To disclose the information for the risk in allogeneic hematopoietic stem cell transplantation (allo-HSCT), we propose a new concept of the risk in allo-HSCT. We analyzed all 94 allo-HSCT cases (86 patients) in our hospital since 1983. The overall survival rate was 56.4%. Among 27 patients considered to be at standard risk judged by conventional risk criteria who underwent initial transplantation from HLA-identical donors, 66.7% of them survived. Univariate statistical analyses among subgroups classified by conventional risk criteria and several reported prognostic factors show significant differences. However, all of them failed to show significant difference because of too much variation between cases in the same subgroup or a too small number of patients as compared with the U.S.A or European transplantation centers. We propose an alternative comprehensive classification of transplantation risk according to two newly-recognized distinct risks, disease state and transplantation risk. This comprehensive classification revealed significance in the multivariate statistical analyses in our hospital. We expect further discussion or the appearance of other beneficial nationwide proposals to evaluate and disclose the risk affecting survival following allo-HSCT.

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The purpose of this study was to evaluate liver graft-versus-host disease (GVHD) after allogeneic myeloablative stem cell transplant (within day100). We retrospectively reviewed the data on 61 patients with incidence of hepatic GVHD, the clinical course, laboratory data and histologic features of the liver biopsy. Between February 1998 and March 2002, 61 patients received an allogeneic myeloablative stem cell transplant. The diagnosis of liver dysfunction was based on marked (more than 3 times the upper normal limit) elevation of serum aminotransferases or on a level above 2mg/dl of total bilirubin. We used criteria for grading (GVHD) on consensus conference. The diagnosis of hepatic “GVHD” was based on classical liver GVHD, on histological GVHD without jaundice or on elevation of serum aminotransferases with other GVHD. Liver function abnormality occurred in 50 out of 61 (82%). The main causes of hepatic dysfunction were hepatic “GVHD” (19 out of 50, 38%). Of the 19 hepatic “GVHD” patients, elevation of serum aminotransferases alone was seen in 13 patients (68%), jaundice alone was seen in 1 patient (5%) and both were seen in 5 patients (27%). The treatment with glucocorticoids was successful in those patients with elevation of serum aminotransferases alone.

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We report on a 6-year-old girl with acute lymphoblastic leukemia (ALL) with 11q23 microdeletion and translocation at the long arm of chromosome 11, which were detected by fluorescence in situ hybridization (FISH) but not by conventional cytogenetics. She was hospitalized because of fever and generalized bone pain. Results of peripheral blood examination included a WBC of 5,400/μl with 12% lymphoblasts. Bone marrow studies showed 75% of early pre-B lineage lymphoblasts with L1 morphology. G-banding chromosome analysis demonstrated a normal karyotype. However, FISH using mixed lineage leukemia (MLL) and 11q subtelomere probes demonstrated 11q23 microdeletion and translocation at the long arm of chromosome 11 to an undefined chromosome. MLL rearrangement was not detected by Southern blotting analysis. The patient achieved complete remission 15 days after receiving high-risk group chemotherapy of the Kyoto University Pediatric Hematology/Oncology Study Group and has remained in complete remission for more than 30 months. Since MLL/11q23 abnormalities confer a poor prognosis in childhood ALL, the accurate detection of such abnormalities is of paramount significance in assigning individual cases to risk categories. The findings from the present case and recent literature indicate that the FISH-based approach is complementary to conventional cytogenetics, and should be systematically used in childhood ALL at diagnosis.

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The patient was a 47-year-old man who was diagnosed in 1989 as having chronic myelogenous leukemia (CML). He had been treated with interferon-α (IFN-α) and hydroxyurea. In August 1999, he was admitted to our hospital for examination of severe anemia and increased platelet count. On admission, his hemoglobin level was 6.3 g/dl, reticulocyte count was 0.7%, WBC count was 5,100/μl, and platelet count was 57.3×10⁴/μl. Bone marrow aspiration showed myeloid hyperplasia and near absence of erythroblasts. Bone marrow karyotype analysis showed a Ph chromosome with additional abnormalities. Pure red cell aplasia (PRCA) with accelerated-phase CML was considered. The IFN-α therapy was discontinued. Hydroxyurea at an increased dosage was effective in controlling the CML. In contrast, administration of cyclosporin A was not effective for the PRCA. The patient's condition was later complicated by acute hepatitis C virus infection. The IFN-α was restarted to control the CML and hepatitis. The patient remained erythroblastopenic and transfusion-dependent for more than 2 years. Association of CML and PRCA is rare. We discuss the mechanisms underlying PRCA occurring during the course of CML.

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A 13-year-old male was diagnosed as having pineal germinoma in July 1998. Since then, he had been treated with tumor excision, radiation and chemotherapy. In June 2002, he was diagnosed as having the chronic phase of chronic myelogenous leukemia (CML), and following treatment with interferon-α, he achieved hematological complete remission. Although CML is rare in secondary leukemia, the present case seemed therapy-related CML because of its clinical course, as the CML occurred after the period with radiation and chemotherapy. This is the first case of secondary CML following therapy for intracranial tumors.

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A 44-year-old man with relapsed acute promyelocytic leukemia (APL), refractory to all-trans-retinoic acid (ATRA), daunorubicin, and cytosine arabinoside, was treated with arsenic trioxide (ATO). ATO was given intravenously at a dose of 0.15 mg/kg/day for 20 days, and the patient achieved complete remission. No serious adverse events related to ATO infusion were observed. He received ATO for 10 days as consolidation therapy and subsequently underwent HLA-matched unrelated donor stem cell transplantation. He remains in molecular remission 10 months after transplant. This case suggests that ATO could be a useful therapy prior to allogeneic stem cell transplantation in relapsed APL.

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