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The Graft-Versus-Myeloma Effect Using Non-Myeloablative Or Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Year: 2010

Type: article

Abstract: Following myeloablative conditioning due to high treatment-related mortality (TRM), some studies have shown an inferior outcome using allogeneic HSCT compared to autologous transplant. More recently, non-myeloablative (NMA) and reduced intensity conditioning (RIC) for allogeneic HSCT was introduced. A prerequisite for this approach is a significant graft-versus-myeloma effect, which has not clearly been demonstrated. Between 1997 and 2005, 177 patients were reported to the CIBMTR following NMA (n=120) or RIC (n=57) and an allogeneic HSCT from an HLA-identical sibling donor. Median age was 50 years (range 24-69). Planned tandem autologous transplant followed by allogeneic HSCT was given to 105 of these patients. Most patients were given peripheral blood stem cells (98%). Outcomes, with a median follow-up of 55 months (range 3-98) and 25 months (range 3-76) respectively for allogeneic HSCT and autologous transplant followed by allogeneic HSCT, see Table below. The following variables were significant in univariate outcomes analyses and were therefore used in the multivariate modelling: age, sex, performance status, IgG vs. non IgG myeloma, disease status and chemosensitivity, prior lines of chemotherapy, donor-recipient sex match, NMA vs. RIC, year of transplant and GVHD as the time dependent covariate. The only factor on multivariate analysis that increased the risk of TRM was acute GVHD (RR 2.38, p=0.018). Only chronic GVHD decreased the probability of relapse on multivariate (RR 0.43, p=0.012), but this effect was not seen in patients with IgG myeloma (n=97, RR 0.7, p=0.3) in comparison to all other types of myeloma (n=80, RR 0.11, p=0.004). Improved PFS was associated with autologous + allogeneic HSCT (RR 3.6, p=0.001) and absence of acute GVHD (p=0.001), but not chronic GVHD (RR 0.9, p=0.7). In conclusion, patients receiving allogeneic HCT for myeloma, chronic GVHD decreased the probability of relapse, but only in patients with non-IgG myeloma. PFS was improved in patients receiving autologous + allogeneic HCT and was decreased in those with acute GVHD.Tabled 1OutcomesAllo onlyAuto+AlloNumber of patients72105Acute GVHD at 100 days, grades (1-4)47 (37-60)%37 (28-46)%Chronic GVHD at 3 years55 (43-67)%58 (43-72)%Treatment Related Mortality (TRM) at 3 years27 (17-38)%16 (10-25)%Relapse at 3 years48 (36-60)%41 (29-54)%Progression-free survival (PFS) at 3 years25 (15-37)%42 (20-43)%Overall Survival at 3 years45 (33-58)%64 (53-75)% Open table in a new tab

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2009.12.242