Outcomes Following Syngeneic Hematopoietic Stem Cell Transplantation for Multiple Myeloma: A Matched Comparison to Autologous Transplantation.

Relapse is the main cause of treatment failure following autologous hematopoietic cell transplantation (HCT) for multiple myeloma (MM). Syngeneic HCT offers the advantage of a myeloma-free-graft. However, a potential disadvantage is the lack of a graft versus myeloma effect (GVM). We compared the probabilities of treatment-related mortality (TRM), disease progression, progression-free survival (PFS) and overall survival (OS) after syngeneic versus autologous HCT for MM done between 1988 and 2003. Median follow up was >70 months in both groups. 43 syngeneic HCT recipients were matched to 170 autologous HCT recipients using a propensity score. A numerical propensity score for each syngeneic HCT recipient was calculated using the variables of age, Durie-Salmon stage at diagnosis, sensitivity to pretransplant therapy, time from diagnosis to HCT and year of HCT. Propensity scores ranged from 0.004–0.286. Syngeneic HCT recipients (cases) were matched in random order to autologous transplant (control) recipients with similar propensity scores. Patients who underwent tandem transplants were excluded. Median age (range) was 53 and 52 years in cases and controls. Most patients in both groups (60% of cases, 64% of controls) were transplanted within 12 months of diagnosis. Except for a higher proportion of patients with IgG myeloma (59% vs. 39%, p<0.01) and PBSC grafts (92% vs. 51%, p<0.01) in the control group there were no statistically significant differences in baseline characteristics of the two groups. 5-year outcomes are summarized in the table.

In multivariate analysis, risks of progression and treatment failure were significantly lower after syngeneic than autologous HCT [disease progression RR= 0.43 (95%CI, 0.23–0.78, p=0.004); treatment failure RR= 0.59 (95%CI 0.35–0.98, p=0.04)]. TRM at 1 year was 14% (5–26) in the syngeneic group and 9% (5–13%) in controls (p=0.33). The 5-year risk of mortality was lower in the syngeneic group but the difference was not statistically significant (RR= 0.61, 95%CI 0.36–1.05, p=0.07). Disease recurrence accounted for 79% of deaths in the autologous and 47% in the syngeneic cohort. We conclude that syngeneic HCT for MM results in superior PFS and lower progression rates compared to autologous HCT, confirming previous smaller analyses and emphasizing the importance of a disease-free graft. Interestingly, these data suggest that relapse rates similar to those observed after nonmyeloablative allogeneic transplantation – another source of tumor free grafts – can occur in the absence of clinical graft versus host disease.