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Predictors of hematologic malignancy relapse in patients with advanced chronic graft-versus-host disease

Abstract

Malignancy relapse remains a major barrier to treatment success in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Chronic graft-versus-host disease (cGVHD) markedly reduces hematologic malignancy relapse risk, but relapses still occur in these patients. Patients (n = 275) with moderate or severe cGVHD were enrolled on the National Cancer Institute (NCI) prospective cross-sectional natural history study (NCT00092235). Subjects were median 36 months after allo-HSCT and were followed subsequently for malignancy relapse and survival. Seventeen patients experienced relapse. In a multivariable model including time-dependent influences on relapse, risk factors associated with increased risk of relapse included shorter time from transplant to cGVHD evaluation (HR 0.279, 95% CI 0.078–0.995) and lower number of prior lines of systemic immunosuppressive therapy for cGVHD (HR 0.260, 95% CI 0.094–0.719). In a model excluding time-dependent influences on relapse risk, lower number of prior lines of systemic immunosuppressive therapy for cGVHD (HR 0.288, 95% CI 0.103–0.804), lower C4 complement level (HR 0.346, 95% CI 0.129–0.923), and higher body mass index (HR 3.222, 95% CI 1.156–8.974), were all associated with increased relapse risk. Parameters indicating cGVHD severity and activity are associated with risk of malignancy relapse. Classical predictors of relapse after allo-HSCT do not seem to be prognostic.

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Fig. 1: Cumulative incidence of malignancy relapse.
Fig. 2: Progression-free survival.
Fig. 3: Cumulative incidence of malignancy relapse by number of prior systemic treatments for chronic GVHD.
Fig. 4: Cumulative incidence of malignancy relapse by C4 complement level.
Fig. 5: Cumulative incidence of malignancy relapse by BMI.

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Acknowledgements

The authors would like to thank all patients and their families for participating in the NIH cGVHD natural history study. This work was supported by the Intramural Research Program of the National Institutes of Health, Center for Cancer Research, NCI; the National Institute for Dental and Craniofacial Research; the National Institute of Arthritis and Musculoskeletal and Skin Diseases; and the National Eye Institute. The views expressed in this work do not represent the official views of the National Institutes of Health or the United States Government.

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Correspondence to Steven Z. Pavletic.

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Ruben, C.L., Pirsl, F., Steinberg, S.M. et al. Predictors of hematologic malignancy relapse in patients with advanced chronic graft-versus-host disease. Bone Marrow Transplant 56, 1584–1592 (2021). https://doi.org/10.1038/s41409-021-01211-2

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