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

ABSTRACT: Despite 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.We systematically searched PubMed, Embase, and the Cochrane Library from 2007.01.01 to 2017.05.03 using the keywords 'allogeneic' and 'myeloma'.A 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.Due 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.

SUBMITTER: Yin X

PROVIDER: S-EPMC5913895 | biostudies-other | 2018

REPOSITORIES: biostudies-other

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

Yin Xuejiao X Tang Liang L Fan Fengjuan F Jiang Qinyue Q Sun Chunyan C Hu Yu Y

Cancer cell international 20180423

<h4>Background</h4>Despite 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.<h4>Patients/methods</h4>We systematically searched PubMed, Embase, and the Cochra ...[more]

PMID: 29713245

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Project description:BackgroundAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is life-saving for severe hematological conditions. However, its outcomes need further improvement, and co-infusion of mesenchymal stem cells (MSCs) may show promise. A growing body of research on this subject exists, while the results of different trials are conflicting. A systematic review and meta-analysis is needed to appraise the real efficacy and safety of MSC co-transplantation in allo-HSCT.MethodsStudies comparing MSC co-transplantation in allo-HSCT with allo-HSCT alone were searched in six medical databases from inception to June 10, 2020. The primary outcomes were engraftment and graft-versus-host disease (aGVHD and cGVHD, respectively). Other outcomes included overall survival (OS), relapse rate (RR), non-relapse mortality (NRM), and immune reconstitution. Information was independently extracted by two investigators. Methodological quality was assessed using the Cochrane Collaboration tool. Meta-analysis was performed using RevMan 5.4.ResultsSix randomized controlled trials (RCTs) and 13 non-randomized controlled trials (nRCTs) were included. MSC co-infusion resulted in shorter times to neutrophil engraftment (RCTs: standardized mean difference (SMD) - 1.20, p = 0.04; nRCTs: SMD - 0.54, p = 0.04) and platelet engraftment (RCTs: SMD - 0.60, p = 0.04; nRCTs: SMD - 0.70, p = 0.01), a lower risk of cGVHD (RCTs: risk ratio (RR) 0.53, p = 0.01; nRCTs: RR 0.50, p < 0.01), and a slightly positive trend towards reducing the risk of aGVHD and NRM, without affecting RR and OS. Subgroup analyses revealed that when MSCs were co-transplanted, children and adolescents, and patients receiving human leukocyte antigen (HLA)-nonidentical HSCT showed improvements in engraftment and incidence of GVHD and NRM; adults and patients who received HLA-identical HSCT had lower cGVHD; patients with malignancies exhibited improvements in GVHD and NRM incidence; and patients with non-malignancies experienced accelerated engraftment. Notably, a reduced OS was observed in patients with hematological malignancies undergoing HLA-identical HSCT.ConclusionMSC co-infusion generally improved engraftment and reduced cGVHD, without increasing mortality or relapse. Regarding aGVHD and NRM, the effects of MSCs were not quite significant. Specifically, our data support the utilization of MSC co-transplantation in children and young individuals with HLA-nonidentical HSCT, but not in adult patients with hematological malignancies undergoing HLA-identical HSCT.

Project description:BACKGROUND:Data are lacking on whether lenalidomide maintenance therapy prolongs the time to disease progression after autologous hematopoietic stem-cell transplantation in patients with multiple myeloma. METHODS:Between April 2005 and July 2009, we randomly assigned 460 patients who were younger than 71 years of age and had stable disease or a marginal, partial, or complete response 100 days after undergoing stem-cell transplantation to lenalidomide or placebo, which was administered until disease progression. The starting dose of lenalidomide was 10 mg per day (range, 5 to 15). RESULTS:The study-drug assignments were unblinded in 2009, when a planned interim analysis showed a significantly longer time to disease progression in the lenalidomide group. At unblinding, 20% of patients who received lenalidomide and 44% of patients who received placebo had progressive disease or had died (P<0.001); of the remaining 128 patients who received placebo and who did not have progressive disease, 86 crossed over to lenalidomide. At a median follow-up of 34 months, 86 of 231 patients who received lenalidomide (37%) and 132 of 229 patients who received placebo (58%) had disease progression or had died. The median time to progression was 46 months in the lenalidomide group and 27 months in the placebo group (P<0.001). A total of 35 patients who received lenalidomide (15%) and 53 patients who received placebo (23%) died (P=0.03). More grade 3 or 4 hematologic adverse events and grade 3 nonhematologic adverse events occurred in patients who received lenalidomide (P<0.001 for both comparisons). Second primary cancers occurred in 18 patients who received lenalidomide (8%) and 6 patients who received placebo (3%). CONCLUSIONS:Lenalidomide maintenance therapy, initiated at day 100 after hematopoietic stem-cell transplantation, was associated with more toxicity and second cancers but a significantly longer time to disease progression and significantly improved overall survival among patients with myeloma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00114101.).

Project description:BackgroundOutpatient autologous stem cell transplantations (ASCTs) in multiple myeloma and lymphoma patients have been shown to reduce the overall costs and improve the quality of life relative to inpatient ASCTs. This systematic review and meta-analysis was performed with the aim of comprehensively comparing the risk of febrile neutropenia developing in ASCT outpatients and inpatients who have multiple myeloma or lymphoma.MethodsTo be eligible for the meta-analysis, studies needed to be either randomized, controlled studies or cohort studies. They also need to have two groups of patients with multiple myeloma or lymphoma who underwent ASCT, with the treatment being provided to one group in an outpatient setting and to the other on an inpatient basis. The studies had to report our primary outcome of interest, the rate of febrile neutropenia after stem cell infusion, for both groups. The Mantel-Haenszel method was used to pool the effect estimates and 95% confidence intervals of each study.ResultsFrom 9 eligible studies, a total of 1940 patients were included in the meta-analysis. Contrary to conventional concerns, the patients who underwent the outpatient ASCT had a significantly lower risk of developing febrile neutropenia than those admitted for ASCT, with a pooled odds ratio (OR) of 0.44 (95% confidence interval [CI]: 0.29-0.65; p?<?0.0001; I2?=?52%). The risk of septicemia was also significantly lower for the outpatients than the inpatients, with a pooled OR of 0.40 (95% CI: 0.16-0.97; p?=?0.04; I2?=?23%). Additional analyses found that the odds of having grade 2-3 mucositis and transplant-related mortality were numerically lower for the outpatient group, although the pooled result was not statistically significant. The odds of surviving at 2-3?years was also numerically higher for the ASCT outpatients, but the difference did not reach statistical significance.ConclusionsThis study found a significantly lower odds of developing febrile neutropenia and septicemia among patients with multiple myeloma and lymphoma who received an outpatient ASCT than among those who had an inpatient ASCT.

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

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

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