Donor Leukocyte Infusions Are Effective in Relapsed Multiple Myeloma After Allogeneic Bone Marrow Transplantation

Abstract

Donor leukocyte infusions (DLI) can induce sustained remissions in patients with acute and chronic myeloid leukemia who relapse after allogeneic bone marrow transplantation (allo-BMT). Also, in multiple myeloma (MM), incidental reports have indicated the existence of a graft-versus-myeloma effect (GVM) induced by allo-reactive T cells. We performed a retrospective study in a larger group of MM patients to characterize better the effect, prognostic factors, and toxicity of this new treatment modality. Thirteen patients with relapsed MM after allo-BMT were studied. Patients received a total of 29 DLI with T-cell doses ranging from 1 × 106/kg to 33 × 107/kg. Repetitive courses, sometimes with escalated cell doses, were undertaken in case of no response to or relapse after DLI. Eight of 13 patients responded: 4 patients achieved a partial remission and 4 patients achieved a complete remission. Dose escalation was effective in 3 patients. The time to response was median 6 weeks (range, 4 to 10 weeks). Major toxicities were secondary to acute and chronic graft-versus-host disease (GVHD), which occurred in 66% and 56% of all patients and in 87% and 85% of the responders, respectively. Two responding patients developed fatal BM aplasia. The only prognostic factors for response were a T-cell dose greater than 1 × 108/kg and the occurrence of GVHD. Seven of nine patients developing acute GVHD responded, as compared with only 1 response in the 4 patients without GVHD and 6 of 7 patients with chronic GVHD responded, whereas no response was observed in the 5 patients without chronic GVHD. DLI are effective in a high percentage of patients with relapsed MM after allo-BMT, although it is associated with a high treatment-related toxicity. The dose of T cells used may be important in determining the GVM effect, with the highest probability of response after infusion of more than 1 × 108 T cells. Because the optimal individual dose may vary, patient-adapted therapy consisting of repeated infusions with escalating dose of donor leukocytes until maximum response is achieved may therefore be preferable.

Allogeneic bone marrow transplantation with T‐cell‐depleted marrow grafts for patients with poor‐risk relapsed low‐grade non‐Hodgkin's lymphoma

“…We believe that the favourable results of allogeneic BMT cannot be explained merely on the basis of the intensive conditioning regimen before BMT, but also on immunological mechanisms after BMT (Meijerink et al, 1994). As already shown for acute leukaemia, chronic myeloid leukaemia and multiple myeloma, one of the additional beneficial effects of BMT, whether or not followed by DLI, is the immune-mediated graft-versus-tumour effect (Horowitz et al, 1990;Kolb et al, 1995;Collins et al, 1997;Lokhorst et al, 1997). Especially in patients with relapsed chronic myeloid leukaemia post-BMT, DLI induce renewed remission in the majority of patients, whereas patients with acute leukaemia respond less favourably to DLI.…”

Update on the Treatment of Multiple Myeloma

“…Eight of 13 patients with relapse of myeloma after an allogeneic bone marrow transplantation responded to donor lymphocyte infusions. Four of the patients had a complete response [12]. At present, a conventional allogeneic transplant is not recommended because of its high mortality.…”

The outcome of unrelated donor stem cell transplantation for patients with multiple myeloma

“…Durable remission post-transplantation is likely to be a result of the graft versus myeloma effect (Tricot et al, 1996). Further support for this effect exists in the lower relapse rate seen following allo-SCT (when compared with autologous procedures) (Bjorkstrand et al, 1996), as well as the ability of donor leucocyte infusions (DLI) to return a patient with relapsing disease to complete remission (CR) (Lokhorst et al, 1997).…”