Autologous Stem Cell Transplantation in Waldenstrom's Macroglobulinemia

The role of autologous stem-cell transplantation (auto-HCT) in Waldenström macroglobulinemia (WM) is not clearly defined. The aim of this study was to analyze the results of auto–HCT in patients with WM and to determine the prognostic factors that have a significant impact on outcome.

We analyzed 16 adult patients (10 males and 6 females) with WM who underwent high-dose chemotherapy and auto–HCT at MDACC between 1/89 and 2/11. Median age at diagnosis was 55 years (range 43–74) and median age at auto-HCT was 55.5 years (range 43–75). Concurrent AL amyloidosis was seen in 6 patients (37%). Median interval from diagnosis to time of progression was 3.1 years (range 0.4– 9.5) and patients had received a median of 2 lines of therapy (range: 1–6) prior to auto-HCT. Seven patients (44%) had either primary refractory disease or were in first remission, while 9 patients (56%) had relapsed disease. Median follow-up in the surviving patients was 3.5 years (range, 1.1– 12.2). Preparative regimens were as follows: 9 patients received Melphalan alone; 2 received Melphalan + Rituximab; 1 underwent Melphalan + total body irradiation (TBI); 2 received Thiotepa + Busulfan + Cyclophosphamide; and 2 received BCNU + Etoposide + Cytarabine + Melphalan + Rituximab (BEAM-R).

Non-relapse mortality was 6.2% at 1 year. All 15 evaluable patients achieved engraftment with a median time to neutrophil engraftment of 11 days (10–46). Fourteen patients were eligible for response evaluation. One patient died within 30 days and one was lost to follow up. Three (21%) patients achieved a CR, while 9 (64%) achieved a PR. The overall response rate was 85%. Progression-free survival (PFS) and overall survival (OS) at 5 years were 36.7% and 56.4%, respectively. Median PFS and OS from auto-HCT were 2.5 and 8.3 years, respectively. The median OS from diagnosis was 12.3 years. On univariate analyses, disease status at auto-HCT (first remission or primary refractory disease) was the strongest predictor of progression (p=0.05; HR 0.1, 95% CI 0.01–1.04), PFS (p=0.01, HR 0.1, CI: 0.01–0.6) and OS (p=0.01). Similarly, the melphalan-based regimens were associated with a longer OS in patients with relapsed disease at auto-HCT (p=0.002). On univariate analyses, LDH level at auto-HCT, number of prior chemotherapy regimens, use of prior cladribine, concurrent AL amyloidosis or International Staging System score (ISSWM) did not have a significant impact on the outcome.

Auto-HCT is a feasible procedure in patients with advanced WM, even when performed later in the course of disease, after a median of 2 lines of therapy. Patients with relapsed disease at auto-HCT have a significantly worse outcome and may require posttransplant therapy.

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