Many papers on treatment protocols in childhood acute myeloid leukemia (AML) have been published in the 1990s. The prognostic factors of childhood AML were analyzed, and patients with AML were classified according to prognostic factors such as ALL. The results of the Japan cooperative study protocol ANLL91 are one of the best previously reported in the literature on this subject. The AML99 protocol which was designed according to cytogenetic analysis, will be promising. On the other hand, new trials are needed to improve the outcome of resistant AML, recurrent AML, and secondary AML.

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A multi-institutional study was performed to determine the clinical significance of a preconditioning regimen containing melphalan and the use of G-CSF for stem cell transplantation in childhood AML. From September 1994 to December 1996, sixty-eight patients (<20 years of age) with AML were enrolled. Patients in the first complete remission (CR1) were classified as standard-risk (SR, n=46) and received busulfan (Bu, 16 mg/ kg) +melphalan (180-210 mg/m²) in both the allogeneic (related, 27; unrelated, 2) and autologous (BMT, 14; PBSCT, 3) transplant setting. Patients in the CR2 or subsequent remission or not in CR were classified as high-risk (HR, n=22), and treated with TBI +melphalan, + etoposide, Bu, or thiotepa in various combinations. The disease-free survival (DFS) rate of the SR group was 73.5% (related BMT, 77%; ABMT, 64.3%) at 3 years, and that of the HR group was 36.4%. Regimen-related toxicity was acceptable in the SR group, but severe mucositis (40.8%) and veno-occlusive disease (18.2%) were observed in the HR group. No serious renal toxicity was observed. Sixty-five patients were eligible for a G-CSF study. G-CSF (300 μg/m²) was administered as a 1-h (14 patients) or 24-h (17 patients) infusion from day 3 or 5 post-transplant (G-CSF group); the remaining 34 patients did not receive G-CSF (non-G-CSF group). No difference occurred in the recovery of granulocytes after the 1-h and 24-h G-CSF infusion regimens, but a significant difference was noted between the G-CSF and the non-G-CSF groups. Moreover, the DFS rate in the G-CSF group was higher than in the non-G-CSF group. We conclude that a preconditioning regimen containing melphalan is feasible and that G-CSF administration is beneficial in the treatment of childhood AML.

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We evaluated the clinical characteristics and outcome of seven patients with acute myeloid leukemia (AML) and Down syndrome at our hospital from 1990 to 1999. The age range at diagnosis was 9-34 (median 20) months, and all cases were diagnosed as having acute megakaryoblastic leukemia (M7), according to FAB classification. These cases were treated by protocol of non-Down syndrome, the doses of which were reduced to 60%-70%; all have continued the first complete remission for 6-113 (median 29) months. The incidence of severe infections during the treatment of AML cases with Down syndrome was equivalent to that of non-Down syndrome, and none has developed heart failure. In this study we achieved 100% event free survival in patients with acute myeloid leukemia and Down syndrome; therefore we concluded that the chance remained to decrease the risk treatment-related mortality by shortening the treatment course or by reducing the doses of anthracyclines and cytarabine.

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We evaluated the safety of peritoneal dialysis and continuous venovenous hemodialysis in patients with lymphoma or leukemia who have a risk of tumor lysis syndrome (TLS) at the time of presentation and initial therapy. Remission induction was achieved by support with dialysis in 11 of 12 patients. Some manageable complications occurred, and one death was a result of MRSA sepsis. We concluded that prophylactic dialysis was a safe procedure. We propose that these patients may be the subjects of prophylactic dialysis, having a huge tumor or advanced stage Burkitt's lymphoma, or both, who showed no decrease of serum uric acid concentration despite aggressive hydration, alkalinization, and administration of allopurinol, or who have hyperkalemia of more than 4.5 mEq/l at the time of presentation.

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The Hematopoietic Stem-Cell Transplantation Committee (previously the Bone Marrow Transplantation Committee) of the Society has conducted an annual registry of hematopoietic stem-cell transplantation in children in Japan since 1983 and published the results until 1997. In 1998, the data of children and adults were combined by using several utilities, and patients from 1991 to 1998 were analyzed and reported in JSHCT monograph, vol. 2. However, since the data of children are not enough in the monograph, more data for children transplanted from 1990 to 1998 are reported in this paper. The DFS rates of patients with severe aplastic anemia who received allogeneic bone marrow transplants are 85.3+7.1% (mean, 95% CI) from I-ILA-matched sibling donors and 72.0+13.1% for BMT from HLA-matched unrelated donors. The DFS rates of patients with AML who underwent transplants in the first CR are 70.5+7.2% for HLA-matched sibling donors, 72.5±10.3% for ABMT and 53.4±11.7% for AutoPBSCT. Statistically significant differences are found between the DFS rate of BMT from HLA-matched sibling donors and from AutoPBSCT (p <0.01) and between the DFS rate of ABMT and that of AutoPBSCT (p <0.05). The DFS rates of patients with ALL who underwent transplants in the first CR are 65.1+11.1% for HLA-matched sibling donors, 52.4+22.8% for ABMT, and 65.9+8.8% for AutoPBSCT. No statistically difference is found among them. The number of transplants reported were 594 for BMT from unrelated donors, 86 for cord blood stem-cell transplantation, and 79 for allogeneic PBSCT.

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L-Asparaginase (L-ASP) is used as a key drug in patients with acute lymphoblastic leukemia (ALL); however, this drug is known to have serious side effects. We had a patient who experienced L-ASP-induced acute pancreatitis in 10 months of treatment for ALL. The pancreas was swollen in the necrotic area, and massive pleural effusion was observed in the left chest. Initial therapies consisted of the maintenance of circulation, relief of pain, decrease of pancreatic secretion (use of H₂-blocker and somatostatin-analogue), and prevention of bacterial infection. The patient developed a pseudocyst of the pancreas later, and it was resolved without surgical intervention. Chemotherapy for ALL was started 60 days later, and the patient remains in remission 24 months after the onset of ALL. The frequency of acute pancreatitis is low, but the management is often difficult. No standard treatment has been established. Various treatment modalities have been recommended for acute pancreatitis ; however, the efficacy has not been proven in most cases. The investigators of group studies should provide information on such rare events as acute pancreatitis.

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An 8-year-old boy with t (16 ; 21) acute myelomonocytic leukemia (AMMOL) relapsed at 8 months after diagnosis during intensive consolidation chemotherapy. He underwent bone marrow transplantation (BMT) (HLA-A, B, C, DR, and DQ matched) from his eldest brother. Although engraftment was obtained, hematological relapse occurred 2 months later. Peripheral blood stem cell infusion and donor lymphocyte infusion were then performed from the same brother without causing acute graft-versus-host disease (GVHD) or achieving a second remission. Thereafter BMT (one allele mismatch for HLA-DR and DQ) was done by using his second elder brother as the donor, and remission was induced after grade II acute GVHD developed in the skin and in the gastrointestinal tract. These findings suggested that remission was induced by an adequate graft-versus-leukemia (GVL) effect because of the differences of HLA-DR and DQ between the patient and the second donor.

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We present a case of Kostmann's syndrome (KS), that developed myelodysplastic syndrome (MDS) and monosomy 7, 24 months after administration of high-dose recombinant human granulocyte colony-stimulating factor (rhG-CSF) for frequent bacterial infections since the 10th day after the patient's birth. The colony assay and RT-PCR analysis of the mRNA expression of the G-CSF receptor in his bone marrow mononuclear cells suggested that differentiation from progenitors to mature neutrophils was, impaired.

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A two-year-old-boy was referred to our hospital because of recurrent head skin ulcers, fever, hepatomegaly, and cervical lymphadenopathy. Blood examination showed pancytopenia and liver dysfunction, and a significant rise of Epstein-Barr VCA-IgG titer. Furthermore, atypical lymphoid cells positive for both EBER-1 and CD3 were found to be infiltrating into the head skin, cervical lymph nodes, and liver biopsied tissue. By the use of Southern blotting, a rearrangement of T cell receptor-β-gene, and monoclonal proliferation of EBV infected cells was identified. He was diagnosed as having peripheral T-cell lymphoma associated with Epstein-Barr virus (EBV-PTCL) and was treated with combination chemotherapy. The patient showed speedy recovery after the treatment. However, hemophagocytosis was observed again, so six courses of COPP-ABVD hybrid therapy and five of ABVD therapy were done. Over the past two years since the end of the treatment, the case has been in remission with no signs of symptoms.

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