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Diffuse Large B Cell Lymphoma (DLBCL) is the most common form of blood cancer. Among the subtypes, the activated B-cell (ABC) subtype is typically more aggressive and associated with worse outcomes. However, the underlying mechanisms are not fully understood. In this study, we performed microarray analysis to identify potential ABC-DLBCL-associated genes. We employed Kaplan–Meier methods and cox univariate analysis to explore the prognostic value of the identified candidate gene Coiled-coil domain containing 50 (CCDC50). Additionally, we used DLBCL cell lines and mouse models to explore the functions and mechanisms of CCDC50. Finally, we isolated CCDC50-bearing exosomes from clinical patients to study the correlation between these exosomes and disease severity. Our results demonstrated that CCDC50 not only showed significantly positive correlations with ABC subtype, tumor stage and number of extranodal sites, but also suggested poor outcomes in DLBCL patients. We further found that CCDC50 promoted ABC-DLBCL proliferation in vitro and in vivo. Mechanistically, CCDC50 inhibited ubiquitination-mediated c-Myc degradation by stimulating the PI3K/AKT/GSK-3β pathway. Moreover, CCDC50 expression was positively correlated with c-Myc at protein levels in DLBCL patients. Additionally, in two clinical cohorts, the plasma CCDC50-positive exosomes differentiated DLBCL subtypes robustly (AUC > 0.80) and predicted disease severity effectively (p < 0.05). Our findings suggest that CCDC50 likely drives disease progression in ABC-DLBCL patients, and the CCDC50-bearing exosome holds great potential as a non-invasive biomarker for subtype diagnosis and prognosis prediction of DLBCL patients. [ABSTRACT FROM AUTHOR]

Background: The hypomethylating agent decitabine is the standard therapy for intermediate or high risk myelodysplastic syndrome (MDS). Methods: In this trial, 191 adult patients with intermediate/high risk MDS (IPSS score ≥ 0.5) randomly received decitabine using a standard regimen (20 mg/m2/day for 5 consecutive days; n = 94) or an extended regimen with lower daily dose (12 mg/m2/day for 8 consecutive days; n = 97) every 4 weeks, for a total of 4 cycles. Results: The median follow‐up was 14 months (range 2–36). The primary end point of overall response rate in the intent‐to‐treat analysis was 41.5% and 38.1% in the standard and extended dosing arms, respectively (p = 0.660). Complete remission and marrow complete remission also did not differ between the two arms. Cytopenia was the most frequent adverse event (76.4%). The median duration of neutropenia per cycle did not differ between the two arms during the first two cycles, but significantly shorter in the extended dosing arm in the third cycle (8.5 vs. 15.5 days, p = 0.049) and in the fourth cycle (8 vs. 14 days, p = 0.294). Conclusion: The 5‐day 20‐mg/m2/day and 8‐day 12‐mg/m2/day decitabine regimens have similar efficacy and safety in patients with intermediate or high risk MDS. [ABSTRACT FROM AUTHOR]

Background: Pilot studies have estimated cancer incidence in patients with systemic lupus erythematous (SLE). However, the results have been inconclusive. To ascertain the correlation between SLE and malignancy more comprehensively and precisely, we conducted a meta-analysis. Methods: PubMed, the Cochrane Library and Embase databases through June 2014, were searched to identify observational studies evaluating the association between SLE and malignancy. The outcomes from these studies were measured as relative risks (RRs). A random or fixed effects model was chosen to calculate the pooled RR according to heterogeneity test. Between-study heterogeneity was assessed by estimating I2 index. Publication bias was assessed by Egger’s test. Results: A total of 16 papers, including 59,662 SLE patients, were suitable for the meta-analysis. Of these papers, 15 reported RRs for overall malignancy, 12 for non-Hodgkin lymphoma (NHL) and lung cancer, 7 for bladder cancer, 6 for Hodgkin lymphoma (HL) and leukemia, 5 for skin melanoma, and liver and thyroid cancers, 4 for multiple myeloma (MM), and esophageal and vaginal/vulvar cancers and 3 for laryngeal and non-melanoma skin cancers. The pooled RRs were 1.28 (95% CI, 1.17–1.41) for overall cancer, 5.40 (95% CI, 3.75–7.77) for NHL, 3.26(95% CI, 2.17–4.88) for HL, 2.01(95% CI, 1.61–2.52) for leukemia, 1.45(95% CI, 1.04–2.03) for MM, 4.19(95% CI, 1.98–8.87) for laryngeal cancer, 1.59 (95% CI, 1.44–1.76) for lung cancer, 1.86(95% CI, 1.21–2.88) for esophageal cancer, 3.21(95% CI, 1.70–6.05) for liver cancer, 3.67(95% CI, 2.80–4.81) for vaginal/vulvar cancer, 2.11(95% CI, 1.12–3.99) for bladder cancer, 1.51(95% CI, 1.12–2.03) for non-melanoma skin cancer, 1.78(95% CI, 1.35–2.33) for thyroid cancer, and 0.65(95% CI, 0.50–0.85) for skin melanoma. Only the meta-analyses of overall malignancy, NHL, and liver and bladder cancers produced substantial heterogeneity (I2, 57.6% vs 74.3% vs 67.7% vs 82.3%). No apparent publication bias was detected except for NHL studies. Conclusions: Our data support an association between SLE and malignancy, not only demonstrating an increased risk for NHL, HL, leukemia, and some non-hematologic malignancies, including laryngeal, lung, liver, vaginal/vulvar, and thyroid malignancies, but also a reduced risk for skin melanoma. Although an increased risk of MM, and esophageal, bladder and non-melanoma skin cancers was identified from the accumulated data in these studies, this observation requires confirmation. [ABSTRACT FROM AUTHOR]

Background: In recent years, epidemiologic studies have reported controversial results relating cigarette smoking to myelodysplastic syndromes (MDS) risk. A meta-analysis was performed to assess such potential relationship between cigarette smoking and incidence of MDS. Methods: A search of literature published before October 2012 for observational studies evaluating the association between cigarette smoking and MDS, returned 123 articles and of these, 14 were selected for this study. The outcomes from these studies were calculated and reported as odds ratios (OR). Quality assessments were performed with the Newcastle-Ottawa Scale. Heterogeneity was evaluated by the I2 index and source of heterogeneity was detected by sensitivity analyses. Finally, publication bias was assessed through visual inspection of funnel plots and Egger’s test. Results: The pooled OR of developing MDS in ever-smokers was 1.45 (95% CI, 1.25 to 1.68) versus non-smokers. Current and former smokers had increased risks of MDS, with ORs of 1.81 (95% CI, 1.24 to 2.66) and 1.67 (95% CI, 1.42 to 1.96), respectively. In subset analyses, ever-smokers had increased risks of developing MDS if they were living in the United States, or in Europe, female in gender, had refractory anemia (RA)/RA with ringed sideroblasts (RARS) or RA with excess blasts (RAEB)/RAEB in transformation (RAEBt), respectively. Our results demonstrated that the association was stronger in individuals who smoked ≥20 cigarettes/day (OR, 1.62; 95% CI, 1.03 to 2.55) versus those who smoked <20 cigarettes/day (OR, 1.36; 95% CI, 1.13 to 1.64). Moreover, individuals who smoked more than 20 pack-years had increased MDS risk (OR, 1.94; 95% CI, 1.29 to 2.92). Conclusion: Our outcomes show that smoking increases the risk of developing MDS in ever-smokers who are current or former smokers. We also demonstrate here that positive association between cigarette smoking and risk of MDS exists, and occurs in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS), which are clonal bone marrow malignancies characterized by ineffective hematopoiesis, incorporate a variety of disorders and have variable prognosis. Although the International Prognostic Scoring System (IPSS) provides a clinical model for risk stratification of patients with primary MDS, notable variability in prognosis is still observed within the same IPSS category. Hypoxia-inducible factor-1α (HIF-1α) is associated with an adverse prognosis in patients with solid tumors and some hematological malignancies. However, the relationship between HIF-1α and clinical outcomes of patients with MDS is unknown. We examined HIF-1α by immunohistochemistry in bone marrow specimens from 81 patients with MDS. Results showed that the expression rate of HIF-1α was 49.4% (40/81). Multivariate analysis including age, bone marrow blast percentage, cytogenetics, hemoglobin, white blood cell count and IPSS score demonstrated that HIF-1α ( p = 0.049, HR = 2.704) was an independent prognostic indicator for MDS. Furthermore, the expression of HIF-1α was correlated with poor overall survival ( p < 0.001) and disease progression ( p = 0.004). In addition, correlation analysis revealed that the expression of HIF-1α was associated with bone marrow blast percentage ( p < 0.001, r = 0.510), hemoglobin count (p < 0.001, r = 0.649) and cytogenetics (p = 0.009, r = 0.287). We also found that decitabine achieved a better therapeutic effect compared to traditional chemotherapy in HIF-1α positive patients. In conclusion, these results suggest that HIF-1α is a vital biomarker for predicting the progression and prognosis of MDS. [ABSTRACT FROM AUTHOR]

T-cell lymphoma-associated hemophagocytic syndrome (T-LAHS) has been frequently reported in Asian countries and is considered with extremely poor prognosis. To summarize its clinical characteristics and explore its early diagnosis and treatment, we retrospectively analyzed the records of 113 patients with aggressive T cell lymphoma, of which 28 were associated with LAHS. According to WHO classification (2001), 22 cases were classified into peripheral T-cell lymphoma (unspecified), 2 into extranodal NK/T-cell lymphoma, and 4 into systemic anaplastic large cell lymphoma. The median survivals of the LAHS and no-LAHS groups were 40 days and 8 months, respectively. The elevating rates of serum lactate dehydrogenase (LDH) (100% vs. 55%), ferritin (100% vs. 64%), fasting triglycerides (79% vs. 43%), and hypofibrinogen (43% vs. 14%)levels were higher in the LAHS group than in the no-LAHS group (P < 0.05), so were bone marrow involvement (57% vs. 32%, P < 0.05)and liver dysfunction (40% vs. 13%, P < 0.05). Eleven of the 28 LAHS patients did not receive any chemotherapy, and 14 received CHOP regimen as initial chemotherapy. Three patients in critical conditions were given plasma exchange and gained the chance of initial chemotherapy. We suggest that in patients presenting with fever, hepatosplenomegaly, cytopenia, and constantly increasing levels of serum LDH, CA125, ferritin, transglutaminase, and β2-microglobulin, T-LAHS should be taken into account. Repeating biopsies of multiple parts of bone marrow may help diagnosis. The therapeutic result of chemotherapy alone or combined for T-LAHS was discouraging and the survival time of most cases was no more than 1 year. Plasmapheresis as initial therapy is worth considering in critical cases. [ABSTRACT FROM AUTHOR]

Summary: 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/m2/day on days 1–2, cytarabine 300 mg/m2 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 × 106 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) × 106/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. [ABSTRACT FROM AUTHOR]

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive myeloid malignancy associated with a poor prognosis. Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) has emerged as a potential treatment strategy for BPDCN, standardized conditioning regimens remain lacking. In this manuscript, we present two cases of BPDCN that were treated with a thiotepa-busulfan-fludarabine (TBF)-based conditioning regimen prior to allo-HSCT. Both cases demonstrated complete remission post-transplantation, sustained donor chimerism, and remission maintenance, suggesting the potential efficacy of the TBF conditioning regimen for BPDCN transplantation. Given the small sample size in our study, we emphasize caution and advocate for larger studies to confirm the efficacy of TBF in the treatment of BPDCN. [ABSTRACT FROM AUTHOR]

Summary Large amounts of azurophilic granules are considered to be a morphological feature of acute promyelocytic leukaemia (APL). However, a small percentage of acute myeloid leukaemia (AML) patients also have a large number of azurophilic granules. A large cohort of 3210 AML patients in our hospital was screened to identify AML patients who had a large number of azurophilic granules. The clinical parameters of these patients were collected and compared with typical AML patients (control Group 1) and APL patients (control Group 2). The incidence of AML with a large number of azurophilic granules was 1.26%. The fibrinogen and D‐dimer levels of patients in the study group were more similar to those of patients in control Group 2, as was the incidence of bleeding events. Additionally, patients in the study group had higher FLT3‐ITD and NPM1 mutation rates than patients in control Group 1. Finally, patients in the study group had a higher 30‐day mortality rate than those in control Group 2 (24.2% vs. 9.09%) and showed a higher 30‐day mortality trend than those in control Group 1. Therefore, we should pay more attention to the prevention of coagulation dysfunction and bleeding events for these patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented discussing the efficacy of a new complex translocation in acute promyelocytic leukemia.

• An oral RIF plus ATRA chemotherapy-free protocol is highly efficacy in APL. • Oral RIF plus ATRA regimen is well-tolerated in postremission therapy for APL. • A home-based model is feasible for APL even in high-risk patients. Realgar-Indigo naturalis formula(RIF)is an oral form of arsenic developed for treatment of acute promyelocytic leukemia (APL). We retrospectively evaluated the efficacy and safety of a novel RIF combined with all-trans retinoic acid (ATRA) based chemotherapy-free approach in newly diagnosed APL patients. Patients received oral ATRA (25 mg/m2/day in 2 divided doses) plus intravenous arsenic trioxide (0.15 mg/kg/day) or oral RIF (60 mg/kg/day in 3 divided doses) as induction chemotherapy, followed by 2 consolidations with ATRA plus RIF and maintenance therapy with intermittent ATRA and RIF. From January 2015 to December 2017, 40 subjects were enrolled. Eighteen subjects were male. Median age was 42 years (range, 14–77 years) and 10 subjects were ≥ 60 years. All subjects achieved a complete morphologic remission after initial induction. Molecular complete remission achieved 100% after second RIF plus ATRA consolidation. Median follow-up of survivors was 27 months (range, 7–43 months). The 2-year event-free survival (EFS) and overall survival (OS) were both 100%. Adverse events were modest and all patients needed only outpatient care during postremission therapy. Compared to our historical RIF plus ATRA with chemotherapy regimen (the Chinese APL07 trial), the inpatient treatment duration was greatly reduced by the RIF plus ATRA regimen. Our data indicates that early switching to RIF plus ATRA based chemotherapy-free approach has yielded encouraging outcomes and might be considered a practicable option to treat patients with newly diagnosed APL. [ABSTRACT FROM AUTHOR]

Resistance to chemotherapy remains a formidable obstacle in acute myeloid leukemia (AML) therapeutic management, necessitating the exploration of optimal strategies to maximize therapeutic benefits. Venetoclax with 3+7 daunorubicin and cytarabine (DAV regimen) in young adult de novo AML patients is evaluated. 90% of treated patients achieved complete remission, underscoring the potential of this regimen as a compelling therapeutic intervention. To elucidate underlying mechanisms governing response to DAV in AML, quantitative phosphoproteomics to discern distinct molecular signatures characterizing a subset of DAV‐sensitive patients is used. Cluster analysis reveals an enrichment of phosphoproteins implicated in chromatin organization and RNA processing within DAV‐susceptible and DA‐resistant AML patients. Furthermore, kinase activity profiling identifies AURKB as a candidate indicator of DAV regimen efficacy in DA‐resistant AML due to AURKB activation. Intriguingly, AML cells overexpressing AURKB exhibit attenuated MCL‐1 expression, rendering them receptive to DAV treatment and maintaining them resistant to DA treatment. Moreover, the dataset delineates a shared kinase, AKT1, associated with DAV response. Notably, AKT1 inhibition augments the antileukemic efficacy of DAV treatment in AML. Overall, this phosphoproteomic study identifies the role of AURKB as a predictive biomarker for DA, but not DAV, resistance and proposes a promising strategy to counteract therapy resistance in AML. [ABSTRACT FROM AUTHOR]

Summary: Gilteritinib, a potent FMS‐like tyrosine kinase 3 (FLT3) inhibitor, was approved for relapsed/refractory (R/R) FLT3‐mutated acute myeloid leukaemia (AML) patients but still showed limited efficacy. Here, we retrospectively analysed the efficacy and safety of different gilteritinib‐based combination therapies (gilteritinib plus hypomethylating agent and venetoclax, G + HMA + VEN; gilteritinib plus HMA, G + HMA; gilteritinib plus venetoclax, G + VEN) in 33 R/R FLT3‐mutated AML patients. The composite complete response (CRc) and modified CRc (mCRc) rates were 66.7% (12/18) and 88.9% (16/18) in patients received G + HMA + VEN, which was higher compared with that in G + HMA (CRc: 18.2%, 2/11; mCRc: 45.5%, 5/11) or G + VEN (CRc: 50.0%, 2/4; mCRc: 50.0%, 2/4). The median overall survival (OS) for G + HMA + VEN, G + HMA and G + VEN treatment was not reached, 160.0 days and 231.0 days. The median duration of remission (DOR) for G + HMA + VEN, G + HMA and G + VEN treatment was not reached, 82.0 days and 77.0 days. Four patients in the G + HMA + VEN group received alloHSCT after remission exhibited prolonged median DOR. The most common grade 3/4 adverse events were cytopenia, febrile neutropenia and pulmonary infection; there were no differences among the three groups. In conclusion, our data demonstrated promising response of G + HMA + VEN combination therapy in R/R FLT3‐mutated AML, and it may be considered an effective therapy bridge to transplantation. [ABSTRACT FROM AUTHOR]

Advances in nanotechnology have provided novel avenues for the diagnosis and treatment of multiple myeloma (MM), a hematological malignancy characterized by the clonal proliferation of plasma cells in the bone marrow. This review elucidates the potential of nanotechnology to revolutionize myeloma therapy, focusing on nanoparticle-based drug delivery systems, nanoscale imaging techniques, and nano-immunotherapy. Nanoparticle-based drug delivery systems offer enhanced drug targeting, reduced systemic toxicity, and improved therapeutic efficacy. We discuss the latest developments in nanocarriers, such as liposomes, polymeric nanoparticles, and inorganic nanoparticles, used for the delivery of chemotherapeutic agents, siRNA, and miRNA in MM treatment. We delve into nanoscale imaging techniques which provide spatial multi-omic data, offering a holistic view of the tumor microenvironment. This spatial resolution can help decipher the complex interplay between cancer cells and their surrounding environment, facilitating the development of highly targeted therapies. Lastly, we explore the burgeoning field of nano-immunotherapy, which employs nanoparticles to modulate the immune system for myeloma treatment. Specifically, we consider how nanoparticles can be used to deliver tumor antigens to antigen-presenting cells, thus enhancing the body's immune response against myeloma cells. In conclusion, nanotechnology holds great promise for improving the prognosis and quality of life of MM patients. However, several challenges remain, including the need for further preclinical and clinical trials to assess the safety and efficacy of these emerging strategies. Future research should also focus on developing personalized nanomedicine approaches, which could tailor treatments to individual patients based on their genetic and molecular profiles. [ABSTRACT FROM AUTHOR]

This letter, published in the Annals of Hematology, reports on a case of a patient with myeloid/lymphoid neoplasm with eosinophilia (MLN-eo) who presented with an osteolytic lesion. The patient experienced progressive osteodynia and was found to have multiple punched-out osteolytic lesions. The patient underwent chemotherapy and achieved bone marrow complete remission, but unfortunately, the osteolytic lesion persisted and the patient eventually died. The study also conducted RNA sequencing and found that osteoclast-related pathways were enriched in the patient's transcriptional profiles. This case highlights the rare occurrence of osteolytic lesions in MLN-eo patients and suggests a potential role of FIP1L1-PDGFRA rearrangement and RUNX1 mutation in causing the osteolytic lesion. [Extracted from the article]

B-cell lymphoma is the most prevalent type of non-Hodgkin lymphoma, for which the standard treatment regimen includes rituximab combined with CHOP. However, some patients may develop interstitial pneumonitis (IP), which can be caused by various factors; one of the most important factors is Pneumocystis jirovecii. It is crucial to investigate the pathophysiology of IP and implement preventive measures since IP can be fatal for some people. The data were collected from the First Affiliated Hospital, Zhejiang University School of Medicine, where patients with B-cell lymphoma received the R-CHOP/R-CDOP regimen with or without prophylactic use of trimethoprim-sulfamethoxazole (TMP-SMX). Multivariable logistic regression and propensity score matching (PSM) were used to investigate any potential association. Eight hundred thirty-one patients with B-cell lymphoma were classified into two groups: the non-prophylaxis group without TMP-SMX (n=699) and the prophylaxis group with TMP-SMX (n = 132). IP occurred in 66 patients (9.4%, all in the non-prophylaxis group), with an onset median of three cycles of chemotherapy. Multiple logistic regression analysis demonstrated that IP incidence was associated with pegylated liposome doxorubicin (OR=3.29, 95% CI 1.84–5.90, P<0.001). After utilizing a 1:1 matching algorithm for PSM, 90 patients from each group were obtained. There was a statistical difference between the two cohorts in the IP incidence (non-prophylaxis 12.2% vs prophylaxis 0.0%, P <0.001). The prophylactic use of TMP-SMX could prevent the occurrence of IP whose risk factor was pegylated liposome doxorubicin after chemotherapy for B-cell lymphoma. [ABSTRACT FROM AUTHOR]

Summary: There have been reports of haematological cancer patients achieving spontaneous remission after being infected with the influenza A or SARS‐COV‐2 virus. Here, we present the first case of long‐term complete remission (CR) induced by influenza A (IAV, H1N1 subtype) in a refractory AML patient and have functionally validated this finding in two different animal disease models. We observed a significant increase in the proportion of helper T cells in the patient after IAV infection. The levels of cytokines, including IL‐2, IL‐4, IL‐6, IL‐10, IL‐17A, IFN‐γ and TNF‐α, were higher in IAV‐infected patients compared with control groups. These findings indicate that the anti‐tumour effects induced by IAV are closely related to the modification of the immune response. Our study provides new evidence of the anti‐tumour effects of IAV from a clinical practice perspective. [ABSTRACT FROM AUTHOR]

This article presents a case report of a 55-year-old man with diffuse large B-cell lymphoma (DLBCL) involving the heart. The patient initially presented with fever, chest discomfort, and echocardiographic findings of masses in the right atrioventricular wall and reduced left ventricular contractility. Further tests revealed enlarged lymph nodes and multiple soft tissue masses in the pericardium and right atrium. The patient was treated with a modified R-CHOP chemotherapy regimen, which resulted in improved symptoms and a reduction in tumor size. The report emphasizes the rarity of cardiac-dominant DLBCL and the importance of early diagnosis and appropriate treatment. [Extracted from the article]

A letter to the editor is presented which discusses the arsenic trioxide which can improve the prognosis in adult patients with acute promyelocytic leukemia (APL)carrying ider(17)(q10)t(15:17) that shows poor response to all-trans retinoic acid (ATRA).

(C and D) PFS and OS of patients with increased mean ctDNA VAF versus patients with no increased mean ctDNA VAF based on pre- and post-treatment ctDNA change, respectively. Twenty-seven patients had pre- and post-treatment plasma-derived ctDNA, and paired baseline BM DNA NGS assessments were included for both concordance analysis and dynamic ctDNA analysis. Three patients with only pre- and post-treatment ctDNA assessments and one patient with only post-treatment ctDNA assessments were used for dynamic ctDNA analysis (Figure 1). [Extracted from the article]

Summary: As reported, SETD2 is recurrently mutated in acute myeloid leukaemia (AML), but knowledge about the specifics is limited. We enrolled 530 consecutive newly diagnosed AML patients in our study, and we analysed the distribution pattern and prognostic role of SETD2 mutation in AML. SETD2 mutation was found to affect 6.3% of AML patients, and it frequently co‐occurred with IDH2, NRAS and CEBPA mutations. SETD2‐mutated patients saw excellent therapeutic responses but failed to gain better survival time than other patients. This could be because of the high recurrence and mortality in SETD2‐mutated patients who have additional mutations, such as NRAS mutation. [ABSTRACT FROM AUTHOR]

Background: Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) as postremission treatment is recommended for Philadelphia‐positive acute lymphoblastic leukemia (Ph+ ALL) in current guidelines. However, comparisons of later generation tyrosine kinase inhibitors (TKIs) plus chemotherapy with allo‐HSCT have yielded similar outcomes. This meta‐analysis was performed to evaluate allo‐HSCT in first complete remission (CR1) versus chemotherapy for adult Ph+ ALL in the TKI era. Methods: Pooled assessment of the hematologic and molecular complete response rates was performed after 3‐month TKI treatment. Hazard ratios (HRs) were determined for disease‐free survival (DFS) and overall survival (OS) benefit with allo‐HSCT. The effect of measurable residual disease status on survival benefit was also analyzed. Results: Thirty‐nine retrospective and prospective single‐arm cohort studies involving 5054 patients were included. Combined HRs indicated that in the general population, allo‐HSCT favorably influenced DFS and OS. Achieving complete molecular remission (CMR) within 3 months after starting induction was a favorable survival prognostic factor regardless of whether the patient had undergone allo‐HSCT. Among the patients with CMR, survival rates in the nontransplant subgroup were comparable with those in the transplant subgroup, with the estimated 5‐year OS of 64% versus 58% and 5‐year DFS of 58% versus 51%, respectively. The use of next‐generation TKIs results in a higher proportion of patients achieving CMR (ponatinib 82% vs. imatinib 53%), while improving survival in nontransplant patients. Conclusion: Our novel findings suggest that combination chemotherapy plus TKIs leads to a comparable survival benefit as with allo‐HSCT for MRD‐negative (CMR) patients. This study provides novel evidence for allo‐HSCT indications for Ph+ ALL in CR1 in the TKI era. In the tyrosine kinase inhibitor (TKI) era, the role and need for allogeneic hematopoietic stem cell transplantation (allo‐HSCT) have now become less certain for adult Philadelphia‐positive acute lymphoblastic leukemia in first complete remission. This meta‐analysis suggests that allo‐HSCT confers no survival advantage on measurable residual disease (MRD)–negative patients; and the use of newer generations of TKIs resulted in more patients achieving MRD‐negative status, effectively improving survival in nontransplant patients. [ABSTRACT FROM AUTHOR]

Patients with adverse risk according to ELN received allo-HSCT if a suitable donor was available, regardless of MRD status; otherwise, they received venetoclax plus modified intermediate-dose cytarabine-based chemotherapy consolidation unless they developed progressive disease or unacceptable toxicity or stopped due to physician or patient decisions. Keywords: acute myeloid leukaemia; DAV; efficacy; safety; venetoclax EN acute myeloid leukaemia DAV efficacy safety venetoclax 568 572 5 04/20/23 20230501 NES 230501 AUTHOR CONTRIBUTIONS Huafeng Wang and Yiyi Yao designed the study, collected and analysed the data, and wrote the first draft of the manuscript. Thus, 12 of the 13 patients (92.3%, 95% CI 64.0%-99.8%) achieved CR after the completion of all cycles of induction, one patient (P7) failed to achieve remission after induction therapy (Figure 1B,C, Table 1). [Extracted from the article]

Acute promyelocytic leukemia (APL) is a medical emergency. In order to evaluate the usefulness of initial coagulation parameters in the predictive value of APL diagnosis, 1304 consecutive newly diagnosed acute leukemia patients, including APL (n = 211), non-APL acute myeloid leukemia (n = 781) and acute lymphoblastic leukemia (n = 312) were retrospectively evaluated between January 2011 and May 2015. The area under curve (AUC) of fibrinogen was the largest among the coagulation markers based on receiver operating characteristic (ROC) analysis. The optimum cutoff value of fibrinogen was 1.87 g/L (AUC = 0.912, sensitivity 80.1% and specificity 88.8%). The optimum cutoff value of D-dimer was 2191 μg/L (AUC = 0.786, sensitivity 81.1% and specificity 67.8%). The AUC difference between the fibrinogen and D-dimer was significant (P < 0.001). Other coagulation markers showed less predictive power. Importantly, in the analysis of high white blood cell count (over 10 × 10 9 /L) subgroup, a low fibrinogen level could efficiently discriminate APL patients from controls (AUC = 0.983, sensitivity 96.4% and specificity 94.4%) with a criterion value ≤1.71 g/L. Thus, our results suggest that a low fibrinogen level could be a key marker in early prediction of APL diagnosis. [ABSTRACT FROM AUTHOR]

This study included 146 primary gastric diffuse large B-cell lymphoma patients. Next-generation RNA sequencing and fluorescent in situ hybridization were performed on tumors from 27 and 38 patients, respectively. Five-year and 10-year overall survival (OS) rates were 77% and 57%, respectively. Lugano and TNM clinical stage were independent survival factors. Tier I mutation was found in 21 patients. The genetic subtypes were A53 (n = 3), MCD (n = 5), BN2 (n = 5), N1 (n = 5), EZB (n = 1), and NOS (n = 8). OS was significantly shorter in high-risk genetic subtypes (A53, MCD, and N1) than low-risk subtypes (BN2, EZB, and NOS). Frequencies of high-risk genetic subtypes were higher in patients with Lugano stage II/IV and TNM clinical stage III + IV than in those with Lugano stage I and TNM clinical stage I + II. Although genetic testing was performed in only a small number of cases, the results suggested that high-risk genetic subtypes were associated with advanced clinical stages and shorter survival. [ABSTRACT FROM AUTHOR]

The combination of rituximab, lenalidomide, and Bruton's tyrosine kinase inhibitor (BTKi) ibrutinib, followed by chemotherapy, has shown high efficacy in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) in Smart Start trial. We aimed to evaluate the efficacy, safety of SMART (rituximab + lenalidomide + BTKi) regimen and SMART–START regimen as a first-line treatment in elderly or unfit DLBCL patients. 31 patients were included, 17 used SMART regimen, with median age 82 years, 14 unfit patients received SMART–START regimen. 14/16 (87.5%) patients in SMART group achieved overall response (OR), with 10/16 (62.5%) achieved complete response (CR). 12/13 (92.3%) patients in SMART–START group achieved OR, with 8/13 (61.5%) achieved CR. With a median follow-up of 15.4 (3–29.1) months, median progression-free survival (PFS) and overall survival (OS) have not been reached, 1-year PFS was 81% in SMART group and 84% in SMART–START group. Common grade 3–4 adverse events (AEs) during SMART regimen were neutropenia (8 [25.8%]), infection (6 [19.4%]) and skin rash (3 [9.7%]). Our study shows that SMART regimen is an effective and safe therapy for elderly DLBCL patients, and SMART–START regimen can be used in unfit patients who could not tolerate intensive chemotherapy in the onset. [ABSTRACT FROM AUTHOR]

The outcome of relapsed/refractory (R/R) acute myeloid leukemia (AML) remains extremely poor. Venetoclax (VEN)-based regimens have shown promise in treating R/R AML. This phase 2 study aimed to systematically evaluate the efficacy and safety of the VAA regimen (VEN plus Cytarabine and Azacitidine) in R/R AML patients. Thirty R/R AML patients were enrolled. The study adopted a stepwise ramp-up of VEN dosing, starting with 100 mg on day 1, escalating to 200 mg on day 2, and reaching 400 mg from day 3 to day 9. Cytarabine (10 mg/m2, q12h) was administered intravenously twice daily from days 1 to 10, and Azacitidine (75 mg/m2) was administered via subcutaneous injection once daily from days 1–7. The primary efficacy endpoint was the composite complete remission rate (CRc), including complete response (CR) and complete response with incomplete blood count recovery (CRi). Secondary endpoints included overall survival (OS), duration of response (DOR), and safety analysis. The CRc rate was 63.3% (19/30), with CR in 36.7% of patients and CRi in 26.7%. Notably, 14 (73.7%) of 19 patients achieving CRc showed undetectable measurable residual disease by flow cytometry. With a median follow-up of 10.7 months, the median OS had not been reached, and the median DOR was 18.3 months. The most common grade 3–4 adverse events (AEs) were neutropenia (100%), anemia (96.7%), thrombocytopenia (90.0%), and leukopenia (90.0%). Infections, with pneumonia being the most prevalent (43.3%), were observed, including one fatal case of Pseudomonas aeruginosa septicemia. There were no treatment-related deaths. The VAA regimen is an effective and safe option for patients with R/R AML, demonstrating a high CRc rate and manageable safety profile. • VAA regimen yields 63.3% CRc rate in R/R AML. • Median DOR reached 18.3 months. • High safety profile with manageable AEs. [ABSTRACT FROM AUTHOR]

Two myelodysplastic syndrome (MDS) celllines, MUTZ-1 and SKM-1 cells, were used to study the effect of arsenic trioxide (As2O3) on hematological malignant cells. As2O3 induced this two cell lines apoptosis via activation of caspase-3/8 and cleavage of poly (ADP-ribose) polymerase (PARP), a DNA repair enzyme. As2O3 reduced NF-κB activity, which was important for inducing MUTZ-1 and SKM-1 cells apoptosis. As2O3 also inhibited the activities of hTERT in MUTZ-1 and SKM-1 cells. Moreover, the NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), had no effect on caspase-8 activation, although PDTC did inhibit MUTZ-1 and SKM-1 cells proliferation. Incubation of MUTZ-1 cells with a caspase-8 inhibitor failed to block As2O3-induced inhibition of NF-κB activity. Our findings suggest that As2O3 may induce apoptosis in MUTZ-1 and SKM-1 cells by two independent pathways: first, by activation of caspase-3/8 and PARP; and second, by inhibition of NF-κB activity, which results in downregulation of hTERT expression. We conclude that hTERT and NF-κB are important molecular targets in As2O3-induced apoptosis. [ABSTRACT FROM AUTHOR]

Background: The implication of mutational variant allelic frequency (VAF) has been increasingly considered in the prognostic interpretation of molecular data in myeloid malignancies. However, the impact of VAF on outcomes of myelodysplastic syndromes (MDS) has not been extensively explored. Methods: Targeted next-generation sequencing was performed in 350 newly diagnosed MDS cases. The associations of mutational VAF of each gene with overall survival (OS) and leukemia-free survival (LFS) were examined by multivariate Cox regression after univariate analysis. Results: Shorter OS was independently associated with DNMT3A VAF (HR 1.020 per 1% VAF increase; 95% CI 1.005–1.035; p = 0.011) and TP53 VAF (HR 1.014 per 1% VAF increase; 95% CI 1.006–1.022; p = 0.001). LFS analyses revealed that TET2 VAF (HR 1.013 per 1% VAF increase; 95% CI 1.005–1.022; p = 0.003) and TP53 VAF (HR 1.012 per 1% VAF increase; 95% CI 1.004–1.021; p = 0.005) were independently associated with faster leukemic transformation. Furthermore, we established nomograms to predict OS and LFS, respectively, by integrating independent mutational predictors into the revised International Prognostic Scoring System. Conclusion: Our study highlights that VAF of certain genes should be incorporated into routine clinical prognostication of survival and leukemic transformation of MDS. [ABSTRACT FROM AUTHOR]

Background: The differential signaling and outcome of patients with p190 or p210 transcripts of BCR-ABL1 have been systematically investigated in chronic myeloid leukemia rather than in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Methods: We analyzed the outcomes and ABL1 mutation profiles in 305 consecutive adult patients with Ph+ ALL treated with chemotherapy plus tyrosine kinase inhibitors. We also studied transcriptome features in two newly diagnosed patients with p190 and p210 using single-cell RNA sequencing (scRNA-seq). Results: P190 and p210 were found in 199 (65%) and 106 (35%) patients, respectively. Compared to patients with p190, a higher white blood cell count (p = 0.05), platelet count (p = 0.047), BCR-ABL1 transcript level (p < 0.001), and lower bone marrow blasts (p = 0.003) were found in patients with p210. Patients with p210 had fewer types of ABL1 mutations (4 vs. 16) and a higher prevalence of T315I and E225K/V mutations (91.3% vs. 68.6%; p = 0.031). Patients with p210 had a similar complete remission rate (91.0% vs. 90.1%; p = 0.805) but a lower complete molecular remission rate at 1 month (9.9% vs. 22.0%; p = 0.031) compared with p190. Patients with p210 had lower 3-year overall survival (OS) and disease-free survival (DFS) rates than those with p190 (3-year DFS: 10.4% vs. 9.2%, p = 0.069, 3-year OS: 44.3% vs. 38.2%, p = 0.018, respectively). Multivariate analysis revealed that p210 was independently associated with worse OS [HR 1.692 (95% CI 1.009–2.838), p = 0.046]. Allogeneic hematopoietic stem-cell transplantation (allo-HSCT) was associated with a better prognosis in patients with p210 (p < 0.0001). In addition, scRNA-seq data showed distinct molecular and cellular heterogeneity between bone marrow cells of the two transcripts. Conclusions: Ph+ ALL patients with p190 and p210 had different clinical characteristics, outcomes, ABL1 mutation profiles, and transcriptome features. Allo-HSCT could improve the outcomes of patients with p210. [ABSTRACT FROM AUTHOR]

Abstract: Currently, there are few studies that address the prognostic significance of baseline additional chromosomal abnormalities (ACAs) in newly diagnosed acute promyelocytic leukemia (APL) patients treated with arsenic trioxide (ATO) as the front-line therapy. A series of 271 consecutive APL patients has been cytogenetically investigated between 2004 and 2011 in our institution. The incidence of ACAs was 27% (46/172) in APL cases with t(15;17). Trisomy 8 was the most recurrent abnormality, accounting for 30% (14/46) of patients with ACAs, followed by +21 (7%, 3/46) and −7/7q (7%, 3/46). Nine cases (14.1%) were found to have additional balanced translocation aberrations, most of them are new and non-recurrent. Treatment protocols consisted of all-trans retinoic acid (ATRA) and chemotherapy with or without the ATO therapy. Overall, patients with and without ACAs had similar complete remission (CR) rates (94% and 98%, respectively, P =0.344). With a median follow-up of 41 months, univariate analysis showed that ACAs did not show any prognostic significance in relapse-free survival (RFS) and overall survival (OS). In addition, ATO treatment was an independent favorable predictor for RFS. Thus, this data provides insights into cytogenetic features of APL, and suggests that ATO-based combination therapy improved RFS in de novo APL patients, while ACAs had no impact on prognosis. [Copyright &y& Elsevier]

Background: Trisomy 8 positivity myelodysplastic syndrome with Behçet's disease is rare. Isolated trisomy 8 is a frequent cytogenetic abnormality in the MDS, but the characteristic of trisomy 8 and the association between trisomy 8 positivity myelodysplastic syndrome and Behçet's disease is unclear.Case Presentation: Here, we reported a 63-year-old man, who presented with fever, abdominal pain and hematochezia. Imaging studies revealed bowel wall thickening and mural hyperenhancement of terminal ileum and cecum. Colonoscopy found multiple round ulcers in terminal ileum, ileocecal valve and multiple yellow dotted pseudomembranous attachments throughout the colon. Capsule endoscopy also revealed multiple irregular ulcers in lower ileum. Serum C-reactive protein levels and fecal calprotectin were abnormally high. The clostridium difficile toxin A and B was positive. However, the patient's intestinal ulcers did not resolve after two weeks course of vancomycin. Considered that the patient was diagnosed as MDS-RAEB2 with a karyotype of 47 XX, + 8. And detailed inquiry of medical history revealed epifolliculitis and frequently recurrent oral ulcers 2 months before admission. A diagnosis of trisomy 8 positivity MDS with BD was made. Then he received glucocorticoid along with the 5th course of azacytidine. The follow-up endoscopy showed significantly improved intestinal ulcer 2 months after treatment. we report a rare disease and provide the diagnose and treatment ideas.Conclusions: We highlight the challenges and the process of thinking about of the diagnosis. This may provide a new idea for the diagnosis of intestinal ulcers. [ABSTRACT FROM AUTHOR]

Background: Myelodysplastic syndrome (MDS) arises from a rare population of aberrant hematopoietic stem and progenitor cells (HSPCs). These cells are relatively quiescent and therefore treatment resistant. Understanding mechanisms underlying their maintenance is critical for effective MDS treatment. Methods: We evaluated microRNA‐126 (miR‐126) levels in MDS patients' sample and in a NUP98‐HOXD13 (NHD13) murine MDS model along with their normal controls and defined its role in MDS HSPCs' maintenance by inhibiting miR‐126 expression in vitro and in vivo. Identification of miR‐126 effectors was conducted using biotinylated miR‐126 pulldown coupled with transcriptome analysis. We also tested the therapeutic activity of our anti‐miR‐126 oligodeoxynucleotide (miRisten) in human MDS xenografts and murine MDS models. Results: miR‐126 levels were higher in bone marrow mononuclear cells from MDS patients and NHD13 mice relative to their respective normal controls (P < 0.001). Genetic deletion of miR‐126 in NHD13 mice decreased quiescence and self‐renewal capacity of MDS HSPCs, and alleviated MDS symptoms of NHD13 mice. Ex vivo exposure to miRisten increased cell cycling, reduced colony‐forming capacity, and enhanced apoptosis in human MDS HSPCs, but spared normal human HSPCs. In vivo miRisten administration partially reversed pancytopenia in NHD13 mice and blocked the leukemic transformation (combination group vs DAC group, P < 0.0001). Mechanistically, we identified the non‐coding RNA PTTG3P as a novel miR‐126 target. Lower PTTG3P levels were associated with a shorter overall survival in MDS patients. Conclusions: MiR‐126 plays crucial roles in MDS HSPC maintenance. Therapeutic targeting of miR‐126 is a potentially novel approach in MDS. [ABSTRACT FROM AUTHOR]

Summary: Minimal residual disease (MRD) is an important independent prognostic factor for relapse and survival in acute lymphoblastic leukaemia (ALL). Compared with adult B‐cell ALL, reports of adult T‐cell ALL (T‐ALL) MRD have been scarce and mostly based on molecular methods. We evaluated the prognostic value of multiparameter flow cytometry (FCM)‐based MRD at the end of induction (EOI‐MRD). The present retrospective study included 94 adult patients with T‐ALL. MRD was detected by six‐ to eight‐colour FCM. Patients who were EOI‐MRD positive had a higher cumulative incidence of relapse (CIR) (87·6% vs. 38·8%, P = 0·0020), and a lower relapse‐free survival (RFS) (5·4% vs. 61·0%, P = 0·0005) and overall survival (OS) (32·7% vs. 69·7%, P < 0·0001) than those who were EOI‐MRD negative. Moreover, for patients who received allogeneic haematopoietic stem cell transplantation (allo‐HSCT) at their first remission, EOI‐MRD positivity was predictive of post‐transplant relapse (2‐year CIR: 68·2% vs. 4·0%, P = 0·0003). Multivariate analysis showed that EOI‐MRD was an independent prognostic factor for CIR [hazard ratio (HR) 2·139, P = 0·046], RFS (HR 2·125, P = 0·048) and OS (HR 2·987, P = 0·017). In conclusion, EOI‐MRD based on FCM was an independent prognostic factor for relapse and survival in adult T‐ALL. For patients who underwent HSCT, EOI‐MRD could be used to identify patients with a high risk of relapse after allo‐HSCT. [ABSTRACT FROM AUTHOR]

Common variable immunodeficiency (CVID) was a kind of primary immunodeficiency disorders with heterogeneous phenotype and genotype. Lipopolysaccharide-responsive and beige-like anchor (LRBA) mutation was identified as disease associated in CVID, advanced genetic method will help to detect atypical cases. We report a case of adult patient manifested as hemophagocytic lymphohistiocytosis (HLH), bone marrow examination suggested prosperity to MDS, manifested as increased immature myeloid cells and dysplastic hematopoiesis. Whole exome sequencing (WES) identified a novel heterogeneous c.1876T > C (p.W626R) mutation in LRBA and four somatic mutations: ASXL1 (c.1967dupA); PTPN11 (c.226G > A), U2AF1 (c.101C > T and c.470A > G), among which ASXL1 was a high-risk marker of clonal hematopoiesis. Combined with her recurrent severe infections and immune abnormalities such as hypoimmunoglobulinemia, the patient was diagnosed with CVID. Subsequent hematopoietic stem cell transplantation saved her from severe cytopenia and immune deficiency. This case report highlights the great promise of utilization of WES for diagnosing rare disease with atypical manifestations and guiding further treatment. [ABSTRACT FROM AUTHOR]

Purpose: To explore the relevance of cytogenetic or molecular genetic abnormalities to clinical variables, including clinical and laboratory characteristics and prognosis in Chinese patients with myelodysplastic syndromes (MDS). Methods: A total of 634 consecutive patients diagnosed with MDS at The First Affiliated Hospital, Zhejiang University School of Medicine from June 2008 to May 2018 were retrospectively included in this study. All patients had evaluable cytogenetic analysis, and 425 patients had MDS‐related mutations sequencing. Results: 38.6% of patients displayed abnormal karyotypes. The most common cytogenetic abnormality was +8 (31%). Sole +8 was related to female (p = 0.002), hemoglobin >10 g/dL (p = 0.03), and <60 years old (p = 0.046). TP53 mutations were associated with complex karyotype (CK) (p < 0.001). DNMT3A mutations correlated with ‐Y (p = 0.01) whereas NRAS mutations correlated with 20q‐ (p = 0.04). The overall survival (OS) was significantly inferior in patients with +8 compared with those with normal karyotype (NK) (p = 0.003). However, the OS of sole +8 and +8 with one additional karyotypic abnormality was not different from NK (p = 0.16), but +8 with two or more abnormalities had a significantly shorter OS than +8 and +8 with one additional karyotypic abnormality (p = 0.02). In multivariable analysis, ≥60 years old, marrow blasts ≥5% and TP53 mutations were independent predictors for poor OS (p < 0.05), whereas SF3B1 mutations indicated better prognosis. Male IDH1 and IDH2 mutations and marrow blasts ≥5% were independent risk factors for worse leukemia free survival (LFS) (p < 0.05). Conclusion: In this population of Chinese patients, trisomy 8 is the most common karyotypic abnormality. Patients with +8 showed a poorer OS compared with patients with NK. Sole +8 and +8 with one additional karyotypic abnormality had similar OS with NK, whereas +8 with two or more abnormalities had a significantly shorter OS. DNMT3A mutations correlated with ‐Y and NRAS mutations correlated with 20q‐. TP53 mutations were associated with CK and had a poor OS. SF3B1 mutations indicated a favorable OS. IDH1 and IDH2 mutations independently indicated inferior LFS. [ABSTRACT FROM AUTHOR]

Chronic myelomonocytic leukemia (CMML) is a rare disease of elderly people characterized by the presence of sustained peripheral blood monocytosis, overlapping features of myeloproliferation, and myelodysplasia. We present a large retrospective study of 156 CMML patients in China. Mean age at diagnosis was 68 years old (range 23‐91). According to the CMML‐specific prognostic scoring system (CPSS), 10 patients (8.3%) were low risk, 27 patients (22.5%) were intermediate‐1 risk, 72 patients (60%) were intermediate‐2 risk, and 11 patients (9.2%) were high risk. A total of 90 patients (57.7%) received hypomethylating agents (HMAs) treatment, 19 patients (12.2%) received chemotherapy and 47 patients (30.1%) received the best supportive care. Seventeen patients (10.9%) underwent allogeneic hematopoietic stem cell transplantation (allo‐SCT) after HMAs treatment or chemotherapy. With a median follow‐up of 35.3 months, overall response rate (ORR) was 69.5% in the HMAs ± chemotherapy group, 79.5% in the HMAs monotherapy group, 60.0% in the HMAs + chemotherapy group, and 37.5% in the chemotherapy group. HMAs monotherapy group had prolonged OS compared with the chemotherapy group (23.57 months vs. 11.73 months; p = 0.035). Patients who achieved ORR had prolonged OS (25.83 months vs. 8.00 months; p < 0.001) and LFS (20.53 months vs. 6.80 months; p < 0.001) compared with those not achieved ORR in the HMA ± chemotherapy group. By univariate analysis, only higher hemoglobulin (≥80 g/L) and lower serum LDH levels (<300 U/L) predicted for better OS and LFS. By multivariate analysis, only Hb ≥ 80 g/L predicted for prolonged OS, Hb ≥ 80 g/L, and monocytes < 3 × 109/L predicted for prolonged LFS. In summary, our study highlights the benefit of HMAs therapy in CMML, but we still need to develop novel therapeutics to achieve better outcomes. [ABSTRACT FROM AUTHOR]

Adult patients with relapsed or refractory T‐cell acute lymphoblastic leukemia (R/R‐T‐ALL) have extremely poor prognosis, representing an urgent unmet medical need. Finding an optimal salvage regimen to bridge transplantation is a priority. The CAG (cytarabine, aclarubicin, and G‐CSF) regimen was initially used by one group in China, showing unexpectedly promising results in 11 R/R‐T‐ALL patients. Here, we report the multicenter results of 41 patients who received the CAG regimen as salvage therapy. After one cycle of the CAG regimen, complete remission and partial remission were achieved in 33 (80.5%) and two (4.9%) patients, respectively. Failure to respond was observed in six patients (14.6%). Early T‐cell precursor (ETP) (n = 26) and non‐ETP (n = 15) patients had a similar CR rate (80.8% vs 80.0%, P =.95). Among 41 patients, allo‐HSCT was successfully performed in 27 (66%) patients (22 in CR and 5 in non‐CR). With a median follow‐up time of 12 months, the estimated 2‐year overall survival and event‐free survival were 68.8% (95% CI, 47.3%‐83.0%) and 56.5% (95% CI, 37.1%‐71.9%), respectively. The CAG regimen was well‐tolerated, and no early death occurred. Our multicenter results show that the CAG regimen is highly effective and safe, representing a novel choice for adult patients with R/R‐T‐ALL and providing a better bridge to transplantation. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate the clinical and molecular characteristics of myelodysplastic syndrome (MDS) patients with monosomal karyotype (MK). Methods: Eighty MDS patients with MK diagnosed between January 2010 and December 2018 were included in the retrospective study. Seventy‐three had complex karyotype (CK) and 46 had very CK (vCK, ≥ 5 abnormalities). Clinical information was collected, and a panel of 37 genes, on which mutations have been previously reported to be associated with MDS patients, was analyzed by next‐generation sequencing. Genetic and biological features and their association with survival were evaluated. Results: Monosomy 5, 7, and 17 were the most frequent and mainly occurred in patients with vCK. While median overall survival (OS) for all patients was 12.8 months with 95% CI 9.1‐16.5, patients with vCK had shorter OS (8.4 months with 95% CI 3.9‐12.8) than those with non‐vCK (16.1 months with 95% CI 11.5‐20.8) (P =.02). At least one gene mutation was detected in 76 patients (95%), TP53 mutations were detected in 57 patients, and their median OS was significantly shorter than those without TP53 mutations (9.5 months with 95% CI 7.5‐11.5 vs 26.1 months with 95% CI 8.0‐44.2, P <.01). In 34 patients who received treatment with decitabine, 25 with TP53 mutations had higher overall response rate than those with wild‐type TP53 (60% vs 22.2%, P =.03). However, OS was still significantly shorter in those with TP53 mutations (10.1 vs 26.1 months, P =.03). Multivariate analysis confirmed that TP53 mutations was an independent poor prognostic factor on OS. Conclusions: CK and vCK overlap in most of the MDS patients with MK. TP53 mutations occur more frequently in MDS patients with vCK, and both TP53 mutations and vCK are adverse prognostic factors. [ABSTRACT FROM AUTHOR]

We retrospectively studied 133 myelodysplastic syndrome patients receiving decitabine during January 2009 and September 2017. The dose of 15 mg/m2/d (n = 83) and 20 mg/m2/d (n = 50) had comparable overall response rates (ORR) (51.8% vs. 52.00%) and complete remission rate (CRR) (15.66% vs. 22.00%). The 15 mg/m2/d group had a lower incidence of grade 3/4 neutropenia (60.24% vs. 88.00%, p <.05) and thrombocytopenia (65.06% vs. 88.00%, p <.05). The 15 mg/m2/d group had a longer median overall survival (OS) (21.60 months vs. 15.23 months, p =.02). The same results were seen in refractory anemia with excess blasts (RAEB) patients: The 15 mg/m2/d group also had comparable ORR, CRR, decreased hematological toxicities and longer OS. Further analysis suggested that survival benefit of 15 mg/m2/d group was mainly in those patients with lower risk stratification. In conclusion, 15 mg/m2/d decitabine is associated with a lower incidence of hematological toxicities and longer OS and may be more suitable for patients with relatively lower risk. [ABSTRACT FROM AUTHOR]

Decitabine and low-dose chemotherapy are common treatments for intermediate and high risk myelodysplastic syndromes (MDS). In this study, we retrospectively assessed the efficacy and toxicity of the two regimens for MDS-refractory anemia with excess blasts (MDS-RAEB) patients. A total of 112 patients with a diagnosis of MDS-RAEB are included. The overall response (OR) and complete remission (CR) rate was comparable between the two groups (OR: 64.1% vs. 66.7%, p = 0.60; CR: 23.4% vs. 31.3%, p = 0.64). The OR rates of 20 mg/m2/day and 15 mg/m2/day decitabine regimen were comparable (69.0% vs. 60.0%, p = 0.46). Overall survival (OS) did not differ significantly between the groups (20.7 vs. 13.5 months, p = 0.17). In a subgroup analysis that included only patients at ≥60 years of age, survival benefit of decitabine was apparent (20.6 vs. 10.0 months, p = 0.03). In hematological toxicities, the lowest count of platelet in the decitabine group was higher significantly. And, the incidence of Grade 3–4 infection in the decitabine group was lower significantly. Our results demonstrate that both decitabine and low-dose chemotherapy are effective for MDS-RAEB, but decitabine was safer. Decitabine might be a better choice for patients at ≥60 years of age. [ABSTRACT FROM AUTHOR]

According to 2008 WHO classification RARS is regarded as less than 5% blasts and more than 15% ring sideroblasts in the bone marrow. In 2016 WHO classification MDS-RS is revised as more than 15% ring sideroblasts or more than 5% ring sideroblasts in the presence of the SF3B1 mutation. In our study, we classified intracellular iron in bone marrow into four types according to the size and quantity of iron granules. We found that there was a significant difference between SF3B1-mutant and SF3B1-wild-type MDS patients in intracellular iron III, intracellular iron IV and ring sideroblasts. We defined intracellular iron (III + IV + RS)%×100 as 'Iron score'. We suggest that the patients carrying SF3B1 mutation with Iron score ≥10 will extend the subtype of MDS-RS, in addition to the current WHO classification criteria. This study gives us a new insight into the relation of SF3B1 mutation and intracellular iron in lower-risk MDS. [ABSTRACT FROM AUTHOR]

It is controversial whether acute myeloid leukemia (AML) patients with 20–29% bone marrow (BM) blasts should be considered AML or myelodysplastic syndromes (MDS). We retrospectively studied 382 patients, including 108 AML with 20–29% BM blasts (AML20–29), 210 AML with ≥30% BM blasts (AML ≥ 30), and 64 MDS with 10–19% BM blasts (MDS-EB2). We found that AML20–29 were more similar to MDS-EB2 in terms of advanced age, less blood count, the increased presence of poor-risk cytogenetics. The frequency of mutated genes in AML20–29 had both the characters of AML and MDS. Median overall survival of AML20–29 and MDS-EB2 were similar and shorter than those of AML ≥ 30 (p =.045). Multivariate analysis showed inferior survival with increased age, low platelet count and FLT3 mutations. Our findings suggest that AML20–29 have clinical features more similar to MDS than AML. [ABSTRACT FROM AUTHOR]

Abstract We retrospectively analyzed 101 primary MDS patients with complex karyotype during January 2010 and April 2017.The median overall survival (OS) time was 13 (95% CI 9.98–16.02) months, and there was no significant difference in OS for different treatment. Chromosome 5/7 involvement was common (78.22%, 79/101) and associated with shorter OS (12 months vs. 28 months, P < 0.01) Monosomal karyotype (MK) is overlapped with CK in 79 patients, but was not statistically associated with shorter OS. While in 59 cases with genes sequenced, 57 (96.61%) patients were found to have at least one mutation of known significance, and TP53 was the most frequent (74.58%, 44/59), the median OS of patients with TP53 mutation was shorter than those without (10 vs. 27 months, P < 0.01). Multivariate analysis demonstrated that only TP53 mutation was the strongest independent prognostic factor for OS. Moreover, high variant allele frequency (VAF) of TP53 mutation (median VAF was 70.00%) was seen and associated with adverse survival (9 months vs. 13 months, p = 0.04). In conclusion, MDS patients with CK implied an unfavorable outcome regardless of any treatment, TP53 mutation occurs at a high frequency and has a higher VAF, both were associated with worse survival. [ABSTRACT FROM AUTHOR]

Purpose: The myelodysplastic syndromes (MDS) are a group of hematologic disorders characterized by the presence of somatically mutated hematopoietic stem cells (HSCs) that increase the risk of progression to secondary acute myeloid leukemia (sAML). Mutations in isocitrate dehydrogenase (IDHmut) are thought to correlate with the increased production of the oncogenic protein 2-hydroxyglutarate (2-HG) in AML. The aim of this study was to examine whether serum 2-HG has utility as a prognostic biomarker, and whether elevated 2-HG levels are predictive of IDH mutations in patients with MDS.Methods: Genetic profiling was utilized to determine the genetic composition of a large cohort of MDS patients, including the presence or absence of IDH1 or IDH2 mutations (n = 281). Serum 2-HG levels were detected by liquid chromatography-tandem mass spectrometry.Results: In the current study of MDS patients, elevated serum 2-HG levels were predictive of inferior overall- and leukemia-free survival irrespective of IPSS risk grouping. Higher serum 2-HG levels predicted the presence of IDH mutations. IDH2mut patients had a higher risk of leukemic transformation. The co-occurrence of DNMT3A or SRSF2 mutations was found to be increased in IDH2mut patients. IDH2 mutations were associated with significantly worse OS and LFS amongst patients with low-risk MDS by IPSS grouping.Conclusions: The noted predictive value of serum 2-HG levels and IDH2 mutations on OS and LFS support the use of biomarkers and/or underlying cytogenetics in novel prognostic scoring systems for MDS. [ABSTRACT FROM AUTHOR]

Early death is the main obstacle for the cure of patients with acute promyelocytic leukemia (APL). We have analyzed risk factors of early death from 526 consecutive newly diagnosed APL patients between 2004 and 2016. The overall incidence of early death was 7.2% (38/526). The peak hazard of early death occurred in the first 0-3 days. Multivariate logistic analysis demonstrated white blood cell (WBC) counts [odds ratio (OR) = 1.039; 95% confidence interval (CI): 1.024-1.055; P < 0.001], age (OR = 1.061; 95% CI: 1.025-1.099; P = 0.001) and platelet counts (OR = 0.971; 95% CI: 0.944-0.999; P = 0.038) were independent risk factors for early death. Furthermore, receiver-operator characteristic (ROC) curve analyses revealed a simple WBC/platelet ratio was significantly more accurate in predicting early death [areas under the ROC curve (AUC) = 0.842, 95% CI: 0.807-0.872) than WBC counts (AUC = 0.793; 95% CI: 0.756-0.827) or Sanz score (AUC = 0.746; 95% CI: 0.706-0.783). We stratified APL patients into four risk subgroups: low risk (WBC ≤ 10 × 109/L, platelet >40 × 109/L), intermediate risk (WBC/platelet <0.2 and age ≤ 60, not in low risk), high risk (WBC/platelet ≥0.2 or age > 60, not in low and ultra-high risk) and ultra-high risk (WBC > 50 × 109/L), the early death rates were 0, 0.6, 12.8, and 41.2%, respectively. In conclusion, we proposed a modified Sanz risk model as a useful predictor of early death risk in patients with APL. [ABSTRACT FROM AUTHOR]

The aim of the study is to better understand the mechanism of relapse and acquired clinical resistance to arsenic trioxide (ATO) and/or all-trans retinoic acid (ATRA). Thirty relapsed acute promyelocytic leukemia (APL) patients were followed. Fifteen patients experienced two or more relapses; nine patients had clinical resistance to ATO-based therapy. The frequency and clinical significance of promyelocytic leukemia (PML)-retinoic acid receptor alpha (RARA) mutational status using Sanger sequencing were evaluated. Overall, eight different types of mutations in the RARA region (V218D, R272Q, T278A, T291I, N299D, R294W, A300G, and L220_F228delinsP) were identified in 11 patients. Eight missense mutations (L211P, C213R, S214L, A216V, L217F, D219H, S221G, and D241G) were found in the PML portion of PML-RARA in 14 patients, with A216V as the predominant mutation. Eight patients were found to harbor both PML and RARA mutations over the course of the disease. The PML-region mutations were associated with response to ATO-based therapy (P < 0.0001), number of relapses (P = 0.001), and early relapse (P = 0.013). Notably, one case sampled at nine different time points showed alternating clonal dominance over the course of treatment. This study demonstrated frequent mutations of PML-RARA and supported a clonal selection model in relation to APL relapse and ATO resistance. [ABSTRACT FROM AUTHOR]

Prognostic factors for patients with acute promyelocytic leukemia (APL) treated in the context of arsenic trioxide (ATO)-based frontline regimes have not been established clearly. We retrospectively analyzed the clinical features, immunophenotypes, Fms-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD), and outcomes of 184 consecutive newly diagnosed APL patients treated by intravenous ATO-based therapy. The median age was 40 years (14–77 years). The early death rate was 4.9% (9/184 patients). With a median follow-up time of 36 months (9–74 months), the 3-year relapse-free survival (RFS) and overall survival (OS) were 93.3% and 92.2%, respectively. Interestingly, there was no meaningful association between 3-year RFS and initial white blood cell count, FLT3-ITD status, or type of PML–RARA isoforms. In multivariable analysis, the CD56 expression was the only independent risk factor in terms of RFS (hazard ratio, 4.70; P = 0.005). These results suggested that ATO-based therapy may ameliorate the unfavorable influence of previously known high-risk features; moreover, CD56 expression remains to be a potentially unfavorable prognostic factor in APL patients. [ABSTRACT FROM AUTHOR]

With limited data available on the low-dose cytarabine, aclarubicin and granulocyte colony-stimulating factor (CAG) regimen in newly diagnosed older patients with acute myeloid leukemia (AML), this study aimed at comparing the efficacy and toxicity of CAG with idarubicin plus cytarabine (IA) remission induction therapy in these patients. A total of 154 consecutive patients (52 with CAG and 102 with IA) were retrospectively analyzed. The patients in the CAG group had a higher median age (68 vs. 65 years, p = 0.002) and a higher proportion of previous myelodysplastic syndrome (25.0% vs. 2.9%, p < 0.0001) compared to those in the IA group. The complete remission rates with the CAG and IA regimens were 55.8% and 52.9% ( p = 0.864). The median overall survival (12.1 vs. 11.7 months, p = 0.650) and 3-year disease-free survival rates (29.6% vs. 48.6%, p = 0.657) were not statistically different in the two groups. The CAG regimen might be an alternative to conventional chemotherapy in older patients with AML. [ABSTRACT FROM AUTHOR]