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Cytokine release syndrome after haploidentical hematopoietic cell transplantation: an international multicenter analysis

Bone Marrow Transplantation volume 56, pages 2763–2770 (2021)Cite this article

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Abstract

Haploidentical related donor transplantation (haplo-HCT) is associated with cytokine release syndrome (CRS). We conducted a multicenter retrospective study to analyze risk factors for CRS and outcomes after haplo-HCT. We included 451 patients from four academic centers receiving both peripheral blood and bone marrow grafts. Severe CRS was more common with PB vs. BM grafts (19.5% vs 4.9%, OR 2.9, p = 0.05). Multivariable analysis identified recipient CMV sero-positivity, prior transplant, HCT-CI score and donor–recipient sex mismatch as risk factors for severe CRS. Outcomes were analyzed with no CRS as the comparison group. Overall survival (OS) was superior with mild CRS (HR 0.64, p = 0.05) and worst with severe CRS (HR 2.12, p = 0.0038). Relapse risk was significantly decreased in both mild CRS (HR 0.38, p < 0.0001) and severe CRS (HR 0.17, p < 0.0001) groups. The risk of non-relapse mortality was notably higher in severe CRS group (HR 8.0, p < 0.0001), but not in mild CRS group. Acute GVHD was similar among groups. Chronic GVHD at 1 year was 18.5% for no CRS, 23% for mild CRS, and 4.3% for severe CRS (p = 0.0023), with the competing risk of early mortality and short follow up of surviving patients contributing to the low chronic GVHD rates in the severe CRS group.

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Fig. 1: Effect of CRS on neutrophil and platelet recovery after haploidentical related donot transplantation.
Fig. 2: Effect of CRS on GVHD outcomes after haploidentical related donor transplantation.
Fig. 3: Effect of CRS on relapse and survival after haploidentical related donor transplantation.

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Acknowledgements

RA is supported by the American Society of Hematology Clinical Research Training Institute, the American Society of Hematology Research Training Award for Fellows, and the National Cancer Institute of the National Institutes of Health under Award Number R25 CA190190.

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Authors and Affiliations

  1. Division of Oncology, Washington University School of Medicine, St. Louis, MO, USA

    Ramzi Abboud

  2. Biostatistics Shared Resource Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA

    Fei Wan

  3. Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan, Italy

    Jacopo Mariotti & Luca Castagna

  4. Hematology and Stem Cell Transplantation, Hospital Pablo Tobón Uribe, Medellín, Colombia

    Marcos Arango

  5. BMT and Cellular Therapy Program, Dana Farber Cancer Center, Harvard Medical School, Boston, MA, USA

    Rizwan Romee

  6. BMT and Cellular Therapy Program, Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

    Mehdi Hamadani & Saurabh Chhabra

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Contributions

RA and SC designed and performed research, analyzed data, and authored the manuscript. JM, MA, LC, RR, and MH performed research and critically reviewed the manuscript. WF analyzed data and reviewed the manuscript.

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Correspondence to Saurabh Chhabra.

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Competing interests

RA has research funding from Incyte Corporation. MH has research support/funding from: Takeda Pharmaceutical Company; Spectrum Pharmaceuticals; Astellas Pharma. Consultancy: Janssen; Incyte Corporation; ADC Therapeutics; Celgene Corporation; Omeros, Verastem, MorphoSys. Speaker’s Bureau: Sanofi Genzyme, AstraZeneca, BeiGene. The authors have no other conflicts relevant to this publication.

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Abboud, R., Wan, F., Mariotti, J. et al. Cytokine release syndrome after haploidentical hematopoietic cell transplantation: an international multicenter analysis. Bone Marrow Transplant 56, 2763–2770 (2021). https://doi.org/10.1038/s41409-021-01403-w

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