Seven-year follow-up of allogeneic transplant using BCNU, etoposide, cytarabine and melphalan chemotherapy in patients with Hodgkin lymphoma after autograft failure: importance of minimal residual disease.

Abstract Allogeneic transplant using reduced intensity conditioning is a therapeutic option for patients with Hodgkin lymphoma (HL) who relapse after an autograft. This was a prospective study of 31 consecutive eligible patients with HL who relapsed after an autograft and underwent an allograft using BEAM (BCNU, etoposide, cytarabine, melphalan) conditioning. At a median follow-up of 7 years the progression-free survival (PFS) was 36% (95% confidence interval [CI] 19-54%) and overall survival (OS) was 42% (95% CI 23-59%). In multivariate analysis only residual disease at the time of transplant predicted outcome, with a 4-year PFS and OS of 62% and 75% for patients with minimal residual disease versus 8% and 8% for patients with gross residual disease, respectively (p = 0.005 and p = 0.001, respectively). This benefit seemed to be irrespective of chemosensitivity, with an OS for patients with chemorefractory yet minimal disease of 71% at 4 years. BEAM allogeneic transplant is effective in producing long-term remissions after autograft failure. Regardless of chemosensitivity, minimizing tumor burden pre-transplant may improve long-term outcome.

Prevention of nausea and vomiting associated with stem cell transplant: results of a prospective, randomized trial of aprepitant used with highly emetogenic preparative regimens.

Uncontrolled delayed nausea and vomiting remains a problem after high-dose preparative regimens used for autologous and allogeneic hematopoietic stem cell transplants. Recently, aprepitant was approved for highly and moderately emetogenic chemotherapy, and, in particular, is effective for decreasing delayed emesis. To evaluate its safety and efficacy in the transplantation setting, we performed a randomized, placebo-controlled, phase 3 trial of aprepitant in combination with ondansetron and dexamethasone in patients treated with ablative preparative regimens. Patients were randomized to receive oral aprepitant or placebo daily with oral ondansetron and dexamethasone during and for 3 days after the completion of the preparative regimen in this prospective randomized, double-blind study. The primary objective was complete response (CR) rate, defined as no emesis with no or mild nausea. Other endpoints included number of emetic episodes, nausea severity assessed using a 100-mm visual analog scale (VAS), the need for rescue antiemetics, and transplantation outcome, including regimen-related toxicity. One hundred eighty-one patients were randomized and 179 patients were eligible for analysis. Overall, CR rates were 81.9% for the aprepitant and 65.8% for the placebo arms (P < .001). Percentages of patients with no emesis all days were 73.3% for aprepitant and 22.5% placebo (P < .001). Mean VAS scores were 16.6 mm aprepitant and 16.9 mm placebo (NS), and there were no differences in the amount of rescue antiemetics used, regimen related toxicity, engraftment, or transplantation outcome. Aprepitant in combination with dexamethasone and ondansetron significantly decreased emesis and significant nausea, whereas not increasing RRT or affecting short-term survival but had no significant impact on the use of PRN antiemetics, or overall VAS nausea scores.

Favourable results with a single autologous stem cell transplant following conditioning with busulphan and cyclophosphamide in patients with multiple myeloma.

Both single and tandem cycles of high dose therapy and autologous peripheral blood stem cell transplantation (ASCT) have been shown to improve survival in multiple myeloma (MM) patients. We report outcomes in 104 MM patients undergoing a single transplant after conditioning with a conventional myeloablative regimen, busulphan and cyclophosphamide. The patients were either in a first (71%), or subsequent remission (29%). Peripheral blood stem cells were mobilized using cyclophosphamide and granulocyte colony stimulating factor. The conditioning regimen consisted of busulphan 0.85 mg/kg given orally every 6 h (16 doses) and cyclophosphamide 60 mg/kg/d given intravenously for 2 d. The entire conditioning, transplant and post-transplant course were in the outpatient setting for 45% patients. At a median follow-up of 26 months (range 2-98 months), the median overall and progression-free survival were 57 months [95% confidence interval (CI) 47-68] and 26 months (95% CI 20-32) respectively. Younger age and higher CD34+ cell dose infused were independently predictive of improved overall and progression-free survival. Busulphan and cyclophosphamide is an effective and well-tolerated preparative regimen for ASCT that can be given to MM patients in the outpatient setting.

BEAM allogeneic transplantation for patients with Hodgkin's disease who relapse after autologous transplantation is safe and effective.

Because few patients failing autologous transplantation for Hodgkin's disease survive long-term, we explored reduced-intensity allografts using BEAM conditioning and early withdrawal of immunosuppression as an alternative to palliative chemotherapy. Ten patients with Hodgkin's disease underwent an allograft, receiving either matched sibling peripheral blood stem cells (5), partially matched sibling bone marrow (1), or matched unrelated bone marrow (4). Graft-versus-host disease (GVHD) prophylaxis was mini-methotrexate and FK-506 with weaning at day 60. The median age of patients was 35 years (range: 21 to 49 years). The median time from initial diagnosis was 73 months (range: 12 to 172 months) and from autograft was 49 months (range: 5 to 143 months). One patient was in CR, 5 patients were in partial remission, 3 were in relapse, and 1 patient had primary refractory disease. All patients' transplants engrafted rapidly, and the 100-day mortality was 0. Two patients developed acute GVHD. Five of the 9 patients beyond 100 days have developed mild chronic GVHD, of which 1 case was progressive and required systemic therapy. All 10 responded: 8 complete responses and 2 partial remissions. Three patients have relapsed (at 2, 6, and 8 months, respectively), 1 has died at 4 months. At a mean of 12 months (range: 1 to 21 months) after allograft, 9 of 10 patients are alive, with 7 in continuous remission. BEAM allogeneic transplantation with early reduction in immunosuppression is safe (no treatment-related deaths) and effective in advanced Hodgkin's disease where autografts have failed. A graft versus lymphoma effect appears to be a significant contributing factor in responding patients.