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.
The effects of HLA-identical sibling donor (ISD) hematopoietic stem cell transplantation (HSCT) on adults with intermediate- or high-risk acute myeloid leukemia (AML) in the first complete remission ...(CR1) are well established. Previous single-center studies have demonstrated similar survival after unmanipulated haploidentical donor (HID) vs ISD HSCT for hematologic malignancies. To test the hypothesis that haploidentical HSCT would be a valid option as postremission therapy for AML patients in CR1 lacking a matched donor, we designed a disease-specific, prospective, multicenter study. Between July 2010 and November 2013, 450 patients were assigned to undergo HID (231 patients) or ISD HSCT (219 patients) according to donor availability. Among HID and ISD recipients, the 3-year disease-free survival rate was 74% and 78% (P = .34), respectively; the overall survival rate was 79% and 82% (P = .36), respectively; cumulative incidences of relapse were 15% and 15% (P = .98); and those of the nonrelapse-mortality were 13% and 8% (P = .13), respectively. In conclusion, unmanipulated haploidentical HSCT achieves outcomes similar to those of ISD HSCT for AML patients in CR1. Such transplantation was demonstrated to be a valid alternative as postremission treatment of intermediate- or high-risk AML patients in CR1 lacking an identical donor. This trial was registered at www.chictr.org as #ChiCTR-OCH-10000940.
•Haploidentical transplant achieves outcomes similar to those of identical-sibling transplant for AML patients in first remission.•Haploidentical transplant is a valid postremission treatment of intermediate- or high-risk AML patients lacking an identical donor.
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.
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.
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).
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.
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.
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.
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.
Haploidentical SCT as upfront therapy was an effective and safe option for SAA patients, with favorable outcomes in experienced centers.
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).
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
MTX on Days 1, 3, or 8 and then combined with corticosteroids or corticosteroids alone weekly.
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.
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.
The trial was registered with clinicaltrials.gov (NCT04960644).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Pediatric acute myeloid leukemia (AML) with t(8;21) (q22;q22) is classified as a low-risk group. However, relapse is still the main factor affecting survival. We aimed to investigate the effect of ...allogeneic hematopoietic stem cell transplantation (allo-HSCT) on reducing recurrence and improving the survival of high-risk pediatric t(8;21) AML based on minimal residual disease (MRD)-guided treatment, and to further explore the prognostic factors to guide risk stratification treatment and identify who will benefit from allo-HSCT.
Overall, 129 newly diagnosed pediatric t(8;21) AML patients were included in this study. Patients were divided into high-risk and low-risk group according to RUNX1-RUNX1T1 transcript levels after 2 cycles of consolidation chemotherapy. High-risk patients were divided into HSCT group and chemotherapy group according to their treatment choices. The characteristics and outcomes of 125 patients were analyzed.
For high-risk patients, allo-HSCT could improve 5-year relapse-free survival (RFS) rate compared to chemotherapy (87.4% vs. 61.9%; P = 0.026). Five-year overall survival (OS) rate in high-risk HSCT group had a trend for better than that in high-risk chemotherapy group (82.8% vs. 71.4%; P = 0.260). The 5-year RFS rate of patients with a c-KIT mutation in high-risk HSCT group had a trend for better than that of patients with a c-KIT mutation in high-risk chemotherapy group (82.9% vs. 75%; P = 0.400). Extramedullary infiltration (EI) at diagnosis was associated with a high cumulative incidence of relapse for high-risk patients (50% vs. 18.4%; P = 0.004); allo-HSCT can improve the RFS (P = 0.009).
allo-HSCT can improve the prognosis of high-risk pediatric t(8;21) AML based on MRD-guided treatment. Patients with a c-KIT mutation may benefit from allo-HSCT. EI is an independent prognostic factor for high-risk patients and allo-HSCT can improve the prognosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Adoptive therapy with cytomegalovirus (CMV)‐specific cytotoxic T lymphocytes (CMV‐CTLs) has emerged as an effective method for CMV infection. However, the efficacy reportedly ranges from 50% to 90%, ...and factors affecting anti‐CMV efficacy have not been established. We investigated the safety and efficacy of adoptive therapy with CMV‐CTLs for CMV infection in 190 patients after haploidentical stem cell transplantation (haplo‐SCT), and importantly, we analyzed the main factors affecting antiviral efficacy. The CMV peak titer decreased from 19 (range, 1.0–503.0) × 103 copies/mL to 3.9 (range, 0–112) × 103 copies/mL after CMV‐CTL infusion. The cumulative complete response (CR) rates in the first, fourth, and sixth weeks after the first CMV‐CTL infusion were 37.9% (95% CI 35.0–40.8), 76.8% (95% CI 70.7–82.9), and 89.5% (95% CI 85.2–93.8), respectively. In multivariate analysis, persistent CMV infection prior to CMV‐CTL infusion (hazard ratio HR 2.29, 95% CI 1.29–4.06, p = .005) and basiliximab treatment within 2 weeks of CMV‐CTL infusion (HR 1.87, 95% CI 1.06–3.81, p = .031) were independent predictors of poor antiviral efficacy of CMV‐CTL therapy. Our data showed that adoptive therapy with CMV‐CTLs is a safe and effective treatment for CMV infection after haplo‐SCT. Persistent CMV infection and basiliximab treatment are correlated with poor anti‐CMV efficacy of CMV‐CTL therapy.
Summary
We explored the prognostic factors for children with very high‐risk (VHR) Philadelphia chromosome (Ph) negative B‐cell acute lymphoblastic leukaemia (B‐ALL) and compared the therapeutic ...effects of intensive chemotherapy and unmanipulated haploidentical haematopoietic stem cell transplantation (haplo‐HSCT) as post‐remission treatment in these patients undergoing first complete remission (CR1). A total of 104 paediatric patients with VHR B‐ALL in CR1 were retrospectively enrolled in this study, including 42 receiving unmanipulated haplo‐HSCT (Group A) and 62 receiving ongoing chemotherapy (Group B). Estimated 3‐year overall survival (OS), disease‐free survival (DFS) and cumulative incidence of relapse (CIR) at 36·2 months median follow‐up were 69·5 ± 4·7%, 63·5 ± 4·8% and 32·4 ± 4·7%, respectively. Maintenance of persistent positive or conversion from negative to positive of measurable residual disease (MRD) and chemotherapy were independent risk factors associated with inferior long‐term survival and higher CIR. OS, DFS, and CIR differed significantly between the groups in patients with persistent positive or negative‐to‐positive MRD. Haplo‐HSCT may be an option for children with VHR Ph‐negative B‐ALL in CR1, especially for patients with persistent positive or negative‐to‐positive MRD, and could achieve better survival than intensive chemotherapy as post‐remission treatment.
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