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• W2018341710 abstract "Severe aplastic anaemia (SAA) causes permanent stem cell damage from which patients do not recover after treatment with antilymphocyte globulin (ALG). To produce peripheral blood values compatible with life, the few remaining stem and precursor cells are put under stress. We defined a 'stress factor' (SF) for various haematopoietic lines as the ratio of the corresponding peripheral blood (PB) value to the total colony number in short-term bone marrow cultures from 86 patients with different outcomes. Both values are expressed as percentage of normal, hence SF averages 1 in normal steady-state haematopoiesis. SF was elevated in all patients, from 2-to 40-fold, with wide variations in different patient groups and striking differences between haematopoietic lineages. In long-term disease-free survivors after ALG (group 1) the mean total colony count was 19% of normal, with a significantly higher proportion of erythroid burst-forming units compared to normal. They had ineffective erythropoiesis with haemoglobin (Hb) values below, and reticulocyte counts above normal; platelet counts were 67% of normal. In contrast, monocyte counts were in the high normal range, resulting in a high SF (18.7 +/- 1.9) for monocytes. In patients who developed paroxysmal nocturnal haemoglobinuria (PNH) after ALG (group 2), ineffective erythropoiesis, reflecting haemolysis, was more pronounced and they had striking relative monocytosis, resulting in a significantly higher SF for monocytes (33.7 +/- 5.7) compared with group 1 (p < 0.0001). High monocyte counts most likely reflect the relative resistance of nucleated cells to complement, compared with red cells and platelets. Patients who developed myelodysplastic syndrome (MDS) or acute myeloid leukaemia (AML) after ALG, with or without PNH (group 3), had the highest SF for monocytes (39 +/- 10). They also had neutrophil counts in the upper range, or above normal, resulting in a high SF for neutrophils: 32 +/- 19. In patients with persisting or relapsing-remitting pancytopenia without a clinically detectable clonal disorder (group 4), all values were strikingly similar to those of the PNH group. In patients who achieved normal PB values after uncomplicated bone marrow transplantation (group 5), the SF averaged 3, but they also had ineffective erythropoiesis and mild relative monocytosis, a possible sign of occult PNH. We conclude that all patients after treatment of SAA have ineffective erythropoiesis and relative monocytosis, and that these abnormalities probably reflect PNH. We suggest that the resulting high SF for the leukocyte - particularly the monocyte line - predisposes to the development of MDS/AML. We discuss how these results may provide some of the missing pieces in the puzzle of SAA/PNH." @default.
• W2018341710 created "2016-06-24" @default.
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• W2018341710 date "2000-01-01" @default.
• W2018341710 modified "2023-09-26" @default.
• W2018341710 title "Cell Cycling Stress in the Monocyte Line as a Risk Factor for Progression of the Aplastic Anaemia/Paroxysmal Nocturnal Haemoglobinuria Syndrome to Myelodysplastic Syndrome" @default.
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• W2018341710 doi "https://doi.org/10.1159/000041002" @default.
• W2018341710 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10705157" @default.
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