Safe and effective use of outpatient non-myeloablative allogeneic stem cell transplantation for myeloma

Multiple myeloma (MM) remains incurable despite widespread deployment of novel agents and high-dose melphalan/autologous stem cell transplantation (ASCT) earlier in the disease course. Recently, non-myeloablative (NMA) allogeneic stem cell transplantation (allo SCT) has been introduced in an attempt to exploit the well-documented graft-versus-myeloma effect (GVM), while at the same time reducing the prohibitively high transplantrelated-mortality (TRM) associated with myeloablative allografting in the past. This approach, however, still results in significant rates of acute and chronic graft-versus-host disease (GVHD) and has limited cytoreductive capability. The sequential use of a cytoreductive and immunosuppressive ASCT followed by a NMA allo SCT (auto-allo SCT), with the aim of reducing TRM and optimizing tumur control through a GVM effect, has been explored by a number of groups and compared prospectively with tandem ASCT. Although this represents a promising approach, a recent meta-analysis of six biological assignment trials of almost 1200 patients found outcome data to be inconsistent because of the various conditioning regimens used, and any improvements in progression-free survival (PFS) and overall survival (OS) are frequently offset by the high allo SCT-associated TRM. We report our single-institution experience of delivering auto-allo SCT for MM in the ambulatory setting, associated with limited toxicity, a low TRM and minimal resource utilization. From May 2008 to December 2012, 33 patients with a diagnosis of MM underwent an auto-allo SCT at the Alfred Hospital. Patients were considered for auto-allo SCT if they were o70 years old, had no significant co-morbidity at the time of transplant, had a suitably matched related or unrelated donor and had achieved at least a partial response (PR) to their latest line of therapy. All tandem auto-allo SCT procedures were performed as an elective treatment programe with the allo SCT timed to occur within 3 months of the ASCT. Patients were selected for an ‘upfront’ (n1⁄4 18) auto-allo SCT if they had high-risk disease defined as having at least 2 of the following criteria at presentation: high-risk cytogenetics, elevated LDH, ISS stage III or less than a PR with an induction regimen that included a novel agent. In contrast, patients transplanted as a ‘deferred’ procedure (n1⁄4 15) underwent a planned auto-allo SCT as salvage therapy for progressive or relapsed disease, usually following initial treatment with highdose melphalan, ASCT and maintenance therapy. Baseline characteristics of all patients included in the cohort are outlined in Table 1. The ASCT conditioning regimen was melphalan 200mg/m on day 1 followed by infusion of G-CSF-mobilized peripheral blood stem cells (minimum dose 2 10/kg) on day 0. Deferred ASCT was performed using cells mobilized and collected prior to the initial ASCT. The NMA allo SCT transplant regimen was administered in the outpatient setting using a conditioning regimen of oral fludarabine 42mg/m on days 4 to 2 followed by 2Gy of total body irradiation (TBI) on day 0 in one fraction. A target cell dose of 2 10/kg CD34þ donor stem cells was infused on day 0. GVHD prophylaxis consisted of cyclosporine (ceased by day 56 for sibling donors and day 180 for unrelated donors in the absence of GVHD) and mycophenolate mofetil (ceased by days 27 and 96 for sibling and unrelated donors respectively). Standard opportunistic infection prophylaxis was routinely employed in all patients. The majority of patients had their allo SCT as an outpatient; four (12%) were electively admitted for geographical reasons alone. Patients