[Azathioprine-associated myelodysplastic syndrome with cytogenetic aberrations].
METHODS
A 49-years-old female with a history of multiple sclerosis and on medication with azathioprine over 5 years amounting to a cumulative dosage of 45 g presented with fatigue and sinus tachycardia.


METHODS
Haematological analysis revealed a pancytopenia with a sustained normochromic anemia (hemoglobin 6,2 g/dl), a mild leukopenia (leucocytes 3500/ microl) and thrombocytopenia (platelets 22000/ microl) requiring platelet substitution. Bone marrow aspirate revealed a dysplasia of all three lineages with reduced thrombopoiesis and ineffective erythropoiesis. Cytogenetic analysis detected a complex aberrant clone including loss of the critically deleted regions in 5q31 and 7q31, as well as structural changes of 12p. The diagnosis was refractory cytopenia with multilineage dysplasia according to the WHO classification of myelodysplastic syndromes.


METHODS
While allogeneic sibling transplantation was planned the patient developed spontaneous recurrent subdural haematoma and died due to persistent bleeding refractory to platelet substitution.


CONCLUSIONS
Treatment with azathioprine may - depending on its cumulative dosage - lead to pancytopenia and subsequent development of myelodysplasia or secondary leukaemia, respectively. Complex genetic alterations involving chromosome 7 are characteristic. Long-lasting treatment with azathioprine needs critical assessment.
Willerding-Möllmann
S
S
Medizinische Klinik II, St. Bernward Krankenhaus Hildesheim.
Wilkens
L
L
Schlegelberger
B
B
Kaiser
U
U
D000740:Anemia / Q000139:chemically induced; D001379:Azathioprine / Q000008:administration & dosage / Q000009:adverse effects*; D001853:Bone Marrow / Q000473:pathology; D001856:Bone Marrow Examination; D002869:Chromosome Aberrations / Q000139:chemically induced*; D002895:Chromosomes, Human, Pair 5 / Q000187:drug effects*; D002897:Chromosomes, Human, Pair 7 / Q000187:drug effects*; D017809:Fatal Outcome; D005221:Fatigue; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000188:drug therapy; D009190:Myelodysplastic Syndromes / Q000139:chemically induced* / Q000235:genetics; D010198:Pancytopenia / Q000139:chemically induced; D013616:Tachycardia, Sinus
D007166:Immunosuppressive Agents; D001379:Azathioprine