Hematology Reports最新文献

{"title":"How We Treat Hemolytic Anemia Due to Pyruvate Kinase Deficiency.","authors":"Sara Tama-Shekan, Valeria Moreno, Ludovic Saba, Chakra P Chaulagain","doi":"10.3390/hematolrep16030054","DOIUrl":"10.3390/hematolrep16030054","url":null,"abstract":"<p><strong>Background: </strong>Pyruvate kinase (PK) deficiency is an inherited red blood cell (RBC) enzyme disorder that results in non-immune chronic hemolytic anemia. Characteristic symptoms of PK deficiency include anemia, fatigue, splenomegaly, jaundice, gallstones, thrombosis, and transfusional iron overload. Previously, treatments aimed at symptomatic management with RBC transfusions, phototherapy, folic acid supplementation, splenectomy, and iron chelation therapy when iron overload was documented. Mitapivat, a recently approved medication for treatment of PK-deficiency hemolytic anemia, is an oral allosteric activator of wild-type and mutant RBC PK enzymes. In this paper, we describe three cases of PK-deficiency anemia treated with mitapivat and describe modern management of this rare hemolytic disorder.</p><p><strong>Methods: </strong>A retrospective healthcare database analysis was conducted to extract relevant information. Both quantitative and qualitative methods were integrated to provide a more comprehensive understanding of the cases.</p><p><strong>Results: </strong>Two patients responded well to treatment with mitapivat, noted by an increase in hemoglobin levels, improvements in hemolytic markers, less frequent or no RBC transfusion requirements, and improvements in fatigue. One patient carrying two non-missense mutations of the <i>PKLR</i> gene did not respond to treatment with mitapivat. As variations in patient-specific factors (including genotype) can lead to different clinical manifestations and responses to treatment, we recommend considering both the phenotype (clinical symptoms and signs) and the genotype of the <i>PKLR</i> gene when making therapeutic decisions about starting a patient on mitapivat.</p><p><strong>Conclusions: </strong>While mitapivat addresses the previously unmet needs of most patients with PK deficiency as the first and only disease-modifying medication to receive approval for this condition, not all patients with PK deficiency are amenable to treatment with mitapivat.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142284430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperbaric Oxygen Therapy during Pregnancy for Critical Anemia Secondary to Sickle Cell Disease with Post-Transfusion Hyperhemolysis: A Case Report.","authors":"Shawn Khan, Connor T A Brenna, Jacob Pendergrast, A Kinga Malinowski, Marcus Salvatori, Rita Katznelson, Jordan Tarshis","doi":"10.3390/hematolrep16030053","DOIUrl":"10.3390/hematolrep16030053","url":null,"abstract":"<p><p><b>Background:</b> Sickle cell disease is the most common human monogenetic disease, and its risks are amplified during pregnancy. <b>Methods</b>: This report describes a 35-year-old woman with HgbSS sickle cell disease who developed hyperhemolysis syndrome after undergoing an exchange transfusion during pregnancy. <b>Results:</b> In addition to conventional medical treatment, the patient received prepartum hyperbaric oxygen therapy (HBOT), totaling 17 treatments for the indication of severe anemia. She experienced significant clinical improvement while undergoing HBOT and ultimately delivered a healthy preterm infant by cesarean section. <b>Conclusions:</b> The risks, benefits, and challenges of using HBOT in this unique context are discussed.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142284431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IgG-k/IgG-λ Para-Osseous Plasmacytoma Relapsed as Soft-Tissue Plasmacytoma with IgA-k Immunophenotype: A Case Report and Review of the Literature on Related Biochemical Aspects.","authors":"Manlio Fazio, Chiara Maria Catena Sorbello, Vittorio Del Fabro, Alessandra Romano, Maria Teresa Cannizzaro, Nunziatina Laura Parrinello, Benedetta Esposito, Sara Frazzetto, Federica Elia, Francesco Di Raimondo, Concetta Conticello","doi":"10.3390/hematolrep16030052","DOIUrl":"10.3390/hematolrep16030052","url":null,"abstract":"<p><p>Neoplastic plasma cells (PCs) proliferation at anatomic sites dislocated from the bone marrow (BM) or their contiguous growth from osseous lesions that disrupt the cortical bone is termed extramedullary multiple myeloma (EMD). EMD still remains challenging from a therapeutic and biological perspective. Pathogenesis has not been completely clarified, and it is generally associated with high-risk cytogenetics (HRCAs). In order to emphasize the clinical and biochemical complexity of this disease, we have decided to describe the case of a patient affected by relapsed-refractory (RR) EMD, which presented as para-osseous plasmacytoma with a bi-phenotypical immunoglobulin (Ig) component and lately relapsed as soft-tissue plasmacytoma with a total immunophenotype switch. We have also hypothesized a correlation between Ig patterns and prognosis and suggested the possible inclusion of these biochemical features in the general risk assessment.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142284441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-Line Combination with Proteasome Inhibitor-Based Treatment and Zoledronic Acid Is Effective in Reducing Later Fractures in Multiple Myeloma Irrespective of Multiple Myeloma Bone Disease at Diagnosis.","authors":"Veera Eskelinen, Elise Nivakoski, Kirsi Launonen, Anu Partanen, Sakari Kakko, Milla E L Kuusisto","doi":"10.3390/hematolrep16030051","DOIUrl":"10.3390/hematolrep16030051","url":null,"abstract":"<p><p>The present study provides real-world evidence on the treatment of multiple myeloma (MM) bone disease with various bisphosphonates combined for different myeloma-specific treatments as no validated data regarding the best combination treatment for bone disease associated with MM are available. We examined retrospectively 345 MM patients treated with autologous stem cell transplantation in Finland during 1996-2020. The median age of the patients was 60 years with a median follow-up time of 50 months (1-339). At diagnosis, 72.1% of the patients had myeloma-associated bone disease and 45.8% had fractures. Most patients (58.8%) received proteasome inhibitor (PI)-containing treatment at first line. MM bone disease was treated in 91.6% of the patients; 49.9% received zoledronic acid (ZA) and 29.9% pamidronate. Inferior overall survival was associated with MM bone disease at diagnosis (<i>p</i> = 0.005) or a fracture at diagnosis (<i>p</i> = 0.003). A later fracture was identified in 29% of the patients, and in those patients without MM bone disease at diagnosis later fractures were less common after ZA treatment (<i>p</i> = 0.049). PI-based treatment plus ZA (<i>p</i> = 0.019) seemed to be the best combination to prevent later fractures, even though the same patient subgroup was more likely to experience relapse (<i>p</i> = 0.018), and also when excluding patients with previous induction therapy without novel agents (<i>p</i> = 0.008). To conclude, this study suggests that the best therapy to prevent later fractures in MM might be PI-based treatment combined with ZA.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lymphocytic Lymphoma Transforming into Hodgkin Lymphoma in Sub-Saharan Africa: Case Report and Literature Review.","authors":"Sokhna Aïssatou Touré, Dibor Niang, Serigne Mourtalla Gueye, Mohamed Keita, Alioune Badara Diallo, Elimane Seydi Bousso, Fatma Dieng, Blaise Felix Faye, Moussa Seck, Saliou Diop","doi":"10.3390/hematolrep16030050","DOIUrl":"10.3390/hematolrep16030050","url":null,"abstract":"<p><p>The Hodgkin variant Richter syndrome (HvRS) is an infrequent complication occurring in 1% of lymphocytic lymphoma/chronic lymphocytic leukemia patients. We report a case of HvRS diagnosed in Sub-Saharan Africa. A 63-year-old patient was consulted for the investigation of an abdominal mass that had been evolving for 5 years prior to admission. His history revealed night sweats, 13% weight loss in 3 months and persistent pruritis. Examination revealed bilateral cervical axillary and inguinal macroadenopathies, painless abdominal distension, pruritic lesions and WHO 2 PS. The blood count showed anemia at 9.5 g/dL. Histology revealed a lymphomatous proliferation of diffuse architecture, nodular in places, with Hodgkin and Sternberg cells associated with small lymphocytes, histiocytes and eosinophilic polymorphs. Immunohistochemistry showed CD20, PAX5, BCL2, CD5, CD23 and MYC positivity; Ki67 at 10% and cyclin D1, BCL6 and CD10 negativity; CD30 positivity on Hodgkin and Sternberg cells that remained CD20 negative; difficulty interpreting CD15; EBV positivity (EBERs); and CD3 and CD5 positivity on reactive T cells. CD138 and kappa and lambda light chains were non-contributory. The extension work-up classified the patient as Ann Arbor stage III B with a Hasenclever score of 3/7. This case illustrates the difficulties in diagnosing HvRS in our countries, where the number of haematopathologists is insufficient and the technical facilities are limited.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of Delayed Transfusion Reactions in Sickle Cell Disease Patients Polytransfused in the Brazilian Amazon.","authors":"Lorena Alves Santos, Anne Cristine Gomes de Almeida, Andrea Monteiro Tarragô, Nina Rosa Gonçalves da Silva, Juliana Nascimento Vitoriano da Silva, Mônica Moura de Souza, Monik Oney Oliveira Nascimento, Marcelo Reis do Nascimento, Ana Caroline Dos Santos Castro, Cinthia Xerez de Albuquerque, Evilázio Cunha Cardoso, José Pereira Moura Neto, Sérgio Roberto Lopes Albuquerque","doi":"10.3390/hematolrep16030049","DOIUrl":"10.3390/hematolrep16030049","url":null,"abstract":"<p><strong>Background: </strong>Sickle cell disease (SCD) affects approximately 100,000 people in the United States and millions worldwide, with the highest prevalence of 70% of SCD being found in individuals of African ethnicity. Delayed hemolytic, alloimmunization, and anamnestic transfusion reactions in multiple transfusion patients need to be investigated and managed to avoid a worsening of the patient's clinical status.</p><p><strong>Objective: </strong>This paper aims to investigate delayed transfusion reactions in SCD patients who were polytransfused in the Brazilian Amazon.</p><p><strong>Material and methods: </strong>The clinical and laboratory indicators of SCD patients with more than four transfusions were investigated. The patients were treated at the Fundação Hospitalar de Hematologia e Hemoterapia do Estado do Amazonas, Brazil.</p><p><strong>Results: </strong>A total of 44 polytransfused patients with SCD were followed. Regarding Rh phenotype, it was possible to observe a frequency of 26.6% (12) patients with the RZRZ (DCE/DCE) phenotype, in addition to 4.5% (two) patients with <i>RH</i> and <i>RHCE</i> variants. It was also possible to observe 20.5% (nine) patients with an alloimmunization reaction, who presented the following alloantibodies: anti-RhD, anti-E, anti-K, anti-Jk^b, anti-N, anti-S, and anti-Di^a, two of which are unidentified. Of these, four (44.4%) patients also presented autoantibodies, anti-e, and three unidentified antibodies, and four (44.4%) patients presented an anamnestic reaction, with anti-RhD, K, and Jkb antibodies. Of the 44 patients monitored, 54.4% (24) had clinical and laboratory indicators of a delayed hemolytic reaction.</p><p><strong>Conclusion: </strong>Delayed transfusion reactions, often neglected, occur frequently. Therefore, transfusions need to be monitored for at least 28 days, with medical investigation of clinical and laboratory indicators to make greater use of this therapeutic resource.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistently High Platelet Factor 4 Levels in an Adolescent with Recurrent Late Thrombotic Complications after SARS-CoV-2 mRNA Vaccination.","authors":"Yoichi Haga, Akira Ohara, Tsuneyoshi Yakuwa, Akari Yamashita, Midori Udo, Masaki Matsuoka, Hiroshi Ohara, Atsushi Yasumoto, Hiroyuki Takahashi","doi":"10.3390/hematolrep16030048","DOIUrl":"10.3390/hematolrep16030048","url":null,"abstract":"<p><p>Thrombosis after severe acute respiratory syndrome coronavirus 2 vaccination is a serious complication in patients with a thrombophilic predisposition. Herein, we present a 17-year-old female who had underlying antiphospholipid syndrome (APS) and developed deep vein thrombosis (DVT) 6 months after her second BNT162b2 vaccine dose. Although she had no family history of thrombosis, she had previously developed DVT at 6 years of age, with thrombus formation in the right common iliac vein and the inferior vena cava, along with concomitant left pulmonary infarction. The patient had received anticoagulant therapy for 6 years after DVT onset, with subsequent treatment cessation for 5 years without recurrence. She received the BNT162b2 vaccine at 17 years of age, 1 week before a routine outpatient visit. Platelet factor 4 elevation was detected 14 days after the first vaccination, persisting for 5 months without thrombotic symptoms. Six months after the second vaccine dose, the DVT recurred and was treated with a direct oral anticoagulant. The vaccine was hypothesized to exacerbate the patient's APS by activating coagulation. Platelet factor 4 levels may indicate coagulation status. When patients predisposed to thrombosis are vaccinated, coagulation status and platelet activation markers should be monitored to prevent DVT development.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemophagocytic Lymphohistiocytosis Triggered by Herpes Simplex Virus 1 and 2: A Narrative Review","authors":"Andria Papazachariou, P. Ioannou","doi":"10.3390/hematolrep16030047","DOIUrl":"https://doi.org/10.3390/hematolrep16030047","url":null,"abstract":"Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening syndrome characterized by an uncontrolled hyperinflammatory reaction. HLH is classified into primary (familial) and secondary (acquired). Secondary HLH is commonly triggered by infections, with viral infections being a leading cause. Its epidemiology and clinical features in cases associated with herpes simplex virus 1 and 2 remain underexplored. This study aimed to review all previously described cases of HSV-1 or -2-triggered HLH and provide information about this syndrome’s epidemiology, microbiology, clinical characteristics, treatment, and outcomes. Methods: A narrative review was performed based on a search in PubMed, the Cochrane Library, and Scopus. Studies published until 27 April 2024 providing relevant data for HLH due to HSV 1 and 2 in humans were included. Results: We identified 29 eligible studies reporting HLH due to HSV 1 and 2, involving 34 patients. Half of them were adults, and half were neonates. Fever and splenomegaly were the most common clinical findings. Most patients were diagnosed with HSV-1 (64.7%), with PCR being the primary diagnostic method. The median duration of in-hospital treatment was 21 days, with acyclovir and steroids being the mainstays of therapy. The overall mortality rate was 41.2%, and AST levels emerged as an independent predictor of mortality. Conclusions: Our findings underscore the need for heightened awareness surrounding HLH triggered by HSV 1 and 2 and the importance of prompt diagnosis and tailored treatment approaches.","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141801736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Candidates for Effective Utilization of Stored Autologous PBSCs in Salvage Transplantation for Multiple Myeloma: Who Benefits Most?","authors":"Amany R. Keruakous, Laura Walker, Molly Denlinger, Mohammad A H Mian, Danielle Bradshaw, Vamsi Kota, Anand P. Jillella","doi":"10.3390/hematolrep16030046","DOIUrl":"https://doi.org/10.3390/hematolrep16030046","url":null,"abstract":"Background/Objectives: High-dose chemotherapy (HD-CHT) followed by autologous stem cell transplantation (ASCT) remains the gold standard for eligible multiple myeloma (MM) patients, even amidst evolving therapeutic options. Clinical trials have demonstrated ASCT’s efficacy in MM, including its potential as salvage therapy after prolonged remission. Peripheral blood stem cells (PBSCs) are now the primary source of hematopoietic stem cells for ASCT. Collecting additional PBSCs post-initial myeloablative conditioning is challenging, leading many centers to adopt the practice of collecting and storing excess PBSCs during initial therapy to support tandem transplants or salvage treatments. The use of salvage ASCT may diminish in the face of novel, highly effective treatments like bispecific antibodies and cellular therapies for relapsed/refractory MM (RRMM). Despite available stored PBSC grafts, salvage ASCTs are underutilized due to various factors, including declining performance status and therapy-related comorbidities. A cost utilization analysis from 2013 revealed that roughly 70% of patients had unused PBSC products in prolonged cryopreservation, costing a significant portion of total ASCT expenses. The average cost for collecting, cryopreserving, and storing PBSCs exceeded $20,000 per person, with more than $6700 spent on unused PBSCs for a second ASCT. A more recent analysis from 2016 underscored the declining need for salvage ASCT, with less than 10% of patients using stored PBSC grafts over a decade. Methods: To address the dilemma of whether backup stem cells remain necessary for myeloma patients, the study investigated strategies to reduce the financial burden of PBSC collection, processing, and storage. It evaluated MM patients undergoing frontline ASCT from January 2012 to June 2022, excluding those with planned tandem transplants and those who had a single ASCT with no stored cells. Discussion: Among the 240 patients studied, the median age at PBSC collection was 61. Notably, only 7% underwent salvage ASCT, with nearly 90% of salvage ASCT recipients being ≤ 61 years old at the time of initial ASCT. The study revealed a decreasing trend in salvage ASCT use with increasing age, suggesting that PBSC collection for a single transplant among elderly patients (>60 years old) could be a cost-effective alternative. Most transplant centers aimed to collect 10 × 106 CD34 + cells/kg, with patients over 65 often requiring multiple collection days. Shifting towards single-transplant collections among the elderly could reduce costs and resource requirements. Additionally, the study recommended implementing strategies for excess PBSC disposal or repurposing on the collection day to avoid additional storage costs. In summary, the decreasing utilization of salvage ASCT in MM, alongside financial considerations, underscores the need for revised stem cell collection policies. Conclusions: The study advocates considering single-transplant PBSC collections ","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141653178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Validation of the Somatic FANCD2 Mutation (c.2022-5C>T) as a Novel Molecular Biomarker for Early Disease Progression in Chronic Myeloid Leukemia: A Case–Control Study","authors":"N. Alanazi, Abdulaziz Siyal, S. Basit, Masood Shammas, S. AlMukhaylid, A. Aleem, Amer Mahmood, Zafar Iqbal","doi":"10.3390/hematolrep16030045","DOIUrl":"https://doi.org/10.3390/hematolrep16030045","url":null,"abstract":"Background: Chronic myeloid leukemia (CML) results from chromosomal translocation t(9;22) leading to the formation of the BCR-ABL fusion oncogene. CML has three stages: the chronic phase (CP), the accelerated phase (AP), and the blast crisis (BC). Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of CML. TKIs work well in CP-CML, and these patients have a survival rate similar to the normal population, but TKIs are less effective in advanced-phase CML. Even with current advances in treatment, BC-CML patients have an average overall survival of less than a year. Early recognition of CML patients at risk of disease progression can help in timely interventions with appropriate TKIs or other therapeutic modalities. Although some markers of disease progression like BCR-ABL kinase domain, ASXL1, and GATA2 mutations are available, no universal and exclusively specific molecular biomarkers exist to early diagnose CML patients at risk of CML progression for timely therapeutic interventions to delay or minimize blast crisis transformation in CML. A recent study found that all BC-CML patients harbored the FANCD2 (c.2022-5C>T) mutation. Therefore, the current study was designed to detect this FANCD2 mutant in AP-CML (early progression phase) and to clinically validate its potential as a novel molecular biomarker of early CML progression from CP to AP. Methods: Our study comprised 123 CP-CML (control group) and 60 AP-CML patients (experimental group) from 2 oncology centers, from January 2020 to July 2023. Mean hemoglobin level, WBC count, platelet count, treatment type, hepatomegaly, splenomegaly, and survival status of AP-CML patients were significantly different from those of CP-CML patients. However, as these clinical parameters cannot help in the early detection of patients at risk of CML progression, there was a need for a clinically validated biomarker of AP-CML. DNA was extracted from the patients’ blood samples, and the FANCD2 gene was sequenced using an Illumina NextSeq500 next-generation sequencer (NGS). Results: The NGS analysis revealed a unique splice-site mutation in the FANCD2 gene (c.2022-5C>T). This mutation was detected in the majority (98.3%) of AP-CML patients but in none of the CP-CML patients or healthy control sequences from genomic databases. The mutation was confirmed by Sanger sequencing. FANCD2 is a member of the Fanconi anemia pathway genes involved in DNA repair and genomic stability, and aberrations of this gene are associated with many cancers. Conclusions: In conclusion, our study shows that the somatic FANCD2 (c.2022-5C>T) mutation is a new molecular biomarker for early CML progression. We recommend further clinical validation of this biomarker in prospective clinical trials.","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":null,"pages":null},"PeriodicalIF":1.1,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141669937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}