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Fatal diffuse alveolar hemorrhage associated with sirolimus after allogeneic hematopoietic cell transplantation

Bone Marrow Transplantation volume 45, pages 1363–1364 (2010)Cite this article

Sirolimus (SRL) inhibits the mammalian target of rapamycin, a cell proliferation protein kinase, resulting in inhibition of T- and B-cell activation.1 SRL is not nephrotoxic and is an alternative to calcineurin inhibitors for prophylaxis and treatment of graft rejection after solid organ transplantation (SOT), and of GVHD after allogeneic hematopoietic cell transplantation (alloHCT).2 The side effects of SRL include myelosuppression, hypertension, hyperlipidemia, glucose intolerance and infection.1 SRL can cause seven distinct and uncommon pulmonary toxicities during SOT, including diffuse alveolar hemorrhage (DAH).3 We report three cases of fatal lung toxicity in alloHCT patients receiving SRL.

Case 3, a 41-year-old woman, underwent HLA-matched sibling alloHCT after BU/CY conditioning in 2007 for AML. Her past medical history included mild obstructive pulmonary disease and a 25 pack-year smoking history. She developed significant acute and chronic GVHD despite tacrolimus and MMF prophylaxis, and was treated with methylprednisolone, anti-thymocyte globulin, Etanercept and Rituximab without improvement. SRL (0.2 mg orally daily) was administered, but she developed hypoxia and extensive bilateral airspace disease. She had continued respiratory failure and died 7 days after SRL cessation. Autopsy revealed bronchopneumonia, alveolar membrane formation, fibrosis and hemorrhage.

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Author notes

  1. A V Patel

    Present address: Arizona Cancer Center, Tucson, AZ, USA,

Authors and Affiliations

  1. Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA

    A V Patel, T Hahn, K Brown, P Paplham, M Syta, M Battiwalla & P L McCarthy

  2. Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY, USA

    P N Bogner

  3. Department of Radiology, Roswell Park Cancer Institute, Buffalo, NY, USA

    P A Loud

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  1. A V Patel
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Correspondence to P L McCarthy.

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Patel, A., Hahn, T., Bogner, P. et al. Fatal diffuse alveolar hemorrhage associated with sirolimus after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 45, 1363–1364 (2010). https://doi.org/10.1038/bmt.2009.339

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