A new approach being investigated in myeloma is the use of a mini (non-myeloablative) allogeneic transplant. Mini-transplants involve the use of moderately high-dose chemotherapy in combination with an allogeneic stem cell transplant. This dose of chemotherapy does not destroy the bone marrow completely, hence the name non-myeloablative. For this reason, this type of transplant appears to be a safer and more tolerable alternative to conventional allogeneic transplants. Because they are allogeneic transplants, immune cells present in the allograft help kill myeloma cells (the graft-versus myeloma effect).

Mini-transplants can be used alone, but are generally not very effective due to limited graft-versus-myeloma effects. They appear to be more effective when used in combination with an autologous stem cell transplant. In this type of tandem transplant, patients first undergo an autologous stem cell transplant, which may provide substantial anti-tumor effects. This is followed by a mini-transplant from a matched donor two to four months later. This strategy is designed to provide a sequential anti-tumor effect from the two transplants and a potential graft-versus-myeloma effect from the allogeneic mini-transplant.

Mini-transplants are still being investigated in clinical trials. Investigators at the University of Arkansas reported their experience with a mini-transplant protocol in 31 patients with relapsed or recently diagnosed high-risk disease who had received one or more autologous transplants. (Badros et al. J Clin Oncol. 2002;20(5):1295-1303.) Patients received a melphalan-based conditioning regimen (100 mg/m² melphalan in addition to cyclosporine for immunosuppression). The data showed that the technique offered excellent disease control, with 61% of patients achieving a CR or near-CR at a median follow-up of 6 months. Compared with historical controls receiving conventional allografts, the mini-transplant procedure had lower early treatment mortality (within the first 100 days; 19% vs. 29%) and improved overall survival at 1 year (71% vs. 45%). However the technique was associated with significant graft-versus-host disease (GVHD). Acute GVHD developed in 18 (58%) of patients and 10 patients progressed to chronic GVHD.

Investigators at the Fred Hutchinson Cancer Research Center also evaluated a mini-transplant strategy in patients with previously treated stage II or III myeloma. (Maloney et al. Blood. 2003;102(9):3447-3457.) In this study, 54 patients aged 29 to 71 years (median, 52 years) with received an autologous transplant followed by a mini-transplant that included total body irradiation (TBI) as a conditioning regimen and immunosuppression with mycophenolate mofetil and cyclosporine. The mini-transplant improved on the responses achieved with the autologous transplant. With a median follow-up of 552 days after receiving the allograft, the overall survival was 78%. Thirty-eight percent of patients experienced early (acute) graft-versus-host disease (GVHD), most of which was moderate in severity, and 46% experienced late (chronic) GVHD that required treatment.

Mini-transplant Results: Hutchinson Study

Parameter Percentage CR 57% PR 26% Rate of acute GVHD 38% Rate of chronic GVHD 46%

Preliminary results from a number of studies of mini-transplants, performed alone or following an autologous transplant, were reported at the American Society of Hematology (ASH) meeting in 2003. The table below includes data from three of the larger studies. Results from the French and Italian studies (mini-transplant following an autotransplant) appear encouraging. In these three studies, early treatment mortality was reduced to approximately 15%, which is still considerably higher than that seen with autotransplants. There are still high risks with these procedures and there are no long-term data regarding their efficacy and safety.

The usefulness of mini-allogeneic transplants in patients with high-risk disease is being investigated. A retrospective multicenter study investigating the impact of chromosome 13 deletion on outcome following mini-allogeneic transplants showed that the deletion was a significant prognostic factor for a higher relapse rate, shorter event-free survival, and higher mortality. (Kroger et al. Blood. 2004;103(11):4056-61.)

Initial results of trials comparing combination autologous/mini-
transplants and tandem autologous transplants show comparable results between the two strategies in patients with high-risk myeloma, so more study is needed.

Ongoing Mini-Allogeneic Stem Cell Transplant Trials in Myeloma as of August 2005 Autologous Peripheral Blood Stem Cell (PBSC) Transplantation Followed By Non-Myeloablative Allogeneic PBSC Transplantation in Patients With Multiple Myeloma •  View trial information A Trial of Tandem Autologous Stem Cell Transplants +/- Post Second Autologous Transplant Maintenance Therapy versus Single Autologous Stem Cell Transplant Followed by Matched Sibling Non-myeloablative Allogeneic Stem Cell Transplant for Patients with Multiple Myeloma •  View trial information Active Immunization of Sibling Stem Cell Transplant Donors Against Purified Myeloma Protein of the Stem Cell Recipient with Multiple Myeloma in the Setting of Non-myeloablative, HLA-matched Allogeneic Peripheral Blood Stem Cell Transplantation (CC# 00-C-0201) •  View trial information UARK 2002-22, A Phase II Study of Non-Myeloablative Therapy Followed by Sibling Allogeneic Transplant in Patients with Multiple Myeloma •  View trial information A Phase II Trial of Autologous Stem Cell Transplant Followed by Miniallogeneic Stem Cell Transplant in Lieu of Standard Allogeneic Bone Marrow Transplantation for Treatment of Multiple Myeloma •  View trial information Allogeneic CD34+ Selected Peripheral Blood Cell Infusion Following Nonmyeloablative Chemotherapy in Patients with Multiple Myeloma •  View trial information A Pilot Study of Nonmyeloablative Chemotherapy and Total Body Irradiation for Allografting Multiple Myeloma Patients From Related or Unrelated Donors Followed by Consolidation Cytotoxic-Immune Therapy •  View trial information