Comparable outcomes after nonmyeloablative hematopoietic cell transplantation with unrelated and related donors

Abstract

We sought to determine whether patients with hematologic malignancies treated by nonmyeloablative hematopoietic cell transplantation (HCT) at a single institution between December 1997 and June 2006 had worse outcomes with grafts from unrelated donors (URDs) (n = 184) compared with HLA-identical related donors (n = 221). The nonmyeloablative preparative regimen consisted of 2 Gy of total body irradiation (TBI) with (78%) or without (22%) fludarabine, along with posttransplantation mycophenolate mofetil (MMF) and cyclosporine (CSa). After adjusting for the HCT comorbidity index, relapse risk, patient age, stem cell source, preparative regimen, previous cytomegalovirus (CMV) infection, and sex mismatch of donor and recipient in multivariate analysis, we found no statistically significant differences between unrelated and related HCT recipients in terms of risk of nonrelapse mortality (NRM; hazard ratio [HR] = 0.98; 95% confidence interval = 0.6-1.6; P = .94), relapse (HR = 1.04; 95% confidence interval = 0.7-1.5; P = .82), or overall mortality (HR = 0.99; 95% confidence interval = 0.7-1.4; P = .94). Overall rates of severe acute and extensive chronic graft-versus-host disease (aGVHD, cGVHD) also were not significantly different between the 2 groups. We conclude that within the limitations of a retrospective study, these results indicate that candidates for nonmyeloablative HCT without suitable related donors may expect similar outcomes with grafts from URDs.

Figures

Figure 1. Non-relapse mortality, relapse or progression, and overall survival according to donor type

Cumulative incidence of non-relapse mortality (A) and relapse or progression (B), and Kaplan-Meier survival estimates (C) among patients with HLA-identical sibling donors (“MRD”, n=221) compared to those with HLA-matched unrelated donors (“URD”, n=184) (p=0.08). The third curve in each panel (“URD adjusted”) shows the projected survival with HLA-matched unrelated donors after adjusting for HCT-comorbidity index, relapse risk category, patient age, stem cell source, prior cytomegalovirus infection and donor/recipient sex-mismatch.

Figure 2. Cumulative incidence of recurrent malignancy and non-relapse mortality (NRM) according to HCT-comorbidity index (CI) and relapse risk categories

The combined groups of patients with related and unrelated donors were categorized according to the presence of pretransplant comorbidities (HCT-CI: 0, 1-2, and ≥ 3) [18] (A, B) and the predicted risk of recurrent malignancy (low, intermediate, and high) [35] (C, D). The cumulative incidence rates of recurrent malignancy (A, C) and NRM (B, D) are shown for respective subgroups of patients.