More than 10¹² tumor cells are present in a leukemia patient at diagnosis. They decrease in number along with the chemotherapy and become undetectable by a microscope. Since the 80's several methods have been invented to visualize the existence of minimal residual disease (MRD). The most useful MRD assays currently available are polymerase chain reaction (PCR) amplification of fusion transcripts and rearranged T-cell receptor and immunoglobulin genes, and flow cytometric (FCM) detection of aberrant immunophenotypes. Both PCR and FCM methods allow detection of 1 leukemic cell in 10, 000 normal cells in at least 90% of patients with acute lymphoblastic leukemia. A number of clinical studies have elucidated that MRD assays are increasingly important in the clinical management of patients with acute leukemia. Several studies in children and adult patients with acute lymphoblastic leukemia and acute myeloid leukemia have shown a strong association between MRD and risk of relapse, irrespective of the methodology used to detect residual disease. Those who are positive for bone marrow MRD have a bad prognosis either after a standard protocol or the salvage therapy and stem cell transplantation for relapsed patients. These findings lead to the idea of modifying the therapeutic regimen according to the amount of MRD. The international BFM group in Europe and Japanese Children's Cancer and Leukemia Study Group (CCLSG) have started MRD-based protocol for ALL children.

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In this report, the recent strategies of pediatric acute myeloid leukemia (AML) excluding Down syndrome and acute promyelocytic leukemia are reviewed. The major pediatric cooperative groups have developed progressively dose-intensified therapeutic approaches based on either modified timing or extended drug exposure. Currently nearly 90% of patients achieve remission and around 50% are long-term survivors with further therapy. Stem cell transplantation has played a central role as a post-remission therapy for AML patients, but recent reports show almost identical results with risk-adapted intensified chemotherapy while autologous transplantation did not result in improved overall survival. The indication for allogeneic transplantation in first complete remission, especially for lower risk patients, leaves an open issue for its toxicity. A significant effort has focused on the development of risk assessment in order to stratify different treatment approach and avoid stem cell transplantation. Both cytogenetics and response to initial therapy have been determined to provide for such risk group stratification. Molecular analysis of AML cells and in vivo response to therapy as detected by measurements of minimal residual disease will be highly predictive measures of outcome. The toxicity of such dose intensified treatments, including stem cell transplantation, significantly limits future attempts at dose intensification of conventional therapies. The development of new agents, especially more AML-specific targeted therapy that minimizes deleterious effects to normal tissue or organs, will be needed.

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Congenital giant platelet disorders comprise a heterogeneous group of rare disorders, characterized by giant platelets, thrombocytopenia and bleeding tendency with variable severity. Many of these disorders share common clinical and laboratory features, and patients are often misdiagnosed with and treated for idiopathic thrombocytopenic purpura. This report summarizes the clinical and laboratory features of the most common giant platelet disorders, Bernard-Soulier syndrome and MYH9 disorders, to make a proper diagnosis.

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Acute Immune-Mediated Thrombocytopenic Purpura (ITP) is one of the most common hematological dis-orders in childhood. Compared to the symptoms such as bruising, petechiae and mucosal bleeding, macroscopic hematuria is uncommon as the first clinical feature in patients with ITP. Here we report a case of macroscopic hematuria as the first presenting clinical feature of ITP associated with primary EBV infection.

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In about 20% of cases of X-linked agammaglobulinemia (XLA), neutropenia is found before the initiation of intravenous immunoglobulin replacement therapy, and Pseudomonas sepsis is fatal in such cases. A one-year-old boy was admitted to our hospital because of convulsion triggered by fever. Laboratory data on admission demonstrated hypogammaglobulinemia (serum immunoglobulin concentrations of IgG < 150 mg/dl, IgA <2 mg/dl and IgM 18 mg/dl) and leukocytopenia (white blood cell count of 1, 800/μl) with severe neutropenia (absolute neutrophil count of 18/μl), and Pseudomonas aeruginosa was isolated from blood culture. No abnormalities on cerebrospinal fluid examination were noted. He was treated with intravenous antibiotics and immunoglobulin, and successfully rescued from Pseudomonas sepsis without sequelae. His leukocyte and neutrophil count increased to the normal range with improvement of infection. A defect of B lymphocytes and mutation of the BTK gene were identified, leading to a diagnosis of XLA. It is important for the early diagnosis of XLA to analyze serum immunoglobulins when we encounter a patient with severe bacterial infection accompanying neutropenia.

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We describe here a successful treatment of a newborn infant with neonatal alloimmune thrombocytopenia (NAIT) employing intensive perinatal care. The mother having a very high titer of anti-HPA-4a conceived the fifth baby. Platelet type of the mother and father was homo-type of HPA-4b and HPA-4a respectively. The second baby had showed severe thrombocytopenia soon after the birth. Considering those facts, we suspected the fifth baby would suffer from NAIT similarly to the second baby. Intensive perinatal care including frequent ultrasonographic monitoring of the fetus without sampling cord blood was performed. The cesarean section was performed after preparing HPA-4b type-platelet-transfusion. High-dose gamma-globulin was administered immediately after birth and the platelet count was maintained without complication (the lowest of platelet count; 11.7×10⁴/μl). We concluded that intensive perinatal care should be done to prevent the complication of hemorrhage in a subsequent baby of previous siblings suffering from NAIT.

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We report a case of a one-year-old girl with concurrent hemophagocytic syndrome (HPS) and pneumonia believed to be caused by Hong Kong type A influenza infection. Analysis of Epstein-Barr virus (EBV) antibody transition, EBV genome copies, and the EBV clonal band of bone marrow cells suggests that HPS was caused by combined infection with EBV and influenza. HPS remitted after treatment with y-globulin, steroid, and cyclosporine A. The patient's outcome was less severe than that typically observed in patients with HPS due to EBV.

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