Donor leukocyte infusions for multiple myeloma

Abstract

Summary:Donor leukocyte infusion (DLI) has well-documented activity in CML, but the role of DLI in other diseases is less well defined. To evaluate the strategy in multiple myeloma (MM) we evaluated 25 MM patients from 15 centers who were treated with DLI. Patients with persistent or recurrent disease after allogeneic BMT received DLI from the original marrow donor (23 matched related, one mismatched family, and one matched unrelated). Chemotherapy was given before DLI in three patients. Two of 22 patients responded completely to DLI alone and three patients responded to the combination of DLI and chemotherapy. Nine patients who had not had sufficient disease control after DLI were given additional DLIs; five of these patients had either complete (two) or partial (three) responses. Thirteen of 25 evaluable patients developed acute GVHD and 11 of 21 evaluable patients developed chronic GVHD; all responders developed GVHD. No patients developed post-DLI pancytopenia. Four patients had responses which lasted Ͼ1 year after DLI, three patients had responses which lasted Ͻ1 year, and three patients had ongoing responses but with followup Ͻ1 year. In conclusion, DLI has anti-myeloma activity but the strategy is limited by no response or short duration of response in a significant percentage of patients and by significant GVHD in the majority of the responders. Graft-versus-host disease (GVHD) occurs in approximately 60% of patients and is closely correlated with disease response. 13 The role of DLI in multiple myeloma (MM) is less certain. Several case reports and small series have documented an apparent graft-versus-myeloma (GVM) effect of DLI, [13][14][15][16][17][18][19][20][21][22][23] and a recent review of the literature 24 suggested an approximately 66% likelihood of response to DLI in myeloma. However, because of the relatively small number of patients reported thus far, and because of the potential for positive reporting bias, the overall usefulness of the approach in MM remains uncertain. To investigate further the role of DLI in MM, we analyzed 25 cases reported from 15 BMT centers. Patients and methods DesignWe collected detailed information from 15 BMT centers about DLIs in 25 patients with MM. Data were collected retrospectively in 13 patients and prospectively in 12. Information collected included the following: demographicspatient sex and age; diagnosis -disease, date of diagnosis, treatment before BMT, and response to treatment; BMTpre-BMT disease status, donor relationship, sex, and degree of histocompatibility, whether the BMT was T cell depleted, occurrence of acute and chronic GVHD; post-BMT relapse -date and extent of relapse, donor chimerism at relapse, and treatment of relapse and response to treatment; DLI -disease extent, pre-DLI chemotherapy and response, date of DLI, total nucleated cell dose, mononuclear cell dose, T cell dose, and concomitant cytokine usage; post-DLI response and complications -response to DLI and date, occurrence of pancytopenia and date, treatment of pancytopenia and res...

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

“…[5,10,11] A more recent survey of 25 patients at 15 centers reported complete responses in only seven patients (28%) who received one or more infusions of donor lymphocytes. [9] In a review of donor lymphocyte infusions for relapsed multiple myeloma, a graft-versus-myeloma effect was noted in 18/22 patients who developed GVHD compared to only 2/7 patients who did not develop GVHD (P = 0.02). [12] These studies suggest that clinical GHVD is not essential for a graft-versus-myeloma effect, but the relationship between the two is very strong.…”

“…[3][4][5]8,9] In initial studies, 50-70% of patients receiving donor lymphocyte infusions for relapsed multiple myeloma have been reported to achieve complete responses. [5,10,11] A more recent survey of 25 patients at 15 centers reported complete responses in only seven patients (28%) who received one or more infusions of donor lymphocytes.…”

“…[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. [3][4][5]8,9] In initial studies, 50-70% of patients receiving donor lymphocyte infusions for relapsed multiple myeloma have been reported to achieve complete responses. [5,10,11] A more recent survey of 25 patients at 15 centers reported complete responses in only seven patients (28%) who received one or more infusions of donor lymphocytes.…”

Tumor antigen immunization of sibling stem cell transplant donors in multiple myeloma

“…Attempts to enhance the GVM effect by donor lymphocyte infusions have resulted in increased incidence of graft-versus-host disease (GVHD). 8,9 Therefore, strategies to enhance the specific antitumor effect of the graft without increasing the risk of GVHD are needed to improve the outcome in allotransplant recipients. To this end, we have vaccinated allotransplant donors against a defined, patient tumor-derived antigen prior to bone marrow harvest.…”

In pursuit of the allo-immune response in multiple myeloma: where do we go from here?

“…The GvM immunological effect, best shown by the use of donor lymphocyte infusions (DLI) to re-induce disease responses after relapse post-AlloSCT, though less potent than that seen with chronic myeloid leukaemia, significantly contributes to the disease-free survival effect noted with AlloSCT in multiple myeloma. 7,8 The published evidence surrounding these two key issues in AlloSCT for multiple myeloma suggests that they are not mutually exclusive in their contribution to long-term disease-free survival in multiple myeloma, though the relevant contribution of each of these effects remains to be clarified. There is evidence that the method and degree of cytoreduction and the GvM effect contribute to longterm disease-free survival in multiple myeloma.…”