Scientific Letters
Vol. 18 No. 1 (2026): Mediterranean Journal of Hematology and Infectious Diseases
https://doi.org/10.4084/MJHID.2026.059

Cytokine release syndrome after haploidentical transplantation is associated with improved survival without increasing transplant-related mortality

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Published: June 30, 2026
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Haplo-identical stem cell transplantation, CRS

Authors

Daniele Avenoso
daniele.avenoso@unibs.it
1- Unit of Blood Diseases and Bone Marrow Transplantation, Department of Clinical and Experimental Science, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy, Italy.
Natalia Difrancesco
Enrico Morello
Gabriele Magliano
Mirko Farina
Vera Radici
Simone Bernardi
Alessandro Leoni
Federica Re
Shreyas Hanmantgad
Domenico Russo
Michele Malagola

Cytokine release syndrome (CRS) following haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is common, but its prognostic significance remains unclear. We retrospectively analyzed 104 consecutive patients undergoing haplo-HSCT (2008–2024); after excluding early infections, 86 patients were evaluable. CRS was defined according to ASTCT criteria. The primary endpoint was overall survival (OS); secondary endpoints included relapse-free survival (RFS), GVHD/relapse-free survival (GRFS), cumulative incidence of relapse (CIR), and transplant-related mortality (TRM). Relapse and TRM were analyzed using competing risk methodology.

CRS occurred in 51% of patients. In the overall cohort, OS was numerically higher in patients with CRS but did not reach statistical significance. In contrast, among patients transplanted beyond first complete remission (CR1), CRS was significantly associated with improved OS (median not reached vs 7.6 months; p = 0.02). In this subgroup, RFS and GRFS also showed consistent trends in favor of CRS, although not statistically significant. The cumulative incidence of relapse was numerically lower in patients with CRS, without reaching statistical significance. TRM was comparable between groups, with no increase in early mortality. No differences were observed in acute or chronic GVHD.

Notably, no patients received specific treatment for CRS, and clinical manifestations resolved following post-transplant cyclophosphamide, supporting an alloimmune origin of the syndrome.

In conclusion, CRS after haplo-HSCT is associated with improved survival in patients with advanced disease, without increased TRM, and may represent a marker of early immune activation and graft-versus-leukemia effect.

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REFERENCES
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Ethics Approval

transplant, CRS, PTCY
Daniele Avenoso, 1- Unit of Blood Diseases and Bone Marrow Transplantation, Department of Clinical and Experimental Science, University of Brescia, ASST Spedali Civili di Brescia, Brescia, Italy

Associate Professor at University of Brescia

Director of the specialty training in haematology at University of Brescia

How to Cite



“Cytokine release syndrome after haploidentical transplantation is associated with improved survival without increasing transplant-related mortality” (2026) Mediterranean Journal of Hematology and Infectious Diseases, 18(1), p. e2026059. doi:10.4084/MJHID.2026.059.
Copyright (c) 2026 Daniele Avenoso, Natalia Difrancesco, Enrico Morello, Gabriele Magliano, Mirko Farina, Vera Radici, Simone Bernardi, Alessandro Leoni, Federica Re, Shreyas Hanmantgad, Domenico Russo, Michele Malagola Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.