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The purpose of this study of patients with pancytopenia in Republic of Djibouti was to identify etiologic factors and attempt to define diagnostic and therapeutic strategies adapted to local conditions. Clinical, biological and radiological assessment was performed in 81 patients hospitalized for pancytopenia. There were 56 men and 25 women. Mean hemoglobin, leukocyte and platelet rates were 56,5 +/- 22,7 g/l, 2,1 +/- 0,7.g/l and 56,2 +/- 24,7 g/l respectively. Vitamin deficiency was the most common cause of pancytopenia (49%), followed by hypersplenism (9%), HIV infection (6%) and leishmaniasis (6%). Vitamin-deficient patients had significantly more severe anemia and thrombopenia and significantly higher mean corpuscular volume than patients with pancytopenia related to other causes. Hemoglobin rate lower than 40 g/L and platelet rate lower than 35 G/L showed a positive predictive values of 90% and 100% respectively for a vitamin deficient pancytopenia. Vitamin deficiency is the most frequent etiology of pancytopenia and causes the most severe cytopenia in Djibouti. Rapid vitamin supplementation after minimal etiologic assessment including a myelogram is an effective treatment strategy for this public health problem.

Hematopoietic reconstitution has been studied in 180 patients after autologous bone marrow transplantation based on peripheral blood cell (PBC) recovery time and marrow progenitor counts sequentially tested for up to 4 years. Several factors that could influence hematopoietic reconstitution have been analyzed including sex, age, diagnosis, disease status, conditioning regimen, graft progenitor content, graft in vitro purging, and postgrafting administration of growth factors. Before transplantation, marrow progenitor values were normal only for colony-forming unit granulocyte macrophage (CFU-GM) in contrast to colony-forming unit-erythroid (CFU-E), burst-forming unit-erythroid (BFU-E), and colony-forming unit-megakaryocyte (CFU-Meg). After transplantation, as described with allogenic grafts, these values remained low for several years, although PBC counts were nearly normalized within a few weeks. Pregraft values were reached after 2 years for CFU-GM and BFU-E, and after 4 years for CFU-E, while CFU-Meg failed to reach pregraft values after this time. Normal levels were reached after 4 years only by CFU-GM. On univariate and multivariate analysis, the following factors appeared to delay both PBC and marrow progenitor reconstitution: underlying disease (particularly acute myeloid leukemias), graft characteristics such as low stem cell content and in vitro purging, conditioning regimens with total body irradiation or busulfan, and lack of postgraft administration of growth factors. In conclusion, high-dose therapy followed by bone marrow transplantation induces a deep and prolonged impairment of hematopoiesis irrespective of any alloimmune reaction or postgraft immunosuppressive therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

A study of CFU-GM sensitivity to mafosfamide was carried out in 67 candidates for ABMT. A lethal dose 95 (LD95) was calculated from the dose-response curve. Despite standardized treatment conditions of marrow buffy-coat cells, LD95 values that were normally distributed (median 100 micrograms/ml; mean +/- SEM 95.6 +/- 4.0 micrograms/ml) varied considerably from patient to patient (range 30-160 micrograms/ml). Three independent factors appeared to confer greater sensitivity of CFU-GM: low patient age, low CFU-GM rate in treated cells and prolonged delay of CFU-GM sensitivity test from last chemotherapy course. In contrast, sex, pathology, disease status, number of previous chemotherapies and use of CY before the test did not influence CFU-GM sensitivity. Forty-six patients were autografted with mafosfamide-treated marrows according to their LD95. The mean percentage of CFU-GM effectively recovered after graft purging was 3.96 +/- 2.09%. All patients engrafted well and their peripheral blood cell recoveries were correlated with graft CFU-GM content evaluated before purging but not after purging or after freezing. In multivariate analysis, this parameter remained the only factor predicting hematopoietic recovery among other patient variables such as sex, age, pathology, disease status, previous chemotherapies or TBI in conditioning regimens. In a subgroup of 39 patients with lymphoid malignancies compared with 25 patients autografted for non-Hodgkin's lymphomas with unpurged marrows, the delay in days (medians) was similar for leukocytes1 x 10(9)/l (19 vs 17 days) and for neutrophils0.5 x 10(9)/l (18 vs 17 days) while it was longer for platelets50 x 10(9)/l (34 vs 128 days).(ABSTRACT TRUNCATED AT 250 WORDS)

In an attempt to improve in vitro pharmacological purging of autologous grafts, the ability of doxorubicin (DOX), alone and in combination with mafosfamide (AZ), to eliminate tumor cells from human bone marrow was assessed. HL60 and Raji cells were mixed with a 20-fold excess of normal marrow cells and were incubated either with DOX (0.4-3.2 micrograms/ml) for 1 h or AZ (20-140 micrograms/ml) for 30 min or both drugs sequentially. Cytotoxicity was evaluated on tumor cells and GM-CFU by clonogenic assays and on earlier hemopoietic progenitors by liquid long-term marrow cultures (LTMC) for 5 weeks. DOX at 3.2 micrograms/ml and AZ at 140 micrograms/ml spared 1.08 and 1.23% of GM-CFU respectively, and yielded similar tumor cell log-kills for HL60 cells (3.04 and 2.95) and Raji cells (3.24 and 3.40). With the combination of AZ and DOX, the best therapeutic index was observed when the cells were incubated with AZ prior to DOX. Under these conditions, AZ at 80 micrograms/ml together with DOX at 1.6 micrograms/ml significantly increased log-kill values for HL60 cells to 3.96 by a synergistic effect and for Raji cells to 3.85 by an additive effect. In LTMC, GM-CFU recovery after treatment with AZ alone and with the combination of AZ and DOX was 59.9 and 20.0%, respectively, while it was 7.9 and 2.9% at culture initiation. These results suggest that the purging efficiency of DOX is comparable to that of AZ and may be enhanced by combination with AZ.