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Azithromycin may increase hematologic relapse rates in matched unrelated donor hematopoietic cell transplant recipients who receive anti-thymocyte globulin, but not in most other recipients

Bone Marrow Transplantation volume 56, pages 745–748 (2021)Cite this article

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Chronic GVHD (cGVHD) of the lung after hematopoietic cell transplant (HCT) typically manifests as bronchiolitis obliterans syndrome (BOS), and is associated with high mortality [1]. Azithromycin is a macrolide antibiotic with anti-inflammatory properties that improves pulmonary outcomes after lung transplantation [2]. Treatment with a combination of fluticasone, azithromycin, and montelukast (FAM) can reduce the rate of pulmonary impairment in HCT recipients with BOS [3]. However, pulmonary impairment after a diagnosis of BOS is often irreversible, highlighting the need to treat BOS early in its course [4]. A randomized controlled trial of prophylactic azithromycin given at the time of pre-HCT conditioning was terminated prematurely due to lower airflow decline-free survival rates in those receiving azithromycin [5]. Post-hoc analyses revealed a 70% increase in the incidence of hematologic relapse at 2 years in the azithromycin arm. This resulted in a warning by the Food and Drug Administration for the long-term use of prophylactic azithromycin to prevent BOS in HCT recipients. Because azithromycin for the treatment of BOS is typically given later in the course of HCT rather than at the time of conditioning, and because hematologic relapse rates generally decline after 1 year post-HCT [6], the concern for relapse may not apply to many HCT recipients receiving azithromycin for the treatment of BOS. We conducted a retrospective chart review of allogeneic HCT recipients. We hypothesized that azithromycin given later in the course of HCT, primarily for the treatment of BOS, would not be associated with higher rates of hematologic relapse.

We collected data on all patients at least 18 years of age undergoing first allogeneic HCT at our institution between February 1999 and March 2018 who developed pulmonary impairment, defined as declines in forced expiratory volume in 1 s (FEV1) of 10% or in mid-expiratory flow rates of 25%, relative to pre-HCT values [7], a population we theorized would be most likely to receive extended courses of azithromycin treatment. It is our institutional policy to administer anti-thymocyte globulin (ATG) to unrelated donor and cord blood transplants, but not to matched related donor (MRD) transplants. All patients received calcineurin-based post-HCT immunosuppression as cGVHD prophylaxis. Haploidentical transplants received post-HCT cyclophosphamide. Our institutional review board approved the study (PA17-0732) with a waiver of informed consent.

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Funding

This work was supported by the NIH/NIAID (K23 AI117024; to AS).

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Authors and Affiliations

  1. Departments of Pulmonary Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Ajay Sheshadri, Badar Patel, Tahreem Ahmed, Muhammad H. Arain, Lara Bashoura & Burton F. Dickey

  2. Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Rima Saliba, Rohtesh S. Mehta, Uday R. Popat, Chitra M. Hosing, Gabriela Rondon, Richard E. Champlin & Amin M. Alousi

  3. Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Houston, TX, USA

    Luis C. Bueno

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  1. Ajay Sheshadri
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Correspondence to Amin M. Alousi.

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Sheshadri, A., Saliba, R., Patel, B. et al. Azithromycin may increase hematologic relapse rates in matched unrelated donor hematopoietic cell transplant recipients who receive anti-thymocyte globulin, but not in most other recipients. Bone Marrow Transplant 56, 745–748 (2021). https://doi.org/10.1038/s41409-020-01073-0

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