Search

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.

Relapse is the main problem after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The outcome of a second allo-HSCT (HSCT2) for relapse post-HSCT has shown promising results in some previous studies. However, little is known about the efficacy of HSCT2 in patients with relapsed/refractory acute leukemia (AL) post-chemotherapy plus modified donor lymphocyte infusion (post-Chemo + m-DLI) after the first allo-HSCT (HSCT1). Therefore, we retrospectively analyzed the efficacy of HSCT2 in 28 patients with relapsed/refractory AL post-Chemo + m-DLI in our center. With a median follow-up of 918 (457-1732) days, 26 patients (92.9%) achieved complete remission, and 2 patients exhibited persistent disease. The probabilities of overall survival (OS) and disease-free survival (DFS) 1 year after HSCT2 were 25.0% and 21.4%, respectively. The cumulative incidences of nonrelapse mortality on day 100 and at 1 year post-HSCT2 were 7.1% ± 4.9% and 25.0% ± 8.4%. The cumulative incidences of relapse were 50.0% ± 9.8% and 53.5% ± 9.9% at 1 and 2 years post-HSCT2, respectively. Risk stratification prior to HSCT1 and percentage of blasts before HSCT2 were independent risk factors for OS post-HSCT2, and relapse within 6 months post-HSCT1 was an independent risk factor for DFS and relapse post-HSCT2. Our findings suggest that HSCT2 could be a salvage option for patients with relapsed AL post-Chemo + m-DLI.

The objective of this study was to compare clinical outcomes between noninherited maternal antigen (NIMA)-mismatched and noninherited paternal antigen (NIPA)-mismatched haploidentical hematopoietic stem cell transplantation (haplo-HSCT) among patients with hematological malignancies and perform a subgroup analysis. We retrospectively analyzed 378 patients with hematological malignancies who received haplo-HSCT from NIMA-mismatched (n = 201) and NIPA-mismatched (n = 177) donors between January 2012 and December 2017. The cumulative incidence of 100-d grades II-IV acute graft-versus-host disease (aGVHD) (19.2% vs. 32.8%, P = 0.003) was significantly lower in NIMA mismatch. Multivariate analysis showed that NIMA mismatch was associated with lower incidence of grades II-IV aGVHD and better overall survival (OS) and disease-free survival (DFS). According to the subgroup analysis, the clinical outcomes of older and/or female NIMA mismatches were comparable to those of younger and/or male NIPA mismatches with respect to grades II-IV aGVHD, chronic GVHD (cGVHD), nonrelapse mortality (NRM), relapse, DFS, and OS. In conclusion, this study confirmed the NIMA effect on aGVHD and demonstrated that NIMA mismatch was associated with better survival. In the NIMA mismatch context, donor age and sex did not seem to influence haplo-HSCT, which provides a basis for the selection of sibling donors.

Background. For patients with B cell acute lymphocytic leukemia (B-ALL) who underwent allogeneic stem cell transplantation (allo-SCT), many variables have been demonstrated to be associated with leukemia relapse. In this study, we attempted to establish a risk score system to predict transplant outcomes more precisely in patients with B-ALL after allo-SCT. Methods. A total of 477 patients with B-ALL who underwent allo-SCT at Peking University People's Hospital from December 2010 to December 2015 were enrolled in this retrospective study. We aimed to evaluate the factors associated with transplant outcomes after allo-SCT, and establish a risk score to identify patients with different probabilities of relapse. The univariate and multivariate analyses were performed with the Cox proportional hazards model with time-dependent variables. Results. All patients achieved neutrophil engraftment, and 95.4% of patients achieved platelet engraftment. The 5-year cumulative incidence of relapse (CIR), overall survival (OS), leukemia-free survival (LFS), and non-relapse mortality were 20.7%, 70.4%, 65.6%, and 13.9%, respectively. Multivariate analysis showed that patients with positive post-transplantation minimal residual disease (MRD), transplanted beyond the first complete remission (≥CR2), and without chronic graft-versus-host disease (cGVHD) had higher CIR (P

The prognosis of 11q23/KMT2A-rearranged (KMT2A-r) acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is poor. Minimal residual disease (MRD) is an important prognostic factor for relapse. Thus, we aimed to identify the evolution of KMT2A before and after allo-HSCT and the efficacy of preemptive immunotherapies for KMT2A-r AL patients receiving allo-HSCT. KMT2A expression was determined through TaqMan-based RQ-PCR technology. Preemptive immunotherapies included interferon-α and donor lymphocyte infusion. We collected 1751 bone marrow samples from 177 consecutive KMT2A-r AL patients. Pre-HSCT KMT2A positivity was correlated with post-HSCT KMT2A positivity (correlation coefficient=0.371, P 0

Background Sequential monitoring of Wilms’ tumor gene 1 (WT1) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) could predict relapse in adult acute myeloid leukemia (AML). However, the prognostic role of WT1 in pediatric AML after allo-HSCT is unclear. Thus, we determined to see whether sequential monitoring of WT1 after allo-HSCT could predict relapse in AML children. Methods Pediatric AML patients receiving allo-HSCT from January 21, 2012 to December 20, 2018 at the Peking University Institute of Hematology were included in this study. WT1 expression level was determined by TaqMan-based reverse transcription-polymerase chain reaction. WT1 sequential monitoring was performed 1, 2, 3, 4.5, 6, 9, and 12 months post-transplantation and at 6-month intervals thereafter. The primary end point was relapse. The secondary end points included disease-free survival (DFS), overall survival (OS), and non-relapse mortality (NRM). Kaplan–Meier analysis was used for DFS and OS estimates, while competing risk analysis was used for estimating relapse and NRM. Results Of the 151 consecutive patients included, the median age was 10 years (range, 1–17). The optimal cutoff value of WT1 within 1 year after allo-HSCT to predict relapse was 0.8% (80 WT1 copies/104 ABL copies), with a sensitivity of 60% and specificity of 79%. Compared with WT1 expression P = 0.001), lower 5-year disease-free survival (DFS, 60.4% vs. 80.8%; P = 0.009), and lower 5-year overall survival (OS, 64.9% vs. 81.6%; P = 0.038) rates. Multivariate analyses showed that WT1 was an independent risk factor for relapse (HR 2.89; 95% confidence interval (CI), 1.25–6.71; P = 0.014). Both the CIR (5-year CIR: 8.3% vs. 11.3%; P = 0.513) and DFS (5-year DFS: 91.7% vs. 80.8%; P = 0.208) were comparable between patients achieving minimal residual disease (MRD) negativity after preemptive interferon-α (IFN-α) treatment and those without MRD after allo-HSCT, which were better than those of MRD-positive patients without preemptive therapies. Conclusions Sequential monitoring of WT1 could predict relapse in pediatric AML after allo-HSCT. WT1-directed immunotherapy may have the potential to prevent relapse and improve survival.

Background The role of pre‐hematopoietic stem cell transplantation (HSCT) cytoreduction with either induction chemotherapy (IC) or hypomethylating agents (HMAs) in treating advanced myelodysplastic syndrome (MDS) remains debatable. We aimed to evaluate pre‐HSCT strategies by comparing the endpoints related to disease control between advanced MDS patients with pre‐HSCT cytoreduction and those with best supportive care. Methods We described 228 consecutive advanced MDS patients who received HSCT from a haploidentical donor (HID, n = 162) or matched related donor (MSD, n = 66) with uniform myeloablative conditioning regimens between January 2015 and December 2018. Of these 228 patients, 131 (57.5%) were treated exclusively with pre‐HSCT best supportive care (BSC), 49 (22.5%) were given HMA, and 48 (21.1%) received both IC and HMA. Propensity score‐matching analysis, multivariate analyses, and subgroup analyses were performed to elucidate the impact of pre‐HSCT strategies on transplant outcomes. Results The 3‐year relapse‐free survival (RFS) rates were 78.2% and 70.0% for the BSC and cytoreduction cohorts (P = 0.189) and were 78.2%, 66.7%, and 73.2% for the BSC, HMA, and HMA+IC groups, respectively (P = 0.269). A propensity score‐matching analysis confirmed that the 3‐year RFS rates were 81.9%, 87.5%, and 66.9% for BSC, cytoreduction complete remission (CR), and cytoreduction non‐CR groups, respectively (P = 0.051). Multivariate analyses demonstrated that pre‐HSCT cytoreduction, older patient age, monosomal karyotype, and interval between diagnosis and HSCT were poor prognostic factors for RFS. In the subgroup analyses, BSC was associated with longer RFS compared to cytoreduction among the younger patients, those with international prognostic scoring system intermediate‐2/high risk at diagnosis, and those with intermediate/poor cytogenetics. Conclusions Different pre‐HSCT therapies did not yield discrepant post‐HSCT outcomes. No benefit in terms of post‐HSCT outcomes were correlated with pre‐HSCT cytoreduction in advanced MDS even for cytoreduction CR patients. Early referral to HSCT is essential for advanced MDS patients.

We aimed to develop a disease risk comorbidity index (DRCI) based on disease risk index (DRI) and Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) in patients receiving haploidentical hematopoietic stem cell transplantation (haplo-HSCT). We identified the prognostic factors of disease-free survival (DFS) in a training subset (n = 593), then assigned a weighted score using these factors to the remaining patients (validation subset; n = 296). The multivariable model identified two independent predictors of DFS: DRI and HCT-CI before transplantation. In this scoring system, we assigned a weighted score of 2 to very high-risk DRI, and assigned a weighted score of 1 to high-risk DRI and intermediate- and high-risk HCT-CI (i.e., haplo-DRCI). In the validation cohort, the three-year DFS rate was 65.2% (95% confidence interval (CI), 58.2%–72.2%), 55.8% (95% CI, 44.9%–66.7%), and 32.0% (95% CI, 5.8%–58.2%) for the low-, intermediate-, and high-risk group, respectively (P = 0.005). Haplo-DRCI can also predict DFS in disease-specific subgroups, particularly in acute leukemia patients. Increasing score was also significantly predictive of increased relapse, increased non-relapse mortality (NRM), decreased DFS, and decreased overall survival (OS) in an independent historical cohort (n = 526). These data confirmed that haplo-DRCI could effectively risk stratify haplo-HSCT recipients and provide a tool to better predict who will best benefit from haplo-HSCT.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been regarded as a potential strategy for myeloid sarcoma (MS). The previous reports focused mainly on matched sibling donor (MSD) or matched unrelated donor (MUD) transplantation. There are no reports on haploidentical HSCT (haplo-HSCT) in MS. We retrospectively reviewed 14 MS patients who underwent haplo-HSCT. All patients achieved complete donor engraftment. The median time for neutrophil engraftment and platelet engraftment were 10 (12–21) days and 18 (8–31) days. The 100-day cumulative incidence of grade II–IV acute graft-versus-host disease (GVHD) and 3-year cumulative incidence of chronic GVHD were 37.7% (95%CI, 23.2–52.1%) and 35.7% (95%CI, 22.2–49.2%). Cytomegalovirus (CMV) reactivation was documented in 86% patients, and only one patient developed CMV pneumonia. Treatment-related mortality occurred in one (7%) patient. The 1- and 3-year cumulative incidence of relapse was 21.4% (95%CI, 11.8–31.1%) and 35.7% (95%CI, 22.4–49.0%). The probability of overall survival at 1 and 3 years was 71.4% (95%CI, 51.3–99.5%) and 64.3% (95%CI, 43.5–95.0%), respectively. The probability of disease-free survival at 1 and 3 years was 71.4% (95%CI, 51.3–99.5%) and 57.1% (95%CI, 36.3–89.9%), respectively. In conclusion, haplo-HSCT is a feasible method for patients with MS who have no MSD or MUD.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective and curative treatment for acute myeloid leukemia (AML). We explored the outcome of haploidentical donor (HID) transplantation for intermediate-risk AML and compared to that of matched sibling donor (MSD) transplants. One hundred twenty-seven consecutive patients with intermediate-risk AML in the first complete remission (CR1) who underwent allo-HSCT between January 1, 2015, and August 1, 2016, were enrolled. Thirty-seven patients received MSD grafts, and 90 received HID grafts. The 2-year leukemia-free survival (LFS) of the HID group was comparable to that of the MSD group: 82.0% ± 4.1% versus 82.7% ± 6.4%, P = 0.457. The 2-year cumulative incidences of relapse and transplantation-related mortality (TRM) were comparable between the HID and MSD groups (relapse, 4.5% ± 0.1%, versus 11.5% ± 0.3%, P = 0.550; TRM, 13.4% ± 0.1% vs. 5.8% ± 0.2%, P = 0.154). The HID recipients had a trend of a lower 2-year cumulative incidence of positive posttransplant flow cytometry (FCM+) and relapse than the MSD recipients (5.6% ± 0.1% vs. 19.9% ± 0.5%, P = 0.092). These results suggest that the outcomes of allo-HSCT with HIDs are comparable to those with MSDs in terms of LFS, TRM, and relapse for intermediate-risk AML in CR1. HIDs could be an alternative to MSDs for intermediate-risk AML.

Haploidentical stem cell transplantation (haplo-SCT) achieves superior or at least comparable clinical outcomes to HLA-matched sibling donor transplantation (MSDT) in treating hematological malignancies. To define the underlying regulatory dynamics, we analyzed time courses of leukemia burden and immune abundance of haplo-SCT or MSDT from multiple dimension. First, we employed two nonirradiated leukemia mouse models which carried human AML-ETO or MLL-AF9 fusion gene to establish haplo-identical and major histocompatibility (MHC)-matched transplantation models and investigated the immune cell dynamic response during leukemia development in vivo. We found that haplo-matching the MHCs of leukemia cells with recipient mouse T cells prolonged leukemic mice survival and reduced leukemia burden. The stronger graft-versus-leukemia activity in haplo-SCT group mainly induced by decreased apoptosis and increased cytotoxic cytokine secretion including tumor necrosis factor-α, interferon-γ, pore-forming proteins and CD107a secreted by T cells or natural killer cells. Furthermore, we conducted a prospective clinical trial which enrolled 135 patients with t(8;21) acute myeloid leukemia that displayed minimal residual disease before transplantation and underwent either haplo-SCT or MSDT. The results showed that the haplo-SCT slowed the kinetics of the leukemia burden in vivo and reduced the cumulative incidence of relapse compared with MSDT. Ex vivo experiments showed that, 1 year after transplantation, cytotoxic T lymphocytes from the haplo-SCT group had higher cytotoxicity than those from the MSDT group during the same period. Our results unraveled the role of immune cells in superior antileukemia effects of haplo-SCT compared with MSDT.

We performed a nested case-control study to investigate the incidence, treatment, and prognosis of central nervous system (CNS) relapse after allogenic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia (AML) and compared the outcomes of patients with CNS relapse following haploidentical donor (HID) HSCT versus identical sibling donor (ISD) HSCT. A total of 37 patients (HID-HSCT, 24; ISD-HSCT, 13) developed CNS relapse after transplantation between January 2009 and January 2019, with an incidence of 1.81%. The median time from transplantation to CNS relapse was 239 days. Pre-HSCT CNS involvement (HR 6.940, 95% CI 3.146–15.306, p

Background aims The efficacy of CD19-targeted chimeric antigen receptor T (CAR T) cells for treatment of relapsed B-cell malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and the long-term outcomes of these patients remain inconclusive. Methods The authors focused on the survival of 35 patients with B-cell acute lymphoblastic leukemia who relapsed after allo-HSCT and received CAR T cells. Results Of the 34 eligible patients, 30 achieved minimal residual disease-negative complete remission (CR), with a total CR rate of 85.7% (79.8–91.6%). There were 14 patients who received various forms of additional therapy after achieving CR. After a median follow-up of 20.7 months, it was noted that 17 patients had relapsed at a median of 4.5 months (2–34 months). The cumulative recurrence rate (RR) at 18 months was 68.3% (57.6–79.0%). Additional treatment did not reduce the RR but seemed to delay the time to relapse (mean: 5.9 months vs 13.1 months; P = 0.046). Patients with a lower tumor burden (≤10%) had a lower RR (25.0% vs 78.6% at 12 months; P = 0.006). The overall survival (OS) rate for the CR patients was 30.0% (20.3–29.7%) at 18 months, with a median OS of 12.7 months. Conclusions The authors’ study indicated that for patients who relapsed after HSCT, although a high CR rate was achieved after CAR T therapy, the long-term efficacy was unsatisfactory. It is necessary to optimize additional treatment, including a second HSCT, to further improve long-term efficacy after CAR T infusion.

ObjectiveWe aimed to establish a model that can predict refractory/recurrent cytomegalovirus (CMV) infection after haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT).MethodsConsecutive acute leukemia patients receiving HID HSCT were enrolled (n = 289). We randomly selected 60% of the entire population (n = 170) as the training cohort, and the remaining 40% comprised the validation cohort (n = 119). Patients were treated according to the protocol registered at https://clinicaltrials.gov (NCT03756675).ResultsThe model was as follows: Y = 0.0322 × (age) – 0.0696 × (gender) + 0.5492 × (underlying disease) + 0.0963 × (the cumulative dose of prednisone during pre-engraftment phase) – 0.0771 × (CD34+ cell counts in graft) – 1.2926. The threshold of probability was 0.5243, which helped to separate patients into high- and low-risk groups. In the low- and high-risk groups, the 100-day cumulative incidence of refractory/recurrent CMV was 42.0% [95% confidence interval (CI), 34.7%–49.4%] vs. 63.7% (95% CI, 54.8%–72.6%) (P < 0.001) for total patients and was 50.5% (95% confidence interval (CI), 40.9%–60.1%) vs. 71.0% (95% CI, 59.5%–82.4%) (P = 0.024) for those with acute graft-versus-host disease. It could also predict posttransplant mortality and survival.ConclusionWe established a comprehensive model that could predict the refractory/recurrent CMV infection after HID HSCT.Clinical Trial Registrationhttps://clinicaltrials.gov, identifier NCT03756675.

Relapse was the major cause of treatment failure in patients with acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to identify the efficacy and safety of preemptive interferon-α (IFN-α) treatment in ALL patients who had minimal residual disease (MRD) after allo-HSCT. Multiparameter flow cytometry and polymerase chain reaction assays were applied for MRD monitoring. Recombinant human IFN-α-2b injections were administered subcutaneously twice weekly in every 4 weeks cycle. Twenty-four (35.3%), 5 (7.4%), 6 (8.8%), and 13 (19.1%) patients achieved MRD negativity at 1, 2, 3, and > 3 months, respectively, after treatment. Seven patients showed grade ≥ 3 toxicities after IFN-α treatment. The 4-year cumulative incidence of total acute graft-versus-host disease (aGVHD), severe aGVHD, total chronic GVHD (cGVHD), and severe cGVHD after treatment was 14.7%, 2.9%, 40.0%, and 7.5%, respectively. The 4-year cumulative incidences of relapse and non-relapse mortality after treatment was 31.9% and 6.0%, respectively. The 4-year probabilities of disease-free survival and overall survival after IFN-α treatment were 62.1% and 71.1%, respectively. Thus, preemptive IFN-α treatment could protect against relapse and improve long-term survival for ALL patients who had MRD after allo-HSCT. The study was registered at https://clinicaltrials.gov as #NCT02185261 (09/07/2014).

The specific description, risk factors, and outcomes of chronic graft-versus-host disease (cGVHD) in pediatric patients with hematologic malignancies after T cell-replete (TCR) myeloablative haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with antithymocyte globulin (ATG)/granulocyte colony-stimulating factor (G-CSF) have not been previously well described. We retrospectively analyzed the incidence, risk factors, and outcomes of cGVHD documented according to the 2014 National Institutes of Health consensus criteria (NIH-CC) in 292 consecutive pediatric patients with hematologic malignancies after TCR myeloablative haplo-HSCT with ATG/G-CSF between January 2015 and December 2017. A total of 170 patients experienced cGVHD. The 3-year cumulative incidence of total cGVHD and mild, moderate, and severe cGVHD was 57.9%, 27.5%, 18.8%, and 11.9%, respectively. Multivariate analysis showed that acute GVHD (aGVHD) grade II-IV (hazard ratio, 1.578; P = .002) was an independent risk factor for cGVHD. Compared to patients without cGVHD, patients with cGVHD demonstrated a lower 3-year relapse (17.6% versus 27.2%; P = .009), a similar 3-year nonrelapse mortality (NRM) (5.9% versus 5.4%; P = .79), and better 3-year disease-free survival (DFS) (77.8% versus 66.9%; P = .007) and overall survival (OS) (81.3% versus 68.6%; P = .001), particularly those with mild or moderate cGVHD; however, no significant impact of severe cGVHD on relapse, NRM, DFS, or OS was seen. In conclusion, the incidence of severe cGVHD in pediatric patients with hematologic malignancies after TCR myeloablative haplo-HSCT with ATG/G-CSF was acceptable. Previous aGVHD grade II-IV was a risk factor for the occurrence of cGVHD. Only mild or moderate cGVHD was associated with a lower risk of relapse, translating into improved DFS and OS in pediatric patients with hematologic malignancies after TCR myeloablative haplo-HSCT with ATG/G-CSF.

Cytomegalovirus (CMV) can cause end-organ diseases including pneumonia, gastroenteritis, retinitis, and encephalitis in hematopoietic stem cell transplantation recipients. Potential differences among different CMV diseases remain uncertain. This study aimed to compare the clinical characteristics, risk factors, and mortality among different CMV diseases. A retrospective nested case-control study was performed based on a cohort of 3862 patients who underwent haploidentical hematopoietic stem cell transplantation at a single-center. CMV diseases occurred in 113 (2.92%) of 3862 haplo-HSCT recipients, including probable CMV pneumonia (CMVP, n = 34), proven CMV gastroenteritis (CMVG, n = 34), CMV retinitis (CMVR, n = 31), probable CMV encephalitis (CMVE, n = 7), and disseminated CMV disease (Di-CMVD, n = 7). Most (91.2%) cases of CMVG developed within 100 days, while most (90.3%) cases of CMVR were late onset. Refractory CMV infection and CMV viral load at different levels were associated with an increased risk of CMVP, CMVG, and CMVR. Compared with patients without CMV diseases, significantly higher non-relapse mortality at 1 year after transplantation was observed in patients with CMVP and CMVR, rather than CMVG. Patients with CMVP, Di-CMVD, and CMVE had higher overall mortality after diagnosis than that of patients with CMVG and CMVR (61.7%, 57.1%, 40.0% vs 27.7%, 18.6%, P = 0.001). In conclusion, the onset time, viral dynamics, and mortality differ among different CMV diseases. The mortality of CMV diseases remains high, especially for CMVP, Di-CMVD, and CMVE.

We aimed to investigate the frequency, risk factors, and outcome of active tuberculosis (TB) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective, nested, case-control study reviewed data from 6236 patients who received allo-HSCT from January 2008 to December 2018 at a single center; thirty-three patients (0.5%) with active TB and 99 controls without active TB after allo-HSCT were identified. We performed propensity score matching by randomly selecting 3 controls for each identified active TB patient according to the time of transplantation and follow-up period. History of pretransplant active TB previously treated and inactive at time of transplantation (P.001) was an independent risk factor. No significant differences in overall survival (P= .342), nonrelapse mortality (P= .497), or incidence of relapse (P= .807) were found. Thirty (90.9%) patients were treated with 4-drug (isoniazid, rifampicin/three rifapentine, pyrazinamide, and ethambutol) or 3-drug combination first-line therapy, with a response rate of 76.7%. Twenty-six (78.8%) patients were treated with first-line and second-line combined therapy, and the response rate was 76.9%. Five (15.2%) patients developed hepatotoxicity. In conclusion, history of pretransplant active TB previously treated and inactive at time of transplantation was an independent risk factor of active TB after allo-HSCT. No significant differences in prognosis between the TB and control groups were found. More studies are needed to help develop standardized therapeutic strategies for patients with post-transplant TB.

Acute pancreatitis (AP) has been recognized as an uncommon yet potentially lethal complication after hematopoietic stem cell transplant (HSCT). This retrospective, nested, case-control study reviewed data from 5284 consecutive patients who underwent allogeneic (allo)-HSCT between 2009 and 2018 at a single center, identifying 40 patients (0.76%) with AP after allo-HSCT. The diagnosis and severity of AP were established and classified according to existing criteria. Younger age (P = .008), grades II to IV acute graft-versus-host disease (P = .010), a history of donor lymphocyte infusion (P = .033), and pre-existing gallstones (P = .003) were independent risk factors of AP after allo-HSCT. Post-transplant AP had a trend to negatively influence overall survival (OS) and nonrelapse mortality (NRM) (P = .063) for allo-HSCT recipients, but no significant difference was found. Patients with moderately severe and severe AP had significantly lower OS (P = .002) and higher NRM (P = .000) than other patients. Based on these findings, a risk score model was also established to predict the occurrence of AP. Our risk score model performed well in terms of discrimination when applied to derivation samples. Patients were classified into a low-risk group (0 to 1 point), a medium-risk group (2 to 3 points), and a high-risk group (4 points or more). Significant difference was observed in AP incidence among the 3 groups. The predictive tool explored by our study might contribute to target high-risk patients and guide personalized AP prevention in allo-HSCT recipients.

Acute graft-vs-host disease (aGVHD) is one of the most important causes of early mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly for those with steroid-refractory (SR)-aGVHD. We aimed to identify the prognostic factors and long-term clinical outcomes of basiliximab treatment for SR-aGVHD. Basiliximab was administered on days 1, 3, and 8, and repeated weekly until aGVHD was less than grade II, or patients showed no response after four doses. Out of 1498 patients receiving allo-HSCT, 230 patients with SR-aGVHD were enrolled. Grade III to IV aGVHD before basiliximab treatment significantly and independently predicted a poorer response to basiliximab in multivariate analysis. And, the cumulative incidence of overall response at 14 days, 28 days, and 56 days after treatment was 41.4% vs 23.1% (P = .023), 70.2% vs 43.6% (P = .002), and 80.1% vs 66.7% (P = .013), respectively. This was for those with grade II and grade III to IV aGVHD. Patients receiving more than four doses of basiliximab had higher rates of infections. The 4-year cumulative incidence of total and severe chronic GVHD after basiliximab treatment was 44.8% (95% CI 38.3%-51.3%) and 2.2% (95% CI 0.3%-4.1%), respectively. The 4-year cumulative incidence of relapse, non-relapse mortality, disease-free survival, and overall survival after basiliximab treatment was 11.3% (95% CI 7.2%-15.4%), 30.0% (95% CI 24.1%-35.9%), 58.7% (95% CI 52.3%-65.1%), and 61.7% (95% CI 55.4%-68.0%), respectively. Comorbidities before allo-HSCT and refined Minnesota aGVHD risk score at diagnosis had significant influences on long-term survival. Thus, basiliximab was a safe and effective treatment for patients with SR-aGVHD.

Stroke is an important complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nevertheless, few studies have been published to analyzed the occurrence and prognosis of stroke after allo-HSCT. From January 2007 to December 2018 in Peking University People's Hospital, 6449 patients received HSCT and there were 2.3% of patients diagnosed with stroke after allo-HSCT (hemorrhagic: 1.0%, ischemic: 1.3%). The median time to hemorrhagic and ischemic stroke after HSCT was 161 days and 137 days, respectively. In total, 8.4% of patients experienced neurological sequelae. The outcome was much worse in patients with stroke than in control subjects. The comparison of prognosis showed no statistical differences between patients with hemorrhagic stroke and those with ischemic stroke. Significant risk factors for hemorrhagic stroke were pretransplant central nervous system leukemia (CNSL), and delayed platelet engraftment. Risk factors associated with the occurrence of ischemic stroke included high-risk disease, prior venous thromboembolism (VTE), grade III-IV acute graft-versus-host disease (aGVHD), and thrombotic microangiopathy (TMA). Haplo-identical transplantation was not a risk factor for stroke and had no impact on the prognosis compared with HLA-matched HSCT. Altogether, these results show that stroke is a severe complication after allo-HSCT. The prognosis of posttransplant stroke did not differ between hemorrhagic and ischemic stroke.

Acute myeloid leukaemia (AML) patients with biallelic mutations of CEBPA (bi CEBPA) have a 30-50% relapse rate. This study established the value of mutations based on next-generation sequencing (NGS) and multiparameter flow cytometric measurable residual disease (MFC-MRD) detection and compared the outcomes. From 2014 to 2018, 124 newly diagnosed bi CEBPA AML patients were treated. The median age was 37·5 (16-69) years. The 3-year cumulative incidence of relapse (CIR), relapse-free survival (RFS) and overall survival (OS) were 33·0%, 64·7% and 84·3%, respectively. Patients without additional mutations and with GATA2 mutations were defined as 'NGS low risk', which was the only favourable independent factor for CIR and RFS of pretreatment parameters. Patients with sustained positive MRD after two consolidation cycles and MRD negative losses at any time were defined as 'MRD high risk', which was the only poor independent factor for CIR, RFS and OS, including pretreatment and post-treatment parameters. In CR2 and non-remission patients who underwent allo-HSCT, superior OS was achieved. We conclude that NGS low risk was a favourable factor in the analysis of pretreatment parameters. MRD risk stratification was an independent prognostic factor in pretreatment and post-treatment parameters. Relapsed patients still have a favourable outcome followed by allo-HSCT.

This study investigated the epidemiological characteristics of cytomegalovirus retinitis (CMVR) after haploidentical hematopoietic stem cell transplantation (HSCT). We studied a cohort of 1466 consecutive patients who had undergone haploidentical HSCT between 2013 and 2017. We documented 34 episodes of CMVR in 31 patients, with a median onset of 167 days after the transplant. The cumulative incidence of CMVR was 2.3% 1 year after the transplant. Multivariate analysis suggested that platelet engraft failure at 100 days, EBV DNAemia, refractory or recurrent CMV DNAemia, and acute graft-versus-host disease were related to the development of CMVR in patients with CMV DNAemia. Patients with ≥3 risk factors (high risk) had a higher 1-year incidence of CMVR than patients with ≤2 risk factors (low risk) (26.2% vs. 0.6%, P

The impact of ABO incompatibility on transplantation outcomes in severe aplastic anemia (SAA) patients receiving haploidentical hematopoietic stem cell transplantation (HSCT) remains controversial without published data. A total of 199 SAA patients receiving haploidentical HSCT from ABO-matched (n = 114), minor ABO-incompatible (n = 47), or major ABO-incompatible donors (n = 38) were included in this study. The median time and cumulative incidences of both myeloid and platelet engraftment in the ABO-compatible and ABO-incompatible groups were similar, and pure red cell aplasia was absent. Minor ABO incompatibility increased the rate of grade III-IV acute graft-versus-host disease (aGVHD) (ABO compatible: 6.14 ± 0.05%, minor incompatible: 19.15 ± 0.34%, and major incompatible: 10.53 ± 0.25%; P = 0.051), but did not influence the rates of grade II-IV aGVHD or chronic GVHD (cGVHD). Minor ABO-incompatibility was identified as an independent risk factor for grade III-IV aGVHD by multivariate analysis (hazard ration (HR) = 4.00 (1.48-10.80), P = 0.006). Chronic GVHD, mortality, and treatment failure were not increased in the minor ABO-incompatible group. For SAA patients receiving haploidentical HSCT, ABO compatible donors are better than ABO minor incompatible donors if several haploidentical donors are available.

Purpose: Graft- versus-host disease (GVHD) is an important complication after human leukocyte antigen (HLA) haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT), which may lead to poor prognosis. Our study intends to identify the efficacy and safety of mesenchymal stem cells (MSCs) for multidrug-resistant (MDR)-GVHD after HID HSCT. Methods: MDR-GVHD was referring to GVHD remaining no response to at least two types of therapy, and hUCB-MSCs were given at the dose of (1.0–2.0) × 106/kg once a week. Results: A total of 21 patients were enrolled in this retrospective study (acute GVHD (aGVHD): n = 14, chronic GVHD (cGVHD): n = 7). The median dose of MSCs was 1.2 × 106 cells/kg (range, 0.8–1.8 × 106) cells/kg, and the median numbers of infusion were 2 (range, 1–7) and 3 (range, 2–12) for MDR-aGVHD and MDR-cGVHD patients, respectively. In MDR-aGVHD patients, the overall response rate (ORR) was 57.1%, including 50.0% complete response (CR) and 7.1% partial response (PR), and the median time to response was 49.5 days (range, 16–118) days. The 2-year probability of overall survival after MSCs was 64.3%. Five patients (35.7%) developed infections after MSCs, and no obvious hematologic toxicities were observed. Five MDR-aGVHD patients died after MSCs treatments because of GVHD progression ( n = 1), severe infection (bacterial central nervous system infection: n = 1; fungal pneumonia: n = 2), and poor graft function ( n = 1). In MDR-cGVHD patients, three patients (42.9%) achieved PR after MSCs and the median time to response was 56 days (22–84) days. The ORRs for moderate and severe cGVHD were 50.0% and 33.3%, respectively. Four MDR-cGVHD patients died after MSCs treatments because of GVHD progression ( n = 2), severe fungal pneumonia ( n = 1), and relapse ( n = 1). Conclusion: MSCs treatment may be safe and effective for MDR-GVHD after HID HSCT.

Severe cardiotoxicity is a fatal complication during high-dose cyclophosphamide (Cy)-based conditioning in hematopoietic stem cell transplant (HSCT) for severe aplastic anemia (SAA). This study aimed to evaluate the feasibility and efficacy of a modified conditioning regimen in haploidentical HSCT (haplo-HSCT) for severe-cardiotoxic-risk SAA patients. This BuCylow Flu conditioning utilized busulfan (Bu, 3.2 mg/kg for 2 days), low-dose Cy (100 mg/kg), fludarabine (150 mg/m2 ), and rabbit antithymocyte globulin (rATG, 10 mg/kg). Compared to BuCy conditioning using high-dose Cy of 200 mg/kg, Bu of 3.2 mg/kg for 2 days, and rATG of 10 mg/kg, the incidence of severe cardiotoxicity of BuCylow Flu conditioning was significantly decreased (2.17% vs 12.80%, p = .032). The engraftment rates (100% for neutrophil and 84.44% for platelet) were favorable. The probabilities of 100-day transplant-related mortality were similar in the BuCylow Flu and the BuCy group (8.75% vs 10.53%, p = .671). Both 1-year overall survival (88.79% vs 84.66%, p = .357) and 1-year failure-free survival (84.78% vs 81.70%, p = .535) were comparable. The BuCylow Flu group had higher rates of cytomegalovirus and Epstein-Barr virus reactivation. In conclusion, the BuCylow Flu provided reduced severe cardiotoxicity, and achieved favorable engraftment and survival. Our results suggest BuCylow Flu conditioning can be a feasible alternative for haplo-HSCT recipients at risk of severe cardiotoxicity.

The efficacy and outcome of therapeutic plasma exchange (TPE) for transplant-associated thrombotic microangiopathy (TA-TMA) remain controversial. We therefore sought to evaluate the outcome and efficacy of TPE in patients with TA-TMA and to identify TA-TMA patients who would benefit from TPE management. Eighty-two patients with TA-TMA were treated with TPE. We reported a response rate of 52% and overall survival rates of 20% and 15% at 100 days and 1 year after TA-TMA, respectively, in TPE-treated patients, with a significantly lower survival in gastrointestinal (GI) bleeding patients (5% vs. 41% in non-GI bleeding patients, P = 0.003). Multivariate analysis revealed that patients with GI bleeding, grade III-IV aGVHD, severe anemia, and a lower cumulative volume of TPE were less likely to respond to TPE. GI bleeding, a lower initial volume of TPE, and elevated total bilirubin were independently associated with 100-day mortality. The leading causes of death were infection, active TA-TMA, and MODS. The results of this large cohort of real-world practice indicate that the efficacy and outcome of TPE for TA-TMA patients without GI bleeding are encouraging, and a higher volume of TPE is warranted to achieve favorable outcomes.

Gut acute graft-versus-host disease (aGVHD) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and is associated with high mortality. Mucosa-associated invariant T (MAIT) cells are a group of innate-like T cells enriched in the intestine that can be activated by riboflavin metabolites from various microorganisms. However, little is known about the function or mechanism of action of MAIT cells in the occurrence of gut aGVHD in humans. In our study, multiparameter flow cytometry (FCM) was used to evaluate the number of MAIT cells and functional cytokines. 16S V34 region amplicon sequencing analysis was used to analyze the intestinal flora of transplant patients. In vitro stimulation and coculture assays were used to study the activation and function of MAIT cells. The number and distribution of MAIT cells in intestinal tissues were analyzed by immunofluorescence technology. Our study showed that the number and frequency of MAIT cells in infused grafts in gut aGVHD patients were lower than those in no-gut aGVHD patients. Recipients with a high number of MAITs in infused grafts had a higher abundance of intestinal flora in the early posttransplantation period (+14 days). At the onset of gut aGVHD, the number of MAIT cells decreased in peripheral blood, and the activation marker CD69, chemokine receptors CXCR3 and CXCR4, and transcription factors Rorγt and T-bet tended to increase. Furthermore, when gut aGVHD occurred, the proportion of MAIT17 was higher than that of MAIT1. The abundance of intestinal flora with non-riboflavin metabolic pathways tended to increase in gut aGVHD patients. MAIT cells secreted more granzyme B, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ under the interleukin (IL)-12/IL-18 stimulation [non-T-cell receptor (TCR) signal] and secreted most of the IL-17 under the cluster of differentiation (CD)3/CD28 stimulation (TCR signal). MAIT cells inhibited the proliferation of CD4+ T cells in vitro. In conclusion, the lower number of MAIT cells in infused grafts was related to the higher incidence of gut aGVHD, and the number of MAIT cells in grafts may affect the composition of the intestinal flora of recipients early after transplantation. The flora of the riboflavin metabolism pathway activated MAIT cells and promoted the expression of intestinal protective factors to affect the occurrence of gut aGVHD in humans.

Studies using third-generation tyrosine kinase inhibitor (TKI) as maintenance therapy after hematopoietic cell transplantation (HCT) for patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) harboring the T315I mutation remain scarce. We conducted a cohort study to evaluate the safety and outcomes of ponatinib maintenance therapy after HCT in Ph+ALL patients with T315I mutation. BCR-ABL kinase domain mutations were assessed using direct sequencing. Twenty-six Ph+ALL patients with T315I mutation who received allogeneic HCT were enrolled. After HCT, ponatinib was administered as a prophylactic regimen (n = 12) or a preemptive therapy (n = 7). Seven patients did not receive maintenance therapy. Adverse events (AEs) occurred in 69.4 % of patients with ponatinib maintenance, but most presented with mild toxicities. Serious non-hematological AEs were not observed. The 5-year disease-free survival (DFS), overall survival (OS), and cumulative incidence of relapse in patients receiving prophylactic ponatinib were 81.5 %, 91.7 %, and 18.5 %, respectively, whereas they were 39.8 %, 46.0 %, and 48.4 % in the total cohort, respectively. The measurable BCR-ABL transcripts in the first three months after HCT was associated with poor DFS and OS, even with ponatinib therapy. We concluded that maintenance therapy with ponatinib is safe after HCT. Patients with T315I mutation who received prophylactic regimen showed promising results with an acceptable relapse rate and encouraging survival. However, patients with measurable BCR-ABL transcripts early post-transplant had poor outcomes.

Background The mixed-lineage leukemia (MLL) gene is located on chromosome 11q23. The MLL gene can be rearranged to generate partial tandem duplications (MLL-PTD), which occurs in about 5-10% of acute myeloid leukemia (AML) with a normal karyotype and in 5-6% of myelodysplastic syndrome (MDS) patients. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently one of the curative therapies available for AML and MDS with excess blasts (MDS-EB). However, how the prognosis of patients with high levels of MLL-PTD after allo-HSCT, and whether MLL-PTD could be used as a reliable indicator for minimal residual disease (MRD) monitoring in transplant patients remains unknown. Our study purposed to analyze the dynamic changes of MLL-PTD peri-transplantation and the best threshold for predicting relapse after transplantation. Methods We retrospectively collected the clinical data of 48 patients with MLL-PTD AML or MDS-EB who underwent allo-HSCT in Peking University People’s Hospital. The MLL-PTD was examined by real-time quantitative polymerase chain reaction (RQ-PCR) at the diagnosis, before transplantation and the fixed time points after transplantation. Detectable MLL-PTD/ABL > 0.08% was defined as MLL-PTD positive in this study. Results The 48 patients included 33 AML patients and 15 MDS-EB patients. The median follow-up time was 26(0.7-56) months after HSCT. In AML patients, 7 patients (21.2%) died of treatment-related mortality (TRM), 6 patients (18.2%) underwent hematological relapse and died ultimately. Of the 15 patients with MDS-EB, 2 patients (13.3%) died of infection. The 3-year cumulative incidence of relapse (CIR), overall survival (OS), disease-free survival (DFS) and TRM were 13.7 ± 5.2, 67.8 ± 6.9, 68.1 ± 6.8 and 20.3% ± 6.1%, respectively. ROC curve showed that post-transplant MLL-PTD ≥ 1.0% was the optimal cut-off value for predicting hematological relapse after allo-HSCT. There was statistical difference between post-transplant MLL-PTD ≥ 1.0% and MLL-PTD P P P P = 0.277). However, whether MLL-PTD ≥ 1% or MLL-PTD Conclusions Our study indicated that MLL-PTD had a certain stability and could effectively reflect the change of tumor burden. The expression level of MLL-PTD after transplantation can serve as an effective indicator for predicting relapse.

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.

Chronic graft-versus-host disease (cGVHD) is a major complication following unmanipulated haploidentical hematopoietic stem cell transplantation (haplo-HSCT). We aimed to identify the risk factors for cGVHD in patients who underwent anti-thymocyte globulin-based haplo-HSCT for acute myeloid leukemia (n = 280). The diagnosis of cGVHD was in accordance with the National Institutes of Health consensus criteria. A total of 169 patients suffered from cGVHD. The patients who had 3 loci mismatched had a higher 8-year incidence of cGVHD (total, 66.0% vs. 53.7%, P = 0.031; moderate to severe, 42.4% vs. 30.1%, P = 0.036) than the patients who had 1 to 2 loci mismatched. The patients who had maternal donors had a higher 8-year incidence of moderate to severe cGVHD (49.2% vs. 32.9%, P = 0.024) compared with the patients who had other donors. The patients who had grades III to IV acute GVHD (aGVHD) had higher 8-year incidence of cGVHD (total, 88.0% vs. 50.4%, P < 0.001; moderate to severe, 68.0% vs. 27.0%, P < 0.001) compared with the patients without aGVHD. In multivariate analysis, grades III to IV aGVHD was the only independent risk factor for cGVHD. Thus, further interventions should be considered in patients with severe aGVHD to prevent cGVHD.

Background Haploidentical transplantation has been proposed as an effective treatment for severe aplastic anemia (SAA). The majority of patients have more than one HLA-haploidentical donor. Herein, we compared the outcomes between different donor-recipient relationships for optimal haploidentical donor selection in acquired SAA. Methods We conducted a multicenter study based on a registered database of 392 patients with SAA treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) between 2006 and 2018. In total, 223 patients received grafts from father donors, 47 from mother donors, 91 from siblings, 29 from children, and 2 from collateral donors. Results Of the 381 patients who survived more than 28 days, 379 (99.5%) recipients were engrafted. The 2-year overall survival (OS) was 86.6 ± 2.5%, 87.1 ± 4.9%, 84.3 ± 3.9%, and 92.2 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, (P = 0.706). The 2-year failure-free survival (FFS) was 82.8 ± 2.7%, 86.7 ± 5.1%, 80.8 ± 4.2%, and 92.5 ± 5.1% for recipients of father, mother, sibling, and child grafts, respectively, (P = 0.508). There was no difference in the incidence of either acute or chronic graft-versus-host disease (GVHD) among the different donor sources in multivariate analyses. There were also no differences in the OS or FFS among the different donor sources in the Cox regression analysis. However, OS was significantly better in the patients with a shorter history of aplastic anemia (< 12 months), better performance status (ECOG scores 0–1), or moderate graft mononuclear cell (MNC) counts (6–10 × 108/kg), and in female recipients with male donors. The FFS was also higher in patients with a shorter history of aplastic anemia (< 12 months) and better performance status (ECOG scores 0–1). Conclusions Fathers, mothers, siblings, and children are all suitable haploidentical donors for patients with SAA.

BACKGROUND This study aimed to determine the impact of the pre- and post-minimal residual disease (MRD) status as well as the peri-transplant MRD kinetics on clinical outcomes in pediatric ALL patients who received haploidentical allografts. METHODS A retrospective study (n = 166) was performed. MRD was determined using multiparameter flow cytometry. RESULTS Pediatric ALL patients with pre-MRDneg had a lower cumulative incidences of relapse (CIR) compared to those with pre-MRDpos (19.7% vs. 41.2%, P = 0.009). Compared to post-MRDneg group, patients with post-MRDpos experienced higher CIR (81.0% vs. 15.9%, P

The role of allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly haploidentical (haplo)-HSCT, in pediatric patients with Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) in the tyrosine kinase inhibitor (TKI) era is unclear. This study aimed to identify prognostic factors and explore the role of haplo-HSCT in the treatment of Ph+ ALL in the TKI era. We analyzed clinical data of Ph+ ALL patients aged 1 to 18 years who received imatinib added to intensive chemotherapy at the start of induction therapy. Among the 68 patients who completed at least 2 consolidation cycles, 44 underwent transplantation (transplant arm) and 24 received continuous TKI with chemotherapy (nontransplant arm). At the 3-year follow-up the cumulative incidence of relapse (CIR), event-free survival (EFS), and overall survival (OS) were 23.5%, 73.4%, and 80.3%, respectively. Multivariate analysis showed that hematologic response (whether complete remission [CR] was achieved) at the induction end, BCR-ABL levels (whether major molecular response [MMR] was achieved) at 3 months, and transplantation were independent affecting factors for CIR, EFS, and OS. In the risk stratification analysis based on the first 2 prognostic factors mentioned above, no significant difference existed between the transplant and nontransplant arms for the probabilities of 3-year OS, EFS, and CIR in the standard-risk group (no poor prognostic factors). Meanwhile, OS, EFS, and CIR rates were significantly better in the transplant arm in the high-risk group (≥1 poor prognostic factor). Among the 44 patients in the transplant arm, 37 underwent haplo-HSCT. Achieving CR at the induction end, MMR at 3 months, and haplo-transplant were also independent favorable factors of CIR, EFS, and OS in the nontransplant and haplo-HSCT arms. Haplo-HSCT showed a significant survival advantage in the high-risk group only. Hematologic response at the induction end and BCR-ABL levels at 3 months are likely to be useful for identifying pediatric Ph+ ALL patients at a high risk of relapse in the TKI era. Children with Ph+ ALL in first CR may benefit from allo-HSCT, particularly those at high risk. Haplo-HSCT could achieve good long-term survival for pediatric Ph+ ALL. Thus, haplo-HSCT can be an alternative approach for high-risk Ph+ ALL patients.

The efficacy of minimal residual disease (MRD)-directed immunotherapy, including interferon-α (IFN- α) treatment and chemotherapy plus granulocyte colony-stimulating factor-primed donor leukocyte infusion (chemo-DLI), was investigated in patients with high-risk myelodysplastic syndrome (MDS) who were MRD-positive after allogeneic hematopoietic stem cell transplantation (allo-HSCT). High-risk MDS patients who received non-T-cell-depleted allo-HSCT at the Peking University Institute of Hematology and were MRD-positive after allo-HSCT were studied (n = 47). The MRD-positive status was considered if leukemia-associated aberrant immune phenotypes or Wilms' tumor gene 1 expression is present in a single bone marrow sample. The cumulative incidence of the relapse and non-relapse mortality 2 years after immunotherapy were 14.5% and 21.4% (P = 0.377) and 9.1% and 0.0% (P = 0.985) for patients in the IFN-α and chemo-DLI groups, respectively. The probability of disease-free and overall survival 2 years after immunotherapy were 76.4% and 78.6% (P = 0.891) and 84.3% and 84.6% (P = 0.972) for patients in the IFN-α and chemo-DLI groups, respectively. Persistent MRD after immunotherapy was associated with poor survival. Thus, the MRD-directed immunotherapy was effective for patients with high-risk MDS who were MRD-positive after allo-HSCT, and the efficacy was comparable between chemo-DLI and IFN-α treatment.

The aim of this study was to investigate the occurrence and severity of chemotherapy plus donor lymphocyte infusion (Chemo-DLI)-associated chronic graft-versus-host disease (cGVHD) in a consecutive cohort of patients with acute leukemia who experienced relapse after allogeneic hematopoietic stem cell transplantation (n = 104). The 5-year cumulative incidence of complete remission after Chemo-DLI was 81.0% (95% CI, 73.3% to 88.7%) and 84.6% (95% CI, 74.5% to 94.7%) in the moderate and severe cGVHD groups, respectively, which was significantly higher than that of the mild cGVHD group at 40.9% (95% CI, 29.3% to 52.5%) and non-cGVHD group at 29.2% (95% CI 23.1% to 35.3%). The cumulative incidence of nonrelapse mortality was comparable between patients with and without cGVHD. The 5-year probabilities of progression-free survival after Chemo-DLI were 42.9% (95% CI, 26.2% to 70.2%) and 34.6% (95% CI, 15.3% to 78.2%) in the moderate and severe cGVHD groups, respectively, which were both significantly higher than those of the mild cGVHD group at 9.1% (95% CI, 2.4% to 34.1%) and non-cGVHD group at 8.3% (95% CI 3.3% to 21.3%). The 5-year probabilities of overall survival after Chemo-DLI were 56.7% (95% CI, 38.9% to 82.7%) and 43.1% (95% CI, 22.1% to 84.0%) in the moderate and severe cGVHD groups, respectively, which were both significantly higher than those of the mild cGVHD group at 9.1% (95% CI 1.8% to 47.1%) and non-cGVHD group at 14.9% (95% CI, 7.3% to 30.2%). Our observations highlight the close relationship between cGVHD and immune-mediated graft-versus-leukemia (GVL) effect in patients with relapse receiving Chemo-DLI; however, mild cGVHD may not be associated with a sufficiently strong GVL effect to induce remission and improve survival.

We aimed to identify the effect of positive stool cultures (PSCs) on the clinical outcomes of patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT) (n = 332). PSCs were observed in 61 patients (PSC group, 18.4%). Enterobacteriaceae in stool specimens was associated with a higher risk of bloodstream infection, and Candida in stool specimens was related to a higher risk of platelet engraftment failure. The cumulative incidence of infection-related mortality 1 year after haplo-HSCT in the PSC group was higher than that of the patients who showed persistently negative stool cultures (NSC group; 19.2% vs. 8.9%, P = 0.017). The probabilities of overall survival (71.4% vs. 83.8%, P = 0.031) and disease-free survival (69.6% vs. 81.0%, P = 0.048) 1 year after haplo-HSCT for the PSC group were significantly lower than those for the NSC group, particularly for patients who had Candida in their stool specimens. In multivariate analysis, Candida in stool specimens significantly increased the risk of mortality and was associated with poorer survival. Our results showed that PSC influenced the clinical outcomes after haplo-HSCT, particularly those who had Candida in their stool specimens.

Purpose: Although myeloablative HLA haploidentical hematopoietic stem cell transplantation (haplo-HSCT) following pretransplant anti-thymocyte globulin (ATG) and granulocyte colony-stimulating factor (G-CSF) stimulated grafts (ATG+G-CSF) has been confirmed as an alternative to HSCT from HLA-matched sibling donors (MSD), the effect of haplo-HSCT on postremission treatment of patients with acute myeloid leukemia (AML) with intermediate risk (int-risk AML) who achieved first complete remission (CR1) has not been defined. Patients and Methods: In this prospective trial, among 443 consecutive patients ages 16–60 years with newly diagnosed de novo AML with int-risk cytogenetics, 147 patients with molecular int-risk AML who achieved CR1 within two courses of induction and remained in CR1 at 4 months postremission either received chemotherapy (n = 69) or underwent haplo-HSCT (n = 78). Results: The 3-year leukemia-free survival (LFS) and overall survival (OS) were significantly higher in the haplo-HSCT group than in the chemotherapy group (74.3% vs. 47.3%; P = 0.0004 and 80.8% vs. 53.5%; P = 0.0001, respectively). In the multivariate analysis with propensity score adjustment, postremission treatment (haplo-HSCT vs. chemotherapy) was an independent risk factor affecting the LFS [HR 0.360; 95% confidence interval (CI), 0.163–0.793; P = 0.011], OS (HR 0.361; 95% CI, 0.156–0.832; P = 0.017), and cumulative incidence of relapse (HR 0.161; 95% CI, 0.057–0.459; P = 0.001) either in entire cohort or stratified by minimal residual disease after the second consolidation. Conclusions: Myeloablative haplo-HSCT with ATG+G-CSF is superior to chemotherapy as a postremission treatment in patients with int-risk AML during CR1. Haplo-HSCT might be a first-line postremission therapy for int-risk AML in the absence of HLA-MSDs. Haplo-HSCT might be superior to chemotherapy as a first-line postremission treatment of intermediate-risk AML in CR1.

Leukemia relapse is still the leading cause of treatment failure after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for B cell acute lymphoblastic leukemia (B-ALL). Relapsed patients with B-ALL after allo-HSCT have a very short median survival. Minimal residual disease (MRD) is predictive of forthcoming hematological relapse after hematopoietic stem cell transplantation (HSCT); furthermore, eliminating MRD effectively prevents relapse. Donor lymphoblastic infusion (DLI) is the main established approach to treat B-ALL with MRD after allo-HSCT. However, about one-third of patients with MRD are non-responsive to DLI and their prognosis worsens. Although donor-derived cluster of differentiation (CD)19-directed chimeric antigen receptor-modified (CAR) T cells (CART19s) can potentially cure leukemia, the efficiency and safety of infusions with these cells have not yet been investigated in patients with MRD after HSCT. Between September 2014 and February 2018, six patients each received one or more infusions of CART19s from HSCT donors. Five (83.33%) achieved MRD-negative remission, and one case was not responsive to the administration of CAR T cells. Three of the six patients are currently alive without leukemia. No patient developed acute graft-versus-host disease (aGVHD), and no patient died of cytokine release syndrome. Donor-derived CAR T cell infusions seem to be an effective and safe intervention for patients with MRD in B-ALL after allo-HSCT and for those who were not responsive to DLI. Keywords: Donor-derived CD19-targeted T cell infusion, Hematopoietic stem cell transplantation, B cell acute lymphoblastic leukemia, Minimal residual disease

Acute myelogenous leukemia (AML) patients with fetal liver tyrosine kinase 3 (FLT3) internal tandem duplications (ITDs) have poor prognoses if treated with chemotherapy only, primarily as they experience increased relapse rates. To determine whether this alteration also affects outcomes after haploidentical donor (HID) allogeneic hematopoietic stem cell transplantation (allo-HSCT), we compared 334 consecutive FLT3-ITD-positive vs -negative patients with AML (other than acute promyelocytic leukemia) who underwent HID-HSCT. FLT3-ITD was detected in 39 of 334 patients (11.7%). The 2-year relapse rates for FLT3-ITD-positive and -negative patients were 16% and 17%, respectively (P = 0.774). The 3-year disease-free survival (DFS) rates for FLT3-ITD-positive and -negative patients were 74% (95% confidence interval [CI]: 64-81) and 73% (95% CI: 70-81), respectively; P = 0.872); while the 3-year overall survival (OS) rates were 72% (95% CI: 67-81) and 77% (95% CI: 72-84), respectively (P = 0.862). FLT3-ITD mutation had no influence on non-relapse mortality (NRM 15% vs 14%, P = 0.463). Multivariate analyses showed that disease status at HSCT and white blood cell count at diagnosis were independent risk factors associated with relapse, DFS, and OS. In conclusion, FLT3 mutation status has no impact on outcomes after HID-HSCT in patients with AML. HID-HSCT is therefore a valid option for AML patients with FLT3-ITD mutation.

Refractory thrombocytopenia is a frequent and severe complication after haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) and lacks effective treatment strategies. Eltrombopag has shown promising results in several thrombocytopenia disorders. We report 38 patients treated with eltrombopag for refractory thrombocytopenia after haplo-HSCT. Eight patients had delayed platelet engraftment, 15 patients had secondary failure of platelet recovery, and 15 patients had poor graft function (PGF). Eltrombopag was initiated at 25 or 50 mg daily, and the dosage was adjusted to a maximum of 50–100 mg daily to maintain platelet between 50 × 109/L and 100 × 109/L. The cumulative incidence of platelet recovery to transfusion independence was 63.2% and to ≥50 × 109/L without transfusion support was 52.3%. Furthermore, neutrophil counts and hemoglobin were also increased in the nine responders with PGF. Nineteen (79.2%) of the 24 responders were able to taper off eltrombopag, and the remaining 5 patients were able to begin a taper. The median duration of treatment was 64 (range 14–195) days. The presence of megakaryocyte before initiation was the only independent factor influencing the efficacy of eltrombopag (P = 0.044). Eltrombopag was well tolerated in all patients. In summary, eltrombopag was a safe and effective therapy for refractory thrombocytopenia after haplo-HSCT.

This study investigated the prognostic factors in patients (n = 89) who experienced relapse and received chemotherapy plus donor leukocyte infusion (Chemo-DLI) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Patients with early relapse ( 6 vs. 6 months after haplo-HSCT), higher bone marrow blast count before chemo-DLI ( 20% vs. 5-19%), and without chronic graft-versus-host disease (cGVHD) after chemo-DLI had a higher rate of progressive disease (PD) and worse progression-free survival (PFS) and overall survival (OS). In multivariate analysis, non-cGVHD after Chemo-DLI and high blast count predicted a higher risk of PD and poorer PFS, and non-cGVHD after Chemo-DLI and early relapse predicted poorer OS. The patients were stratified into three groups according to these three risk factors. Patients with all three risk factors (n = 14) had the highest PD rate and poorest survival compared with those with one or two risk factors (n = 63) or no risk factors (n = 12). Thus, early relapse, high leukemia burden before Chemo-DLI, and non-cGVHD after Chemo-DLI can predict outcomes in patients who have experienced relapse and received Chemo-DLI after haplo-HSCT. New therapeutic strategies should be identified for these patients.