IntroductionPloidy is a highly significant prognostic factor in childhood acute lymphoblastic leukemia (ALL). 1 A hyperdiploid karyotype with more than 50 chromosomes (particularly those with trisomies for 4, 10, 17, 18) identifies patients with a favorable outcome. 2,3 By contrast, hypodiploidy (modal chromosome number fewer than 46) is associated with a poor outcome. [4][5][6][7][8][9] The majority of hypodiploid patients show 45 chromosomes in their leukemic cells and have a significantly better outcome than patients with fewer than 45 chromosomes. 5 It is not uncommon for leukemic cells with 23 to 29 and 33 to 39 chromosomes to undergo doubling of the hypodiploid clone such that the modal chromosome number may fall in the hyperdiploid or triploid range, 10 respectively. Analysis of the specific pattern of chromosomal gains and losses or flow cytometric determination of DNA content can identify such doubled populations.Hypodiploidy with fewer than 45 chromosomes is very uncommon. In a large MRC study, excluding patients with an established chromosomal structural abnormality, 5% of patients had hypodiploidy of which only 1% had fewer than 45 chromosomes in their leukemic clone. 5 To better understand the epidemiology, prognostic factors, and treatment outcome for children and adolescents with ALL and fewer than 45 chromosomes, 139 cases were collected from 10 participating cooperative groups and large single institutions in the United States and Europe for investigation. This article represents a record review from studies that were previously approved by each institution's local IRB. Informed consent was obtained in accordance with the Declaration of Helsinki. Patients, materials, and methods PatientsStudy groups or institutions reviewed their own records and identified ALL patients with fewer than 45 chromosomes who were registered on ALL clinical trials between 1986 and 1996. A predefined data set was collected for each patient and the data were sent to a central coordinating center for review. Of the 173 patients for whom data were submitted, 2 were ineligible because their date of diagnosis did not meet study entrance criteria, and 32 had karyotypes that were not evaluable. Thus, 139 cases were eligible. Cases were accrued from the following groups: AIEOP-3; BFM-5; CCG-33; COALL-3; DANA FARBER-4; POG-44; SJCRH-6; UK-20; NO-PHO-6; and EORTC-15. Most of the patients received treatment on higher-risk regimens. Nine patients underwent bone marrow transplantation in first remission. Statistical methodsAnalyses were based on patient follow-up through December 2003. Clinical, demographic, and laboratory features of the various hypodiploid For personal use only. on May 11, 2018. by guest www.bloodjournal.org From subgroups were compared using 2 tests for homogeneity of proportions. Outcome was analyzed using life table methods and associated statistics. The primary end points examined were event-free survival (EFS) and overall survival (OS) from study entry; events included induction failure due to refractory leu...

A prospective randomized trial of therapy for severe aplastic anemia was designed to compare early bone marrow transplantation with conventional treatments. All patients with a sibling matched at the major histocompatibility region were transplanted. Transplantation was performed with 17–100 (median 33) days of original diagnosis. Conventional treatments included transfusion support with or without androgens. Twenty-four of 36 patients intered on the transplant arm are alive after 4–20 (median 9) mo with full marrow reconstitution. Only two are limited by chronic graft-versus-host disease. In contrast only 12 of 31 conventionally treated patients are alive. Six of these survivors have improved, five incompletely. The 19 nontransplant deaths have occurred within 1–11 (median 3) mo of diagnosis. Compared to nontransplant regimens, early transplantation more effectively restores normal marrow function and decreases the acute mortality of severe marrow aplasia (p = 0.006). Pending longer follow-up, early marrow transplantation appears to be the most effective available treatment for severe aplastic anemia.

Graft failure was analyzed in 625 patients receiving allogeneic bone marrow transplants from HLA-identical sibling donors as treatment for severe aplastic anemia. Sixty-eight (11%) had no or only transient engraftment. Second bone marrow transplants were successful in achieving extended survival in 16 of 27 patients with transient initial engraftment but in none of ten patients with no sign of engraftment after the first transplant. The major factors associated with a reduced risk of graft failure were use of radiation for pretransplant immunosuppression and use of cyclosporine rather than methotrexate or T- cell depletion of the donor bone marrow for prophylaxis against graft-v- host disease (GVHD). Among 266 patients prepared for transplantation with cyclophosphamide alone, the risk of graft failure was increased in patients who received previous transfusions and reduced in those who received corticosteroids for previous therapy. Neither cell dose nor administration of donor buffy coat cells affected the probability of engraftment. Although use of radiation in conditioning reduced graft failure, survival was not improved. Posttransplant treatment with cyclosporine and avoidance of pretransplant blood transfusions were associated with improved survival.