Hematology

Wang, Xia; Zhang, Ye; Liu, Xuntao; Zhou, Sutao; Cheng, Peng; Zhang, Bizhu; Zhang, Bin

2024 Hematology

doi: 10.1080/16078454.2024.2416724

Objective The use of cobalt alloys in medical implants poses a high risk of cobalt exposure, yet there is a lack of evidence regarding the association between blood cobalt levels and anemia. This study aimed to explore the link between blood cobalt levels and the onset of anemia and to identify potential threshold levels of blood cobalt that could affect anemia. Methods The US National Health and Nutrition Examination Survey data from 2017 to 2020 were analyzed for this cross-sectional study. This study primarily employed multivariate logistic regression, stratified interaction analysis, restricted cubic splines (RCS), and threshold effect analysis to explore the relationship between blood cobalt concentration and anemia. Results The study included 5510 participants and among them 12.2% were diagnosed with anemia. Logistic regression model indicates a positive correlation between blood cobalt levels and the risk of anemia. RCS shows that the relationship between ln cobalt concentration and anemia was non-linear (J-shaped). The ln cobalt inflection point was approximately 0.81. The odds ratio of anemia with ln cobalt ≥ 0.81 was 4.00 (95% CI: 2.95–5.43, p < 0.001), the odds ratio of anemia with ln cobalt < 0.81 was 0.73 (95% CI: 0.45–1.18, p = 0.201). Conclusions The analysis unveiled a non-linear relationship, indicating that elevated blood cobalt levels were linked to a heightened likelihood of developing anemia in middle-aged and older adults; the cut-off value of ln cobalt was approximately 0.81. The findings of this study warrant further investigation.

Zhong, Xushu; Wang, Jia; Dai, Yang; Huang, Xiaoou; Liu, Jiazhuo; Xiang, Bing; Ma, Hongbing

2024 Hematology

doi: 10.1080/16078454.2024.2433172pmid: 39585800

The combination of venetoclax (VEN) with hypomethylating agents (HMAs) improves survival in patients with acute myeloid leukemia (AML) and may cause neutropenia requiring combined antifungal therapy or prophylaxis. The inhibition of cytochrome P450 activity by azole antifungal agents leads to elevated blood concentrations of VEN. This study aimed to evaluate the efficacy and safety of venetoclax plus azacitidine (AZA) with azoles in newly diagnosed AML patients. The primary endpoints included complete remission (CR), complete remission with incomplete blood cell recovery (CRi), composite CR (CRc, CR + CRi), blood cell recovery time and incidence of infections. The CRc was 50.0% in the azole group and 56% in the nonazole group (p > 0.05). In the azole group, the median recovery times for patients with ANC >500 cells/mm3 and ANC >1,000 cells/mm3 were 19 and 25 days, respectively. For the nonazole group, the corresponding times were 16 and 19 days (p < 0.05). In the azole group, the median durations for patients with a PLT >50,000/mm3 and >100,000/mm3 were 18 and 20 days, respectively. For the nonazole group, the corresponding times were 16 and 19 days (p > 0.05). The incidences of fungal and bacterial infections were not significantly different (30.8% vs 26.1% and 50.0% vs 56.0%) (p > 0.05). The cost-effectiveness ratio of the azole group is lower. There was no significant difference between VEN + AZA with or without azole in terms of efficacy, infection, or partial hematological toxicity. However, the combination of azoles may prolong the neutrophil recovery time. Azole combination could reduce the amount of venetoclax and improve health economics.

Liu, Yang; Zhang, Suqian; Tan, Yajuan

2024 Hematology

doi: 10.1080/16078454.2024.2337307pmid: 38573223

Objective: To study whether and, if so, how honokiol overcome dexamethasone resistance in DEX-resistant CEM-C1 cells. Methods: We investigated the effect of honokiol (0–20 µM) on cell proliferation, cell cycle, cell apoptosis and autophagy in DEX-resistant CEM-C1 cells and DEX-sensitive CEM-C7 cells. We also determined the role of c-Myc protein and mRNA in the occurrence of T-ALL associated dexamethasone resistance western blot and reverse transcription-qPCR (RT-qPCR) analysis. Results: Cell Counting Kit (CCK)−8 assay shows that DEX-resistant CEM-C1 cell lines were highly resistant to dexamethasone with IC50 of 364.1 ± 29.5 µM for 48 h treatment. However, upon treatment with dexamethasone in combination with 1.5 µM of honokiol for 48 h, the IC50 of CEM-C1 cells significantly decreased to 126.2 ± 12.3 µM, and the reversal fold was 2.88. Conversely, the IC50 of CEM-C7 cells was not changed combination of dexamethasone and honokiol as compared to that of CEM-C7 cells treated with dexamethasone alone. It has been shown that honokiol induced T-ALL cell growth inhibition by apoptosis and autophagy via downregulating cell cycle-regulated proteins (Cyclin E, CDK4, and Cyclin D1) and anti-apoptotic proteins BCL-2 and upregulating pro-apoptotic proteins Bax and led to PARP cleavage. Honokiol may overcome dexamethasone resistance in DEX-resistant CEM-C1 cell lines via the suppression of c-Myc mRNA expression. Conclusion: The combination of honokiol and DEX were better than DEX alone in DEX-resistant CEM-C1 cell lines. Honokiol may regulate T-ALL-related dexamethasone resistance by affecting c-Myc.

García-Vélez, Danae; Gallardo-Pérez, Moisés Manuel; Cruz-Pérez, Gloria Erendy; Melgar-de-la-Paz, Miranda; Hamilton-Avilés, Luis Enrique; Negrete-Rodríguez, Paola; Lira-Lara, Olivia; Robles-Nasta, Max; Olivares-Gazca, Juan Carlos; Garcés-Eisele, Solón Javier; Ruiz-Delgado, Guillermo J.; Ruiz-Argüelles, Guillermo Jose

2024 Hematology

doi: 10.1080/16078454.2024.2417517pmid: 39446050

The objective of this study is to explore the possibility of treating APL patients fully as outpatients. A total of 21 consecutive APL patients were identified over 30 years in the Centro de Hematología y Medicina Interna de Puebla, at Clínica Ruiz, but only 17 were studied, treated as outpatients, and followed for at least 1 month; they were observed for median of 95 months, their median age was 27 years and all were treated with ATRA, prednisone, and adriamycin as outpatients. Treatment was completed on an outpatient basis in 15/17 cases. Molecular remission was achieved in 16/17 patients. The median follow-up was 95 months (IQR 19 - 360). The median OS and LFS were not reached, and the 12-month LFS was 94%. We have confirmed that APL can be treated entirely on an outpatient basis: this observation is of utmost relevance in a resource-limited setting, such as those prevailing in low- and middle-income countries.

Hu, Miao; Ma, Yanfen; Jia, Keli; Liu, SaSa; Jing, Huarong; Li, Ruicheng

2024 Hematology

doi: 10.1080/16078454.2024.2377849pmid: 38994877

Objectives To explore the changes in the coagulation function of patients newly diagnosed with multiple myeloma (MM) at different stages and with different M protein types, and to analyze the correlation between coagulation indexes and β2-microglobulin (β2-MG). Methods A total of 371 Patients with newly diagnosed MM (n = 371) and healthy controls (n = 48) were selected from January 2016 to December 2022. Baseline data, β2-MG and coagulation index values were collected. Indexes included prothrombin time (PT), activated partial thromboplastin time (APPT), fibrinogen (FIB), thrombin time (TT), fibrinogen degradation products (FDP), and D-dimer(D-D). Patients were divided into different groups according to the Durie-Salmon staging system (DS), the International Staging System (ISS) and disease classification (M protein type). The levels of these six indexes were compared among the groups and the correlation between each index and β2-MG was analyzed. Results Compared to the normal control group, the levels of PT, FIB, TT, FDP and D-D in the MM group were significantly higher (all P < 0.001). As DS and ISS staging increased, the levels of PT, TT, FDP and D-D also increased significantly (all P < 0.001). β2-MG was positively correlated with PT, TT, and FDP levels (Spearman r = 0.157, 0.270, 0.108, respectively; all P < 0.05), and negatively correlated with FIB (r = −0.220, P < 0.001). Significant differences existed in the levels of these six indexes among different M protein types (all P < 0.001). Among them, PT and APTT increased significantly in the IgA-κ group, FIB increased in the λ light chain group, TT increased in the IgG-κ group, FDP increased in the κ light chain group, and D-D increased in the IgG-λ group. Conclusions The degree of coagulation dysfunction in MM patients increases with disease stage and abnormal increases of various coagulation indicators occur in different M protein types and are closely related to β2-MG.

Tachibana, Takayoshi; Tanaka, Masatsugu; Noguchi, Yuma; Najima, Yuho; Sadato, Daichi; Harada, Yuka; Tamai, Yotaro; Doki, Noriko; Nakajima, Hideaki

2024 Hematology

doi: 10.1080/16078454.2024.2360843pmid: 38828928

The outcomes of relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) resistant to new drugs such as tyrosine kinase inhibitors, inotuzumab ozogamicin (InO) and blinatumomab are dismal. We treated two cases of Ph+ALL resistant to these drugs that achieved long-term survival after treatment with chimeric antigen receptor (CAR)-T cell therapy or a second allogeneic hematopoietic stem cell transplantation (HCT) with a sequential conditioning regimen. Case 1: A 15-year-old boy was diagnosed with Ph+ALL. Despite the second HCT after the treatment of ponatinib and blinatumomab, hematological relapse occurred. InO was ineffective and he was transferred to a CAR-T center. After the CAR-T cell therapy, negative measurable residual disease (MRD) was achieved and maintained for 38 months without maintenance therapy. Case 2: A 21-year-old man was diagnosed with Ph+ALL. Hematological relapse occurred after the first HCT. Despite of the treatment with InO, ponatinib, and blinatumomab, hematological remission was not achieved. The second HCT was performed using a sequential conditioning regimen with clofarabine. Negative MRD was subsequently achieved and maintained for 42 months without maintenance therapy. These strategies are suggestive and helpful to treat Ph+ALL resistant to multiple immunotherapies.

Yang, Jiapeng; Zhu, Xiaohua; Zhang, Honghong; Fu, Yang; Li, Zifeng; Xing, Ziping; Yu, Yi; Cao, Ping; Le, Jun; Jiang, Junye; Li, Jun; Wang, Hongsheng; Qian, Maoxiang; Zhai, Xiaowen

2024 Hematology

doi: 10.1080/16078454.2024.2381169pmid: 39046131

Background: Acute myeloid leukemia (AML) with t(8;21) manifests as a diverse hematological malignancy. Although it was categorized into a favorable subtype, 30–40% of patients experience relapse. The objective of this research was to devise a nomogram for the accurate anticipation of both overall survival (OS) and cancer-specific survival (CSS) in t(8;21) AML. Methods: From the Surveillance, Epidemiology, and End Results (SEER) database, individuals diagnosed with t(8;21) AML from 2000 to 2018 were selected. Prognostic factors for t(8;21) AML were identified using Cox regression analysis and Akaike Information Criterion (AIC), forming the basis for constructing prognostic nomograms. Results: Key variables, including first primary tumor, age group, race, and chemotherapy, were identified and integrated into the nomogram. The C-index values for the nomograms predicting OS and CSS were 0.753 (validation: 0.765) and 0.764 (validation: 0.757), respectively. Ultimately, based on nomogram scores, patients were stratified into high-risk and low-risk groups, revealing significant disparities in both OS and CSS between these groups (P < 0.001). Conclusion: This study innovatively crafted nomograms, incorporating clinical and therapeutic variables, to forecast the 1-, 3-, and 5-year survival rates for individuals with t(8;21) AML.

Zhang, Wenxue; Chen, Xian; Wang, Zhe; Wang, Qing; Feng, Jiao; Wang, Dexin; Wang, Zhichao; Tang, Jiaxin; Qing, Shiyu; Zhang, Yunyuan

2024 Hematology

doi: 10.1080/16078454.2024.2335421pmid: 38568025

Objectives Identifying the specific biomarkers and molecular signatures of MM might provide novel evidence for MM prognosis and targeted therapy. Methods Bioinformatic analyses were performed through GEO and TCGA datasets. The differential expression of HIST1H2BH in MM sample was validated by the qRT-PCR. And the CCK-8 assay was performed to detect the proliferation activity of HIST1H2BH on MM cell lines. Results A total of 793 DEGs were identified between bone marrow plasma cells from newly diagnosed myeloma and normal donors in GSE6477. Among them, four vital genes (HIST1H2AC, HIST1H2BH, CCND1 and TCF7L2) modeling were constructed. The increased HIST1H2BH expression was correlated with worse survival of MM based on TCGA datasets. The transcriptional expression of HIST1H2BH was significantly up-regulated in primary MM patients. And knockdown HIST1H2BH decreased the proliferation of MM cell lines. Conclusions We have identified up-regulated HIST1H2BH in MM patients associated with poor prognosis using integrated bioinformatical methods.

Xin, Fei; Yu, Yan-Hui; Shen, Xu-Liang; Zhang, Guo-Xiang

2024 Hematology

doi: 10.1080/16078454.2024.2350319pmid: 38748459

Objectives: The purpose of this study was to compare the effectiveness of the combination of venetoclax and hypomethylating agents with the HAG regimen. Methods: We studied 52 cases of newly diagnosed AML and 26 cases of relapsed refractory AML, (including AML patients with treatment-related and ELN-adverse risk disease (n = 50)). These patients were treated with venetoclax and hypomethylating agents and HAG regimens, respectively. Results: Twenty-nine patients newly diagnosed with acute myeloid leukemia were treated with VEN-HMA (venetoclax-hypomethylating agent), while 23 patients were treated with HAG. The median age of the VEN-HMA group was 70 years, while the HAG group had a median age of 69 years. The VEN-HMA group achieved a significantly higher rate of complete remission (82.7%) compared to the cohort treated with the HAG regimen (21.7%) (P < 0.001). At the same time, the VEN-HMA group exhibited a significant survival advantage compared to the HAG treatment group(HR = 0.328, 95%CI: 0.158-0.683, P = 0.003). In patients with relapsed and refractory acute myeloid leukaemia, 43.8% of patients in the VEN-HMA treatment group achieved complete remission, which was similar to the 50% in the HAG treatment group (P > 0.99). The median overall survival was similar between the VEN-HMA and HAG groups, with 4 and 3.67 months, respectively (P = 0.290). Conclusions: In conclusion, our analyses indicated that VEN-HMA resulted in better therapeutic outcomes compared to HAG for newly diagnosed AML patients, with higher rates of complete remission and overall survival. In relapsed/refractory AML patients, there was no significant difference in the efficacy of the two treatments and further studies with larger sample sizes are warranted.

Bhattarai, Abhinav; Shah, Sangam; Yadav, Rukesh; Dhakal, Garima; Neupane, Raksha; Paudel, Sunil; Bhandari, Pragya; Abu Serhan, Hashem; Sah, Ranjit; Sah, Sanjit; Barboza, Joshuan J.

2024 Hematology

doi: 10.1080/16078454.2023.2293497pmid: 38112182

Background and objective: Graft versus host disease (GVHD) is the common complication seen after allogeneic hematopoietic stem cell transplantation (HSCT) and a pleomorphic syndrome that resembles autoimmune and other immunologic disorders, leading to profound immune dysregulation and organ dysfunction. The most common targets of GVHD are skin, gastrointestinal tract and liver. GVHD is classified as acute graft versus host disease (aGvHD) if it occurs within the first 100 days after HSCT and chronic graft versus host disease(cGVHD) if it occurs after day 100. The skin is most frequently and earliest affected by aGvHD, followed by the gastrointestinal tract and liver. An ideal biomarker would predict the onset and severity of clinical acute GVHD and help to direct management, and this is an area of active research regarding the use of biomarkers for diagnosis and prognosis of acute GVHD. Recently, elafin has been identified as a potential plasma biomarker for aGVHD. Method: We searched the databases PubMed, Cochrane library, and medRxiv for all studies investigating the Diagnostic or prognostic role of elafin in GVHD. We set the search strategy incorporating the search terms, ‘elafin’, ‘graft versus host’, and ‘GVHD’, and operated using the Boolean operators ‘AND’, and ‘OR’. Thus, retrieved articles were then exported on an Excel® sheet, and duplicates were removed. The systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After selecting the study based on inclusion criteria, data on study characteristics and biomarker description was extracted on a pre-determined data extraction table on the Microsoft Excel version. The quality assessment of the included studies was determined using the QUIPS tool. Result: The search revealed 547 studies and 6 studies that met the eligibility criteria of this review have been included. The major finding of our study is the significant elevation of elafin in skin aGVHD. Conclusion: Elafin is a significant biomarker for diagnosis and prognosis of skin aGVHD and should be assessed within 2 weeks of the onset of the disease.