Allogeneic transplantation for multiple myeloma: further evidence for a GVHD-associated graft-versus-myeloma effect

Abstract

Summary:We report a series of 37 consecutive patients with multiple myeloma (MM) who received an allograft between 1990 and 2000 at our institution. Median age was 47 years, and nearly 70% of patients were Durie-Salmon stage III. A median of five cycles of chemotherapy were given before transplant, with a median interval between diagnosis and transplant of 9.3 months. We report a nonrelapse mortality rate of 22% with a median followup period of 40 months, whereas complete remission (CR) rate at 12 months is estimated at 57%. Treatment failure rate and overall survival at 40 months are estimated at 52% and 32%, respectively. The number of chemotherapy cycles prior to allotransplantation achieved borderline statistical significance as a poor prognosis factor for overall survival (P ‫؍‬ 0.05), while the presence of chronic graft-versus-host disease (cGVHD) was significantly correlated with CR achievement (P ‫؍‬ 0.036). Our study confirms that early allografting in MM can yield toxicity rates significantly lower than those associated with historical cohorts, and supports the hypothesis that cumulative chemotoxicity has a negative influence on mortality and survival rates. More importantly, our study clearly demonstrates an association between cGVHD and CR and brings further evidence in favor of a graft-versus-myeloma effect. Bone Marrow Transplantation (2001) 28, 841-848.

Favorable long-term outcome of patients with multiple myeloma using a frontline tandem approach with autologous and non-myeloablative allogeneic transplantation

“…[7][8][9] Factors associated with improved PFS included fewer treatments before transplant, grade I acute GvHD and presence of chronic GvHD. This protective effect of chronic GvHD, [10][11][12][13][14] response after donor lymphocyte infusion 15,16 and the discovery of antibodies against highly expressed myeloma-associated Ags 17 following allogeneic transplant are additional clinical observations supporting the existence of a graft-versus-myeloma (GvMM) effect.…”

“…Recently, allogeneic HSCT has received less enthusiasm due to prohibitive (20-30%) non-relapse mortality (NRM) associated with myeloablative conditioning 11 and high relapse rates (50-70%), following non-myeloablative (NMA) transplant. 18 Several controlled trials comparing autologous transplant alone to a tandem approach have questioned the survival benefits of NMA allogeneic HSCT for newly diagnosed MM patients, leading to conflicting results.…”

“…19 However, these randomized studies used different HSCT conditioning regimens, GvHD prophylaxis and non-transplant strategies in the control arm with various follow-up durations, which make comparisons difficult. Nevertheless, some studies 11,20 have reported long-term survival rates in the range of 20-30%.…”

Is there still a role for allogeneic stem-cell transplantation in multiple myeloma?

“…A small retrospective report of 37 patients who received conventional allografts for multiple myeloma found that among 15 patients who achieved complete response, 11 had chronic GVHD while four did not. [6] Individual case reports have documented a graftversus-myeloma effect in association with GVHD when immunosuppression was withdrawn. [7] Small series of patients with multiple myeloma who developed post-allograft relapses and who subsequently were infused with allogeneic leukocytes from their original stem-cell donors have clearly demonstrated a graft-versus-myeloma effect that was associated with GVHD.…”

Isolated orbital relapse of multiple myeloma in a patient with severe chronic GVHD after allogeneic hematopoietic SCT

“…Although cGVHD is associated with a graft-versus-myeloma effect preventing relapse after alloHSCT, 6 relapses with extramedullary manifestations appear to occur more frequently due to altered biology and local immunological escape effects. 7,8 Furthermore, malignant plasma cells may have survived in the fatty tissue of the orbit, potentially providing a sanctuary for persistence of malignant cells.…”