Cessation of intensive treatment with recombinant human erythropoietin is followed by secondary anemia.

Little information is available on the evolution of erythropoiesis after interruption of recombinant human erythropoietin (rHuEpo) therapy. Iron-overloaded rats received 20 daily injections of rHuEpo. During treatment, reticulocytes, soluble transferrin receptor (sTfR), and hematocrit increased progressively. This was accompanied by a substantial expansion of spleen erythropoiesis but a decrease in the bone marrow. Five weeks after treatment, rats developed a significant degree of a regenerative anemia. Erythropoietic activity, as assessed by reticulocytes, sTfR, erythroid cellularity, iron incorporation into heme, and the number of erythroid colonies, was severely depressed 3 weeks after cessation of rHuEpo. This was followed by regeneration of erythroblasts and reticulocytes at weeks 6 to 7 post-Epo, but erythroid progenitors recovered only partially by that time. The anemia was definitely corrected 2 months after cessation of rHuEpo treatment. Serum Epo levels remained elevated for several weeks, but the sensitivity of marrow erythroid precursors to Epo was preserved. No rat antibodies to rHuEpo were detected, and serum from post-Epo animals did not exert any inhibitory activity on erythropoiesis. In conclusion, after cessation of intensive rHuEpo therapy, there was a strong inhibition of erythropoietic activity with secondary anemia followed by late recovery. This was not due to antibodies or other soluble inhibitory factors, a defect in endogenous Epo production, or a loss of sensitivity to Epo. This may rather represent intrinsic erythroid marrow exhaustion, mostly at the level of erythroid progenitors but also at later stages of erythropoiesis.

Deletion of the 5'-ABL region: a recurrent anomaly detected by fluorescence in situ hybridization in about 10% of Philadelphia-positive chronic myeloid leukaemia patients.

Inclusion of the BCR-ABL ES probe in routine cytogenetics led to the identification of a subgroup of Philadelphia positive (Ph+) chronic myeloid leukaemia patients characterized by a 5'-ABL deletion. This anomaly was observed in 5/51 cases (9.8%). Cytological and clinical data suggest that the 5'-ABL deletion may be associated with dysplastic features of polymorphonuclear cells and metamyelocytes and a short chronic phase duration.

A four-parameter index of marrow dysplasia has predictive value for survival in myelodysplastic syndromes.

Marrow dysplasia is a major characteristic of patients with myelodysplastic syndrome (MDS), along with marrow blastosis, cytopenia and cytogenetic anomalies. However, the impact of the degree of marrow dysplasia on survival has not been fully assessed. In this retrospective analysis of 111 patients selected according to the IPSS criteria of MDS diagnosis, the presence or absence of 21 dysplasia characteristics recognizable in bone marrow smears stained by the May-Grünwald-Giemsa method was correlated with patient survival. Using Cox proportional hazards regression analysis, megaloblastosis (MEGALO), neutrophil agranularity (AGRAN) and hypogranularity (HYPOGRAN) were highly significant predictors (p < 0.005), and Pelger-Huët anomaly (PELGHUET) a significant predictor (p = 0.05), of patient survival. The regression analysis yielded a dysplasia-based risk index (DI) where DI = 1.26 MEGALO + 0.82 AGRAN - 1.08 HYPOGRAN + 0.45 PELGHUET. The two subgroups of 60 and 47 patients with DI < or = 0 and > 0 showed highly significant differences in median survivals (2.6 vs 1.1 yrs; p <0.0001). Multivariate analysis further showed that DI offered additional predictive power that was independent of that provided by the IPSS (p=0.002 and 0.001 respectively). Analysis of survival curves stratified for IPSS and DI showed that the additional predictive power offered by inclusion of the DI essentially concerned the IPSS low/INT-1 risk categories. Further stratification for age did not improve survival prediction. The data indicate that a set of 4 dysplasia parameters can offer some prediction for survival of MDS patients in addition to that provided by the IPSS. Further multicenter studies should aim at including some form of evaluation of the degree of dysplasia in prognostic systems.

Translocation (2;3)(p21;q26) as the sole anomaly in a case of primary myelofibrosis.

Translocation t(2p;3q) is a rare but recurrent finding in myeloid disorders. We present the first case of primary myelofibrosis with t(2;3)(p21;q26) as the sole chromosomal anomaly. The comparison with the 11 other previously published myeloid-associated t(2p;3q) cases confirms that this nonrandom translocation involves a pluripotent stem cell and is associated with a poor prognosis.

[Myelodysplastic syndromes: preleukemic syndromes]. / Les syndromes myélodysplasiques: syndromes préleucémiques.

The myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by peripheral blood cytopenias with a hypercellular bone marrow exhibiting dyspoiesis. The predominant in elderly patients are associated with a high risk of progression to acute myelogenous leukemia. The etiology of MDS is unknown in most cases. About 10% of MDSs are secondary. MDS are classified by the French American British (FAB) classification into five subgroups. The incidence of the disorders is difficult to estimate but it seems to be increasing. Clonal cytogenetic aberrations are found in 30 to 50% of de novo MDS. The only currative treatment for MDS is allogeneic bone marrow transplantation.