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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.

There was some heterogenity in low or intermediate risk acute myeloid leukemia (AML) stratified by European LeukemiaNet (ELN), the optimal post-remission treatment for an individual favorable and intermediate risk genetics AML patient has not yet been established. HLA-mismatched stem cell micro-transplantation (MST), a novel apporoach of transplantation, which may improve outcomes and avoid graft versus host disease (GVHD) in first complete remission (CR1) AML patients. We retrospectively analyzed the efficacy, safety and survival of the 63 patients with favorable or intermediate risk AML received MST, autologous stem cell transplantation (ASCT) or cytarabine single agent (CSA) as post-remission treatment from January 2014 to August 2021. Neutrophil recovery time was shorter in the MST group than CSA group. There was no significant difference in three groups of infection and bleeding. The 2-year cumulative incidences of relapse were 27.27%, 29.41% and 41.67% in the MST, ASCT and CSA groups, respectively. During the period of follow-up, there were 21 patients (33.3%) died to relapse, including 6(9.52%), 5(7.94%) and 10 (15.84%) deaths in MST, ASCT and CSA groups, respectively. The estimated overall survival (OS) and relapse free survival (RFS) at 2 years were 62.2% vs 50.0% (P = 0.101) and 57.1% vs 50.0% (P = 0.136) in MST and CSA group (P = 0.101) for patients over 60 years. The estimated OS at 2 years was 100.0%, 66.2%, and 69.1% in MST, ASCT and CSA group ( MST vs CSA, P = 0.044), meanwhile, the estimated RFS at 2 years was 100.0%, 65.4%, and 59.8% ( MST vs CSA, P = 0.050) in patients ≤ 60 years. We concluded that MST, ASCT and CSA were all acceptable options for favorable and intermediate risk AML patients as post-remission treatment. Moreover, MST could not only improve the prognosis of the elderly but also prolong the OS and RFS of low or intermediate-risk patients ≤ 60 years.

Introduction: Diffuse large B cell lymphoma (DLBCL) is a highly heterogeneous tumor mainly occuring in the elderly, with approximately 40% of cases occurring in patients over 70 years old and this proportion will increase in the future. High grade B cell lymphomas (HGBL) with MYC and BCL2 and BCL6 rearrangements, so called triple-hit lymphomas (HGBL-THL), which usually presents a high-aggressive clinical behavior as well as to be associated with a very poor outcome. However, there are no standard treatment strategies for very elderly HGBL-DHL/THL patients, it still remains a challenge for clinicians. Case Presentaion: we report a case of a 95-year-old patient diagnosed with diffuse large B-cell lymphoma (HGBL-THL, non-germinal central type, stage IV group A, IPI 5 points, high risk group), coronary atherosclerotic heart disease (paroxysmal atrial fibrillation, cardiac insufficiency), hypertension, treated with chemotherapy, radiotherapy and targeted drug therapy obtained better outcome of keeping alive for 1 year. Conclusion: For very elderly HGBL-THL patients, a careful assessment of performance, nutritional status and comorbidities are needed before treatment. Novel therapies including immunotherapy, targeted therapy and chimeric antigen receptor T (CAR-T) cell therapy may provide benefit.

Retinoic acid receptor gamma (RARG) belongs to the nuclear receptor superfamily and has 90% homology to RAR alpha (RARA) and RAR beta. The promyelocytic leukemia (PML)-RARA fusion gene has been implicated in acute promyelocytic leukemia (APL). RARG gene rearrangement has been identified in a rare subtype of acute myeloid leukemia (AML) that resembles APL. To date, only 10 cases of gene rearrangements involving RARG (nucleoporin [NUP]98-RARG, promyelocytic leukemia protein-RARG, cleavage and polyadenylation-specific factor 6-RARG, or nucleophosmin [NPM]1-RARG-NPM1) have been reported. These patients show characteristics similar to APL, including bone marrow morphology, coagulation abnormality, and immunophenotype; however, they are resistant to all-trans retinoic acid and arsenic trioxide treatment. Moreover, there is no optimal therapeutic regimen for this subtype of AML. In this study, we report the clinical presentation and experimental findings of a case of AML with NUP98-RARG gene fusion similar to APL and review other cases of RARG gene rearrangement described in the literature.

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...

To explore the relationship between platelet count and bleeding score in immune thrombocytopenia purpura (ITP) and compare the clinical practicability of two bleeding grading systems with adult patients with ITP.A total of 204 patients were retrospectively analyzed with the ITP bleeding scale (IBLS) and the ITP bleeding assessment tool (version 2016) (ITP-2016). The correlation between the two bleeding score systems and the relations among the platelet counts were respectively analyzed.(1) There is a linear relationship between platelet count and bleeding score, no matter which scoring system it is based on (rs = -0.429,There is good responsiveness, strong assessment consistency, close correlation between ITP-2016 and IBLS. ITP-2016 takes less time-consuming in clinical application. It can be used as an effective tool of condition judgement, risk assessment and efficacy evaluation of patients with ITP.

Rituximab has been frequently used as a second-line treatment for patients with immune thrombocytopenia (ITP). Recently, several studies have proposed low-dose (100 mg or 100mg/m2 per week for 4 weeks) rituximab instead of the standard dose of 375mg/m2 per week for 4 weeks to treat ITP patients. The aim of this review was to systematically evaluate the efficacy and safety of low-dose rituximab for patients with ITP. Pubmed, Web of Science, Cochrane Library and Embase were searched to identify the clinical studies published in full text or abstract that met the predefined inclusion criteria. Efficacy analysis was restricted to the studies enrolling five or more patients. While safety analysis was evaluated based on all the studies reported adverse events. Nine studies (329 patients) were included for effect assessment of low-dose rituximab treatment on the patients with ITP. The pooled overall response rate was 63% (95% CI, 0.54-0.71) while the pooled complete response was 44% (95% CI, 0.33-0.55). Thirty-one patients were reported to experience adverse effects associated with rituximab, among them 30 cases suffered mild to moderate side-effects (grade1-2). Only one patient developed into interstitial pneumonia (grade3). No death was reported. Low-dose rituximab exhibited a satisfactory efficacy and safety profile, indicating that this regimen is a promising therapy for ITP, and should be further investigated through randomized clinical trials with standard-dose rituximab.

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 theOur findings suggest that TARP might be a potential prognostic marker of AML and serve as a promising immunotherapeutic target.

Background: Abnormal spindle-like microcephaly-associated protein (ASPM) has been implicated in the aggressive behavior of several malignant tumors. However, its potential effects on diffuse large B-cell lymphoma (DLBCL) still remain unknown. Methods: ASPM levels were determined by immunohistochemically in DLBCL tissues from 54 patients and 15 reactive lymphoid hyperplasia (RLH) tissues as control, and its association with clinical features and overall survival were evaluated. The effects of ASPM on cell growth, cell apoptosis and cell cycle of DLBCL cells were assessed. Bioinformatics, quantitative RT-PCR and western blotting were conducted for mechanic investigation. Results: ASPM expression was upregulated in DLBCL tissues compared with RLH tissues. Its high expression was correlated with inferior clinicopathological characteristics and poor outcomes of DLBCL patients. Multivariate analysis revealed that high ASPM expression emerged as an independent factor for poor prognosis. In DLBCL cell lines, silencing of ASPM suppressed cell growth, induced cell apoptosis and arrested the cell cycle. Mechanically, effects of ASPM knockdown on DLBCL cells were partially dependent on its block of the Wnt/β-catenin pathway. Conclusion: Collectively, our results suggested that ASPM potentially served as a predictive biomarker of DLCBL tumorigenesis and prognosis, representing a potential therapeutic target for DLCBL.

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.

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.

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.

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.

This study investigated the efficacy and safety of low-dose lenalidomide combined with dexamethasone in elderly patients with relapsed and refractory multiple myeloma (MM).Thirty-two elderly patients with refractory and recurrent MM (median age: 64 years) were treated with low-dose lenalidomide (LD-R) combined with dexamethasone (D). LD-R (10 mg/d) was administered orally for 21 days and D (40 mg/d) was administered twice a day on days 1-4, 9-12, and 17-20. The treatment lasted 2-8 28-day cycles.After two cycles, the complete, very good partial, and partial remission rates were 12.5% (4/32), 25.0% (8/32), and 34.4% (11/32), respectively. The overall response rate was 71.9% (23/32). After a 24-month follow-up, 23 patients responded to therapy, three were in complete remission, four were stable, and 16 exhibited disease progression. In addition, median time-to-progression was 13 months. Observed side effects were hypodynamia, gastrointestinal reaction, peripheral neuritis, and mild hypocytosis.Low-dose lenalidomide in combination with dexamethasone is an effective and safe treatment for relapsed and refractory MM in elderly patients.

The objective of the present study was to investigate the anticancer efficacy of dimercaptosuccinic acid modified iron oxide (DMSA-Fe3O4) magnetic nanoparticles (MNPs) combined with arsenic trioxide (As2O3) and doxorubicin (ADM) in non-Hodgkin's lymphoma (NHL) cell line (Raji cells). The growth inhibition rate of Raji cells was determined by MTT assay. Characteristics of DMSA-Fe3O4 MNPs and distribution of nanoparticles taken up by Raji cells were observed under a transmission electron microscopy (TEM). Further, apoptosis of cells and intracellular concentration of ADM were detected by flow cytometry (FCM). DAPI staining was used to view apoptotic cellular morphology. Subsequently, transcription and protein expression levels of bcl-2, NFKB, survivin, bax, p53 and caspase-3 were determined by reverse transciptase polymerase chain reaction (RT-PCR) and Western blotting analysis, respectively. The results of MTT assay indicated that the inhibition of Raji cells by the combined form of ADM and As2O3 was significantly higher than either ADM or As2O3 alone. However, ADM-As2O3 MNPs proved superior over all other groups. TEM observation revealed that the majority of MNPs were quasi-spherical with an average diameter of about 18 nm and the MNPs taken up by cells were located in the endosome vesicles of cytoplasm. The apoptotic rate and accumulation of intracellular ADM in ADM-As2O3 MNPs group were significantly higher than those in control, ADM, As2O3 and ADM+As2O3, groups. In addition, DAPI staining of Raji cells from ADM-As,O3 MNPs group clearly exhibited more morphological changes (severe structural alterations) than other groups. Moreover, transcription and protein expression of bcl-2, NFKB, survivin, bax, p53 and caspase-3 of Raji cells were regulated at the most remarkable extent in ADM-As2O3, MNPs group as compared with other groups. These findings suggest that the antitumor efficacy of the combination of novel ADM-As2O3, MNPs on Raji cells would be a promising strategy for lymphoma therapy.

The role of tissue inhibitor of metalloproteinase-2 (TIMP-2) in extramedullary infiltration of acute leukemia is unclear. We demonstrated in our previous study that the up-regulation of TIMP-2 promoted SHI-1 cell invasion in vitro. We investigated in the present study whether TIMP-2 would have the same effect in vivo. A retroviral vector carrying human TIMP-2 cDNA was constructed and transfected into SHI-1 cells. Three subclone cells (S1, S2 and S3) that highly expressed TIMP-2 were selected to establish nude mouse models of acute leukemia. Times of leukemic onset in mice of S1, S2 and S3 groups were all earlier than that of the SHI-1 group, whereas the survival times of S1, S2 and S3 groups were all shorter than that of the SHI-1 group (p0.05). Histopathological results demonstrated severe leukemic infiltration in numerous organs in each group. Reverse transcription polymerase chain reaction (RT-PCR) assay showed that several organs expressed the MLL/F6 fusion gene. Moreover, the numbers of organs infiltrated by leukemic cells in S1, S2 and S3 groups were more than those in the SHI-1 group (p0.05). Up-regulating TIMP-2 expression enhanced SHI-1 cell invasion in nude mice and resulted in more severe leukemia infiltration. This phenomenon suggests that targeted therapy with TIMP-2 for acute leukemia should be performed with prudence.

Acute promyelocytic leukemia (APL) is a common myeloid leukemia. At the newly diagnosed stage, it can be fatal because of the serious complication-disseminated intravascular coagulation. With the advent and early application of all-trans retinoic acid, most APL patients can achieve a long-term survival, and only a minority of patients will develop extramedullary relapse after remission. The most common site of extramedullary relapse is central nervous system, while other sites are relatively rare. Here, we report a particularly rare APL patient who experienced extramedullary relapse with lumbar spine as the isolated site after a rather long time of remission for 16 years. At the time of relapse, the main clinical manifestations of the patient are obvious low back pain, weakness in lower limbs and limitation of activity. After treatment of local radiotherapy combined with ATRA and arsenic trioxide, the patient achieved and maintained a second complete remission by now.