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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: In recent years, umbilical cord blood has gradually become a crucial alternative source of stem cells for related and unrelated bone marrow or peripheral blood hematopoietic stem cell transplantation, which is increasingly used in the treatment of hematological malignancies in children. OBJECTIVE: To compare the clinical efficacy of sibling donor umbilical cord blood transplantation and unrelated umbilical cord blood transplantation for treating hematological malignancies in children. METHODS: The clinical data of children with hematological malignancies who received umbilical cord blood transplantation at the Hematopoietic Stem Cell Transplantation Center of the First Affiliated Hospital of Zhengzhou University between January 1, 1998 and December 31, 2018 was retrospectively analyzed. All the patients received myelablative conditioning regimen, and cyslosporine A combined with or without mycophenolate mofetil were concurrently adopted for graft-versus-host disease prophylaxis. RESULTS AND CONCLUSION: (1) Two patients in the sibling donor umbilical cord blood transplantation group and three in the unrelated umbilical cord blood transplantation group did not attain hematological engraftment and subsequently died from infection, and other patients succeeded in hematological engraftment. The median time of neutrophil and platelet engraftment in the sibling donor umbilical cord blood transplantation and unrelated umbilical cord blood transplantation groups was [17 days (11-43 days), 18 days (12-45 days), P=0.307] and [20.5 days (15-50 days), 27 days (18-56 days), P=0.773]. There was no significant difference between the two groups. (2) The incidence of acute graft-versus-host disease and chronic graft-versus-host disease in the sibling donor umbilical cord blood transplantation and unrelated umbilical cord blood transplantation groups was 36% vs. 43% (P=0.737) and 15% vs. 33% (P=0.412). There was no significant difference between the two groups. There was also no significant difference in the incidence of infection after transplantation between sibling donor umbilical cord blood transplantation and unrelated umbilical cord blood transplantation groups (56% vs. 71%, P=0.343). (3) There were no significant differences in the 2-year overall survival (61% vs. 36%, P=0.301), or 2-year relapse-free survival (56% vs. 33%, P=0.151). The 5-year overall survival and 5-year relapse-free survival in the sibling donor umbilical cord blood transplantation and unrelated umbilical cord blood transplantation groups were 54% vs. 24% (P=0.044) and 50% vs. 20% (P=0.039). The results showed that there was a significant difference in long-term survival rate between two groups. (4) Our results reveal that both sibling donor umbilical cord blood transplantation and unrelated umbilical cord blood transplantation are safe, effective and applicable for children with hematological malignancies. In particular, there are significant benefits in the long-term survival of substitute donor transplantation for pediatric patients with hematological malignancies.
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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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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.
Subject(s)
Adult , Animals , Humans , Rabbits , Antilymphocyte Serum , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Peripheral Blood Stem Cell Transplantation , Retrospective Studies , Transplantation ConditioningABSTRACT
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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Objective@#To compare incidence and clinical features of hemorrhage cystitis (HC) after haploidentical donor (HID) allogeneic hematopoietic stem cell transplantation (HSCT) and matched sibling donor (MSD) HSCT.@*Methods@#Medical records of 609 (including 406 HID-HSCT and 203 MSD-HSCT cases) hematologic malignancies patients treated with HSCT undergoing myeloablative conditioning regimen from January 2011 to December 2012 were analyzed retrospectively.@*Results@#HC occurred 183 in HID and 17 ones in MSD respectively. The cumulative incidence of HC in HID group was higher than in MSD group[ (45.6±2.5) % vs (8.5±2.0) %, χ2=77.331, P<0.001], and the cumulative incidence of severe HC (grade 3-4) in HID cases was also higher than in MSD ones[ (11.2±1.9) % vs (2.1±1.1) %, χ2=12.883, P<0.001]. All HCs were occurred within 180 days in both groups. The median time to onset in two groups were 27 days after HSCT (range 0-177 days) and 29 days after HSCT (range 6-72 days) respectively (P=0.766) . The median duration of HC in two groups were 21 days (range 3-157 days) and 13 days (range 5-67 days) , respectively (P=0.182) . The total efficiency of treatment in two groups were 69.9% and 70.6% respectively (χ2=0.003, P=1.000) .@*Conclusion@#The cumulative incidences of HC and severe HC were higher in HID cases than in MSD ones. The median time to onset and median duration of HC and therapeutic outcome between HID and MSD were comparable.
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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.
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BACKGROUND: There has been changed in estimation of the stem cell content of the graft for several decades. However, there is not always correlating the transplanted cell dose with hematologic recovery, and there are few reports in human leukocyte antigen (HLA)-matched sibling allogeneic bone marrow transplantation (AlloBMT) in Korea. The purpose of this study is to report the influence of number of transplanted cell dose on hematologic recovery and the clinical outcomes in HLA-matched sibling AlloBMT. METHODS: Between June 1999 and March 2004, 31 AlloBMT from HLA-matched sibling donor was done in patients with hematologic malignancy. All patients were conditioned with busulfan and cyclophosphamide. Short course methotrexate and cyclosporine regimen was used for prophylaxis of graft-versus-host disease. We analyzed hematologic recovery time and clinical outcomes according to transplanted cell dose. RESULTS: There were 16 male and 15 female patients, with a median age of 34 years (range, 16~48). Underlying diseases were 17 acute myeloid leukemia, 4 acute lymphoblastic leukemia, 3 myelodysplastic syndrome (high-risk), and 7 chronic myelogenous leukemia. The median number of total nucleated cell (TNC), mononuclear cell (MNC) and CD34+ cell infused was 3.95x10(8)/kg (range, 1.67~7.30x10(8)/kg), 0.65x10(8)/kg (range, 0.11~2.50x10(8)/kg), and 2.32x106/kg (range, 0.35~7.45x106/kg), respectively. The median days of neutrophil and platelet engraftment (ANC>500/microliter and platelet > 20,000/L without transfusion) were 15 (range, 10~19), 16 (range, 7~37), respectively. Relationship between the rate of neutrophil engraftment and the number of infused TNC was only statistically significant (P=0.038, R2=0.328). This study showed survival benefit with the increment of CD34+ cell dose without significance statistically (P=0.082). CONCLUSION: Although the dose of the number of transplanted MNC and CD34+ cells had no influence on granulocyte or platelet recovery, the number of TNC had only a beneficial effect on neutrophil recovery. The transplanted dose of CD34+ cells, rather than those of TNC and MNC may be related with better survival.