induced aplastic anemia along with the ingestion of topamax were considered as possible causes of the bone marrow depression , although topamax is not classically associated with blood dyscrasias . a peripheral blood smear revealed 54% immature cells , true thrombocytopenia and the absence of hemolysis . because her pancytopenia did not resolve , a bone marrow biopsy was warranted , which revealed a b - cell lymphoproliferative disorder ( fig . 1 , fig . 2 ) . however , markers were diffusely positive for cd10 and cd20 and a subsequent flow cytometry confirmed precursor b - cell all . molecular genetic analysis was positive for the philadelphia chromosome , which occurs in 25% of the adult all cases . the incidence increases with age , approaching 50% in patients older than 50 years of age . all cases with a positive philadelphia chromosome have a worse prognosis and therefore our patient immediately received induction chemotherapy . all typically affects patients between 2 and 5 years of age with symptoms of fever , bleeding , bone pain and lymphadenopathy . our patient was diagnosed with precursor b - cell all at the age of 51 with no risk factors ( including family history ) in the setting of recent topamax use , acute hepatitis a , and high epstein - barr viral titers . unlike other anti - epileptic drugs , there are no reports of topamax causing bone marrow dysplasia at either therapeutic dosages for seizures or migraine headaches . on the other hand , ebv - induced aplastic anemia presents in the setting of burkitt 's lymphoma , acute infection or reactivation in the immunodeficient . however , our patient 's laboratory evaluation revealed an ebv igg antibody and ebna igg antibody consistent with an old or convalescent ebv infection . thus , the possibility of an acute ebv hepatitis or topamax - induced bone marrow suppression in the aforementioned setting would be nullified even in the absence of the peripheral smear or bone marrow results . acute hepatitis a manifests as fever , nausea , vomiting , abdominal pain , and jaundice . fecal - oral transmission is predominant , which explains the increased prevalence of acute hepatitis a in developing countries . although major hematologic manifestations of acute hepatitis a are rare , transient granulocytopenia and thrombocytopenia are often seen with extremes of aplastic anemia [ 2 , 3 , 4 ] . hepatitis a virus can induce an autoimmune reaction   and chromosomal damage in the hematopoietic system with subsequent stem - cell failure . in some cases , liver cell damage impairs the detoxifying metabolism of drugs with subsequent bone marrow toxicity [ 7 , 8 ] . viral hepatitis a has numerous mechanisms of action , which allows it to impact the bone marrow in a complex way [ 5 , 6 ] . the major differential in our case was related to hepatitis a - induced aplastic anemia , which was ruled out with the peripheral smear as well as the bone marrow biopsy . there are several models reviewed by the national institute of health that support an infectious etiology to all induction . one of the models specifically views all as a rare response to a childhood infection and assumes that the leukemia - inducing effect is related to the timing of the infection , with a greater leukemic effect with later infections as opposed to those which occurred in infancy . in fact , this suspicion was so strong that various viruses from the polyomaviridae family , such as jc virus and bk virus , have been sequenced and compared to childhood all sequences ; however , there was no causal relationship with these viruses . in a review regarding the etiology of acute childhood leukemias , it was concluded that delayed dysregulated responses to common infectious agents played a major part in the conversion of preleukemic clones that were present genetically into overt precursor b - cell all . if common infectious agents can induce such a transformation , one can only speculate the impact of a severe viral infection , such as acute hepatitis a. this concept supports the classic ' two - hit hypothesis ' in many ' nature combined with nurture ' models of disease , which describe a genetically predisposed individual ( nature ) , who is environmentally exposed to a severe insult ( nurture ) . similar models have been referenced in the pathogenesis of inflammatory bowel disease in relation to gut microbial flora . additionally , in the pediatric population , it is difficult to assess the degree of delay and transformation into overt all as there are numerous variables which influence the outcome in patients at risk . however , this issue is not significant in our patient due to the timing and course of her acute hepatitis a infection . lastly , there is the rare possibility that precursor b - cell all developed independently of her acute hepatitis a , but there are no reported cases in the literature where acute hepatitis a independently occurred in a chronological fashion with precursor b - cell all . our patient had been serially followed by her primary care physician throughout her life and had never had any evidence of blood dyscrasias . immediately prior to her hepatitis a infection , she had been in good health and had a normal laboratory evaluation . approximately 2 weeks after her acute hepatitis infection , she had a low hct at another hospital ; then she developed pancytopenia 2 weeks later , at the time she was admitted to our facility . in a thorough review of the literature , no reported cases with this type of temporal and causal relationship of a proven viral infection subsequently inducing acute lymphoblastic transformation were found . we propose that this viral transformation was induced through one of the previously mentioned mechanisms , such as chromosomal damage to the hematopoietic system . in conclusion , this case illustrates a temporal , chronological , and causal relationship in which bone marrow transformation was induced by an acute hepatitis a infection leading to precursor b - cell all in the absence of any other known risk factors . to our knowledge , this is the first such case reported in the literature .
backgroundprecursor b - cell acute lymphoblastic leukemia accounts for 2% of all lymphoid neoplasms in the united states and occurs most frequently in childhood , but can also occur in adults with a median age of 39 years . 
 it is more commonly seen in males and in caucasians.case reportwe present a case of a 51-year - old caucasian female with the development of precursor b - cell acute lymphoblastic leukemia after suffering acute hepatitis a 4 weeks prior to her diagnosis . she presented with malaise for a month without spontaneous bruising / bleeding , infections , or b - 
 symptoms , such as fevers , night sweats , or unintentional weight loss.conclusionnonspecific viral transformation of bone marrow has been discussed in the literature , but we specifically describe hepatitis a - induced adult - onset precursor b - cell acute lymphoblastic leukemia , which is the first reported case in the literature .