High-dose cyclophosphamide therapy associated with diffuse alveolar hemorrhage after allogeneic hematopoietic stem cell transplantation

Respiration. 2013;86(6):453-61. doi: 10.1159/000345592. Epub 2012 Dec 29.

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/m(2) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / adverse effects*
  • Case-Control Studies
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects*
  • Dose-Response Relationship, Drug
  • Female
  • Glucocorticoids / therapeutic use
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hemorrhage / etiology*
  • Hemorrhage / therapy
  • Humans
  • Leukemia / therapy
  • Lung Diseases / etiology*
  • Lung Diseases / therapy
  • Male
  • Multivariate Analysis
  • Premedication
  • Pulmonary Alveoli*
  • Respiration, Artificial
  • Retrospective Studies
  • Risk Factors
  • Transplantation, Homologous

Substances

  • Antineoplastic Agents, Alkylating
  • Glucocorticoids
  • Cyclophosphamide