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

Patel, Amitkumar; Hahn, Theresa; Bogner, Paul N.; Loud, Peter A.; Brown, Karen; Paplham, Pamela; Syta, Margaret; Battiwalla, Minoo; McCarthy, Philip L.

doi:10.1038/bmt.2009.339

Cited by 11 publications

(9 citation statements)

References 9 publications

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“…More than 80 case reports have shown pulmonary toxicity secondary to sirolimus in adults with SOT but literature is sparse regarding this complication in HCT patients . One case series reported three HCT adult patients who succumbed to diffuse alveolar hemorrhage and respiratory failure thought to be secondary to sirolimus . In addition, literature search at the time of publication found no reports regarding sirolimus‐induced lung disease in pediatric HCT patients and strikingly few cases reported in pediatric SOT recipients .…”

Section: Discussionmentioning

confidence: 99%

Sirolimus‐induced interstitial lung disease following pediatric stem cell transplantation

Garrod

Goyal

Weiner

2015

Pediatric Transplantation

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Sirolimus-induced ILD is a known but rare complication in adults who have undergone SOT. However, little is known about this adverse effect in children. Diagnosis of sirolimus-induced ILD can be challenging, especially in patients who have difficulty participating in lung function testing. We present a case of presumed sirolimus-induced ILD in a pediatric stem cell transplant patient who developed polycythemia and hypoxemia. To our knowledge, no other cases of sirolimus-induced pulmonary toxicity in children after HCT have been reported.

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Section: Discussionmentioning

confidence: 99%

Sirolimus‐induced interstitial lung disease following pediatric stem cell transplantation

Garrod

Goyal

Weiner

2015

Pediatric Transplantation

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“…102 Sirolimus, used for acute GVHD prophylaxis 103 and for primary immunosuppression in active chronic GVHD, causes rare pulmonary toxicities that may be severe and fatal. 104,105 The predominant histologic patterns are organizing pneumonia, pulmonary hemorrhage, diffuse alveolar damage, and in a minority of cases pulmonary alveolar proteinosis. 104,106 The mainstay of treatment is discontinuation of the drug with or without corticosteroids (1 mg/kg/d), which typically results in complete resolution of symptoms within 2 to 4 months.…”

Section: Drugs With Known Toxicities In Hematopoietic Cell Transplantmentioning

confidence: 99%

Early Onset Noninfectious Pulmonary Syndromes after Hematopoietic Cell Transplantation

Vusse

Madtes

2017

Clinics in Chest Medicine

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This article reviews the noninfectious pulmonary syndromes that cause morbidity and mortality early after hematopoietic cell transplantation with an emphasis on risk factors, clinical manifestations, treatment, and outcomes. The first section covers idiopathic pneumonia syndrome and its subtypes: peri-engraftment respiratory distress syndrome, diffuse alveolar hemorrhage, delayed pulmonary toxicity syndrome, and cryptogenic organizing pneumonia. The second section covers pulmonary toxicities of chemotherapies and immunosuppressive agents used in this setting. The final section covers less common syndromes, including pulmonary alveolar proteinosis, venous thromboembolism, pulmonary cytolytic thrombi, pulmonary venoocclusive disease, and transfusion-related acute lung injury.

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“…Additionally, renal transplant data have confirmed lower rates of nephrotoxicity with sirolimus [23]. Still, sirolimus has disadvantages, such as it can only be given orally and can cause pulmonary toxicity [24–26]. Here, sirolimus was well tolerated, with only 2 patients experiencing significant side effects, both with recovery after discontinuing the drug.…”

Section: Discussionmentioning

confidence: 99%

Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide Using Non–First-Degree Related Donors

Elmariah

Kasamon

Zahurak

et al. 2018

Biology of Blood and Marrow Transplantation

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Outcomes of nonmyeloablative (NMA) haploidentical (haplo) blood or marrow transplant (BMT) with post-transplantation cyclophosphamide (PTCy) using non-first-degree relatives are unknown. We evaluated 33 consecutive adult patients (median age, 56 years) with hematologic malignancies who underwent NMA haplo T cell-replete BMT with PTCy at Johns Hopkins using second- or third-degree related donors. Donors consisted of 10 nieces (30%), 9 nephews (27%), 7 first cousins (21%), 5 grandchildren (15%), and 2 uncles (6%). Thirty-one patients (94%) reached full donor chimerism by day 60. The estimated cumulative incidence (CuI) of grades II to IV acute graft-versus-host disease (aGVHD) at day 180 was 24% (90% confidence interval [CI], 9% to 38%). Only 1 patient experienced grades III to IV aGVHD. At 1 year the CuI of chronic GVHD was 10% (90% CI, 0% to 21%). The CuI of nonrelapse mortality at 1 year was 5% (90% CI, 0% to 14%). At 1 year the probability of relapse was 31% (90% CI, 12% to 49%), progression-free survival 64% (90% CI, 48% to 86%), and overall survival 95% (90% CI, 87% to 100%). The 1-year probability of GVHD-free, relapse-free survival was 57% (90% CI, 41% to 79%). NMA haplo BMT with PTCy from non-first-degree relatives is an acceptably safe and effective alternative donor platform, with results similar to those seen with first-degree relatives.

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

Cited by 11 publications

References 9 publications

Sirolimus‐induced interstitial lung disease following pediatric stem cell transplantation

Sirolimus‐induced interstitial lung disease following pediatric stem cell transplantation

Early Onset Noninfectious Pulmonary Syndromes after Hematopoietic Cell Transplantation

Haploidentical Bone Marrow Transplantation with Post-Transplant Cyclophosphamide Using Non–First-Degree Related Donors

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