Outcome of high-dose cytarabine-based induction therapy followed by hematopoietic stem cell transplantation in acute myeloid leukemia: influence of karyotype.

One-hundred-twenty consecutive adult patients aged 15-69 years (median 40) with acute myeloid leukemia (AML) excluding t(15;17) received induction therapy comprising idarubicin, high-dose cytarabine and etoposide. Planned post-induction treatment included two courses of moderate-intensity consolidation therapy followed by stem cell transplantation. 11 patients (9%) died during induction therapy. The complete remission (CR) rate with a single cycle of induction therapy was 71%. The overall CR rate, after salvage chemotherapy but excluding allogeneic transplantation for primary refractory disease, was 82%. CR rates with one cycle of therapy for patients with good, intermediate and poor karyotype were 96, 72 and 41%, respectively (P<0.0001). The impact of karyotype on the overall CR rate was also significant (96 vs. 88 vs. 59%; P=0.001). Overall, 84 of 98 patients (86%) attaining CR underwent autologous (n=59), allogeneic (n=23) or syngeneic (n=2) hematopoietic stem cell transplantation in first CR. The 5-year overall survival (OS) of 43% (95% CI: 34-52%) was significantly influenced by the karyotype: good 73%, intermediate 41%, and poor 18% (P=0.0001). These data suggest that the sequence of therapy employed is active in AML, but additional steps are needed to improve the outcome of patients with intermediate- and high-risk cytogenetic abnormalities.

Prognostic features of splenic lymphoma with villous lymphocytes: a report on 129 patients.

Splenic lymphoma with villous lymphocytes (SLVL) is a low-grade B-cell lymphoma defined in the World Health Organization classification as the leukaemic form of splenic marginal zone lymphoma. Presenting features and response to therapy have been described, but information on prognostic factors is scanty. Clinical, laboratory and follow-up data were collected on 129 patients with SLVL to determine features predicting disease behaviour and survival. Diagnosis was made on clinical, morphological and immunophenotypic features and, where available, bone marrow and spleen histology. Median age was 69 years (range 39-90 years) and male:female ratio, 0.9. The majority had splenomegaly, but lymphadenopathy and hepatomegaly were rare. Median Hb was 11.8 g/dl, white blood cell count was 16 x 10(9)/l and platelet count was 145 x 10(9)/l; 27% of patients had monoclonal protein in serum and/or urine. While 27% of patients remained untreated, 10% transformed to high-grade lymphoma. Median follow-up was 61 months and median survival was 13 years, with 72% of patients alive at 5 years. Cox regression analysis showed that increasing age, anaemia, thrombocytopenia and lymphocytosis > 16 x 10(9)/l were independent adverse predictors of overall survival. However, only anaemia and lymphocytosis > 16 x 10(9)/l remained highly significant independent prognostic factors when only deaths due to lymphoma were analysed. Splenectomized patients fared better than those receiving chemotherapy only (P = 0.001 for SLVL deaths). We conclude that SLVL is mainly a disease of the elderly with a relatively benign course but, when treatment is required, splenectomy is beneficial.

Incidence of MLL rearrangement in acute myeloid leukemia, and a CALM-AF10 fusion in M4 type acute myeloblastic leukemia.

To determine the incidence of the mixed lineage leukemia (MLL) gene rearrangements in acute myeloid leukemia (AML) without cytogenetically-detected 11q23 abnormalities, we screened 64 cases of AML at diagnosis for MLL rearrangement by FISH. Three cases (4.7%) had a MLL rearrangement detected; one was shown to have a cryptic t(11;22)(q23;q11) and another to have a t(9;11)(p21-22;q23) which had been missed by the conventional cytogenetic study. No 11q23 structural abnormality was visible in the third case. Twenty-six of the 64 cases were further studied by Southern blotting and DNA hybridization, and four of these cases (15%) were found to have MLL rearrangement: in three of these, FISH had not detected any abnormality. FISH was also used to confirm MLL involvement in eight cases of AML that had a cytogenetic abnormality at 11q23; in one of these, Southern blot did not show a rearrangement. The survival of patients with MLL abnormalities identified by cytogenetics, FISH and/or DNA analysis was significantly worse than that of patients without MLL abnormalities (event-free survival p = 0.016) although two patients with a t(9;11)(p21-22;q23) were long-term survivors, consistent with this particular translocation having a better prognosis. One further case with a cytogenetic abnormality close to 11q23 was studied; it was found to have a t(10;11)(p13;q21), and the breakpoints were shown by FISH to involve the Clathrin Assembly Lymphoid Myeloid (CALM) gene at 11q21 and the AF10 gene at 10p13. Our data confirm the value of combining cytogenetic, FISH and molecular analyses to define the incidence and precise nature of MLL and 11q23 abnormalities in AML.