Allogeneic haematopoietic stem cell transplantation (allo-HSCT) remains the only curative therapy for patients with high-risk myelodysplastic syndrome (MDS). However, the optimal timing and value of pretransplant cytoreduction and post-transplant maintenance remain unclear, and transplant-modifiable variables are not well defined in real-world settings. We retrospectively analysed 215 consecutive MDS patients who underwent allo-HSCT. Clinical, molecular and transplant-related factors were evaluated for their impact on relapse, relapse-free survival (RFS) and overall survival (OS). TP53 mutation, complex karyotype, and positive measurable residual disease (MRD) after cytoreductive treatment were associated with increased relapse risk. Among transplant-related variables, younger donor age (<42 years) and higher CD34+ cell dose (≥3.1 × 106/kg) significantly reduced relapse risk. Notably, pretransplant cytoreduction did not confer measurable benefit on outcomes. In contrast, post-transplant maintenance therapy significantly reduced relapse incidence and prolonged RFS. Pretransplant cytoreduction offers limited clinical value, whereas post-transplant maintenance and modifiable transplant variables (CD34+ cell dose and donor age) substantially improve outcomes after allo-HSCT for MDS. These findings highlight actionable strategies that may refine transplant decision-making and optimize outcomes in clinical practice.

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 analyze the efficacy and immunological differences of anti-T-lymphocyte globulin ( ATLG ) and anti-thymocyte globulin ( ATG ) in allogeneic hematopoietic stem cell transplantation. Methods We retrospectively reviewed the patients who underwent allogeneic hematopoietic stem cell transplantation in the First Affiliated Hospital of Zhengzhou University between August 2023 and December 2024 . According to the use of ATLG or ATG before transplantation to prevent graft-versus-host disease, they were divided into the ATLG group (n=44) and the ATG group (n=136). We analyzed the incidence of GVHD, Epstein–Barr virus (EBV) and cytomegalovirus (CMV) infections, recurrence rates, and non-relapse mortality (NRM) in the two groups. The peripheral blood counts and lymphocyte subset data were collected at 1 month, 2 months and 3 months post-hematopoietic stem cell reinfusion to assess the immunological differences. Results There was no significant differences between groups in the incidence of II-IV aGVHD, III-IV aGVHD, cGVHD ,CMV-related infection, recurrence rate, or NRM. In the ATG group, 21 patients (15.44 % ) developed EBV-associated infection, which was significantly higher than that in the ATLG group ( P = 0.005 ). At 1 month, 2 months and 3 months post-transplant, absolute counts of peripheral lymphocytes, monocytes, eosinophils, and basophils showed no significant differences between groups. The lymphocyte subset analysis revealed that the CD19 + B cell count in the ATLG group was significantly higher than those in the ATG group at 2 months ( Median = 66.09, P = 0.020 ) and 3 months ( Median = 70.68, P = 0.014 ) post-transplant. No significant differences were observed in CD4 + T cells, CD8 + T cells, NK cells or NKT cells between the groups. Conclusion Compared with the ATG group, ATLG was associated with a lower incidence of EBV-associated infection and a faster CD19 + B cells recovery, suggesting better humoral immune reconstruction. The rates of GVHD , relapse and NRM were comparable between the two groups.

OBJECTIVE:To explore the efficacy and apoptosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute myeloid leukemia (AML) with ASXL1 mutation. METHODS:The clinical data of 80 AML patients with ASXL1 mutation treated in our hospital from January 2019 to December 2021 were retrospectively analyzed. The clinical characteristics of the patients were summarized, and the therapeutic effect and prognostic factors of allo-HSCT for the patients were analyzed. RESULTS:Among the 80 patients, 38 were males and 42 were females, and the median age was 39(14-65) years. There were 17 patients in low-risk group, 25 patients in medium-risk group and 38 patients in high-risk group. ASXL1 mutation co-occurred with many other gene mutations, and the frequent mutated genes were TET2 (71.25%), NRAS (18.75%), DNMT3A (16.25%), NPM1 (15.00%), CEBPA (13.75%). Among medium and high-risk patients, 29 underwent allo-HSCT, while 34 received chemotherapy. The 2-year overall survival (OS) rate and disease-free survival (DFS) rate of the allo-HSCT group were 72.4% and 70.2%, while those of the chemotherapy group were 44.1% and 34.0%, respectively. The statistical analysis showed significant differences between the two groups (both P < 0.01). Multivariate analysis showed that age at transplantation >50- years and occurrence of acute graft-versus-host disease after transplantation were poor prognostic factors for OS and DFS in transplantation patients. CONCLUSION:Allo-HSCT can improve the prognosis of AML patients with ASXL1 mutation.

6529 Background: Inaticabtagene autoleucel (Inati-cel) is a CD19-specific chimeric antigen receptor (CAR) T-cell product, featuring a CD19 scFv derived from the clone HI19α and a 4-1BB/CD3-ζ costimulatory domain, which was approved in China for adult patients with relapsed or refractory B-acute lymphoblastic leukemia (r/r B-ALL) in November 2023. Methods: We conducted the multi-center, non-interventional real-world study (NCT06450067) to evaluate Inati-cel for adult B-ALL patients. Between November 20, 2023, and November 13, 2024, 62 patients received Inati-cel and were evaluable. The median age was 37.5 (range, 14-76) years, with 13 patients aged≥60 years. At screening, 16 cases relapsed after hematopoietic stem cell transplantation (HSCT), 4 cases were primary refractory, and over 70% of patients carried high-risk genetic abnormity. The median infusion dose was 0.60 (range: 0.46-0.9) ×10 8 CAR-T live cells. Results: The data as of December 30, 2024, with a median follow-up of 3.8 months (range: 0.5–12.4 months), 89.5% achieved MRD-negative ORR after Inati-cel in r/r patients, including 31 with CR and 3 with CRi (table1). Nine patients with MRD-positive at screening, the MRD-negativity rate reached 100% after Inati-cel. After Inati-cel, 26 patients had MRD results detected by q-PCR, and 92.3% obtained negative results. After achieving CR/CRi, 4 patients subsequently underwent allo-HSCT in remission. The median DOR, OS and RFS have not been reached with and without censoring patients at subsequent allo-HSCT. Among the evaluable patients, the 1-year RFS and DOR rates were 76.2% and 74.1%, respectively. Seven patients experienced relapses, including 3 CD19+ relapses, 2 CD19- relapses, and 2 with unclear CD19 status. It is worth noting that in 6 cases of extramedullary disease, 4 cases were effective, but 2 cases relapsed within 3 months after Inati-cel. All patients who received the Inati-cel infusion were alive, except for one death from disease progression. The most common adverse events (AEs) of special interest were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Fifty-one percent of patients developed CRS, but grade 3 or higher CRS and ICANS only occurred in 3.2% and 1.6% of patients, respectively; all patients recovering without sequelae, no AE-related deaths. Conclusions: The real-world use of Inati-cel demonstrates a high MRD-negative ORR in adult B-ALL. The safety profile was manageable, with a low incidence of grade ≥3 CRS and ICANS in the real-world setting. Longer follow-up data will be presented. Clinical trial information: NCT06450067 . Efficacy profiles treated with Inati-cel. Response r/r B-ALL at enrollment，n=32 isolated extramedullary disease, n=6 MRD-pos, n=4 MRD-neg, n=20 CR or CRi （No. of patients） 30 4 - - Rate 93.7% 66.7% - - CR, No. (%) 27(84.3%) 4(66.7%) - - CRi, No. (%) 3 (9.4%) - - - MRD-neg rate,No. (%) 30/30 (100%) - 4/4 (100%) - 1-year DOR rate 67.4% 93.3% 1-year RFS rate 68.2% 93.8%

Introduction Limited therapeutic options are available for adult patients with B-cell acute lymphoblastic leukemia (B-ALL) who relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). With conventional therapies, the prognosis for such relapsed B-ALL cases remain dismal. However, CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy has achieved high complete remission (CR) rates in this setting. Inaticabtagene autoleucel (Inati-cel) is a CD19- CAR T cell featuring a CD19 single-chain variable fragment (scFv) derived from an HI19a clone and a 4-1BB/CD3-ζ costimulatory domain. It has demonstrated a high minimal residual disease (MRD)-negative CR/CR with incomplete count recovery (CRi) rate (85.4%) and an estimated 2-year overall survival (OS) rate of 55.2% (Wang Y. et al., Blood Adv., 2025). We report real-world data on Inati-cel use in patients with B-ALL who relapsed after HSCT, evaluating its potential to improve treatment outcomes. Methods We conducted a multi-institutional real-world study of Inati-cel (NCT06450067), enrolling patients treated from 2024 onwards. Key endpoints included OS, overall response rate (ORR), minimal residual disease (MRD) negativity rate, duration of response (DOR), relapse-free survival (RFS), and CAR-T-related adverse events (AEs). Both OS and RFS were calculated from the day of Inati-cel infusion. Results From January 8, 2024, to July 20, 2025, 156 patients received Inati-cel. Of these cases, 31 in post-HSCT relapses underwent efficacy and safety evaluations. Their median age was 36 years (range: 20–61 years). The patients were pretreated with a median of 2 prior lines of therapy (range: 1–5 lines). Prior therapies included blinatumomab (38.7%) and inotuzumab ozogamicin (22.6%). Eleven (35.5%) had extramedullary relapses, including 7 with central nervous system leukemia. High-risk genetic alterations carried by the patients included Ph positivity (13, 41.9%), TP53 deletion or mutation (3, 9.7%), mixed-lineage leukemia rearrangement (3, 9.7%), and alterations in IKZF1 (5, 16.1%). The median infusion dose was 0.60 (range: 0.42–1.00) × 108 viable CAR-T cells. All but one patient received bridging therapy. The median interval from apheresis to reinfusion was 37 days (range: 20–98 days). With a median follow-up of 7.33 months (range: 0.85–16.93 months), the best ORR across all caese was 83.9%; among responders, the MRD negativity rate (assessed using flow cytometry) was 96.2%. Notably, of the 11 with extramedullary disease, the ORR was 72.7%. Post-infusion, Inati-cel expansion was observed even in caese with MRD-negative CR pre-infusion, peaking around day 14. The longest duration of detectability was 12 months post-infusion in a caes in sustained CR. Notably, detectable CAR-T cells were observed in some patients' cerebrospinal fluid. While the median OS and RFS have not yet been reached, the estimated 1-year OS, RFS, and DOR rates were 64.5%, 69.8%, and 83.2%, respectively. Patients with and without prior blinatumomab exposure had similar OS (p = 0.62) and RFS (p = 0.58); the same was true for prior inotuzumab ozogamicin exposure (p = 0.86 and p = 0.67, respectively). Among patients who received sequential maintenance therapy versus those who did not, the 12-month OS and RFS were 91.2% vs. 51.3% (p = 0.185) and 91.6% vs. 55.4% (p = 0.031), respectively. No cases underwent subsequent allo-HSCT while in remission. Subsequent maintenance therapies included tyrosine kinase inhibitors (TKIs; n = 6), low-dose chemotherapy (n = 5), and inotuzumab ozogamicin (n = 3). Two relapses were observed, both with CD19-positive patients. Five patients died: 3 from disease progression, 1 from infection, and 1 from unknown causes (more than 3 months after Inati-cel infusion). The most common AEs of special interest were cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The incidence rates of CRS and ICANS were 45.2% and 3.2%, respectively, while grade ≥ 3 CRS and ICANS occurred in 3.2% and 0.0%, respectively. In the 11 extramedullary patients, no ICANS and no ≥ grade 3 CRS occurred. All patients recovered without sequelae. ConclusionReal-world data demonstrate that Inati-cel exhibits excellent efficacy in patients with B-ALL who relapse after HSCT and in patients with active extramedullary disease; its safety was also established. Extended follow-up is warranted to fully characterize the long-term outcomes of Inati-cel use.

OBJECTIVES:To investigate the regulatory mechanism of aurora kinase B (AURKB) for promoting malignant phenotype of osteosarcoma cells. METHODS:HA-Vector or HA-AURKB was transfected in 293T cells to identify the molecules interacting with AURKB using immunoprecipitation combined with liquid chromatography-tandem mass spectrometry followed by verification with co-immunoprecipitation and Western blotting. In cultured osteosarcoma cells with lentivirus-mediated RNA interference of AURKB or DHX9 or their overexpression, the changes in cell proliferation, migration, and invasion activities were observed with EDU and Transwell assays. Mechanistic analysis was performed using Co-IP and in vivo ubiquitination experiments to detect the interaction between AURKB and DHX9 and the phosphorylation and ubiquitination levels of DHX9. Western blotting was used to detect the effect of AURKB and DHX9 on activation of nuclear factor-κB (NF-κB) signaling. RESULTS:AURKB was highly expressed in osteosarcoma cell lines, and in osteosarcoma 143B cells, AURKB silencing significantly reduced cell proliferation, migration and invasion abilities. Interactions between AURKB and DHX9 were detected, and they were both highly expressed in osteosarcoma tissues; silencing AURKB reduced the protein expression of DHX9, and AURKB overexpression increased DHX9 phosphorylation. Silencing AURKB did not significantly affect the transcription and translation of DHX9 but accelerated its degradation and ubiquitination. Overexpression of DHX9 effectively reversed the effects of AURKB silencing on IKBα protein and phosphorylated p65, promoted nuclear translocation of p65 to activate the NF-κB signaling pathway, and enhanced the proliferation, migration, and invasion abilities of cultured osteosarcoma cells. CONCLUSIONS:AURKB overexpression promotes the malignant phenotype of osteosarcoma cells by activating the NF-κB signaling pathway via regulating DHX9.

Background: Recent miRNA profiling studies have implicated the potential use of miRNAs as as diagnostic and prognostic indicators in acute myeloid leukemia (AML), which has been reportedly implicated in the interplay with certain mRNAs. Herein this study, we intend to characterize the functional relevance of SPOP/miR-183/METAP2 axis in AML in vivo and in vitro. Methods: Differentially expressed mRNAs and downstream regulatory miRNA were predicted by in silico analysis. We induced SPOP/miR-183/METAP2 overexpression or inhibition to examine their effects on AML cell proliferation and apoptosis in vitro and tumor growth in vivo , along with their interaction with β-catenin. Results: SPOP and miR-183 were highly expressed, while METAP2 was poorly expressed in patient peripheral blood samples and cell lines of AML. SPOP accelerated the proliferation of AML cells and repressed apoptosis. Mechanistically, SPOP enhanced β-catenin protein stability and nuclear translocation leading to upregulated expression of miR-183. MiR-183 facilitated proliferation and inhibited apoptosis of AML cells by targeting METAP2. Furthermore, miR-183 inhibition and METAP2 overexpression reversed SPOP-induced AML cell malignancy. Besides, in vitro findings were reproduced by in vivo findings. Conclusion: SPOP stimulated AML malignant progression by inducing β-catenin stability and miR-183/METAP2 axis activation, highlighting a potential therapeutic target against AML recurrence and metastasis.

ObjectiveTo compare the efficacy and safety of venetoclax (VEN) in combination with chemotherapy (chemo) versus chemo alone in the treatment of acute myeloid leukemia (AML).MethodTo compare the efficacy and/or safety of VEN+chemo versus chemotherapy alone for AML, PubMed, Embase, Web of Science, and the Cochrane Library were used to searching up to June 2023. Comparisons included complete remission (CR), CR with incomplete hematologic recovery (CRi), morphologic leukemia-free state (MLFS), overall response rate (ORR), and adverse events (AEs).ResultA total of 9 articles were included, including 3124 patients. The baseline characteristics between two patient groups were similar. The combined analysis showed that compared with the group receiving chemo alone, the VEN+chemo group exhibited higher rates of CR, CRi, MLFS and ORR. Additionally, the VEN+chemo group had longer event-free survival (EFS) and overall survival (OS) durations. The incidence rates of AEs and serious AEs (SAEs) were similar between the two groups, but the early 30-day mortality rate was lower in the VEN+chemo group than in the chemo alone group.ConclusionThe VEN+chemo therapy demonstrates significant efficacy and safety profile in AML patients. However, more prospective studies are needed in the future to provide more accurate and robust evidence for treatment selection in patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023439288, identifier CRD42023439288.

Objective: The study aimed to evaluate pre-allogeneic hematopoietic stem cell transplantation (allo-HSCT) treatment, compare the endpoints related to disease management between pre-HSCT cytoreduction patients and upfront transplantation patients with higher-risk myelodysplastic syndrome (MDS). Methods: A total of 90 higher-risk MDS patients administered allo-HSCT in the Hematology Department of the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed, which included 28 patients with upfront transplantation and 62 patients with pre-transplant cytoreduction, including 30 patients received hypomethylating agents (HMA) and 32 patients received hypomethylating agents and induction chemotherapy (HMA+IC). Difference between the two groups regarding hematopoietic reconstruction, graft-versus-host disease (GVHD), relapse rate, non-relapse death (NRM), overall survival (OS) and relapse-free survival (RFS) was compared.Results: No significant differences in OS, DFS and NRM were found between the upfront transplantation and pre -transplant cytoreduction groups, and cumulative cGVHD occurrence and relapse rates were 35.7 % and 14.5 % (P = 0.029), and 10.7 % and 12.9 % (p = 0.535), respectively. Survival rates were significantly higher in the upfront transplantation and HMA+IC groups compared with the HMA group (3-year OS: 67.9 %, 68.8 %, 43.3 %, P = 0.039; 3-year RFS: 64.3 %, 62.5 %, 43.3 %, P = 0.107; 3-year NRM: 25.0 %, 21.9 %, 50.0 %, P = 0.025). Compared with the upfront transplantation group, overall response to cytoreductive therapy (OR) and non -response to cytoreductive therapy (NR), 3-year OS were 67.9 %, 73.0 % and 32.0 % (P < 0.001), 3-year RFS were 64.3 %, 73.0 % and 24.0 % (P < 0.001) and 3-year NRM were 25.0 %, 21.6 %, and 56.0 %, respectively (P < 0.001). Upfront transplantation (n = 11) had better OS and RFS compared with the cytoreductive group (n = 10) in patients with >= 10 % bone marrow blast cells before transplantation (3-year OS: 63.64 %, 22.22 %, p = 0.010; 3-year DFS: 63.64 %, 20.00 %, p = 0.012, respectively).Conclusion: The pre-transplant treatment regimen was an independent prognostic factor of OS and NRM. If the donor is suitable, upfront transplantation may provide longer survival in higher-risk MDS patients, which, however, may also increase the incidence of cGVHD. Even in patients with bone marrow blast cells >= 10 % before transplantation, upfront transplantation was not worse than transplantation after cytoreductive therapy. While waiting for a transplant, HMA+IC therapy may be a good pre-transplant treatment option.

To explore the characteristics of hemogram in patients with aplastic anemia (AA), especially mean corpuscular volume (MCV) and red cell distribution width (RDW). We examined the blood routine of 180 new-onset AA patients and used 166 patients with myelodysplastic syndrome (MDS) as controls. Among the 180 AA patients, 105 (58.3%) were diagnosed with severe AA (SAA), while 75 (41.7%) were diagnosed with non-severe AA (NSAA). Compared to MDS, patients with SAA generally had unfavorable hemogram, including significantly lower white blood cell (WBC), absolute neutrophil count (ANC), hemoglobin (Hb), platelet (PLT) and reticulocyte counts (RET). However, WBC, ANC and lymphocyte counts were higher in the NSAA group than in the MDS group; Hb and Ret were comparable between the two groups. 8.5% of SAA patients and 58.1% of NSAA patients presented with macrocytic anemia, whereas 25.7% of SAA and 64.0% of NSAA had a high RDW. In the MDS group, 54.7% of patients presented with macrocytic anemia, and 84.7% had increased RDW. WBC, ANC, PLT, and Ret in a high-RDW group (25.7% of SAA) were significantly higher than in a normal-RDW group (74.3% of SAA). Overall, most SAA patients exhibited normocytic-normochromic anemia, and their hemograms decreased more significantly; more than half of NSAA patients showed macrocytic-heterogeneous anemia, and their hemograms were similar to those of MDS. Patients with elevated RDW may have better residual bone marrow hematopoietic function than those with normal RDW but with more severe anemia.

In adults with acute lymphoblastic leukemia (ALL), post-transplant relapse is a major risk factor for mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our study investigated the efficacy and safety of decitabine (dec) with ALL patients post-transplantation. We performed a retrospective cohort study to assess the efficacy of decitabine (dec) with post-transplant ALL at the First Affiliated Hospital of Zhengzhou University from February 2016 to September 2021. A total of 141 consecutive ALL patients were analyzed and divided into decitabine (dec, n = 65) and control (ctrl, n = 76) groups based on whether they were treated with decitabine after allo-HSCT. The 3-year cumulative incidence of relapse (CIR) rate in the dec group was lower than that in the ctrl group (19.6% vs. 36.1%, p = 0.031), with a hazard ratio of 0.491 (95% confidence interval [CI], 0.257–0.936). Additionally, subgroup analyses revealed that the 3-year CIR rate of T-ALL and Ph-negative B-ALL patients in the dec and ctrl groups was 11.7% vs. 35.9% and 19.5% vs. 42.2% ( p = 0.035, p = 0.068) respectively. In summary, ALL patients, especially those with T-ALL and Ph-negative B-ALL, may benefit from decitabine as maintenance therapy following allo-HSCT.

Aplastic anemia (AA) is a potentially fatal bone marrow failure syndrome characterized by a paucity of hematopoietic stem cells and progenitor cells with varying degrees of cytopenia and fatty infiltration of the bone marrow space. Recent advances in genomics have uncovered a link between somatic mutations and myeloid cancer in AA patients. At present, the impact of these mutations on AA patients remains uncertain. We retrospectively investigated 279 AA patients and 174 patients with myelodysplastic syndromes (MDS) and performed targeted sequencing of 22 genes on their bone marrow cells using next-generation sequencing (NGS). Associations of somatic mutations with prognostic relevance and response to treatment were analyzed. Of 279 AA patients, 25 (9.0%) patients had somatic mutations, and 20 (7.2%) patients had one mutation. The most frequently mutated genes were ASXL1(3.2% of the patients), DNMT3A (1.8%) and TET2 (1.8%). In the MDS group, somatic mutations were detected in 120 of 174 (69.0%) patients, and 81 patients (46.6%) had more than one mutation. The most frequently mutated genes were U2AF1 (24.7% of the patients), ASXL1 (18.4%) and TP53 (13.2%). Compared with MDS patients, AA patients had a significantly lower frequency of somatic mutations and mostly one mutation. Similarly, the median variant allele frequency was lower in AA patients than in MDS patients (6.9% vs. 28.4%). The overall response of 3 and 6 months in the somatic mutation (SM) group was 37.5% and 66.7%, respectively. Moreover, there was no significant difference compared with the no somatic mutation (N-SM) group. During the 2-years follow-up period, four (20%) deaths occurred in the SM group and 40 (18.1%) in the N-SM group, with no significant difference in overall survival and event-free survival between the two groups. Our data indicated that myeloid tumor-associated somatic mutations in AA patients were detected in only a minority of patients by NGS. AA and MDS patients had different gene mutation patterns. The somatic mutations in patients with AA were characterized by lower mutation frequency, mostly one mutation, and lower median allelic burden of mutations than MDS. Somatic mutations were a common finding in the elderly, and the frequency of mutations increases with age. The platelet count affected the treatment response at 3 months, and ferritin level affected the outcome at 6 months, while somatic mutations were not associated with treatment response or long-term survival. However, our cohort of patients with the mutation was small; this result needs to be further confirmed with large patient sample.

Myeloid sarcoma is a rare manifestation of acute myeloid leukemia (AML) and is associated with poor overall survival (OS). The optimal treatment remains unclear. The study retrospectively evaluated 118 patients with myeloid sarcoma who were treated at the First Affiliated Hospital of Zhengzhou University from January 2010 to July 2021. All cases were diagnosed by tissue biopsy. 41 patients underwent genetic mutation analysis. The most frequent genetic mutations were KIT (16.6%), followed by TET2 (14.6%), and NRAS (14.6%). The median survival time of 118 patients was 4 months (range, 1–51 months), while the median survival time of 11 patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) was 19 months (range, 8–51 months). 4 (36.4%) of the 11 patients experienced relapse within 1 year after transplantation. 1 patient died from a severe infection. Of the 6 surviving patients, 5 patients have received maintenance treatment with decitabine after transplantation, and all remained in a state of recurrence-free survival. Patients with myeloid sarcoma have a very unfavorable outcome. Allo-HSCT is an effective treatment option. Recurrence remains the main cause of transplant failure. Maintenance treatment with decitabine after transplantation can prolong the recurrence-free survival time, although these results must be verified in a study with expanded sample size.

目的 观察达雷妥尤单抗(Dara)治疗复发/难治性急性白血病(R/R-AL)的效果.方法 回顾性分析2019年1月至2021年6月在郑州大学第一附属医院接受Dara治疗的7例R/R-AL患者的临床资料.结果 治疗前,7例患者均存在CD38表达,中位表达量为91％(50％～100％).所有患者接受Dara治疗中位次数为4(1～6)次.5例(71.4％)患者采用Dara联合化疗,1例(14.3％)采用Dara联合全反式维甲酸,1例(14.3％)采用Dara单药治疗.治疗后1例(14.3％)患者获得完全缓解(CR),3例(42.9％)患者获得部分缓解(PR),总有效率为57.2％.其中1例难治急性髓系白血病(AML)患者经2个剂量Dara联合化疗后CR,现已无病生存11个月,1例复发急性淋巴细胞白血病患者经2个剂量Dara联合化疗后骨髓微小残留病下降90.2％,2例髓外浸润患者经Dara治疗后复查CT示淋巴结及软组织肿块明显缩小,评估为PR.结论 Dara可成功诱导难治AML完全缓解并维持较长的无病生存期,同时可能对髓外病变产生抗肿瘤作用.

OBJECTIVETo analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients.METHODSBone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH).RESULTSGene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression.CONCLUSIONThere are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.

急性前体T淋巴细胞白血病(early T-cell precursor acute lymphoblastic leukemia,ETP-ALL)是2016 年世界卫生组织淋巴造血组织肿瘤分类提出的属于T细胞急性淋巴母细胞白血病/淋巴瘤的一种罕见、高危的亚型,E TP细胞起源于造血干细胞,保留了一定的多向分化潜能[1 -2].其定义基于白血病细胞的免疫表型,典型特征为 CD7 +、CD1 a-、CD8 -、CD5 -(dim <75％),同时伴随1 个或多个干细胞或髓系抗原标志(CD117、CD34、HLA -DR、CD13、CD33、CD11 b 或CD65 )[3].患者接受治疗后继发骨髓增生异常综合征(myelodysplastic syndromes,MDS ),后进展为急性髓系白血病(acute myelogenous leukemia,AML),目前未见报道.ETP-ALL 和 AML 肿瘤细胞系别来源不同, 2种疾病出现于同一患者极其罕见.现将郑州大学第一附属医院血液内科收治的1 例ETP-ALL缓解后继发MDS后进展为AML患者的诊断及治疗过程结合文献复习.报告如下.

We aimed to validate and prove the novel risk score models of acute myeloid leukemia (AML)-specific disease risk group (AML-DRG) and AML-Hematopoietic Cell Transplant-composite risk (AML-HCT-CR) in patients with acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (AHCT). Among the 172 AML patients analysed, 48.3% (n = 83) were females. Median age was 31.5 years (range 14 to 62 years), two patients was more than 60 years old (1.2%). Median follow-up was 44 months (range 1 to 94 months). According to the AML-DRG model, 109, 49 and 14 patients were in low-, intermediate- and high-risk group, respectively. According to the AML-HCT-CR model, 108, 30, 20 and 14 patients were in low-, intermediate-, high- and very high-risk group, respectively. Our results showed that the AML-DRG and AML-HCT-CR models significantly predicted cumulative incidence of relapse (p < 0.001; p < 0.001). But AML-DRG model was not associated with NRM (p = 0.072). Univariate analysis showed that the AML-DRG model could better stratify AML patients into different risk groups compared to the AML-HCT-CR model. Multivariate analysis confirmed that prognostic impact of AML-DRG and AML-HCT-CR models on post-transplant OS was independent to age, sex, conditioning type, transplant modality, and stem cell source (p < 0.001; p < 0.001). AML-DRG and AML-HCT-CR models can be used to effectively predict post-transplant survival in patients with AML receiving AHCT. Compared to AML-HCT-CR score, the AML-DRG score allows better stratification and improved survival prediction of AML patients post-transplant.

目的 观察U2AF1基因突变的成人急性髓系白血病(AML)患者的临床特征及预后.方法 对2016年1月至2019年12月就诊于郑州大学第一附属医院的690例AML患者的病历资料进行回顾性分析.按U2AF1突变与否将患者分为U2AF1未突变组(652例)和U2AF1突变组(38例).比较两组临床特征及预后.结果 690例AML患者中,U2 AF1突变率为5.5％,常合并ASXL1、NRAS、SETBP1等基因突变.与U2 AF1未突变组相比,U2 AF1突变组外周血白细胞计数(WBC)、骨髓原始细胞比率低,预后中等及不良染色体核型多见,+8核型较多(P<0.05).在625例可评估疗效的AML患者中,单因素分析发现,U2AF1突变组中位总生存期(OS)、中位无进展生存期(PFS)较U2AF1未突变组短,完全缓解(CR)率、2 a OS率较U2AF1未突变组低(P<0.05).与未突变组相比,U2AF1 S34F突变组CR率较低,中位OS较短(P<0.05);两者中位PFS比较,差异无统计学意义(P>0.05).U2AF1 S34Y突变组中位PFS较未突变组短(P<0.05);两者CR率、中位OS比较,差异无统计学意义(P>0.05).多因素分析发现,U2AF1突变是影响<60岁AML患者OS、PFS的独立危险因素,1～2个疗程内达CR、接受造血干细胞移植、CEBPA双突变是影响<60岁AML患者OS及PFS的有利因素(P<0.05).结论 U2AF1突变在AML患者中发生率低,常与其他基因突变共存,预后中等及不良染色体核型多见.不同突变位点的预后意义不同.U2AF1突变是年轻(<60岁)AML患者的预后不良因素.