BackgroundBlinatumomab, a bispecific T-cell engager (BiTE), has significantly improved the efficacy of B-ALL treatment. However, its association with immune effector cell-associated neurotoxicity syndrome (ICANS) has garnered increasing attention. This study analyzes two cases of ICANS to explore the challenges in recognizing clinical symptoms and standardizing management.Case presentationCase 1 involved a 69-year-old male with B-ALL, harboring TP53 and DNMT3A mutations, who developed grade 2 ICANS following blinatumomab treatment. Therapy was continued without interruption, and symptoms resolved with levetiracetam intervention. Case 2 was a 29-year-old male with B-ALL and ETV6::RUNX1 fusion gene, who developed grade 4 ICANS (seizures, impaired consciousness, epileptic episodes) on day 4 of blinatumomab therapy. The patient required intensive care and comprehensive intervention, leading to symptom resolution but discontinuation of treatment. Neither case exhibited central nervous system infiltration, and cranial CT scans showed no abnormalities.Discussion and conclusionICANS may be associated with cytokine release, blood-brain barrier disruption, and genetic background, presenting with heterogeneous symptoms. Elderly patients or those with specific genetic mutations may face increased risks, necessitating individualized dose adjustments (e.g., stepwise dosing) and close monitoring of neurological functions and cytokines (e.g., IL-6). Early recognition of subtle symptoms (e.g., tremors) combined with corticosteroids and antiepileptic drugs can improve outcomes. The use of blinatumomab requires careful balancing of efficacy and neurotoxicity, particularly in high-risk patients. This case report provides valuable insights for the clinical recognition and management of ICANS.

Abstract Background Treatment outcomes for high-risk B-ALL remain suboptimal. Blinatumomab, a CD19/CD3 bispecific T-cell engager, has shown efficacy in trials, but real-world data in Chinese high-risk patients are limited. Methods This single-center retrospective study analyzed 29 high-risk B-ALL patients treated with blinatumomab (7–28 days/cycle). We assessed short-term efficacy (MRD negativity rate), safety, and the impact of genetic factors and treatment duration. Results The overall MRD negativity rate after one cycle of blinatumomab was 82.8% (24/29). All patients with the Ph-like subtype (3/3, 100%) and 71.4% (10/14) of Ph+ patients achieved MRD negativity. However, clinical outcomes were inferior in patients harboring specific genetic alterations: 50% (2/4) of patients with the BCR::ABL1 T315I mutation experienced early relapse, and only one of two patients with E2A::PBX1 rearrangement achieved transient MRD negativity. The median event-free survival (EFS) was 9.6 months (95% CI: 6–16.75). Grade ≥ 3 hematologic toxicity occurred in 48.3% (14/29) of the patient cohort. Conclusion Blinatumomab achieved high short-term MRD response rates in high-risk B-ALL. Inferior outcomes appeared to be associated with the presence of BCR::ABL1 T315I mutations and E2A::PBX1 rearrangements.

BACKGROUND:The death rate of hematological malignancies is high, and the death rate of patients with COVID-19 infection is further increased. Although there have been expert consensus and relevant guidelines to introduce the recommendations of the guidelines for patients with hematological malignancies complicated with COVID-19 infection, there is limited understanding of the clinical characteristics of Chinese patients with acute leukemia complicated with COVID-19 infection. AIMS:This study aimed to analyze the clinical manifestations, mortality, and determinants of viral shedding duration in Chinese AL patients infected with COVID-19. METHODS:We conducted a retrospective study of 100 AL patients with COVID-19 infection in Henan Province, China, from December 1, 2022, to January 31, 2023. Data on demographics, leukemia subtype, symptoms, treatments (antibiotics/antivirals), and viral shedding duration were collected. Follow-up was conducted over three months to assess mortality. Univariate and multivariate analyses were performed to identify risk factors. RESULTS:The median age was 49.5 years (58% male, 42% female), with 76% having acute myeloid leukemia (AML) and 24% acute lymphoblastic leukemia (ALL). Most patients (86%) were asymptomatic. Antibiotics and antivirals were administered to 35% and 25% of patients, respectively. Severe cases and fatalities exhibited prolonged viral shedding. Neutropenic patients on antibiotics had significantly extended shedding duration, whereas antiviral therapy or delayed primary disease management shortened it. The overall mortality rate was 6%. Univariate analysis identified neutropenia as a key mortality risk factor, though multivariate analysis showed no significant associations. CONCLUSION:Early antiviral treatment may reduce viral shedding duration and potentially mitigate symptom severity and mortality in AL patients with COVID-19. Neutropenia emerged as a critical factor influencing outcomes. These findings underscore the importance of tailored therapeutic strategies for this high-risk population.

Background and aimMucormycosis is a life-threatening invasive fungal infection. This study aimed to analyze the clinical characteristics of patients with hematologic malignancies complicated with mucormycosis.MethodsThis retrospective study investigated the clinical characteristics, epidemiological features, treatment, and prognosis of 46 patients with hematological diseases and Mucor infection as indicated by mNGS from August 28, 2020 to September 11, 2023. Metagenomic next-generation sequencing (mNGS) refers to the application of high-throughput sequencing technology for the comprehensive analysis of nucleic acid content in patient samples, facilitating the detection and characterization of microbial DNA and/or RNA, and then comparing and analyzing the results with an information database to determine the types of pathogenic microorganisms present in the sample.ResultsThe median age of admission for the included patients was 49 years (9-78). Multivariate analysis identified age over 60 years (p = 0.006 < 0.05), high-dose corticosteroids (p = 0.001 < 0.05), neutropenia lasting more than 10 days (p = 0.041 < 0.05), and two or more Mucor infections (p = 0.004 < 0.05) were independent risk factors for OS in patients with hematological diseases. Moreover, differences between groups were analyzed using the Fisher exact probability method, and no significant difference was observed in the efficacy of various types of antifungal therapies.ConclusionPatients with hematologic malignancies benefit greatly from early diagnosis and treatment when suspected of Mucor infection. mNGS is an important supplementary method for early diagnosis of Mucor infection. Moderated use of corticosteroids, reducing the duration of neutropenia, and enhancing autologous immune function are important measures to reduce patient mortality rate.

Abstract Background: Acute leukemia is the most common hematological malignancy, mainly including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Nucleophosmin 1 mutations (mNPM1) occur in 20%-30% of AML patients. Patients with mNPM1 have a 5-year survival rate of ~50%, with a median overall survival (OS) of 6.1-7.3 months in relapsed/refractory (R/R) patients. The gene rearrangement of the lysine methyltransferase 2A (KMT2Ar) occurs in ~10% of acute leukemia patients. Patients with a KMT2A rearrangement have a 5-year survival rate of ~20%-25%, with a median OS 2.4-6 months in R/R patients. Menin is a scaffolding protein that interacts with aberrant NPM1 or KMT2A to upregulate the HOXA/MEIS1 pathway, resulting in leukemogenesis. Menin inhibitors are a new class of targeted therapy that inhibit the interaction of menin and KMT2A, thus allowing differentiation of blasts. Zefamenib is a potent small molecule inhibitor targeting menin. In mouse studies, zefamenib has been shown to significantly reduce the tumor burden and reduce the proliferation of leukemia cell in peripheral blood, bone marrow, and spleen. Zefamenib has also demonstrated anti-leukemia efficacy and safety in relapsed/refractory acute leukemia patients in a phase 1 dose escalation/dose optimization study; results were presented at ASH in 2024. Of the 28 patients with mNMP1 or KMT2Ar treated with the RP2D of 600 mg BID, the overall response rate and CR/CRh rate was 89.3% and 57.1%, respectively. No patient had a dose-limiting toxicity, and the toxicity profile was acceptable with 2 pts with grade 1 QT prolongation and 2 pts with grade 2 differentiation syndrome. This study is currently enrolling in the phase 2 portion and is designed to evaluate the efficacy, safety, pharmacokinetics (PK), and efficacy of zefamenib in Chinese patients with relapsed/refractory acute leukemia. Study Design and Methods: This study (NCT06052813) is a phase 2, multicenter, open-label study of zefamenib monotherapy in Chinese patients with relapsed/refractory acute leukemias who have either a KMT2A or or an NPM1 gene mutation. Key eligibility criteria include patients diagnosed with relapsed/refractory acute leukemia (including AML, ALL, and mixed lineage leukemia, excluding acute promyelocytic leukemia) according to the World Health Organization 2022 criteria, bone marrow morphological changes (blasts/immature cells ≥5%), confirmed NPM1 gene mutation or KMT2A or NUP98 rearrangement, and meet one of the following four conditions: (i) primary refractory disease; (ii) first relapse and duration of first response ≤12 months; (iii) relapsed/refractory disease after 2 or more lines of therapy; (iv) relapse after allogeneic hematopoietic stem cell transplantation. Zefamenib will be administered twice daily for 28-day treatment cycles until disease progression/recurrence, intolerable toxicity, loss to follow-up, withdrawal of informed consent, death, or the investigator's judgment to terminate the study drug, whichever occurs first. The primary objective of the phase 2 dose expansion phase is to evaluate the efficacy of zefamenib in 30-48 patients using the RP2D dose obtained in phase 1. The patients will be divided into 3 cohorts (10-16 patients per cohort): (A) patients with AML with NPM1 mutations; (B) patients with AML with KMT2A rearrangements; and (C) other patients, including patients with relapsed/refractory ALL or mixed lineage leukemia with KMT2A rearrangement; patients with AML with NUP98 rearrangement; patients with AML or ALL with other types of gene alterations that meet protocol requirements. The primary endpoint for the phase 2 dose expansion phase CRc (CR+CRh+CRi). Key secondary endpoints include CR, CR+CRh, objective response rate, MRD negative remission rate, duration of response, duration of CR+CRh, duration of CRc, EFS, OS, cumulative relapse rate, cumulative mortality, safety, and pharmacokinetics. Based on the phase 1 results of this study, a global phase 2 study assessing the efficacy and safety of zefamenib monotherapy in acute leukemias with NUP98r, HOXA9r, or mNPM1 will be started in Q2 2026.

ObjectiveTo evaluate the clinical efficacy of maintenance therapy with sorafenib combined with interferon α-1b, interleukin-2, and thalidomide (the ITI regimen) in patients with FLT3-ITD-positive acute myeloid leukemia (AML).Methods19 FLT3-ITD(+) AML patients were retrospectively analyzed, who received the sorafenib combined with ITI regimen as maintenance therapy after achieving remission at Affiliated Cancer Hospital of Zhengzhou University (January 2014–December 2024). Minimal residual disease (MRD) levels were monitored, and clinical outcomes, including survival duration, were assessed.ResultsThis study included 19 patients (9 males, 10 females) with a median age at diagnosis of 59 years (range: 21–76). The median white blood cell count was 32.25×109/L (range: 0.7–254×109/L). Among them, 13 patients (68.4%) maintained sustained MRD negativity during sorafenib combined with TI regimen therapy, while 3 patients experienced morphological relapse and 3 had molecular relapse. Median overall survival (mOS) was not reached, with 12- and 24-month OS rates of 100% (19/19) and 94.7% (18/19), respectively. During maintenance therapy with sorafenib combined with ITI, median relapse-free survival (mRFS) was also not reached, with 12- and 24-month RFS rates of 73.7% (14/19) and 57.9% (11/19), respectively.ConclusionThe sorafenib combined with ITI regimen is an effective maintenance therapy for FLT3-ITD (+) AML, significantly reducing relapse risk and prolonging survival.

Abstract Introduction: Inaticabtagene autoleucel (Inati-cel), featuring a CD19 scFv derived from the HI19a clone and a 4-1BB/CD3-ζ costimulatory domain, was approved in China for adult patients with r/r B-ALL and demonstrated high MRD-negative CR/CRi rate (85.4%) and an estimated 2-year OS rate of 55.2% (Wang Y et al. Blood Adv. 2025). Here, we report the real-world outcomes with more patients and key subgroups described. Methods: The multi-center real-world study (NCT06450067) was conducted from 2023. The endpoints included overall remission rate (ORR), minimal residual disease (MRD) negativity rate, overall survival (OS), relapse-free survival (RFS) and other relevant measures. Both OS and RFS were calculated from the day of Inati-cel infusion. Results: From November 20, 2023, to July 22, 2025, 210 patients underwent leukapheresis, with 156 receiving Inati-cel and 145 included in efficacy and safety analyses. Fifty-four patients underwent apheresis but did not receive the infusion due to manufacture failure (4 pts: 1 for insufficient lymphocytes in the apheresis product, 1 for low CD4/CD8 ratio, and 2 for unknown reasons) or infection (2 pts), or still waiting for infusion. The median age was 39 years (range, 13-76), with 28 patients aged≥60 years. Patients were pretreated with a median of 1 prior lines of therapy (range 1-5). Prior immunotherapies included: HSCT (21.4%), inotuzumab ozogamicin (18.6%), and blinatumomab (28.3%). There were 81 (55.9%) R/R ALL patients:15 (10.3%) primary refractory and 26 (17.9%) with extramedullary lesions, and 64 (44.1%) in CR1 (12 MRD-positive and 52 MRD-negative). About 50% carried high-risk genetic abnormity such as TP53 deletion or mutation (7.6%), MLL rearrangement (9.7%), alterations of IKZF1 (16.6%), Ph-like (4.8%), alterations of PAX5 (5.5%). The median infusion dose was 0.60 (range: 0.42-1.14) ×108CAR-T live cells, with 88% of patients receiving bridge therapy. With a median follow-up of 6.18 months (range: 0.85–19.13months), the BOR in all patients was 92.4% (134/145), and among the cases with remission, the MRD negativity rate was 97.8%. In R/R ALL caess, the BOR and MRD negativity rate were 86.4% (70/81) and 97.1%, respectively. Among the 12 patients with MRD-positive, the MRD-negativity rate reached 100%. Of the 26 patients with extramedullary disease, the ORR was 80%; notably of the 16 patients with CNSL, 15 attained CR. Of the 71 patients with available MRD results assessed by q-PCR or NGS for IG rearrangement after Inati-cel, 87.3% achieved MRD negative. Following infusion, expansion of Inati-cel was observed, even in patients with MRD-negative CR prior to infusion, with peaking around day 14. The longest detectability lasted up to 15 months post-infusion in a patient maintaining CR. The median OS, RFS and DOR have not been reached. The estimated 1-year OS, RFS and DOR rates were 89.3%, 78.1% and 84.7%, respectively. Seven proceeded to allo-HSCT following Inati-cel. Among all responsed patients no significant differences were observed in OS and RFS (P = 0.59 and 0.60, respectively) regardless of the subsequent transplant status, however, significant difference in RFS was observed between patients with subsequent anti-tumor treatment and those without (P = 0.003). Thirteen relapses were observed, with 6 CD19-positive, 6 CD19-negative, and 1 with unknown CD19 status. In the univariate analysis, the number of prior treatment lines, age, previous exposure to blinatumomab, or inotuzumab ozogamicin, and prior history of HSCT were not identified as significant prognostic factors for RFS and OS. A total of 9 patients died: 5 died from disease progression, 2 from transplant-related complications, 1 from infection, and 1 from unknown causes. The most common adverse events (AEs) of special interest were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The incidence rates of CRS and ICAN were 53.8% and 4.9%, respectively, while grade ≥3 CRS and ICANS occurring in 2.8% and 2.8%, respectively. All patients recovered without sequelae, with 38 treated with corticosteroids, and 33 with tocilizumab or siltuximab. Conclusion: Real-world data on Inati-cel corroborates its robust response rate, favorable toxicity profile, and survival benefits. Inati-cel demonstrates efficacy in patients with active extramedullary diseases, particularly those with CNSL. In vivo expansion was observed across different disease states.

OBJECTIVE:To retrospectively investigate the short-term efficacy and safety of the triple-drug combination regimen of venetoclax + azacitidine + homoharringtonine (VAH regimen) in patients with acute myeloid leukemia (AML). METHODS:Retrospective analysis was conducted on a total of 45 patients with newly diagnosed or refractory/relapsed AML, who were admitted to the Affiliated Cancer Hospital of Zhengzhou University, the First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, the Huaihe Hospital of Henan University, and The First Affiliated Hospital of Xinxiang Medical University from July 2022 to October 2024 and treated with the VAH regimen. The overall response rate and safety of this regimen were analyzed, and the relevant literature was reviewed. RESULTS:In the 23 newly treated patients, the overall response rate (ORR) (CR+CRi) was 65.2 % on day 15 of the VAH regimen and 82.6 % on day 29 after the end of cycle 1. The median duration of grade 3-4 neutropenia was 12.6 days. In the 22 refractory/relapsed patients, the ORR (CR+CRi) was 68.2 % on day 15 of the VAH regimen and 86.4 % on day 29 after the end of cycle 1, and the median duration of neutropenia was 14.4 days. The most common adverse reactions were myelosuppression and infection, both of which were within controllable limits. There was no death due to adverse reactions during treatment. CONCLUSION:The VAH regimen yields a high remission rate in newly diagnosed and refractory/relapsed AML patients. This retrospective study provides a novel treatment strategy for AML patients.

Background Adult patients with B-cell acute lymphoblastic leukemia (B-ALL) harboring high-risk molecular alterations face an unfavorable prognosis. Traditional treatment modalities, including chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT), are associated with a high recurrence risk in this population. Inaticabtagene Autoleucel (Inati-cel) injection, the only CD19-targeted chimeric antigen receptor T-cell (CAR-T) product approved by China's National Medical Products Administration (NMPA) for adult relapsed/refractory (R/R) B-ALL, has shown potential efficacy in real-world settings for subgroups with high-risk molecular alterations. However, its clinical effectiveness in this specific patient population requires further elucidation. Methods This multicenter, non-interventional real-world study( ClinicalTrials.gov identifier: NCT06450067) enrolled 41 adult B-ALL patients with high-risk molecular alterations who received Inati-cel treatment between December 2023 and June 2025. The cohort included 12 males and 29 females with a median age of 42 years (range: 30-58 years) and a median follow-up duration of 166 days (95% confidence interval [CI]: 103-202 days).The timing of Inati-cel administration was determined based on physician's clinical judgment and patient preference. Following CAR-T cell infusion, patients were either administered combination therapy or underwent observational follow-up. The primary endpoint was defined as recurrence-free survival (RFS). Results In the overall cohort, the median RFS and overall survival (OS) were both not reached. Among the 41 patients, the distribution of high-risk molecular alterations was as follows: 9 cases with MLL rearrangements, 19 cases with IKZF1 alterations (including 7 mutations and 12 deletions), 4 cases with TP53 mutations, and 9 cases with ≥2 high-risk factors. Statistical analysis revealed that the median RFS in the ≥2 high-risk factors group was 101 days (95% CI: 0-345 days). This values were significantly shorter than those in the MLL rearrangements/IKZF1 alterations groups (median RFS not reached, P=0.00064).Regarding treatment timing, 13 patients received Inati-cel during first complete remission with minimal residual disease negativity (CR1-MRD⁻), 3 patients in CR1 with minimal residual disease positivity (CR1-MRD⁺), and 25 patients in refractory or relapsed (R/R) status. The CR1-MRD⁻ group exhibited a trend toward superior median RFS compared to the combined CR1-MRD⁺ and R/R group (not reached vs. 404 days [95% CI: 30-777 days], P=0.073).In terms of post-CAR-T management, 20 patients received combination therapy (including three patients received tyrosine kinase inhibitors, one patients received zanubrutinib, two patients received pomalidomide, three patients received venetoclax, one patients received blinatumomab, one patients received inotuzumab ozogamicin, and four patients received allo-HSCT), while 21 patients underwent observation only. No significant difference in median RFS was observed between the two groups (404 days [95% CI: 104-703 days] vs. not reached, P=0.49).The incidence rates of CRS and ICANS were 68.3% and 7.3%, respectively, while grade ≥ 3 CRS and ICANS occurred in 2.4% and 4.9%, respectively. All patients recovered without sequelae. Conclusion In adult B-ALL patients with high-risk molecular alterations, Inati-cel demonstrates favorable efficacy, partially mitigating the adverse prognosis associated with isolated MLL rearrangements or IKZF1 alterations. However, patients with ≥2 high-risk aberrations exhibit significantly shortened RFS. Front-line consolidation with CAR-T during CR1-MRD⁻ in patients with high-risk molecular alterations may yield better RFS outcomes compared to treatment administered in R/R or MRD⁺ settings. No RFS benefit from post-CAR-T combination therapy was observed in this cohort, highlighting the need for validation with longer follow-up durations and larger patient cohorts.

Objective:To investigate the efficacy and safety of venetoclax (Ven) in combination with hypomethylating agents (HMAs) for the treatment of mixed-phenotype acute leukemia (MPAL). Methods:From July 2023 to April 2025, 4 newly diagnosed MPAL patients treated with Ven combined with HMAs at the Affiliated Cancer Hospital of Zhengzhou University, Luoyang Central Hospital and Anyang Regional Hospital were retrospectively analyzed to determine the efficacy and safety of this treatment. The relevant published studies were reviewed. Results:This study included four patients (2 males, 2 females) with a median age of 47 years (range: 40-80 years). Three patients were classified as having B/myeloid MPAL, and one was classified as having T/myeloid MPAL. All patients achieved complete remission (CR) after one cycle of venetoclax combined with HMAs. Notably, Patient 3, who tested positive for the BCR::ABL1 fusion gene, received additional tyrosine kinase inhibitor (TKI) therapy. The median duration of myelosuppression during induction therapy was 26 days (range: 7-36). Patients 1 and 4 developed infections during induction, which were controlled with aggressive antimicrobial treatment and supportive care. In contrast, Patients 2 and 3 tolerated the regimen well without significant adverse events. Conclusion:The treatment of MPAL with Ven combined with HMAs achieved a high remission rate and can be used as an alternative treatment for MPAL.

BACKGROUND:HMPL-306 has equally high inhibitory activity against mutated isocitrate dehydrogenases 1 and 2 (mIDH1/2). METHODS:This first-in-human, phase 1 dose-escalation/dose-expansion study (this study was registered at ClinicalTrials.gov: NCT04272957) enrolled patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) harboring mIDH1 and/or mIDH2. Patients received 25-250 mg of HMPL-306 orally once daily (QD) in a 28-day treatment cycle. Primary objectives were safety, tolerability, and recommended phase 2 dose (RP2D), and the secondary objective was preliminary efficacy. FINDINGS:A total of 76 patients were enrolled. No dose-limiting toxicities were observed, and the maximum tolerated dose was not reached. RP2D was 250 mg QD for cycle 1 and 150 mg QD from cycle 2 onward. Common (≥10%) grade ≥3 treatment-related adverse events included platelet count decreased, anemia, neutrophil count decreased, and white blood cell count decreased. In patients who received 150 mg, 250 mg, or the RP2D (N = 59), rates of complete remission (CR)+CR with partial hematologic recovery were 34.6% and 36.4% in the mIDH1 (n = 26) and mIDH2 (n = 33) subgroups, respectively, and among these, CR with minimal residual disease negative rates were 77.8% and 50.0%, respectively. The median overall survival was 13.4 months in patients with mIDH1 and 13.1 months in patients with mIDH2. CONCLUSIONS:HMPL-306 showed an acceptable safety profile and promising preliminary efficacy. A phase 3, randomized study of HMPL-306 in R/R AML (this study was registered at ClinicalTrials.gov: NCT06387069) has been initiated. FUNDING:HUTCHMED Limited, National Key Research and Development Program of China, National Natural Science Foundation of China, and Peking University Medicine Fund for world's leading discipline or discipline cluster development.

Contezolid, an oxazolidinone antibiotic, is recognized for its comparable antimicrobial activity to linezolid, with a distinct advantage of reduced hematological toxicity. This retrospective analysis aims to evaluate the safety and efficacy profile of contezolid in the treatment of Gram-positive bacterial infections (GPI) in hematological patients. A retrospective analysis was conducted on adult hematological patients with confirmed or suspected GPI who received contezolid for at least three days following chemotherapy or hematopoietic stem cell transplantation (HSCT) at Henan Cancer Hospital between April 2022 and June 2024. Comprehensive data collection included demographic variables, treatment protocols, infection profiles, microbiological data, and clinical outcomes. The study included 132 patients (47.5 ± 18.0 years), 61.4

IntroductionThis case is reported due to its novelty in demonstrating the efficacy of avapritinib, a selective KIT inhibitor, in a rare systemic mastocytosis-associated acute myeloid leukemia (SM-AML) patient with non-D816V KIT mutations and RUNX1::RUNX1T1 fusion. Avapritinib is established for KIT D816V-mutant advanced systemic mastocytosis (AdvSM). However, its role in non-D816V KIT mutant SM-AHN post-allogeneic hematopoietic stem cell transplantation (Allo-HSCT) remains unexplored, highlighting the need to document this therapeutic challenge and outcome.Case presentationA 15-year-old Asian male with SM-AML underwent induction chemotherapy, targeted therapy, and Allo-HSCT, but experienced graft failure with persistent mastocytosis. Post-Allo-HSCT avapritinib was initiated due to high proportion of mast cells (MCs). After 14 months, the patient achieved minimal residual disease (MRD)-negative complete remission, full donor chimerism (100%), and sustained hematologic recovery without adverse events. MC burden declined from 14.06% to 0.3%, and RUNX1::RUNX1T1 fusion became undetectable.ConclusionThis case highlights avapritinib’s potential as a salvage therapy for non-D816V KIT mutant SM-AML post-Allo-HSCT, effectively reducing MC clones and restoring donor chimerism. It suggests that avapritinib may bridge therapeutic gaps for atypical KIT-mutant systemic mastocytosis with associated hematologic neoplasm (SM-AHN) that is ineligible for Allo-HSCT or relapsed. Prospective trials are warranted to validate its efficacy, optimize dosing, and explore synergies with Allo-HSCT, offering new strategies for these high-risk patients.

Background: Patients (pts) with R/R DLBCL who failed with multi-agent therapy have a poor prognosis. MRG001 is a CD20-directed antibody drug conjugate (ADC) composed of a chimeric anti-CD20 monoclonal antibody (mAb) conjugated to the monomethyl auristatin E (MMAE) via a valine citrulline linker. MRG001 had shown clinical efficacy in the previous R/R DLBCL study [Yuqin Song, Blood, 2021]. To further enhance the efficacy, we explored the combination therapy. Orelabrutinib, a new-generation bruton's tyrosine kinase (BTK) inhibitor, has no off-target impact on interleukin-2 (IL-2)-inducible T cell kinase pathway. It can preserve NK-cell-mediated antibody-dependent cellular cytotoxicity (ADCC) induced by anti-CD20 mAb and enhanced the apoptosis of tumor cells, which may have compelling mechanistic synergy with MRG001. Preclinical study had shown the addition of orelabrutinib to anti-CD20 mAb had produced promising anti-tumor effects in B-cell lymphomas [Yu H, Mol Ther Oncolytics, 2012]. To validate the synergistic potential of combining these two agents, we conducted the multicenter Phase II study, aimed to evaluate the safety and efficacy of MRG001 in combination with Orelabrutinib in R/R DLBCL. Here we reported the preliminary results. Methods: Pts aged ≥18 years with ECOG PS 0-2, histologically diagnosed R/R DLBCL who had failed at least 1 prior therapy were enrolled. All pts received MRG001 1.8 mg/kg intravenously once every 3 weeks, Orelabrutinib 150 mg orally once daily, from day 2 to day 21 in 21-day cycles, until disease progression, unacceptable toxicity, or withdrawal. The primary endpoint was overall response rate (ORR) assessed by investigators according to the Lugano response criteria, secondary endpoints were progression free survival (PFS), duration of response (DoR) and safety. Results: As of the data cutoff date (Jun 20, 2025), 22 pts were enrolled and received ≥1 dose of MRG001 and orelabrutinib. Of these pts, 2pts withdrew early and 4 pts had not yet reached their first tumor evaluation, resulting in 16 efficacy-evaluable pts with ≥1 post-baseline tumor assessment. The median follow-up was 3.8 months (range: 1.8–5.5). Baseline characteristics of the enrolled cohort (n=22) reflected a heavily pretreated population: the median age was 58 years (32-74); 11 (50.0%) pts were male; 14 (68.6%) pts had an ECOG PS 1 and 3 (13.6%) pts had an ECOG PS 2; the median prior therapy lines was 3 (1-10), with 11 (50.0%) pts having received ≥3 prior lines; and 8 (36.4%) presenting with bulky disease (≥7.5cm). Among the 16 efficacy-evaluable pts, ORR was 75.0% (95% CI: 47.6, 92.7), comprising 4 (25.0%) complete responses (CR) pts and 8 (50.0%) partial responses (PR) pts. An additional 3 pts (18.8%) achieved stable disease, yielding a disease control rate (DCR) of 93.8% (95% CI: 69.8, 99.8). Median progression-free survival (PFS), duration of response (DoR), and overall survival (OS) were not yet mature at the time of analysis. Notably, high activity was observed in key high-risk subgroups. Among the 4 pts previously exposed to anti-CD3/CD20 bispecific antibodies, 3 pts achieved PR and 1 pt achieved CR (ORR 100%). In the 8 evaluable pts with ≥3 prior lines, ORR was 87.5% and DCR was 100.0%. For the 4 evaluable pts with bulky disease, ORR was 50.0% and DCR was 100.0%. Treatment related adverse events (TRAEs) occurred in 21 of 22 (95.5%) pts. The most commonly reported TRAEs were neutrophil count decreased (72.7%), white blood cell count decreased (63.6%), anemia (50.0%), and platelet count decreased (50.0%). Grade 3/4 TRAEs were observed in 14 (63.6%) pts, predominantly neutrophil count decreased (54.5%), and white blood cell count decreased (36.4%). No treatment-related tumor lysis syndrome occurred, and no TRAEs led to discontinuation or death. Conclusion: Phase II results show that MRG001 combined with Orelabrutinib had clinically encouraging antitumor activity in pts with R/R DLBCL. Additionally, the safety profile was manageable, and pts tolerated treatment well. The trial is still ongoing.

Objective: To compare and analyze the clinical characteristics of acute myeloid leukemia (AML) related to the treatment of hematological tumors and solid tumors. Methods: The laboratory and clinical data of 41 patients with treatment-related AML (t-AML) in the Department of Hematology, Henan Cancer Hospital from January 2014 to December 2021 were retrospectively analyzed, and they were divided into hematological tumor group and solid tumor group. Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: The median interval from the first tumor diagnosis to t-AML in 41 patients was 21.0 (16.5-46.0) months; 24 (58.5%) had abnormal expression of lymphoid antigen, 28 (68.3%) had abnormal karyotype, 18 cases (43.9%) were positive for fusion gene, and 28 cases (68.3%) were positive for gene mutation; the median recurrence-free survival (RFS) was 11.0 months, and the median overall survival (OS) was 11.5 months. The proportion of acute promyelocytic leukemia ([APL], 0.0, 0/13), complete response ([CR],18.2%, 2/11), median OS (4.5 months) and median RFS (2.5 months) of t-AML patients in the hematological tumor group were significantly lower than those in the solid tumor group (35.7%, 10/28; 68.0%, 17/25; not reach; not reach), but the proportion of M4 /M5 (93.2%,12/13) was significantly higher than that in the solid tumor group (53.6%,15/18; all P values<0.05). Through subgroup analysis, the proportion of patients with positive PML-RARa and good prognosis karyotypes in the solid tumor group (35.7%, 10/28; 46.4%, 13/28) was significantly higher than that in the hematological tumor group (0.0, 0/13; 0.0, 0/13; P<0.05), while the proportion of patients with intermediate karyotypes (42.9%, 12/28) was significantly lower than that in the hematological tumor group (84.6%, 11/13; P<0.05), the difference was statistically significant. The CR rate (90.0%, 9/10), median OS (not reach) and median RFS (not reach) in the t-APL group were higher than those in the t-AML (without t-APL) group (38.5%, 10/26; 6 months; 8 months; P<0.05). After excluding the effect of t-APL patients, there was no significant difference in the CR rate, median OS and median RFS between the solid tumor group (8; 9 months; not reach) and the hematological tumor group (2; 4 months; 2 months; P>0.05). Univariate analysis showed that the primary tumor belongs to hematological tumor was a common risk factor for OS and RFS in t-AML patients (P<0.10). Conclusions: Compared with patients with t-AML secondary to solid tumors, patients with t-AML secondary to hematological tumors have poorer treatment effects and poorer prognosis. After excluding the effect of t-APL patients, there are no significant differences in the treatment efficacy and prognosis between the two types of t-AML patients.

Thirty refractory relapsed acute myeloid leukemia (R/R AML) patients who received salvage allo-HSCT with MeCBA conditioning regimen from January 2018 to June 2022 at Henan Cancer Hospital were included, and their clinical data were reviewed. There were 16 males and 14 females among the 30 patients with a median age of 37 (16-53) years. There were 3 sibling allograft donor transplants, 1 unrelated donor transplant, and 26 haplotype transplants. The median course of pre-transplant chemotherapy was 4 (3-22). The time of neutrophil engraftment was 14 (9-22) days and 18 (10-40) days for platelet. The 30-day cumulative incidence of neutrophil engraftment was 100% and the 100-day cumulative incidence of platelet engraftment was 96.7% (95% CI 85.4% -97.5% ). 22 (73.3% ) patients experienced grade 1-2 gastrointestinal reactions, and there was no grade 3-4 organ toxicity. With a median follow-up of 37.1 months, the overall survival (OS) rate, event-free survival (EFS) rate, cumulative recurrence rate (CIR), and non-recurrence mortality (NRM) rate at 3 years after transplantation were 70.0% (95% CI 50.3% -83.1% ), 65.3% (95% CI 44.8% -79.8% ), 21.2% (95% CI 9.2% -44.4% ) and 16.7% (95% CI 7.3% -35.5% ), respectively.

Systemic mastocytosis (SM) is a subset of rare neoplasms characterized by clonal proliferation of aberrant mast cells (MCs) and their accumulation in >= 1 extracutaneous organs, which typically associates with activating KIT mutations.(1) SM with an associated hematological neoplasm (AHN) is the second most common type of SM in Mayo series (similar to 40%),(2) with challenging diagnosis because the mast cell infiltration may hide behind the AHN component and vice versa.(3-5) This is particularly applicable to acute myeloid leukemia (AML) because the histological examination of bone marrow (BM) has not been established as a standard diagnostic tool. Moreover, the concomitant hematological neoplasm often shares a KIT mutation and/or other clonal genetic abnormalities with neoplastic MCs. AML with t(8;21) (q22;q22)/RUNX1::RUNX1T1 [t(8;21) AML] represents 4% to 8% of all AMLs, which is categorized to the genetically favorable risk group.(6) Meanwhile, KIT mutations, most frequently at position D816, are detectable in up to 20% to 47% of patients with t(8;21) AML and associate with decreased remission duration and inferior overall survival (OS).(7-10) Previous case reports, case-series, and/or literature reviews have described the potential association of KIT mutant t(8;21) AML [KITpos t(8;21) AML] with underlying SM.(11)(,)(12) Owing to a lack of literature on investigating similarities and differences between SM-t(8;21) AML and KITpos t(8;21) AML, we carried out this retrospective cohort study from multiple Chinese centers to compare clinical and molecular features between these 2 groups. Between January 2009 and December 2022, 24 patients with SM-t(8;21) AML and 212 with KITpos t(8;21) AML diagnosed and treated in 16 Chinese centers were eligible. All patients were screened for SM by BM smear, flow cytometry, and/or BM histological examination. Details of the study design, patient population, treatment regimen, and statistical analysis have been described in supplemental Data. This study was approved by the responsible ethics committees and performed in accordance with the Declaration of Helsinki.

Efficacy and safety analysis of the combination of decitabine priming followed by CHAG chemotherapy in treatment of relapsed/refractory(r/r) acute myeloid leukemia (AML). Between January 2013 and June 2020, 62 r/r AML patients in our center receiving therapy including combination of decitabine and CHAG pre-excitation regimen were enrolled. Primary objectives were overall response (ORR: complete remission + partial remission), adverse events, overall survival (OS) and relapse-free survival (RFS). There were 46 patients (74.2%) with complete remission (CR), 5 patients (8.06%) with partial remission (PR), ORR was 82.2%. Main adverse events were bone marrow suppression, fever and infection, and no chemotherapy-related deaths occurred. The median RFS time was 4.3 months (0.3 ~ 65 months), and median OS time was 7.75 months (1 ~ 66.3 months). Decitabine priming followed by CHAG regimen is effective and tolerated in patients with r/r AML, and can be used as a salvage treatment for patients with r/r AML.

患者, 女, 59岁。2021年12月11日因体检发现白细胞偏低就诊于当地医院, 血常规示:WBC 1.5×109/L, HGB 105 g/L, PLT 258×109/L, 中性粒细胞计数0.2×109/L。骨髓细胞形态学显示原始细胞58%。染色体核型:47, XX, +8[2]/46, XX[5]。免疫分型倾向于急性髓系白血病(AML)。二代测序(NGS)检出ASXL1、DNMT3A、IDH1突变。当地医院诊断为AML。遂给予DA方案诱导缓解治疗, 具体为:柔红霉素(DNR)60 mg/m2第1～3天, 阿糖胞苷(Ara-C)100 mg/m2第1～7天, 1个疗程后疗效评估示未缓解。后患者接受阿扎胞苷(AZA)联合CAG方案治疗, 具体为:AZA100 mg第1～7天;G-CSF 300 μg, 每12 h 1次, 第0～14天;阿克拉霉素(Acla)20 mg/d第1～4天;Ara-C 15 mg, 每12 h 1次, 第1～14天, 疗效评估示仍未缓解。后患者接受维奈克拉(Ven)单药治疗1个周期后获得缓解。后续分别接受了1个周期Ven、2个周期中剂量Ara-C、1个周期Ven巩固治疗(具体用药不详)。在Ven维持治疗中疾病复发。融合基因检测示BCR::ABL1(p210)13.97%。染色体核型:46, XX,t(9;22)(q34;q11)[4]/46,XX[10]。