Hematology, Transfusion and Cell Therapy最新文献

{"title":"HEPATIC VENO-OCCLUSIVE DISEASE","authors":"Barbaros Şahin Karagün","doi":"10.1016/j.htct.2025.106198","DOIUrl":"10.1016/j.htct.2025.106198","url":null,"abstract":"<div><div>Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (VOD/SOS), is a severe complication which usually occurs due to conditioning regimens used for hematopoietic stem cell transplantation (HSCT). It is characterized by hepatomegaly, hyperbilirubinemia, ascites and right upper quadrant pain and usually develops within the first 20-30 days after transplant. It is accepted to be a result of endothelium and hepatocyte damage caused by chemotherapy and radiotherapy of the conditioning regimen.</div><div>Current studies suggest that the primary site of toxic injury is the hepatocyte, subsequently followed by damage to the central veins in zone 3 of the hepatic acinus and sinusoidal endothelial cells. Early changes include fibrin deposition, venous occlusion, progressive venous micro-thrombosis and sinusoidal occlusion. These changes lead to severe clinical problems including portal hypertension, hepatorenal syndrome and hepatocellular necrosis, which may ultimately result in multiorgan dysfunction (MOD) and death. Previously, the Baltimore and Seattle criteria were used for VOD/SOS diagnosis; however, the limitations of these criteria for VOD/SOS diagnosis (especially in anicteric children and those who have symptom onset after 21 days), led to establishment of the EBMT (European Society for Blood and Marrow Transplantation) 2017 VOD/SOS criteria which evaluates pediatric and adult patients separately. The EBMT 2017 criteria is comprised of laboratory and clinical findings such as transfusion-resistant thrombocytopenia, unexplained weight gain, hepatomegaly, ascites and elevation in bilirubin levels. Despite the advantages brought by this criteria, it is still difficult to diagnose VOD/SOS.</div><div>Several approaches to prevent its development of VOD/SOS were put forth, including individualized dosing of chemotherapy, reduction of the intensity of the conditioning regimens, close monitoring of the levels of busulfan and cyclophosphamide and also reducing their use. Prostaglandin E1 and tissue-plasminogen activator with or without concurrent heparin have been explored in VOD/SOS treatment; however, these approaches have shown little success, as is the case with supportive treatments. Defibrotide (DF) emerged as the most promising medication for both prophylaxis and treatment in patients with VOD/SOS. DF is a single-stranded polydeoxyribonucleotide with anti-inflammatory, anti-ischemic, anti-thrombotic, and thrombolytic properties in addition to its protective effects on endothelial cells. DF is approved for adult and pediatric patients with VOD/SOS with renal or pulmonary dysfunction after HSCT in the United States, and for severe VOD/SOS post-HSCT in patients aged >1 month in the European Union. In addition, several studies have examined DF prophylaxis can reduce the incidence of VOD/SOS in high-risk patients. Although the literature is unanimous for the use of DF in patients diagnosed with VOD/SOS, its use as a pr","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106198"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796931","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":"CURRENT TREATMENT APPROACHES IN ELDERLY PATIENTS WITH ACUTE MYELOID LEUKEMIA","authors":"Fatma Arikan","doi":"10.1016/j.htct.2025.106197","DOIUrl":"10.1016/j.htct.2025.106197","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with a median age at diagnosis of 68 years. Estimated 5-year survival differs significantly by age and is <10% for patients older than 60 years (1). Older patients represent highly heterogeneous group and require careful evaluation of comorbidities and frailty. When selecting a treatment plan for older patients, physicians must carefully weigh the risk of adverse events and the potential impact on quality of life (QOL) against possible survival benefits. They are generally unsuitable for curative treatment options such as intensive chemotherapy and hematopoietic stem cell transplantation. Consequently, treatment strategies aimed at improving outcomes and patient compliance continue to evolve.</div><div>Lower intensity regimens include hypomethylating agents (HMA), such as azacitidine or decitabine, or low-dose cytarabine (LDAC). The introduction of azacitidine in 2012 and decitabine in 2015 significantly transformed the treatment landscape for these patients (2-4). However, HMA monotherapy has been associated with remission rates of 30% or less and survival of under one year (2, 5). As HMA therapy is considered the standard backbone for AML patients unfit for intensive chemotherapy, the majority of phase III trials have been designed to evaluate novel agents in combination with HMA versus HMA alone. In 2018, azacitidine and venetoclax combination was approved for patients with newly diagnosed AML aged ≥75 years old or ineligible for intensive chemotherapy (6). The VIALE-A trial demonstrated improved overall survival (OS) with venetoclax-azacitidine versus plasebo-azacitidine (14.7 and 9.6 months, respectively). Moreover, with long term follow-up, patients achieving CR/CRi with measurable residual disease (MRD) negativity had a longer median OS (34.2 months) compared to those without MRD response (18.7 months) (7). Profound cytopenias accompanied by concurrent infections, bone marrow evaluations during treatment cycles to evaluate cellularity, treatment delays, and prolonged hospitalizations are frequently observed. Nevertheless, due to its manageable side effect profile and a protocol allowing dose and schedule modifications, venetoclax-azacitidine has become a first-line treatment for elderly AML patients worldwide who are unfit for intensive therapy. Similarly, the VIALE-C trial, which randomized patients to LDAC/venetoclax versus LDAC/placebo, demonstrated improved CR/Cri (48% vs 13%) and OS (8.4 vs 4.1 months) in the venetoclax arm.(8)</div><div>The combination of HMAs with other agents, together with the establishment of genetic risk profiles and identification existing mutations, underscores the importance of individualized therapy. Among promising agents, Ivosidenib monotherapy or its combination with HMA has shown superiority in OS, CR/Cri, and EFS for IDH- 1mutated de novo AML (AGILE trail) (9). Patients with TP53 alterations, however, continue to expe","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106197"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796933","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":"THE TREATMENT ALGORITHM FOR SICKLE CELL DISEASE","authors":"Metin Çil","doi":"10.1016/j.htct.2025.106183","DOIUrl":"10.1016/j.htct.2025.106183","url":null,"abstract":"<div><div>Sickle cell disease (SCD) is an autosomal recessive hemoglobinopathy characterized by the polymerization of Hemoglobin S (HbS), which results from a point mutation in the β-globin gene. The clinical heterogeneity of the disease is dictated by a complex interplay of three core pathophysiological mechanisms: vaso-occlusion (VOC), driven by erythrocyte rigidity secondary to deoxy-HbS polymerization; chronic hemolytic anemia, resulting from a shortened erythrocyte lifespan; and a state of chronic sterile inflammation and ischemia-reperfusion injury, triggered by the scavenging of nitric oxide (NO) by cell-free hemoglobin. While HbSS and HbS/β⁰-thalassemia genotypes constitute the most severe phenotypes, therapeutic algorithms are designed to target these fundamental molecular underpinnings.</div></div><div><h3>Foundational Management and Prevention in SCD</h3><div>The cornerstone of modern SCD management is rooted in proactive and preventive medicine. Early diagnosis through newborn screening programs facilitates the immediate initiation of penicillin prophylaxis (from 2 months to 5 years of age) and comprehensive vaccinations (against <em>Pneumococcus, Meningococcus</em>, and <em>H. influenzae</em>), which dramatically reduce the risk of invasive pneumococcal disease secondary to functional asplenia. Primary stroke prevention in the pediatric population (ages 2-16) relies on annual Transcranial Doppler (TCD) screening. A time-averaged mean of maximum velocity exceeding 200 cm/sec is an absolute indication for initiating a chronic transfusion program, a measure proven to reduce stroke risk by over 90%. Hydroxyurea remains the cornerstone of this foundational care, recommended for all patients with severe genotypes over the age of 9 months. When titrated to the maximum tolerated dose (MTD), its pleiotropic effects—including the induction of fetal hemoglobin (HbF) and its anti-inflammatory and anti-adhesive properties—significantly modify the disease course.</div></div><div><h3>Management of Acute Complications</h3><div>Acute complications warrant standardized and aggressive intervention. The management of vaso-occlusive crises (VOCs) necessitates rapid, multimodal analgesia, featuring the administration of parenteral opioids and non-steroidal anti-inflammatory drugs (NSAIDs) within 30 to 60 minutes of presentation. Acute Chest Syndrome (ACS), a leading cause of mortality, is managed with broad-spectrum antibiotics, supplemental oxygen, and transfusion support. In cases of severe ACS, the 2020 American Society of Hematology (ASH) guidelines recommend exchange transfusion over simple transfusion to rapidly decrease the HbS fraction to less than 30%. Similarly, acute ischemic stroke constitutes a hematologic emergency that mandates immediate exchange transfusion to reduce the HbS level to below 30%.</div></div><div><h3>Chronic Complications and Disease-Modifying Therapies</h3><div>For patients with a suboptimal response to or intolerance of hyd","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106183"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796981","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":"LABORATORY EVALUATION IN MYELOMA: WHICH TESTS SHOULD BE PREFERRED DURING DIAGNOSIS AND FOLLOW-UP?","authors":"Burcu Altındağ Avcı","doi":"10.1016/j.htct.2025.106202","DOIUrl":"10.1016/j.htct.2025.106202","url":null,"abstract":"<div><h3>Introduction</h3><div>Multiple myeloma (MM) is a plasma cell malignancy characterized by clonal proliferation of abnormal plasma cells, production of monoclonal immunoglobulins, and organ dysfunction, often defined by the CRAB criteria (hypercalcemia, renal impairment, anemia, and bone disease). Laboratory testing is central to diagnosis, risk assessment, and monitoring during therapy and remission.</div></div><div><h3>Baseline Evaluation at Diagnosis</h3><div><strong>Hematology and Biochemistry</strong></div><div>- CBC with differential → detection of anemia, leukopenia, or thrombocytopenia.</div><div>- Biochemistry panel → creatinine, urea, calcium, albumin, LDH.</div><div>- β2-microglobulin and albumin → incorporated into the Revised International Staging System (R-ISS).</div><div>- CRP may reflect disease activity (IL-6 driven).</div></div><div><h3>Monoclonal Protein Studies</h3><div>- Serum protein electrophoresis (SPEP): quantifies the M-spike.</div><div>- Urine protein electrophoresis (UPEP, 24 h): detects Bence Jones proteinuria.</div><div>- Immunofixation (serum and urine): confirms the type of heavy and light chain.</div><div>- Serum free light chain (sFLC) assay: critical for light-chain, non-secretory, and oligo-secretory myeloma.</div><div><strong>Bone Marrow Examination</strong></div><div>- Morphology: percentage of plasma cells.</div><div>- Multiparameter flow cytometry: demonstrates clonality and immunophenotype.</div><div>- Cytogenetics/FISH: identifies high-risk abnormalities (del[17p], t[4;14], t[14;16]) that influence prognosis.</div><div><strong>Laboratory Evaluation During Follow-Up</strong></div><div><strong>Routine Monitoring</strong></div><div>- M-protein quantification (SPEP/UPEP): mainstay of monitoring.</div><div>- Immunofixation: required to confirm complete response.</div><div>- sFLC assay: sensitive tool for relapse, especially in light-chain disease.</div><div>- CBC, renal function, calcium, LDH, β2-microglobulin: routine for treatment toxicity and disease burden.</div><div><strong>Advanced Monitoring</strong></div><div>- Minimal Residual Disease (MRD): assessed via next-generation flow cytometry or next-generation sequencing. MRD negativity correlates with superior survival and is increasingly used as a response endpoint.</div><div>- Mass spectrometry and liquid biopsy are promising future tools for detecting residual disease with high sensitivity.</div><div><strong>Preferred Tests in Clinical Practice</strong></div><div>- At diagnosis: a comprehensive panel including SPEP, UPEP, serum/urine immunofixation, sFLC, bone marrow studies (with cytogenetics/FISH), and advanced imaging is essential.</div><div>- During follow-up: routine monitoring can be streamlined to SPEP and sFLC, supplemented by basic hematology and chemistry. UPEP is reserved for patients with baseline significant proteinuria.</div><div>- In specialized centers: MRD testing should be incorporated, especially in clinical trials, to refine re","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106202"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796995","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":"ACQUIRED PYRUVATE KINASE DEFICIENCY FOLLOWED BY MYELODYSPLASTIC SYNDROME: A CASE REPORT","authors":"Salih Sertaç Durusoy,&nbsp;Sinem Çubukçu,&nbsp;Gönül Irmak","doi":"10.1016/j.htct.2025.106170","DOIUrl":"10.1016/j.htct.2025.106170","url":null,"abstract":"<div><h3>Introduction</h3><div>Pyruvate kinase (PK) deficiency is an autosomal recessive red blood cell (RBC) enzymopathy leading to chronic hemolysis. It is the second most common RBC enzymopathy and the most frequent cause of chronic hemolytic anemia due to an enzyme defect. PK enzymes consist of various isoforms encoded by PKLR and PKM genes, which catalyze the conversion of phosphoenolpyruvate (PEP) to pyruvate and ATP in the final step of glycolysis. Clinically significant PK deficiency is associated with PKLR mutations. Acquired PK deficiency is extremely rare, and its molecular basis remains unclear. Some cases have been associated with AML. Here we present a rare case of acquired PK deficiency followed by myelodysplastic syndrome (MDS).</div></div><div><h3>Case Presentation</h3><div>A 70-year-old male presented with fatigue, weakness, and jaundice. Laboratory findings were as follows: WBC: 7.0 × 10⁹/L, Hemoglobin: 7.9 g/dL, MCV: 101 fL, Platelets: 601 × 10⁹/L, Total bilirubin: 1.6 mg/dL (indirect: 1.0 mg/dL), LDH: 280 U/L. Other biochemical parameters were within normal limits. Hemoglobin electrophoresis was normal. Direct and indirect Coombs tests were negative. Haptoglobin was 14 mg/dL (low). Erythrocyte PK activity was reduced at 3.16 U/g Hb (reference: 4.4–5.9). G6PD activity and osmotic fragility were normal.</div><div>The patient had no prior anemia history. Genetic analysis for PKLR mutations was negative, supporting an acquired form. During follow-up, bilirubin increased to 8.6 mg/dL, LDH rose to 800 U/L, and hemoglobin decreased to 6.0 g/dL. The patient was taking gliclazide for diabetes mellitus, which was discontinued due to suspicion of hemolysis induction. Bilirubin subsequently decreased. Bone marrow biopsy showed dysplastic erythroid changes without blast increase, consistent with MDS. The patient initially required two RBC transfusions weekly, but after gliclazide withdrawal, the requirement decreased to one unit every two weeks. Genetic testing for MDS is ongoing.</div></div><div><h3>Discussion &amp; Conclusion</h3><div>Acquired PK deficiency is extremely rare. In this case, a 70-year-old patient developed PK deficiency followed by a diagnosis of MDS. While congenital hemolytic anemias usually present in younger patients, clinicians should be aware that acquired cases may appear later in life. Careful evaluation of medications and bone marrow disorders is essential in elderly patients with unexplained hemolysis.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106170"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796503","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":"Familial Multiple Myeloma in a Post-Renal Transplant Patient: A Case of Smoldering Multiple Myeloma with Strong Family History","authors":"Ali Turunç,&nbsp;Birol Güvenç","doi":"10.1016/j.htct.2025.106127","DOIUrl":"10.1016/j.htct.2025.106127","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Familial multiple myeloma represents approximately 1-2% of all MM cases, characterized by the occurrence of MM in two or more first-degree relatives. While the exact genetic mechanisms remain unclear, several familial clustering studies suggest inherited susceptibility genes and shared environmental factors. Immunosuppression following solid organ transplantation may accelerate malignant transformation in genetically predisposed individuals, creating a unique clinical scenario requiring specialized monitoring and management approaches.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Case Report&lt;/h3&gt;&lt;div&gt;A 50-year-old female with a complex medical history presented with fatigue, weakness, and anemia. Her medical background included type 1 diabetes mellitus diagnosed in 1982 at age 8, progression to end-stage renal disease secondary to diabetic nephropathy in 2001, and successful deceased donor kidney transplantation in 2007. She remained on chronic immunosuppressive therapy with mycophenolic acid (Myfortic®) and cyclosporine (Sandimmun®) with stable graft function.&lt;/div&gt;&lt;div&gt;The patient's family history was remarkable for multiple myeloma: her mother was alive with confirmed MM diagnosis, and her brother had previously died from MM after receiving treatment. This strong familial clustering placed her in the high-risk category for hereditary MM predisposition.&lt;/div&gt;&lt;div&gt;Physical examination revealed pallor consistent with anemia, but no lymphadenopathy, bone tenderness, or other significant findings. Laboratory evaluation demonstrated significant anemia (hemoglobin 7.8 g/dL, hematocrit 26.2%) with normocytic indices (MCV 87 fL). Renal function remained stable post-transplant, and serum calcium was within normal limits.&lt;/div&gt;&lt;div&gt;Protein studies revealed elevated beta-2 fraction on serum protein electrophoresis with positive IgG-kappa monoclonal band on immunofixation electrophoresis. Free light chain analysis showed elevated kappa (40.7 mg/L) with kappa/lambda ratio of 1.86.&lt;/div&gt;&lt;div&gt;Bone marrow examination demonstrated 3-4% plasma cells with flow cytometry confirming CD138+/CD38+ phenotype and kappa light chain restriction (80% kappa, 20% lambda), establishing clonality. Comprehensive FISH analysis was negative for high-risk cytogenetic abnormalities including p53 deletion, del(13q), t(11;14), and t(4;14).&lt;/div&gt;&lt;div&gt;Lumbar MRI revealed disc protrusions without lytic bone lesions. Genetic analysis for FMF mutations was performed given potential inflammatory contributions, showing R202Q heterozygosity and other polymorphisms without pathogenic significance.&lt;/div&gt;&lt;div&gt;Based on the presence of IgG-kappa monoclonal protein, 3-4% clonal bone marrow plasma cells, anemia, and absence of hypercalcemia or lytic lesions, the patient was diagnosed with smoldering multiple myeloma.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Discussion&lt;/h3&gt;&lt;div&gt;This case illustrates several important aspects of familial MM. The strong family history with both maternal and sibling involvement sugg","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106127"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796548","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":"IRON CHELATİON İN MYELODYSPLASTİC SYNDROMES: WHO AND WHEN?","authors":"Hande Oğul Sücüllü","doi":"10.1016/j.htct.2025.106181","DOIUrl":"10.1016/j.htct.2025.106181","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Red blood cell (RBC) transfusions are the cornerstone of supportive care in patients with myelodysplastic syndromes (MDS). While transfusions alleviate symptomatic anemia, they inevitably lead to progressive iron accumulation in patients. This transfusional iron overload may exert toxic effects on the heart, liver, endocrine system, ultimately contributing to increased morbidity and mortality. Timely initiation of iron chelation therapy has become an important consideration in the comprehensive management of MDS.&lt;/div&gt;&lt;div&gt;Chelation is primarily indicated for patients with lower-risk MDS (IPSS low or Int-1) who are expected to have longer survival, who remain transfusion-dependent. In such patients, iron overload not only threatens organ function also worsens prognosis. Multiple studies have shown that transfusion dependence is a negative prognostic factor, and retrospective analyses suggest that iron chelation may improve overall survival. Chelation is also particularly important in patients who are candidates for allogeneic stem cell transplantation, since excess iron has been associated with inferior transplant outcomes. By reducing systemic iron burden, chelation help optimize organ function and improve transplant eligibility.&lt;/div&gt;&lt;div&gt;The decision is usually guided by transfusion history and serum ferritin levels. Most guidelines recommend considering chelation after approximately 20–30 units of RBC transfusions or when serum ferritin persistently exceeds 2500 ng/mL. The therapeutic goal is to maintain ferritin below 1000 ng/mL, minimizing iron-mediated oxidative stress and tissue damage. While serum ferritin is an imperfect surrogate, it remains a practical marker. More advanced techniques such as MRI T2* or SQUID can provide direct estimates of hepatic iron, but their availability is limited.&lt;/div&gt;&lt;div&gt;Three chelators are currently in clinical use. Deferoxamine, administered subcutaneously or intramuscularly, is effective but limited by its parenteral route. Deferasirox, an oral once-daily agent, has become the preferred choice in many cases and is FDA-approved for transfusion-related iron overload. Randomized trials in lower-risk MDS demonstrated that deferasirox reduced ferritin, improved event-free survival, and even enhanced hematologic response in some patients. However, renal, hepatic toxicity require careful monitoring. Deferiprone, another oral agent, is mainly approved for thalassemia, can be considered when other chelators fail, though its use in MDS remains limited due to risk of agranulocytosis.&lt;/div&gt;&lt;div&gt;Chelation has been associated with improved overall survival in observational studies, prospective trials provide encouraging evidence. Beyond survival, reversal of some iron-related cardiac, hepatic damage has been documented, underscoring its importance. Monitoring should include serial ferritin, renal, liver function, vigilance for adverse events. Individualization is critical: patients with advanced or high-risk","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106181"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796693","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":"REFRACTORY CHRONIC MYELOID LEUKEMIA: A REVIEW OF CURRENT THERAPEUTIC LANDSCAPE AND EMERGING CHALLENGES","authors":"DENİZ ÖZMEN","doi":"10.1016/j.htct.2025.106185","DOIUrl":"10.1016/j.htct.2025.106185","url":null,"abstract":"<div><div>Chronic myeloid leukemia (CML) has become a paradigm of targeted therapy success; however, a proportion of patients develop refractory disease, marked by failure or intolerance to multiple TKIs. Optimal management requires integrating molecular, clinical, and patient-related factors into therapeutic decision-making [1,2].</div></div><div><h3>Mechanisms of Resistance and Genetic Complexity</h3><div>Resistance is commonly mediated by BCR::ABL1 kinase domain mutations. While second-generation TKIs (dasatinib, nilotinib, bosutinib) address many resistant clones, the T315I substitution remains uniquely sensitive to ponatinib [3,4]. Beyond kinase domain changes, clonal evolution with mutations in ASXL1, RUNX1, IKZF1, TP53, and DNMT3A has been increasingly recognized. These lesions, frequently encountered in advanced phases, are associated with poor response to TKIs, higher risk of progression, and inferior survival [5,6].</div></div><div><h3>Current Therapeutic Approaches</h3><div>Ponatinib remains the agent of choice for patients harboring T315I or compound mutations, with careful risk management to mitigate vascular events [4]. Asciminib, a first-in-class STAMP inhibitor targeting the myristoyl pocket of BCR::ABL1, has emerged as a major advance. By restoring kinase autoinhibition, asciminib demonstrated superior efficacy and tolerability over bosutinib in the ASCEMBL trial [3] and has shown promising results in real-world refractory populations.</div></div><div><h3>TKI Selection Considerations</h3><div>In clinical practice, TKI selection is guided by a combination of mutational status and comorbidities. Specific mutations confer resistance to certain TKIs, making mutation-directed sequencing essential. At the same time, patient comorbidities such as cardiovascular, pulmonary, or metabolic disease influence drug tolerability and safety, thereby shaping the optimal therapeutic choice [1,7].</div></div><div><h3>Beyond TKIs</h3><div>For patients failing multiple TKIs, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only potentially curative approach, particularly in younger and high-risk patients [1,2]. Novel strategies under investigation include rational TKI combinations (e.g., asciminib plus ponatinib), immunotherapeutic approaches, and targeted inhibition of epigenetic regulators [8].</div></div><div><h3>Conclusion</h3><div>Refractory CML reflects the biological and clinical complexity of disease progression beyond BCR::ABL1 dependence. While ponatinib and asciminib have redefined therapeutic opportunities, additional high-risk mutations highlight the need for precision medicine strategies. Tailored TKI sequencing, integration of comorbidity profiles, and timely transplantation remain central pillars, while ongoing translational research promises to expand future options [7,8].</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106185"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796835","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":"WALDENSTRÖM MACROGLOBULINEMIA","authors":"Zekeriya Aksöz","doi":"10.1016/j.htct.2025.106184","DOIUrl":"10.1016/j.htct.2025.106184","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Waldenström Macroglobulinemia (WM) is a rare disease. The median age at diagnosis is 70 years and approximately 60 percent of patients are male. The etiology of WM is not fully understood. Approximately 90-95% of WM patients have mutations in the MYD88 L265P gene and 40% have recurrent mutations in the CXCR4 gene.&lt;/div&gt;&lt;div&gt;The clonal B cell population leads to abnormal monoclonal IgM production. The pentameric configuration of IgM molecules increases serum viscosity, slowing blood flow through capillaries. In patients with WM, clonal B cells can directly infiltrate hematopoietic tissues, causing cytopenias (e.g., anemia, thrombocytopenia, neutropenia), lymphadenopathy, hepatomegaly, and/or splenomegaly. Rarely, plasmacytoid lymphocytes may infiltrate the central nervous system or meninges.&lt;/div&gt;&lt;div&gt;Most patients with WM present with nonspecific constitutional symptoms but up to a quarter of patients may be asymptomatic at diagnosis. Common symptoms include weakness, fatigue, weight loss, and nose and gum bleeding.&lt;/div&gt;&lt;div&gt;Bone marrow aspiration and biopsy demonstrating lymphoplasmacytic lymphoma is an important component of the diagnosis of WM. The biopsy specimen is usually hypercellular and densely infiltrated with lymphoid and plasmacytoid cells. Intranuclear vacuoles containing IgM monoclonal protein (Dutcher bodies) are common in the malignant cells of WM.&lt;/div&gt;&lt;div&gt;The following criteria must be met for a diagnosis of WM:&lt;/div&gt;&lt;div&gt; &lt;!--&gt;• IgM monoclonal gammopathy (any level) must be present in the serum.&lt;/div&gt;&lt;div&gt; &lt;!--&gt;• ≥10% of the bone marrow biopsy specimen must show infiltration by small lymphocytes with plasmacytoid or plasma cell differentiation (lymphoplasmacytic features or lymphoplasmacytic lymphoma) and an intertrabecular pattern.&lt;/div&gt;&lt;div&gt; &lt;!--&gt;• The infiltrate should express a typical immunophenotype (e.g., surface IgM+, CD5-/+, CD10-, CD11c-, CD19+, CD20+, CD22+, CD23-, CD25+, FMC7+, CD103-, CD138-). The plasmacytic component will be CD138+, CD38+, and CD45- or less prominent.&lt;/div&gt;&lt;div&gt;The differential diagnosis includes chronic lymphocytic leukemia, marginal zone and mantle cell lymphoma.&lt;/div&gt;&lt;div&gt;Not every VM patient requires treatment. For asymptomatic patients, follow-up without treatment every 3-6 months is recommended.&lt;/div&gt;&lt;div&gt;Treatment is indicated for patients with symptomatic WM if any of the following are attributable to WM:&lt;/div&gt;&lt;div&gt; &lt;!--&gt;• Systemic symptoms: B symptoms such as recurrent fever, severe night sweats, fatigue and/or unintentional weight loss&lt;/div&gt;&lt;div&gt; &lt;!--&gt;• Cytopenias: Hemoglobin ≤10 g/dL or platelet count &lt;100,000/microL; cold agglutinin anemia, immune hemolytic anemia, and/or thrombocytopenia&lt;/div&gt;&lt;div&gt; &lt;!--&gt;• Symptomatic or large (≥5 cm) lymphadenopathy, symptomatic splenomegaly and/or tissue infiltration&lt;/div&gt;&lt;div&gt; &lt;!--&gt;• End-organ damage: Hyperviscosity, peripheral neuropathy, immunoglobulin light chain (AL) amyloidosis with organ dysfunction, symptomatic cryoglobulinemi","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106184"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796836","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":"CHRONİC LYMPHOCYTIC LEUKEMIA (CLL): IMMUNOGENETICS AND DIAGNOSIS","authors":"Meryem Şener","doi":"10.1016/j.htct.2025.106209","DOIUrl":"10.1016/j.htct.2025.106209","url":null,"abstract":"&lt;div&gt;&lt;div&gt;CLL is a monoclonal proliferation of mature B lymphocytes defined by an absolute clonal count ≥5 × 10⁹/L in blood. CLL is clinically heterogeneous: some patients remain asymptomatic for years, whereas others need multiple lines of therapy. BCR biology and immunogenetics. A central driver of CLL biology is B-cell receptor (BCR) signaling. Compared with normal B cells, CLL cells display low IgM expression, variable responses to antigen, and tonic activation of anti-apoptotic pathways. Gene-expression and tissue array studies show up-regulation of BCR-pathway genes in lymph nodes and marrow versus blood, highlighting microenvironmental homing. The IGHV mutation status is a key immunogenetic marker: about 60% of patients have IGHV mutated ≥2% from germline (typically indolent course), while ∼40% have unmutated IGHV (&lt;2%), associated with faster progression and shorter survival before the era of BCR-targeted therapies. Roughly 30% of cases carry stereotyped BCRs; certain stereotyped subsets (e.g., 1 and 2) predict higher-risk disease. Cytogenetic lesions. Recurrent abnormalities identified by FISH (and, when needed, stimulated metaphase karyotype) include del(13q14.3) (most common; favorable when isolated), trisomy 12 (intermediate risk), del(11q22.3) involving ATM (bulky nodes, aggressive disease in younger patients), and del(17p13.1) affecting TP53 (worst prognosis, poor response to traditional chemotherapy). Complex karyotype (≥3 abnormalities) adversely impacts time to treatment and overall survival. Because clonal evolution can occur even without therapy, FISH (± cytogenetics) should be reassessed before each line of treatment, particularly to detect new del(17p). Gene mutations and microRNAs. CLL genomes are relatively simple (≈20 nonsynonymous changes and ≈5 structural lesions on average) and lack a unifying driver. Recurrently mutated genes include SF3B1, NOTCH1, MYD88, ATM, and TP53. NOTCH1 mutations (∼15%) often co-occur with trisomy 12 and may confer reduced sensitivity to anti-CD20 antibodies and increased risk of Richter transformation; SF3B1 relates to DNA-damage responses; TP53 mutations rise from ∼5% in early untreated disease to ∼40% in advanced disease, frequently coexisting with del(17p). ATM mutations (10–15%) often accompany del(11q). MYD88 mutations are enriched in IGHV-mutated CLL and associate with a more indolent course. Non-coding alterations are also relevant: del(13q14.3) deletes the miR-15/16 cluster, derepressing anti-apoptotic programs (e.g., BCL2); loss of miR-181a and over-expression of miR-155 further support leukemic survival. Immune dysregulation. Beyond the malignant clone, CLL features innate and adaptive immune defects: reduced complement, qualitative neutrophil and NK-cell dysfunction, CD4⁺ T-cell exhaustion with impaired cytotoxicity, Th1→Th2 polarization, and T-regulatory expansion. Hypogammaglobulinemia is common (≈85% over the disease course), with low IgG/IgA correlating with infections. Diagno","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106209"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796840","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}