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An optimal strategy for mobilizing hematopoietic stem cells in poorly mobilizing patients with multiple myeloma (MM) and lymphoma has not yet been determined. We retrospectively analyzed the efficacy and safety of etoposide combined with cytarabine (etoposide 75 mg/m2, daily d1∼2; Ara-C 300 mg/m2, every 12 h d1∼2), plus pegfilgrastim (6 mg d6) in 32 patients with MM or lymphoma, among whom 53.1% were defined as "proven poor mobilizers." This approach resulted in adequate mobilization (≥2.0 × 106 CD34+ cells/kg) in 93.8% of patients and optimal mobilization (≥5.0 × 106 CD34+ cells/kg) in 71.9% of patients. A total of 100% of patients with MM reached at least 5 × 106 CD34+ cells/kg collected, the amount required for double autologous stem cell transplant. In total, 88.2% of patients with lymphoma reached at least 2 × 106 CD34+ cells/kg collected, the amount required for a single autologous stem cell transplant. This was achieved with a single leukapheresis in 78.1% of cases. A median peak number of 42.0/μL circulating CD34+ cells and a median number of blood CD34+ cells counts in 6.7 × 106/L were collected among 30 successful mobilizers. Approximately 6.3% of patients required plerixafor rescue, which was successful. Nine (28.1%) of the 32 patients suffered grade 2∼3 infections, and 50% required platelet transfusions. We conclude that chemo-mobilization with etoposide, Ara-C and pegfilgrastim in poorly mobilizing patients with MM or lymphoma is very effective and has acceptable toxicity. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced nausea and vomiting (CINV) is common in patients with lymphoma and multiple myeloma (MM) receiving high-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT). Despite a standard triple antiemetic regimen of a neurokinin-1 (NK1) receptor antagonist (RA), a 5-hydroxytryptamine-3 (5-HT3) RA, and dexamethasone is recommended, how to control the protracted CINV in ASCT setting remains an intractable problem. Here, we retrospectively analyze CINV data of 100 patients who received either SEAM (semustine, etoposide, cytarabine, melphalan) or MEL140-200 (high-dose melphalan) before ASCT, evaluate the efficacy and safety of multiple-day administration of fosaprepitant combined with tropisetron and olanzapine (FTO), and compare the results to those of patients who received a standard regimen of aprepitant, tropisetron, and dexamethasone (ATD). The overall rate of complete response (CR), defined as no emesis and no rescue therapy, is 70% in the FTO group compared to 36% in the ATD group. Although CR rates are comparable in the acute phase between the two groups, significantly more patients treated by FTO achieve CR in the delayed phase than those treated by ATD (74% vs. 38%, p < 0.001). Moreover, FTO treatment significantly reduced the percentage of patients who are unable to eat, as well as the requirement for rescue medications. Both regimens are well tolerated and most adverse events (AEs) were generally mild and transient. In conclusion, the antiemetic strategy containing multiple-day administration of fosaprepitant is safe and effective for preventing CINV in lymphoma and MM patients, particularly in the delayed phase. [ABSTRACT FROM AUTHOR]

Background: There is no consensus on the optimal secondary antifungal prophylaxis (SAP) regimen in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). The purpose of this study was to evaluate the efficacy and safety of posaconazole oral suspension as secondary prophylaxis of invasive fungal disease (IFD) for allo-HSCT patients.Methods: We retrospectively reviewed clinical data from prior IFD patients who received posaconazole oral suspension as systemic antifungal prophylaxis between June 2016 and January 2021 and have a follow-up period of 1 year after HSCT. The clinical outcomes of patients with a prior history of IFD (n = 30) and those without (n = 93) were compared.Results: The 1-year cumulative incidence of prophylaxis failure was 58.3% in the group with prior history of IFD and 41.6% in the group without a prior history of IFD (p = 0.459). The cumulative incidence of proven, probable or possible IFD within 1 year after allo-HSCT was 23.1% in the group with prior history of IFD and 14.1% in the group without prior history of IFD (p = 0.230). There was no significant difference between the cumulative incidence of proven or probable IFD within 1-year after allo-HSCT in the group with a prior history of IFD and the group without (p = 0.807). Multivariate logistic regression revealed cytomegalovirus disease as risk factor for post-transplantation IFD occurrence in posaconazole oral suspension prophylaxis. There was not a significant difference in overall survival between the patients with IFD history and those without (P = 0.559).Conclusions: Our study support that allo-HSCT recipients with a prior history of IFD and normal GI absorption can choose posaconazole oral suspension as a safe and effective SAP option. [ABSTRACT FROM AUTHOR]

Haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HSCT) has emerged as a novel strategy to treat patients suffering from severe aplastic anemia (SAA) who lack matched donors due to the availability and easy access to sources of donors. Anti-human leukocyte antigen donor-specific antibodies (DSAs) have been found to influence the outcome of Haplo-HSCT. Between March 2016 and March 2020, 7 SAA patients with DSAs underwent Haplo-HSCT in our center. We employed a modified protocol of post-transplantation cyclophosphamide and plasma exchange aiming to decrease the levels of DSAs. All 7 patients successfully achieved hematopoietic reconstruction. The median follow-up is 31 (range, 8 to 45) months. They survived and were transfusion-independent in the absence of clonality. No occurrence of primary or secondary graft failure has been noted among any of the patients. There was no severe acute and chronic GVHD occurred. This protocol is effective for Haplo-HSCT in SAA patients with DSAs, which provides an option for the SAA patients without other alternative donor. [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]

Patients with primary refractory or early relapsed acute myeloid leukemia (AML) have a dismal prognosis, and the treatment options for these patients are limited. The present study retrospectively examined the efficacy and toxicities of the combination of cladribine 5 mg/m2 per day and intermediate-dose cytarabine 1 g/m2 per day for 5 days and granulocyte colony-stimulating factor (G-CSF) as a salvage treatment in 36 patients with relapsed/refractory AML. Among these, 32 patients had de novo AML, and the remaining 4 patients had secondary AML. The median age for the study cohort was 45.8 years. According to the European LeukemiaNet prognostic index, 5 patients had favorable risk, 18 had intermediate risk, and 11 had poor risk. The complete remission was achieved in 58% of the patients with tolerable toxicities. Fifteen patients underwent stem cell transplantation later. Patients who underwent allogeneic hematopoietic stem cell transplantation had a significantly improved 1-year overall survival compared with those who did not (73% vs. 29%, P < 0.001). The results suggested that, as a salvage regimen, modified cladribine, cytarabine, and G-CSF were effective and well tolerated for patients with relapsed/refractory AML, especially for patients who underwent subsequent stem cell transplantation. [ABSTRACT FROM AUTHOR]

A single injection of 12 mg pegfilgrastim was used to mobilize peripheral blood progenitor cells (PBPCs) from healthy donors in some studies. The purpose of this study was to determine if 6 mg of pegfilgrastim was effective and safe for mobilizing CD34+ cells in donors for allogeneic hematopoietic stem cell transplantation. We conducted a retrospective case-matched design. A single dosage of 6 mg pegfilgrastim was used to mobilize PBPCs from 60 healthy donors. Granulocyte colony-stimulating factor (G-CSF, 10 μg/kg) was administered daily to the matched donors. Leukapheresis was scheduled to commence on day 4 of the mobilization regimen. The median yielded CD34+ cell in the pegfilgrastim group was higher than those in the G-CSF group, at 5.06 × 106/kg recipient weight. The 73.3% of donors mobilized with pegfilgrastim yielded >4 × 106 cells/kg CD34+ cells in a single apheresis procedure when compared to the 33.3% of donors mobilized with G-CSF (P < 0.001). The myeloid-derived suppressor cells (MDSC) proportion in the pegfilgrastim group was significantly higher than that in the G-CSF group (P < 0.001). The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was higher in the G-CSF group than that in the pegfilgrastim group (26.7% vs. 11.7%), without statistical difference. In comparison to the G-CSF group, the pegfilgrastim group had a reduced median pain intensity numerical rating scale score (1 vs. 2). A single 6 mg dosage of pegfilgrastim is effective and safe for allogeneic PBPCs collection from healthy donors. Pegfilgrastim may decrease the incidence of aGVHD by boosting MDSCs, which need further investigation. [ABSTRACT FROM AUTHOR]

Relapse and graft-versus-host disease (GVHD) are the important complications influencing mortality for patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). GVHD prophylaxis based on post-transplant cyclophosphamide (PTCy) or antithymocyte globulin (ATG) is widely used in haploidentical HSCT (haplo-HSCT). We developed a modified intensified conditioning regimen including fludarabine (Flu) and investigated the effect of ATG-PTCy combination on transplant outcomes in high-risk AML and MDS compared with those patients who received only ATG as GVHD prophylaxis. A total of 80 patients with high-risk AML and MDS were divided into two groups and assigned to one-to-one pairing. The modified ATG-PTCy group had more infused mononuclear cells, CD34-positive cells and CD3-positive cells than those in the ATG group (P < 0.05). The amount of platelet transfusion was higher in the ATG group than the modified ATG-PTCy group [2 (range, 1–6) U vs 2 (range, 1–5) U, P = 0.005]. The median of platelet recovery was better in the modified ATG-PTCy group than in the ATG group (12 days vs 13 days, P = 0.041). The infection rates of bacteria, fungi and virus at 100 days after transplantation were similar in both groups. Compared with the ATG group, individuals who received the modified ATG-PTCy regimen had higher 2-year GVHD- and relapse-free survival(GRFS) [60.0% (95%CI, 44.9–75.1%) vs 34.8% (95%CI, 19.9–49.7%), P = 0.028]; lower 180-day incidence of II-IV acute GVHD (aGVHD) [15.0% (95%CI, 4.0–26.0%) vs 39.8% (95%CI, 23.9–55.7%), P = 0.029]; lower 1-year incidence of moderate to severe chronic GVHD (cGVHD) [2.9% (95%CI, 2.0–3.8%) vs 19.6% (95%CI, 5.3–33.9%), P = 0.039]; and without an increase in the 2-year cumulative incidence of relapse (CIR) [19.5% (95%CI, 6.6–32.4%) vs 30.4% (95%CI, 15.3–45.5%), P = 0.291]. High-dose stem cells can promote blood cell implantation. The modified ATG-PTCy combination was associated with decreased risk of aGVHD and cGVHD, no increased risk of recurrence, and improved GRFS. It represents an effective strategy for high risk AML and MDS. [ABSTRACT FROM AUTHOR]

Background: Both all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3) have proven to be very effective in obtaining high clinical complete remission (CR) rates in acute promyelocytic leukemia (APL). Methods: In this study, 73 newly diagnosed APL subjects were treated with an ATRA and As2O3 combination treatment in remission induction and post remission therapy. Tumor burden was examined with PCR of the PML-RAR fusion transcripts, and side effects were evaluated by means of clinical examination. Results: The results showed that ATRA/As2O3 combination therapy yielded a CR rate of 94.5% (69/73) with a shorter time to enter CR (median: 27 days; range: 21-43 days). Four cases failed to enter CR; three of these died of cerebral hemorrhage and disseminated intravascular coagulation (DIC) within 72 hours of starting induction therapy, one older patient died of severe pulmonary infection. The early death rate was 5.5% (4/73). All 69 cases that obtained CR remained in good clinical remission after a follow-up of 35-74 months (median: 52 months).The drug toxicity profile with the use of As2O3 showed mainly hepatotoxicity. Liver dysfunction was slight in most cases. There were no severe side effects in long term follow-up. Conclusion: We conclude that APL patients may benefit from the use of the combination of ATRA and As2O3 in either remission induction or consolidation/maintenance. [ABSTRACT FROM AUTHOR]

In this study, the deep belief network (DBN) algorithm was used to identify the Wilm's tumor 1 (WT1) gene expression levels, and then, the role of WT1 expression in the classification of acute myeloid leukemia (AML) was explored. 121 AML patients diagnosed in the hospital from 2017.10 to 2019.10 were selected as the research subjects and set as the AML group. Another 9 non-leukemia patients were selected as the control group. The expression levels of WT1 in the two groups were compared, and DBN was used to classify the patients based on the WT1 expression levels. The real-time quantitative PCR was used to detect the abnormalities of FLT3, PML-RAR, and other molecular markers at different WT1 expression levels. The results showed that the expression of WT1 in AML patients was significantly higher than that in non-leukemia patients. The expression of WT1 in patients of M3 type was the highest, and that was the lowest in patients of the M5 type. The accuracy, precision, recall, and F1 indexes for WT1 expression identification using deep belief network were 94.06%, 93.82%, 93.59%, and 93.63%, respectively. In conclusion, deep learning technology is very sensitive in identifying the molecular biology markers in AML patients, which provides a reference for efficient and intelligent disease diagnosis. [ABSTRACT FROM AUTHOR]

Background: Pure red cell aplasia (PRCA) following allogeneic hematopoietic stem cell transplantation (allo‐HSCT) with ABO major incompatibility is characterized by transfusion dependent anemia. No standard treatment existed for PRCA following allo‐HSCT yet. Study Design and Methods: We conducted a retrospective study, and reported our experience with the use of avatrombopag and lower dose rituximab to treat five patients with PRCA subsequent to major ABO‐incompatible allo‐HSCT. Results: Five cases of PRCA were identified from 72 patients who underwent allo‐HSCT with major or bidirectional ABO mismatch. Cumulative incidence at Day +60 was 6.9% (5/72) at our center. All donor and recipient blood groups were A+ and O+, respectively. In the first three cases we reported, patients received erythropoietin, plasma exchange, and donor lymphocyte infusion, but none of them had any effect. After 4 weeks of treatment with low dose rituximab (100 mg/week) combined with avatrombopag (40 mg/day), favorable outcomes were obtained. According to the aforementioned experience, Cases 4 and 5 were administered low‐dose rituximab and avatrombopag in 3 months after transplantation, and erythroid response was observed on 3 weeks after treatment. Our patients tolerated low‐dose rituximab and avatrombopag well and experienced rapid efficacy, with a median duration of 3 weeks. Furthermore, no severe infection or thrombocytosis necessitated a dose adjustment. Conclusion: Low‐dose rituximab and avatrombopag may be an effective treatment for patients with PRCA after major ABO‐incompatible allo‐HSCT. The patients should be treated at least 90 days post transplantation if conventional erythropoietin therapy fails. [ABSTRACT FROM AUTHOR]

Background: Recently, an increasing number of studies have suggested dual-specificity phosphatase 23 (DUSP23) is a critical factor in the development of diffuse connective tissue disease and may be a valuable biomarker for primary human cancers. However, there is a lack of comprehensive studies on the prognostic significance of DUSP23 expression in acute myeloid leukemia (AML). Methods: RNA sequencing data from The Cancer Genome Atlas (TCGA) (AML = 173), Genotype-Tissue Expression (GTEx) (healthy controls = 70) and GEO (AML = 461, healthy controls = 76) databases were used to compare DUSP23 expression between AML patients and healthy controls. The overall survival (OS) of DUSP23 in AML was evaluated using Kaplan-Meier Cox regression. Furthermore, univariate Cox regression and multivariate Cox regression analysis were used to determine whether DUSP23 was an independent prognostic factor for AML. We then verified the expression level and prognostic significance of DUSP23 in our cohort (AML = 128, healthy controls = 31). In addition, functional enrichment analysis of DUSP23-related DEGs was performed through gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) network analysis. Results: The expression level of DUSP23 is significantly higher in AML patients than in healthy controls in TCGA, GTEx, GEO databases and our cohort. By multivariate analysis, high expression of DUSP23 is a poor prognostic indicator of OS in the TCGA database. Next, we verified the role of DUSP23 as an adverse prognostic biomarker in our cohort. Enrichment analysis of related genes showed that DUSP23 may regulate important signal pathways in hematological tumors including the MAPK pathways. It is suggested by the PPI network that DUSP23, along with IMP3, MRPL4, MRPS12, POLR2L, and ATP5F1D may play a role in the process of AML. Conclusion: The study demonstrated high expression of DUSP23 could serve as a poor independent prognostic biomarker in AML. [ABSTRACT FROM AUTHOR]

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]

Objective: Phospholipase D (PLD) is known to participate in several aspects of cellular processes including cell mitosis, migration, phagocytosis, and membrane vesicle trafficking. The role of PLD has been investigated in multiple cancers except hematologic malignances. Methods: We enrolled 291 patients with de novo acute myeloid leukemia (AML) and detected PLD1 mRNA expression levels of their bone marrow samples by quantitative real-time PCR (qRT-PCR). Clinical relevance of PLD1 was assessed using Kaplan–Meier analysis, univariate analysis, and multivariate analysis. Results: Compared to healthy donors, AML patients had higher mRNA levels of PLD1, which was significantly associated with FAB classification. Importantly, patients with low levels of PLD1 had impaired overall survival and event-free survival. Moreover, univariate and multivariate analyses confirmed that PLD1 expression was an independent prognostic factor for AML. Conclusion: PLD1 represented a useful diagnostic marker and prognostic factor for AML. [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]

The transcription factor interferon regulatory factor 8 (IRF8), as a member of the IRF family, is essential for myeloid cell differentiation. However, the precise role of IRF8 in the pathogenesis of acute myeloid leukemia (AML) remains unknown. By using multivariate analysis, we discovered that high IRF8 expression was an independent poor predictor of overall survival (OS) in AML patients from our clinical follow-up study. The proliferation of three AML cell lines was significantly inhibited by shRNA-mediated knockdown of IRF8, owing to cell cycle S-phase arrest. Furthermore, we demonstrated that knocking down IRF8 could suppress the expression of CyclinA and CyclinB1, resulting in a shift in cell cycle distribution. Loss of IRF8 in AML cells decreased the expression of STAT3 and phosphor-STAT3 (pSTAT3), which are key factors in JAK/STAT signal pathway and are important for AML progression. Using a xenograft mouse model, we discovered the antiproliferative effect of losing IRF8 in vivo. In conclusion, this study found that IRF8 may play a prognostic factor and therapeutic target in AML. [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]

Reduced-toxicity conditioning (RIC) regimens are used for allogeneic hematopoietic stem cell transplantation in older patients. However, successful outcomes are hindered by graft-versus-host disease (GVHD), treatment-related mortality, and relapse, particularly after haploidentical donor hematopoietic stem cell transplantation (HID-HSCT). The aim of this study was to evaluate the effectiveness of an RIC conditioning regimen that included a combination of cyclosporin A, methotrexate (on day + 1), mycophenolate, lower doses of post-transplantation PTCy (40 mg/kg on day + 3), and ATG (7.5 mg/kg) as GVHD prophylaxis prior to haplo-stem cell transplantation (haplo-SCT) in older patients.Methods: We retrospectively analyzed outcomes in 55 patients ≥ 55 years of age with hematologic malignancies treated with fludarabine, cytarabine, busulfan, and low-dose cyclophosphamide as the conditioning regimen between January 1, 2019, and November 30, 2023.Results: Neutrophil engraftment was successful in all patients within 28 days, with 54 patients (98.2%) achieving complete donor chimerism. The cumulative incidence of non-relapse mortality was 0% at 30 days, 7.5% at 100 days, and 19% at 1 year. The cumulative incidence of grade II–IV acute graft-versus-host disease (aGVHD) was 25% (95%CI, 15−38%), whereas that of grade III–IV aGVHD was 9.1% (95% CI, 3.3−19%). The cumulative incidence of extensive chronic graft-versus-host disease at 1 year was 3.6% (95%CI, 0.66–11%). The cumulative incidences of relapse, overall survival, and GVHD-free/relapse-free survival at 1 year were 9.0%, 71.6%, and 67.1%, respectively.Conclusions: An RIC conditioning regimen, including a combination of lower PTCy/ATG as GVHD prophylaxis, followed by haplo-SCT, might be a promising option for appropriately selected older patients. [ABSTRACT FROM AUTHOR]

The management of patients with acute myeloid leukemia (AML) remains a challenge because of the complexity and heterogeneity of this malignancy. Despite the recent approval of several novel targeted drugs, resistance seems inevitable, and clinical outcomes are still suboptimal. Increasing evidence supports the use of natural plants as an important source of anti-leukemic therapeutics. Licochalcone A (LCA) is an active flavonoid isolated from the roots of licorice, Glycyrrhiza uralensis Fisch., possessing extensive anti-tumor activities. However, its effects on AML and the underlying mechanisms remain unknown. Here, we showed that LCA decreased the viability of established human AML cell lines in a dose- and time-dependent manner. LCA significantly induced mitochondrial apoptotic cell death, accompanied by the downregulation of MCL-1, upregulation of BIM, truncation of BID, and cleavage of PARP. A prominent decline in the phosphorylation of multiple critical molecules, including AKT, glycogen synthase kinase-3β (GSK3β), ERK, and P38 was observed upon LCA treatment, indicating PI3K and MAPK signals were suppressed. Both transcription and translation of c-Myc were also inhibited by LCA. In addition, LCA enhanced the cytotoxicity of the BCL-2 inhibitor venetoclax. Furthermore, the anti-survival and pro-apoptotic effects were confirmed in primary blasts from 10 patients with de novo AML. Thus, our results expand the applications of LCA, which can be regarded as a valuable agent in treating AML. [Display omitted] [ABSTRACT FROM AUTHOR]

B The PDGFRB locus at 5q32-33 in 89% of cells by FISH: nuc ish(5, PDGFRB × 2), (3, PDGFRB × 2), (5, PDGFRB sep 3, PDGFRB × 1) [356/400]. 10.3324/haematol.2009.016345 5 Xu X, Lu Q, Wang Z. Identification of a Novel CSNK2A1-PDGFRB fusion gene in a patient with myeloid neoplasm with eosinophilia. Dear Editor, In 2016, the WHO released a report stating that myeloid/lymphoid neoplasm with eosinophilia are usually associated with I PDGHRA i , I PDGFRB i , I FGFR1 i , and I PCM1-JAK2 i fusion gene [[1]]. [Extracted from the article]

Acute myeloid leukemia (AML) is a highly heterogeneous and rapidly progressive hematopoietic neoplasm characterized by frequent relapses and variable prognoses. The development of new treatment options, therefore, is of crucial importance. Platycodin D (PD) is a triterpenoid saponin, extracted from the roots of the traditional Chinese herbal medicine Platycodon grandiflorum (Jacq.) A. DC., which has been reported to exhibit therapeutic potential against a broad range of cancers. Although the effects of PD on AML remain unclear, in the present study, we observed a concentration-dependent reduction in the viability of multiple human AML cell lines in response to treatment with PD. In addition to triggering mitochondria-dependent apoptosis via the upregulation of BAK and BIM, treatment with PD also induced cell cycle arrest at the G0/G1 phase. Western blot analyses revealed marked suppression of the phosphorylation of protein kinase B (AKT), glycogen synthase kinase-3β, ribosomal protein S6, and extracellular signal-regulated kinase (ERK) by PD, in turn implying the participation of the phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK)/ERK pathways. Pre-incubation with LY294002, MK2206, AR-A014418, or U0126 was consistently found to significantly aggravate PD-induced inhibition of viability. Additionally, PD combined with the B-cell lymphoma 2 (BCL2) inhibitor venetoclax elicited synergistically enhanced cytotoxic effects. The anti-leukemic activity of PD was further validated using primary samples from de novo AML patients. Given the results of the present study, PD may be a potent therapeutic candidate for the treatment of 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]

• We provide a recommendation for the treatment of multi-hit MM. • Lenalidomide has an advantage in improving the early ORR of multi-hit MM. • Tandem-ASCT can further prolong the long-term survival rate of multi-hit MM. • We analyzed factors affecting survival of MM with and without ASCT by univariate and multivariate analyses. In order to investigate the efficacy of lenalidomide, bortezomib and dexamethasone (VRD) induction chemotherapy regimen combined with tandem autologous stem cell transplantation (ASCT) in treating multi-hit multiple myeloma (MM), we analyzed 252 cases of newly diagnosed MM treated with the bortezomib-containing induction chemotherapy from June 2016 to June 2019. According to the fluorescence in situ hybridization (FISH) results on diagnosis, the patients were divided into multi-hit MM group (47 cases), single-hit MM group (81 cases), and standard-risk group (124 cases). Our analysis showed that R-ISS stageⅢ in transplantation group and R-ISS stageⅢ, multi-hit and VGPR or above was not achieved at the fourth cycle of chemotherapy in non-transplantation group were independent factors for poor prognosis by univariate and multivariate analyses. Moreover, the overall response rate (ORR) of VRD induction chemotherapy group was significantly higher than that of the non-VRD group in the single-hit and multi-hit groups (P = 0.021, P = 0.032); In terms of ASCT, tandem-ASCT can significantly improve the 2-year PFS (77.8 ± 3.9 %) and OS (83.3 ± 5.6 %) of multi-hit MM (P = 0.024, P = 0.037), while single-ASCT only has a limited effect on PFS (61.5 ± 3.0 %) and OS (71.9 ± 4.5 %) (P = 0.115, P = 0.155). [ABSTRACT FROM AUTHOR]