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Diffuse alveolar hemorrhage: An underreported complication of transplant associated thrombotic microangiopathy

Bone Marrow Transplantation volume 57, pages 889–895 (2022)Cite this article

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Abstract

Hematopoietic stem cell transplantation-associated thrombotic microangiopathy (TA-TMA) and diffuse alveolar hemorrhage (DAH) are well recognized post-transplant complications that carry a high risk of mortality; however, the risk of DAH complicating the course of transplant patients with TA-TMA is not well understood. We conducted a ten-year retrospective study at our institution to determine the incidence of DAH in a cohort of pediatric patients with TA-TMA and described their presentation and outcomes. Additionally, autopsy slides, when available, were reviewed to assess for histological evidence of microvascular injury and alveolar hemorrhages. A total of 58 pediatric patients with TA-TMA were identified. Of these, 14 (24%) had DAH. Majority of DAH cases occurred within a week of TA-TMA diagnosis (n = 8, 57%, range 0-698 days). Mortality was 100% for patients with DAH and TA-TMA. Infections were found to be a significant risk factor for DAH in TA-TMA. Autopsy was performed in 11 of the 14 patients, and pulmonary slides were available for review in ten cases. 70% cases had pathological evidence of microvascular injury, concerning for pulmonary TA-TMA. We conclude that DAH is a potentially fatal complication in patients with TA-TMA and may be a result of pulmonary microangiopathy.

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Fig. 1: Kaplan–Meier curve depicting survival rates in patients with TA-TMA without DAH (dotted line) and TA-TMA with DAH (solid line).
Fig. 2: Pathologic findings at autopsy.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Authors and Affiliations

  1. Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX, USA

    S. Agarwal, M. E. Scheurer & S. E. Sartain

  2. Texas Children’s Cancer and Hematology Center, Texas Children’s Hospital, Houston, TX, USA

    S. Agarwal, S. Bhar, C. Martinez & S. E. Sartain

  3. Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA

    N. Cortes-Santiago

  4. Center for Epidemiology and Population Health, Baylor College of Medicine, Houston, TX, USA

    M. E. Scheurer

  5. Department of Pediatrics, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA

    S. Bhar & C. Martinez

  6. Department of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA

    S. L. McGovern

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  1. S. Agarwal
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  7. S. E. Sartain
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Contributions

SA, SB, CM, and SES were involved in study design, data collection and manuscript writing, and proof reading. NCS reviewed all the autopsy specimens and wrote the autopsy section in results and discussion and SLM reviewed the data regarding radiation therapy. MES helped with statistical analyses.

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Correspondence to S. Agarwal.

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Agarwal, S., Cortes-Santiago, N., Scheurer, M.E. et al. Diffuse alveolar hemorrhage: An underreported complication of transplant associated thrombotic microangiopathy. Bone Marrow Transplant 57, 889–895 (2022). https://doi.org/10.1038/s41409-022-01644-3

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