Pub Date : 2025-12-01DOI: 10.1016/j.htct.2025.106115
Naciye Nur Tozluklu, Birol Güvenç
<div><h3>Introduction</h3><div>Chronic lymphocytic leukemia represents the most common adult leukemia in Western countries, with autoimmune hemolytic anemia occurring as a complication in 5-10% of cases. AIHA as the presenting feature of CLL is uncommon, particularly in young adults where CLL incidence is extremely rare. The immunophenotypic heterogeneity of CLL, including atypical variants, may influence both clinical presentation and treatment response.</div></div><div><h3>Case Reports</h3><div>Case 1: An 84-year-old female presented with progressive fatigue, weakness, and dyspnea. Laboratory evaluation revealed severe anemia (Hb: 9.3 g/dL), marked leukocytosis (42.36 × 10³/μL), and thrombocytopenia. Direct antiglobulin test was strongly positive (3+), confirming warm-type AIHA. Flow cytometry demonstrated classic CLL immunophenotype: CD19+ (93%), CD5+ (95%), CD23+ (84%), CD20+ (52%), with absent CD38 expression suggesting favorable-risk disease. Bone marrow biopsy confirmed CLL/SLL with 50% infiltration. Treatment with prednisolone rapidly resolved hemolysis, followed by ibrutinib therapy for CLL. The patient achieved sustained remission over 12 months with corticosteroid discontinuation after 3 months.</div><div>Case 2: A 25-year-old male presented with dyspnea, palpitations, and fatigue. Initial workup revealed severe anemia (Hb: 7.8 g/dL), reticulocytosis (6.8%), and elevated LDH with spherocytes on peripheral smear. Direct antiglobulin test was strongly positive (4+). Investigation revealed lymphocytosis (14,200/mm³, 68% lymphocytes) with atypical CLL immunophenotype: CD5+/CD19+/FMC7+/CD23-, distinguishing it from typical CLL while excluding mantle cell lymphoma through negative cyclin D1. TP53 abnormalities were absent. Initial prednisolone therapy provided insufficient response, prompting rituximab monotherapy (375 mg/m² × 4 cycles). The patient achieved complete hematologic response with hemoglobin normalization (11.6 g/dL), reticulocyte count resolution, and lymphocytosis improvement.</div></div><div><h3>Discussion</h3><div>These cases illustrate important clinical principles in CLL-associated AIHA management. The elderly patient presented with classic CLL immunophenotype and favorable prognostic markers (CD38-negative), supporting the choice of BTK inhibitor therapy appropriate for her age and comorbidities. The young adult case demonstrated atypical CLL immunophenotype (FMC7+/CD23-), representing a variant phenotype that required careful differentiation from mantle cell lymphoma.</div><div>The treatment approaches differed significantly based on age and disease characteristics. The elderly patient benefited from targeted therapy (ibrutinib) combined with corticosteroids, while the young patient achieved excellent response with rituximab monotherapy after steroid failure. This highlights the importance of individualized treatment selection based on patient factors and disease biology.</div><div>Both cases emphasize the critical role o
{"title":"Autoimmune Hemolytic Anemia as the Presenting Feature of Chronic Lymphocytic Leukemia: Two Contrasting Cases Across Different Age Groups","authors":"Naciye Nur Tozluklu, Birol Güvenç","doi":"10.1016/j.htct.2025.106115","DOIUrl":"10.1016/j.htct.2025.106115","url":null,"abstract":"<div><h3>Introduction</h3><div>Chronic lymphocytic leukemia represents the most common adult leukemia in Western countries, with autoimmune hemolytic anemia occurring as a complication in 5-10% of cases. AIHA as the presenting feature of CLL is uncommon, particularly in young adults where CLL incidence is extremely rare. The immunophenotypic heterogeneity of CLL, including atypical variants, may influence both clinical presentation and treatment response.</div></div><div><h3>Case Reports</h3><div>Case 1: An 84-year-old female presented with progressive fatigue, weakness, and dyspnea. Laboratory evaluation revealed severe anemia (Hb: 9.3 g/dL), marked leukocytosis (42.36 × 10³/μL), and thrombocytopenia. Direct antiglobulin test was strongly positive (3+), confirming warm-type AIHA. Flow cytometry demonstrated classic CLL immunophenotype: CD19+ (93%), CD5+ (95%), CD23+ (84%), CD20+ (52%), with absent CD38 expression suggesting favorable-risk disease. Bone marrow biopsy confirmed CLL/SLL with 50% infiltration. Treatment with prednisolone rapidly resolved hemolysis, followed by ibrutinib therapy for CLL. The patient achieved sustained remission over 12 months with corticosteroid discontinuation after 3 months.</div><div>Case 2: A 25-year-old male presented with dyspnea, palpitations, and fatigue. Initial workup revealed severe anemia (Hb: 7.8 g/dL), reticulocytosis (6.8%), and elevated LDH with spherocytes on peripheral smear. Direct antiglobulin test was strongly positive (4+). Investigation revealed lymphocytosis (14,200/mm³, 68% lymphocytes) with atypical CLL immunophenotype: CD5+/CD19+/FMC7+/CD23-, distinguishing it from typical CLL while excluding mantle cell lymphoma through negative cyclin D1. TP53 abnormalities were absent. Initial prednisolone therapy provided insufficient response, prompting rituximab monotherapy (375 mg/m² × 4 cycles). The patient achieved complete hematologic response with hemoglobin normalization (11.6 g/dL), reticulocyte count resolution, and lymphocytosis improvement.</div></div><div><h3>Discussion</h3><div>These cases illustrate important clinical principles in CLL-associated AIHA management. The elderly patient presented with classic CLL immunophenotype and favorable prognostic markers (CD38-negative), supporting the choice of BTK inhibitor therapy appropriate for her age and comorbidities. The young adult case demonstrated atypical CLL immunophenotype (FMC7+/CD23-), representing a variant phenotype that required careful differentiation from mantle cell lymphoma.</div><div>The treatment approaches differed significantly based on age and disease characteristics. The elderly patient benefited from targeted therapy (ibrutinib) combined with corticosteroids, while the young patient achieved excellent response with rituximab monotherapy after steroid failure. This highlights the importance of individualized treatment selection based on patient factors and disease biology.</div><div>Both cases emphasize the critical role o","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106115"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796553","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}
<div><h3>Introduction</h3><div>Histiocytic sarcoma (HS) is an exceptionally rare and aggressive hematopoietic malignancy, representing less than 1% of hematologic neoplasms [1]. No standardized therapeutic regimen exists; patients are often treated with lymphoma-like regimens such as CHOP or ICE, with limited efficacy and median survival of approximately six months [2,1]. Recent advances in molecular pathology have revealed recurrent BRAF^V600E mutations, ALK rearrangements, and PD-L1 expression, providing new diagnostic and therapeutic implications [3]. Case-based evidence suggests that PD-1 inhibitors may induce durable responses in select patients with PD-L1–positive HS [4,5].</div></div><div><h3>Case Presentation</h3><div>A 28-year-old male presented with abdominal pain and swelling. Imaging demonstrated a large intra-abdominal mass with peritoneal implants. Histopathology confirmed HS, positive for CD45, CD163, and CD14, with a Ki-67 index of 80%. Bone marrow biopsy was normocellular. Molecular analysis excluded BRAF and ALK alterations but demonstrated PD-L1 expression with a tumor proportion score (TPS) of 1–49% and a combined positive score (CPS) of 35%. The patient was started on ICE chemotherapy (ifosfamide, carboplatin, etoposide). Following biomarker analysis, nivolumab was introduced beginning with the second cycle. The treatment was well tolerated, and subsequent PET-CT demonstrated marked metabolic regression with clinical improvement. Follow-up abdominal imaging confirmed complete radiological response, with disappearance of the initially described mesenteric mass.</div></div><div><h3>Conclusion</h3><div>Discussion HS poses a therapeutic challenge because of its aggressive course and lack of standardized therapy [2,1]. Conventional chemotherapy regimens have limited durability, and reported responses are often transient. The presence of PD-L1 expression provided a rationale for incorporating a PD-1 inhibitor, even at moderate expression levels, consistent with emerging literature [4]. Previous case reports have demonstrated clinical benefit from pembrolizumab and nivolumab in PD-L1–positive HS, including durable complete responses [5]. In this patient, radiological assessment corroborated complete remission after combined ICE and nivolumab, supporting the potential role of checkpoint inhibition in improving depth of response. This case represents one of the few documented examples of combining intensive chemotherapy with checkpoint blockade in HS, highlighting the potential synergistic role of immunotherapy.Conclusion This case illustrates the rarity and therapeutic complexity of HS. The addition of nivolumab to ICE chemotherapy, guided by PD-L1 expression, resulted in meaningful clinical response in a young patient with advanced disease. These findings underscore the importance of integrated histopathological and molecular assessment in guiding personalized management for HS.Keywords: Histiocytic sarcoma; Nivolumab; ICE protocol;
{"title":"THERAPEUTIC CHALLENGE IN HISTIOCYTIC SARCOMA: A CASE REPORT OF NIVOLUMAB ADDITION TO THE ICE PROTOCOL","authors":"Ali Turunç, Berrak Çağla Şenol Arslan, Ayşegül Ezgi Çetin, Birol Güvenç","doi":"10.1016/j.htct.2025.106119","DOIUrl":"10.1016/j.htct.2025.106119","url":null,"abstract":"<div><h3>Introduction</h3><div>Histiocytic sarcoma (HS) is an exceptionally rare and aggressive hematopoietic malignancy, representing less than 1% of hematologic neoplasms [1]. No standardized therapeutic regimen exists; patients are often treated with lymphoma-like regimens such as CHOP or ICE, with limited efficacy and median survival of approximately six months [2,1]. Recent advances in molecular pathology have revealed recurrent BRAF^V600E mutations, ALK rearrangements, and PD-L1 expression, providing new diagnostic and therapeutic implications [3]. Case-based evidence suggests that PD-1 inhibitors may induce durable responses in select patients with PD-L1–positive HS [4,5].</div></div><div><h3>Case Presentation</h3><div>A 28-year-old male presented with abdominal pain and swelling. Imaging demonstrated a large intra-abdominal mass with peritoneal implants. Histopathology confirmed HS, positive for CD45, CD163, and CD14, with a Ki-67 index of 80%. Bone marrow biopsy was normocellular. Molecular analysis excluded BRAF and ALK alterations but demonstrated PD-L1 expression with a tumor proportion score (TPS) of 1–49% and a combined positive score (CPS) of 35%. The patient was started on ICE chemotherapy (ifosfamide, carboplatin, etoposide). Following biomarker analysis, nivolumab was introduced beginning with the second cycle. The treatment was well tolerated, and subsequent PET-CT demonstrated marked metabolic regression with clinical improvement. Follow-up abdominal imaging confirmed complete radiological response, with disappearance of the initially described mesenteric mass.</div></div><div><h3>Conclusion</h3><div>Discussion HS poses a therapeutic challenge because of its aggressive course and lack of standardized therapy [2,1]. Conventional chemotherapy regimens have limited durability, and reported responses are often transient. The presence of PD-L1 expression provided a rationale for incorporating a PD-1 inhibitor, even at moderate expression levels, consistent with emerging literature [4]. Previous case reports have demonstrated clinical benefit from pembrolizumab and nivolumab in PD-L1–positive HS, including durable complete responses [5]. In this patient, radiological assessment corroborated complete remission after combined ICE and nivolumab, supporting the potential role of checkpoint inhibition in improving depth of response. This case represents one of the few documented examples of combining intensive chemotherapy with checkpoint blockade in HS, highlighting the potential synergistic role of immunotherapy.Conclusion This case illustrates the rarity and therapeutic complexity of HS. The addition of nivolumab to ICE chemotherapy, guided by PD-L1 expression, resulted in meaningful clinical response in a young patient with advanced disease. These findings underscore the importance of integrated histopathological and molecular assessment in guiding personalized management for HS.Keywords: Histiocytic sarcoma; Nivolumab; ICE protocol;","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106119"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796697","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}
Pub Date : 2025-12-01DOI: 10.1016/j.htct.2025.106125
Berrak Çağla Şenol, Ayşegül Ezgi Çetin, Ali Turunç, Birol Güvenç
<div><h3>Case Report</h3><div>A 59-year-old male (weight: 65 kg, height: 168 cm) presented in September 2024 with a progressively enlarging mass in the right maxillary region extending toward the temporal area with sphenoid bone proximity. The patient complained of maxillary distortion and pain but denied B symptoms including fever, night sweats, or weight loss.</div><div>Physical examination revealed facial asymmetry with palpable right maxillary swelling. Initial biopsy of the maxillary mass demonstrated CD20-positive extranodal marginal zone lymphoma consistent with MALT lymphoma histology.</div><div>Staging F-18 FDG PET/CT performed on October 4, 2024, revealed a hyperintense soft tissue mass in the right maxillary region with sphenoid bone invasion showing SUVmax 6.81. Additionally, a 16 × 10 mm lymph node in the right level 2 cervical chain demonstrated SUVmax 4.22. No pathological FDG uptake was detected in the thorax, abdomen, or skeletal system, confirming localized disease.</div><div>Based on the diagnosis of localized EMZL with bone invasion and cervical lymph node involvement, standard R-CHOP chemotherapy was initiated on September 24, 2024. The regimen consisted of rituximab 375 mg/m² (day 1), cyclophosphamide 750 mg/m² (day 1), doxorubicin 50 mg/m² (day 1), vincristine 1.4 mg/m² (day 1), and prednisolone 100 mg daily for 5 days. Supportive care included G-CSF (filgrastim) for neutropenia prophylaxis and antiemetics (ondansetron, granisetron).</div><div>During treatment, the patient developed E. coli pneumonia, which resolved with appropriate antibiotic therapy and supportive care. Despite this complication, the treatment protocol was successfully completed.</div><div>Interim PET-CT evaluation on December 25, 2024, demonstrated significant metabolic response with maxillary lesion SUVmax decreasing from 6.81 to 2.92, accompanied by dimensional reduction. Cervical lymph node involvement was no longer detectable, yielding a Deauville score of 2, consistent with partial metabolic remission.</div><div>Follow-up PET-CT after completion of 4 cycles in March 2025 revealed complete disappearance of pathological FDG uptake throughout the body. The maxillary region showed no residual mass formation, maintaining Deauville score 2, confirming complete metabolic remission.</div><div>The patient tolerated treatment well overall and entered surveillance follow-up without evidence of systemic dissemination or bone marrow involvement.</div></div><div><h3>Discussion</h3><div>This case represents a rare presentation of EMZL involving the maxillofacial region with sphenoid bone invasion. The excellent response to standard R-CHOP therapy challenges the traditional approach of radiotherapy alone for localized EMZL, particularly in cases with bone involvement where complete surgical resection may not be feasible. The use of PET-CT for treatment response assessment proved invaluable, providing objective metabolic parameters through Deauville scoring system.
{"title":"Primary Extranodal Marginal Zone Lymphoma of the Maxilla with Sphenoid Bone Invasion: Excellent Response to R-CHOP Therapy","authors":"Berrak Çağla Şenol, Ayşegül Ezgi Çetin, Ali Turunç, Birol Güvenç","doi":"10.1016/j.htct.2025.106125","DOIUrl":"10.1016/j.htct.2025.106125","url":null,"abstract":"<div><h3>Case Report</h3><div>A 59-year-old male (weight: 65 kg, height: 168 cm) presented in September 2024 with a progressively enlarging mass in the right maxillary region extending toward the temporal area with sphenoid bone proximity. The patient complained of maxillary distortion and pain but denied B symptoms including fever, night sweats, or weight loss.</div><div>Physical examination revealed facial asymmetry with palpable right maxillary swelling. Initial biopsy of the maxillary mass demonstrated CD20-positive extranodal marginal zone lymphoma consistent with MALT lymphoma histology.</div><div>Staging F-18 FDG PET/CT performed on October 4, 2024, revealed a hyperintense soft tissue mass in the right maxillary region with sphenoid bone invasion showing SUVmax 6.81. Additionally, a 16 × 10 mm lymph node in the right level 2 cervical chain demonstrated SUVmax 4.22. No pathological FDG uptake was detected in the thorax, abdomen, or skeletal system, confirming localized disease.</div><div>Based on the diagnosis of localized EMZL with bone invasion and cervical lymph node involvement, standard R-CHOP chemotherapy was initiated on September 24, 2024. The regimen consisted of rituximab 375 mg/m² (day 1), cyclophosphamide 750 mg/m² (day 1), doxorubicin 50 mg/m² (day 1), vincristine 1.4 mg/m² (day 1), and prednisolone 100 mg daily for 5 days. Supportive care included G-CSF (filgrastim) for neutropenia prophylaxis and antiemetics (ondansetron, granisetron).</div><div>During treatment, the patient developed E. coli pneumonia, which resolved with appropriate antibiotic therapy and supportive care. Despite this complication, the treatment protocol was successfully completed.</div><div>Interim PET-CT evaluation on December 25, 2024, demonstrated significant metabolic response with maxillary lesion SUVmax decreasing from 6.81 to 2.92, accompanied by dimensional reduction. Cervical lymph node involvement was no longer detectable, yielding a Deauville score of 2, consistent with partial metabolic remission.</div><div>Follow-up PET-CT after completion of 4 cycles in March 2025 revealed complete disappearance of pathological FDG uptake throughout the body. The maxillary region showed no residual mass formation, maintaining Deauville score 2, confirming complete metabolic remission.</div><div>The patient tolerated treatment well overall and entered surveillance follow-up without evidence of systemic dissemination or bone marrow involvement.</div></div><div><h3>Discussion</h3><div>This case represents a rare presentation of EMZL involving the maxillofacial region with sphenoid bone invasion. The excellent response to standard R-CHOP therapy challenges the traditional approach of radiotherapy alone for localized EMZL, particularly in cases with bone involvement where complete surgical resection may not be feasible. The use of PET-CT for treatment response assessment proved invaluable, providing objective metabolic parameters through Deauville scoring system. ","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106125"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796699","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}
Pub Date : 2025-12-01DOI: 10.1016/j.htct.2025.106186
Tanju Atamer
<div><div>Thrombosis occurs when the delicate balance between prothrombotic and anticoagulant forces is impaired. It usually develops due to multiple factors. When multiple risk factors come together, the anticoagulant systems cannot resist procoagulant forces and thrombosis may develop as a result.</div><div>Thrombosis due to hypercoagulability is usually seen clinically as venous thromboembolism (VTE) and rarely as arterial thrombosis. VTE can be seen as deep vein thrombosis (DVT) or pulmonary embolism. DVT most often manifests itself in the legs and rarely in the abdominal or intra-pelvic veins.</div><div>The hereditary or acquired factors are involved in the etiology of venous thromboembolism. Clinically, VTE is observed in those who are due to hereditary factors, while venous or arterial thromboses may be observed in those who are due to acquired causes. Hypercoagulability due to acquired causes is observed more often (70%) and they have a greater risk of thrombosis.</div><div>Venous thromboembolism is reported to occur in 1/10,000 people per year under the age of 40 and 1/1000 people per year over the age of 75. Hereditary thrombophilia causes are rare in the population. Although different rates are reported according to the world geography, The R506Q mutation in coagulation factor V, also known as the Factor V Leiden (FVL) mutation is the most common among them (3-8%). It is rare in far east countries. FVL mutation is the most common cause among hereditary hypercoagulabilities (50%). Clinically, young age, idiopathic thrombosis, thrombosis in an unusual place (upper extremity, mesenteric vein, portal vein, renal vein, cerebral vein) are noteworthy. Recurrence of thrombosis and a family history of venous thromboembolism are common.</div><div>Since the findings are not specific in the diagnosis of venous thromboembolism, the patient's medical history, family history and examination findings should be evaluated together. Determination of thrombosis risk scores, D-Dimer test, blood chemistry, lung X-ray and ECG are included as the first examinations in the patient. In patients with a negative D-Dimer test, a further examination is usually not needed. The subject of which tests to perform and when to perform in VTE cases requires expertise. In cases of idiopathic thrombosis, occurring at a young age, or recurrent, genetic or coagulation tests may be planned. Since test results may be misleading during the acute thrombosis period, it is more appropriate to schedule the tests a few weeks later or after the end of treatment. In patients with a high thrombosis risk score and elevated D-dimer levels, extremity vein Doppler ultrasonography and computed pulmonary angiography are used as imaging studies.</div><div>Oral or parenteral anticoagulants are used in the treatment of venous thromboembolism. These include low molecular weight heparin, FXa inhibitors (apixaban, rivaroxaban), and vitamin K antagonist (warfarin). The most commonly used are low-mol
{"title":"HYPERCOAGULABILITY: ETIOLOGY, DIAGNOSIS AND TREATMENT PRINCIPLES","authors":"Tanju Atamer","doi":"10.1016/j.htct.2025.106186","DOIUrl":"10.1016/j.htct.2025.106186","url":null,"abstract":"<div><div>Thrombosis occurs when the delicate balance between prothrombotic and anticoagulant forces is impaired. It usually develops due to multiple factors. When multiple risk factors come together, the anticoagulant systems cannot resist procoagulant forces and thrombosis may develop as a result.</div><div>Thrombosis due to hypercoagulability is usually seen clinically as venous thromboembolism (VTE) and rarely as arterial thrombosis. VTE can be seen as deep vein thrombosis (DVT) or pulmonary embolism. DVT most often manifests itself in the legs and rarely in the abdominal or intra-pelvic veins.</div><div>The hereditary or acquired factors are involved in the etiology of venous thromboembolism. Clinically, VTE is observed in those who are due to hereditary factors, while venous or arterial thromboses may be observed in those who are due to acquired causes. Hypercoagulability due to acquired causes is observed more often (70%) and they have a greater risk of thrombosis.</div><div>Venous thromboembolism is reported to occur in 1/10,000 people per year under the age of 40 and 1/1000 people per year over the age of 75. Hereditary thrombophilia causes are rare in the population. Although different rates are reported according to the world geography, The R506Q mutation in coagulation factor V, also known as the Factor V Leiden (FVL) mutation is the most common among them (3-8%). It is rare in far east countries. FVL mutation is the most common cause among hereditary hypercoagulabilities (50%). Clinically, young age, idiopathic thrombosis, thrombosis in an unusual place (upper extremity, mesenteric vein, portal vein, renal vein, cerebral vein) are noteworthy. Recurrence of thrombosis and a family history of venous thromboembolism are common.</div><div>Since the findings are not specific in the diagnosis of venous thromboembolism, the patient's medical history, family history and examination findings should be evaluated together. Determination of thrombosis risk scores, D-Dimer test, blood chemistry, lung X-ray and ECG are included as the first examinations in the patient. In patients with a negative D-Dimer test, a further examination is usually not needed. The subject of which tests to perform and when to perform in VTE cases requires expertise. In cases of idiopathic thrombosis, occurring at a young age, or recurrent, genetic or coagulation tests may be planned. Since test results may be misleading during the acute thrombosis period, it is more appropriate to schedule the tests a few weeks later or after the end of treatment. In patients with a high thrombosis risk score and elevated D-dimer levels, extremity vein Doppler ultrasonography and computed pulmonary angiography are used as imaging studies.</div><div>Oral or parenteral anticoagulants are used in the treatment of venous thromboembolism. These include low molecular weight heparin, FXa inhibitors (apixaban, rivaroxaban), and vitamin K antagonist (warfarin). The most commonly used are low-mol","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106186"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796830","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}
Pub Date : 2025-12-01DOI: 10.1016/j.htct.2025.106175
Birol Güvenç
<div><h3>Introduction</h3><div>Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma, comprising approximately 5–7% of cases. Unlike classical HL, NLPHL is characterized by CD20-positive “popcorn” cells (LP cells), lacks Epstein-Barr virus association, and tends to follow an indolent course. Accurate diagnosis is critical, as the therapeutic approach differs substantially. We report an early-stage NLPHL case in a young woman managed successfully without chemotherapy, emphasizing the value of histopathological precision and risk-adapted therapy.</div></div><div><h3>Methods</h3><div>A 33-year-old woman presented with a painless cervical swelling. Physical examination revealed enlarged left cervical and supraclavicular lymph nodes. She had no B symptoms such as fever, night sweats, or weight loss. Blood counts and biochemistry were within normal limits. An excisional biopsy of a lymph node was performed, followed by immunohistochemistry and whole-body 18F-FDG PET-CT for staging. Bone marrow aspiration and biopsy were also conducted to rule out marrow involvement.</div></div><div><h3>Results</h3><div>Histopathological examination demonstrated nodular architecture containing scattered lymphocyte-predominant (LP) cells. Immunophenotyping revealed strong CD20 and Pax5 expression, with negativity for CD3 and CD15. CD21 staining highlighted an expanded follicular dendritic cell meshwork, confirming the diagnosis of NLPHL.</div><div>PET-CT showed FDG-avid lymph nodes localized to the left cervical and supraclavicular regions, with a maximum SUV of 27.9. No pathological uptake was seen in the mediastinum, abdomen, bones, or spleen. Bone marrow biopsy was normocellular without evidence of infiltration. The disease was staged as Stage IA (non-bulky), CD20-positive NLPHL.</div><div>The patient was treated with rituximab monotherapy (375 mg/m<sup>2</sup> weekly for 4 doses), followed by involved-field radiotherapy (30 Gy) to the involved nodal regions. Given her age and reproductive status, fertility preservation was discussed before initiating treatment. The plan aimed to minimize long-term toxicity while maintaining curative potential.</div></div><div><h3>Discussion</h3><div>This case illustrates several important themes. First, accurate histological subtyping allowed for a deviation from standard chemotherapy-based HL protocols. Second, the use of rituximab and radiotherapy alone is an emerging and evidence-supported strategy for early-stage NLPHL, particularly in CD20-positive, non-bulky cases. Third, the patient’s demographic—young and female—makes chemotherapy-free management especially attractive given concerns about fertility and late effects. Finally, the case has strong educational value, highlighting the need to distinguish NLPHL from classical HL and indolent B-cell lymphomas, both histologically and metabolically.</div></div><div><h3>Conclusion</h3><div>This case demonstrates how a rare Hodgkin lymphoma subty
{"title":"Early-Stage Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL) in a Young Woman: A Rare Subtype Managed Without Chemotherapy","authors":"Birol Güvenç","doi":"10.1016/j.htct.2025.106175","DOIUrl":"10.1016/j.htct.2025.106175","url":null,"abstract":"<div><h3>Introduction</h3><div>Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma, comprising approximately 5–7% of cases. Unlike classical HL, NLPHL is characterized by CD20-positive “popcorn” cells (LP cells), lacks Epstein-Barr virus association, and tends to follow an indolent course. Accurate diagnosis is critical, as the therapeutic approach differs substantially. We report an early-stage NLPHL case in a young woman managed successfully without chemotherapy, emphasizing the value of histopathological precision and risk-adapted therapy.</div></div><div><h3>Methods</h3><div>A 33-year-old woman presented with a painless cervical swelling. Physical examination revealed enlarged left cervical and supraclavicular lymph nodes. She had no B symptoms such as fever, night sweats, or weight loss. Blood counts and biochemistry were within normal limits. An excisional biopsy of a lymph node was performed, followed by immunohistochemistry and whole-body 18F-FDG PET-CT for staging. Bone marrow aspiration and biopsy were also conducted to rule out marrow involvement.</div></div><div><h3>Results</h3><div>Histopathological examination demonstrated nodular architecture containing scattered lymphocyte-predominant (LP) cells. Immunophenotyping revealed strong CD20 and Pax5 expression, with negativity for CD3 and CD15. CD21 staining highlighted an expanded follicular dendritic cell meshwork, confirming the diagnosis of NLPHL.</div><div>PET-CT showed FDG-avid lymph nodes localized to the left cervical and supraclavicular regions, with a maximum SUV of 27.9. No pathological uptake was seen in the mediastinum, abdomen, bones, or spleen. Bone marrow biopsy was normocellular without evidence of infiltration. The disease was staged as Stage IA (non-bulky), CD20-positive NLPHL.</div><div>The patient was treated with rituximab monotherapy (375 mg/m<sup>2</sup> weekly for 4 doses), followed by involved-field radiotherapy (30 Gy) to the involved nodal regions. Given her age and reproductive status, fertility preservation was discussed before initiating treatment. The plan aimed to minimize long-term toxicity while maintaining curative potential.</div></div><div><h3>Discussion</h3><div>This case illustrates several important themes. First, accurate histological subtyping allowed for a deviation from standard chemotherapy-based HL protocols. Second, the use of rituximab and radiotherapy alone is an emerging and evidence-supported strategy for early-stage NLPHL, particularly in CD20-positive, non-bulky cases. Third, the patient’s demographic—young and female—makes chemotherapy-free management especially attractive given concerns about fertility and late effects. Finally, the case has strong educational value, highlighting the need to distinguish NLPHL from classical HL and indolent B-cell lymphomas, both histologically and metabolically.</div></div><div><h3>Conclusion</h3><div>This case demonstrates how a rare Hodgkin lymphoma subty","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106175"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796897","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}
Pub Date : 2025-12-01DOI: 10.1016/j.htct.2025.106158
Esra Nur Saygeçitli, Hüseyin Koçak, Ali Turunç, Birol Güvenç
Objective
Introduction: Chronic myelomonocytic leukemia (CMML) is a clonal hematologic malignancy with features of both myelodysplastic and myeloproliferative neoplasms [1]. Transformation into acute myeloid leukemia (AML) occurs in 15–20% of cases, while extramedullary presentation as myeloid sarcoma is exceedingly rare and associated with aggressive disease and poor prognosis [2,7].
Case report
Case Presentation
A 64-year-old male diagnosed with CMML in 2024 was treated with azacitidine, achieving hematologic response after four cycles. Following the tenth cycle, he developed a cervical mass with compressive symptoms. Excisional biopsy confirmed myeloid sarcoma involving the cervical lymph node. Concurrent bone marrow analysis revealed 100% cellularity with grade 2/4 reticulin fibrosis, monocytic proliferation, and 15–16% blasts, consistent with CMML-2. Immunohistochemistry showed CD33+ and MPO+ staining, negative for CD34, CD117, and TdT. Systemic chemotherapy was planned, but the patient deteriorated rapidly with pneumosepsis and died.
Conclusion
DiscussionExtramedullary transformation of CMML into myeloid sarcoma is a rare clinical event, with limited cases reported [3]. Diagnosis can be challenging due to morphologic overlap with lymphoma, underscoring the necessity of immunophenotypic confirmation [6]. Therapeutic options remain limited, ranging from AML-type induction regimens to hypomethylating agents combined with venetoclax, and allogeneic stem cell transplantation for eligible patients [4,5,8]. However, outcomes remain poor, with median survival after extramedullary progression of ∼6 months [1,7].ConclusionThis case illustrates the rare transformation of CMML-2 into myeloid sarcoma with cervical lymph node involvement, highlighting diagnostic complexity, limited treatment options, and rapid disease progression. Early biopsy of new masses and bone marrow reassessment are crucial for timely diagnosis, while novel therapeutic strategies are urgently needed to improve outcomes.
{"title":"TRANSFORMATION OF CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML) INTO MYELOID SARCOMA: A RARE CASE WITH CERVICAL LYMPH NODE INVOLVEMENT","authors":"Esra Nur Saygeçitli, Hüseyin Koçak, Ali Turunç, Birol Güvenç","doi":"10.1016/j.htct.2025.106158","DOIUrl":"10.1016/j.htct.2025.106158","url":null,"abstract":"<div><h3>Objective</h3><div><strong>Introduction:</strong> Chronic myelomonocytic leukemia (CMML) is a clonal hematologic malignancy with features of both myelodysplastic and myeloproliferative neoplasms [1]. Transformation into acute myeloid leukemia (AML) occurs in 15–20% of cases, while extramedullary presentation as myeloid sarcoma is exceedingly rare and associated with aggressive disease and poor prognosis [2,7].</div></div><div><h3>Case report</h3><div><strong>Case Presentation</strong></div><div>A 64-year-old male diagnosed with CMML in 2024 was treated with azacitidine, achieving hematologic response after four cycles. Following the tenth cycle, he developed a cervical mass with compressive symptoms. Excisional biopsy confirmed myeloid sarcoma involving the cervical lymph node. Concurrent bone marrow analysis revealed 100% cellularity with grade 2/4 reticulin fibrosis, monocytic proliferation, and 15–16% blasts, consistent with CMML-2. Immunohistochemistry showed CD33+ and MPO+ staining, negative for CD34, CD117, and TdT. Systemic chemotherapy was planned, but the patient deteriorated rapidly with pneumosepsis and died.</div></div><div><h3>Conclusion</h3><div>DiscussionExtramedullary transformation of CMML into myeloid sarcoma is a rare clinical event, with limited cases reported [3]. Diagnosis can be challenging due to morphologic overlap with lymphoma, underscoring the necessity of immunophenotypic confirmation [6]. Therapeutic options remain limited, ranging from AML-type induction regimens to hypomethylating agents combined with venetoclax, and allogeneic stem cell transplantation for eligible patients [4,5,8]. However, outcomes remain poor, with median survival after extramedullary progression of ∼6 months [1,7].ConclusionThis case illustrates the rare transformation of CMML-2 into myeloid sarcoma with cervical lymph node involvement, highlighting diagnostic complexity, limited treatment options, and rapid disease progression. Early biopsy of new masses and bone marrow reassessment are crucial for timely diagnosis, while novel therapeutic strategies are urgently needed to improve outcomes.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106158"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796977","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}
Pub Date : 2025-12-01DOI: 10.1016/j.htct.2025.106203
Mahmut Bakır Koyuncu
<div><div>Graft-versus-host disease (GvHD) remains one of the most significant complications following allogeneic hematopoietic stem cell transplantation (HSCT), contributing substantially to morbidity and mortality despite advances in conditioning regimens, donor selection, and prophylactic strategies. Understanding the etiopathogenesis of acute and chronic GvHD is essential for improving risk stratification, tailoring prophylaxis, and designing novel targeted therapies.</div><div>Acute GvHD (aGvHD) typically develops within the first 100 days post-transplant and arises from a multi-step immunopathological cascade. Conditioning regimens induce extensive tissue damage, releasing danger-associated molecular patterns (DAMPs) and pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6, which activate host antigen-presenting cells (APCs). Activated APCs prime donor T cells, leading to the expansion of alloreactive effector T cells. These T cells infiltrate target organs—most prominently the skin, gastrointestinal tract, and liver—mediating tissue destruction via cytotoxic molecules (perforin, granzyme) and further amplification of the inflammatory milieu. Regulatory T cell (Treg) dysfunction, microbial translocation from intestinal damage, and loss of epithelial integrity amplify these effects. Emerging evidence highlights the contribution of innate immune cells, the microbiome, and cytokine networks in shaping the severity and trajectory of aGvHD.</div><div>Chronic GvHD (cGvHD), in contrast, is a complex, multifactorial syndrome that shares features with autoimmune and fibrotic disorders. It generally manifests beyond day 100, although temporal overlap with aGvHD is increasingly recognized. The pathogenesis of cGvHD involves sustained immune dysregulation, including aberrant thymic recovery, impaired central and peripheral tolerance, and persistence of autoreactive and alloreactive T and B cells. B cell hyperactivity, autoantibody production, and activation of germinal center–like reactions contribute to chronic inflammation. Crosstalk between T follicular helper cells, pathogenic B cells, and fibroblasts drives tissue remodeling and fibrosis. Key target organs include the skin, lungs, liver, eyes, and mucous membranes, with progressive organ dysfunction severely impacting quality of life. Recent studies underscore the importance of profibrotic cytokines (e.g., TGF-β, PDGF) and aberrant tissue repair pathways in perpetuating cGvHD.</div><div>Advances in molecular and cellular profiling have provided novel insights into both acute and chronic disease mechanisms. High-throughput sequencing, proteomic analyses, and microbiome studies have identified candidate biomarkers for early diagnosis, disease monitoring, and therapeutic stratification. These findings are paving the way toward precision medicine approaches, including selective inhibition of JAK/STAT pathways, B cell depletion strategies, adoptive Treg therapy, and microbiota modulation. Despite t
{"title":"ACUTE AND CHRONIC GRAFT-VERSUS-HOST DISEASE: INSIGHTS INTO ETIOPATHOGENESIS","authors":"Mahmut Bakır Koyuncu","doi":"10.1016/j.htct.2025.106203","DOIUrl":"10.1016/j.htct.2025.106203","url":null,"abstract":"<div><div>Graft-versus-host disease (GvHD) remains one of the most significant complications following allogeneic hematopoietic stem cell transplantation (HSCT), contributing substantially to morbidity and mortality despite advances in conditioning regimens, donor selection, and prophylactic strategies. Understanding the etiopathogenesis of acute and chronic GvHD is essential for improving risk stratification, tailoring prophylaxis, and designing novel targeted therapies.</div><div>Acute GvHD (aGvHD) typically develops within the first 100 days post-transplant and arises from a multi-step immunopathological cascade. Conditioning regimens induce extensive tissue damage, releasing danger-associated molecular patterns (DAMPs) and pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6, which activate host antigen-presenting cells (APCs). Activated APCs prime donor T cells, leading to the expansion of alloreactive effector T cells. These T cells infiltrate target organs—most prominently the skin, gastrointestinal tract, and liver—mediating tissue destruction via cytotoxic molecules (perforin, granzyme) and further amplification of the inflammatory milieu. Regulatory T cell (Treg) dysfunction, microbial translocation from intestinal damage, and loss of epithelial integrity amplify these effects. Emerging evidence highlights the contribution of innate immune cells, the microbiome, and cytokine networks in shaping the severity and trajectory of aGvHD.</div><div>Chronic GvHD (cGvHD), in contrast, is a complex, multifactorial syndrome that shares features with autoimmune and fibrotic disorders. It generally manifests beyond day 100, although temporal overlap with aGvHD is increasingly recognized. The pathogenesis of cGvHD involves sustained immune dysregulation, including aberrant thymic recovery, impaired central and peripheral tolerance, and persistence of autoreactive and alloreactive T and B cells. B cell hyperactivity, autoantibody production, and activation of germinal center–like reactions contribute to chronic inflammation. Crosstalk between T follicular helper cells, pathogenic B cells, and fibroblasts drives tissue remodeling and fibrosis. Key target organs include the skin, lungs, liver, eyes, and mucous membranes, with progressive organ dysfunction severely impacting quality of life. Recent studies underscore the importance of profibrotic cytokines (e.g., TGF-β, PDGF) and aberrant tissue repair pathways in perpetuating cGvHD.</div><div>Advances in molecular and cellular profiling have provided novel insights into both acute and chronic disease mechanisms. High-throughput sequencing, proteomic analyses, and microbiome studies have identified candidate biomarkers for early diagnosis, disease monitoring, and therapeutic stratification. These findings are paving the way toward precision medicine approaches, including selective inhibition of JAK/STAT pathways, B cell depletion strategies, adoptive Treg therapy, and microbiota modulation. Despite t","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106203"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796985","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}
Pub Date : 2025-12-01DOI: 10.1016/j.htct.2025.106204
Utku Aygüneş
Thalassemia major is a severe hereditary hemoglobinopathy characterized by ineffective erythropoiesis and transfusion-dependent anemia. Regular red blood cell transfusions remain the cornerstone of supportive treatment; however, they inevitably result in progressive iron overload due to the absence of physiological mechanisms for iron excretion. Iron accumulation predominantly affects the liver, heart, and endocrine organs, leading to cirrhosis, cardiomyopathy, arrhythmias, and multiple endocrinopathies. Consequently, iron chelation therapy constitutes a fundamental component of long-term management in patients with thalassemia major.
The first clinically available chelating agent was deferoxamine (DFO) promotes urinary and fecal iron excretion. Long-term use of DFO has significantly improved survival by reducing iron-related cardiac mortality. Nevertheless, its administration—via subcutaneous or intravenous infusion for 8–12 hours on most days of the week—poses substantial challenges to adherence, particularly in pediatric and adolescent populations.
To address these limitations, oral chelators were developed. Deferiprone (DFP) is effective in reducing myocardial iron burden and preventing cardiac dysfunction, although it carries the risk of agranulocytosis, requiring strict hematological monitoring. Deferasirox (DFX) has demonstrated efficacy in maintaining negative iron balance and reducing hepatic iron concentration, thereby improving adherence and overall patient satisfaction.
In cases of severe or refractory iron overload, combination therapy has been employed. The concurrent use of DFO and DFP exhibits synergistic effects, particularly in the clearance of cardiac iron. Emerging data also support the potential benefits of combining DFO with DFX in select clinical scenarios. These strategies allow for individualized treatment based on iron burden, organ involvement, and patient tolerance.
Monitoring of chelation efficacy is essential. Serum ferritin is widely utilized as a surrogate marker of body iron, though it may be confounded by inflammation or hepatic injury. T2-star magnetic resonance imaging provides a more reliable and non-invasive quantification of cardiac and hepatic iron, enabling timely therapeutic adjustments and prevention of irreversible organ damage.
Chelation therapy has transformed the prognosis of thalassemia major, shifting the natural history from early mortality to survival into adulthood with improved quality of life. Nevertheless, challenges persist, including variability in drug availability, treatment adherence, and adverse event profiles. Future perspectives include optimization of chelation regimens, development of safer agents, and curative approaches such as gene therapy and hematopoietic stem cell transplantation, which may ultimately reduce or eliminate the lifelong requirement for transfusion and chelation.
{"title":"CHELATION THERAPY IN THALASSEMIA","authors":"Utku Aygüneş","doi":"10.1016/j.htct.2025.106204","DOIUrl":"10.1016/j.htct.2025.106204","url":null,"abstract":"<div><div>Thalassemia major is a severe hereditary hemoglobinopathy characterized by ineffective erythropoiesis and transfusion-dependent anemia. Regular red blood cell transfusions remain the cornerstone of supportive treatment; however, they inevitably result in progressive iron overload due to the absence of physiological mechanisms for iron excretion. Iron accumulation predominantly affects the liver, heart, and endocrine organs, leading to cirrhosis, cardiomyopathy, arrhythmias, and multiple endocrinopathies. Consequently, iron chelation therapy constitutes a fundamental component of long-term management in patients with thalassemia major.</div><div>The first clinically available chelating agent was deferoxamine (DFO) promotes urinary and fecal iron excretion. Long-term use of DFO has significantly improved survival by reducing iron-related cardiac mortality. Nevertheless, its administration—via subcutaneous or intravenous infusion for 8–12 hours on most days of the week—poses substantial challenges to adherence, particularly in pediatric and adolescent populations.</div><div>To address these limitations, oral chelators were developed. Deferiprone (DFP) is effective in reducing myocardial iron burden and preventing cardiac dysfunction, although it carries the risk of agranulocytosis, requiring strict hematological monitoring. Deferasirox (DFX) has demonstrated efficacy in maintaining negative iron balance and reducing hepatic iron concentration, thereby improving adherence and overall patient satisfaction.</div><div>In cases of severe or refractory iron overload, combination therapy has been employed. The concurrent use of DFO and DFP exhibits synergistic effects, particularly in the clearance of cardiac iron. Emerging data also support the potential benefits of combining DFO with DFX in select clinical scenarios. These strategies allow for individualized treatment based on iron burden, organ involvement, and patient tolerance.</div><div>Monitoring of chelation efficacy is essential. Serum ferritin is widely utilized as a surrogate marker of body iron, though it may be confounded by inflammation or hepatic injury. T2-star magnetic resonance imaging provides a more reliable and non-invasive quantification of cardiac and hepatic iron, enabling timely therapeutic adjustments and prevention of irreversible organ damage.</div><div>Chelation therapy has transformed the prognosis of thalassemia major, shifting the natural history from early mortality to survival into adulthood with improved quality of life. Nevertheless, challenges persist, including variability in drug availability, treatment adherence, and adverse event profiles. Future perspectives include optimization of chelation regimens, development of safer agents, and curative approaches such as gene therapy and hematopoietic stem cell transplantation, which may ultimately reduce or eliminate the lifelong requirement for transfusion and chelation.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106204"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796986","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}
Pub Date : 2025-12-01DOI: 10.1016/j.htct.2025.106136
Mürüvvet Seda AYDIN , Mehmet BAŞTÜRK , Funda CERAN , Simten DAĞDAŞ , Gülsüm ÖZET
<div><h3>Objective</h3><div>Disseminated intravascular coagulation (DIC) has been reported in 8-25% of acute lymphoblastic leukemia (ALL). Coagulopathy may accompany leukemia at diagnosis and during the induction phase and negatively impact prognosis. However, recognizing coagulopathy during this period can be challenging due to the accompanying bone marrow failure. Furthermore, distinguishing between asparaginase-associated hypofibrinogenemia and disseminated intravascular coagulation is challenging in clinical practice. It is important to determine which patients are at clinical risk and how they should be managed.</div></div><div><h3>Methodology</h3><div>Fifty patients with ALL followed at our center, diagnosed between 16.August.2019 and 17.June.2025 were retrospectively evaluated. The relationship between the patients' coagulation parameters and clinical data at diagnosis and during the induction period was investigated.</div></div><div><h3>Results</h3><div>The median age at diagnosis was 39 (18-79), and the majority of the patients were male (31/19). Nine of the patients had T-ALL, 17 had Ph-positive B-ALL, and 24 had Ph-negative B-ALL. The median follow-up duration was 15.3 (0.2-71.9) months. At the time of diagnosis, mild hypofibrinogenemia (<200 mg/dL) was detected in 8 (17%) and severe hypofibrinogenemia (<100 mg/dL) was detected in 2 (4%) patients. During the induction phase, mild hypofibrinogenemia was detected in 36 (72%) and severe hypofibrinogenemia was detected in 11 (22%) patients. No statistically significant association was found between mild or severe hypofibrinogenemia at diagnosis and induction phase with age, gender, and ALL subtype. Fibrinogen level at diagnosis was lower in patients who developed mild hypofibrinogenemia at induction phase compared to those who did not (median 278 vs. 453) (p=0.004). In patients who received an asparaginase-containing induction regimen, both mild hypofibrinogenemia (92.9% vs. 63.9%) and severe hypofibrinogenemia (42.9% vs. 13.9%) were observed more frequently at induction phase (p=0.039 and p=0.036, respectively). In patients with mild hypofibrinogenemia at induction, the requirement for cryoprecipitate or fresh frozen plasma (FFP) was higher than in patients with normal fibrinogen levels (55.6% vs. 21.4%, p=0.030). D-dimer levels at diagnosis were higher in Ph-positive B-ALL than in Ph-negative B-ALL (median 15 vs. 4.3; p=0.030). D-dimer levels at induction phase were also higher in patients requiring cryoprecipitate or FFP (median 14.6 vs. 7.1; p=0.07). Early mortality (in the first 30 days) was 1 (2%), and was not associated with bleeding or thrombosis. No statistically significant association was found between age, gender, disease subtype, fibrinogen and D-dimer levels at diagnosis and induction phase, asparaginase use, or cryoprecipitate or FFP requirement and overall survival.</div></div><div><h3>Conclusion</h3><div>In this study, we demonstrated that hypofibrinogenemia, while o
目的8-25%的急性淋巴细胞白血病（ALL）存在弥散性血管内凝血（DIC）。凝血功能障碍可能伴随白血病在诊断和诱导阶段，并对预后产生负面影响。然而，由于伴随的骨髓衰竭，在此期间识别凝血功能障碍可能具有挑战性。此外，区分天冬酰胺酶相关的低纤维蛋白原血症和弥散性血管内凝血在临床实践中具有挑战性。确定哪些患者有临床风险以及如何对其进行管理是很重要的。方法对8月16日确诊的急性淋巴细胞白血病患者50例进行随访。2019年和6月17日。回顾性评价了2025例。探讨诊断时和诱导期患者凝血参数与临床资料的关系。结果确诊年龄中位数为39岁（18 ~ 79岁），男性居多（31/19）。其中T-ALL 9例，B-ALL ph阳性17例，B-ALL ph阴性24例。中位随访时间为15.3（0.2-71.9）个月。在诊断时，8例（17%）患者检测到轻度低纤维蛋白原血症（200 mg/dL）， 2例（4%）患者检测到重度低纤维蛋白原血症（100 mg/dL）。在诱导期，36例（72%）患者检测到轻度低纤维蛋白原血症，11例（22%）患者检测到重度低纤维蛋白原血症。诊断和诱导阶段轻度或重度低纤维蛋白原血症与年龄、性别和ALL亚型之间无统计学意义的关联。在诱导期发生轻度低纤维蛋白原血症的患者诊断时的纤维蛋白原水平低于未发生轻度低纤维蛋白原血症的患者（中位数278对453）（p=0.004）。在接受含天冬酰胺酶诱导方案的患者中，轻度低纤维蛋白原血症（92.9% vs. 63.9%）和重度低纤维蛋白原血症（42.9% vs. 13.9%）在诱导期更常见（p=0.039和p=0.036分别）。诱导时轻度低纤维蛋白原血症患者对冷冻沉淀或新鲜冷冻血浆（FFP）的需求高于纤维蛋白原水平正常的患者（55.6% vs. 21.4%, p=0.030）。诊断时ph阳性B-ALL患者的d -二聚体水平高于ph阴性B-ALL患者（中位数15 vs. 4.3; p=0.030）。在需要低温沉淀或FFP的患者中，诱导期d -二聚体水平也较高（中位数14.6 vs. 7.1; p=0.07）。早期死亡率（前30天）为1%(2%)，与出血或血栓形成无关。年龄、性别、疾病亚型、诊断和诱导阶段纤维蛋白原和d -二聚体水平、天冬酰胺酶使用、冷冻沉淀或FFP需求与总生存率之间没有统计学意义的关联。在这项研究中，我们证明了低纤维蛋白原血症，虽然在ALL的诊断中观察到，但在诱导期尤其普遍。诱导期的低纤维蛋白原血症是由诊断时的纤维蛋白原水平和使用含天冬酰胺酶的方案决定的。随后，在诱导阶段，由低纤维蛋白原血症决定的含有凝血因子的血液制品的消耗。虽然凝血功能障碍增加了血液制品使用的频率，但观察到它对患者的生存没有负面影响。对于新诊断的ALL患者，不论是否使用天冬酰胺酶，都应重新审查临床指南，并根据大规模研究进行更新。
{"title":"IMPAIRED COAGULATION AT DIAGNOSIS AND INDUCTION PHASE OF ACUTE LYMPHOBLASTIC LEUKEMIA","authors":"Mürüvvet Seda AYDIN , Mehmet BAŞTÜRK , Funda CERAN , Simten DAĞDAŞ , Gülsüm ÖZET","doi":"10.1016/j.htct.2025.106136","DOIUrl":"10.1016/j.htct.2025.106136","url":null,"abstract":"<div><h3>Objective</h3><div>Disseminated intravascular coagulation (DIC) has been reported in 8-25% of acute lymphoblastic leukemia (ALL). Coagulopathy may accompany leukemia at diagnosis and during the induction phase and negatively impact prognosis. However, recognizing coagulopathy during this period can be challenging due to the accompanying bone marrow failure. Furthermore, distinguishing between asparaginase-associated hypofibrinogenemia and disseminated intravascular coagulation is challenging in clinical practice. It is important to determine which patients are at clinical risk and how they should be managed.</div></div><div><h3>Methodology</h3><div>Fifty patients with ALL followed at our center, diagnosed between 16.August.2019 and 17.June.2025 were retrospectively evaluated. The relationship between the patients' coagulation parameters and clinical data at diagnosis and during the induction period was investigated.</div></div><div><h3>Results</h3><div>The median age at diagnosis was 39 (18-79), and the majority of the patients were male (31/19). Nine of the patients had T-ALL, 17 had Ph-positive B-ALL, and 24 had Ph-negative B-ALL. The median follow-up duration was 15.3 (0.2-71.9) months. At the time of diagnosis, mild hypofibrinogenemia (<200 mg/dL) was detected in 8 (17%) and severe hypofibrinogenemia (<100 mg/dL) was detected in 2 (4%) patients. During the induction phase, mild hypofibrinogenemia was detected in 36 (72%) and severe hypofibrinogenemia was detected in 11 (22%) patients. No statistically significant association was found between mild or severe hypofibrinogenemia at diagnosis and induction phase with age, gender, and ALL subtype. Fibrinogen level at diagnosis was lower in patients who developed mild hypofibrinogenemia at induction phase compared to those who did not (median 278 vs. 453) (p=0.004). In patients who received an asparaginase-containing induction regimen, both mild hypofibrinogenemia (92.9% vs. 63.9%) and severe hypofibrinogenemia (42.9% vs. 13.9%) were observed more frequently at induction phase (p=0.039 and p=0.036, respectively). In patients with mild hypofibrinogenemia at induction, the requirement for cryoprecipitate or fresh frozen plasma (FFP) was higher than in patients with normal fibrinogen levels (55.6% vs. 21.4%, p=0.030). D-dimer levels at diagnosis were higher in Ph-positive B-ALL than in Ph-negative B-ALL (median 15 vs. 4.3; p=0.030). D-dimer levels at induction phase were also higher in patients requiring cryoprecipitate or FFP (median 14.6 vs. 7.1; p=0.07). Early mortality (in the first 30 days) was 1 (2%), and was not associated with bleeding or thrombosis. No statistically significant association was found between age, gender, disease subtype, fibrinogen and D-dimer levels at diagnosis and induction phase, asparaginase use, or cryoprecipitate or FFP requirement and overall survival.</div></div><div><h3>Conclusion</h3><div>In this study, we demonstrated that hypofibrinogenemia, while o","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106136"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797075","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}
Pub Date : 2025-12-01DOI: 10.1016/j.htct.2025.106200
Şifa Şahin
<div><h3>Introduction</h3><div>Thalassemia comprises inherited disorders characterized by reduced globin chain synthesis, leading to an imbalance between α- and β-globin chains. Ineffective erythropoiesis (IE) is the long-term outcome of a complex interaction of molecular mechanisms, primarily involving the bone marrow and its intricate bidirectional communication with the liver, spleen, and gut, ultimately leading to the production of pathological RBCs. IE is the primary driver of thalassemia and the main contributor to most of the clinical manifestations of this disorder. In patients with β-thalassemia, the bone marrow contains approximately six times more erythroid precursors than in healthy individuals, and the rate of apoptotic cell death is nearly four times higher than normal (1).</div><div>In thalassemia, the altered differentiation of erythroid progenitors appears to worsen IE, coupled with increased proliferation and apoptosis, ultimately leading to anemia, extramedullary hematopoiesis, splenomegaly, and systemic iron overload. Therefore, advanced characterization of the molecular foundations of these complex processes is crucial for developing effective disease-modifying therapies. Therapeutic approaches seek to modulate pathways that reduce iron absorption (for example, activating hepcidin through Tmprss6 antisense oligonucleotides—ASOs) or pathways that increase erythropoiesis (e.g., erythropoietin [EPO] administration or modulating red blood cell (RBC) synthesis via control of transferrin receptor 2 [Tfr2]) or activin II Receptor Ligand Traps (2).</div></div><div><h3>Pathophysiology of Ineffective Erythropoiesis</h3><div>Erythropoiesis is a tightly regulated process producing billions of functional red blood cells (RBCs) daily. In thalassemia, this process is disrupted. The hallmark is the substantial expansion of early-stage erythroid precursors in the bone marrow in response to elevated erythropoietin, coupled with premature death of late-stage precursors, resulting in a low output of mature RBCs.</div><div>Therapeutic Strategies Targeting IE Building on the mechanistic understanding of IE, therapies aim to address the underlying pathology rather than merely treating anemia or iron overload.</div><div> <!-->1. Activin II Receptor Ligand Traps Luspatercept is a leading therapeutic that traps TGF-β superfamily ligands (including GDF11 and Activin A). By sequestering these ligands, luspatercept prevents receptor binding, promoting terminal erythroid maturation and reducing IE. Clinical trials show that luspatercept significantly increases hemoglobin and reduces transfusion requirements in β-thalassemia.</div><div> <!-->2. Targeting Iron Metabolism Novel agents modulate iron metabolism to reduce iron overload and improve erythropoiesis. Ferroportin inhibitors (e.g., VIT-2763) aim to block iron export from cells. Other strategies aim to enhance hepcidin activity or inhibit erythroferrone (ERFE) (4).</div><div> <!-->3. Gene Therapy and
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