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Current Oncology Reports Aug 2023This article summarizes the current state of knowledge of hairy cell leukemia (HCL) regarding presentation, diagnosis, therapy, and monitoring, including perspectives on... (Review)
Review
PURPOSE OF REVIEW
This article summarizes the current state of knowledge of hairy cell leukemia (HCL) regarding presentation, diagnosis, therapy, and monitoring, including perspectives on emergent therapies.
RECENT FINDINGS
Over the past decade, there has been enormous progress in the understanding of the biology of HCL which has led to the development of novel therapeutic strategies. The maturation of data regarding existing management strategies has also lent considerable insight into therapeutic outcomes and prognosis of patients treated with chemo- or chemoimmunotherapy. Purine nucleoside analogs remain the cornerstone of treatment, and the addition of rituximab has deepened and prolonged responses in the upfront and relapsed setting. Targeted therapies now have a more defined role in the management of HCL, with BRAF inhibitors now having a potential in the first-line setting in selected cases as well as in relapse. Next-generation sequencing for the identification of targetable mutations, evaluation of measurable residual disease, and risk stratification continue to be areas of active investigation. Recent advances in HCL have led to more effective therapeutics in the upfront and relapsed setting. Future efforts will focus on identifying patients with high-risk disease who require intensified regimens. Multicenter collaborations are the key to improving overall survival and quality of life in this rare disease.
Topics: Humans; Leukemia, Hairy Cell; Antineoplastic Agents; Quality of Life; Rituximab; Prognosis; Multicenter Studies as Topic
PubMed: 37097545
DOI: 10.1007/s11912-023-01419-z -
Advances in Hematology 2023Graft-versus-host disease (GVHD) is a potentially fatal complication of allogeneic hematopoietic stem cell transplant. The mainstay of treatment is corticosteroids,... (Review)
Review
BACKGROUND
Graft-versus-host disease (GVHD) is a potentially fatal complication of allogeneic hematopoietic stem cell transplant. The mainstay of treatment is corticosteroids, which are ineffective in 30-50% of cases. Steroid-refractory GVHD (SR-GVHD) confers a poor prognosis, with high mortality rates despite appropriate therapy. While there is no reliable treatment for SR-GVHD, a variety of novel therapeutic options are slowly emerging and have yet to be examined simultaneously.
OBJECTIVES
This review evaluates the potential of novel therapeutic options, as well as their efficacy and safety, for the treatment of SR-GVHD. . The literature search was conducted in PubMed, Cochrane, and Embase, employing MeSH terms and keywords. The studies had to be prospective phases 1, 2, or 3. We excluded retrospective and nonoriginal studies.
RESULTS
While the only approved drug for acute GVHD is ruxolitinib with an impressive overall response rate of 73.2% and a complete response of 56.3%, several monoclonal antibodies and other agents are currently under investigation, offering promising results. These include anti-CD2, anti-CD147, IL-2 antagonist, a mixture of anti-CD3 and anti-CD7 antibodies, anti-CD25, monoclonal antibody to a4b7 on T-cells, anti-CD26, pentostatin, sirolimus, denileukin diftitox, infliximab, itacitinib, and alpha-1 antitripsin. However, the toxicities associated with these novel drugs need further investigation. For chronic GVHD, approved options include ruxolitinib with an ORR of up to 62%, ibrutinib with an ORR of up to 77%, and belumosudil with an ORR of up to 77%. Meanwhile, emerging treatments include tyrosine kinase inhibitors such as nilotinib, rituximab, and low-dose IL-2, as well as axatilimab and pomalidomide.
CONCLUSION
While their efficacy needs to be better evaluated through large-scale, multicenter, randomized clinical trials, these novel agents show potential and could provide a better alternative for SR-GVHD treatment in the future.
PubMed: 38094101
DOI: 10.1155/2023/9949961 -
Frontiers in Immunology 2023Arecoline is an alkaloid extracted from betel nut, which has various pharmacological effects. In the present study, we showed that arecoline aggravated experimental...
Arecoline is an alkaloid extracted from betel nut, which has various pharmacological effects. In the present study, we showed that arecoline aggravated experimental acute ulcerative colitis (UC) induced by dextran sodium sulfate (DSS) in mice. We measured body weight and colon length, evaluated disease activity index, colon pathology sections, and levels of colonic inflammatory factors. Arecoline exacerbated the clinical signs of UC and the colonic inflammatory response in mice. The results of 16S rRNA sequencing of fecal samples showed a significant decrease in the percentage of probiotic bacteria , and and a significant increase in the percentage of conditionally pathogenic bacteria and after arecoline treatment. Serum untargeted metabolomics showed that arecoline intervention reduced the levels of ergothioneine, pentostatin, diadenosine tetraphosphate and other metabolites and modulated nicotinate and nicotinamide metabolism, metabolic pathways, glyoxylate and dicarboxylate metabolism, and other metabolic pathways of intestinal microorganisms. According to the combined microbial and metabolite analysis, arecoline influences metabolite levels by modulating the intestinal microbiota. In summary, it was found that arecoline treatment exacerbated colonic injury and intestinal inflammatory responses in UC mice, disrupted the host's intestinal flora, and affected changes in flora metabolites, thereby exacerbating the development of colonic inflammation. Therefore, the consumption of betel nut can be associated with the risk of aggravating UC.
Topics: Animals; Mice; Colitis, Ulcerative; Arecoline; Gastrointestinal Microbiome; RNA, Ribosomal, 16S
PubMed: 37492574
DOI: 10.3389/fimmu.2023.1197922 -
Current Oncology (Toronto, Ont.) Nov 2023T-prolymphocytic leukemia (T-PLL) is a rare malignancy of mature T-cells with distinct clinical, cytomorphological, and molecular genetic features. The disease typically... (Review)
Review
T-prolymphocytic leukemia (T-PLL) is a rare malignancy of mature T-cells with distinct clinical, cytomorphological, and molecular genetic features. The disease typically presents at an advanced stage, with marked leukocytosis, B symptoms, hepatosplenomegaly, and bone marrow failure. It usually follows an aggressive course from presentation, and the prognosis is often considered dismal; the median overall survival is less than one year with conventional chemotherapy. This case report describes a patient with T-PLL who, after an unusually protracted inactive phase, ultimately progressed to a highly invasive, organ-involving disease. After initial treatments failed, a novel treatment approach resulted in a significant response.
Topics: Humans; Alemtuzumab; Leukemia, Prolymphocytic; Leukemia, Prolymphocytic, T-Cell
PubMed: 37999147
DOI: 10.3390/curroncol30110727 -
Frontiers in Oncology 2023Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of CD19 CD5 clonal B lymphocytes in the blood, bone marrow, and peripheral lymphoid organs....
Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of CD19 CD5 clonal B lymphocytes in the blood, bone marrow, and peripheral lymphoid organs. Treatment options for patients range from historical chemoimmunotherapy (CIT) to small molecule inhibitors targeting pro-survival pathways in leukemic B cells, such as the Bruton's tyrosine kinase inhibitor ibrutinib (IBR). Using biobanked blood samples obtained pre-therapy and at standard response evaluation timepoints, we performed an in-depth evaluation of the blood innate and adaptive immune compartments between pentostatin-based CIT and IBR and looked for correlations with clinical sequelae. CD4 conventional T cells and CD8 cytotoxic T cells responded similarly to CIT and IBR, although exhaustion status differed. Both treatments dramatically increased the prevalence and functional status of monocyte, dendritic cell, and natural killer cell subsets. As expected, both regimens reduced clonal B cell levels however, we observed no substantial recovery of normal B cells. Although improvements in most immune subsets were observed with CIT and IBR at response evaluation, both patient groups remained susceptible to infections and secondary malignancies during the study.
PubMed: 38111528
DOI: 10.3389/fonc.2023.1302038 -
Cureus Oct 2023Hairy cell leukemia variant (HCLv) is a sporadic, B-cell non-Hodgkin lymphoma classified under chronic lymphoproliferative disorders. HCLv usually presents with easy...
Hairy cell leukemia variant (HCLv) is a sporadic, B-cell non-Hodgkin lymphoma classified under chronic lymphoproliferative disorders. HCLv usually presents with easy fatigue, dragging pain abdomen, anemia, splenomegaly, hepatomegaly, initially leukocytosis followed by leucopenia, hairy cells in the smear and bone marrow, and an increased risk of infections. There is hypercellular bone marrow, and cytopenias are secondary to hypersplenism. It is essential to differentiate HCL from disorders like classic hairy cell leukemia (HCLc), splenic marginal zone lymphoma, and splenic diffuse red pulp lymphoma, as these are biologically different, with divergent approaches and outcomes. HCLv is poorly responsive or primary refractory to standard purine analogs cladribine or pentostatin. It has lower response rates to even cladribine and rituximab combination, a standard of care for classic HCL with very good response rates. Here, we present a case of an elderly male who presented with splenomegaly and leukocytosis, diagnosed as HCLv, and was treated with a cladribine and rituximab-based regime but showed residual cells in bone marrow on flow cytometry at six months post-treatment. There were no residual cells in peripheral blood in flow cytometry. Various aspects of the disease are discussed here with a detailed literature analysis. There is a definite unmet need for research on better treatment options in HCLv to improve its overall outcome.
PubMed: 38022018
DOI: 10.7759/cureus.47085