Takako Kawakami

SEVERE HEMORRHAGIC COLITIS CAUSED BY DASATINIB IN PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA

Dasatinib, an oral inhibitor of ABL and SRC family tyrosine kinases, is an effective drug for patients with Philadelphia chromosome positive (Ph+) leukemia, especially for those who develop resistance or who are intolerant to imatinib [1]. The most frequent adverse effects are myelosuppression, diarrhea, nausea, and peripheral edema. As a result of the wide use of dasatinib, reports of unexpected side effects have increased: pannuculitis [2], lung abnormalities [1, 3], and modulation of glucose metabolism [4]. The mechanism of each of these side effects is not clearly elucidated, but possible explanations include unintended off-target kinase inhibitory effect [1, 3]. Although gastrointestinal (GI) hemorrhage is a well-known complication of dasatinib therapy that has been reported in multiple occasions, few cases have shown hemorrhagic colitis without thrombocytopenia and ulcer [5–7].

Novel breakpoints of the EWS gene and the WT1 gene in a desmoplastic small round cell tumor.

We report here a 15-year-old boy with an intraabdominal desmoplastic small round cell tumor (DSRCT). Cytogenetic analysis of the tumor cells showed the chromosomal translocation (11;22). Reverse-transcriptase polymerase chain reaction and sequencing analysis revealed a chimeric transcriptional message of the EWS gene exon 10 fused to the WT1 gene exon 8. The typical chimeric transcript seen in DSRCT is an in-frame fusion of EWS exon 7 to WT1 exon 8. The tumor in this case had a novel and longer chimeric transcript, which should be a potent transcription factor. Genetic analysis is a very powerful and specific aid in the differential diagnosis of small round cell tumors.

Successful unrelated donor bone marrow transplantation for shwachman-diamond syndrome with leukemia

Shwachman-Diamond syndrome (SDS) is a rare congenital disorder featuring exocrine pancreatic insufficiency, growth retardation, and bone marrow dysfunction. Reports suggest that nearly 25% of all cases are complicated with leukemia. Although stem cell transplantation is the sole option for these patients, successful results are rarely obtained. Poor outcomes are often related to graft failure and cardiac and other organ toxicitics. We describe in this report successful unrelated donor bone marrow transplantation for a patient with SDS who progressed to acute myelogenous leukemia. The patient received attenuated intensified chemotherapy because of his intolerance to ordinary chemotherapy and went into remission. Sustained unrelated donor bone marrow engraftment was accomplished after treatment with a reduced amount of cyclophosphamide and antithymocyte globulin with 12 Gy of total body irradiation as a conditioning regimen. To the best of our knowledge, this report is the first to describe unrelated donor bone marrow transplantation with complete engraftment for an SDS patient with myelogenous leukemia.

Severe bleeding tendency in a patient with Bernard-Soulier syndrome associated with a homozygous single base pair deletion in the gene coding for the human platelet glycoprotein Ibα

Purpose The genetic basis of Bernard-Soulier syndrome (BSS) was studied to clarify a relationship between severe clinical manifestations and gene abnormality. Patient and Methods A patient with BSS had a severe bleeding tendency that was sometimes life threatening. Flow cytometric analysis of the patients and normal control platelets was performed to study which glycoprotein (GP) was impaired in glycoprotein Ib/V/IX complex. The genes encoding GPIbα from the patients and control genomic DNA were amplified and directly sequenced. Results Flow cytometric analysis revealed a defect of GPIbα on the surface of the patients platelets. A homozygous single base pair deletion was identified in seven repeats of adenine at positions 1932 to 1938 in the GPIbα gene. This mutation, which has been previously reported, results in a frameshift and predicts a premature stop codon leading to a truncated peptide that cannot fix on the platelet membrane. Conclusion This patients severe clinical phenotype would be explained by this mutation in the GPIbα gene.

Chromosomal aberration in lipoblastoma: A case with 46,XX,ins(8;6)(q11.2;q13q27)

Chromosomal aberrations involving 8q11.2 have been reported in lipoblastoma. We report here a case of lipoblastoma with new chromosomal aberration. 46,XX,ins(8;6)(q11.2;q13q27). Cytogenetic analysis would facilitate the clinical differentiation between myxoid liposarcoma and the pathologically similar lipoblastoma and the identification of genetic loci related to cellular growth.

CD48 expression on leukocytes in infectious diseases: Flow cytometric analysis of surface antigen

Background: The function of CD48, one of the pan leukocyte cell surface antigens, is not yet well understood. CD48 was recently shown to enhance the CD40‐mediated activating signal to B lymphocytes. As CD48 is one of the activation antigens of monocytes, neutrophils and lymphocytes, a change of its expression on the cells could be expected in infectious diseases.

Haemophagocytic lymphohistiocytosis following measles vaccination

A 19-month-old girl developed haemophagocytic lymphohistiocytosis following a measles vaccination. She developed persistent high fever 1 week after vaccination, and then showed pancytopenia, liver dysfunction and hepatosplenomegaly with marked haemophagocytosis. Based on the clinical and laboratory findings, she was diagnosed as having haemophagocytic lymphohistiocytosis probably due to measles vaccination. She did not respond fully to first-line immunosuppressive therapy and required immunochemotherapy with cytotoxic drugs. Conclusion: to the best of our knowledge, this is the first detailed report of haemophagocytic lymphohistiocyosis associated with measles vaccination documented in the English literature. Haemophagocytic lymphohistiocyosis should be kept in mind as one of the rare adverse effects of vaccination.

Successful treatment of acute myeloid leukaemia in a patient with ataxia telangiectasia

Ataxia telangiectasia (AT) is a rare autosomal recessive multisystem disorder characterised by cerebellar degeneration, immunodeficiency and cancer predisposition. Around 10% of AT patients develop lymphoid malignancies, but the development of myeloid leukaemia with AT (AT‐AML) is extremely rare, and there have been no previous publications regarding suitable therapies. Here, we first describe a successful therapeutic experience in a patient with AT‐AML (FAB‐M1) who attained remission after induction therapy and maintained stable disease for a year. To minimise therapy‐induced toxicity, low‐dose induction was applied first, though this was obviously insufficient and the patient subsequently responded well to dose‐intensified short‐term chemotherapy. In this report, we suggest a curative therapeutic approach for AT‐AML, though the issue of how best to manage patients with cancer complicated by immunodeficiency remains undecided.