Therapy-related myelodysplasia and/or acute myeloid leukaemia after autologous haematopoietic progenitor cell transplantation in a prospective single centre cohort of 221 patients

Abstract

To evaluate the incidence and the predictive signs of therapy-related myelodysplasia and/or acute myeloid leukaemia (tMDS/tAML), we undertook a prospective study over a 4-year period of 221 patients who underwent autologous haematopoietic progenitor cell transplantation. Only seven patients (3.1%) were identified to have tMDS/tAML. Peripheral cytopenia was the first sign; diagnosis could be achieved by cytological analysis of bone marrow smears using World Health Organization criteria. All patients presented with bi- or trilineage dysplasia. Haematopoietic reconstitution was significantly delayed in patients progressing to tMDS/tAML compared with the control group. Typical cytogenetic abnormalities were observed in five of seven patients. The mean time interval between transplantation and cytological diagnosis, or detection of cytogenetic abnormalities, was 20.0 months and 31.2 months respectively. Pantelomeric fluorescence analysis using quantitative fluorescence in situ hybridization enabled us to make two major observations: (i) the fluorescence intensity in metaphases of all autografted patients was weak, and highly variable between tMDS patients; (ii) a drastic reduction of the telomere fluorescence intensity was observed in two patients who rapidly evolved to acute leukaemia. In conclusion, early detection of tMDS/tAML could be achieved by close follow-up of the bone marrow repopulation, and confirmed by cytological bone marrow examination and cytogenetic study. Our results address the implication of several factors, such as the initial telomeric status, and the effect of cytogenetic abnormalities and clonal expansion on bone marrow repopulation.