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The consensus recommendations in 2018 from The Chinese Society of Hematology (CSH) on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation (allo-HSCT) facilitated the standardization of clinical practices of allo-HSCT in China and progressive integration with the world. There have been new developments since the initial publication. To integrate recent developments and further improve the consensus, a panel of experts from the CSH recently updated the consensus recommendations, which are summarized as follows: (1) there is a new algorithm for selecting appropriate donors for allo-HSCT candidates. Haploidentical donors (HIDs) are the preferred donor choice over matched sibling donors (MSDs) for patients with high-risk leukemia or elderly patients with young offspring donors in experienced centers. This replaces the previous algorithm for donor selection, which favored MSDs over HIDs. (2) Patients with refractory/relapsed lymphoblastic malignancies are now encouraged to undergo salvage treatment with novel immunotherapies prior to HSCT. (3) The consensus has been updated to reflect additional evidence for the application of allo-HSCT in specific groups of patients with hematological malignancies (intermediate-risk acute myeloid leukemia (AML), favorable-risk AML with positive minimal residual disease, and standard-risk acute lymphoblastic leukemia). (4) The consensus has been updated to reflect additional evidence for the application of HSCT in patients with nonmalignant diseases, such as severe aplastic anemia and inherited diseases. (5) The consensus has been updated to reflect additional evidence for the administration of anti-thymocyte globulin, granulocyte colony-stimulating factors and post-transplantation cyclophosphamide in HID-HSCT.

Between 2008 and 2019, 58,914 hematopoietic stem cell transplantations (HSCTs) were reported to the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) throughout China. In this report, we focus on 2019 data and describe current trends in HSCT in China. There was continued growth in transplant activity in China, with a rapid increase in haploidentical HSCT. In 2019, a total of 12,323 cases of HSCT were reported from 149 transplant teams, 78% (9597 cases) were allogeneic HSCTs. Haploidentical donor (HID) HSCT accounted for 60% (5771 cases) of allogeneic HSCT. The most common indications for allogeneic HSCT for malignant disease were acute myeloid leukemia (AML) (37%) and acute lymphoblastic leukemia (ALL) (24%), and the largest proportion of non-malignant diseases comprised aplastic anemia (AA) (13%). Multiple stem cell source composed 70% of HID and 28% of MSD, which was typical in China. The BuCy based regimen (59%) was the most popular conditioning regimen for allogeneic HSCT, followed by the BuFlu based regimen (23%) and TBI-based regimen (12%). This survey clearly shows comprehensive information about the current state and recent trends for HSCT in China. Further efforts should be made to obtain detailed information.

Background Low-dose post-transplant cyclophosphamide (PTCy) in conjunction with anti-thymocyte globulin (ATG) appears as a potentially effective graft-versus-host disease (GVHD) prevention strategy in haploidentical hematopoietic cell transplant (haplo-HCT). Our study aims to assess the efficacy of this regimen. Methods We extended our prospective study in patients treated with low-dose PTCy (14.5 mg/kg on days 3 and 4) in ATG/granulocyte colony-stimulating factor (G-CSF)-based regimen and compared the results to the contemporary cohort of patients without low-dose PTCy (ATG cohort). Both study cohort and control are transplanted from maternal donor or collateral relatives. Results We identified 239 consecutive patients (ATG-PTCy cohort = 114; ATG cohort = 125). All patients but one in ATG cohort achieved myeloid engraftment by day 30 post-HCT. We found that both the cumulative incidence of 100-day grade III–IV aGvHD and non-relapse-mortality (NRM) in the ATG-PTCy cohort was significantly reduced than that in the ATG group (5% vs 18%; P  = 0.003; and 6% vs 15%; P = 0.045); the 2-year cumulative incidences of relapse and overall survival were comparable between the two cohorts (13% vs 14%; P  = 0.62; and 83% vs 77%; P  = 0.18, respectively). Furthermore, GVHD-free, relapse-free survival (GRFS) was significantly improved in the ATG-PTCy arm (63% vs 48%; P  = 0.039). In multivariate analysis, the joint treatment resulted in lower grade II–IV acute GVHD (HR 0.58; P  = 0.036), grade III–IV aGvHD (HR 0.28; P  = 0.006), chronic GVHD (HR 0.60; P  = 0.047), NRM (HR 0.26; P  = 0.014), and higher GRFS (HR 0.59; P  = 0.021) but slower myeloid and platelet recovery (HR 0.29 and 0.30; both P  < 0.001). Conclusions These results suggested that ATG/PTCy (low-dose) can reduce both acute and chronic GVHD as compared with standard ATG-based prophylaxis using maternal donor or collateral relatives at particular high GVHD risk.

Background Haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) is an alternative treatment method for severe aplastic anemia (SAA) patients lacking suitable identical donors and those who are refractory to immunosuppressive therapy (IST). The current study evaluated the feasibility of upfront haploidentical HSCT in SAA patients. Methods We conducted a multicenter study based on a registry database. One hundred fifty-eight SAA patients who underwent upfront transplantation between June 2012 and September 2015 were enrolled. Results Eighty-nine patients had haploidentical donors (HIDs), and 69 had matched related donors (MRDs) for HSCT. The median times for myeloid engraftment in the HID and MRD cohorts were 12 (range, 9–20) and 11 (range, 8–19) days, with a cumulative incidence of 97.8 and 97.1% ( P  = 0.528), respectively. HID recipients had an increased cumulative incidence of grades II–IV acute graft-versus-host disease (aGVHD) (30.3 vs. 1.5%, P  < 0.001), grades III–IV aGVHD (10.1 vs. 1.5%, P  = 0.026), and chronic GVHD (cGVHD) (30.6 vs. 4.4%, P  < 0.001) at 1 year but similar extensive cGVHD (3.4 vs. 0%, P  = 0.426). The three-year estimated overall survival (OS) rates were 86.1 and 91.3% ( P  = 0.358), while the three-year estimated failure-free survival (FFS) rates were 85.0 and 89.8% ( P  = 0.413) in the HID and MRD cohorts, respectively. In multivariate analysis, survival outcome for the entire population was significantly adversely associated with increased transfusions and poor performance status pre-SCT. We did not observe differences in primary engraftment and survival outcomes by donor type. Conclusions Haploidentical SCT as upfront therapy was an effective and safe option for SAA patients, with favorable outcomes in experienced centers.

Macrophages (MΦs) are an important immune cell population that are essential for tissue homeostasis and disease pathogenesis. MΦs are now classified as either M1, which produce pro-inflammatory cytokines, or M2, which produce antiinflammatory cytokines. The impact of granulocyte colony-stimulating factor (G-CSF) on MΦs in humans is unclear. Moreover, little is known about the association between MΦ subsets in allografts and the occurrence of acute graft-versus-host disease (aGVHD) in patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the current study, we found that the M1/M2 ratio was markedly decreased in both G-CSF-treated bone marrow (post-BM) and G-CSF-treated peripheral blood from healthy donors. Post-BM MΦs exhibited reduced migration and increased phagocytosis. Moreover, post-BM MΦs reduced the percentage of Th1 and Tc1 lineages and increased the percentage of Th2, Tc2, and Treg lineages. Patients who received BM grafts with a higher M1/M2 ratio exhibited a higher incidence of grade 2–4 aGVHD. In summary, our data indicate that G-CSF decreases the M1/M2 ratio in BM grafts from healthy donors, which may contribute to preventing the occurrence of grade 2–4 aGVHD in patients after allo-HSCT.

Background This study compared the effects of pre-transplantation minimal residual disease (pre-MRD) on outcomes in AML patients who underwent human leukocyte antigen-matched sibling donor transplantation (MSDT) or who received unmanipulated haploidentical allografts. Methods A retrospective study ( n  = 339) and a prospective study ( n  = 340) were performed. MRD was determined using multiparameter flow cytometry. Results Either after retrospective or prospective analysis, patients with negative pre-MRD (pre-MRDneg) had a lower incidence of relapse than those with positive pre-MRD (pre-MRDpos) in MSDT settings ( P  < 0.001 for all), but relapse was comparable in Haplo-SCT settings for patients with pre-MRDneg versus pre-MRDpos ( P  = 0.866 and 0.161, respectively). In either the retrospective ( n  = 65) or the prospective study ( n  = 76), pre-MRDpos subjects receiving Haplo-SCT experienced a lower incidence of relapse than those who underwent MSDT ( P  < 0.001 and p  = 0.017, respectively). Of the patients with pre-MRDpos in either the total ( n  = 141) or the subgroup excluding cases which received donor lymphocyte infusion (DLI; n  = 105), those who underwent MSDT had a higher incidence of relapse than those receiving haplo-SCT ( P  < 0.01 for all). Multivariate analysis showed that, for pre-MRDpos cases, haplo-SCT was associated with a low incidence of relapse and with better LFS and OS in either retrospective group, prospective group, combination groups, or subgroup not including cases which received DLI. Conclusions The results indicated that, for pre-MRD-positive AML patients, haplo-SCT was associated with lower incidence of relapse and better survival, suggesting a stronger anti-leukemia effect.

Background There is an urgent unmet need for effective initial treatment for acute graft-versus-host disease (aGVHD) adding to the standard first-line therapy with corticosteroids after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Methods We performed a multicentre, open-label, randomized, phase 3 study. Eligible patients (aged 15 years or older, had received allo-HSCT for a haematological malignancy, developed aGVHD, and received no previous therapies for aGVHD) were randomly assigned (1:1) to receive either 5 mg/m 2 MTX on Days 1, 3, or 8 and then combined with corticosteroids or corticosteroids alone weekly. Results The primary endpoint was the overall response rate (ORR) on Day 10. A total of 157 patients were randomly assigned to receive either MTX plus corticosteroids ( n  = 78; MTX group) or corticosteroids alone ( n  = 79; control group). The Day 10 ORR was 97% for the MTX group and 81% for the control group ( p  =  . 005). Among patients with mild aGVHD, the Day 10 ORR was 100% for the MTX group and 86% for the control group ( p  = .001). The 1-year estimated failure-free survival was 69% for the MTX group and 41% for the control group ( p  =  . 002). There were no differences in treatment-related adverse events between the two groups. Conclusions In conclusion, mini-dose MTX combined with corticosteroids can significantly improve the ORR in patients with aGVHD and is well tolerated, although it did not achieve the prespecified 20% improvement with the addition of MTX. Trial registration The trial was registered with clinicaltrials.gov (NCT04960644).

To define the efficacy of a single dose of 375 mg/m2 rituximab for DSA-positive patients with 2000 ≤ MFI < 10,000, we enrolled a prospective clinical cohort including patients with positive DSA treated with rituximab (n = 55, cohort A), a matched-pair cohort including cases with negative DSA (n = 110, cohort B) and a historical cohort including subjects with 2000 ≤ MFI < 10,000 without receiving any treatment for DSA (n = 22, cohort C). The incidences of primary poor graft function (PGF) in cohort A and cohort B were 5% and 1% (P = 0.076), respectively, both of which were lower than that in cohort C (27%, P < 0.001, for all). Rituximab was associated with a reduced incidence of primary PGF (HR 0.200, P = 0.023). The 3-year nonrelapse mortality of patients in cohort A and cohort B were 23% and 24%, respectively, both of which were lower than that in the cohort C (37%), although no statistical significance was observed. These results led to a low 3-year overall survival in patients in the cohort C (58%) compared with those in the cohort A (71%) and the cohort B (73%). We suggest that a single dose of rituximab could be effectively used to prevent the onset of primary PGF. The prospective cohort of this study is registered at http://www.chictr.org.cn/ChiCTR-OPC-15006672.

Background Poor graft function (PGF) or prolonged isolated thrombocytopenia (PT), which are characterized by pancytopenia or thrombocytopenia, have become serious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our previous single-arm trial suggests that N -acetyl-L-cysteine (NAC) prophylaxis reduced PGF or PT after allo-HSCT. Therefore, an open-label, randomized, phase 3 trial was performed to investigate the efficacy and tolerability of NAC prophylaxis to reduce PGF or PT after allo-HSCT. Methods A phase 3, open-label randomized trial was performed. Based on the percentage of CD34 + VEGFR2 (CD309) + endothelial cells (ECs) in bone marrow (BM) detected by flow cytometry at 14 days before conditioning, patients aged 15 to 60 years with acute leukemia undergoing haploidentical HSCT were categorized as low-risk (EC ≥ 0.1%) or high-risk (EC < 0.1%); patients at high risk were randomly assigned (2:1) to receive NAC prophylaxis or nonprophylaxis. The primary endpoint was PGF and PT incidence at +60 days post-HSCT. Results Between April 18, 2019, and June 24, 2021, 120 patients with BM EC <0.1% were randomly assigned for NAC (group A, N = 80) or nonprophylaxis (group B, N = 40), and 105 patients with EC≥0.1% (group C) were also analyzed. The +60 days incidence of PGF and PT was 7.5% (95% CI, 1.7 to 13.3%) and 22.5% (95% CI, 9.1 to 35.9%) in group A and group B (hazard ratio, 0.317; 95% CI, 0.113 to 0.890; P = 0.021) and 11.4% (95% CI, 5.2 to 17.6%) in group C (hazard ratio, 0.643; 95% CI, 0.242 to 1.715; P = 0.373). Consistently, NAC prophylaxis gradually improved BM ECs and CD34 + cells in group A, whereas reduced their reactive oxygen species (ROS) levels post-HSCT. Within 60 days post-HSCT, the most common grade 3 to 5 adverse events for the NAC and control groups were infections (19/80 [24%] vs. 10/40 [25%]) and gastrointestinal adverse events (16/80 [20%] vs. 7/40 [18%]). There were no treatment-related deaths. Conclusions N -Acetyl-L-cysteine prophylaxis can prevent the occurrence of poor hematopoietic function and is well tolerated in haploidentical HSCT. It may offer a potential pathogenesis-oriented therapeutic approach for patients with poor hematopoietic function. Trial registration This trial was registered at ClinicalTrials.gov as #NCT03967665.

Background Previous reports suggest a benefit associated with haploidentical donor transplantation (HIDT) compared to matched sibling donor transplantation (MSDT) in certain contexts, and the choice of optimal candidates warrants further investigation. Methods We designed a prospective genetically randomized study to evaluate donor options between acute lymphoblastic leukemia (ALL) patients positive for measurable residual disease (MRD) pre-transplantation who underwent HIDT ( n = 169) or MSDT ( n = 39). Results The cumulative incidence of positive MRD post-transplantation was 26% (95% CI, 19–33%) and 44% (95% CI, 28–60%) for HIDT and MSDT, respectively ( P = 0.043). Compared to the HIDT cohort, the MSDT cohort had a higher 3-year cumulative incidence of relapse (CIR; 47%, 95% CI, 31–63% vs. 23%, 95% CI, 17–29%; P = 0.006) and lower 3-year probability of leukemia-free survival (LFS; 43%, 95% CI, 27–59% vs. 65%, 95% CI, 58–72%; P = 0.023) and overall survival (OS; 46%, 95% CI, 30–62% vs. 68%, 95% CI, 61–75%; P = 0.039), without a difference in non-relapse-mortality (10%, 95% CI, 1–19% vs. 11%, 95% CI, 6–16%; P = 0.845). Multivariate analysis showed that HIDT is associated with a low CIR (HR = 0.364; 95% CI, 0.202–0.655; P = 0.001) and better LFS (HR = 0.414; 95% CI, 0.246–0.695; P = 0.001) and OS (HR = 0.380; 95% CI, 0.220–0.656; P = 0.001). Conclusions HIDT is better than MSDT in view of favorable anti-leukemia activity for patients with pre-transplantation MRD positive ALL. The current study paves the way to determine that haploidentical donors are the preferred choice regardless of available matched sibling donors in a subgroup population. Trial registration ClinicalTrials.gov Identifier: NCT02185261. Registered July 9, 2014. https://clinicaltrials.gov/ct2/show/NCT02185261?term=NCT02185261&draw=2&rank=1 .