Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients.

To comparatively assess first-line treatment with fludarabine and 2 anthracycline-containing regimens, namely CAP (cyclophosphamide, doxorubicin plus prednisone) and ChOP (cyclophosphamide, vincristine, prednisone plus doxorubicin), in advanced stages of chronic lymphocytic leukemia (CLL), previously untreated patients with stage B or C CLL were randomly allocated to receive 6 monthly courses of either ChOP, CAP, or fludarabine (FAMP), stratified based on the Binet stages. End points were overall survival, treatment response, and tolerance. From June 1, 1990 to April 15, 1998, 938 patients (651 stage B and 287 stage C) were randomized in 73 centers. Compared to ChOP and FAMP, CAP induced lower overall remission rates (58.2%; ChOP, 71.5%; FAMP; 71.1%; P <.0001 for each), including lower clinical remission rates (CAP, 15.2%; ChOP, 29.6%; FAMP, 40.1%; P =.003). By contrast, median survival time did not differ significantly according to randomization (67, 70, and 69 months in the ChOP, CAP, and FAMP groups, respectively). Incidences of infections (< 5%) and autoimmune hemolytic anemia (< 2%) during the 6 courses were similar in the randomized groups, whereas fludarabine induced, compared to ChOP and CAP, more frequent protracted thrombocytopenia (P =.003) and less frequent nausea-vomiting (P =.003) and hair loss (P <.0001). For patients with stage B and C CLL first-line fludarabine and ChOP regimens both provided similar overall survival and close response rates, and better results than CAP. However, there was an increase in clinical remission rate and a trend toward a better tolerance of fludarabine over ChOP that may influence the choice between these regimens as front-line treatments in patients with CLL.

[Hemiplegia and contralateral multiple aseptic osteonecrosis]. / Hémiplégie et ostéonécroses aseptiques multiples controlatérales.

A patient who received treatment for acute myelogenous leukemia (chemotherapy, irradiation, corticosteroid therapy) developed cerebral radionecrosis with hemiplegia (treated by corticosteroids) then multiple foci of osteonecrosis on the nonparalyzed side. The mechanisms which may have prevented osteonecrosis from occurring on the side of the hemiplegia are discussed.

Effects of cryopreservation on the adherent layer of human long-term bone marrow cultures: study of cell phenotypes.

This report describes the effects of cryopreservation on the adherent layer of human long-term bone marrow cultures (HLTBMC). Stromal cells are believed to be the most important cells of medullar microenvironment to regulate hematopoiesis. To study effects of cryopreservation, we compared the cell phenotypes of adherent layers of fresh and frozen-thawed bone marrows. To characterize stromal cells we used monoclonal antibodies reacting with components of these cells (CGA-7 alpha SM and gamma SM actin isoforms; HHF-35, all muscle actin isoforms; BMS-1, stromal cell lysosomes). The other components studied were: fibronectin (BMS-2 monoclonal antibody) and hematopoietic cells (monoclonal antibodies against CD45, CD33, and CD14). Results show a decrease of cells positive for CGA-7, HHF-35, and BMS-1, in adherent layer of HLTBMC of frozen-thawed bone marrows. Expression of BMS-2 is unchanged, and CD45 and CD14-positive cells proportionately increased. These results are consistent with an impairment of stromal cell proliferation in frozen-thawed marrows, without impairment of most stromal cell functions. The difference between stromal cell and hematopoietic cell kinetics seems to be an additional fact suggesting a different origin for both cell populations.

HIV-associated thrombocytopenia: in vitro megakaryocyte colony formation in 10 patients.

In vitro bone-marrow megakaryocyte colony formation was studied in 10 patients with HIV-associated thrombocytopenia to investigate the mechanism of thrombocytopenia. Increased colony formation was observed in 3 patients and decreased growth in 7 patients. No relationship was noted between the growth potential of megakaryocyte progenitors and platelet count, number of CD4+ celts, platelet response to azidothymidine, and platelet count 7 days after culture. In all patients, megakaryocyte morphology was abnormal: blebbing of the membrane and abnormal chromatin with separated lobes of nuclei. Further studies are needed to determine if growth potential of megakaryocyte progenitors is useful in understanding the mechanism of thrombocytopenia in HIV-infected individuals.

In vitro megakaryocyte colony formation in patients with idiopathic thrombocytopenic purpura: differences between acute and chronic ITP.

In vitro megakaryocyte colony formation from the bone marrow of patients with acute idiopathic thrombocytopenic purpura (ITP) or chronic ITP was compared using a plasma clot system. The number of megakaryocyte colony-forming units (CFU-Meg) was significantly higher (p less than 0.05) in acute ITP compared to chronic ITP (54.3 +/- 68.4 vs. 12.9 +/- 15.3/10(5) nonadherent mononuclear cells, mean +/- SD), and significantly lower (p less than 0.05) in chronic ITP compared to controls (12.9 +/- 15.3 vs. 22.8 +/- 15.9). A significant correlation was observed between platelet recovery 7 and 30 days after culture, and the number of CFU-Meg (r = 0.49 and 0.45, respectively, p less than 0.05). An inverse correlation was observed between platelet count at the time of culture and the number of Megs per colony (r = -0.48, p less than 0.05). These results indicated a difference between acute and chronic ITP in the ability to promote in vitro Meg colony formation and may suppose a different immune mechanism for thrombocytopenia in these two disorders.

Spontaneous in vitro megakaryocyte colony formation in primary thrombocythemia: relation to platelet factor 4 plasma level and beta-thromboglobulin/platelet factor 4 ratio.

Seventeen patients with primary thrombocythemia (PT) were evaluated for in vitro bone marrow megakaryocyte progenitors (CFU-MK) using a plasma clot system. The aim of this study was to find out whether spontaneous growth of CFU-MK could be used in the diagnosis of PT. The number of CFU-MK was normal in 7 patients and reduced in 10 patients. In the absence of stimulating factor, CFU-MK grew spontaneously in 12 patients, while in 5 patients no spontaneous CFU-MK were observed. The mean plasma level of platelet factor 4 (PF4) was significantly higher (p less than 0.05) in patients without spontaneous CFU-MK (59.8 +/- 59.6 IU/ml; mean +/- SD) compared to patients with (18.1 +/- 20.7 UI/ml). The mean plasma level of beta-thromboglobulin did not differ between patients with or without spontaneous CFU-MK. The beta-thromboglobulin/PF4 ratio was significantly higher (p less than 0.01) in patients with spontaneous CFU-MK (9.9 +/- 7.1) compared to patients without (3.1 +/- 1.4). These results suggest that PF4 could inhibit in vitro spontaneous growth of CFU-MK.

Carbohydrate composition of human megakaryocyte membranes in culture: identification using binding of seven lectins.

Seven tetramethylrhodamine B isothiocyanate- (TRITC) labeled lectins: lens culinaris (LCH), ulex europeus-1 (UEA-1), lycopersicon esculentum (LEA), wheat germ agglutinin (WGA), dolichos biflorus (DBA), soybean agglutinin (SBA) and erythrina cristagalli (ECA) were applied on cultured human megakaryocytes (Megs) detected by immunofluorescence. All stages of Megs (from lymphocyte-like Megs to mature Megs) and platelets were labeled by LCH, LEA, UEA-1 and WGA. ECA binds to platelets but only to some Megs. DBA did not bind to platelets but did bind to some Megs, irrespective of stage. SBA binds to all stages of Megs, but did not bind to platelets. These results indicate the presence of mannose, glucose (LCH), sialic acid (WGA), and glucosamine (UEA-1, LEA, WGA) on the surface of all cells of the Meg lineage, a variable presence of galactosamine (DBA, SBA, ECA), and a discrepancy in the presence of some galactosamine compounds between platelets and Megs (DBA, SBA).