Abstract
BACKGROUND: Allogeneic stem cell transplantation (allo-SCT) with reduced-intensity conditioning (RIC) is gaining increasing acceptance in relapsed/refractory (R/R) Hodgkin’s lymphoma (HL), but there are little or no outcome data with matched unrelated donors (MUDs).
METHODS: Fifty-eight patients with relapsed or refractory Hodgkin’s lymphoma (HL) underwent allogeneic stem cell transplantation (allo-SCT) following a reduced-intensity conditioning (RIC) regimen from a matched related donor (MRD; n=25) or a matched unrelated donor (MUD; n=33). The median age was 32 years (range 19–59). The median number of chemotherapy regimens received prior to allo-SCT was five (range 2–9). Forty-eight (83%) patients had received a prior autologous (auto) SCT. The median time to progression after auto-SCT was five months (1–34). Disease status at SCT was sensitive relapse (n=30) or refractory relapse (n=28). The conditioning regimen employed was fludarabine (125–130 mg/m sq over 4–5 days), melphalan (140 mg/m sq IV over 2 days) (FM) and antithymocyte globulin (thymoglobulin 6 mg/kg over 3 days) was added for the most recent fourteen MUD transplants. Graft-vs-host disease (GVHD) prophylaxis included tacrolimus and mini-methotrexate.
RESULTS: Chimerism studies indicated 100% donor-derived engraftment in all patients (100%). Cumulative 100-day and 2-year transplant-related mortality (TRM) were 7% and 15%, respectively, (100-day TRM MRD vs. MUD 6% vs. 8%, p=ns; 2-year MRD vs. MUD 13% vs. 16%, p=ns). The cumulative incidence of acute (grade II–IV) GVHD (first 100 days) was 28% (MRD vs. MUD 12% vs. 39%, p=0.04). The cumulative incidence of chronic GVHD at any time was 74% (MRD vs. MUD 57% vs. 89%, p=0.003). Fourteen pts (24%) received a total of 25 (range 1–5) donor leukocyte infusions (DLIs) for disease progression/relapse (PD). Five of them (35%) received salvage chemotherapy as well, and nine (64%) developed acute GVHD after the DLI. Thirty-six patients (62%) are alive (23 in remission) with a median follow-up of 24 months (4–78). The f/up is 23 months (4–53) for alive pts always in remission. Twenty-two patients (38%) expired, and relapse-related mortality was 24%. Projected 2-year overall (OS) and progression-free (PFS) survival are 64% (49–76) and 32% (20–45), with projected 2-year PD at 55% (43–70). There was no statistically significant difference between MRD and MUD transplants with regard to OS (p=0.1), PFS (p=0.9) and PD (p=0.8). There was a clear trend for the response status prior to allo-SCT (complete response, complete response undefined vs. all others) to favorably impact PFS (p=0.07) and PD (p=0.049), but not OS (p=0.4). Partial responders and patients with stable or refractory disease fared similarly with regard to OS and PFS.
CONCLUSIONS: Despite the expected higher incidence of acute and chronic GVHD, MUD RIC allo-SCTs had TRM, PFS, and OS comparable to MRD allo-SCTs. Day 100, 2-year TRM and OS/PFS data appear very encouraging in these very high-risk, extensively pretreated patients. Response status at transplant seems to affect outcome, and PD remains a major obstacle. The use of unrelated donors would greatly expand donor availability for these patients.
Fludarabine-melphalan as a preparative regimen for reduced-intensity conditioning allogeneic stem cell transplantation in relapsed and refractory Hodgkin's lymphoma: the updated M.D. Anderson Cancer Center experience