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Objective: To investigate whether haplotype hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of pre transplant minimal residual disease (Pre-MRD) positive acute B lymphoblastic leukemia (B-ALL) compared with HLA- matched sibling donor transplantation (MSDT) . Methods: A total of 998 patients with B-ALL in complete remission pre-HSCT who either received haplo-HSCT (n=788) or underwent MSDT (n=210) were retrospectively analyzed. The pre-transplantation leukemia burden was evaluated according to Pre-MRD determinedusing multiparameter flow cytometry (MFC) . Results: Of these patients, 997 (99.9% ) achieved sustained, full donor chimerism. The 100-day cumulative incidences of neutrophil engraftment, platelet engraftment, and grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) were 99.9% (997/998) , 95.3% (951/998) , and 26.6% (95% CI 23.8% -29.4% ) , respectively. The 3-year cumulative incidence of total chronic GVHD was 49.1% (95% CI 45.7% -52.4% ) . The 3-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) of the 998 cases were 17.3% (95% CI 15.0% -19.7% ) and 13.8% (95% CI 11.6% -16.0% ) , respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 69.1% (95% CI 66.1% -72.1% ) and 73.0% (95% CI 70.2% -75.8% ) , respectively. In the total patient group, cases with positive Pre-MRD (n=282) experienced significantly higher CIR than that of subjects with negative Pre-MRD [n=716, 31.6% (95% CI 25.8% -37.5% ) vs 14.3% (95% CI 11.4% -17.2% ) , P<0.001]. For patients in the positive Pre-MRD subgroup, cases treated with haplo-HSCT (n=219) had a lower 3-year CIR than that of cases who underwent MSDT [n=63, 27.2% (95% CI 21.0% -33.4% ) vs 47.0% (95% CI 33.8% -60.2% ) , P=0.002]. The total 998 cases were classified as five subgroups, including cases with negative Pre-MRD group (n=716) , cases with Pre-MRD<0.01% group (n=46) , cases with Pre-MRD 0.01% -<0.1% group (n=117) , cases with Pre-MRD 0.1% -<1% group (n=87) , and cases with Pre-MRD≥1% group (n=32) . For subjects in the Pre-MRD<0.01% group, haplo-HSCT (n=40) had a lower CIR than that of MSDT [n=6, 10.0% (95% CI 0.4% -19.6% ) vs 32.3% (95% CI 0% -69.9% ) , P=0.017]. For patients in the Pre-MRD 0.01% -<0.1% group, haplo-HSCT (n=81) also had a lower 3-year CIR than that of MSDT [n=36, 20.4% (95% CI 10.4% -30.4% ) vs 47.0% (95% CI 29.2% -64.8% ) , P=0.004]. In the other three subgroups, the 3-year CIR was comparable between patients who underwent haplo-HSCT and those received MSDT. A subgroup analysis of patients with Pre-MRD<0.1% (n=163) was performed, the results showed that cases received haplo-HSCT (n=121) experienced lower 3-year CIR [16.0% (95% CI 9.4% -22.7% ) vs 40.5% (95% CI 25.2% -55.8% ) , P<0.001], better 3-year LFS [78.2% (95% CI 70.6% -85.8% ) vs 47.6% (95% CI 32.2% -63.0% ) , P<0.001] and OS [80.5% (95% CI 73.1% -87.9% ) vs 54.6% (95% CI 39.2% -70.0% ) , P<0.001] than those of MSDT (n=42) , but comparable in 3-year NRM [5.8% (95% CI 1.6% -10.0% ) vs 11.9% (95% CI 2.0% -21.8% ) , P=0.188]. Multivariate analysis showed that haplo-HSCT was associated with lower CIR (HR=0.248, 95% CI 0.131-0.472, P<0.001) , and superior LFS (HR=0.275, 95% CI 0.157-0.483, P<0.001) and OS (HR=0.286, 95% CI 0.159-0.513, P<0.001) . Conclusion: Haplo HSCT has a survival advantage over MSDT in the treatment of B-ALL patients with pre MRD<0.1% .
Subject(s)
Humans , B-Lymphocytes , Graft vs Host Disease , HLA Antigens/genetics , Haplotypes , Hematopoietic Stem Cell Transplantation/adverse effects , Leukemia, B-Cell/complications , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Neoplasm, Residual , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Recurrence , Retrospective Studies , SiblingsABSTRACT
BACKGROUND: A great progress has been achieved in the allogeneic hematopoietic stem cell transplantation for aplastic anemia. However, graft-versus-host disease and graft failure after transplantation are still the main causes of non-relapse death, which seriously affect the survival of patients. OBJECTIVE: To summarize the current status and progress of allogeneic hematopoietic cell transplantation in the treatment of aplastic anemia. METHODS: The first author retrieved PubMed, CNKI, WanFang and VIP databases for the articles concerning allogeneic hematopoietic stem cell transplantation for aplastic anemia published from January 1990 to September 2019. The keywords were “aplastic anemia, matched sibling donor hematopoietic stem cell transplantation, unrelated donor hematopoietic stem cell transplantation, haploidentical hematopoietic stem cell transplantation, cord blood transplantation” in Chinese and English, respectively. Finally 55 eligible articles were included for result analysis. RESULTS AND CONCLUSION: HLA-matched sibling donor allogeneic hematopoietic stem cell transplantation is the first choice. Unrelated donor hematopoietic stem cell transplantation may be an effective and feasible first-line therapy in pediatric severe aplastic anemia patients with no matched sibling donors. Haploidentical hematopoietic stem cell transplantation and cord blood transplantation can also be important transplantation methods for severe aplastic anemia when lack of HLA-matched donors.
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Objective To evaluate the efficacy of unrelated donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for leukemic children .Methods Clinical data of 54 leukemic children undergoing allo-HSCT were retrospectively analyzed from May 2006 to March 2018 .According to the source of donor ,they were divided into matched sibling donor allo-HSCT group (MSD ,n = 27 ) and unrelated donor group (URD ,n= 27) .The clinical outcomes of leukemic children receiving URD allo- HSCT were assessed and those in MSD allo-HSCT group were enrolled as control .Results One patient with refractory AML was not implanted in URD group and the remaining 53 cases were successful in hematopoietic reconstitution .The time of neutrophil and platelet ,the incidence of acute graft-versus-host disease (aGVHD ) , chronic GVHD (cGVHD ) , generalized cGVHD and their transplant-related complications including pulmonary complications ,hemorrhagic cystitis between two groups were not statistically different (P> 0 .05) .The incidence of serious aGVHD ,cytomegalovirus (CMV) and EB virus (EBV) infection was significantly higher in URD group than that in MSD group (P< 0 .05) .The proportion of non-recurrent deaths in URD and MSD groups was 80％ and 31 .3％ respectively and the difference between two groups was statistically significant ( P = 0 .041) .The 3- year disease-free survival rate (DFS) of URD group and MSD group was (52 .9 ± 9 .8 )％ ,(38 .5 ± 8 .7 )％ and the overall 3-year survival rate (OS) was (57 .9 ± 9 .5)％ and (46 .5 ± 9 .7)％ respectively . The inter-group difference was not statistically significant ( P > 0 .05 ) .Conclusions In leukemic children ,although the incidence of complications post URD allo-HSCT is significantly increased , the prognosis is comparable to MSD allo-HSCT .It is a good choice when there is no suitable sibling donor .
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Background@#Several studies have shown that detection of minimal residual disease (MRD) in acute myeloid leukemia (AML) is an independent prognostic factor. This study aimed to evaluate the significance of dynamic MRD pretransplantation on outcome of AML patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*Methods@#We retrospectively analyzed 145 consecutive AML patients undergoing allo-HSCT in complete remission status between June 2013 and June 2016. MRD was determined with multiparameter flow cytometry after the first and second courses of chemotherapy and pre-HSCT.@*Results@#In matched sibling donor transplantation (MSDT) settings, patients with positive MRD had higher cumulative incidence of relapse (CIR) than those without MRD after the first (32.3 ± 9.7% vs. 7.7 ± 3.1%, χ = 3.661, P = 0.055) or second course of chemotherapy (57.1 ± 3.6% vs. 12.5 ± 2.7%, χ = 8.759, P = 0.003) or pre-HSCT (50.0 ± 9.7% vs. 23.0 ± 3.2%, χ = 5.547, P = 0.019). In haploidentical SCT (haplo-SCT) settings, the MRD status at those timepoints had no significant impact on clinical outcomes. However, patients with persistent positive MRD from chemotherapy to pre-HSCT had higher CIR than those without persistent positive MRD both in MSDT and haplo-SCT settings. Patients with persistent positive MRD underwent MSDT had the highest relapse incidence, followed by those with persistent positive MRD underwent haplo-SCT, those without persistent MRD underwent haplo-SCT, and those without persistent MRD underwent MSDT (66.7 ± 9.2% vs. 38.5 ± 6.0% vs. 18.8 ± 8.7% vs. 12.0 ± 1.0%, χ = 20.763, P < 0.001). Multivariate analysis showed that persistent positive MRD before transplantation was associated with higher CIR (hazard ratio [HR] = 1.69, 95% confidence interval [CI]: 1.200-2.382, P = 0.003), worse leukemia-free survival (HR = 1.812, 95% CI: 1.168-2.812, P = 0.008), and overall survival (HR = 2.354, 95% CI: 1.528-3.627, P < 0.001).@*Conclusion@#Our results suggest that persistent positive MRD before transplantation, rather than positive MRD at single timepoint, could predict poor outcome both in MSDT and haplo-SCT settings.
Subject(s)
Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Young Adult , Flow Cytometry , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Pathology , Therapeutics , Neoplasm, Residual , Diagnosis , Prognosis , Retrospective Studies , Transplantation, HomologousABSTRACT
Objective@#To explore the effectiveness of a novel GVHD prophylaxis regimen containing low-dose anti-T lymphocyte globulin (ATG) in patients undergoing peripheral blood stem cell transplantation (PBSCT) from HLA-matched sibling donors (MSD) given both the patients and donors were aged over forty years old.@*Methods@#From March 2013 to April 2017, 98 patients with hematologic malignancies were enrolled in the study. Standard GVHD prophylaxis consisted of the administration of cyclosporine A/tacrolimus and a short course of methotrexate. In ATG group, 43 patients received low-dose rabbit ATG (Sanofi, 1.5 mg/kg per day for 3 consecutive days) before PBSCT. A retrospective matched-pair analysis was performed and 55 matched controls were available. The therapeutic process and clinical outcome were retrospectively analyzed.@*Results@#①Neutrophil engraftment was achieved earlier in ATG group than the control one [13(11-17)d vs 14(12-24)d, P=0.001]. The time to platelet engraftment was similar between the two groups [14(11-43)d vs 15(11-42)d, P=0.071]. ②The cumulative incidence of aGVHD was significantly lower in ATG group [25.6% (95%CI 13.7%-39.3%) vs 49.1% (95%CI 35.2%-61.6%), P=0.018]. The incidences of grade Ⅱ-Ⅳ aGVHD [18.6% (95%CI 8.6%-31.5%) vs 23.6% (95%CI 13.4%-35.6%), P=0.509] and cGVHD [49.6% (95% CI 31.6%-65.3%) vs 56.4% (95% CI 41.4%-69.0%), P=0.221] were not significantly different between the two groups. ③The 1-year cumulative incidence of CMV viremia was similar between the two groups [21.1%(95%CI 10.3%-34.5%) vs 31.1% (95%CI 18.8%-44.2%), P=0.429]. ④The cumulative incidences of disease relapse [24.0%(95%CI 11.5%-38.9%) vs 24.0% (95% CI 12.1%-38.2%), P=0.608), non-relapse mortality [10.2% (95% CI 3.1%-22.1%) vs 21.6% (95% CI 9.4%-37.0%), P=0.411] and DFS [65.8% (95%CI 50.3%-81.3%) vs 54.4% (95%CI 37.7%-71.1%), P=0.955] were comparable between the two groups. 2-year overall survival (OS) was significantly better in ATG group than the control one [83.8% (95% CI 71.8%-90.0%) vs 58.0% (95% CI 42.2%-73.9%), P=0.019].@*Conclusion@#The addition of low-dose ATG decreased the incidence of aGVHD and improved OS. The incidences of viral infections and disease relapse remained to be similar between the two groups. These results suggested that elderly patients undergoing MSD-PBSCT may benefit from this low-dose ATG containing GVHD prophylaxis regimen.
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Objective To assess the effectiveness of unrelated donor (URD) allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of severe aplastic anemia (SAA),and the difference between URD allo-HSCT and matched sibling donor (MSD) allo-HSCT.Methods According to the source of donors,the SAA patients subject to allo-HSCT were divided into MSD allo-HSCT group (MSD group) and URD allo-HSCT group (URD group) from October 2001 to December 2016 in Henan Cancer Hospital.The efficacy and transplantation related complications were compared between two groups.Results There were no statistically significant differences in hematopoietic reconstitution and graft rejection between two groups.The incidence of grade Ⅱ-Ⅳ acute GVHD and chronic GVHD was higher in the URD group than in the MSD group (30.76％ vs.8.57％,P =0.026;26.92％ vs.5.71％,P =0.021).However,other transplant-related complications including pulmonary complications and hemorrhagic cystitis,incidence of EBV and CMV reactivation and venous occlusive disease showed no significant difference between two groups.The estimated 5-year over survival was (73.6 ± 8.7) ％ in the MSD group and (72.7 ± 9.5) ％ in the URD group (P =0.878).There was no significant difference in 5-year disease-free survival between two groups (73.6 ± 8.7％ vs.70.3 ± 10.2,P =0.668).Conclusion URD-HSCT is a novel treatment approach and could be considered as first-line therapy in selected patients without MSD.
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The outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been improved over past 50 years due to the advances in HLA matching and increasing sources of HSC donors,such as developments and progressions of HLA-matched sibling donor transplantation (MSDT),umbilical cord transplantation (UCBT/CBT),unrelative donor transplantation (URDT),and HLA haploidentical transplantation (haplo-SCT).To review and discuss progressions in field of allo-HSCT,we studied relative advances reports of Education Program Book,54th-ASH,2012.Howeover,the outcomes of allo-HSCT can be quite different according to different diseases,disease phase or patient age.Furthermore,according to our local experiences,we emphasize again significance of HSCT donor safety.