Summary The incidence of cytogenetic abnormalities in childhood de novo acute myeloid leukaemia (AML) and its prognostic significance was assessed in an Israeli paediatric referral centre. Cytogenetic analysis was successful in 86 of 97 children (<20 years of age) diagnosed between 1988 and 2002 with de novo AML. Fluorescence in situ hybridization analysis detected new information in 11 of them, leading to reassignment in cytogenetic group classification. The incidence of the various cytogenetic subgroups was as follows: normal – 9%; t(11q23) – 22%; t(8;21) – 13%; t(15;17) – 8%; inv(16) – 3·4%; abn(3q) – 4·6%; 7/7q‐(sole or main) – 5·8%; del(9q)(sole) and +21(sole) – 4·6% each; t(8;16) – 2·3%; t(6;9), t(1;22), +8(sole) – 1·1% each; and miscellaneous – 18%. The overall survival (OS) and event‐free survival (EFS) (4 years) for 94 patients treated with the modified Berlin‐Frankfürt‐Münster (BFM) AML protocols (non‐irradiated) were 59·9% (SE = 5%) and 55·7% (SE = 5%), respectively, and for the favourable t(8;21), t(15;17) and inv(16), OS was 60% (SE = 15%), 83% (SE = 15%) and 100% respectively. For the normal group it was 62% (SE = 17%), miscellaneous 64% (SE = 12%), t(11q23) 44·6% (SE = 11%) and of the −7/7q‐, del(9q)(sole) or t(6;9), none had survived at 4 years. The incidence of cytogenetic subgroups in the Israeli childhood AML population and their outcome were similar to other recently reported paediatric series. Cytogenetic abnormalities still carry clinical relevance for treatment stratification in the context of modern chemotherapy.

Chronic lymphocytic leukemia (CLL) is a malignant clonal expansion of CD5+B lymphocytes. The CD5+B lymphocytes have been postulated to produce autoantibodies. CLL patients may demonstrate features of autoimmunity including autoimmune hemolytic anemia. However, the origin of the autoantibodies causing the hemolysis is not clear. The present studies were performed to determine whether these autoantibodies are the products of the neoplastic B-CLL clones. Immunoglobulins (Ig) were eluted from washed red blood cells (RBC) obtained from two CLL patients at the time they had autoimmune (DAT-direct antiglobulin test-positive) hemolytic anemia. The light chain phenotypes of these eluted autoantibodies were determined and found to be monotypic with exact correlation to the light chain expressed on the surface of the B-CLL clones. Elutions from RBC of DAT negative patients or normal volunteers failed to demonstrate measurable amounts of Ig. In contrast, Ig eluted from RBC obtained from SLE patients with DAT positive hemolytic anemia found to be polyclonal autoantibodies exhibiting both light chain types. Furthermore, CD5+B lymphocytes obtained from the same two CLL patients (DAT+) produce, in vitro understimulation with phorbal myristate acetate (PMA), monoclonal antibodies which react and bind to RBC. Thus these studies provide direct evidence demonstrating that the antibodies causing the autoimmune hemolytic anemia in our two CLL patients are the products of the B-CLL neoplastic clones.

SummaryOwing to the increased central nervous system (CNS) relapse risk in T-cell acute lymphoblastic leukaemia (ALL), it is unclear whether preventive cranial radiation (pCRT) can be safely omitted. In this study, pCRT was replaced by extended triple intrathecal therapy (TIT) in prednisone good early responders -medium-risk (MR) group, accounting for 76% of T-ALL patients. From 1989 to 2003, 143 T-ALL patients aged 1-18 years were enrolled in the Israel National Studies (INS) 89 (n = 84) and INS 98 (n = 59) trials, based on ALL-Berlin-Frankfurt-Munster (BFM) 86/90 and ALL-BFM 95 protocols, respectively. Five-year event-free survival (EFS) of the MR group in the INS 89 (n = 60) was 70 ± 5AE9% and the INS 98 (n = 43), 83AE7 ± 5AE6% (P = 0AE12); the cumulative incidence (CI) of any CNS relapse was 5AE0 ± 2AE8% and 2AE3 ± 2AE3% (P = 0AE50), respectively. There was no difference in outcome between MR patients with a white blood cell count (WBC) ‡100 · 10 9 /l treated with extended TIT (n = 17) or pCRT (n = 10).For all T-ALL patients, 5-year EFS was 61AE9 ± 5AE3% in INS 89 and 72AE9 ± 5AE8% in INS 98, (P = 0AE21); the CI of any CNS relapse was 7AE1 ± 2AE8% and 1AE7 ± 1AE7% (P = 0AE142), respectively. Outcome of T-ALL MR patients given extended TIT in the context of BFM-based protocols with long-term follow-up appeared to be comparable to studies in which a larger proportion of patients was irradiated, and was associated with low risk of CNS relapse, regardless of the WBC.

A 30-year-old man presented with an episode of deep vein thrombosis. He was found to have primary antiphospholipid syndrome with anticardiolipin antibodies and protein S deficiency. All other investigations were negative. Three months later, anticardiolipin antibodies were negative and protein S levels were normal. The transient presence of anticardiolipin antibodies and functional protein S deficiency in this patient suggests a new mechanism for the association between anticardiolipin antibodies and venous thrombosis.

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