R. De Bock

A myelodysplastic syndrome preceding acute lymphoblastic leukaemia

The bone marrow of a patient with pancytopenia showed dyserythro‐poiesis, dysmegakaryocytopoiesis and 13% blasts. The patient was hypertransfused and the pancytopenia resolved completely for 1 month, while the blastic infiltration in the bone marrow remained. Three months later a frank acute lymphoblastic leukaemia developed.

Clinical trial of low-dose Ara-C in the treatment of acute leukemia and myelodysplasia.

SummaryIn a multicenter analysis, the effect of low-dose cytosine arabinoside (Ara-C) (10 mg/m2 q 12 h subcutaneously for a minimum of 15 days) has been assessed in 13 patients with acute leukemia (10 myeloid -AML-, 3 lymphocytic -ALL-) and 7 patients with dysmyelopoietic syndromes (DMPS), conditions classified as refractory anemia with an excess of blasts (RAEB). Seven patients suffering from acute leukemia and 1 with DMPS in blastic transformation displayed a leukocytosis of more than 10×109/1. Three out of 7 DMPS, 1 out of 10 AML achieved a complete remission, 1 out of 3 ALL-patients reached a partial remission twice. Seven patients showed a blast clearing in the bone marrow and peripheral blood, in another 7 instances examination of the bone marrow was not performed after therapy because of early death. The majority of patients were in their late phase of disease and refractory to conventional chemotherapy. Only 5 patients had no pretreatment at first presentation before low-dose Ara-C was initiated. At least for the DMPS-group, this therapeutic approach seems to be of some benefit.

Dexamethasone compared to prednisolone for adults with acute lymphoblastic leukemia or lymphoblastic lymphoma: final results of the ALL-4 randomized, phase III trial of the EORTC Leukemia Group

Background Corticosteroids are a standard component of the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. Our aim was to determine whether dexamethasone results in a better outcome than prednisolone. Design and Methods Adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma were randomized to receive, as part of their induction therapy on days 1–8 and 15–22, either dexamethasone 8 mg/m2 or prednisolone 60 mg/m2. Those who reached complete remission were given two courses of consolidation therapy with high-dose cytarabine and mitoxantrone and methotrexate and asparaginase. Subsequently patients younger than 50 years, with a suitable donor, were to undergo allogeneic stem cell transplantation, whereas the others were planned to receive either an autologous stem cell transplant or high-dose maintenance chemotherapy with prophylactic central nervous system irradiation. Randomization was done with a minimization technique. The primary endpoint was event-free survival and the analyses was conducted on an intention-to-treat basis. Results Between August 1995 and October 2003, 325 patients between 15 to 72 years of age were randomized to receive either dexamethasone (163 patients) or prednisolone (162 patients). After induction and the course of first consolidation therapy, 131 (80.4%) patients in the dexamethasone group and 124 (76.5%) in the prednisolone group achieved complete remission. No significant difference was observed between the two treatment groups with regards to 6-year event-free survival rates (±SE) which were 25.9% (3.6%) and 28.7% (3.5%) in the dexamethasone and prednisolone groups, respectively (P=0.82, hazard ratio 0.97; 95% confidence interval, 0.75–1.25). Disease-free survival after complete remission was also similar in the dexamethasone and prednisolone groups, the 6-year rates being 32.3% and 37.5%, respectively (hazard ratio 1.03; 95% confidence interval 0.76–1.40). The 6-year cumulative incidences of relapse were 49.8% and 53.5% (Gray’s test: P=0.30) while the 6-year cumulative incidences of death were 18% and 9% (Gray’s test: P=0.07). Conclusions In the ALL-4 trial in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma, treatment with dexamethasone did not show any advantage over treatment with prednisolone.

Flow cytometric analysis of T-lymphocyte subpopulations in B-cell chronic lymphocytic leukemia: Correlation with clinical stage

SummarySeveral authors have studied the T-lymphocyte subpopulations in B-cell chronic lymphocytic leukemia (B-CLL), but previous studies were performed after preceding enrichment procedures, which are known to cause selective losses of certain subpopulations. To correct for this deficiency we used flow cytometric analysis, which enabled us to measure subpopulations directly on total blood samples. We studied T-lymphocyte subsets with OKT monoclonal antibodies in 45 patients with B-CLL. Serum levels of IgG, IgA and IgM were assayed simultaneously and findings were correlated with clinical stage (Rai classification). The absolute number of CD 4-positive cells decreased in more advanced Rai stages, while the absolute number of CD 8-positive cells increased, resulting in a progressive reduction in CD 4/8 ratio. Results from patients in stages with equal prognosis (Rai I and II, Rai III and IV) were similar and when these results were grouped the observed differences were highly significant and clearly correlated with all prognostic groups.

Hypoplastic acute leukemia: description of eight cases and search for hematopoietic inhibiting activity

SummaryHypoplastic acute leukemia (HAL) is characterized by pancytopenia and by hypocellularity of the bone marrow. The marrow contains equal to or more than 30% myeloblasts. Absence of tissue infiltrates and/or tumor masses is mandatory. Eight patients are described here. They do not fit into the FAB classification for either acute nonlymphocytic leukemia (ANLL) or myelodysplastic syndrome (MDS), except for one patient who subsequently proved to have a chronic myelomonocytic leukemia (CMML). The median age is 65 years. Two patients, including the CMML patient, are alive, 22 and 6 months from diagnosis. Six patients have died. The median survival is 8 months. Normal bone marrow cells cultured either with HAL sera or with HAL peripheral blood mononuclear cells as feeders and exogenous GMCSF yielded subnormal CFU-GM counts. This might indicate inhibitory activity of HAL serum and defective stimulatory activity of HAL peripheral blood mononuclear cells.

Cytogenetic and DNA-flow cytometric studies of separated blasts

With Percoll density gradients, blasts from peripheral blood and bone marrow could be separated with a significant enrichment, and very often with a high degree of purity. This allowed a study of selected cases, where the separated sample exhibited chromosome abnormalities and/or an abnormal DNA content distribution (as measured by DNA-flow cytometry). The anomalies were shown to be associated with the separated blast fraction.