ABSTRACT
Objective:To explore the clinical efficacy and risk factors of umbilical cord mesenchymal stem cells (UCMSCs) infusion at an early stage (i.e.gross hematuria) for hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:The relevant clinical data were retrospectively reviewed for 300 patients undergoing allo-HSCT from January 2016 to July 2021.According to the presence or absence of HC, they were assigned into two groups of HC (n=89) and non-HC (control, n=211). According to whether or not receiving an infusion of UCMSCs, 51 patients of HC degree Ⅱ-Ⅳ were divided into two groups of UCMSC infusion and non-infusion.The risk factors of HC after allo-HSCT were analyzed by χ2 test.Logistic regression was employed for multivariate analysis of P<0.05.Mann-Whitney U test was utilized for statistically analyzing the duration of gross hematuria and urinary tract irritation symptoms and evaluating the clinical efficacy of UCMSCs infusion for HC. Results:Among them, 89 (29.67%) developed HC post-allo-HSCT.Clinical grades were Ⅰ (n=38, 42.70%), Ⅱ (n=36, 40.45%), Ⅲ (n=13, 14.61%) and Ⅳ (n=2, 2.25%). The median occurrence time was 29 (21.5-35.0) days post-allo-HSCT.In univariate analysis, age ≤30 years, haploid transplantation, antithymocyte globulin (ATG), acute graft-versus-host disease (aGVHD), CMV-DNA positive pretreatment significantly boosted the risk of HC ( P<0.05). In multivariate analysis, aGVHD was an independent risk factor for HC ( OR=10.281, 95% CI: 1.606-65.813, P=0.014). Among 89 HC patients, 38 grade Ⅰ patients were complete remission(CR). Among 51 patients of grade Ⅱ-Ⅳ HC, the outcomes were CR (n=48) and non-remission(NR)(n=3). And 24/51 of them received UCMSCs plus conventional treatment.The duration of gross hematuria was shorter in UCMSCs infusion group than that in UCMSCs non-infusion group [12(9-17) vs 17(12.0-26.5) day] and the difference was statistically significant ( P=0.045). And the duration of urinary tract irritation symptoms was shorter in UCMSCs infusion group than that in UCMSCs non-infusion group [18(11-30) vs 27(18.0-35.5) days] and the difference was statistically significant ( P=0.048). Conclusions:Indicated for post-ALLO-HSCT HC, infusion of UCMSCs may significantly shorten the course of disease.Age ≤30 years, haploid transplantation and preconditioning with positive ATG, aGVHD and CMV-DNA may boost the risks of HC post-allo-HSCT.And aGVHD is an independent risk factor for HC after allo-HSCT.
ABSTRACT
Objective:To evaluate the safety and efficacy of bortezomib plus highdose melphalan (L-phenylalanine nitrogen mustard) (Bor-HDM) pretreatment regimen for multiple myeloma (MM) with autologous hematopoietic stem cell transplantation (ASCT).Methods:From August 2008 to December 2021, the relevant clinical data were retrospectively reviewed for 58 MM patients undergoing MM transplantation.The conditioning regimens were Bor-HDM (n=36) and HDM (n=22). Non-hematopoietic adverse reactions, hematopoietic reconstruction time, remission rate post-ASCT and minimal negative rate of residual disease (MRD) on flow cytometry within 3 months post-ASCT and survivals were analyzed.Results:In Bor-HDM and HDM groups, median time of neutrophil engraftment was 12(8-30) and 11(8-29) day and median time of platelet reconstitution 16(8-33) and 16(7-32) day respectively.There was no significant inter-group difference ( P=0.890, P=0.638). In Bor-HDM group, the most common non-hematological adverse reactions were nausea (n=21, 58.0%) and diarrhea (n=11, 30.6%). There was no transplant-related death.Complete remission (CR) rate was (25/36, 69.4%) versus (9/22, 40.9%). The inter-group difference was statistically significant ( P=0.032). Median follow-up period was 29.0(2.0-91.0) vs. 20.5(5.0-114.0) month, 3-year progression-free survival(PFS)62.1% vs. 39.7% and 3-year overall survival(OS) 83.8% vs. 62.5%.There were relapse (n=10 vs.10) and death (n=6 vs. 7). Median PFS in Bor-HDM and HDM groups was non-attained and 27 months( P=0.047) and median OS time non-attained and 40 months respectively ( P=0.282). Multivariate analysis revealed that CR was an independent risk factor for PFS ( HR=28.896, 95% CI: 6.130-136.198, P<0.001). Non-CR was an independent risk factor for OS ( HR=3.843, 95% CI: 1.334-11.071, P=0.013; HR=28.595, 95% CI: 6.273-130.355, P<0.001). Conclusions:Bor-HDM pretreatment regimen of ASCT is both safe and efficacious for MM patients.