Clinical Research
Relapse to prior autograft and chronic graft-versus-host disease are the strongest prognostic factors for outcome of melphalan/fludarabine-based dose-reduced allogeneic stem cell transplantation in patients with multiple myeloma

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Abstract

We evaluated prognostic factors of melphalan/fludarabine-based dose-reduced allografts in patients with multiple myeloma. From 1998 to 2002, 120 patients with multiple myeloma were treated with melphalan/fludarabine followed by allogeneic stem cell transplantation. The cumulative risk at 1 year for treatment-related mortality (TRM) was 18% (95% confidence interval [CI], 12%–28%). In a multivariate analysis, relapse after prior high-dose chemotherapy was the most significant risk factor for TRM (hazard ratio [HR], 2.80; 95% CI, 1.16–6.74; P = .02), relapse (HR, 4.14; 95% CI, 2.04–8.38; P < .001), event-free survival (HR, 3.11; 95% CI, 1.77–5.46; P < .001), and overall survival (HR, 2.69; 95% CI, 1.35–5.35; P = .005). In addition, relapse was also significantly diminished by chronic graft-versus-host disease (GVHD) in a time-dependent Cox model (HR, 0.37; 95% CI, 0.16–0.87; P = .02). At transplantation, 8% of the patients were in complete remission, whereas 27% had progressive disease. After allografting, 49% achieved complete remission, and 38% achieved partial remission. In a subgroup of patients with chemosensitivity at transplantation and no relapse after prior high-dose chemotherapy who underwent transplantation with peripheral blood stem cells (n = 46), the cumulative risk of TRM at 1 year was only 8% (95% CI, 1%–54%). The 2-year estimated event-free and overall survival was 60% (95% CI, 42%–78%) and 75% (95% CI, 59%–91%), respectively, for related donors (n = 34) and was 81% (95% CI, 59%–100%) and 92% (95% CI, 76%–100%), respectively, for unrelated donors (n = 12).

Keywords

Allogeneic stem cell transplantation
Dose-reduced conditioning
Nonmyeloablative transplantation
Graft-versus-host disease
Autologous stem cell transplantation
Multiple myeloma

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