Long-term follow-up of haploidentical haematopoietic stem cell transplantation in paediatric patients with high-risk acute myeloid leukaemia: Report from a single centre.

Data from 200 children with high-risk acute myeloid leukaemia who underwent their first haploidentical haematopoietic stem cell transplantation (haplo-HSCT) between 2015 and 2021 at our institution were analysed. The 4-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 71.9%, 62.3% and 32.4% respectively. The 100-day cumulative incidences of grade II-IV and III-IV acute graft-versus-host disease (aGVHD) were 41.1% and 9.5% respectively. The 4-year cumulative incidence of chronic GVHD (cGVHD) was 56.1%, and that of moderate-to-severe cGVHD was 27.3%. Minimal residual disease (MRD)-positive (MRD+) status pre-HSCT was significantly associated with lower survival and a higher risk of relapse. The 4-year OS, EFS and CIR differed significantly between patients with MRD+ pre-HSCT (n = 97; 63.4%, 51.4% and 41.0% respectively) and those with MRD-negative (MRD-) pre-HSCT (n = 103; 80.5%, 73.3% and 23.8% respectively). Multivariate analysis also revealed that acute megakaryoblastic leukaemia without Down syndrome (non-DS-AMKL) was associated with extremely poor outcomes (hazard ratios and 95% CIs for OS, EFS and CIR: 3.110 (1.430-6.763), 3.145 (1.628-6.074) and 3.250 (1.529-6.910) respectively; p-values were 0.004, 0.001 and 0.002 respectively). Thus, haplo-HSCT can be a therapy option for these patients, and MRD status pre-HSCT significantly affects the outcomes. As patients with non-DS-AMKL have extremely poor outcomes, even with haplo-HSCT, a combination of novel therapies is urgently needed.

Comparison of outcomes for patients with acute myeloid leukemia undergoing haploidentical stem cell transplantation in first and second complete remission.

There was no consensus on whether prognostic advantages existed when transplant conducted at first complete remission (CR1) stage than at second complete remission (CR2) stage for patients with AML who received haploidentical hematological stem cell transplantation (haplo-HSCT). In 768 consecutive AML patients who received haplo-HSCT from January 2014 to December 2017, a 1:2 ratio matched-pair analysis was performed, 69 patients who in CR2 group and 138 CR1 patients were enrolled. Hematopoietic recovery, graft versus host disease (GVHD), relapse, transplant related mortality (TRM), disease-free survival (DFS) and overall survival (OS) were compared in two groups, and further evaluated in low-, intermediate-, and high-risk subgroups. The cumulative incidences of 30-day myeloid recovery and 90-day platelet recovery were comparable in CR1 and CR2 groups. The cumulative incidences of grade II-IV and grade III-IV aGVHD were not significantly different. The cumulative incidences of relapse at 3-year and 5-year in these two groups were 12.4% versus 11.6% (P = 0.880) and 12.4% versus 17.5% (P = 0.322). The cumulative incidences of TRM at 3-year and 5-year were both 10.9% versus 23.2% (P = 0.019). The probability of DFS at 3-year and 5-year were 76.7% versus 65.2% (P = 0.029) and 76.7% versus 59.3% (P = 0.009). The probability of OS at 3-year and 5-year were 81.8% versus 68.1% (P = 0.026) and 76.7% versus 59.3% (P = 0.026). In the intermediate-risk group, TRM was lower in CR1 group, DFS and OS of CR1 group were superior to CR2 group. In conclusion, haplo-HSCT at CR1 stage was of better prognosis for intermediate-risk AML patients than at CR2 stage.

Effects of isolated central nervous system involvement evaluated by multiparameter flow cytometry prior to allografting on outcomes of patients with acute lymphoblastic leukemia.

Introduction: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a major strategy to cure patients with acute lymphoblastic leukemia (ALL). The aim of this study was to evaluate whether isolated flow cytometry (FCM)-positive central nervous system (CNS) involvement before allo-HSCT is clinically significant. Methods: The effects of isolated FCM-positive CNS involvement prior to transplantation on the outcomes of 1406 ALL patients with complete remission (CR) were retrospectively investigated. Results: Patients were classified into isolated FCM-positive CNS involvement (n=31), cytology-positive CNS involvement (n = 43), and negative CNS involvement (n = 1332) groups. Among the three groups, the 5-year cumulative incidence of relapse (CIR) values were 42.3%, 48.8%, and 23.4%, respectively (P<0.001). The 5-year leukemia-free survival (LFS) values were 44.7%, 34.9%, and 60.8%, respectively (P<0.001). Compared with the negative CNS group (n=1332), the 5-year CIR of the pre-HSCT CNS involvement group (n=74) was higher (46.3% vs. 23.4%, P<0.001], and the 5-year LFS was inferior (39.1% vs. 60.8%, P<0.001). Multivariate analysis indicated that four variables, T-cell ALL, in second complete remission or beyond (CR2+) at HSCT, pre-HSCT measurable residual disease positivity, and pre-HSCT CNS involvement, were independently associated with a higher CIR and inferior LFS. A new scoring system was developed using the following four variables: low-risk, intermediate-risk, high-risk, and extremely high-risk groups. The 5-year CIR values were 16.9%, 27.8%, 50.9%, and 66.7%, respectively (P<0.001), while the 5-year LFS values were 67.6%, 56.9%, 31.0%, and 13.3%, respectively (P<0.001). Conclusion: Our results suggest that ALL patients with isolated FCM-positive CNS involvement are at a higher risk of recurrence after transplantation. Patients with pre-HSCT CNS involvement had higher CIR and inferior survival outcomes.

Predicting short-term and long-term mortalities from sepsis in patients who receive allogeneic haematopoietic stem cell transplantation.

Patients who receive allogeneic haematopoietic stem cell transplantation (allo-HSCT) may develop sepsis, which result in a highly intensive care unit admission rate and mortality. Therefore, short-term and long-term prognostic models for sepsis after allo-HSCT are urgently needed. We enrolled patients receiving allo-HSCT who developed sepsis after allo-HSCT at Peking University People's Hospital between 2012 and 2021, including 287 patients who received allo-HSCT in 2018-2021 in the derivation cohort, and 337 patients in 2012-2017 in the validation cohort. Multivariate logistic regression analysis was used to identify prognostic factors, and these identified factors were incorporated into two scoring models. Seven independent factors (acute graft-versus-host disease (GVHD), chronic GVHD (cGVHD), total bilirubin, lactate dehydrogenase (LDH) and organ dysfunction [renal, lung and heart]) were included in the 6-month prognostic model, and six factors (cGVHD, C-reactive protein, LDH, organ dysfunction [lung, neurologic and coagulation]) were included in the 14-day prognostic model. The area under the receiver operating characteristic curves, calibration plots and decision curve analysis demonstrated the robust predictive performance of the models, better than the Sequential Organ Failure Assessment score. Early identification of patients with high risk of 6-month and 14-day death may allow clinicians to provide timely treatments and improve the therapeutic effects.

Machine learning algorithm as a prognostic tool for Epstein-Barr virus reactivation after haploidentical hematopoietic stem cell transplantation.

Epstein-Barr virus (EBV) reactivation is one of the most important infections after hematopoietic stem cell transplantation (HSCT) using haplo-identical related donors (HID). We aimed to establish a comprehensive model with machine learning, which could predict EBV reactivation after HID HSCT with anti-thymocyte globulin (ATG) for graft-versus-host disease (GVHD) prophylaxis. We enrolled 470 consecutive acute leukemia patients, 60% of them (n = 282) randomly selected as a training cohort, the remaining 40% (n = 188) as a validation cohort. The equation was as follows: Probability (EBV reactivation) =   1 1       +       e x p ( - Y ) , where Y = 0.0250 × (age) - 0.3614 × (gender) + 0.0668 × (underlying disease) - 0.6297 × (disease status before HSCT) - 0.0726 × (disease risk index) - 0.0118 × (hematopoietic cell transplantation-specific comorbidity index [HCT-CI] score) + 1.2037 × (human leukocyte antigen disparity) + 0.5347 × (EBV serostatus) + 0.1605 × (conditioning regimen) - 0.2270 × (donor/recipient gender matched) + 0.2304 × (donor/recipient relation) - 0.0170 × (mononuclear cell counts in graft) + 0.0395 × (CD34+ cell count in graft) - 2.4510. The threshold of probability was 0.4623, which separated patients into low- and high-risk groups. The 1-year cumulative incidence of EBV reactivation in the low- and high-risk groups was 11.0% versus 24.5% (P < .001), 10.7% versus 19.3% (P = .046), and 11.4% versus 31.6% (P = .001), respectively, in total, training and validation cohorts. The model could also predict relapse and survival after HID HSCT. We established a comprehensive model that could predict EBV reactivation in HID HSCT recipients using ATG for GVHD prophylaxis.

A Prognostic Model Based on Clinical Biomarkers for Heart Failure in Adult Patients Following Allogeneic Hematopoietic Stem Cell Transplantation.

Heart failure (HF) is an uncommon but serious cardiovascular complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Unfortunately, knowledge about early mortality prognostic factors in patients with HF after allo-HSCT is limited, and an easy-to-use prognostic model is not available. This study aimed to develop and validate a clinical-biomarker prognostic model capable of predicting HF mortality following allo-HSCT that uses a combination of variables readily available in clinical practice. To investigate this issue, we conducted a retrospective analysis at our center with 154 HF patients who underwent allo-HSCT between 2008 and 2021. The patients were separated according to the time of transplantation, with 100 patients composing the derivation cohort and the other 54 patients composing the external validation cohort. We first calculated the univariable association for each variable with 2-month mortality in the derivation cohort. We then included the variables with a P value <.1 in univariate analysis as candidate predictors in the multivariate analysis using a backward stepwise logistic regression model. Variables remaining in the final model were identified as independent prognostic factors. To predict the prognosis of HF, a scoring system was established, and scores were assigned to the prognostic factors based on the regression coefficient. Finally, 4 strongly significant independent prognostic factors for 2-month mortality from HF were identified using multivariable logistic regression methods with stepwise variable selection: pulmonary infection (P = .005), grade III to IV acute graft-versus-host disease (severe aGVHD; P = .033), lactate dehydrogenase (LDH) >426 U/L (P = .049), and brain natriuretic peptide (BNP) >1799 pg/mL (P = .026). A risk grading model termed the BLIPS score (for BNP, LDH, cardiac troponin I, pulmonary infection, and severe aGVHD) was constructed according to the regression coefficients. The validated internal C-statistic was .870 (95% confidence interval [CI], .798 to .942), and the external C-statistic was .882 (95% CI, .791-.973). According to the calibration plots, the model-predicted probability correlated well with the actual observed frequencies. The clinical use of the prognostic model, according to decision curve analysis, could benefit HF patients. The BLIPS model in our study can serve to identify HF patients at higher risk for mortality early, which might aid designing timely targeted therapies and eventually improving patients' survival and prognosis.

Comparison of haploidentical hematopoietic stem cell transplantation with chemotherapy in older adults with acute myeloid leukemia.

Acute myeloid leukemia (AML) outcomes are very poor in older patients. Haploidentical stem cell transplantation (haplo-SCT) helps to achieve long-term survival. However, the benefit of haplo-SCT versus chemotherapy is unclear in older adults with AML. Outcomes were retrospectively compared among patients aged 55‒65 years for chemotherapy consolidation or haplo-SCT for AML in the first complete remission with intermediate to high-risk disease. Forty-six patients who underwent chemotherapy and 38 patients who underwent haplo-SCT were evaluated in the final analysis. Compared with the chemotherapy group, patients in the haplo-SCT group had significantly better overall survival (OS) (74.0% versus 23.9% at 36 months, p = 0.005) and leukemia-free survival (LFS) (74.0% versus 21.6%, p < 0.001). The cumulative incidence of relapse (CIR) was significantly lower in the haplo-SCT group (17.3% versus 75.4%, p < 0.001). Treatment-related mortality (TRM) was similar in the haplo-SCT and chemotherapy groups (7.9% versus 4.8%, p = 0.587). In the multivariate analysis, haplo-SCT was associated with improved OS, LFS, and decreased CIR. Haplo-SCT did not affect TRM. In conclusion, our data suggest that haploidentical transplant may be an alternative to consolidation chemotherapy as post-remission therapy in patients with intermediate or high-risk AML aged 55‒65 years. Further well-designed studies are needed to validate this result.

The adverse impact of ecotropic viral integration site-1 (EVI1) overexpression on the prognosis of acute myeloid leukemia with KMT2A gene rearrangement in different risk stratification subtypes.

INTRODUCTION: AML patients with KMT2A-MLLT3 and other 11q23 abnormalities belong to the intermediate and high-risk level groups, respectively. Whether the poor prognostic value of Ecotropic Viral Integration site-1 (EVI1) overexpression suits either the subtypes of KMT2A-MLLT3 or Non-KMT2A-MLLT3 AML patients (intermediate and high risk group) needs to be further investigated. METHODS: We retrospectively analyzed the clinical characteristics of 166 KMT2A-r and KMT2A-PTD AML patients. RESULTS: For the Non-KMT2A-MLLT3 group, patients in the EVI1-high subgroup had shorter OS and DFS and higher CIR than those in the EVI1-low subgroup (p = .027, p = .018, and p = .020, respectively). Additionally, both KMT2A-MLLT3 and Non-KMT2A-MLLT3 patients who received chemotherapy alone had poorer prognosis than patients who also received allogeneic hematopoietic stem cell transplant (allo-HSCT) regardless of their EVI1 expression level (all p < .001). For transplanted patients with KMT2A-MLLT3 or Non-KMT2A-MLLT3 rearrangement, the EVI1-high subgroup had worse prognosis than the EVI1-low subgroup (all p < .05). The 2-year CIR of the KMT2A-MLLT3 and Non-KMT2A-MLLT3 groups with high EVI1 expression was high (52% and 49.6%, respectively). However, for patients with low EVI1 expression, the 2-year CIR of transplanted patients with KMT2A-MLLT3 and Non-KMT2A-MLLT3 was relatively low. CONCLUSIONS: Our study showed that for the Non-KMT2A-MLLT3 group, the EVI1-high group had shorter OS and DFS than the EVI1-low group. High EVI1 expression showed an adverse effect in AML with KMT2A rearrangement in different risk stratification subtypes. For the EVI1-high patients with non-KMT2A-MLLT3 rearrangement, other novel regimens towards relapse should be taken into consideration.

Optimized therapeutic strategy for patients with refractory or relapsed acute myeloid leukemia: long-term clinical outcomes and health-related quality of life assessment.

BACKGROUND: Patients with refractory or relapsed acute myeloid leukemia (AML) have poor survival, necessitating the exploration of optimized therapeutic strategy. Here, we aimed to investigate clinical outcomes and health-related quality of life (HR-QoL) after total therapy, which included allogeneic hematopoietic stem cell transplantation (allo-HSCT), and prophylactic donor lymphocyte infusion (DLI) in the early phase after transplantation, followed by multiple measurable residual disease (MRD) and graft-versus-host disease (GvHD)-guided DLIs. METHODS: Consecutive patients who had refractory or relapsed AML and had received non-T-cell-depleted allo-HSCT at Peking University Institute of Hematology were included in the study. If the patients achieved complete remission at 30 days after transplantation and had no evidence of relapse, severe infection, organ failure, and active GvHD at the time of planned DLI, prophylactic DLI was administered at 30 days after transplantation for human leukocyte antigen (HLA)-matched related HSCT or at 45-60 days after transplantation for haploidentical or unrelated HSCT. Subsequently, multiple DLIs were administered based on MRD results and whether they developed GvHD after transplantation. RESULTS: A total of 105 patients were eligible. Eighty-seven patients received prophylactic DLI (group B), while 18 did not receive prophylactic DLI (group A). Among 105 patients, the cumulative incidence of grade 2-4 acute GvHD and chronic GvHD was 40.6% (95% confidence interval [CI] = 30.6%-50.6%) and 73.3% (95% CI = 67.4%-79.2%), respectively. The cumulative incidence of relapse (CIR), transplant-related mortality (TRM), and leukemia-free survival (LFS) at 5 years after transplantation were 31.5% (95% CI = 21.9%-41.1%), 22.1% (95% CI = 11.3%-32.9%), and 46.4% (95% CI = 36.8%-56.0%), respectively. In group B, the CIR, TRM, and LFS at 5 years after transplantation were 27.6% (95% CI = 17.6%-37.6%), 21.6% (95% CI = 11.2%-32.0%), and 50.8% (95% CI = 40.0%-61.6%), respectively. At the end of follow-up, 48 patients survived, and more than 90% of survivors had satisfactory recoveries of HR-QoL. CONCLUSIONS: Our study indicated that total therapy is not only associated with decreased CIR, comparable TRM, and better long-term LFS, but also with satisfactory HR-QoL for refractory or relapsed AML, compared with those of standard of care therapy reported previously. Therefore, total therapy may be an optimized therapeutic strategy for refractory or relapsed AML.

Immune Reconstitution of Patients Who Recovered From Steroid-Refractory Acute Graft-Versus-Host Disease After Basiliximab Treatment.

We aimed to identify the characteristics of immune reconstitution (IR) in patients who recovered from steroid-refractory acute graft-versus-host disease (SR-aGVHD) after basiliximab treatment. A total of 179, 124, 80, and 92 patients were included in the analysis for IR at 3, 6, 9, and 12 months, respectively, after haploidentical donor hematopoietic stem cell transplantation (HID HSCT). We observed that IR was fastest for monocytes and CD8+ T cells, followed by lymphocytes, CD3+ T cells, and CD19+ B cells and slowest for CD4+ T cells. Almost all immune cell subsets recovered comparably between patients receiving <5 doses and ≥5 doses of basiliximab. Most immune cell subsets recovered comparably between SR-aGVHD patients who recovered after basiliximab treatment and event-free HID HSCT recipients. Patients who recovered from SR-aGVHD after basiliximab treatment experienced satisfactory IR, which suggested that basiliximab may not have prolonged the negative impact on IR in these patients.

Safety and outcomes of maintenance therapy with third-generation tyrosine kinase inhibitor after allogeneic hematopoietic cell transplantation in Philadelphia chromosome positive acute lymphoblastic leukemia patients with T315I mutation.

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.

Donor CSF3R with the rs3917980A/G or G/G genotype is correlated with better leukemia-free survival after allogenic hematopoietic stem cell transplantation.

Polymorphisms in the granulocyte colony-stimulating factor receptor gene (GCSFR, CSF3R) have been reported to be associated with peripheral blood stem cell enrichment and hematological diseases. The aim of our study was to investigate the effects of donor CSF3R allelic polymorphisms on the outcomes of allogeneic stem cell transplantation. A total of 273 patients who were diagnosed with hematological diseases and treated with allogeneic hematopoietic stem cell transplantation(allo-HSCT) were enrolled in this study. Single-nucleotide polymorphisms in CSF3R were genotyped by targeted next-generation sequencing. There were six types of CSF3R genotypes with percentages over 1%. LFS and OS analyses showed that recipients receiving grafts from healthy donors with a rs3917980 G/G or A/G genotype had higher LFS rates than those receiving grafts from donors carrying a rs22754272 T/C genotype and the double-negative group (p = 0.036). Univariate cox analysis showed that donor CSF3R with the rs2275472 T/C genotype was associated with higher transplantation-related mortality (TRM) rates (HR = 2.853, 95% CI: 1.405-5.792, p = 0.00371) and lower rates of leukemia-free survival (LFS) (HR = 1.846; 95% CI: 1.018-3.347, p = 0.0435). In addition, donor CSF3R with the rs3917980G/G or A/G genotype was associated with better overall survival (OS) rates (HR = 0.560, 95% CI: 0.3162-0.9916, p = 0.047) and lower TRM rates (HR = 0.497, 95% CI: 0.2628-0.9397, p = 0.0315). Furthermore, multivariate cox analysis found that rs2275472 T/C genotype was an independent risk factors for TRM rates (HR = 3.210, 95% CI: 1.573-6.55, p = 0.001), while no statistical difference was found between rs3917980G/G or A/G genotype and clinical outcomes. Our findings demonstrate the important prognostic value of genetic variations in donor CSF3R to predict clinical outcomes in patients undergoing allo-HSCT.

Association of dietary intake of n-3 polyunsaturated fatty acids with breast cancer risk in pre- and postmenopausal Chinese women.

OBJECTIVE: This study aimed to evaluate the associations between breast cancer risk and intake of n-3 polyunsaturated fatty acids (PUFAs) and/or n-3 PUFA subclasses in Chinese women, and determine whether these associations varied with menopausal status or clinical characteristics. METHODS: A hospital-based case-control study including 1,589 cases and 1,621 age-frequency-matched controls was conducted. Dietary data were assessed by a validated food frequency questionnaire. Odds ratios (ORs) and 95% confidence intervals were obtained using multiple unconditional logistic regression models after controlling for potential confounders. RESULTS: Higher intake of marine n-3 PUFAs and total n-3 PUFAs was associated with lower risk of breast cancer, with adjusted OR quartile 4 v.1 (95% confidence intervals) of 0.68 (0.55-0.84) and 0.56 (0.42-0.75), respectively. Dietary a-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid were also inversely associated with breast cancer risk, with adjusted ORs (95% confidence intervals) of 0.51 (0.38-0.70), 0.68 (0.55-0.84), 0.68 (0.55-0.85), and 0.76 (0.61-0.94), respectively. In stratified analyses, these inverse associations between risk and dietary n-3 PUFAs were more evident among premenopausal women and women with ER+, PR+ and ER+PR+ tumors. A decreased risk of breast cancer was significantly associated with increasing n-3 PUFA intake in obese/overweight women, but not in women of normal weight. There was a significant interaction between linoleic acid and marine n-3 PUFAs. CONCLUSIONS: High intake of n-3 PUFAs and n-3 PUFA subtypes was associated with a lower risk of breast cancer, especially among premenopausal women and women with ER+ and/or PR+ subtype breast cancer.

Efficacy and safety of CD19 CAR-T cell therapy for acute lymphoblastic leukemia patients relapsed after allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for B-cell acute lymphoblastic leukemia (B-ALL). Although allo-HSCT can be curative for some B-ALL patients, relapse still occurs in some patients following allo-HSCT. Conventional chemotherapies show poor efficacy in B-ALL patients who have relapsed following allo-HSCT. In the past decade, chimeric antigen receptor T-cell (CAR-T) therapy has shown to be efficacious for B-ALL patients. In particular, autologous CD19 CAR-T therapy results in a high remission rate. However, there are challenges in the use of CD19 CAR-T therapy for B-ALL patients who have relapsed following allo-HSCT, including the selection of CAR-T cell source for manufacturing, post-CAR-T graft-versus-host disease (GVHD) risk, maintenance of long-term efficacy after remission through CAR-T therapy, and whether a consolidative second transplant is needed. In this review, we describe the current status of CAR-T therapy for B-ALL patients who have relapsed following allo-HSCT, the advantages and disadvantages of various CAR-T cell sources, the characteristics and management of GVHD following CAR-T therapy, and the risk factors that may affect long-term efficacy.

Prevalence and risk factors of antibodies to HLA according to different cut-off values of mean fluorescence intensity in haploidentical allograft candidates: A prospective study of 3805 subjects.

The importance of anti-HLA antibodies in transplantation settings, such as HLA-mismatched or haploidentical hematopoietic stem cell transplantation and platelet refractoriness, is widely recognized. In previous reports, it was mentioned that several cut-off values of donor-specific anti-HLA antibodies mean fluorescence intensity (MFI) were related to graft rejection in the environment of HLA mismatched stem cell transplantation and the aim of this study was to investigate the prevalence and risk factors of anti-HLA antibodies according to those cut-off values of MFI. A total of 3805 patients with hematologic disease were prospectively enrolled and analyzed. When using MFI of anti-HLA antibodies ≥500, ≥1000, ≥1500, ≥2000, ≥5000, and ≥ 10,000 as cut-off values for positivity, the prevalence of class I or II anti-HLA antibodies ranged from 4.6% to 20.2% in all cases. When the MFI cut-off value was ≥500 for positivity, multivariate analysis indicated that platelet transfusion, underlying disease, and pregnancy were the most important risk factors for the presence of anti-HLA antibodies for the total patients. Subgroup analysis according to age, gender, and underlying disease showed that pregnancy was the most important risk factor for the presence of anti-HLA antibodies. For all patients (n = 3805), when anti-HLA antibody positivity was defined according to different MFI cut-off values, including ≥1000, ≥1500, ≥2000, ≥5000, and ≥ 10,000, an association of platelet transfusion and pregnancy with anti-HLA antibodies was also demonstrated. Our results suggest that pregnancy and platelet transfusion are the main risk factors for the prevalence of anti-HLA antibodies in haploid allograft candidates, providing evidence for guiding the evaluation of anti-HLA antibodies and helping donor selection for HLA-mismatched transplant candidates.

Combination of KIT and FLT3-ITD mutation status with minimal residual disease levels guides treatment strategy for adult patients with inv(16) acute myeloid leukemia in first complete remission.

Although several studies have investigated the benefits of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with inv (16) acute myeloid leukemia (AML) in first complete remission (CR1) individually stratified by KIT or FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation status or minimal residual disease (MRD) levels, evaluation based on the combination of mutation status and MRD levels remains absent. This study included 157 adult patients with inv (16) AML who were consecutively diagnosed and receiving treatment at our center. A total of 50 (31.6%) patients had KIT mutations (KITMU ), and the risk of relapse was significantly higher in patients with KITMU than in patients with KITWT (p < 0.001). A total of 12 patients (7.6%) had FLT3-ITD, and FLT3-ITD+ tended to be related to a higher risk of relapse (p = 0.14). KITMU , FLT3-ITD and MRD3-H (beta subunit of core binding factor-myosin heavy chain 11 levels >0.2% after course 2 of consolidation therapy) were independent adverse prognostic factors for relapse with patients who received allo-HSCT at CR1 were censored at the time of transplantation. After combination, patients were categorized into molecularly defined high-risk (M-HR; KITMU or FLT3-ITD+ with MRD3-H; n = 30), low-risk (M-LR; KITWT and FLT3-ITD- with MRD3-L; n = 45) and intermediate-risk (M-IR; others; n = 70) groups. For the M-HR group, allo-HSCT significantly improved both cumulative incidence of relapse cumulative incidence of relapse (CIR) and overall survival (OS) (11.1% vs. 92.6%, p < 0.001; 90.0% vs. 34.1%, p = 0.019). For the M-IR group, allo-HSCT significantly improved CIR but did not affect OS (14.1% vs. 62.2%, p = 0.0004; 73.3% vs. 68.3%, p = 0.43). For the M-LR group, allo-HSCT had no significant effect on both CIR and OS (0% vs. 35.1%, p = 0.31; 100% vs. 78.8%, p = 0.22). Therefore, the combination of KIT and FLT3-ITD mutation status with MRD levels may identify inv (16) AML patients with high-risk who can benefit from allo-HSCT in CR1.

Prednisone plus IVIg compared with prednisone or IVIg for immune thrombocytopenia in pregnancy: a national retrospective cohort study.

Background: The responses of intravenous immunoglobulin (IVIg) or corticosteroids as the initial treatment on pregnancy with ITP were unsatisfactory. This study aimed to assess the safety and effectiveness of prednisone plus IVIg versus prednisone or IVIg in pregnant patients with immune thrombocytopenia (ITP). Methods: Between 1 January 2010 and 31 December 2020, 970 pregnancies diagnosed with ITP at 19 collaborative centers in China were reviewed in this observational study. A total of 513 pregnancies (52.89%) received no intervention. Concerning the remaining pregnancies, 151 (33.04%) pregnancies received an initial treatment of prednisone plus IVIg, 105 (22.98%) pregnancies received IVIg alone, and 172 (37.64%) pregnancies only received prednisone. Results: Regarding the maternal response to the initial treatment, no differences were found among the three treatment groups (41.1% for prednisone plus IVIg, 33.1% for prednisone, and 38.1% for IVIg). However, a significant difference was observed in the time to response between the prednisone plus IVIg group (4.39 ± 2.54 days) and prednisone group (7.29 ± 5.01 days; p < 0.001), and between the IVIg group (6.71 ± 4.85 days) and prednisone group (p < 0.001). The median prednisone duration in the monotherapy group was 27 days (range, 8-195 days), whereas that in the combination group was 14 days (range, 6-85 days). No significant differences were found among these three treatment groups in neonatal outcomes, particularly concerning the neonatal platelet counts. The time to response in the combination treatment group was shorter than prednisone monotherapy. The duration of prednisone application in combination group was shorter than prednisone monotherapy. The combined therapy showed a lower predelivery platelet transfusion rate than IVIg alone. Conclusion: These findings suggest that prednisone plus IVIg may represent a potential combination therapy for pregnant patients with ITP.

A comprehensive model to predict severe acute graft-versus-host disease in acute leukemia patients after haploidentical hematopoietic stem cell transplantation.

BACKGROUND: Acute graft-versus-host disease (aGVHD) remains the major cause of early mortality after haploidentical related donor (HID) hematopoietic stem cell transplantation (HSCT). We aimed to establish a comprehensive model which could predict severe aGVHD after HID HSCT. METHODS: Consecutive 470 acute leukemia patients receiving HID HSCT according to the protocol registered at https://clinicaltrials.gov (NCT03756675) were enrolled, 70% of them (n = 335) were randomly selected as training cohort and the remains 30% (n = 135) were used as validation cohort. RESULTS: The equation was as follows: Probability (grade III-IV aGVHD) = [Formula: see text], where Y = -0.0288 × (age) + 0.7965 × (gender) + 0.8371 × (CD3 + /CD14 + cells ratio in graft) + 0.5829 × (donor/recipient relation) - 0.0089 × (CD8 + cell counts in graft) - 2.9046. The threshold of probability was 0.057392 which helped separate patients into high- and low-risk groups. The 100-day cumulative incidence of grade III-IV aGVHD in the low- and high-risk groups was 4.1% (95% CI 1.9-6.3%) versus 12.8% (95% CI 7.4-18.2%) (P = 0.001), 3.2% (95% CI 1.2-5.1%) versus 10.6% (95% CI 4.7-16.5%) (P = 0.006), and 6.1% (95% CI 1.3-10.9%) versus 19.4% (95% CI 6.3-32.5%) (P = 0.017), respectively, in total, training, and validation cohort. The rates of grade III-IV skin and gut aGVHD in high-risk group were both significantly higher than those of low-risk group. This model could also predict grade II-IV and grade I-IV aGVHD. CONCLUSIONS: We established a model which could predict the development of severe aGVHD in HID HSCT recipients.