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

Claire L Ruben, Filip Pirsl, Seth M Steinberg, Noa G Holtzman, Laura Parsons-Wandell, Judy Baruffaldi, Lauren M Curtis, Sandra A Mitchell, Ana Zelic Kerep, Edward W Cowen, Ann Berger, Galen O Joe, Manuel B Datiles 3rd, Jacqueline W Mays, Steven Z Pavletic, Claire L Ruben, Filip Pirsl, Seth M Steinberg, Noa G Holtzman, Laura Parsons-Wandell, Judy Baruffaldi, Lauren M Curtis, Sandra A Mitchell, Ana Zelic Kerep, Edward W Cowen, Ann Berger, Galen O Joe, Manuel B Datiles 3rd, Jacqueline W Mays, Steven Z Pavletic

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.

Conflict of interest statement

Competing Interests

The authors have no competing financial interests in relation to the work.

Figures

Figure 1:
Figure 1:
Cumulative incidence of malignancy relapse.
Figure 2:
Figure 2:
Progression-free survival. Patients were censored at time of last follow-up.
Figure 3:
Figure 3:
Cumulative incidence of malignancy relapse by number of prior systemic treatments for chronic GVHD.
Figure 4:
Figure 4:
Cumulative incidence of malignancy relapse by C4 complement level.
Figure 5:
Figure 5:
Cumulative incidence of malignancy relapse by BMI.

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