The establishment of regenerative medicine is dependent on stem cells. Stem cells are classified into two groups : tissue stem cells, which can be detected in various tissues even in adulthood, and embryonic stem (ES) cells. Recently, not only human ES cells with normal phenotypes but also those with genetic disorders have been established. Moreover, multipotent stem cells, equivalent to ES cells, were generated from neonatal mouse testis. The further investigation of these stem cells leads to the establishment of effective regenerative medicine without harmful events.

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Recent advances in identification of signaling molecules activated in a tumor-specific manner or associated with tumor-specific genomic recombination have disclosed many candidate therapeutic targets in tumors. In the field of hematological malignancies, we have already experienced the remarkable clinical efficacies of imatinib mesylate for CML, ATRA for APL as well as rituximab for B cell lymphoma. A number of molecular targeted agents are now under clinical trials and some of them are promising.

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Anti-tumor necrosis factor-alpha antibody (infliximab) was administrated for the control of graft-versushost disease (GVHD) in four pediatric patients after allogeneic hematopoietic stem cell transplantation (HSCT). In two patients with acute GVHD, two doses each of infliximab (5-10 mg/kg/dose) were administered when the immunosuppressants such as tacrolimus and cyclosporine A needed to be reduced or discontinued due to the occurrence of thrombotic microangiopathy (TMA) or tacrolimus-associated encephalopathy. In the other two patients with refractory chronic GVHD, three doses of infliximab (each 5 mg/kg/dose) were administered at 43 + and 48 + months for the treatment of severe skin and muscular lesions including scleroderma. In our cases infliximab was effective in improving the clinical manifestations in 3 patients, particularly in the status of transplant-related endothelial cell damage conditions such as TMA and tacrolimus-associated encephalopathy. The optimal timing and doses remain to be determined to obtain the maximal effect of infliximab in the treatment of acute as well as chronic GVHD in HSCT recipients.

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We have done regular long-term continuous replacement therapy for 5 patients with hemophilia A and l patient with hemophilia B. Among 6 patients, 2 patients with hemophilia A and 1 patient with hemophilia B were regularly replaced before the age of 1 year old as soon as diagnosis was confirmed. Patients with hemophilia A received 25 IU/kg factor VIII three times a week, and the patient with hemophilia B received 25-50 IU/kg factor IX twice a week. They have been engaged in normal activities including sports participation without hemophilic arthropathy since receiving the regular long-term continuous replacement therapy. We suggest that the regular long-term continuous re-placement therapy improves quality of life in children with hemophilia A and B.

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A 4-year-old boy with microcytic anemia without iron deficiency is reported. Isoelectrofocusing analysis showed an abnormal hemoglobin (Hb) band likely to be Hb Lepore syndrome, one of the thalassemia-like disorders. He was then diagnosed with Hb Lepore (Washington-Boston type) syndrome by specific gap PCR. While patients with a mild type of thalassemia or thalassemia-like syndrome should have normal life prognoses, definite diagnosis is important because of the problems of hereditary counseling.

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We described an 8-year-old boy with acute lymphoblastic leukemia (ALL) associated with ureteral calculi. During induction chemotherapy, he complained of severe abdominal pain, which might have initially been caused by vincristine-induced enteroparalysis. He was treated with gas exhaust and enema, but pain deteriorated. Abdominal echogram and enhanced computerized tomography disclosed urolithiasis and left hydronephrosis. The calculi were excreted by massive hydration therapy, and were composed mainly of calcium oxalate. He was diagnosed as having fugitive hypercalciuria. The ureteral calculi in this patient might been caused by familial diathesis, administration of corticosteroid and acetazolamide, and long-term bed rest. Urolithiasis should be considered in a patient who complains of abdominal pain during induction chemotherapy for ALL.

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Chronic granulomatous disease (CGD) is an inherited disorder caused by the abnormalities of NADPH oxidase in phagocytic cells. Stem cell transplantation (SCT) from an HLA-identical donor is an effective treatment for patients with CGD. However, SCT with myeloablative conditioning carries a high incidence of serious complications and death. We report a 21-year-old man with CGD who was successfully treated with allogeneic bone marrow transplantation (alloBMT) from his HLA-identical brother following a nonmyeloablative conditioning regimen consisting of cyclophosphamide, fludarabine and a low dose of total body irradiation. Engraftment was rapidly achieved without any toxicity or complication. Partial donor chimerism following alloBMT was converted to complete donor chimerism and nomal oxidase activity of neutrophils was induced by several donor lymphocyte infusions (DLI) from his HLA-identical brother. At 30 months after transplant, the patient is in excellent clinical and hematological condition, maintaining complete chimerism. We suggest that alloBMT preceded by nonmyeloablative conditioning and followed by DLI may constitute a successful mode of therapy for patients with CGD.

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We present two patients who developed hemophagocytic syndrome (HPS) associated with all trans-retinoic acid (ATRA) after induction chemotherapy for acute promyelocytic leukemia (M3). Case 1 : A 4-year-old girl was diagnosed as having M3 and was treated with chemotherapy including ATRA. Thirty days after starting chemotherapy, she developed HPS. Case 2 : A 17-year-old boy was diagnosed as having M3 and was also treated with chemotherapy including ATRA. Thirty-seven days after starting chemotherapy, he developed HPS. A drug-lymphocyte stimulation test against ATRA was positive in case 2. In both cases, the patients recovered immediately after treatment with prednisolone, with no recurrence of HPS, although the patients received ATRA during subsequent consolidation or maintenance chemotherapy phases. We speculate that the HPS-associated ATRA administration following induction chemotherapy was due to enhancement of hypercytokinemia during the hematological recovery period or was one of the late onset symptoms of ATRA syndrome.

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In this paper, we describe two acute lymphoid leukemia cases with invasive fungal infection in allogeneic stem cell transplanation. One suffered from fungal hepatosplenic abscess without identification of causal species and the other had pulmonary aspergillosis as a result of neutropenia following intensive chemotherapy and allogeneic stem cell transplantation. Their diseases were refractory to amphotericin B and nephrotoxicity developed. Therefore, amphotericin B was replaced with micafungin in both cases. In both patients, clinical and laboratory findings got better and hepatosplenic abscess and pulmonary aspergillosis were almost healed without adverse reaction. Thus, micafungin appears to be a useful and safe anti-fungal agent for refractory invasive fungal infection including aspergillus infection in children undergoing stem cell transplantation.

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It is known that erythroleukemia (AML-M6) is extremely rare among AML; therefore there have been very few reports on pediatric cases of erythroleukemia. Recently, there has been a tendency to deal with erythroleukemia in the same category as refractory anemia with excess of blasts (RAEB). We encountered a 9-month-old girl with RAEB-AML-M6 syndrome. She suffered from recurrent fever since the age of 6 months, and then she revealed thrombocytopenia and hepatosplenomegaly. The bone marrow specimens revealed erythroid hyperplasia, and showed myelodysplastic changes in the erythroid, myeloid, and megakaryocytic lineage. The ratio of myeloid blasts other than erythroblasts was 9%. Cytochemical analysis was performed; the blasts were peroxidase and periodic acid-Schiff positive. After intensive chemotherapy, she received unrelated cord blood transplantation (CBT) after a conditioning regimen consisting of busulfan and melphalan. For graft-versus-host disease prophylaxis, cyclosporine A and methylprednisolone were administered. She has been in complete remission for 18 months after CBT. The authors suggest that CBT could be considered in the treatment of patients with RAEB-AML-M6 syndrome.

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