Acta Haematologica最新文献

{"title":"Acute Febrile Neutrophilic Dermatosis (Sweet Syndrome) in Acute Myeloid Leukemia Patients: A 28-Year Institutional Experience.","authors":"Emily A Cowen, Dulce M Barrios, Melissa P Pulitzer, Andrea P Moy, Stephen W Dusza, Susan De Wolf, Mark B Geyer, Alina Markova","doi":"10.1159/000535399","DOIUrl":"10.1159/000535399","url":null,"abstract":"<p><strong>Introduction: </strong>Sweet syndrome (SS) is well known to be associated with underlying hematologic malignancies. The incidence and qualities of SS among novel targeted therapies for acute myeloid leukemia (AML) have not yet been described.</p><p><strong>Methods: </strong>Through retrospective review of 19,432 patients diagnosed with acute/chronic leukemia or myelodysplastic syndromes/myeloproliferative neoplasms (MDS+/-MPN) over 28 years, we calculated the incidence of SS in the setting of select hematologic malignancies and described the clinicopathologic characteristics of SS in patients with onset of SS after initiation of novel AML-targeted therapies.</p><p><strong>Results: </strong>Overall incidence of SS was 0.36% (95% CI: 0.27-0.45%), which was significantly higher among patients with AML (50/5,248, 0.94%; 95% CI: 0.71-1.25%). Nine AML patients were on 4 classes of novel targeted treatments - IDH1/2 inhibitor alone, FLT3 inhibitor, IDH2 and DOT1L inhibitor, and anti-CD33 therapy. In therapies inducing myeloid blast differentiation, SS occurred at later onset following treatment.</p><p><strong>Conclusions: </strong>In AML patients with fever and unusual skin lesions, physicians may consider SS earlier, which may shorten time to diagnosis. Future assessments of SS among patients treated with novel therapies for AML and molecular studies of biopsies may help further explain this dermatologic adverse event with earlier diagnosis and management of neutrophilic dermatoses in these patients.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"457-464"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic Lymphocytic Leukemia: Disease Biology.","authors":"Stefan Koehrer, Jan A Burger","doi":"10.1159/000533610","DOIUrl":"10.1159/000533610","url":null,"abstract":"<p><strong>Background: </strong>B-cell receptor (BCR) signaling is crucial for normal B-cell development and adaptive immunity. In chronic lymphocytic leukemia (CLL), the malignant B cells display many features of normal mature B lymphocytes, including the expression of functional B-cell receptors (BCRs). Cross talk between CLL cells and the microenvironment in secondary lymphatic organs results in BCR signaling and BCR-driven proliferation of the CLL cells. This critical pathomechanism can be targeted by blocking BCR-related kinases (BTK, PI3K, spleen tyrosine kinase) using small-molecule inhibitors. Among these targets, Bruton tyrosine kinase (BTK) inhibitors have the highest therapeutic efficacy; they effectively block leukemia cell proliferation and generally induce durable remissions in CLL patients, even in patients with high-risk disease. By disrupting tissue homing receptor (i.e., chemokine receptor and adhesion molecule) signaling, these kinase inhibitors also mobilize CLL cells from the lymphatic tissues into the peripheral blood (PB), causing a transient redistribution lymphocytosis, thereby depriving CLL cells from nurturing factors within the tissue niches.</p><p><strong>Summary: </strong>The clinical success of the BTK inhibitors in CLL underscores the central importance of the BCR in CLL pathogenesis. Here, we review CLL pathogenesis with a focus on the role of the BCR and other microenvironment cues.</p><p><strong>Key messages: </strong>(i) CLL cells rely on signals from their microenvironment for proliferation and survival. (ii) These signals are mediated by the BCR as well as chemokine and integrin receptors and their respective ligands. (iii) Targeting the CLL/microenvironment interaction with small-molecule inhibitors provides a highly effective treatment strategy, even in high-risk patients.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"8-21"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11753505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10285002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerated Chronic Lymphocytic Leukemia and Richter Transformation in the Era of Novel Agents.","authors":"Ilana Levy Yurkovski, Tamar Tadmor","doi":"10.1159/000533664","DOIUrl":"10.1159/000533664","url":null,"abstract":"<p><strong>Background: </strong>Tremendous developments in the field of chronic lymphocytic leukemia (CLL) in recent years have led to a revolutionary change in the treatment approach, which today is based on targeted treatments with a good response and optimal prognosis. Nevertheless, CLL can present or progress to \"accelerated CLL\" (A-CLL) or to \"Richter transformation\" (RT) and these two entities have a more aggressive course and are still characterized by challenges in the fields of diagnosis and therapy. In the current review, we summarized the latest knowledge in terms of diagnostic approaches to A-CLL, available treatments and clinical trials, for both A-CLL and RT which still pose an unmet need and require additional basic and clinical investigations.</p><p><strong>Summary: </strong>A-CLL is a rare and underdiagnosed entity that probably stands in the \"gray zone\" between CLL and RT, generally holding an intermediate prognosis. Its diagnosis is mainly based on histological findings including expanded proliferation centers, increased mitotic activity, and/or high Ki-67 index. Due to its rarity, its treatment approach has still not been defined, but it seems that novel agents, especially Bruton tyrosine kinase inhibitors (BTKi), are effective. As for RT, the standard therapy still consists of chemo-immunotherapy followed by stem-cell transplantation for fit responders with a dismal prognosis. New approaches are recently adopted including B-cell inhibition via novel agents (BTKi, venetoclax), T-cell engagers (checkpoint inhibitors, bispecific antibodies [BiTe] or the chimeric antigen receptor [CAR] technology), antibody-drug conjugates, or drug combinations. Although both CAR-T and BiTe seem promising, especially when combined with BTKi, evidence is still insufficient, and patients should generally be recruited in clinical trials.</p><p><strong>Key messages: </strong>The field of CLL has been a subject of major advances in recent years, but A-CLL and RT remain topics of \"unmet need\" and require further studies to identify the best diagnostic approach and a more effective treatment.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"73-83"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10156315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Importance of Minimal Residual Disease in the Era of Targeted Therapies in Chronic Lymphocytic Leukemia.","authors":"Othman Al-Sawaf","doi":"10.1159/000534846","DOIUrl":"10.1159/000534846","url":null,"abstract":"<p><strong>Background: </strong>The level of minimal residual disease (MRD), often binarized into detectable or undetectable MRD according to certain thresholds, is strongly associated with long-term outcomes after chemo- and chemoimmunotherapy.</p><p><strong>Summary: </strong>Driven by our improved understanding of the biology of chronic lymphocytic leukemia (CLL), the recent decade has shown a shift from chemotherapy-based regimens to regimens based on targeted agents that exploit distinct biological vulnerabilities of CLL. These targeted agents can be broadly classified into inhibitors of Bruton tyrosine kinase (BTK) and BCL2 as well as CD20-directed antibodies. Depending on which agent and which combination of agents is used, the levels or status of MRD can have varying clinical relevance. This has implications on the prognosis after therapy as well as on possible strategies to guide treatment duration and intensity.</p><p><strong>Key messages: </strong>This review summarizes the main discoveries related to MRD in the context of targeted therapies. Furthermore, it provides an overview on current hurdles and caveats related to the implementation of MRD in regular clinical care and summarize open research questions that need to be addressed with future clinical studies.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"22-32"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71410150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiplex Proteomics in the Identification of Potential Biomarkers of Very Severe Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease in Allogeneic Hematopoietic Cell Transplant Patients Treated with Defibrotide.","authors":"Ram Vasudevan Nampoothiri, Lisa Avery, Ivan Pasic, Ioannis Prassas, Eleftherios Diamandis, Fotios V Michelis","doi":"10.1159/000535706","DOIUrl":"10.1159/000535706","url":null,"abstract":"<p><strong>Introduction: </strong>Despite well-established clinical criteria for diagnosis of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) following allogeneic hematopoietic cell transplantation (HCT), there is a lack of established diagnostic protein biomarkers.</p><p><strong>Methods: </strong>Prospective samples were collected from patients with very severe SOS/VOD at diagnosis and days +3, +7, +14, and +30 post-initiation of defibrotide. Samples from age-matched controls with no VOD were collected at days +14, +30, +60, +90, and +180 following allogeneic HCT. Serum samples were analyzed for 2,925 protein levels by antibody-based proximity extension assay (PEA). Mean differences in the log-transformed abundance values were compared using t tests in a volcano plot.</p><p><strong>Results: </strong>Five patients with very severe SOS/VOD and 5 control patients were compared. Ten proteins were identified that showed a statistically significant and log-transformed 3-fold increase in concentration. They were CALCA, CCL20, GPR37, IGFBP4, IL1RL1, SLC39A14, SPINK4, FABP3, MYL3, and CHCHD10. Four different proteins, namely, CD83, leukocyte associated immunoglobulin-like receptor 2 (LAIR2), CD7, and HEM6 showed a significant decrease with defibrotide treatment. SOS/VOD resolved in 80% (n = 4) of patients, while 1 patient deceased due to SOS/VOD.</p><p><strong>Conclusion: </strong>PEA technology identified 10 proteins that were significantly elevated in patients with very severe SOS/VOD. Prospective studies in a larger cohort using this technology may be able to conclusively identify diagnostic protein biomarkers for SOS/VOD.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"511-524"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139705729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum.","authors":"","doi":"10.1159/000537722","DOIUrl":"10.1159/000537722","url":null,"abstract":"","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"249"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11777140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluoroquinolone Prophylaxis during Conventional Chemotherapy or Hematopoietic Stem Cell Transplantation for Acute Leukemia - Pros and Cons.","authors":"Tomer Hoffman, Alaa Atamna, Vladislav Litchevsky, Irina Amitai, Dafna Yahav","doi":"10.1159/000535119","DOIUrl":"10.1159/000535119","url":null,"abstract":"<p><strong>Background: </strong>Prophylaxis with fluoroquinolones (FQ) is commonly used in patients with acute leukemia (AL) during neutropenia. This practice is supported by an older meta-analysis reporting reduced mortality using FQ prophylaxis. Later meta-analyses have failed to reproduce this finding, presumably due to higher background FQ resistance rates limiting their effectiveness.</p><p><strong>Summary: </strong>This article reviews the pros and cons of FQ prophylaxis mainly in patients with AL. Most current guidelines do not support universal prophylaxis but rather recommend a selective approach, weighing the benefits against the risks. This recommendation is based on the lack of mortality benefit reported in more recent meta-analyses. FQ prophylaxis was demonstrated to reduce bacteremia and febrile neutropenia episodes, although mostly in trials performed in low-resistance settings (&lt;20%), whereas current FQ resistance rates may reach 30-60%. Other disadvantages of FQ include potential adverse events, antibiotic resistance development, cost, increase in Gram-positive infections and resistant Gram-negative infections following prophylaxis, Clostridioides difficile infection, and an effect on gut microbiota.</p><p><strong>Key messages: </strong>Taking the above into consideration, alternative approaches other than universal FQ prophylaxis should be considered. Centers with high FQ resistance rates may consider either withholding prophylaxis or providing selective prophylaxis for high-risk patients screened negative for FQ-resistant bacteria.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"186-197"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Donor Lymphocyte Infusion Is a Feasible Way to Improve Survival in Patients with Acute Myeloid Leukemia and Myelodysplastic Syndromes Who Relapse after Allogeneic Stem Cell Transplantation.","authors":"Lia Minculescu, Joanne Reekie, Soeren Lykke Petersen, Brian Thomas Kornblit, Ida Schjoedt, Niels Smedegaard Andersen, Lisbeth Pernille Andersen, Anne Fischer-Nielsen, Eva Kannik Haastrup, Lone Smidstrup Friis, Henrik Sengelov","doi":"10.1159/000534315","DOIUrl":"10.1159/000534315","url":null,"abstract":"<p><strong>Introduction: </strong>Donor lymphocyte infusion (DLI) is used to induce remission in patients who relapse after allogeneic stem cell transplantation (allo-HSCT). During the last decade, the hypomethylating agent Azacitidine has been used together with DLI for a synergistic graft-versus-leukemia (GVL) effect. Here, we report results of DLI/Azacitidine treatment from a retrospective single-center study.</p><p><strong>Methods: </strong>Fifty AML/MDS patients treated for relapse after allo-HSCT between 2001 and 2020 with DLI at the Department of Hematology, at Rigshospitalet, Copenhagen University Hospital were included for analyses. A subgroup of patients who obtained complete remission (CR) after reinduction chemotherapy, received DLI in combination with low-dose (32 mg/m2) Azacitidine.</p><p><strong>Results: </strong>Overall survival in all patients after DLI treatment was 59% at 2 years and 20% at 5 years. Relapse-free survival in patients in CR prior to DLI was 32% after 2 years and 7% after 5 years. In the DLI + low-dose-Azacitidine group, 5-year relapse-free survival was 40%.</p><p><strong>Conclusion: </strong>DLI remains an effective treatment in post-transplant relapse leaving one-fifth of patients' long-term survivors. Our results support the concomitant use of low-dose Azacitidine in the future use of DLI in order to enhance the GVL effect of donor lymphocytes.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"325-332"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41187817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frontline Therapy in Chronic Lymphocytic Leukemia.","authors":"Miguel Arguello-Tomas, Nil Albiol, Carol Moreno","doi":"10.1159/000534730","DOIUrl":"10.1159/000534730","url":null,"abstract":"<p><strong>Background: </strong>The treatment landscape of chronic lymphocytic leukemia (CLL) has tremendously evolved in the last decades, thanks to the introduction of more effective therapies.</p><p><strong>Summary: </strong>Frontline therapy for patients with CLL includes chemoimmunotherapy (CIT) and pathway inhibitors (PIs) (i.e., bruton tyrosine kinase inhibitors and BCL2 inhibitors); the latter has proved to be more effective than CIT mainly in patients with high-risk features (e.g., TP53 aberrations and unmutated IGHV) with acceptable toxicity. Combinations of PIs are playing the protagonist role as frontline therapy for CLL.</p><p><strong>Key messages: </strong>In this article, the management of treatment-naïve patients with CLL is discussed.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"47-59"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71410149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Markers in the Era of Targeted Therapies.","authors":"Sorang Kang, Inhye E Ahn","doi":"10.1159/000533704","DOIUrl":"10.1159/000533704","url":null,"abstract":"<p><strong>Background: </strong>Small molecules targeting Bruton's tyrosine kinase (BTK) and B-cell lymphoma-2 have become the standard of care for the treatment of chronic lymphocytic leukemia (CLL), replacing chemoimmunotherapy (CIT) in most clinical settings. Ongoing trials explore targeted combinations and minimal residual disease-driven treatment cessation. These dramatic shifts in the current and upcoming treatment landscape of CLL raise the need to reevaluate existing prognostic markers and develop novel ones.</p><p><strong>Summary: </strong>This review examines prognostic markers in CLL patients treated with standard and investigational targeted therapies. Specifically, initial treatment of TP53 aberrant patients with a BTK inhibitor can achieve 70% progression-free survival (PFS) at 5 years, outperforming the 15% 5-year PFS with a CIT regimen containing fludarabine, cyclophosphamide, and rituximab (FCR). The prognostic implications of the immunoglobulin heavy chain variable gene (IGHV) mutation status have also changed. Unmutated IGHV is associated with inferior PFS and overall survival after FCR and inferior PFS with fixed-duration therapy with venetoclax and anti-CD20 monoclonal antibody but not with continuous BTK inhibitor treatment.</p><p><strong>Key messages: </strong>(1) Genetic variables (e.g., TP53 aberration, IGHV mutation, complex karyotype) have a prognostic significance in CLL patients treated with targeted therapy. (2) Understanding the prognostic and predictive values of these markers is critical for the development of a risk-adapted treatment strategy in CLL.</p>","PeriodicalId":6981,"journal":{"name":"Acta Haematologica","volume":" ","pages":"33-46"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10230923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}