High response rate in refractory and poor-risk multiple myeloma after allotransplantation using a nonmyeloablative conditioning regimen and donor lymphocyte infusions

Abstract

Standard allogeneic stem cell transplant (allo-SCT) regimens have been associated with a high transplant-related mortality (TRM) in multiple myeloma (MM). Nonmyeloablative therapy can establish stable engraftment after allo-SCT and maintain the antitumor effect with less toxicity, which is important in heavily pretreated and elderly patients. We report on 16 poor-risk MM patients receiving allo-SCT from an HLA-matched (n ‫؍‬ 14) or mismatched (n ‫؍‬ 2) sibling following conditioning with melphalan 100 mg/m 2 (MEL-100). Ten patients had refractory relapse, 4 responsive relapse, and 2 patients were in near complete remission (nCR) with poor-prognosis disease. Patients had received 1 (n ‫؍‬ 9) or 2 (n ‫؍‬ 7) prior autotransplants. Donor lymphocyte infusions (DLIs) were given to 14 patients with no clinical evidence of graft versus host disease (GVHD) either to attain full donor chimerism (n ‫؍‬ 4) or to eradicate residual disease (n ‫؍‬ 10). Fifteen patients showed myeloid engraftment, and 12 patients were full donor chimeras at day

Follow‐up of patients with progressive multiple myeloma undergoing allografts after reduced‐intensity conditioning

“…The delayed immune reconstitution following serotherapy with ATG may have been the cause of serious opportunistic infections observed in a proportion of patients, as previously observed in a study of patients receiving Campath-1H for GVHD prophylaxis . In addition, ATG administration may also lead to a reduced graft-versus-myeloma effect, which may explain the low rate of CR observed in the present study compared with other trials (Slavin et al, 1998;Badros et al, 2001;Giralt et al, 2001;Khouri et al, 2001;Michallet et al, 2001) and also progression during the first year post allograft documented in nine out of the 17 patients who could be evaluated.…”

“…One of the reasons for the acceptable TRM in this study was the low incidence of severe, acute GVHD. Other non-myeloablative conditioning regimens have been reported to be associated with a higher incidence of acute GVHD grade II-IV of 38-60% (Badros et al, 2001;Giralt et al, 2001;McSweeney et al, 2001). The in vivo use of ATG, with its prolonged half-life, as part of the conditioning regimen in our study might have contributed to the low incidence of GVHD.…”

Reduced intensity conditioning and prophylactic DLI can cure patients with high-risk acute leukaemias if complete donor chimerism can be achieved

“…Other authors have also reported a high rate of acute and chronic GvHD after prophylactic DLI. [32][33][34][35] A higher transplant-related mortality was reported in these studies after dose-reduced 32,33 as well as after standard high-dose conditioning. 34,35 The optimal time point and cell dose of DLI have not been established.…”

Rapid enrichment of human papillomavirus (HPV)‐specific polyclonal T cell populations for adoptive immunotherapy of cervical cancer

“…The infusion of donor lymphocytes after allo-SCT has proven relatively successful in the treatment of relapsing hematological malignancies. 16,17 In these cases, effective therapy is often based on the in vivo induction of T cells specific for minor histocompatibility antigens expressed in host-cells of hematological origin. 18 However, the incorporation of allo-SCT in the treatment of solid tumors has been less successful.…”