Allogeneic stem-cell transplantation for multiple myeloma: a systematic review and meta-analysis from 2007 to 2017

Abstract

BackgroundDespite recent advances, multiple myeloma (MM) remains incurable. However, the appearance of allogeneic stem cell transplantation (allo-SCT) through graft-versus-myeloma effect provides a potential way to cure MM to some degree. This systematic review aimed to evaluate the outcome of patients receiving allo-SCT and identified a series of prognostic factors that may affect the outcome of allo-SCT.Patients/methodsWe systematically searched PubMed, Embase, and the Cochrane Library from 2007.01.01 to 2017.05.03 using the keywords ‘allogeneic’ and ‘myeloma’.ResultsA total of 61 clinical trials involving 8698 adult patients were included. The pooled estimates (95% CI) for overall survival (OS) at 1, 2, 3 and 5 years were 70 (95% CI 56–84%), 62 (95% CI 53–71%), 52 (95% CI 44–61%), and 46 (95% CI 40–52%), respectively; for progression-free survival were 51 (95% CI 38–64%), 40 (95% CI 32–48%), 34 (95% CI 27–41%), and 27 (95% CI 23–31%), respectively; and for treatment-related mortality (TRM) were 18 (95% CI 14–21%), 21 (95% CI 17–25%), 20 (95% CI 13–26%), and 27 (95% CI 21–33%), respectively. Additionally, the pooled 100-day TRM was 12 (95% CI 5–18%). The incidences of grades II–IV acute graft-versus-host disease (GVHD) and chronic GVHD were 34 (95% CI 30–37%) and 51 (95% CI 46–56%), respectively. The incidences of relapse rate (RR) and death rate were 50 (95% CI 45–55%) and 51 (95% CI 45–57%), respectively. Importantly, disease progression was the most major cause of death (48%), followed by TRM (44%). The results failed to show an apparent benefit of allo-SCT for standard risk patients, compared with tandem auto-SCT. In contrast, all 14 trials in our study showed that patients with high cytogenetic risk after allo-SCT had similar OS and PFS compared to those with standard risk, suggesting that allo-SCT may overcome the adverse prognosis of high cytogenetic risk.ConclusionDue to the lack of consistent survival benefit, allo-SCT should not be considered as a standard of care for newly diagnosed and relapsed standard-risk MM patients. However, for patients with high-risk MM who have a poor long-term prognosis, allo-SCT may be a strong consideration in their initial course of therapy or in first relapse after chemotherapy, when the risk of disease progression may outweigh the transplant-related risks. A large number of prospective randomized controlled trials were needed to prove the benefits of these therapeutic options.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0553-8) contains supplementary material, which is available to authorized users.

Comparison of Outcomes of Allogeneic Hematopoietic Cell Transplantation for Multiple Myeloma Using Three Different Conditioning Regimens

“…Similarly, Freytes et al [28], from the Center for International Blood and Marrow Transplant Research, reported 3-year PFS and OS of 6% and 20%, respectively, in patients who received an RIC allo-HCT in a salvage setting. Further, a recent meta-analysis that combined data from 7 clinical trials confirmed the favorable prognostic impact of remission status at transplantation on [29]. Several studies have suggested that allo-HCT can overcome high-risk cytogenetic abnormalities [30,31].…”

Allogeneic Stem Cell Transplantation in Relapsed/Refractory Multiple Myeloma Treatment: Is It Still Relevant?

“…It is the general consensus that a RIC regimen is preferable [33] and this trend was also seen in our cohort. Previous comparative data of the two conditioning regimens showed that RIC had a lower NRM, but the relapse rate was higher compared with MAC regimens [11]. Long term follow-up research conducted by Sahebi et al reported that 10% of patients who received RIC-alloSCT experienced late relapse after 6-12 years post-transplant [34].…”

“…Currently, the majority of the available data on alloSCT in MM is heavily geared towards the Caucasian population [11]. Considering that the treatment choices and subsequently the outcomes of MM are particularly governed by treatment option availabilities and health policies [12], the apparent paucity of Asian data propelled us to investigate the outcomes of alloSCT in Korean MM patients.…”

PERCEPT myeloma: a protocol for a pilot randomised controlled trial of exercise prehabilitation before and during autologous stem cell transplantation in patients with multiple myeloma

“…There is acknowledged variation in symptoms and consequences of treatment experienced by patients with different bloods cancers, and between undergoing allogeneic SCT and ASCT 16 18. Studies among allogeneic SCT recipients highlight the intensive nature of the medical intervention and its associated symptom burden and consequences, most notably graft versus host disease (GvHD) and an increased risk of treatment-associated mortality 19. In contrast, with autologous transplantation the mortality is considerably lower and there is no risk of GvHD, with its attendant risk of infections and short-term and long-term morbidity 18.…”