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Summary: We aimed to identify the efficacy of haploidentical related donor (HID) haematopoietic stem cell transplantation (HSCT) in adolescent and young adults (AYAs) with acute myeloid leukaemia (AML) in a large cohort. Consecutive AML AYAs (15–39 years old, n = 599) receiving HID HSCT in complete remission (CR) were included. The 3‐year cumulative incidence of measurable residual disease occurrence, relapse and non‐relapse mortality after HID HSCT was 28.6% (95% CI: 25.0–32.2), 11.6% (95% CI: 9.0–14.2) and 6.7% (95% CI: 4.7–8.7) respectively. The 3‐year probability of event‐free survival, leukaemia‐free survival (LFS) and overall survival (OS) after HID HSCT was 60.7% (95% CI: 56.9–64.8), 81.7% (95% CI: 78.7–84.9) and 85.6% (95% CI: 82.8–88.4) respectively. In multivariable analysis, AML risk category at diagnosis and comorbidity burdens before HID HSCT were independently associated with LFS and OS. Compared to the older adults (≥ 40 years, n = 355) with AML receiving HID HSCT in CR during the same time period, AYAs have a lower incidence of non‐relapse mortality and higher probabilities of LFS and OS. Thus, we firstly confirmed the safety and efficacy of HID HSCT in AYAs with AML‐CR. [ABSTRACT FROM AUTHOR]

Summary: Haploidentical allogeneic haematopoietic stem cell transplantation (haplo‐HSCT) is a significant alternative treatment for severe aplastic anaemia (SAA). To improve this process by modifying the risk stratification system, we conducted a retrospective study using our database. 432 SAA patients who received haplo‐HSCT between 2006 and 2020 were enrolled. These patients were divided into a training (n = 288) and a validation (n = 144) subset randomly. In the training cohort, longer time from diagnosis to transplantation, poorer Eastern Cooperative Oncology Group (ECOG) status and higher haematopoietic cell transplantation‐specific comorbidity index (HCT‐CI) score were independent risk factors for worse treatment‐related mortality (TRM) in the final multivariable model. The haplo‐HSCT scoring system was developed by these three parameters. Three‐year TRM after haplo‐HSCT were 6% [95% confidence interval (CI), 1–21%], 21% (95% CI, 7–40%), and 47% (95% CI, 20–70%) for the low‐, intermediate‐, and high‐risk group, respectively (P < 0·0001). In the validation cohort, the haplo‐HSCT scoring system also separated patients into three risk groups with increasing risk of TRM: intermediate‐risk [hazard ratio (HR) 2·45, 95% CI, 0·92–6·53] and high‐risk (HR 11·74, 95% CI, 3·07–44·89) compared with the low‐risk group (P = 0·001). In conclusion, the haplo‐HSCT scoring system could effectively predict TRM after transplantation. [ABSTRACT FROM AUTHOR]

Summary: Hepatitis E virus (HEV) is increasingly found to cause hepatitis in allogeneic haematopoietic stem cell transplantation (HSCT) patients. However, little is known about HEV infection in patients receiving haploidentical HSCT (haplo‐HSCT). Here, we retrospectively evaluate the incidence and clinical course of HEV infection in haplo‐HSCT patients. From January 2014 to July 2017, 177 patients with unexplained elevated transaminases after receiving haplo‐HSCT at Peking University Institute of Haematology were screened for HEV using HEV serology. HEV RNA was assessed in blood samples when HEV‐IgG and/or IgM antibodies were positive. Acute HEV infection was identified in 7 patients (3·9%), 1 of whom had developed a chronic HEV infection. The median time from haplo‐HSCT to HEV infection was 17·5 (range, 6–55) months. HEV infection was confirmed by the presentation of anti‐HEV IgM + anti‐HEV IgG (rising) (n = 5) or HEV‐RNA + anti‐HEV IgM + anti‐HEV IgG (n = 2). None of the patients died of HEV infection directly: 2 patients with HEV infection died showing signs of ongoing hepatitis, and 5 patients cleared HEV with a median duration of HEV infection of 1·5 (range, 1·0–5·7) months. In conclusion, HEV infection is a rare but serious complication after haplo‐HSCT. We recommend screening of HEV in haplo‐HSCT. [ABSTRACT FROM AUTHOR]

Abstract A key issue in the haploiedntical hematopoietic stem cell transplantation (haplo-HSCT) setting is the search for the best donor, because donor selection can significantly impact the clinical outcomes. We aimed to identify the role of collateral related donors (CRDs) in donor selection for haplo-HSCT through comparing the clinical outcomes between CRDs (n = 60) and maternal donors (MDs, n = 296), which were the last choice of donor selection in immediate related donors (IRDs). The cumulative incidence of graft-versus-host disease was comparable between CRDs and MDs. The 5-year cumulative incidence of relapse and non-relapse mortality was 22.0% (95% CI, 11.3%–32.7%) versus 17.4% (95% CI, 13.0%–21.8%) (P = 0.455) and 25.0% (95% CI, 13.9%–36.1%) versus 23.1% (95% CI, 18.2%–28.0%) (P = 0.721) for the CRDs and MDs, respectively. The 5-year probabilities of disease-free survival and overall survival was 53.2% (95% CI, 40.4%–66.0%) versus 59.5% (95% CI, 53.8%–65.2%) (P = 0.406) and 56.5% (95% CI, 43.8%–69.2%) versus 61.8% (95% CI, 56.1%–67.5%) (P = 0.458) for the CRDs and MDs, respectively. Female donor/male recipient (FDMR) CRDs were associated with the poorest clinical outcomes, and the clinical outcomes of non-FDMR CRDs were comparable to those of MDs. In summary, our results showed that CRDs did not showed superiority over MDs. Thus, IRDs should be the first choice of donor selection, and CRDs could only be the donors for those without IRDs. [ABSTRACT FROM AUTHOR]

This study aimed to validate the capability of the Center for International Blood and Marrow Transplant Research (CIBMTR) prognostic scoring system to predict outcomes of patients with myelodysplastic syndromes (MDS) who had undergone HLA-haploidentical related donor hematopoietic stem cell transplantation (haplo-HSCT). We also propose and validate a more suitable prognostic scoring system. A total of 157 patients with MDS who underwent haplo-HSCT were enrolled. The CIBMTR prognostic scoring system could predict the 2-year clinical outcomes, but failed to predict the 100-day clinical outcomes after haplo-HSCT. Our multivariable model identified 2 independent predictors of overall survival: age and monosomal karyotype (MK). Weighted scores of 5, 3, and 2 were assigned to age ≥50 years, age 30 to 49 years, and MK, respectively, and a 2-category system was created: low (score ≤3) and high (score >3). Our refined prognostic scoring system can predict both the 100-day and 2-year clinical outcomes after haplo-HSCT. Our findings indicate that the CIBMTR prognostic scoring system is predictive of the outcomes of patients with MDS following haplo-HSCT, and that older patients with MDS and/or patients with MK should be closely monitored after haplo-HSCT. [ABSTRACT FROM AUTHOR]

Background: Antithymocyte globulin (ATG) is an important component of conditioning regimens to prevent severe graft-versus-host disease (GVHD) in patients undergoing unmanipulated, haploidentical stem cell transplantation (haplo-SCT). However, to the authors' knowledge, the optimal dose of ATG is unknown.Methods: In this prospective, randomized trial, the authors compared the long-term outcomes of 2 ATG doses (rabbit thymoglobulin) used in myeloablative conditioning before unmanipulated haplo-HSCT. Patients were randomly assigned (1:1) to received 10 mg/kg (ATG-10) or 6 mg/kg (ATG-6) of ATG. Analysis of disease-free survival, GVHD-free/recurrence-free survival (GRFS), disease recurrence, nonrecurrence mortality, and chronic GVHD (cGVHD) included the entire population. Late effects were assessed in disease-free patients who had survived for at least 6 months and had received regular follow-up evaluations.Results: A total of 224 patients were recruited. The median follow-up period was 1614 days (range, 28-1929 days). The rate of infection-related deaths in ATG-10 arm was double that of the ATG-6 arm (14.3% vs 7.1%; P = .084). The 5-year cumulative incidence was comparable between the ATG-6 and ATG-10 groups for disease recurrence (12.8% vs 13.4%; P = .832) and nonrecurrence mortality (11.6% vs 17.0%; P = .263). The 5-year probability of disease-free survival was comparable between the groups (75.6% vs 69.6%; P = .283). The 5-year cumulative incidence of cGVHD was found to be higher with ATG-6 (75.0% vs 56.3% [P = .007] and moderate-to-severe cGVHD: 56.3% vs 30.4% [P<.0001]) as well as that for late effects (71.2% vs 56.9%; P = .043). The 5-year probability of GRFS was higher in the ATG-10 group (41.0% vs 26.8%; P = .008). In the multivariate analysis, ATG-10 was found to be associated with a lower risk of cGVHD and improved GRFS.Conclusions: ATG-10 was found to be associated with better GVHD prevention and superior GRFS, but an increase in infection-related deaths. Cancer 2017;123:2881-92. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (HSCT) is an important therapy option for children with acute myeloid leukemia (AML) resistant to the first course of induction chemotherapy (IC 1st ). We aimed to identify the efficacy of unmanipulated haploidentical HSCT (haplo-HSCT) in children with AML in the first complete remission and whether children resistant (IC 1st -resistant; n = 38) or sensitive (IC 1st -sensitive; n = 59) to the IC 1st can achieve comparable outcomes. The cumulative incidence of grades III to IV acute graft-versus-host disease (GVHD) and severe chronic GVHD was .0% versus 20.1% ( P  = .038) and 21.7% versus 13.2% ( P  = .238), respectively, for the IC 1st -resistant and IC 1st -sensitive groups. The 3-year cumulative incidence of relapse and nonrelapse mortality was 22.2% versus 7.6% ( P  = .061) and 5.3% versus 10.8% ( P  = .364), respectively, for the IC 1st -resistant and IC 1st -sensitive groups. The 3-year probability of overall survival and disease-free survival was 76.3% versus 83.0% ( P  = .657) and 72.5% versus 81.6% ( P  = .396), respectively, for the IC 1st -resistant and IC 1st -sensitive groups. Multivariate analysis failed to show significant differences in survival rates between the groups. Thus, our results show that unmanipulated haplo-HSCT may overcome the poor prognostic significance of IC 1st -resistance in children with AML, and it is valid as a postremission treatment for children with IC 1st -resistant AML lacking an HLA-matched donor. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective therapy for children with high-risk acute lymphoblastic leukemia (ALL). Human leukocyte antigen (HLA)-haploidentical HSCT (haplo-HSCT) or umbilical cord blood transplantation (UCBT) are both important alternative sources of stem cells for those without an HLA-identical sibling donor or unrelated matched donor. We aimed to compare the therapeutic effects of single UCBT and unmanipulated haplo-HSCT in high-risk ALL children ( n = 129). Hematopoietic recovery was significantly faster in haplo-HSCT recipients than in UCBT recipients. The 2-year cumulative incidences of relapse in the haplo-HSCT and UCBT groups were 16.1% and 24.1%, respectively ( p = 0.169). The 2-year cumulative incidences of non-relapse mortality in the haplo-HSCT and UCBT groups were 12.8% and 18.8%, respectively ( p = 0.277). The 2-year probabilities of overall survival in the haplo-HSCT and UCBT groups were 82.0% and 69.6%, respectively ( p = 0.071), and the 2-year probability of disease-free survival in the haplo-HSCT group was higher than in the UCBT group (71.0% vs. 57.2%, p = 0.040). However, several variables (such as leukocyte count and cytogenetics at diagnosis) were different between the groups, and a possible center effect should also be considered. In addition, only mild and moderate chronic graft-versus-host disease (GVHD) was associated with significantly improved survival compared to those without chronic GVHD in multivariate analysis. Thus, our results show that both unmanipulated haplo-HSCT and UCBT are valid for high-risk ALL children lacking a HLA matched donor, and both strategies expand the donor pool for children in need. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective post-consolidation therapy and curative option for adult patients with Philadelphia chromosome-negative (Ph-negative) acute lymphoblastic leukemia (ALL) in first complete remission (CR1). A human leukocyte antigen (HLA)-haploidentical related donor (haplo-RD) is one of the most important alternative sources for those without HLA-identical sibling donor (ISD). The present study aimed to evaluate the outcomes of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) in adult Ph-negative ALL CR1 patients ( n = 183). We produced an unmanipulated haplo-HSCT protocol including granulocyte colony stimulating factor (G-CSF) for all donors, intensive immune suppression, anti-thymocyte globulin, and combination of G-CSF-primed bone marrow harvest and G-CSF-mobilized peripheral blood stem cells harvest as the source of stem cell grafts. The median age for high-risk versus low-risk groups were 29 versus 23 years. Three-year incidences of relapse mortality and nonrelapse mortality for high-risk versus low-risk groups were 7.1% versus 11.1% ( p = 0.498) and 18.0% versus 16.2% ( p = 0.717), respectively. Three-year probabilities of disease-free survival and overall survival for high-risk versus low-risk groups were 67.6% versus 68.2% ( p = 0.896) and 74.9% versus 72.7% ( p = 0.981), respectively. Multivariate analysis showed that limited cGVHD and a lower pre-HSCT comorbidity burden were associated with better outcomes. In summary, comparable outcomes were observed among high- and low-risk Ph-negative ALL CR1 patients after haplo-HSCT. Haplo-RD could be considered for adults with Ph-negative ALL in CR1 as an important alternative source of donors in cases when no ISD is available. [ABSTRACT FROM AUTHOR]

We examined the incidence, risk factors, treatment, and clinical outcomes of extramedullary relapse (EMR) in 961 acute leukemia patients undergoing HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) between 2002 and 2013. Multiple control subjects were selected at random from the same cohort and matched to EMR cases for diagnosis, disease status at HSCT, age at the time of the HSCT, and year of HSCT. Forty patients exhibited EMR, with a median time to EMR of 207 days. The cumulative incidence of EMR was 4.0% at 3 years, and the incidence was higher in acute lymphoblastic leukemia patients compared with acute myeloid leukemia patients (5.6% versus 2.4%). In the multivariate analysis, non–complete remission (CR) status at HSCT (hazard ratio [HR] = 4.6; P = .018) and non–chronic graft-versus-host disease after HSCT (HR = 3.2; P < .001) were the independent risk factors for EMR after haplo-HSCT. Twenty-seven patients received combination treatments, and the proportion of patients who achieved CR was higher than those who received single treatment. Multifocal involvement at EMR (HR = 2.7; P = .024) and non-CR after EMR treatments (HR = 4.6; P < .001) were the independent risk factors for poor survival rates among EMR patients. We found that graft-versus-leukemia effect may help to prevent EMR after haplo-HSCT. [ABSTRACT FROM AUTHOR]

• This study represents the first specific report on the incidence, risk factors, and outcomes of primary PT after haplo-HSCT. • The incidence of primary PT after haplo-HSCT was 10.1%. • Primary PT was associated with poorer survival and higher TRM along with older age, grades II to IV acute GVHD, and EBV infection after haplo-HSCT. The aim of this study was to evaluate the incidence, risk factors, and outcomes of primary prolonged isolated thrombocytopenia (PT) after haploidentical hematopoietic stem cell transplant (haplo-HSCT). We retrospectively analyzed patients who received haplo-HSCT for various hematologic malignancies at Peking University Institute of Hematology between January 2015 and December 2016. Of the 918 patients, 93 (10.1%) developed primary PT. We designed a propensity score method-based study. For each primary PT patient control subjects (1:3) were selected using a propensity score–matching method. A total of 372 recipients were enrolled in the study: 93 in the PT group and 279 in the control group. Multivariate analysis showed that age older than 25 years (P =.002), median mononuclear cells (P =.000), median CD34+ counts (P =.003), history of grades II to IV acute graft-versus-host disease (GVHD; P =.000), and Epstein-Barr virus (EBV) infection after haplo-HSCT (P =.016) were independent risk factors for primary PT. Primary PT was significantly associated with higher transplant-related mortality (TRM; P <.001), inferior overall survival (P =.001), and disease-free survival (P =.005). In conclusion, the incidence of primary PT after haplo-HSCT was 10.1%. Primary PT was associated with poorer survival and higher TRM along with older age, grades II to IV acute GVHD, and EBV infection after haplo-HSCT. [ABSTRACT FROM AUTHOR]

We examined the incidence, risk factors, treatments, and clinical outcomes of post-transplantation lymphoproliferative disorder (PTLD) after unmanipulated haploidentical (haplo) hematopoietic stem cell transplantation (HSCT) in 1184 patients between 2006 and 2012. Age-, transplantation time–, and transplantation duration–matched controls were randomly selected from the same cohort. Forty-five patients experienced PTLD. The median time from HSCT to PTLD occurrence was 61 (range, 33 to 360) days and the 1-year cumulative incidence of total PTLD after haplo-HSCT was 3.0%. In multivariate analysis, a lower absolute count of CD8 + T lymphocytes at day 30, a lower absolute count of immunoglobulin M at day 30, and cytomegalovirus DNAemia after HSCT were significantly associated with higher risk of PTLD. The 2-year probability of overall survival (OS) after HSCT was 42.8%, which was comparable between the probable PTLD and the proven PTLD patients. Patients who received rituximab-based therapy had significantly better 2-year OS (48.2% versus 13.2%, P = .02). Thus, we were able to identify individuals at a high risk of developing PTLD after unmanipulated haplo-HSCT. Rituximab-based therapy can help to improve the outcomes of PTLD patients. [ABSTRACT FROM AUTHOR]

[Display omitted] Given that randomized studies testing the long-term impact of antithymocyte globulin (ATG) dosing are scarce, we report the results of an extended follow-up from the original trial. In our prospective, multicenter, randomized trial, 408 leukemia patients 14–65 years of age who underwent haploidentical hematopoietic cell transplantation (haplo-HCT) under our original "Beijing Protocol" were randomly assigned one-to-one to ATG doses of 7.5 mg/kg (n = 203, ATG-7.5) or 10 mg/kg (n = 205, ATG-10.0) at four sites. Extended follow-up (median 1968 d (range: 1300–2710 d) indicated comparable 5-year probabilities of moderate-to-severe chronic graft-versus-host disease (GVHD) (hazard ratio (HR): 1.384, 95% confidence interval (CI): 0.876–2.189, P = 0.164), nonrelapse mortality (HR: 0.814, 95% CI: 0.526–1.261, P = 0.357), relapse (HR: 1.521, 95% CI: 0.919–2.518, P = 0.103), disease-free survival (HR: 1.074, 95% CI: 0.783–1.473, P = 0.658), and GVHD-free/relapse-free survival (HR: 1.186, 95% CI: 0.904–1.555, P = 0.219) between groups (ATG-7.5 vs. ATG-10.0). The 5-year rate of late effects did not differ significantly. However, the cytomegalovirus/Epstein-Barr virus-related death rate was much higher in the ATG-10.0 cohort than in the ATG-7.5 cohort (9.8% vs. 1.5%; P = 0.003). In summary, patients undergoing haplo-HCT benefit from 7.5 mg/kg ATG compared to 10.0 mg/kg ATG based on a balance between GVHD and infection control. ATG (7.5 mg/kg) is potentially regarded as the standard regimen in the platform. These results support the optimization of ATG use in the "Beijing Protocol", especially considering the potential economic advantage in developing countries. [ABSTRACT FROM AUTHOR]

Background Herpes simplex virus (HSV)-1/2 can still be reactivated after allogeneic haematopoietic stem cell transplantation (allo-HSCT) even when the prophylactic acyclovir is used. However, the risk factors for HSV-1/2 viremia and the clinical outcomes following unmanipulated haploidentical HSCT remain unknown. Objectives and study design Nineteen patients with HSV-1/2 viremia and fifty-seven patients without HSV-1/2 viremia which were selected using the case-pair method after undergoing haploidentical HSCT were enrolled. We analysed the risk factors for HSV-1/2 viremia and compared the clinical outcomes between the two groups. Results The risk factors for HSV-1/2 viremia included HLA disparity ≥2 loci (p = 0.049) and cytomegalovirus (CMV) reactivation (p = 0.028). The incidences of platelet engraftment, oral mucositis and severe haemorrhagic cystitis (HC) in patients with and without HSV-1/2 viremia were 77% and 94% (p = 0.003), 78% and 13% (p = 0.000), and 25% and 6% (p = 0.04), respectively. Moreover, the median time to platelet engraftment in patients with and without HSV-1/2 viremia was +25 days (range, +11–+80) and +17 days (range, +8–+67) (p = 0.004), respectively. According to the multivariate analyses, HSV-1/2 viremia was associated with delayed platelet engraftment (p = 0.038), a higher incidence of oral mucositis (p = 0.000) and severe HC (p = 0.038). However, HSV-1/2 viremia was not associated with non-relapse mortality (34.0% vs. 31.5%, p = 0.26), leukaemia-free survival (60.9% vs. 57.9%, p = 0.46) and overall survival (61.2% vs. 60.7%, p = 0.37). Conclusions Based on our study results, we recommend that HSV-1/2 PCR should be performed upon clinical suspicion of HSV-1/2 infection. [ABSTRACT FROM AUTHOR]

Allogeneic stem cell transplantation (SCT) is currently the only curative treatment option for chronic myeloid leukemia (CML) patients with BCR-ABL T315I mutations. We report the outcome of SCT in 22 patients with T315I + CML, most (n = 16) from haploidentical family donors (HID-SCT). At the time the mutation was detected, 8 patients were in the chronic phase (CP), 7 in the accelerated phase (AP), and 7 in the blast phase (BP). At the time of SCT 7 were in the CP, 8 in the AP or returning to the CP post-AP (AP/AP-CPn), and 7 in the BP or returning to CP post-BP (BP/BP-CPn). The cumulative incidence of grades III to IV acute graft-versus-host disease was 9.1%. Chronic graft-versus-host disease was observed in 60.0% of patients, including 25.0% who suffered from severe disease. Four patients died of transplant-related complications at a median interval from SCT of 16.3 months. The estimated 2-year leukemia-free survival rate was 80.0%, 72.9%, and 0% in CP, AP/AP-CPn and BP/BP-CPn groups at the time of SCT, respectively. After a median follow-up of 17.3 months from SCT, 14 patients are alive, including 13 in complete molecular response and 1 with an extramedullary relapse. In conclusion, HID-SCT is a potentially curative treatment for T315I + CML patients. For patients in CP/AP, immediate SCT might result in promising survival. The outcome of patients in BP with T315I + mutation remains very poor. [ABSTRACT FROM AUTHOR]