High-Dose Cyclophosphamide Therapy Associated with Diffuse Alveolar Hemorrhage after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Background: The occurrence of diffuse alveolar hemorrhage (DAH) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rare but severe. There are few reports that have examined the correlation between pre-HSCT chemotherapeutic exposure and DAH. Objectives: We examine the role of pre-HSCT chemotherapeutic exposure, conditioning regimens, pre-HSCT comorbidities and transplant-related complications in the development of DAH after allo-HSCT and evaluate the effect of the high-dose corticosteroid strategy on DAH. Methods: A retrospective nested case-control study was designed. Cases with DAH and controls matched for year of allo-HSCT and length of follow-up were identified from a cohort of 597 patients who underwent allo-HSCT between 2006 and 2011 for acute leukemia. Results: Twenty-two patients suffered from DAH; the mean age at the time of presentation was 30.4 years (±12.9) and the mean time to presentation was 7.8 months (±8.1) post-HSCT. The pre-HSCT cyclophosphamide exposure and the cumulative cyclophosphamide dose were significantly higher among the DAH cases compared with the controls, and the cumulative cyclophosphamide dose of ≥5 g/m² was independently associated with DAH (OR = 3.4, p = 0.030). High-dose corticosteroid treatment did not significantly improve survival. Conclusions: From these results we can identify patients who are at a higher risk of developing DAH after allo-HSCT, and we found that high-dose corticosteroid therapy may not alter the poor outcome associated with this syndrome.