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Post-transplantation cyclophosphamide (PTCy) can reduce the incidence of graft versus host disease (GVHD) and this intervention is often applied on adults with hematologic malignancy. However, the high relapse rate hinders the development of the intervention and data of PTCy used on children with hematologic malignancy remains limited. In order to overcome issue of high relapse rate in PTCy treatment, we used fludarabine (Flu), enhanced dose of cytarabine (Ara-C, 9 g/m2), busulfan (Bu), Cy, anti-thymocyte globulin (ATG) combined with PTCy for an intensified conditioning regimen. A total of 22 children with acute leukemia received intensified PTCy conditioning regimen (PTCy intensified group). We matched with 18 children who received modified Bu-Cy and ATG conditioning regimen in the same period (ATG group). The two-year cumulative incidences of grade II–IV acute GVHD was significantly lower in PTCy intensified group (13.6 ± 7.7% vs 38.9 ± 11.5%, P = 0.048). Two-year GVHD-free relapse free survival (GRFS) in PTCy seems to be better among the increment group despite not being significant (63.3 ± 10.3% vs 35.4 ± 11.9%, P = 0.092). The positive rate of minimal residual disease after transplantation was significantly lower than that before transplantation (20.0% vs 2.5%, P = 0.029). In conclusion, ATG and PTCy combined with Flu-based increased intensity conditioning regimen is effective for acute leukemia in children. It could reduce GVHD rate significantly and potentially improve GRFS. [ABSTRACT FROM AUTHOR]

Introduction: Recent studies have suggested that CD300A was an oncogene in acute myeloid leukemia (AML) development. However, the clinical relevance and biological insight into CD300A expression in AML are still not well understood. The present study aimed to examine the expression characteristics of CD300A in AML and confirmed its clinical significance for AML. Methods: Quantification of the CD300A transcript was performed in 119 AML patients by real-time quantitative PCR in bone marrow blasts. The predictive significance of CD300A expression on the clinical outcomes of AML was assessed using overall survival (OS) and relapse-free survival (RFS). The published Cancer Genome Atlas (TCGA) data were used as an external validation for survival analysis and pathway analyses. Results: In comparison with monocytes from healthy peripheral blood cells, the expression levels of CD300A in AML cells were higher. Patients in the intermediate and adverse risk categories by WHO criteria (2018) had higher CD300A expression levels than those in the favorable risk category (p < 0.001). AML patients with high expression of CD300A had a higher early death rate (p = 0.029), lower complete remission rate (p = 0.042), higher death rate (p < 0.001) and relapse rate (p = 0.002), and shorter OS (p < 0.0001) and RFS (p < 0.0001). Through multivariable analysis, high CD300A expression in AML was also an independent poor prognostic factor. The CAMP and CGMP-PKG signaling pathways may be stimulated by increased CD300A expression levels, which may be important for the development of AML. Conclusions: The expression levels of CD300A were associated with risk stratification and the clinical relevance of AML. High CD300A expression may act as an independent adverse prognostic factor for OS and RFS in AML. [ABSTRACT FROM AUTHOR]

Diffuse large B cell lymphoma (DLBCL) is the most common hematological malignancy and is one of the most frequent non-Hodgkin lymphomas. Large-scale genomic studies have defined genetic drivers of DLBCL and their association with functional and clinical outcomes. However, the lymphomagenesis of DLBCL is yet to be fully understood. In the present study, four computational tools OncodriveFM, OncodriveCLUST, integrated Cancer Genome Score and Driver Genes and Pathways were used to detect driver genes and driver pathways involved in DLBCL. The aforementioned tools were also used to perform an integrative investigation of driver genes, including co-expression network, protein-protein interaction, copy number variation and survival analyses. The present study identified 208 driver genes and 31 driver pathways in DLBCL. IGLL5, MLL2, BTG2, B2M, PIM1, CARD11 were the top five frequently mutated genes in DLBCL. NOTCH3, LAMC1, COL4A1, PDGFRB and KDR were the 5 hub genes in the blue module that were associated with patient age. TP53, MYC, EGFR, PTEN, IL6, STAT3, MAPK8, TNF and CDH1 were at the core of the protein-protein interaction network. PRDM1, CDKN2A, CDKN2B, TNFAIP3, RSPO3 were the top five frequently deleted driver genes in DLBCL, while ACTB, BTG2, PLET1, CARD11, DIXDC1 were the top five frequently amplified driver genes in DLBCL. High EIF3B, MLH1, PPP1CA and RECQL4 expression was associated with decreased overall survival rate of patients with DLBCL. High XPO1 and LYN expression were associated with increased overall survival rate of patients with DLBCL. The present study improves the understanding of the biological processes and pathways involved in lymphomagenesis. The driver genes, EIF3B, MLH1, PPP1CA, RECQL4, XPO1 and LYN, pave the way for developing prognostic biomarkers and new therapeutic strategies for DLBCL. [ABSTRACT FROM AUTHOR]

Salvianolic acid A (SAA), one of the main derivatives of Salvia miltiorrhiza, has been shown to possess anti-inflammatory and anti-thrombotic activities. Its role in inhibiting tumor growth, however, remains elusive. The aim of this study was to investigate the effect of SAA on acute myeloid leukemia (AML). Here, SAA showed a dose-dependent cell viability inhibition and apoptosis induction in AML cells. At the molecular level, SAA increased the expression of Bak and decreased the expression of Bcl-xL, following by PARP cleavage and caspase-3 activation. SAA also markedly attenuated Akt phosphorylation in AML cells. In a xenograft mouse model, SAA significantly suppressed the growth of AML tumors in vivo. Furthermore, SAA exhibited a more profound pro-apoptotic effect on primary AML cells than on bone marrow mononuclear cells from patients with benign diseases. Therefore, the pro-apoptotic and anti-tumor properties of SAA suggested its promising therapeutic value for AML. [ABSTRACT FROM AUTHOR]

Inhibin-β A (INHBA) is a ligand of the transforming growth factor β superfamily and associated with tumorigenesis and tumor progression in solid tumors. In this study, we investigated the expression levels and clinical significance ofINHBAin acute myeloid leukemia (AML). The results showed that high expression ofINHBAwas significantly correlated with elderly age (>60 years) (p = .038), adverse cytogenetic risks (p = .034), negativeNPM1mutation (p = .016), positiveFLT3internal tandem duplications (p = .011), and low hemoglobin levels (<60 g/dL) (p = .04). Patients with high levels ofINHBAhad poor responses to therapies as indicated by lower complete remission rate (p = .004), higher early death rate (p = .018), and shorter relapse-free survival (p = .04) and overall survival (p = .003). Moreover, multivariate analysis showed that high expression ofINHBAwas an independent adverse prognostic factor for AML. Taken together, our study suggested that high expression ofINHBAwas an adverse prognostic factor forde novoAML. [ABSTRACT FROM AUTHOR]

A chemotherapy-based mobilization regimen in patients who mobilize poorly, based on etoposide, cytarabine and pegfilgrastim (EAP), has recently been introduced. The aim of this prospective study was to investigate the efficacy and safety of the EAP regimen in patients with poorly mobilizing multiple myeloma (MM) or lymphoma. This single-arm clinical trial was performed at eight public hospitals in China and was registered as a clinical trial (NCT05510089). The inclusion criteria were; (1) diagnosis of MM or lymphoma, (2) defined as a 'poor mobilizer' and (3) aged 18-75 years. The EAP regimen consisted of etoposide 75 mg/m 2 /day on days 1-2, cytarabine 300 mg/m 2 every 12 h on days 1-2 and pegfilgrastim 6 mg on day 6. The primary endpoint of the study was the ratio of patients achieving adequate mobilization (≥2.0 × 10 6 CD34 + cells/kg). From 1 September 2022 to 15 August 2023, a total of 58 patients were enrolled, 53 (91.4%) achieved adequate mobilization, while 41 (70.7%) achieved optimal mobilization with a median number of cumulative collected CD34 + cells was 9.2 (range 2.1-92.7) × 10 6 /kg and the median number of apheresis per patient of 1.2. The median time from administration of the EAP regimen to the first apheresis was 12 days. Approximately 8.6% of patients required plerixa for rescue, which was successful. Twelve (20.7%) of the 58 patients suffered grade 2-3 infections, while 25 (43.1%) required platelet transfusions. The duration of neutrophil and platelet engraftment was 11 days. In conclusion, these results suggest that the EAP mobilization regimen might be a promising option for poorly mobilizing patients with MM or lymphoma., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Myeloid-derived suppressor cells (MDSC) are powerful immunomodulatory cells that play an important role in infectious and inflammatory disorders, but the correlation between graft MDSC amount and early transplant outcomes remains unknown in allogeneic hematopoietic stem cell transplantation. We collected data from 91 patients with acute leukemia undergoing haploidentical allogeneic hematopoietic stem cell transplantation. The grafts were analyzed in terms of CD34+ cells, CD3+ T cells and subpopulation, and MDSC (HLA-DR -/low CD33 + CD16 - ) by flow cytometry. The cutoff value of the MDSC proportion in the graft on the receiver operating curve was 8.89%, with a sensitivity of 0.833 and specificity of 0.852. Day +100 cumulative incidences of II-IV and III-IV acute graft-versus-host disease (aGVHD) in the low MDSC group were 73.5% and 38.8%, respectively, and that in the high MDSC group were 5.3% and 0%, with a significant difference in incidences of II-IV and III-IV aGVHD ( P <0.001). The overall survival, relapse-free survival, and GVHD-relapse-free survival (GRFS) at 1 year were 66.3% versus 80.5% ( P =0.043), 71.6% versus 71.7% ( P =0.248), and 22.1% versus 62.8% ( P <0.001), respectively. No significant difference in the cumulative incidence of relapse between the 2 groups was observed. Multivariate analysis revealed that higher MDSC proportions were associated with a lower risk of II-IV aGVHD. Graft MDSC proportion exceeding 8.89% was significantly associated with higher overall survival and GRFS. The prophylaxis of antithymocyte globulin+post-transplant cyclophosphamide and higher MDSC proportion in the graft were favorable factors for improving GRFS. In conclusion, graft MDSC proportion may be a significant predictor of aGVHD., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Salvianolic acid A (SAA), one of the main derivatives of Salvia miltiorrhiza, has been shown to possess anti-inflammatory and anti-thrombotic activities. Its role in inhibiting tumor growth, however, remains elusive. The aim of this study was to investigate the effect of SAA on acute myeloid leukemia (AML). Here, SAA showed a dose-dependent cell viability inhibition and apoptosis induction in AML cells. At the molecular level, SAA increased the expression of Bak and decreased the expression of Bcl-xL, following by PARP cleavage and caspase-3 activation. SAA also markedly attenuated Akt phosphorylation in AML cells. In a xenograft mouse model, SAA significantly suppressed the growth of AML tumors in vivo. Furthermore, SAA exhibited a more profound pro-apoptotic effect on primary AML cells than on bone marrow mononuclear cells from patients with benign diseases. Therefore, the pro-apoptotic and anti-tumor properties of SAA suggested its promising therapeutic value for AML.

Objective: To delineate the clinical features and prognostic significance of acquired trisomy 21 (+21) in 31 patients with acute myeloid leukemia (AML)., Methods: Chromosome specimen was prepared from bone marrow samples using a direct method and (or) cultivation, and their karyotypes were analyzed with R banding. The clinical features, chemotherapeutic effect and survival status of patients with acquired +21 were evaluated., Results: Cytogenetic studies were successfully performed on 3 329 patients with newly diagnosed AML, among which 31 (0.93%) had acquired +21. And 16 (0.48%) of the 31 patients had +21 as the sole abnormality. The most frequent subgroup of bone marrow morphology was AML-M5b, and its total number was 12 (38.7%) of the total. Thirty patients among those with +21 received standard chemotherapy. The complete remission (CR) rate (63% vs. 80%, P< 0.05) and median overall survival (OS) (7 months vs. 15 months, P< 0.01) of AML patients with acquired +21 were both lower than those without. Age (60 years or older) was associated with a significantly lower CR rate (30% vs. 80%, P< 0.05) and shorter median OS (4 months vs. 12 months, P< 0.01). Comparing to acquired +21 with other additional abnormalities, acquired +21 solely was associated with a lower median OS (6 months vs. 12 months, P< 0.05), but did not affect the CR rate (60% vs. 67%, P> 0.05). Three patients undergoing allogenetic hematopoietic stem cell transplantation (allo-HSCT) were still alive at the end of follow-up. Their survival time have reached 56, 36 and 105 months, respectively, which were remarkably longer than those only received chemotherapy (P< 0.01)., Conclusion: The presence of acquired +21 in patients with AML has a adverse prognosis with or without other additional abnormalities. Older age (60 years or older) and +21 alone predicted relatively poorer outcome. Allo-HSCT was expected to prolong the survival time of AML patients with acquired +21.

Objective: To investigate the clinical efficacy of all-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) in induction and maintenance therapy in newly diagnosed acute promyelocytic leukemia (APL)., Methods: A retrospective analysis of 298 newly diagnosed APL patients from the department of hematology, First Affiliated Hospital of Zhejiang University since September 2004 to December 2013, including 177 cases with ATRA plus ATO and 116 ATRA plus chemotherapy (CT), was performed to investigate the clinical efficacy between the low-intermediate (WBC≤10×10⁹/L) and high (WBC>10×10⁹/L) risk APL patients, respectively., Results: For the low-intermediate risk patients, the relapse rate in ATRA plus CT and ATRA plus ATO are 22.0% and 6.1% (P=0.004), respectively; the 3 years estimated relapse-free survival (RFS) are 78.0% and 92.9% (P=0.021), respectively. For the high risk patients, the relapse rate in ATRA plus CT and ATRA plus ATO are 25.0% and 5.2% (P=0.035), respectively; the 3 years estimated RFS rate were 80.8% and 93.0% (P=0.021), respectively. But the rate of early death (ED), complete remission (CR) and overall survival (OS) between the two therapy protocols had no statistical difference (P>0.05)., Conclusion: ATRA plus ATO in induction and maintenance therapy might prolong the RFS time of the low-intermediate risk APL patients and decrease the relapse rate of the low, intermediate and high risk APL patients.

Objective: To explore the expression and clinical significance of Musashi2 (MSI2) gene in de novo acute myeloid leukemia (AML)., Methods: Real-time quantitative PCR (RQ-PCR) was used to measure the expression of MSI2 gene in 181 de novo AML patients. Correlation between the expression level and clinical features of such patients was explored., Results: Transcript of the MSI2 gene was detected in 181 AML patients, with the median expression level being 2.341 (0.1124-58.8566). By contrast, CD34+ cells from 10 healthy controls had a much lower expression level (P=0.012), and the expression level of MSI2 in 24 patients with complete remission was significant lower than de novo patients (P=0.021). Based on the median expression level, such patients were divided into low expression group and high expression group. Patients from the high expression group had significantly higher rate of high white blood cell count (78% vs. 63%, P=0.034). Compared with MSI2-low group, FLT3-ITD mutation were much more common in MSI2-high group (28% vs. 7%, P=0.002). The expression level of MSI2 in aberrant karyotypes was much higher than that in favorable karyotypes (the median expression level was 2.7726 and 2.0733, P=0.035). Kaplan-Meier analysis showed that the overall survival in high expression group of MSI2 was lower than the low expression group, with the median survival time being 28 months and 12 months, respectively (P=0.045)., Conclusion: De novo AML patients have a higher level of MSI2 gene expression. And the latter is much more common in those with high white blood cell count and aberrant karyotypes, and has a positive correlation with FLT3-ITD mutation. High expression of MSI2 gene may be a predictor for poorer prognosis among AML patients.