Hematologic Malignancies
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Moraima Jiménez ◽  
Elisa Roldan ◽  
Candela Fernández- Naval ◽  
Guillermo Villacampa ◽  
Monica Martinez-Gallo ◽  

Recent studies have demonstrated a suboptimal humoral response to SARS-CoV-2 mRNA vaccines in patients diagnosed with hematologic malignancies, however data about cellular immunogenicity is scarce. In this study we aimed to evaluate both the humoral and cellular immunogenicity one month after the second dose of the mRNA-1273 vaccine. Antibody titers were measured by the Elecsys and LIAISON Anti-SARS-CoV-2 S assay while T-cell response was assessed by Interferon-Gamma-Release-immuno-Assay technology. Overall, 76.3% (184/241) of patients developed humoral immunity and the cellular response rate was 79% (184/233). Hypogammaglobulinemia, lymphopenia, active hematological treatment and anti-CD20 therapy during the last 6 months were associated with an inferior humoral response. Conversely, age over 65 years, active disease, lymphopenia and immunosuppressive treatment for GvHD were associated with an impaired cellular response. A significant dissociation between humoral and cellular response was observed in patients treated with anti-CD20 therapy, being the humoral response of 17.5% whereas the cellular response was 71.1%. In these patients B-cell aplasia was confirmed while T cell counts were preserved. In contrast, humoral response was observed in 77.3% of patients under immunosuppressive treatment for GvHD, while only 52.4% had cellular response. The cellular and humoral response to the SARS-CoV-2 mRNA-1273 vaccine in patients with hematological malignancies is highly influenced by the presence of treatments like anti-CD20 therapy and immunosuppressive agents. This observation has implications for the further management of these patients.

Ari Pelcovits ◽  
Adam J. Olszewski ◽  
Dominic Decker ◽  
Dana Guyer ◽  
Thomas W. Leblanc ◽  

Children ◽  
2021 ◽  
Vol 8 (12) ◽  
pp. 1083
Hye-ji Han ◽  
Kyung Taek Hong ◽  
Hyun Jin Park ◽  
Bo Kyung Kim ◽  
Hong Yul An ◽  

It is complicated to establish a consensus on the management and diagnosis of malignancy-triggered hemophagocytic lymphohistiocytosis (M-HLH) in children, as an initial presentation of malignancy is complicated. In this paper, we analyze the clinical characteristics and outcomes of eight pediatric patients in which M-HLH was the initial presentation of malignancy. All patients had hematologic malignancies: three subcutaneous panniculitis-like T-cell lymphomas, two acute lymphoblastic leukemias, two anaplastic large cell lymphomas, and a systemic EBV + T-cell lymphoma of childhood. The incidence rate of M-HLH among leukemia and malignant lymphoma patients in our institution was 1.9%. From the initial diagnosis of HLH, the median time taken to be diagnosed as a malignancy was about 1.3 months. The majority of patients received HLH-targeted immunosuppression and/or etoposide at first. The patients’ clinical response to treatment for HLH and malignancies were varied. Five out of the eight patients died, one of whom died due to HLH-related cerebral edema after the initiation of chemotherapy. The median overall survival was 1.6 years. In order to improve the survival rate, the early detection of M-HLH, rapid screening for malignancy, and complete control of M-HLH with HLH-directed therapy followed by a thorough response monitoring are required.

2021 ◽  
Vol 12 ◽  
Weihao Wang ◽  
Tao Hong ◽  
Xiaoqi Wang ◽  
Rui Wang ◽  
Yuxuan Du ◽  

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most effective and potentially curative treatment for a variety of hematologic malignancies. However, graft-versus-host disease (GVHD) is a major obstacle that limits wide application of allo-HSCT, despite the development of prophylactic strategies. Owing to experimental and clinical advances in the field, GVHD is characterized by disruption of the balance between effector and regulatory immune cells, resulting in higher inflammatory cytokine levels. A reduction in regulatory T cells (Tregs) has been associated with limiting recalibration of inflammatory overaction and maintaining immune tolerance. Moreover, accumulating evidence suggests that immunoregulation may be useful for preventing GVHD. As opposed to CD4+ Tregs, the CD8+ Tregs population, which constitutes an important proportion of all Tregs, efficiently attenuates GVHD while sparing graft-versus-leukemic (GVL) effects. CD8+ Tregs may provide another form of cellular therapy for preventing GVHD and preserving GVL effects, and understanding the underlying mechanisms that different from those of CD4+ Tregs is significant. In this review, we summarize preclinical experiments that have demonstrated the role of CD8+ Tregs during GVHD and attempted to obtain optimized CD8+ Tregs. Notably, although optimized CD8+ Tregs have obvious advantages, more exploration is needed to determine how to apply them in the clinic.

2021 ◽  
Mohammad-Mehdi Mehrabinejad ◽  
Fatemeh Moosaie ◽  
Hojat Dehghanbanadaki ◽  
Abdolkarim Hajighadery ◽  
Mahya Shabani ◽  

Abstract Background Immunocompromised (IC) patients are at higher risk of severe SARS-CoV-2 infection, morbidity, and mortality compared to general population. They should be prioritized for primary prevention through vaccination. In this study, we aimed to evaluate the efficacy of COVID-19 mRNA vaccines in IC patients through a systematic review and meta-analysis approach. Method PubMed-MEDLINE, Scopus, and Web of Science were searched for original articles reporting the immunogenicity of two doses of mRNA COVID-19 vaccines in adult patients with IC condition between June 1, 2020 and September 1, 2021. Meta-analysis was performed using either random or fixed effect according to the heterogeneity of the studies. Subgroup analysis was performed to identify potential sources of heterogeneity. Results A total of 26 studies on 3207 IC patients and 1726 healthy individuals were included. The risk of seroconversion in IC patients was 48% lower than those in controls (RR= 0.52 [0.42, 0.65]). IC patients with autoimmune condition were 54% and patients with malignancy were 42% more likely to have positive seroconversion compared to those with transplant (P<0.01). Subgroup meta-analysis based on type of malignancy, revealed significantly higher proportion of positive seroconversion in solid organ compared to hematologic malignancies (RR= 0.88 [0.85, 0.92] vs. 0.61 [0.44, 0.86], P= 0.03). Subgroup meta-analysis based on type of transplantation (kidney vs. others), showed no statically significant between group difference of seroconversion (P= 0.55). Conclusions IC patients, especially transplant patients, developed lower immunogenicity with two-dose of COVID-19 mRNA vaccines. Among patients with IC, those with autoimmune condition and solid organ malignancies are mostly benefited from COVID-19 vaccination. Findings from this meta-analysis, could aid health care policy makers upon making decision regarding the importance of the booster dose or more strict personal protections in the IC patients.

Blood ◽  
2021 ◽  
Margaret A Ferris ◽  
Amanda M Smith ◽  
Sharon E Heath ◽  
Eric J Duncavage ◽  
Matthew J Oberley ◽  

DNMT3A Overgrowth Syndrome (DOS, also known as Tatton-Brown Rahman Syndrome/TBRS) is one of several overgrowth syndromes with complex phenotypes caused by constitutional mutations in genes encoding epigenetic regulators. The clinical features of DOS are variable but include overgrowth (tall stature and/or obesity) and intellectual disability. DNMT3A is essential for de novo DNA methylation and plays an important role in hematopoiesis. Somatic mutations in DNMT3A are among the most common initiating mutations in normal karyotype acute myeloid leukemia (AML) patients and in elderly people with clonal hematopoiesis. The natural history of DOS has not been fully explored since the first description of this rare condition in 2014. Because of the association of somatic DNMT3A mutations and leukemia development, we assessed information from the ~200 known DOS patients world-wide and were able to document eight with hematologic malignancies. Based on this prevalence, we suggest DOS is a cancer predisposition syndrome, especially for hematologic malignancies. Using recommendations from an expert panel, we suggest DOS patients should be prospectively monitored for hematologic malignancies, which may allow for early intervention and permit its natural history to be better defined.

Cureus ◽  
2021 ◽  
Jose C Alvarez-Payares ◽  
Angel Molina ◽  
Simon Gallo ◽  
Julian Ramirez ◽  
Juan Hernandez ◽  

Scott W. Strum ◽  
Laszlo Gyenis ◽  
David W. Litchfield

AbstractProtein kinase CSNK2 (CK2) is a pleiotropic serine/threonine kinase frequently dysregulated in solid and hematologic malignancies. To consolidate a wide range of biological and clinically oriented data from this unique kinase in cancer, this systematic review summarises existing knowledge from in vitro, in vivo and pre-clinical studies on CSNK2 across 24 different human cancer types. CSNK2 mRNA transcripts, protein levels and activity were found to be routinely upregulated in cancer, and commonly identified phosphotargets included AKT, STAT3, RELA, PTEN and TP53. Phenotypically, it frequently influenced evasion of apoptosis, enhancement of proliferation, cell invasion/metastasis and cell cycle control. Clinically, it held prognostic significance across 14 different cancers, and its inhibition in xenograft experiments resulted in a positive treatment response in 12. In conjunction with commentary on preliminary studies of CSNK2 inhibitors in humans, this review harmonises an extensive body of CSNK2 data in cancer and reinforces its emergence as an attractive target for cancer therapy. Continuing to investigate CSNK2 will be crucial to advancing our understanding of CSNK2 biology, and offers the promise of important new discoveries scientifically and clinically.

Istemi Serin ◽  
Mehmet Hilmi Dogu

Aim: The objective of this article was to compare the efficiency of azacitidine (AZA) and decitabine (DAC) in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) who are not suitable for high-dose chemotherapy. Materials and methods: MDS and AML patients who were treated with hypomethylating agents (HMAs) between January 2005 and 2020 were evaluated retrospectively. Results: No statistically significant difference was found between the patients who received AZA or DAC in AML patients. In MDS group, the rate of patients who achieved remission was statistically significantly higher in patients who received DAC (p = 0,032). Conclusion: The advantage in terms of response for MDS and no survival difference between AZA and DAC for AML and MDS patients will be an important contribution to the literature.

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