Azathioprine induced myelosuppression in renal transplant recipients: A study of 30 patients

Summary: Administration of azathioprine (Aza) to renal transplant recipients is not infrequently complicated by myelosuppression, but most studies have evaluated only the effects of short‐term administration of the drug. There is a lack of data on the frequency and outcome of myelosuppression after long‐term administration of Aza. In a retrospective analysis of 210 live related renal transplant recipients on azathioprine, a total of 33 episodes of myelosuppression were encountered in 30 (14.3%) patients. Myelosuppression occurred 2 weeks to 67 months (mean 16.8 ± 16.7 months) after starting Aza therapy. Whereas 30.3% of the episodes were noted within 2 months of starting Ma, 69.7% developed after this period. Leucopenia (n= 31) was the most frequent finding, followed by anaemia (n= 18) and thrombocytopenia (n= 16). There were 12 episodes of pancytopenia and one patient developed pure red cell aplasia. Bone marrow examination (n= 12) revealed hypocellularity and moderate megaloblastosis. A higher cumulative dose of Aza was associated with more prolonged myelosuppression. Following discontinuation of Aza, 20 patients recovered after periods varying from 2 weeks to 9 months (mean 2.6 ± 2.4 months). In three patients, myelosuppression persisted for over 12 months and was presumably irreversible. Seven patients died within 2 months of development of myelosuppression. Presence of pancytopenia, a total leucocyte count less than 2000/mm3 and graft dysfunction predicted a fatal outcome. Reinstitution of Aza in a lower dose was followed by a second episode of myelosuppression in three out of 12 (25%) patients. We conclude that a high cumulative Aza dose increases the risk of development of prolonged myelo suppression. Development of irreversible myelosuppression, as noted in three patients, has not been reported previously. Reinstitution of Aza should preferably be avoided in patients who have recovered from an episode. of prolonged myelosuppression.