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Hemato, Volume 4, Issue 2 (June 2023) – 5 articles

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12 pages, 667 KiB  
Review
Renal Disorders Associated with Waldenström Macroglobulinaemia, IgM MGUS and IgM-Producing B-Cell Lymphoproliferative Disorders
by Guy Pratt, Hannah V. Giles and Jennifer H. Pinney
Hemato 2023, 4(2), 184-195; https://doi.org/10.3390/hemato4020015 - 14 Jun 2023
Viewed by 1695
Abstract
Renal disorders are uncommonly associated with IgM MGUS and Waldenström macroglobulinaemia (WM). Data are limited to large case series that suggest that related renal involvement occurs in 5% of patients with WM. Although uncommon, there is a much greater variety of renal pathologies [...] Read more.
Renal disorders are uncommonly associated with IgM MGUS and Waldenström macroglobulinaemia (WM). Data are limited to large case series that suggest that related renal involvement occurs in 5% of patients with WM. Although uncommon, there is a much greater variety of renal pathologies associated with WM and IgM MGUS than that seen in patients with multiple myeloma, where cast nephropathy predominates. In WM, uncommonly direct infiltration of the renal system by lymphoma or cast nephropathy with a high light-chain level can occur. AL amyloidosis can present with nephrotic syndrome as a feature with IgM MGUS or WM. Cryoglobulinaemia and light-chain deposition disease are other important potential causes of renal impairment with IgM MGUS and WM. There are other rarer monoclonal gammopathy of renal significance (MGRS) conditions characterised by typically isolated kidney disease that are causally related to a B-cell or plasma-cell clonal disorder usually in a precancerous MGUS state, although in some renal pathologies, the association is less clear. Central to the majority of these diagnoses is the need for an accurate renal histological diagnosis, and management requires close joint working of renal and haematology teams. Full article
(This article belongs to the Special Issue Waldenström Macroglobulinaemia and Related Conditions)
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14 pages, 1004 KiB  
Review
SARS-CoV-2 Immunity in Hematopoietic Stem Cell Transplant and Cell Therapy Recipients: What Do We Know, and What Remains to Be Determined?
by José Luis Piñana, Manuel Guerreiro and Carlos Solano
Hemato 2023, 4(2), 170-183; https://doi.org/10.3390/hemato4020014 - 26 May 2023
Cited by 1 | Viewed by 1733
Abstract
Hematopoietic stem cell transplantation (HSCT) results in profound immunosuppression for the first few months after the procedure, requiring patients to be revaccinated against childhood vaccine-preventable infectious diseases. Patients who undergo allo-HSCT are at high risk of bacterial, fungal, and viral infections, with infectious [...] Read more.
Hematopoietic stem cell transplantation (HSCT) results in profound immunosuppression for the first few months after the procedure, requiring patients to be revaccinated against childhood vaccine-preventable infectious diseases. Patients who undergo allo-HSCT are at high risk of bacterial, fungal, and viral infections, with infectious complications responsible for at least one third of deaths. Even before the COVID-19 pandemic, respiratory virus infections were known to be more severe in HSCT recipients. The pandemic has highlighted the vulnerability of HSCT recipients, who experience an increased risk of morbidity and mortality after COVID-19 compared with healthy populations due to their severe immunodeficiency status. However, the current pandemic has also provided an exceptional scenario to better understand the immune response to SARS-CoV-2 cases and mRNA vaccines in HSCT recipients, including those receiving CD19-directed chimeric antigen receptor T cell (CAR-T) therapy. Researchers have focused on the role of the immune system in protecting against severe SARS-CoV-2 in patients with hematologic malignancies, including HSCT recipients. Insights gained during the pandemic will likely soon be used to improve preventive strategies in this population against viral infections in the near future. This narrative review summarizes the current knowledge on SARS-CoV-2 immunity in HSCT and cell therapy recipients following SARS-CoV-2 cases or vaccination. Full article
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12 pages, 814 KiB  
Review
Use of Letermovir for CMV Prophylaxis after Allogeneic Hematopoietic Stem Cell Transplantation: Review of the Literature and Single-Center Real-Life Experience
by Jessica Gill, Davide Stella, Irene Dogliotti, Chiara Dellacasa, Luisa Giaccone and Alessandro Busca
Hemato 2023, 4(2), 158-169; https://doi.org/10.3390/hemato4020013 - 28 Apr 2023
Cited by 1 | Viewed by 2004
Abstract
Cytomegalovirus (CMV) reactivation after allogeneic hematopoietic stem cell transplant (allo-HSCT) is mainly due to an increase of latent viremia in previously exposed patients. Furthermore, CMV reactivation in this setting has a significant impact on patient survival. Traditional approach to CMV reactivation post allo-HSCT [...] Read more.
Cytomegalovirus (CMV) reactivation after allogeneic hematopoietic stem cell transplant (allo-HSCT) is mainly due to an increase of latent viremia in previously exposed patients. Furthermore, CMV reactivation in this setting has a significant impact on patient survival. Traditional approach to CMV reactivation post allo-HSCT was a pre-emptive treatment with antivirals in the case of increased viremia. However, since 2017, a new antiviral compound, letermovir, has been introduced in clinical practice and is deeply changing the common CMV approach. The toxicity profile of letermovir allowed its use in prophylaxes in patients at high risk of CMV reactivation. This review will focus on the present role of letermovir post allo-HSCT and discuss some possible future applications of the drug. Finally, our single center CMV management in view of the recent introduction of letermovir will be discussed. Full article
23 pages, 1700 KiB  
Review
BTK Inhibitors and Other Targeted Therapies in Waldenström Macroglobulinemia
by Karan L. Chohan and Prashant Kapoor
Hemato 2023, 4(2), 135-157; https://doi.org/10.3390/hemato4020012 - 13 Apr 2023
Cited by 1 | Viewed by 2752
Abstract
Waldenström macroglobulinemia (WM) is a rare, non-Hodgkin lymphoma that remains incurable. Rituximab, an anti-CD20 monoclonal antibody has been the cornerstone of treatment against WM, and its combination with an alkylator, bendamustine, achieves durable remission in treatment-naive patients with symptomatic WM. However, novel “druggable” [...] Read more.
Waldenström macroglobulinemia (WM) is a rare, non-Hodgkin lymphoma that remains incurable. Rituximab, an anti-CD20 monoclonal antibody has been the cornerstone of treatment against WM, and its combination with an alkylator, bendamustine, achieves durable remission in treatment-naive patients with symptomatic WM. However, novel “druggable” targets that have been identified within the clonal lymphoplasmacytic cells in WM have resulted in a rapid development of targeted therapies in both the frontline and relapsed and refractory (R/R) settings. Several agents directed against the known targets have shown promising efficacy, with mostly manageable toxicities. The class of Bruton’s tyrosine kinase (BTK) inhibitors has transformed the therapeutic landscape for patients with WM, given their convenient oral dosing and strong efficacy, with high rates of attainment of very good partial response (VGPR). The tolerability of the next-generation BTK inhibitors appears to be superior to that of the first-in-class agent, ibrutinib. Targeted therapies from other classes have also demonstrated efficacy in both single-agent and combination regimens. Inhibitors of proteasome BCL-2, mTOR and PI-3 kinase have demonstrated efficacy in WM. Emerging therapies under investigation will continue to further shape the management paradigm, especially in the R/R setting. These include bispecific antibodies, radiotherapeutic agents and chimeric antigen receptor T-cell (CART) cell therapies. This review outlines the current literature and future direction of targeted therapies in WM. Full article
(This article belongs to the Special Issue Waldenström Macroglobulinaemia and Related Conditions)
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23 pages, 1955 KiB  
Perspective
What’s New in the Classification, Diagnosis and Therapy of Myeloid Leukemias
by Marco Pizzi, Carmela Gurrieri and Attilio Orazi
Hemato 2023, 4(2), 112-134; https://doi.org/10.3390/hemato4020011 - 29 Mar 2023
Viewed by 11495
Abstract
Myeloid leukemias are a broad group of hematological disorders, characterized by heterogeneous clinical and biological features. In recent years, unprecedented genetic discoveries and clinical–biological correlations have revolutionized the field of myeloid leukemias. The most relevant changes have specifically occurred in acute myeloid leukemia [...] Read more.
Myeloid leukemias are a broad group of hematological disorders, characterized by heterogeneous clinical and biological features. In recent years, unprecedented genetic discoveries and clinical–biological correlations have revolutionized the field of myeloid leukemias. The most relevant changes have specifically occurred in acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML), chronic myeloid leukemia (CML) and myeloid neoplasms (MNs) with eosinophilia. The recently published International Consensus Classification (ICC) of myeloid neoplasms has addressed these changes, providing an updated framework and revised diagnostic criteria for such entities. This is also the aim of the 5th edition of the WHO classification of hematopoietic tumors, whose preliminary version was published in 2022. Parallel to this, new therapeutic options and novel molecular targets have changed the management of many myeloid entities, including AML and CML. This review aims to address the most relevant updates in the classification and diagnosis of AML, CMML, CML and MNs with eosinophilia. The state of the art of treatment and future therapeutic options for such disorders are also discussed. Full article
(This article belongs to the Section Leukemias)
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