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Although CAR-T cell therapy has been particularly successful as a treatment for B cell malignancies, effectively treating acute myeloid leukemia with CAR remains a greater challenge. Multiple preclinical studies and clinical trials are underway, including on AML-related surface markers that CAR-T cells can target, such as CD123, CD33, NKG2D, CLL1, CD7, FLT3, Lewis Y and CD70, all of which provide opportunities for developing CAR-T therapies with improved specificity and efficacy. We also explored specific strategies for CAR-T cell treatment of AML, including immune checkpoints, suicide genes, dual targeting, genomic tools and the potential for universal CAR. In addition, CAR-T cell therapy for AML still has certain risks and challenges, including cytokine release syndrome (CRS) and haematotoxicity. Despite these challenges, as a new targeting method for AML treatment, CAR-T cell therapy still has great prospects. Ongoing research aims to further optimize this treatment mode. [ABSTRACT FROM AUTHOR]

Summary: Venetoclax (VEN) in combination with hypomethylating agents (HMAs) is considered the standard of treatment for individuals with newly diagnosed acute myeloid leukaemia (AML) who are ineligible for intensive chemotherapy. We conducted a retrospective analysis that encompassed 16 critically ill patients newly diagnosed with AML who were admitted to the intensive care unit (ICU) and received the VEN and HMA regimen. Among them, 13 were primary AML, and three were MDS‐transformed AML. The mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 18.9, and the mean sepsis‐related organ failure assessment score (SOFA) was 6.2. The average length of the ICU stay was 27.3 days. The median duration of VEN administration was 16 days. After the first course of VEN + HMA, 12 cases (75%) achieved complete remission (CR) or CR with incomplete haematological recovery (CRi). Among the five patients harbouring TP53 mutations, the overall response rate (ORR) was 90%. All patients experienced grade 3–4 haematological adverse events (AEs). With a median follow‐up of 9.5 months (range: 0.5–23), the overall survival (OS) rate was 43.75%. TP53‐wild patients and CR state after the first course of VEN–HMA indicated better survival. The combination of VEN and HMA has demonstrated a significantly elevated therapeutic response rate in newly diagnosed AML patients with critical illness. [ABSTRACT FROM AUTHOR]

Background: Elderly patients with acute myeloid leukemia or myelodysplastic syndromes (AML/MDS) have historically had poor prognoses. However, there has been a recent increase in the use of allogenic hematopoietic stem cell transplantation (allo-HSCT) are in this patient population. Nevertheless, the optimal choice of donor type for the patients remains an unmet need. Limited data exist on the use of allo-HSCT in elderly patients with AML/MDS from China. To better understand and optimize the selection of donor type for the elderly patients, particularly for those with refractory or relapsed disease, in comparison with the previous studies in the US and Europe. Methods: Our retrospective study enrolled 259 patients aged over 55 years who underwent their first allo-HSCT between April 2015 and August 2022. These patients were divided into three groups based on donor type: haploidentical related donor group (haploidentical related donor transplantation [HID], n = 184), matched sibling donor group (matched sibling donor transplantation [MSD], n = 39), and matched unrelated donor group (matched unrelated donor transplantation [MUD], n = 36). Statistics were performed with the chi-square test, the log-rank and Fine-Gray tests. Results: The median age of the cohort was 57 years (range: 55–75) and 26.25% of patients were over 60 years old. Younger patients had a higher incidence of acute graft-versus-host disease (HR = 1.942, P = 0.035), faster neutrophil recovery (HR = 1.387, P = 0.012), and better overall survival (HR = 0.567, P = 0.043) than patients aged ≥ 60 years across the entire cohort. Patients with refractory or relapsed (R/R) diseases had delayed neutrophil engraftment (P = 0.010, HR = 0.752) and platelet engraftment (P < 0.001, HR = 0.596), higher incidence of relapses (HR = 2.300, P = 0.013), and inferior relapse-free survival (RFS) (HR = 1.740, HR = 0.016) regardless of donor type. When it came to graft-versus-host-disease-free, relapse-free survival (GRFS), MUDs turned out to be superior to HIDs (HR = 0.472, P = 0.026) according to the multivariable analysis. In contrast, we found MSDs had an inferior GRFS to HIDs in parallel (HR = 1.621, P = 0.043). Conclusion: The choice of donor type did not significantly affect the outcomes of allo-HSCT. However, when considering the quality of post-transplant life, MUDs or HIDs from younger donors may be the optimal choice for elderly patients. [ABSTRACT FROM AUTHOR]

Adult patients with newly diagnosed de novo acute myeloid leukemia (AML), who had less than a 50% reduction in blast numbers and with > 15% residual blasts after first cycle of induction chemotherapy, defined as type 1 primary refractory (REF1), have grave prognosis. We retrospectively analyzed the data of 58 patients with REF1 who received salvage treatments with curative intension to evaluate the impact of salvage regimens with regard to response and overall survival (OS). Seventeen patients received intermediate- or high-dose cytarabine (ID/HD Ara-C) based intensive salvage chemotherapy, 36 patients received G-CSF primed less intensive chemotherapy and 5 patients received novel targeted drugs based low intensive therapy. The CR/CRi and MLFS rate was 6/17 and 2/17, 14/36 and 3/36, 3/5 and 0/5, respectively. The median OS for the whole cohort was 20.3 months. Median OS was comparable between the 3 arms. Overall, 42 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), 14 patients in the intensive arm, 24 patients in the less intensive arm and 4 patients in the low intensive arm. Median survival for allo-HSCT patients was significantly longer than for non-allo-HSCT patients (38.8 months vs. 2.1 months, p < 0.001). In multivariate analysis, achievement of CR/CRi after the salvage regimen were predictive of OS. We conclude that no significant difference in outcome among traditional salvage regimens in patients with REF1. G-CSF primed less intensive chemotherapy could serve as an alternative of ID/HD Ara-C based intensive chemotherapy and allo-HSCT is indispensable for long-term survival. [ABSTRACT FROM AUTHOR]

CD19/CD22 dual-targeting chimeric antigen receptor T-cell therapy bridging to allogeneic haematopoietic stem cell transplantation for B-cell acute lymphoblastic leukaemia delays platelet recovery and increases risks of cytomegalovirus and Epstein-Barr virus viremia after transplantation Twenty-nine patients received CD19 and CD22 dual-targeting CAR-T therapy prior to HSCT (CD19/CD22 dual-targeting CAR-T group), 43 patients received CD19 single-targeting CAR-T-cell therapy prior to HSCT (CD19 single-targeting CAR-T group) and 97 patients did not receive CAR-T therapy prior to transplantation (non-CAR-T group). Dear Editor, Chimeric antigen receptor T (CAR-T) cell therapy has been one of the most promising strategies to achieve improved complete remission (CR) in patients with refractory/relapsed B-cell acute lymphoblastic leukaemia (B-ALL) but remissions can be short-lived.[1] Increasing evidence gathered from recent studies has shown that CAR-T-cell therapy alongside complementary allo-haematopoietic stem cell transplantation (HSCT) may achieve more durable long-term remission than CAR-T-cell therapy alone.[2] However, whether this combinational therapy is capable of exerting its impact on HSCT-related complications remains unclear. [Extracted from the article]

Since 2019, the SARS-CoV-2 pandemic has become a global issue due to its high fatality rate. Over time, the characteristics of the virus have evolved and led to the creation of an omicron strain with higher infectivity but a significantly decreased fatality rate. For patients in urgent need of hematopoietic stem cell transplantation (HSCT), whether the SARS-CoV-2 infection status of donors has a significant impact on HSCT recipients should be clarified. To estimate the transplantation risk of SARS-CoV-2-positive donors, 24 patients who underwent HSCT from December 1, 2022 to January 30, 2023 were retrospectively included. The ratio of the observation group (SARS-CoV-2-positive donors, n = 12) to the control group (SARS-CoV-2-negative donors, n = 12) was 1:1. We observed the time of hematopoietic reconstruction, donor chimerism, severe infection, acute graft vs host disease, and hepatic vein occlusion disease during hematopoietic reconstruction. In the observation group, the average time of myeloid hematopoietic reconstruction was 11.58 days, and in the control group, it was 12.17 days (P =.3563 [>.05]). On average, all patients achieved a 90% donor chimerism rate of +13.58 (±4.5) days (P =.5121 [>.05]). The average percentage of patients that achieved successful hematopoietic reconstruction was 96.75% in the observation group and 96.31% in the control group (P =.7819 [>.05]). A total of 6 adverse events occurred during this study: 3 in the observation group and 3 in the control group. Our preliminary results showed favorable short-term outcomes in recipients of SARS-CoV-2-positive HCST donors. [ABSTRACT FROM AUTHOR]

Of the 42 patients who failed the first salvage treatment, 22 achieved a response after subsequent induction treatment and proceeded to allo-HSCT in remission, while the remaining 20 patients underwent allo-HSCT with active disease. Fifty-nine patients achieved a response after the first salvage treatment, 57 patients proceeded to allo-HSCT in remission, and 2 patients relapsed and underwent allo-HSCT with active disease. [Extracted from the article]

I DDX41 i mutations were detected in 0.6% (2/329) adult ALL patients of our cohorts comparable with a recent report.[10] Previous studies showed that I DDX41 i -mutated patients of MNs presented as male predominance and old age. Germline DDX41 mutations define a significant entity within adult MDS/AML patients. We found three variants in I DDX41 i (p.R525H, p.G530D and p.Y259C) and confirmed the germline origin of p.Y259C of I DDX41 i by Sanger sequencing. [Extracted from the article]

We retrospectively explored the prognostic impact of DAT mutations at diagnosis in 122 RUNX1mut AML patients. RUNX1 missense mutation was dominant in the RUNT domain, and frameshift mutation was dominant in the TAD domain. DAT mutations occurred in 38.5% of RUNX1mut AML. After propensity score matching, DATpos patients had worse two-year relapse-free survival (RFS) than DATneg patients (p =.041). Moreover, RUNX1high (VAF ≥ 37.6%) patients showed poorer two-year overall survival (OS) and RFS than RUNX1low (VAF < 37.6%) patients (OS, p =.033; RFS, p =.027), especially in the RUNX1highDATpos group. Additionally, multivariate analysis confirmed that DAT mutations at diagnosis were an independent adverse factor for RFS. There were no significant differences in two-year OS and RFS between DATpos and DATneg patients or between RUNX1high and RUNX1low patients who undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Collectively, DAT mutations at diagnosis were adverse factors for RFS, and allo-HSCT could likely improve the poor outcomes of these patients. [ABSTRACT FROM AUTHOR]

Both of our patients were diagnosed with a mixed phenotype of CML-BP, a rare type, and there is no real consensus between the therapeutic regimens for these patients. After transplantation, the patient was regularly monitored and evaluated, and at the last follow-up on September 4, 2022, the patient showed a deep molecular response (DMR) with levels of I BCR::ABL1 i SP IS sp < 0.0032%. Here, we reported for the first time that venetoclax plus olverembatinib was a powerful and effective induction treatment for two patients diagnosed with relapsed/refractory CML-BP. Recently, several studies have shown promising efficacy of venetoclax-based therapies in MPAL [[10]], which motivated us to explore treatment with venetoclax plus olverembatinib in relapsed/refractory (R/R) CML-BP patients with a mixed phenotype. [Extracted from the article]

In fact, several retrospective analyses have shown that the outcomes were comparable after allo-HSCT for patients who had received either treatments or no treatment [[3]]. Patients with Auer rods had significantly better 3-year OS than patients without Auer rods (84.4% vs 61%, I p i = 0.04) (Fig. Yi Wang, Yaoyao Shen, and Jiaqian Qi are co-first authors Dear Editor, Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative treatment for patients with myelodysplastic syndrome (MDS) [[1]]. Therefore, Auer rods may be a useful biomarker for facilitating clinicians in evaluating whether debulking treatment as a bridge to allo-HSCT may be of benefit for patients. [Extracted from the article]

Persistence of CAR-T cell function is associated with relapse rate after CAR-T therapy, while co-stimulatory agents are highly concerned with the persistence of CAR-T cells. In this study, we designed and constructed a series of BCMA-targeting second-generation CAR constructs containing CD28, 41BB, and OX40 molecules, respectively, to identify the costimulatory domains most favorable for persistence. The results of routine in vitro studies showed that OX40-CAR-T and 41BB-CAR-T had similar antitumor effects and were superior to CD28-CAR-T in terms of proliferation and cytotoxicity. Although difficult to distinguish by conventional functional assays, OX40-CAR-T cells exhibited greater proliferation and enhanced immune memory than 41BB-CAR-T cells with the repeated stimulation assay by BCMA-expressing target cells. In vivo studies further demonstrated that OX40-CAR-T cells had stronger proliferative activity than 41BB-CAR-T cells, which was highly consistent with the in vitro antitumor activity and proliferation results. Our study provides for the first time a scientific basis for designing OX40-CAR-T cell therapy to improve relapse in patients with MM after CAR-T treatment. [ABSTRACT FROM AUTHOR]

Central nervous system complications (CNSCs) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are common and may be a significant source of morbidity and mortality. We performed a retrospective study of 153 pediatric patients who underwent allo-HSCT to determine CNSC type, incidence, and impact on survival. A total of 34 patients (22.2%) developed CNSCs. The cumulative incidence of CNSCs at 100 days and 3 years was 18.30 and 22.73%, respectively. The most common CNSC was calcineurin inhibitor (CNI)-associated neurotoxicity (50.0%). Risk factors for CNSCs were the time from diagnosis to HSCT ≥4.8 months (p = 0.032) and the development of acute graft-versus-host disease (aGVHD) grade III–IV (p = 0.002). CNSCs after allo-HSCT negatively impacted overall survival (hazard ratio [HR] 1.97, p = 0.043) and nonrelapse mortality (HR 4.84, p < 0.001). In conclusion, CNSCs after allo-HSCT are associated with poor outcomes; patients with severe aGVHD and/or late transplantation should be given more attention. [ABSTRACT FROM AUTHOR]

Abstract: Extramedullary relapse (EMR) of acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a contributor to post-transplantation mortality and remains poorly understood, especially the different characteristics of EMR in patients with acute myelogenous leukemia (AML) and those with acute lymphoblastic leukemia (ALL). To investigate the incidence, risk factors, and clinical outcomes of EMR for AML and ALL, we performed a retrospective analysis of 362 patients with AL who underwent allo-HSCT at the First affiliated Hospital of Soochow University between January 2001 and March 2012. Compared with patients with AML, those with ALL had a higher incidence of EMR (12.9% versus 4.6%; P = .009). The most common site of EMR was the central nervous system, especially in the ALL group. Multivariate analyses identified the leading risk factors for EMR in the patients with AML as advanced disease status at HSCT, hyperleukocytosis at diagnosis, history of extramedullary leukemia before HSCT, and a total body irradiation–based conditioning regimen, and the top risk factors for EMR in the patients with ALL as hyperleukocytosis at diagnosis, adverse cytogenetics, and transfusion of peripheral blood stem cells. The prognosis for EMR of AL is poor, and treatment options are very limited; however, the estimated 3-year overall survival (OS) was significantly lower in patients with AML compared with those with ALL (0 versus 18.5%; P = .000). The characteristics of post–allo-HSCT EMR differed between the patients with AML and those with ALL, possibly suggesting different pathogenetic mechanisms for EMR of AML and EMR of ALL after allo-HSCT; further investigation is needed. [Copyright &y& Elsevier]

Aim To analyze allele mismatches of HLA-A, -B, -C, -DRB1, -DQB1 and haplotype mismatch of donor-recipient pairs on the outcome of haploidentical transplantation combined with a third part cord blood unit. Methods 230 pairs of donor-recipient were performed HLA-A, B, C, DRB1, DQB1 typing using SBT and SSOP methods from January 2012 to December 2014. Results Pairs were divided into HLA-5/10, 6/10, 7/10 and ⩾8/10 groups according to HLA-A, B, C,DRB1 and DQB1 high resolution typing and matched degrees, the 3-year probability of overall survival (OS) for each group were 48.7%, 59.3%, 71.1%, 38.3%( P = 0.068) respectively. HLA>6/10 matched group associated with significant favorable effect on OS compared with HLA-5/10 matched one ( P = 0.041).When the HLA class I antigen matched on the recipient and donor, improved OS and event free survival (EFS) in HLA-6/10 matched group than in HLA-5/10 matched one ( P = 0.017, P = 0.088), especially in single HLA-A loci allele matched one ( P = 0.013, P = 0.013), were observed. As to the third part cord blood unit, sharing the same haplotype with the recipient-donor pairs produced better platelet recovery than the misfit one (95.3% vs 86.2%, P = 0.007), similar result was found in terms of neutrophil recovery (98.8% vs 96.1%, P = 0.022). Conclusions HLA locus mismatch and haplotype mismatch of the donor and recipient should be useful for selection of the most optimum donor. Co-infused of an unrelated cord blood unit sharing the same haplotype with the recipient-donor pairs could improve hematopoietic recovery. [ABSTRACT FROM AUTHOR]