Allogeneic bone marrow transplantation (ALLO BMT): Role of t cell depletion (TCD) and graft versus host disease (GVHD)

Multiple myeloma is incurable with standard chemotherapy and has a median survival of 3 years from the time of diagnosis. In contrast, alloBMT is potentially curative. It offers the advantage of a tumor-free graft and the potential to induce a graft versus myeloma (GVM) response in the host. However, the toxicity of alloBMT can be considerable in myeloma patients because of their older age and associated comorbidities. From June 1991 to April 2000, 51 patients with multiple myeloma received alloBMTs at Johns Hopkins Hospital using TCD by elutriation in an attempt to reduce toxicity. The median age at transplant was 49 years (range 36 - 62), 29 were men and 22 women. All patients received a busulfan (16 mg/kg) / cyclophosphamide (200 mg/kg) preparative regimen. The transplant-related mortality was 24% (12/51). Twenty-five percent (13/51) developed GVHD (7 with Stage 2) and two died. Of the 39 surviving patients, 26 have relapsed at a median of 12 months (range 5 - 48). Nine patients have died as a result of recurrrent disease. With a median follow-up of 22 months (range 2 - 92), the overall eventfree survival (EPS) is 20% at 4 years with a trend for patients who developed GVHD to do better. Patients with GVHD had an EPS of 40% at 40 months versus 18% at 40 months in patients without GVHD. In addition, 11 of the 27 relapses were treated with donor lymphocyte infusions (DLI) (+ chemotherapy in 5). Six of the 11 patients treated with DLI +/chemotherapy achieved a remission and 4 of these 6 developed GVHD in response to DLI. Thus far. no one has relapsed after DLI with a median follow-up of 11 months (range 0 - 46). TCD of donor marrow leads to acceptable toxicity in a group of patients at high risk for transplant-related complications. Our data suggest that the anti-tumor activity of the cytotoxic conditioning regimen plays a limited role in controlling myeloma. Conversely, alloBMT has potent immunologie GVM activity. Strategies that augment the immunemediated GVM effect while minimizing the preparative regimen toxicity should further improve the outcome of alloBMT for myeloma.