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Optimal post-remission treatment for individual favorable and intermediate risk acute myeloid leukemia (AML) patients has not yet been established. Human leukocyte antigen (HLA)-mismatched stem cell microtransplantation (MST), may improve outcomes and avoid graft-versus-host disease in patients with first complete remission of AML. We retrospectively analyzed the efficacy, safety, and survival of 63 patients with favorable- or intermediate-risk AML who received MST, autologous stem cell transplantation (ASCT), or cytarabine single agent (CSA) as post-remission treatment from January 2014 to August 2021. The neutrophil recovery time was shorter in the MST group than in the CSA group. The 2-year cumulative incidences of relapse in the MST, ASCT, and CSA groups were 27.27%, 29.41%, and 41.67%, respectively. During follow-up, 21 patients (33.30%) died of relapse, including six (9.52%), five (7.94%), and 10 (15.84%) in the MST, ASCT, and CSA groups, respectively. The estimated 2-year overall survival (OS) and relapse-free survival (RFS) were 62.20% vs. 50.00% (P = 0.101) and 57.10% vs. 50.00% (P = 0.136), in the >60 years MST and CSA groups (P = 0.101). The estimated 2-year OS was 100%, 66.20%, and 69.10% in the MST, ASCT, and CSA groups (MST vs CSA, P = 0.044), meanwhile, the estimated 2-year RFS was 100%, 65.40%, and 59.80% in patients ≤60 years. MST, ASCT, and CSA are acceptable post-remission treatments for patients with favorable- and intermediate-risk AML and may not only improve the prognosis of the elderly but also prolong the OS and RFS of favorable- or intermediate-risk patients ≤60 years. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the incidence and prognostic significance of common cytogenetic and molecular abnormalities in patients with TP53-mutated and non-TP53-mutated acute myeloid leukemia (AML). We retrospectively analyzed the clinical data of 326 patients with newly diagnosed AML hospitalized in our institution between October 2015 and June 2021. Classification variables were reported as percentages and compared by χ2 tests. Survival rates were evaluated by the Kaplan-Meier method. The incidence of TP53 mutations in AML patients in this clinic was 9.8%, of whom 87.5% patients were over 50 years old. The common concurrent mutations of TP53 were DNMT3A, IDH2, NRAS and TET2. Patients with a TP53 variant allele frequency (VAF) ≤ 40% had better overall survival (OS) than patients with a VAF >40%. Compared with non-TP53-mutated patients, significantly more TP53-mutated patients were gene-fusion negative, +mar, – 7/del (7q), – 5/del (5q), – 17/17p-, – 12/12p-, incomplete (inc) karyotype, or complex karyotype (CK), and had FLT3-ITD or IDH2 mutations, as well as a lower complete remission (CR) rate (31.3%) and higher recurrence rate (80.0%). The 2-year OS rates of TP53-mutated and non-TP53-mutated patients were 18.8% and 47.3%, respectively (P < 0.001). Univariate analysis showed that non-TP53-mutated patients with MLL family gene fusion, +mar or – 17/17p – karyotype, and FLT3-ITD mutations had a poor prognosis, while t(8; 21) karyotype was associated with a better prognosis. TP53-mutated patients with – 7/del (7q) or – 5/del (5q) karyotype had a poor prognosis. The cytogenetic and molecular landscapes differed between TP53-mutated and non-TP53-mutated patients, and some abnormalities had different values between them. [ABSTRACT FROM AUTHOR]

Prognostic nutritional index has been found to be related to the clinical outcomes of patients with cancer. However, its role in myelodysplastic syndromes (MDS) patients is unclear. We aimed to assess the value of nutritional status in predicting the prognosis of MDS patients. Totally 121 MDS patients were analyzed retrospectively. The prognostic nutritional index (PNI) was used to assess nutritional status of the patients. The bio-informatics tool X-tile was used to define the threshold, and accordingly patients were divided into PNIlow and PNIhigh groups, the characteristics were compared between two groups. The PNIhigh was associated with better OS (Overall Survival) than PNIlow in MDS patients (Median OS, 28.03 months versus 19.63 months, P = 0.0205). But there were no statistical differences in PFS (Progression-Free-Survival) between the two groups (P = 0.9373). The univariable and multivariable COX proportional hazard analysis adjusted for age, gender, platelet count, HB level and IPSS-R scores, and the results showed that PNI is a useful index in the evaluation of the OS of MDS (HR 0.588, 95%CI 0.374–0.926, P = 0.024). PNI would be a simple and immediately available tool for predicting the prognosis of MDS. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to develop a prognostic model for chronic lymphocytic leukemia (CLL). Methods: GEO2R was used to retrieve the gene expression data of CLL and normal B cells from the Gene Expression Omnibus (GEO; GSE22529 and GSE50006 datasets) database. Practical Extraction and Report Language was used to extract the gene expression and overall survival (OS) data of CLL patients from the Chronic Lymphocytic Leukemia – ES (CLLE-ES) project in the International Cancer Genome Consortium (ICGC) database. Cox regression with Lasso was used to create and validate a prognostic model for CLL. Results: A total of 267 genes exhibited differential expression between CLL and normal B cells. Cox univariate analysis identified 14 DEGs that correlated with OS. Lasso multivariate evaluation demonstrated that AKAP12 and IGFBP4 are independent prognostic factors for CLL. Kaplan-Meier survival analysis revealed a significant association between the estimated risk score and survival. The area under the receiver operating characteristic curve was calculated to be 0.97, indicating high predictive accuracy. In addition, high AKAP12 and IGFBP4 risk scores were associated with the high incidence of trisomy 12q. Conclusion: Taken together, AKAP12 and IGFBP4 are independent prognostic factors for CLL. [ABSTRACT FROM AUTHOR]

Objective: This study was conducted in order to study the clinical characteristics, prognostic factors, and treatment outcomes in patients with primary central nervous system lymphoma (PCNSL). Materials and Methods: The data of a total of 5,166 PCNSL patients diagnosed between 2000 and 2018 from the Surveillance, Epidemiology, and End Results (SEER) database were obtained. Results: The mean age was 63.1 ± 14.9 years, with a male to female ratio of 1.1:1.0. The most common histologic subtype was diffuse large B-cell lymphoma (DLBCL) (84.6%). The 1-, 3-, and 5-year overall survival (OS) rates were 50.1%, 36.0%, and 27.2%, respectively, and the corresponding disease-specific survival (DSS) rates were 54.4%, 41.3%, and 33.5%, respectively. Multivariate analysis with Cox regression showed that race, sex, age, marital status, surgical resection, and chemotherapy were independent prognostic factors for OS and DSS, but radiotherapy was only for OS. Nomograms specially for DLBCL were established to predict the possibility of OS and DSS. The concordance index (C-index) values of OS and DSS were 0.704 (95% CI 0.687–0.721) and 0.698 (95% CI 0.679–0.717), suggesting the high discrimination ability of the nomograms. Conclusion: Surgical resection and/or chemotherapy was favorably associated with better OS and DSS. However, radiotherapy was not beneficial for OS and DSS in the long term. A new predictive nomogram and a web-based survival rate calculator we developed showed favorable applicability and accuracy to predict the long-term OS for DLBCL patients specifically. [ABSTRACT FROM AUTHOR]

Objectives: Extramedullary multiple myeloma (EMM) is a relatively less frequent subentity of multiple myeloma (MM) and is generally considered to be a poor prognostic factor. Novel agents and hematopoietic stem cell transplantation (HSCT) have led to a significant improvement in the progression-free survival and overall survival of patients with MM, but outcomes of EMM remain dismal. Little is known regarding the role of novel therapies in this setting. This review summarizes the current available data regarding the roles of proteasome inhibitors, immunomodulators, monoclonal antibodies, chimeric antigen receptor (CAR)-T cell therapy and HSCT in EMM. Methods: A systematic literature review through PubMed was conducted to summarize the published evidence on the therapeutic developments of novel agents and HSCT in EMM. Literature sources published in English were searched, using the terms multiple myeloma, extramedullary and treatment. Results: Long-term outcomes of EMM patients remain dismal despite the utilization of novel agents and HSCT. The standard therapy of EMM has not been established. EMM should be managed as high-risk disease and treated accordingly. Discussion and conclusion: This review will provide an insight on the current and emerging treatment strategies as well as their efficacy in EMM. Further subgroup analyses in large prospective trials focusing on EMM is needed to help optimize the therapy. [ABSTRACT FROM AUTHOR]

Acute myeloid leukaemia (AML) is a haematopoietic malignancy with a dismal outcome. Consequently, risk stratification based on more effective prognostic biomarkers is crucial to make accurate therapy decisions. T cell receptor gamma alternative reading frame protein (TARP) has been reported in prostate and breast cancers, but its correlation with AML remains unclear. Differential expression of TARP mRNA in different AML subtypes was analysed using the UALCAN online platform. Its relationship with baseline clinical attributes, survival and efficacy were analysed based on three GSE1159, GSE425 and GSE6891 microarray datasets downloaded from Gene Expression Omnibus (GEO) and Oncomine databases. Quantitative real-time PCR was performed to determine mRNA levels of TARP in bone marrow mononuclear cells (BMMCs) isolated from AML patients. TARP was significantly overexpressed in AML patients. In AML, relatively low TARP expression was associated with the CBFβ-MYH11 fusion gene. The proportion of FLT3 mutations was significantly higher in non-adolescent and young adult (non-AYA, >39 years of age) AML patients who had high TARP levels but not in AYA (15–39 years) patients. High expression of TARP was related to poor outcome by univariate analysis but not by multivariate analysis and unsatisfactory therapeutic effects, which could be overcome by haematopoietic stem cell transplantation (HSCT). Our findings suggest that TARP might be a potential prognostic marker of AML and serve as a promising immunotherapeutic target. [ABSTRACT FROM AUTHOR]

Background: Clonal hematopoiesis (CH) can be found in various myeloid neoplasms (MN), such as myelodysplastic syndromes (MDS), myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN), also in pre-MDS conditions. Methods: Cytogenetics is an independent prognostic factor in MDS, and fluorescence in-situ hybridization (FISH) can be used as an adjunct to karyotype analysis. In the past 5 years, only 35 of 100 newly diagnosed MDS and MDS/MPN patients were identified abnormalities, who underwent the FISH panel. In addition, we examined a cohort of 51 cytopenic patients suspected MDS or MDS/MPN with a 20-gene next generation sequencing (NGS), including 35 newly diagnosed MN patients and 16 clonal cytopenias of undetermined significance (CCUS) patients. Results: Compared with the CCUS group, the MN group had higher male ratio (22/13 vs 10/6), cytogenetics abnormalities rate (41.4% vs 21.4%) and frequency of a series of mutations, such as ASXL1 (28.6% vs 25%), U2AF1 (25.7% vs 25%), RUNX1 (20% vs 0.0%); also, higher adverse mutations proportion (75% vs 85.2%), and double or multiple mutations (54.3% vs 43.75%). There were 7 MN patients and 4 CCUS patients who experienced cardio-cerebrovascular embolism events demonstrated a significant difference between the two groups (25% vs 20%). Ten of the 11 patients had somatic mutations, half had DNA methylation, while the other half had RNA splicing. Additionally, six patients had disease transformation, and four patients had mutated U2AF1, including two CCUS cases and two MDS-EB cases. Following up to January 2021, there was no significant difference in over survival between the CCUS and MN groups. Conclusion: NGS facilitates the diagnosis of unexplained cytopenias. The monitoring and management of CCUS is necessary, also cardio-cerebrovascular embolism events in patients with CH need attention in the clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: It is common of chronic phase chronic myeloid leukemia (CML-CP) patients coexisting anemia at diagnosis, but the role of anemia on the prognosis is not clear. This study aims to explore impact of anemia on outcomes of CML-CP patients in TKI era. Methods: In the retrospective study, 258 newly diagnosed CML patients treated with TKIs were enrolled. Patients with moderate anemia (Hb ≤ 90 g/L) and non-moderate anemia (Hb > 90 g/L) were compared. Results: The incidence of moderate anemia at the time of CML diagnosis was 34.8%. Compared with patients with non-moderate anemia, patients with moderate anemia had higher proportion of intermediate-high Sokal risks and more aggressive characteristics such as higher WBC counts, higher percent of myeloblasts and basophils. However, there were no statistical differences in terms of optimal response rates, 5-year PFS and OS between the two groups. Conclusion: Moderate anemia is a common concomitant symptom in CML-CP patients and is associated with high-risk CML, but its occurrence does not affect the survival of CML-CP patients in TKI era. [ABSTRACT FROM AUTHOR]

The FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) gene mutation is present in ~20% of patients with de novo acute myeloid leukemia (AML). Patients with an FLT3-ITD mutation have a poor prognosis. However, the prognostic function of FLT3-ITD combined with other cytogenetic abnormalities are not clear. In the present study, a retrospective analysis of 103 newly diagnosed patients with AML was performed. The results revealed that the overall survival (OS) and recurrence-free survival (RFS) times were significantly longer in patients with an FLT3-ITD mutation combined with other favorable risk genes, compared with in those patients with a single FLT3-ITD mutation (P=0.0361 and P=0.0426). Sorafenib combined with chemotherapy significantly improved the overall response rate (ORR) when compared with mono-chemotherapy (P=0.039), but no significant differences were observed in the OS and RFS. In conclusion, favorable-risk cytogenetics may improve the clinical outcomes of patients with FLT3-ITD-mutated AML, but adverse-risk cytogenetics may not further worsen the prognosis. Sorafenib combined with chemotherapy may increase the ORR but would not result in a longer OS and RFS. [ABSTRACT FROM AUTHOR]

Objectives: Circular RNA (circRNA), a covalently closed loop structure lacking poly-adenylated tails, has attracted attention with the rapid development of its detection techniques such as bioinformatics and RNA sequencing. CircRNA plays important roles in several cell signaling pathways that are associated with cancer biogenesis, including acting as miRNA sponges, transcriptional regulators, protein adaptors and protein translators. The role of circRNA in hematological malignancy has been revealed recently. The purpose of this study was to explore the role of circRNA in hematological malignancy. Methods: A comprehensive literature review was conducted through Pubmed to summarize the published evidence on the circRNAs in hematological malignancies. English literature sources since 1976 were searched, using the terms circRNA, hematological malignancy. Results: CircRNAs can regulate the gene expression of hematological malignancies mainly through adsorbing several miRNAs. Some circRNAs are potential biomarkers and therapeutic targets in hematological malignancies, such as acute myloid leukemia (AML), chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). Conclusion: CircRNAs play an important biological function and have great diagnostic and prognostic value in hematological malignancies. [ABSTRACT FROM AUTHOR]

The specific prognostic factors and the long-term effects of different treatment options in APL remain unclear. In this retrospective study, 70 APL patients were treated with ATRA + DNR/DA or ATRA + ATO regimens for induction therapy and DA or ATRA + ATO for consolidation and maintenance therapy. The prognostic factors and treatment effects on outcome were analyzed. Results showed that the 5-year OS in low-intermediate risk and high risk groups were 95.63% and 100%, and the 5-year RFS were 95.34% and 100%, respectively, the early mortality rate was 4.28%. No significant difference was found on OS and RFS with different regimens, but side-effects and treatment-related mortality rates were lower in ATRA + ATO group. CD34 expression, FLT3-ITD mutation and PML-RARA isoform had no significance on OS and RFS. In conclusion, cytogenetic and molecular abnormalities had no influence on effect of APL patients; ATRA + ATO sequential maintenance may alleviate complications, treatment-related mortality, and the previously high risk factors. [ABSTRACT FROM AUTHOR]

The prognosis of patients with relapsed/refractory acute myeloid leukemia (R/R AML) is poor, with a 3-year overall survival rate of 10%. Patients with translocation (t)(11;19)(q23;p13) have a higher risk of relapse and there is no optimal regimen for these patients. The present study treated two young patients with t(11;19)(q23;p13) AML, who relapsed after one or two cycles of consolidation, with a salvage treatment consisting of sequential cladribine, cytarabine and etoposide (CLAE) and allogeneic hematopoietic stem cell transplantation (allo-HSCT). Both neutrophil and platelet engraftments were achieved within 15 days, and no severe transplant-related complications and graft-versus-host diseases were observed. Following allo-HSCT, both patients achieved complete hematologic and cytogenetic remission. Decitabine was used for the prophylaxis of relapse. The two patients remained alive and disease-free for 100 days following allo-HSCT. The results presented here suggest that CLAE regimen sequential with allo-HSCT may be effective in treating patients with R/R AML, with t(11;19)(q23;p13). However, further studies and a larger sample size are required to validate the effectiveness of this treatment regimen. [ABSTRACT FROM AUTHOR]