[Experience with an international study on standard-risk relapsed childhood acute lymphoblastic leukemia (IntReALL SR 2010 study) in Japan].

Many effective new agents for relapsed childhood acute lymphoblastic leukemia (ALL) are now becoming available, and international standard chemotherapy should be developed to optimize use of these agents. Randomized controlled trials (RCTs) are needed to establish a standard treatment, but few have been conducted for relapsed childhood ALL in Japan due to the small patient population. Participation in international RCTs is necessary to access sufficient patients for informative study results, but differences in approved drugs and healthcare systems between countries make this challenging. In 2014, the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) participated in an international study on standard-risk relapsed childhood ALL (IntReALL SR 2010) involving two RCTs and multiple drugs not approved in Japan, which was addressed by replacing the unapproved drugs with alternative approved drugs with the same or similar efficacy. This article discusses the historical background of treatment development for relapsed childhood ALL, our experience in participating in the IntReALL SR 2010 trial, and prospects for treating relapsed childhood ALL.

Case Report: MYH9-related disease caused by Ala44Pro mutation in a child with a previous diagnosis of chronic immune thrombocytopenia.

MYH9-related disease, a rare autosomal dominant platelet disorder characterized by thrombocytopenia, giant platelets, and leukocyte inclusion bodies, may mimic immune thrombocytopenia in children unless suspected and carefully excluded. Here, we present a case involving a three-year-old girl with mild bleeding symptoms since infancy, previously diagnosed with chronic immune thrombocytopenia. The patient exhibited isolated thrombocytopenia and lacked any family history of thrombocytopenia, hearing impairment, or renal failure. Examination of peripheral blood smears via light microscopy revealed significant platelet macrocytosis with giant platelets and basophilic Döhle-like bodies in the neutrophils. Subsequent sequencing analysis of MYH9 gene identified a p.Ala44Pro mutation. Throughout a six-year follow-up period, the patient's condition remained stable. Our report underscores the significance of identifying leukocyte inclusion bodies in peripheral blood smears and considering MYH9-related diseases, even in instances of chronic macrothrombocytopenia devoid of familial history or non-hematological manifestations.

TBI, etoposide, and cyclophosphamide conditioning for intermediate-risk relapsed childhood acute lymphoblastic leukemia.

BACKGROUND: In children with intermediate-risk relapsed acute lymphoblastic leukemia (ALL), allogeneic hematopoietic stem cell transplantation (allo-HSCT) has markedly improved the outcome of patients with an unsatisfactory minimal residual disease (MRD) response. Total body irradiation (TBI), etoposide (ETP), and cyclophosphamide (CY) have been shown to be equivalent to or better than TBI + ETP for conditioning, so we hypothesized that even greater survival could be achieved due to recent advances in HSCT and supportive care. PROCEDURE: We prospectively analyzed the efficacy and safety of allo-HSCT with a unified conditioning regimen of TBI + ETP + CY in children with intermediate-risk relapsed ALL, based on MRD in the bone marrow after induction, from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) ALL-R08-II nationwide cohort (UMIN000002025). RESULTS: Twenty patients with post-induction MRD ≥ 10-3 and two not evaluated for MRD underwent allo-HSCT. Engraftment was confirmed in all patients, and no transplantation-related mortality was observed. The 3-year event-free survival and overall survival rates after transplantation were 86.4% ± 7.3% and 95.5% ± 4.4%, respectively. CONCLUSION: Allo-HSCT based on post-induction MRD with TBI + ETP + CY conditioning was feasible in Japanese children with intermediate-risk relapsed ALL.