Key Points• Tandem autologous/reducedintensity allogeneic transplantation is superior to autologous transplantation alone in multiple myeloma.Long-term follow-up of prospective studies comparing allogeneic transplantation to autologous transplantation in multiple myeloma is few and controversial. This is an update at a median follow-up of 96 months of the European Group for Blood and Marrow Transplantation Non-Myeloablative Allogeneic stem cell transplantation in Multiple Myeloma (NMAM)2000 study that prospectively compares tandem autologous/reduced intensity conditioning allogeneic transplantation (auto/RICallo) to autologous transplantation alone (auto). There are 357 myeloma patients up to age 69 years enrolled. Patients with an HLA-identical sibling were allocated to auto/RICallo (n 5 108) and those without to auto alone (n 5 249). At 96 months progression-free survival (PFS) and overall survival (OS) were 22% and 49% vs 12% (P 5 .027) and 36% (P 5 .030) with auto/RICallo and auto respectively. The corresponding relapse/progression rate (RL) was 60% vs 82% (P 5 .0002). Non-relapse mortality at 36 months was 13% vs 3% (P 5 .0004). In patients with the del(13) abnormality corresponding PFS and OS were 21% and 47% vs 5% (P 5 .026), and 31% (P 5 .154). Long-term outcome in patients with multiple myeloma was better with auto/RICallo as compared with auto only and the auto/RICallo approach seemed to overcome the poor prognostic impact of del(13) observed after autologous transplantation. Follow up longer than 5 years is necessary for correct interpretation of the value of auto/RICallo in multiple myeloma. (Blood. 2013;121(25):5055-5063) Introduction Despite improvements in survival of patients with multiple myeloma by treatment with new drugs such as thalidomide, bortezomib, and lenalidomide, documented cures of the disease are lacking. Allogeneic hematopoietic stem cell transplantation has been studied, but results have been controversial. [1][2][3][4][5][6][7] Recently, we published the first results of a prospective Non-Myeloablative Allogeneic stem cell transplantation in Multiple Myeloma study (NMAM2000) comparing tandem autologous (auto)/reduced intensity conditioning allogeneic transplantation (RICallo) with autologous transplantation-single (auto) or tandem(auto/auto).8 Although superior progression-free survival (PFS), overall survival (OS), and relapse rate (RL) using the tandem auto/RICallo treatment modality was documented using appropriate tests for crossing curves, interpretation of the results has been controversial. This update of the study, after a median follow-up of 96 months, supports and strengthens the previous conclusion that the tandem auto/RICallo approach prolongs PFS and OS long term due to lower progression/relapse rate. This is true both using an intention to treat analysis and an analysis that compares only those patients who received treatment according to protocol. Considering this study started in the era predating "novel" agents, our results suggest that reports of the "death" ...

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BackgroundThiotepa-busulfan-fludarabine (TBF) is a widely used conditioning regimen in single umbilical cord blood transplantation (SUCBT). More recently, it was introduced in the setting of non-T cell depleted haploidentical stem cell transplantation (NTD-Haplo). Whether TBF based conditioning provides additional benefit in transplantation from a particular alternative donor type remains to be established.MethodsThis was a retrospective study based on an international European registry. We compared outcomes of de-novo acute myeloid leukemia patients in complete remission receiving NTD-Haplo (n = 186) vs. SUCBT (n = 147) following myeloablative conditioning (MAC) with TBF. Median follow-up was 23 months. Treatment groups resembled in baseline characteristics.ResultsSUCBT was associated with delayed engraftment and higher graft failure. In multivariate analysis no statistically significant differences were observed between the two groups in terms of acute or chronic graft-versus-host disease (GvHD) (HR = 1.03, p = 0.92 or HR = 1.86, p = 0.21) and relapse incidence (HR = 0.8, p = 0.65). Non-relapse mortality (NRM) was significantly higher in SUCBT as compared to NTD-Haplo (HR = 2.63, p = 0.001); moreover, SUCBT did worse in terms of overall survival (HR = 2.18, p = 0.002), leukemia-free survival (HR = 1.94, p = 0.007), and GvHD relapse-free survival (HR = 2.38, p = 0.0002).ConclusionsOur results suggest that TBF-MAC might allow for a potent graft-versus-leukemia, regardless of the alternative donor type. Furthermore, in patients receiving TBF-MAC, survival with NTD-Haplo may be better compared to SUCBT due to decreased NRM.Electronic supplementary materialThe online version of this article (10.1186/s13045-018-0655-8) contains supplementary material, which is available to authorized users.

Background: The assessment of minimal residual disease (MRD) by flow cytometry (FC) has a prognostic impact in acute myeloid leukemia (AML), despite the low sensitivity in predicting relapse. Nonetheless, the role of leukemic-associated immunophenotypes (LAIPs)-related specificity on the sensitivity of MRD has not been clarified yet. In this respect, we accomplished this study.Methods: LAIP-frequencies of bone marrow samples from healthy donors and patients after treatment were quantified and subdivided in "categories of specificity" named as: "strong," "good," and "weak." At the following, the diagnostic performance of MRD was investigated in terms of sensitivity, specificity, predictive values, likelihood ratio (LR).Results: "Strong" LAIPs were identified by CD7, CD2, CD4, and CD56 markers while "weak" LAIPs, independently of coexpressed markers, were mainly observed in CD33+ cells. MRD identified patients with significantly low DFS and OS but showed a low sensitivity in predicting relapse. Interestingly, majority of recurrences was noticed in patients with two LAIPs and lacking of "strong" LAIPs or only with one "good" LAIP.Thus, only patients showing one "strong" or two "good" LAIPs were considered suitable for MRD monitoring and selected to be further investigated. In this subset, positive MRD predicted a poor prognosis. Moreover, a higher sensitivity, negative predictive value (NPV) and LR-were observed after comparison with the previous series.Conclusions: These data highlight the relevant role of LAIP classification in "categories of specificity" in improving the sensitivity of MRD as assessed by FC. K E Y W O R D S acute myeloid leukemia, categories of specificity, flow cytometry, leukemia-associated immunophenotypes (LAIPs), minimal residual disease