One hundred ten patients with multiple myeloma (MM) failing to achieve at least nearcomplete remission (nCR) after a first autologous stem cell transplantation (ASCT) were scheduled to receive a second ASCT (85 patients) or a reduced-intensity-conditioning allograft (allo-RIC; 25 patients), depending on the human leukocyte antigen (HLA)-identical sibling donor availability. There was a higher increase in complete remission (CR) rate (40% vs 11%, P ‫؍‬ .001) and a trend toward a longer progression-free survival (PFS; median, 31 months vs not reached, P ‫؍‬ .08) in favor of allo-RIC. In contrast, it was associated with a trend toward a higher transplantationrelated mortality (16% vs 5%, P ‫؍‬ .07), a 66% chance of chronic graft-versus-host disease and no statistical difference in event-free survival and overall survival. Although the PFS plateau observed with allo-RIC is very encouraging, this procedure is associated with high morbidity and mortality, and therefore it should still be considered investigational and restricted to well-designed prospective clinical trials. IntroductionAutologous stem cell transplantation (ASCT) has become the standard of care in the up-front therapy for younger patients with multiple myeloma (MM). [1][2][3] In 2 randomized trials, double ASCT was superior to a single transplantation in patients failing to achieve complete remission (CR) or very good partial response after the first transplantation. 4,5 However, despite tandem ASCT, patients continue to relapse and there is no survival plateau. Allogeneic stem cell transplantation is the best potential curative approach. 6,7 However, a transplantation-related mortality (TRM) rate of 30% to 50% constitutes its major limitation. [6][7][8] The use of dose-reduced intensity conditioning (allo-RIC) has reduced the TRM to 10% to 20%. 9-15 Interestingly, promising results with autograft followed by an allo-RIC have been reported. 11,13 However, only 2 trials comparing the efficacy of double ASCT versus a single autograft followed by an allo-RIC have been published and they show contradictory results. 14,15 We report the results achieved with a second ASCT versus allo-RIC in chemosensitive patients failing to achieve CR or near-complete remission (nCR) after a first ASCT. Methods Patients and treatment planPatients diagnosed with symptomatic MM between October 1, 1999, and December 31, 2004, who were younger than 70 years were included in the Programa para el Estudio y la Terapéutica de las Hemopatías Malignas y Grupo Español de Mieloma (PETHEMA/GEM)-2000 trial. They received 6 cycles of vincristine, carmustine (BCNU), melphalan, cyclophosphamide, prednisone (VBMCP)/vincristine, BCNU, adriamycin, dexamethasone (VBAD) chemotherapy 16 followed by a first ASCT. Patients failing to achieve CR or nCR (ie, persistence of a serum or urine M-protein on the electrophoretic pattern) were scheduled to receive either a secondASCT conditioned with CVB (cyclophosphamide, etoposide, BCNU) or melphalan (MEL)-200 or an allo-RIC conditioned with fludarabine 2...

Abstract-Bone marrow mononuclear cells (BMCs) from 20 patients with extensive reperfused myocardial infarction (MI) were used to assess their myocardial regenerative capability "in vitro" and their effect on postinfarction left ventricular (LV) remodeling. Human BMCs were labeled, seeded on top of cryoinjured mice heart slices, and cultured. BMCs showed tropism for and ability to graft into the damaged mouse cardiac tissue and, after 1 week, acquired a cardiomyocyte phenotype and expressed cardiac proteins, including connexin43. In the clinical trial, autologous BMCs (78Ϯ41ϫ10 6 per patient) were intracoronarily transplanted 13.5Ϯ5.5 days after MI. There were no adverse effects on microvascular function or myocardial injury. No major cardiac events occurred up to 11Ϯ5 months. At 6 months, magnetic resonance showed a decrease in the end-systolic volume, improvement of regional and global LV function, and increased thickness of the infarcted wall, whereas coronary restenosis was only 15%. No changes were found in a nonrandomized contemporary control group. Thus, BMCs are capable of nesting into the damaged myocardium and acquire a cardiac cell phenotype in vitro as well as safely benefiting ventricular remodeling in vivo. Large-scale randomized trials are needed now to assess the clinical efficacy of this treatment.

Quality of response post-transplantation, notably CR, is significantly associated with EFS and OS prolongation in newly diagnosed patients with MM. There were trends toward similar associations with pretransplantation response status.