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Corticosteroids as graft-versus-host disease prophylaxis for allogeneic hematopoietic cell transplant recipients with calcineurin inhibitor intolerance.
Puckrin, Robert; Kwan, Alex Chi Fung; Blosser, Nikki; Leyshon, Catherine; Duggan, Peter; Daly, Andrew; Zepeda, Victor; Stewart, Douglas; Chaudhry, Ahsan; Storek, Jan; Jamani, Kareem.
Affiliation
  • Puckrin R; Tom Baker Cancer Centre and University of Calgary, Calgary, Alberta, Canada. Electronic address: robert.puckrin@ahs.ca.
  • Kwan ACF; Cross Cancer Institute and University of Alberta, Edmonton, Alberta, Canada.
  • Blosser N; Tom Baker Cancer Centre and University of Calgary, Calgary, Alberta, Canada.
  • Leyshon C; Tom Baker Cancer Centre and University of Calgary, Calgary, Alberta, Canada.
  • Duggan P; Tom Baker Cancer Centre and University of Calgary, Calgary, Alberta, Canada.
  • Daly A; Tom Baker Cancer Centre and University of Calgary, Calgary, Alberta, Canada.
  • Zepeda V; Tom Baker Cancer Centre and University of Calgary, Calgary, Alberta, Canada.
  • Stewart D; Tom Baker Cancer Centre and University of Calgary, Calgary, Alberta, Canada.
  • Chaudhry A; Tom Baker Cancer Centre and University of Calgary, Calgary, Alberta, Canada.
  • Storek J; Tom Baker Cancer Centre and University of Calgary, Calgary, Alberta, Canada.
  • Jamani K; Tom Baker Cancer Centre and University of Calgary, Calgary, Alberta, Canada.
Cytotherapy ; 25(10): 1101-1106, 2023 10.
Article in En | MEDLINE | ID: mdl-37306643
ABSTRACT
BACKGROUND

AIMS:

Although calcineurin inhibitors (CNIs) have a well-established role in the prevention of graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT), their use can be limited by significant toxicities, which may result in premature treatment discontinuation. The optimal management of patients with CNI intolerance is unknown. The objective of this study was to determine the effectiveness of corticosteroids as GVHD prophylaxis for patients with CNI intolerance.

METHODS:

This retrospective single-center study included consecutive adult patients with hematologic malignancies who underwent myeloablative peripheral blood allogeneic HCT with anti-thymocyte globulin, CNI, and methotrexate GVHD prophylaxis in Alberta, Canada. Multivariable competing-risks regression was used to compare cumulative incidences of GVHD, relapse, and non-relapse mortality between recipients of corticosteroid versus continuous CNI prophylaxis, and multivariable Cox proportional hazards regression was applied to compare overall survival, relapse-free survival (RFS) and moderate-to-severe chronic GVHD and RFS.

RESULTS:

Among 509 allogeneic HCT recipients, 58 (11%) patients developed CNI intolerance and were switched to corticosteroid prophylaxis at median 28 days (range 1-53) after HCT. Compared with patients who received continuous CNI prophylaxis, recipients of corticosteroid prophylaxis had significantly greater cumulative incidences of grade 2-4 acute GVHD (subhazard ratio [SHR] 1.74, 95% confidence interval [CI] 1.08-2.80, P = 0.024), grade 3-4 acute GVHD (SHR 3.22, 95% CI 1.55-6.72, P = 0.002), and GVHD-related non-relapse mortality (SHR 3.07, 95% CI 1.54-6.12, P = 0.001). There were no significant differences in moderate-to-severe chronic GVHD (SHR 0.84, 95% CI 0.43-1.63, P = 0.60) or relapse (SHR 0.92, 95% CI 0.53-1.62, P = 0.78), but corticosteroid prophylaxis was associated with significantly inferior overall survival (hazard ratio [HR] 1.77, 95% CI 1.20-2.61, P = 0.004), RFS (HR 1.54, 95% CI 1.06-2.25, P = 0.024), and chronic GVHD and RFS (HR 1.46, 95% CI 1.04-2.05, P = 0.029).

CONCLUSIONS:

Allogeneic HCT recipients with CNI intolerance are at increased risks of acute GVHD and poor outcomes despite institution of corticosteroid prophylaxis following premature CNI discontinuation. Alternative GVHD prophylaxis strategies are needed for this high-risk population.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hematopoietic Stem Cell Transplantation / Graft vs Host Disease Type of study: Etiology_studies / Observational_studies / Risk_factors_studies Limits: Adult / Humans Language: En Journal: Cytotherapy Journal subject: TERAPEUTICA Year: 2023 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hematopoietic Stem Cell Transplantation / Graft vs Host Disease Type of study: Etiology_studies / Observational_studies / Risk_factors_studies Limits: Adult / Humans Language: En Journal: Cytotherapy Journal subject: TERAPEUTICA Year: 2023 Document type: Article