Pub Date : 2025-12-01DOI: 10.1016/j.htct.2025.106113
Naciye Nur Tozluklu, Birol Güvenç
<div><h3>Introduction</h3><div>Dasatinib is a potent second-generation tyrosine kinase inhibitor widely used in chronic myeloid leukemia (CML) treatment, particularly in patients intolerant to imatinib. While generally well-tolerated, dasatinib can cause various adverse effects including pleural effusions, cytopenias, and gastrointestinal symptoms. However, progressive enterocolitis resembling inflammatory bowel disease (IBD) is rarely reported and poses diagnostic challenges due to clinical and endoscopic similarities to IBD.</div></div><div><h3>Case Report</h3><div>A 71-year-old female with a 20-year history of achalasia was diagnosed with chronic myeloid leukemia in 2021 following evaluation for leukocytosis and typical hematological findings. Initial treatment with imatinib 400 mg daily was discontinued due to severe facial edema. Subsequently, dasatinib 100 mg daily was initiated as second-line therapy.</div><div>Concurrent with dasatinib initiation, the patient developed new gastrointestinal symptoms previously absent in her medical history, including abdominal pain, intermittent diarrhea, altered bowel habits, and occasional hematochezia. These symptoms progressively worsened over subsequent years despite achieving hematological remission.</div><div>Physical examination in 2021 revealed stable vital signs with mild diffuse abdominal tenderness without hepatosplenomegaly. Laboratory investigations confirmed BCR-ABL positivity establishing CML diagnosis, with leukocytosis (WBC >50,000/µL) and normal renal and hepatic function. Hematological remission was maintained throughout 2022-2025 follow-up period.</div><div>Colonoscopy performed in February 2022 revealed minimal terminal ileal hyperemia with edematous and granular colonic mucosa, raising suspicion for ulcerative colitis or Crohn's disease. Histopathological examination of biopsies showed chronic active colitis with cryptitis, terminal ileitis, and eosinophilic infiltration, but lacked granulomas or specific features diagnostic of IBD. Previous biopsies from November 2021 demonstrated similar chronic active colitis and cryptitis without diagnostic specificity.</div><div>Despite endoscopic findings suggestive of IBD, the absence of characteristic histopathological features and progressive symptom worsening during dasatinib therapy raised suspicion for drug-induced enterocolitis. In 2025, when gastrointestinal symptoms significantly intensified, dasatinib was discontinued.</div><div>Remarkably, within approximately two months of dasatinib discontinuation, all gastrointestinal symptoms completely resolved, providing strong evidence for drug-induced etiology rather than IBD.</div></div><div><h3>Discussion</h3><div>This case demonstrates a rare but clinically significant adverse effect of dasatinib therapy. While gastrointestinal symptoms are recognized side effects of tyrosine kinase inhibitors, progressive enterocolitis mimicking IBD is uncommon and poses diagnostic challenges.</div><di
{"title":"Dasatinib-Induced Progressive Enterocolitis Mimicking Inflammatory Bowel Disease in a Patient with Chronic Myeloid Leukemia: A Case Report","authors":"Naciye Nur Tozluklu, Birol Güvenç","doi":"10.1016/j.htct.2025.106113","DOIUrl":"10.1016/j.htct.2025.106113","url":null,"abstract":"<div><h3>Introduction</h3><div>Dasatinib is a potent second-generation tyrosine kinase inhibitor widely used in chronic myeloid leukemia (CML) treatment, particularly in patients intolerant to imatinib. While generally well-tolerated, dasatinib can cause various adverse effects including pleural effusions, cytopenias, and gastrointestinal symptoms. However, progressive enterocolitis resembling inflammatory bowel disease (IBD) is rarely reported and poses diagnostic challenges due to clinical and endoscopic similarities to IBD.</div></div><div><h3>Case Report</h3><div>A 71-year-old female with a 20-year history of achalasia was diagnosed with chronic myeloid leukemia in 2021 following evaluation for leukocytosis and typical hematological findings. Initial treatment with imatinib 400 mg daily was discontinued due to severe facial edema. Subsequently, dasatinib 100 mg daily was initiated as second-line therapy.</div><div>Concurrent with dasatinib initiation, the patient developed new gastrointestinal symptoms previously absent in her medical history, including abdominal pain, intermittent diarrhea, altered bowel habits, and occasional hematochezia. These symptoms progressively worsened over subsequent years despite achieving hematological remission.</div><div>Physical examination in 2021 revealed stable vital signs with mild diffuse abdominal tenderness without hepatosplenomegaly. Laboratory investigations confirmed BCR-ABL positivity establishing CML diagnosis, with leukocytosis (WBC >50,000/µL) and normal renal and hepatic function. Hematological remission was maintained throughout 2022-2025 follow-up period.</div><div>Colonoscopy performed in February 2022 revealed minimal terminal ileal hyperemia with edematous and granular colonic mucosa, raising suspicion for ulcerative colitis or Crohn's disease. Histopathological examination of biopsies showed chronic active colitis with cryptitis, terminal ileitis, and eosinophilic infiltration, but lacked granulomas or specific features diagnostic of IBD. Previous biopsies from November 2021 demonstrated similar chronic active colitis and cryptitis without diagnostic specificity.</div><div>Despite endoscopic findings suggestive of IBD, the absence of characteristic histopathological features and progressive symptom worsening during dasatinib therapy raised suspicion for drug-induced enterocolitis. In 2025, when gastrointestinal symptoms significantly intensified, dasatinib was discontinued.</div><div>Remarkably, within approximately two months of dasatinib discontinuation, all gastrointestinal symptoms completely resolved, providing strong evidence for drug-induced etiology rather than IBD.</div></div><div><h3>Discussion</h3><div>This case demonstrates a rare but clinically significant adverse effect of dasatinib therapy. While gastrointestinal symptoms are recognized side effects of tyrosine kinase inhibitors, progressive enterocolitis mimicking IBD is uncommon and poses diagnostic challenges.</div><di","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106113"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796554","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.2025.106126
Berra Nur İşçi, Birol Güvenç
<div><h3>Case report</h3><div>Primary bone lymphoma represents less than 1% of all malignant bone tumors and approximately 3% of extranodal lymphomas. Diffuse large B-cell lymphoma constitutes the most common histological subtype of primary bone lymphoma, typically affecting adults with a slight male predominance. The clinical presentation often mimics primary bone sarcomas, potentially leading to diagnostic delays. Double-expressor lymphomas, characterized by MYC and BCL2 protein co-expression, constitute 20-30% of DLBCL cases and are associated with inferior outcomes compared to standard DLBCL, requiring consideration of intensified treatment regimens.</div><div>A 29-year-old male presented with several months of progressive upper extremity pain, swelling, and limited range of motion involving the long bones and scapula. The clinical presentation initially raised suspicion for osteosarcoma or soft tissue sarcoma, prompting orthopedic evaluation and excisional biopsy.</div><div>Macroscopic examination revealed approximately 4 cm of grayish-white to brown tissue fragments submitted for histopathological analysis. Microscopic evaluation demonstrated cellular morphology consistent with lymphoproliferative disease rather than sarcomatous features, prompting comprehensive immunohistochemical evaluation.</div><div>Immunohistochemical analysis confirmed lymphoid origin with positive LCA (leukocyte common antigen) staining. B-cell lineage was established by strong, diffuse CD20 positivity (80-85% of cells). The tumor demonstrated germinal center B-cell phenotype with BCL6 expression in 80-85% of cells. Critically, MYC expression was present in 40-45% of tumor cells, suggesting double-expressor status pending BCL2 confirmation.</div><div>The proliferation index was extremely high with Ki-67 staining positive in 80-85% of cells, indicating highly aggressive biology. Negative staining for MyoD1, CD34, S100, and CD3 excluded sarcomatous differentiation and T-cell lymphoma.</div><div>Based on the constellation of findings, the diagnosis of high-grade diffuse large B-cell lymphoma with germinal center phenotype and suspected double-expressor features was established. The anatomical location involving upper extremity long bones and scapula confirmed primary bone lymphoma classification.</div><div>Additional molecular studies were recommended including FISH analysis for MYC, BCL2, and BCL6 rearrangements to distinguish between double-expressor and double-hit lymphoma. Comprehensive next-generation sequencing panel evaluation was suggested focusing on prognostically relevant genes including TP53, CDKN2A/B, NOTCH1/2, EZH2, and other lymphoma-associated mutations.</div></div><div><h3>Discussion</h3><div>This case illustrates several important clinical and pathological considerations. Primary bone DLBCL in young adults is uncommon and may present diagnostic challenges due to clinical similarity to primary bone sarcomas. The initial clinical suspicion of sarcoma nec
{"title":"Double-Expressor Diffuse Large B-Cell Lymphoma of Bone and Soft Tissue in a 29-Year-Old Patient: A Rare Case Report","authors":"Berra Nur İşçi, Birol Güvenç","doi":"10.1016/j.htct.2025.106126","DOIUrl":"10.1016/j.htct.2025.106126","url":null,"abstract":"<div><h3>Case report</h3><div>Primary bone lymphoma represents less than 1% of all malignant bone tumors and approximately 3% of extranodal lymphomas. Diffuse large B-cell lymphoma constitutes the most common histological subtype of primary bone lymphoma, typically affecting adults with a slight male predominance. The clinical presentation often mimics primary bone sarcomas, potentially leading to diagnostic delays. Double-expressor lymphomas, characterized by MYC and BCL2 protein co-expression, constitute 20-30% of DLBCL cases and are associated with inferior outcomes compared to standard DLBCL, requiring consideration of intensified treatment regimens.</div><div>A 29-year-old male presented with several months of progressive upper extremity pain, swelling, and limited range of motion involving the long bones and scapula. The clinical presentation initially raised suspicion for osteosarcoma or soft tissue sarcoma, prompting orthopedic evaluation and excisional biopsy.</div><div>Macroscopic examination revealed approximately 4 cm of grayish-white to brown tissue fragments submitted for histopathological analysis. Microscopic evaluation demonstrated cellular morphology consistent with lymphoproliferative disease rather than sarcomatous features, prompting comprehensive immunohistochemical evaluation.</div><div>Immunohistochemical analysis confirmed lymphoid origin with positive LCA (leukocyte common antigen) staining. B-cell lineage was established by strong, diffuse CD20 positivity (80-85% of cells). The tumor demonstrated germinal center B-cell phenotype with BCL6 expression in 80-85% of cells. Critically, MYC expression was present in 40-45% of tumor cells, suggesting double-expressor status pending BCL2 confirmation.</div><div>The proliferation index was extremely high with Ki-67 staining positive in 80-85% of cells, indicating highly aggressive biology. Negative staining for MyoD1, CD34, S100, and CD3 excluded sarcomatous differentiation and T-cell lymphoma.</div><div>Based on the constellation of findings, the diagnosis of high-grade diffuse large B-cell lymphoma with germinal center phenotype and suspected double-expressor features was established. The anatomical location involving upper extremity long bones and scapula confirmed primary bone lymphoma classification.</div><div>Additional molecular studies were recommended including FISH analysis for MYC, BCL2, and BCL6 rearrangements to distinguish between double-expressor and double-hit lymphoma. Comprehensive next-generation sequencing panel evaluation was suggested focusing on prognostically relevant genes including TP53, CDKN2A/B, NOTCH1/2, EZH2, and other lymphoma-associated mutations.</div></div><div><h3>Discussion</h3><div>This case illustrates several important clinical and pathological considerations. Primary bone DLBCL in young adults is uncommon and may present diagnostic challenges due to clinical similarity to primary bone sarcomas. The initial clinical suspicion of sarcoma nec","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106126"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796701","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.2025.106208
Şebnem İzmir Güner
<div><div>Graft‐versus‐host disease (GvHD) is an important complication that can be observed after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The incidence of Acute GvHD (aGvHD) is around 30%-50% in HLA fully matched allo-HSCT. aGvHD is also common in haploidentical and matched unrelated donor transplantation.</div><div>The mechanism underlying tissue damage in aGvHD is massive inflammatory cytokine secretion. Proinflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6] are seen, as well as the increased expression of the receptor repertoire (pattern recognition receptors) on antigen-presenting cells.</div><div>The most important risk factor for GvHD is HLA mismatch. Other risk factors include sex disparity between donor and recipient, the intensity of the conditioning regimen, increased age, multiparous female donors, ineffective GvHD prophylaxis, and the source of the graft. A study showed that aGvHD was significantly more common with total body irradiation involving a myeloablative regimen and peripheral stem cell transplantation from a fully matched related donor.</div><div>GvHD can be acute or chronic based on the clinical presentation and its occurrence after or before 100 days after allo-HSCT. aGvHD may occur beyond this arbitrary cut-off of 100 days. The widely accepted National Institutes of Health consensus criteria havebeen used to classify GvHD. GvHD is divided into four subclasses: 1) Classic aGvHD: Diagnostic and distinctive features of chronic GvHD (cGvHD) are absent. Clinical features of aGvHD and present within 100 days of allo-HSCT or donor lymphocyte infusion (DLI). 2) Persistent and/or recurrent late-onset aGvHD: Features of classic aGvHD without diagnostic manifestations of cGvHD occurring beyond 100 days after allo-HSCT or DLI. 3) Classic cGvHD: Present at any time after HSCT. Diagnostic and distinctive features of cGvHD are present without aGvHD. 4) Overlap syndrome; Features of both cGvHD and aGvHD can be seen.</div><div>The most commonly affected organsa are:Skin,eyes,oral mucosa,liver,GIS tract,genital organs,lungs,joints and fascia.</div><div>The most important step for the prevention of GvHD is minimizing risk factors with donor selection and a preparative regimen. GvHD prophylaxis is essential for patients undergoing allo-HSCT. Guidelines for GvHD prophylaxis have been proposed by the European Group for Blood and Marrow Transplantation and European LeukemiaNet . The most common form of GvHD prophylaxis has been the combination of cyclosporine and a short course of methotrexate, which demonstrated improved survival compared to either drug alone. Both cyclosporine and tacrolimus decreased the proliferation of T-lymphocytes . Tacrolimus plus methotrexate is better in decreasing the risk for aGvHD than the combination of cyclosporine and methotrexate, particularly in unrelated HSCT. Both regimens are considered as cornerstones for most GvHD prevention strategies for patient
{"title":"GRAFT VERSUS HOST DISEASE PROPHYLAXIS","authors":"Şebnem İzmir Güner","doi":"10.1016/j.htct.2025.106208","DOIUrl":"10.1016/j.htct.2025.106208","url":null,"abstract":"<div><div>Graft‐versus‐host disease (GvHD) is an important complication that can be observed after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The incidence of Acute GvHD (aGvHD) is around 30%-50% in HLA fully matched allo-HSCT. aGvHD is also common in haploidentical and matched unrelated donor transplantation.</div><div>The mechanism underlying tissue damage in aGvHD is massive inflammatory cytokine secretion. Proinflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6] are seen, as well as the increased expression of the receptor repertoire (pattern recognition receptors) on antigen-presenting cells.</div><div>The most important risk factor for GvHD is HLA mismatch. Other risk factors include sex disparity between donor and recipient, the intensity of the conditioning regimen, increased age, multiparous female donors, ineffective GvHD prophylaxis, and the source of the graft. A study showed that aGvHD was significantly more common with total body irradiation involving a myeloablative regimen and peripheral stem cell transplantation from a fully matched related donor.</div><div>GvHD can be acute or chronic based on the clinical presentation and its occurrence after or before 100 days after allo-HSCT. aGvHD may occur beyond this arbitrary cut-off of 100 days. The widely accepted National Institutes of Health consensus criteria havebeen used to classify GvHD. GvHD is divided into four subclasses: 1) Classic aGvHD: Diagnostic and distinctive features of chronic GvHD (cGvHD) are absent. Clinical features of aGvHD and present within 100 days of allo-HSCT or donor lymphocyte infusion (DLI). 2) Persistent and/or recurrent late-onset aGvHD: Features of classic aGvHD without diagnostic manifestations of cGvHD occurring beyond 100 days after allo-HSCT or DLI. 3) Classic cGvHD: Present at any time after HSCT. Diagnostic and distinctive features of cGvHD are present without aGvHD. 4) Overlap syndrome; Features of both cGvHD and aGvHD can be seen.</div><div>The most commonly affected organsa are:Skin,eyes,oral mucosa,liver,GIS tract,genital organs,lungs,joints and fascia.</div><div>The most important step for the prevention of GvHD is minimizing risk factors with donor selection and a preparative regimen. GvHD prophylaxis is essential for patients undergoing allo-HSCT. Guidelines for GvHD prophylaxis have been proposed by the European Group for Blood and Marrow Transplantation and European LeukemiaNet . The most common form of GvHD prophylaxis has been the combination of cyclosporine and a short course of methotrexate, which demonstrated improved survival compared to either drug alone. Both cyclosporine and tacrolimus decreased the proliferation of T-lymphocytes . Tacrolimus plus methotrexate is better in decreasing the risk for aGvHD than the combination of cyclosporine and methotrexate, particularly in unrelated HSCT. Both regimens are considered as cornerstones for most GvHD prevention strategies for patient","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106208"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796839","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.2025.106196
Aysu Timuroğlu
<div><div>Myelofibrosis (MF) is a Philadelphia chromosome-negative chronic myeloproliferative neoplasm characterized by fibrosis in the bone marrow, cytopenias and extramedullary hematopoiesis (1). In the 2022 International Consensus Classification (ICC) and the 5th edition of the World Health Organization (WHO) classification, myelofibrosis is subclassified as prefibrotic and overt primary myelofibrosis (2).</div><div>The 2022 WHO or ICC criteria should be used for PMF diagnosis. The disease is a clonal stem cell disorder, with the most common genetic mutations are JAK2 V617F (60%), MPL (13.6%) and calreticulin (CALR) (22-35%). Approximately 90% of PMF patients have these mutations, while triple-negative cases have non-driver mutations. Chromosomal abnormalities may also be observed in PMF (1, 3-5).</div><div>After diagnosis, prognostic risk scoring is performed for the treatment and management of patients. Symptoms are assessed using the myeloproliferative neoplasm symptom assessment form. IPSS, DIPSS, DIPSS Plus, MIPSS70, MIPSS70+v2, and GIPSS are the scoring systems used in PMF. Patients are divided into low/high risk groups, the reatment planning is based on this and patient’s symptoms (6-7).</div><div>The only curative and survival-enhancing treatment method in PMF is allogeneic hematopoietic stem cell transplantation (ASCT), which has high mortality and morbidity rates. In high-risk PMF patients, the treatment decision is primarily shaped by whether the patient is a candidate for ASCT. Treatments other than ASCT are currently aimed more at palliative care, controlling symptoms, and reducing spleen size (2).</div><div>In patients with low-risk PMF who are asymptomatic, they may be observed only or included in a clinical trial. In symptomatic patients, hydroxyurea, ruxolitinib, or interferon may be used, or enter a clinical trial (2).</div><div>In PMF, treatment decisions related to symptoms are made by considering anemia, splenomegaly, and constitutional symptoms. Especially in patients with prominent anemia, androgens, prednisolone, lenalidomide, thalidomide, and pomalidomide may be preferred if the patient does not have splenomegaly. New studies are investigating the efficacy of combining ruxolitinib with immunomodulatory agents. The efficacy of erythropoiesis-stimulating agents is limited, and studies show that luspatercept has a low effect in PMF patients. Momelotinib and pacritinib are also other treatment options for these patients and they have positive effects on increasing erythropoietic activity, splenomegaly and constitutional symptoms (2,3,8,9).</div><div>In patients with anemia, splenomegaly, and constitutional symptoms, momelotinib should be the first choice. If splenomegaly is present alone, hydroxyurea, interferon, or ruxolitinib may be preferred. In patients resistant to ruxolitinib, fedratinib or momelotinib is preferred, while pacritinib is recommended in thrombocytopenic cases (2,10-13).</div><div>There are studies on ma
{"title":"INNOVATIVE TREATMENTS FOR MYELOFIBROSIS","authors":"Aysu Timuroğlu","doi":"10.1016/j.htct.2025.106196","DOIUrl":"10.1016/j.htct.2025.106196","url":null,"abstract":"<div><div>Myelofibrosis (MF) is a Philadelphia chromosome-negative chronic myeloproliferative neoplasm characterized by fibrosis in the bone marrow, cytopenias and extramedullary hematopoiesis (1). In the 2022 International Consensus Classification (ICC) and the 5th edition of the World Health Organization (WHO) classification, myelofibrosis is subclassified as prefibrotic and overt primary myelofibrosis (2).</div><div>The 2022 WHO or ICC criteria should be used for PMF diagnosis. The disease is a clonal stem cell disorder, with the most common genetic mutations are JAK2 V617F (60%), MPL (13.6%) and calreticulin (CALR) (22-35%). Approximately 90% of PMF patients have these mutations, while triple-negative cases have non-driver mutations. Chromosomal abnormalities may also be observed in PMF (1, 3-5).</div><div>After diagnosis, prognostic risk scoring is performed for the treatment and management of patients. Symptoms are assessed using the myeloproliferative neoplasm symptom assessment form. IPSS, DIPSS, DIPSS Plus, MIPSS70, MIPSS70+v2, and GIPSS are the scoring systems used in PMF. Patients are divided into low/high risk groups, the reatment planning is based on this and patient’s symptoms (6-7).</div><div>The only curative and survival-enhancing treatment method in PMF is allogeneic hematopoietic stem cell transplantation (ASCT), which has high mortality and morbidity rates. In high-risk PMF patients, the treatment decision is primarily shaped by whether the patient is a candidate for ASCT. Treatments other than ASCT are currently aimed more at palliative care, controlling symptoms, and reducing spleen size (2).</div><div>In patients with low-risk PMF who are asymptomatic, they may be observed only or included in a clinical trial. In symptomatic patients, hydroxyurea, ruxolitinib, or interferon may be used, or enter a clinical trial (2).</div><div>In PMF, treatment decisions related to symptoms are made by considering anemia, splenomegaly, and constitutional symptoms. Especially in patients with prominent anemia, androgens, prednisolone, lenalidomide, thalidomide, and pomalidomide may be preferred if the patient does not have splenomegaly. New studies are investigating the efficacy of combining ruxolitinib with immunomodulatory agents. The efficacy of erythropoiesis-stimulating agents is limited, and studies show that luspatercept has a low effect in PMF patients. Momelotinib and pacritinib are also other treatment options for these patients and they have positive effects on increasing erythropoietic activity, splenomegaly and constitutional symptoms (2,3,8,9).</div><div>In patients with anemia, splenomegaly, and constitutional symptoms, momelotinib should be the first choice. If splenomegaly is present alone, hydroxyurea, interferon, or ruxolitinib may be preferred. In patients resistant to ruxolitinib, fedratinib or momelotinib is preferred, while pacritinib is recommended in thrombocytopenic cases (2,10-13).</div><div>There are studies on ma","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106196"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796901","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.2025.106133
Songül Beskisiz Dönen, Vehbi Demircan Abdullah, Karakuş Mehmet Orhan Ayyıldız
<div><h3>Introduction</h3><div>Non-Hodgkin lymphomas are malignant neoplasms of lymphoid tissue, and a subset present with extranodal involvement. The head and neck region represents one of the clinically relevant localizations. Sinonasal B-cell lymphomas are a rare subtype, most often manifesting as diffuse large B-cell lymphoma (DLBCL), and typically show aggressive clinical behavior. Relapses most frequently involve cervical lymph nodes, the orbit, and the central nervous system.</div><div>Ocular involvement is rare, usually presenting as orbital masses or ocular adnexal lymphoma. Vitreoretinal infiltration is even more unusual and has been described only infrequently.</div><div>In this case report, we present an elderly male patient with nasal cavity B-cell lymphoma who developed relapse with vitreoretinal involvement, aiming to emphasize the diagnostic and therapeutic aspects of this rare condition.</div></div><div><h3>Case Presentation</h3><div>A 71-year-old male was diagnosed three years earlier with nasal cavity B-cell lymphoma. Bone marrow biopsy at diagnosis showed no systemic involvement. He received four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and achieved complete remission.</div><div>Three years later, he presented with decreased vision in the left eye. Orbital MRI showed tortuosity of the optic nerve and slight widening of the perioptic space (Figure 1). Cranial MRI revealed only age-related changes. Cytology and flow cytometry of vitreous fluid demonstrated CD20 and CD79a positivity with high proliferative activity, consistent with B-cell neoplasia.</div><div>PET-CT revealed limited FDG uptake (SUVmax 5.02) in the anterior aspect of the left orbit (Figure 2), with no additional systemic involvement. Based on his disease history, systemic high-dose methotrexate combined with cytarabine and intrathecal therapy was initiated. Radiotherapy was also considered.</div><div>He was referred to another specialized center for possible intravitreal chemotherapy. Despite systemic treatment, follow-up revealed that the patient had died.</div></div><div><h3>Discussion and Conclusion</h3><div>Sinonasal B-cell lymphomas are uncommon, most often exhibiting DLBCL histology with aggressive clinical features. Relapses most frequently involve cervical nodes, orbital structures, or the central nervous system. Although orbital disease is recognized, vitreoretinal infiltration is exceedingly rare and has been reported in less than 5% of cases in large series.</div><div>Diagnosis is challenging, as ocular involvement may present with non-specific symptoms such as visual impairment or vitreous opacities, requiring cytology, immunophenotyping, and immunohistochemistry of vitreous samples for confirmation.</div><div>Therapeutic options include systemic high-dose methotrexate and cytarabine, with intrathecal therapy commonly added for central nervous system prophylaxis. Radiotherapy may contribute to local contr
{"title":"VITREORETINAL INVOLVEMENT IN NASAL CAVITY B-CELL LYMPHOMA: A RARE FORM OF RELAPSE","authors":"Songül Beskisiz Dönen, Vehbi Demircan Abdullah, Karakuş Mehmet Orhan Ayyıldız","doi":"10.1016/j.htct.2025.106133","DOIUrl":"10.1016/j.htct.2025.106133","url":null,"abstract":"<div><h3>Introduction</h3><div>Non-Hodgkin lymphomas are malignant neoplasms of lymphoid tissue, and a subset present with extranodal involvement. The head and neck region represents one of the clinically relevant localizations. Sinonasal B-cell lymphomas are a rare subtype, most often manifesting as diffuse large B-cell lymphoma (DLBCL), and typically show aggressive clinical behavior. Relapses most frequently involve cervical lymph nodes, the orbit, and the central nervous system.</div><div>Ocular involvement is rare, usually presenting as orbital masses or ocular adnexal lymphoma. Vitreoretinal infiltration is even more unusual and has been described only infrequently.</div><div>In this case report, we present an elderly male patient with nasal cavity B-cell lymphoma who developed relapse with vitreoretinal involvement, aiming to emphasize the diagnostic and therapeutic aspects of this rare condition.</div></div><div><h3>Case Presentation</h3><div>A 71-year-old male was diagnosed three years earlier with nasal cavity B-cell lymphoma. Bone marrow biopsy at diagnosis showed no systemic involvement. He received four cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and achieved complete remission.</div><div>Three years later, he presented with decreased vision in the left eye. Orbital MRI showed tortuosity of the optic nerve and slight widening of the perioptic space (Figure 1). Cranial MRI revealed only age-related changes. Cytology and flow cytometry of vitreous fluid demonstrated CD20 and CD79a positivity with high proliferative activity, consistent with B-cell neoplasia.</div><div>PET-CT revealed limited FDG uptake (SUVmax 5.02) in the anterior aspect of the left orbit (Figure 2), with no additional systemic involvement. Based on his disease history, systemic high-dose methotrexate combined with cytarabine and intrathecal therapy was initiated. Radiotherapy was also considered.</div><div>He was referred to another specialized center for possible intravitreal chemotherapy. Despite systemic treatment, follow-up revealed that the patient had died.</div></div><div><h3>Discussion and Conclusion</h3><div>Sinonasal B-cell lymphomas are uncommon, most often exhibiting DLBCL histology with aggressive clinical features. Relapses most frequently involve cervical nodes, orbital structures, or the central nervous system. Although orbital disease is recognized, vitreoretinal infiltration is exceedingly rare and has been reported in less than 5% of cases in large series.</div><div>Diagnosis is challenging, as ocular involvement may present with non-specific symptoms such as visual impairment or vitreous opacities, requiring cytology, immunophenotyping, and immunohistochemistry of vitreous samples for confirmation.</div><div>Therapeutic options include systemic high-dose methotrexate and cytarabine, with intrathecal therapy commonly added for central nervous system prophylaxis. Radiotherapy may contribute to local contr","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106133"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796976","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.2025.106150
Yakup ÜNSAL , Murat GÜLTEKİN , Nurettin KURT , Muhammed MURATI , Shahad ISMAEL , Güler DELİBALTA , Serdar Bedii Omay
<div><h3>Objective</h3><div>Autoimmune encephalitis (AE) is a group of encephalitides caused by immune-mediated inflammatory disorders of the brain. While B cell–mediated autoimmunity is observed in many patients, some subtypes also involve T cell–mediated mechanisms. AE-related antibodies are classified into three groups: paraneoplastic antibodies, synaptic antibodies, and antibodies of uncertain significance. Paraneoplastic antibodies are frequently associated with systemic tumors and show poor responsiveness to immunotherapy. Synaptic antibodies, on the other hand, display variable associations with systemic tumors but are generally more responsive to immunotherapy. The diagnosis of AE is based on clinical features, radiological findings (such as abnormalities on T2 and FLAIR brain MRI), slow-wave activity in the temporal lobe, cerebrospinal fluid (CSF) pleocytosis, and the exclusion of alternative causes. Although antibody detection remains one of the best diagnostic tools, many cases may still be seronegative. Common paraneoplastic antibodies include anti-Hu, anti-Yo, anti-CV2, anti-Ma2, anti-Ri, anti-amphiphysin, ZIC4, and GAD65. Major synaptic autoantibodies include anti-NMDA, anti-AMPA, anti-GABA-B receptor, anti-CASPR, and anti-LG1. Antibody-positive AE represents a distinct subgroup of encephalopathies characterized by autoimmune responses against various antigens in the brain parenchyma<sup>1,2</sup>. Due to clinical, imaging, and laboratory similarities with infectious and other autoimmune encephalitides, AE remains a diagnostic challenge. Patients typically present with subacute memory and cognitive decline over days to weeks. Encephalopathic syndromes may include behavioral changes, psychosis, seizures, and coma, reflecting a broad neuropsychiatric spectrum³. In addition to supportive and antiepileptic therapies, early initiation of immunosuppressive treatment is essential. First-line immunosuppressive therapies in AE include corticosteroids, intravenous immunoglobulin, and plasma exchange⁴<sup>,</sup>⁵. For patients unresponsive to first-line treatments, second-line therapies include anti-CD20 monoclonal antibodies (rituximab and ofatumumab), mycophenolate mofetil, cyclophosphamide, and azathioprine. In refractory cases, third-line therapies such as daratumumab, bortezomib, obinutuzumab, tocilizumab, anakinra, tofacitinib, and intrathecal methotrexate may be considered⁵. Several studies have demonstrated that the use of ofatumumab, a second-generation CD20 monoclonal antibody, results in reduced antibody titers and significant clinical improvement in AE⁶<sup>,</sup>⁷.</div></div><div><h3>Case report</h3><div>A 22-year-old female patient was admitted to an ICU in Kosovo in June 2025 with impaired consciousness and was intubated. Her Glasgow Coma Scale (GCS) score was 3. She was transferred to our hospital’s intensive care unit on June 19, 2025, with a presumptive diagnosis of autoimmune encephalitis. A brain MRI performed externally
{"title":"HEMATOLOGICAL APPROACHES IN AUTOIMMUNE ENCEPHALITIS: OFATUMUMAB EXPERIENCE","authors":"Yakup ÜNSAL , Murat GÜLTEKİN , Nurettin KURT , Muhammed MURATI , Shahad ISMAEL , Güler DELİBALTA , Serdar Bedii Omay","doi":"10.1016/j.htct.2025.106150","DOIUrl":"10.1016/j.htct.2025.106150","url":null,"abstract":"<div><h3>Objective</h3><div>Autoimmune encephalitis (AE) is a group of encephalitides caused by immune-mediated inflammatory disorders of the brain. While B cell–mediated autoimmunity is observed in many patients, some subtypes also involve T cell–mediated mechanisms. AE-related antibodies are classified into three groups: paraneoplastic antibodies, synaptic antibodies, and antibodies of uncertain significance. Paraneoplastic antibodies are frequently associated with systemic tumors and show poor responsiveness to immunotherapy. Synaptic antibodies, on the other hand, display variable associations with systemic tumors but are generally more responsive to immunotherapy. The diagnosis of AE is based on clinical features, radiological findings (such as abnormalities on T2 and FLAIR brain MRI), slow-wave activity in the temporal lobe, cerebrospinal fluid (CSF) pleocytosis, and the exclusion of alternative causes. Although antibody detection remains one of the best diagnostic tools, many cases may still be seronegative. Common paraneoplastic antibodies include anti-Hu, anti-Yo, anti-CV2, anti-Ma2, anti-Ri, anti-amphiphysin, ZIC4, and GAD65. Major synaptic autoantibodies include anti-NMDA, anti-AMPA, anti-GABA-B receptor, anti-CASPR, and anti-LG1. Antibody-positive AE represents a distinct subgroup of encephalopathies characterized by autoimmune responses against various antigens in the brain parenchyma<sup>1,2</sup>. Due to clinical, imaging, and laboratory similarities with infectious and other autoimmune encephalitides, AE remains a diagnostic challenge. Patients typically present with subacute memory and cognitive decline over days to weeks. Encephalopathic syndromes may include behavioral changes, psychosis, seizures, and coma, reflecting a broad neuropsychiatric spectrum³. In addition to supportive and antiepileptic therapies, early initiation of immunosuppressive treatment is essential. First-line immunosuppressive therapies in AE include corticosteroids, intravenous immunoglobulin, and plasma exchange⁴<sup>,</sup>⁵. For patients unresponsive to first-line treatments, second-line therapies include anti-CD20 monoclonal antibodies (rituximab and ofatumumab), mycophenolate mofetil, cyclophosphamide, and azathioprine. In refractory cases, third-line therapies such as daratumumab, bortezomib, obinutuzumab, tocilizumab, anakinra, tofacitinib, and intrathecal methotrexate may be considered⁵. Several studies have demonstrated that the use of ofatumumab, a second-generation CD20 monoclonal antibody, results in reduced antibody titers and significant clinical improvement in AE⁶<sup>,</sup>⁷.</div></div><div><h3>Case report</h3><div>A 22-year-old female patient was admitted to an ICU in Kosovo in June 2025 with impaired consciousness and was intubated. Her Glasgow Coma Scale (GCS) score was 3. She was transferred to our hospital’s intensive care unit on June 19, 2025, with a presumptive diagnosis of autoimmune encephalitis. A brain MRI performed externally","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106150"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796518","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.2025.106172
Şule Çalışkan Kamış, Meryem Sena Doğan, Nihal Boz, Metin Çil, Defne Ay Tuncel, Mehmet Deniz Erhan, Utku Aygüneş, Ganiye Begül Yağcı, Barbaros Şahin Karagün
Objective
Cold agglutinin disease (CAD) is a form of autoimmune hemolytic anemia caused by antibodies—typically immunoglobulin M (IgM), and less frequently IgA or IgG—that target antigens on the surface of erythrocytes. Although the etiology may involve infections or immunologic disorders, most cases are idiopathic. The clinical picture results from hemolysis triggered by antibodies that become active at cold temperatures, leading to degenerative changes in the erythrocyte membrane and autoagglutination. This causes a drop in erythrocyte count and hematocrit, while MCV, MCH, and MCHC values appear markedly elevated. Peripheral blood smears often reveal erythrocyte agglutination. Here in, we present a case of cold agglutinin disease secondary to COVID-19 infection.
Case Presentation
A 14-year-old previously healthy girl was initially treated with amoxicillin-clavulanate for upper respiratory tract infection symptoms, including fever and cough. Her symptoms worsened, and she tested positive for COVID-19 at an outside hospital. She was diagnosed with lobar pneumonia, and significant anemia noted during follow-up prompted her referral to our institution, Türkiye.
Upon admission to our pediatric intensive care unit, three consecutive hemogram samples were clotted and could not be analyzed. Venous blood gas revealed hemoglobin (Hb) of 4.2 g/dL. Biochemical analyses showed LDH: 724 U/L (range 110-295 U/L), total bilirubin: 1.85 mg/dL (range 0.3-1.2 mg/dL), direct bilirubin: 0.29 mg/dL (range 0-0.2 mg/dL), and haptoglobin: 0.38 g/L (range 0.35-2.5 g/L). Direct Coombs test was negative. Peripheral smear demonstrated erythrocyte agglutination clusters. Blood samples were delivered to the laboratory in warm water immediately after collection to prevent in vitro agglutination. Repeat tests showed Hb: 8.2 g/dL, MCV: 100 fL, and a markedly elevated MCHC of 683 g/dL.
Quantitative cold agglutinin testing could not be performed due to technical limitations at our center. In addition to pneumonia treatment, the patient was started on methylprednisolone at 2 mg/kg/day for presumed cold agglutinin disease. She was discharged on day 10 of treatment and her steroid therapy was tapered and discontinued by day 21. At follow-up on day 21, the patient’s hemoglobin had increased to 13.9 g/dL, and no erythrocyte agglutination was observed on peripheral smear.
Conclusion
This case highlights a rare pediatric presentation of cold agglutinin disease associated with COVID-19 infection, complicated by severe hemolysis and lobar pneumonia. Early recognition and a multidisciplinary approach including corticosteroids and supportive care played a critical role in the patient's favorable outcome.
{"title":"COLD AGGLUTININ DISEASE ASSOCIATED WITH COVID-19 INFECTION IN A PEDIATRIC PATIENT: A RARE CASE PRESENTING WITH SEVERE HEMOLYTIC ANEMIA AND LOBAR PNEUMONIA","authors":"Şule Çalışkan Kamış, Meryem Sena Doğan, Nihal Boz, Metin Çil, Defne Ay Tuncel, Mehmet Deniz Erhan, Utku Aygüneş, Ganiye Begül Yağcı, Barbaros Şahin Karagün","doi":"10.1016/j.htct.2025.106172","DOIUrl":"10.1016/j.htct.2025.106172","url":null,"abstract":"<div><h3>Objective</h3><div>Cold agglutinin disease (CAD) is a form of autoimmune hemolytic anemia caused by antibodies—typically immunoglobulin M (IgM), and less frequently IgA or IgG—that target antigens on the surface of erythrocytes. Although the etiology may involve infections or immunologic disorders, most cases are idiopathic. The clinical picture results from hemolysis triggered by antibodies that become active at cold temperatures, leading to degenerative changes in the erythrocyte membrane and autoagglutination. This causes a drop in erythrocyte count and hematocrit, while MCV, MCH, and MCHC values appear markedly elevated. Peripheral blood smears often reveal erythrocyte agglutination. Here in, we present a case of cold agglutinin disease secondary to COVID-19 infection.</div></div><div><h3>Case Presentation</h3><div>A 14-year-old previously healthy girl was initially treated with amoxicillin-clavulanate for upper respiratory tract infection symptoms, including fever and cough. Her symptoms worsened, and she tested positive for COVID-19 at an outside hospital. She was diagnosed with lobar pneumonia, and significant anemia noted during follow-up prompted her referral to our institution, Türkiye.</div><div>Upon admission to our pediatric intensive care unit, three consecutive hemogram samples were clotted and could not be analyzed. Venous blood gas revealed hemoglobin (Hb) of 4.2 g/dL. Biochemical analyses showed LDH: 724 U/L (range 110-295 U/L), total bilirubin: 1.85 mg/dL (range 0.3-1.2 mg/dL), direct bilirubin: 0.29 mg/dL (range 0-0.2 mg/dL), and haptoglobin: 0.38 g/L (range 0.35-2.5 g/L). Direct Coombs test was negative. Peripheral smear demonstrated erythrocyte agglutination clusters. Blood samples were delivered to the laboratory in warm water immediately after collection to prevent in vitro agglutination. Repeat tests showed Hb: 8.2 g/dL, MCV: 100 fL, and a markedly elevated MCHC of 683 g/dL.</div><div>Quantitative cold agglutinin testing could not be performed due to technical limitations at our center. In addition to pneumonia treatment, the patient was started on methylprednisolone at 2 mg/kg/day for presumed cold agglutinin disease. She was discharged on day 10 of treatment and her steroid therapy was tapered and discontinued by day 21. At follow-up on day 21, the patient’s hemoglobin had increased to 13.9 g/dL, and no erythrocyte agglutination was observed on peripheral smear.</div></div><div><h3>Conclusion</h3><div>This case highlights a rare pediatric presentation of cold agglutinin disease associated with COVID-19 infection, complicated by severe hemolysis and lobar pneumonia. Early recognition and a multidisciplinary approach including corticosteroids and supportive care played a critical role in the patient's favorable outcome.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106172"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796523","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.2025.106143
Naciye Nur Tozluklu, Birol Güvenç
<div><h3>Introduction</h3><div>Marginal zone lymphoma (MZL) with plasmacytic differentiation can mimic other B-cell entities—particularly CLL/SLL and lymphoplasmacytic lymphoma (LPL)—and often presents in the elderly with cytopenias rather than bulky nodal disease. Correct classification is critical, as comorbidity and frailty frequently constrain treatment intensity. We report a bone marrow–dominant, plasmacytoid MZL in an 84-year-old woman successfully managed with rituximab monotherapy.</div></div><div><h3>Methods</h3><div>We conducted a single-patient, retrospective case review of prospectively collected clinical, laboratory, pathology, and imaging data. Diagnostic workflow integrated complete blood count, immunoglobulin quantification, bone marrow histology with immunohistochemistry (IHC), multiparameter flow cytometry, and FDG-PET/CT. Treatment selection followed a frailty-adapted decision process.</div></div><div><h3>Results</h3><div>An 84-year-old woman presented with progressive fatigue and dyspnea on exertion. Baseline labs showed leukocytosis with marked lymphocytosis and macrocytic pancytopenia (WBC 22.2 × 10^9/L; absolute lymphocytes 18.4 × 10^9/L; Hb 8.1 g/dL; MCV 105 fL; platelets 42 × 10^9/L). Immunoglobulins were not suggestive of LPL/WM (IgM 0.73 g/L; IgG 13.6 g/L; IgA 1.7 g/L). FDG-PET/CT revealed mediastinal/abdominal lymphadenopathy, splenomegaly, and a sternal cortical irregularity suspicious for osseous involvement.</div><div>Bone marrow biopsy was hypercellular (∼95%) with ∼90% interstitial/patchy small-to-intermediate B-cell infiltration; reticulin fibrosis 0/4; Congo red negative. IHC supported a non-CLL, non-mantle phenotype: CD20 strong positive; CD5, CD23, CD10, cyclin D1, annexin A1, TRAP all negative. Flow cytometry demonstrated a clonal mature B-cell population (CD19+, CD20+, CD38+, cCD79a+) without CLL-type markers (CD5/CD23 negative). Plasmacytic differentiation was present, yet serum IgM remained normal, arguing against LPL/WM. Overall, findings established marginal zone lymphoma with plasmacytic differentiation, stage IV-A (marrow ± splenic/possible bone involvement).</div><div>Given advanced age, cytopenias, and frailty, cytotoxic chemo-immunotherapy was deferred. The patient received rituximab monotherapy with antiviral prophylaxis and supportive care (transfusion as needed). Treatment was well tolerated; early follow-up showed clinical improvement with rising hemoglobin and platelet counts and reduction in lymphocytosis.</div></div><div><h3>Discussion</h3><div>This case highlights three practice points. First, plasmacytic differentiation in MZL can masquerade as CLL or LPL/WM; a disciplined panel—CD5/CD23/cyclin D1 negativity with strong CD20 and compatible flow cytometry—prevents misclassification. Second, serological context matters: normal IgM helped exclude LPL/WM despite plasmacytoid histology. Third, in the very elderly/frail, rituximab monotherapy is a rational, lower-toxicity strategy that can revers
{"title":"Marrow-Dominant Marginal Zone Lymphoma with Plasmacytic Differentiation in a Frail and old patient: Immunophenotypic Pitfalls and Rituximab-Only Strategy","authors":"Naciye Nur Tozluklu, Birol Güvenç","doi":"10.1016/j.htct.2025.106143","DOIUrl":"10.1016/j.htct.2025.106143","url":null,"abstract":"<div><h3>Introduction</h3><div>Marginal zone lymphoma (MZL) with plasmacytic differentiation can mimic other B-cell entities—particularly CLL/SLL and lymphoplasmacytic lymphoma (LPL)—and often presents in the elderly with cytopenias rather than bulky nodal disease. Correct classification is critical, as comorbidity and frailty frequently constrain treatment intensity. We report a bone marrow–dominant, plasmacytoid MZL in an 84-year-old woman successfully managed with rituximab monotherapy.</div></div><div><h3>Methods</h3><div>We conducted a single-patient, retrospective case review of prospectively collected clinical, laboratory, pathology, and imaging data. Diagnostic workflow integrated complete blood count, immunoglobulin quantification, bone marrow histology with immunohistochemistry (IHC), multiparameter flow cytometry, and FDG-PET/CT. Treatment selection followed a frailty-adapted decision process.</div></div><div><h3>Results</h3><div>An 84-year-old woman presented with progressive fatigue and dyspnea on exertion. Baseline labs showed leukocytosis with marked lymphocytosis and macrocytic pancytopenia (WBC 22.2 × 10^9/L; absolute lymphocytes 18.4 × 10^9/L; Hb 8.1 g/dL; MCV 105 fL; platelets 42 × 10^9/L). Immunoglobulins were not suggestive of LPL/WM (IgM 0.73 g/L; IgG 13.6 g/L; IgA 1.7 g/L). FDG-PET/CT revealed mediastinal/abdominal lymphadenopathy, splenomegaly, and a sternal cortical irregularity suspicious for osseous involvement.</div><div>Bone marrow biopsy was hypercellular (∼95%) with ∼90% interstitial/patchy small-to-intermediate B-cell infiltration; reticulin fibrosis 0/4; Congo red negative. IHC supported a non-CLL, non-mantle phenotype: CD20 strong positive; CD5, CD23, CD10, cyclin D1, annexin A1, TRAP all negative. Flow cytometry demonstrated a clonal mature B-cell population (CD19+, CD20+, CD38+, cCD79a+) without CLL-type markers (CD5/CD23 negative). Plasmacytic differentiation was present, yet serum IgM remained normal, arguing against LPL/WM. Overall, findings established marginal zone lymphoma with plasmacytic differentiation, stage IV-A (marrow ± splenic/possible bone involvement).</div><div>Given advanced age, cytopenias, and frailty, cytotoxic chemo-immunotherapy was deferred. The patient received rituximab monotherapy with antiviral prophylaxis and supportive care (transfusion as needed). Treatment was well tolerated; early follow-up showed clinical improvement with rising hemoglobin and platelet counts and reduction in lymphocytosis.</div></div><div><h3>Discussion</h3><div>This case highlights three practice points. First, plasmacytic differentiation in MZL can masquerade as CLL or LPL/WM; a disciplined panel—CD5/CD23/cyclin D1 negativity with strong CD20 and compatible flow cytometry—prevents misclassification. Second, serological context matters: normal IgM helped exclude LPL/WM despite plasmacytoid histology. Third, in the very elderly/frail, rituximab monotherapy is a rational, lower-toxicity strategy that can revers","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106143"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796527","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.2025.106191
Salih Sertaç Durusoy
<div><div>Platelet function disorders (PFDs) represent a diverse group of qualitative platelet defects that often remain underdiagnosed despite normal platelet counts. Their clinical relevance extends beyond hematology, as undetected PFDs contribute to perioperative bleeding, complications in oncology, and challenges in balancing hemostasis with cardiovascular protection during antiplatelet therapy. For hematologists, timely recognition of these disorders is critical for optimal patient care.</div><div>Inherited PFDs (IPFDs) include Glanzmann thrombasthenia, Bernard–Soulier syndrome, and RUNX1-associated familial platelet disorder, each characterized by distinct receptor or signaling abnormalities. These range from impaired fibrinogen binding (αIIbβ3 defects) to defective adhesion (GPIb–IX–V complex deficiencies). Syndromic forms such as Wiskott–Aldrich syndrome illustrate the intersection of platelet dysfunction, immune dysregulation, and malignancy predisposition. The spectrum of bleeding can vary considerably. Acquired PFDs are more frequent and clinically impactful. Drugs such as aspirin and P2Y12 inhibitors, uremia, advanced liver disease, myeloproliferative neoplasms, and xtracorporeal circulation all compromise platelet activation or secretion. Given their prevalence, distinguishing pharmacologic platelet inhibition from true dysfunction is a practical challenge in routine hematology.</div><div>Diagnosis requires a structured, tiered approach. Clinical history and bleeding scores remain the foundation, but must be complemented by laboratory assays. Initial testing should exclude von Willebrand disease, while light transmission aggregometry, flow cytometry, and secretion assays provide functional insights. Next-generation sequencing now allows precise molecular classification of many IPFDs, though accessibility remains uneven. Novel technologies, including microfluidics and whole-blood shear assays, ...</div><div>Therapeutic strategies depend on etiology and severity. Antifibrinolytics and desmopressin are often sufficient for mild bleeding; platelet transfusions and recombinant factor VIIa are mainstays for severe inherited forms, particularly Glanzmann thrombasthenia complicated by alloimmunization. Hematopoietic stem cell transplantation offers curative potential in selected syndromic disorders. In acquired dysfunction, correcting underlying disease or adjusting medications is essential. Personalized perioperative pla...</div><div>Future challenges include diagnostic delays, variability in laboratory availability, and unequal global access to advanced therapies. However, rapid integration of genomics, standardized testing protocols, and emerging hemostatic agents promise to redefine clinical management. Collaborative registries and international networks will be essential to accelerate discovery and translate innovation into equitable care.</div><div>In conclusion, PFDs embody a nuanced and evolving frontier in hematology. By integrating
{"title":"PLATELET FUNCTION DISORDERS: CONTEMPORARY INSIGHTS AND FUTURE DIRECTIONS","authors":"Salih Sertaç Durusoy","doi":"10.1016/j.htct.2025.106191","DOIUrl":"10.1016/j.htct.2025.106191","url":null,"abstract":"<div><div>Platelet function disorders (PFDs) represent a diverse group of qualitative platelet defects that often remain underdiagnosed despite normal platelet counts. Their clinical relevance extends beyond hematology, as undetected PFDs contribute to perioperative bleeding, complications in oncology, and challenges in balancing hemostasis with cardiovascular protection during antiplatelet therapy. For hematologists, timely recognition of these disorders is critical for optimal patient care.</div><div>Inherited PFDs (IPFDs) include Glanzmann thrombasthenia, Bernard–Soulier syndrome, and RUNX1-associated familial platelet disorder, each characterized by distinct receptor or signaling abnormalities. These range from impaired fibrinogen binding (αIIbβ3 defects) to defective adhesion (GPIb–IX–V complex deficiencies). Syndromic forms such as Wiskott–Aldrich syndrome illustrate the intersection of platelet dysfunction, immune dysregulation, and malignancy predisposition. The spectrum of bleeding can vary considerably. Acquired PFDs are more frequent and clinically impactful. Drugs such as aspirin and P2Y12 inhibitors, uremia, advanced liver disease, myeloproliferative neoplasms, and xtracorporeal circulation all compromise platelet activation or secretion. Given their prevalence, distinguishing pharmacologic platelet inhibition from true dysfunction is a practical challenge in routine hematology.</div><div>Diagnosis requires a structured, tiered approach. Clinical history and bleeding scores remain the foundation, but must be complemented by laboratory assays. Initial testing should exclude von Willebrand disease, while light transmission aggregometry, flow cytometry, and secretion assays provide functional insights. Next-generation sequencing now allows precise molecular classification of many IPFDs, though accessibility remains uneven. Novel technologies, including microfluidics and whole-blood shear assays, ...</div><div>Therapeutic strategies depend on etiology and severity. Antifibrinolytics and desmopressin are often sufficient for mild bleeding; platelet transfusions and recombinant factor VIIa are mainstays for severe inherited forms, particularly Glanzmann thrombasthenia complicated by alloimmunization. Hematopoietic stem cell transplantation offers curative potential in selected syndromic disorders. In acquired dysfunction, correcting underlying disease or adjusting medications is essential. Personalized perioperative pla...</div><div>Future challenges include diagnostic delays, variability in laboratory availability, and unequal global access to advanced therapies. However, rapid integration of genomics, standardized testing protocols, and emerging hemostatic agents promise to redefine clinical management. Collaborative registries and international networks will be essential to accelerate discovery and translate innovation into equitable care.</div><div>In conclusion, PFDs embody a nuanced and evolving frontier in hematology. By integrating","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106191"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796694","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.2025.106121
Sema SEÇİLMİŞ, Fevzi ALTUNTAŞ
<div><h3>Introduction and Objective</h3><div>Langerhans cell histiocytosis (LCH) is a rare clonal proliferative disease that can involve one or more organs (1). In adults, multisystem involvement is generally predominant (68.6%), whereas single-system involvement is less common (2). The clinical spectrum is broad, with bone, skin, and lungs being the most frequently affected organs. The treatment approach varies according to the extent of the disease, and the optimal treatment strategy has not yet been clearly defined(3-6).</div><div>This study aimed to evaluate the demographic characteristics, sites of involvement, treatments administered, and treatment responses of adult LCH cases diagnosed at our center.</div></div><div><h3>Methods</h3><div>Medical records of adult patients diagnosed with LCH at our center between 2002 and 2024 were retrospectively reviewed. Patient age, sex, sites of involvement, treatment regimens, treatment responses, and follow-up durations were recorded.</div></div><div><h3>Results</h3><div>A total of 10 patients (9 male, 1 female) were analyzed. The median age was 31.5 years (range: 20–76). The median follow-up duration was 5.8 years (approximately 69 months). Three patients (30%) had multisystem involvement, and seven patients (70%) had single-system involvement. The most common site of involvement was bone (80%), followed by skin (20%) and lymph nodes (10%). Diabetes insipidus was detected in one patient (10%).</div><div>Treatment approaches were heterogeneous. Five patients received radiotherapy (RT), three patients were treated with a vinblastine and prednisolone combination, one patient with multisystem involvement received cladribine combined with RT, one patient was given prednisolone monotherapy, and one patient was followed without treatment.</div><div>A response was achieved in all patients after initial treatment. Two patients (20%) experienced relapse, both in those with bone involvement only. The patient treated with cladribine remains in long-term complete remission. No mortality was observed.</div><div>Feature</div><div>Value</div><div>Total number of patients</div><div>10</div><div>Median age (years)</div><div>31.5 (20–76)</div><div>Median follow-up duration</div><div>5.8 years (approximately 69 months)</div><div>Male/Female</div><div>9/1</div><div>Multisystem</div><div>3 (30%)</div><div>Single-system</div><div>7 (70%)</div><div>Most common involvement</div><div>Bone (80%)</div><div>Relapse</div><div>2 (20%)</div><div>Mortality</div><div>0</div></div><div><h3>Discussion</h3><div>In adult Langerhans cell histiocytosis, multisystem involvement is reported as the most common form in the literature; however, in our study, single-system involvement was detected in 70% of patients. This discrepancy may be explained by differences in patient referral patterns to our center, follow-up of pulmonary LCH cases in chest disease clinics, variations in staging due to the retrospective design, and demographic factors.Th
{"title":"LANGERHANS CELL HISTIOCYTOSIS: SINGLE-CENTER EXPERIENCE","authors":"Sema SEÇİLMİŞ, Fevzi ALTUNTAŞ","doi":"10.1016/j.htct.2025.106121","DOIUrl":"10.1016/j.htct.2025.106121","url":null,"abstract":"<div><h3>Introduction and Objective</h3><div>Langerhans cell histiocytosis (LCH) is a rare clonal proliferative disease that can involve one or more organs (1). In adults, multisystem involvement is generally predominant (68.6%), whereas single-system involvement is less common (2). The clinical spectrum is broad, with bone, skin, and lungs being the most frequently affected organs. The treatment approach varies according to the extent of the disease, and the optimal treatment strategy has not yet been clearly defined(3-6).</div><div>This study aimed to evaluate the demographic characteristics, sites of involvement, treatments administered, and treatment responses of adult LCH cases diagnosed at our center.</div></div><div><h3>Methods</h3><div>Medical records of adult patients diagnosed with LCH at our center between 2002 and 2024 were retrospectively reviewed. Patient age, sex, sites of involvement, treatment regimens, treatment responses, and follow-up durations were recorded.</div></div><div><h3>Results</h3><div>A total of 10 patients (9 male, 1 female) were analyzed. The median age was 31.5 years (range: 20–76). The median follow-up duration was 5.8 years (approximately 69 months). Three patients (30%) had multisystem involvement, and seven patients (70%) had single-system involvement. The most common site of involvement was bone (80%), followed by skin (20%) and lymph nodes (10%). Diabetes insipidus was detected in one patient (10%).</div><div>Treatment approaches were heterogeneous. Five patients received radiotherapy (RT), three patients were treated with a vinblastine and prednisolone combination, one patient with multisystem involvement received cladribine combined with RT, one patient was given prednisolone monotherapy, and one patient was followed without treatment.</div><div>A response was achieved in all patients after initial treatment. Two patients (20%) experienced relapse, both in those with bone involvement only. The patient treated with cladribine remains in long-term complete remission. No mortality was observed.</div><div>Feature</div><div>Value</div><div>Total number of patients</div><div>10</div><div>Median age (years)</div><div>31.5 (20–76)</div><div>Median follow-up duration</div><div>5.8 years (approximately 69 months)</div><div>Male/Female</div><div>9/1</div><div>Multisystem</div><div>3 (30%)</div><div>Single-system</div><div>7 (70%)</div><div>Most common involvement</div><div>Bone (80%)</div><div>Relapse</div><div>2 (20%)</div><div>Mortality</div><div>0</div></div><div><h3>Discussion</h3><div>In adult Langerhans cell histiocytosis, multisystem involvement is reported as the most common form in the literature; however, in our study, single-system involvement was detected in 70% of patients. This discrepancy may be explained by differences in patient referral patterns to our center, follow-up of pulmonary LCH cases in chest disease clinics, variations in staging due to the retrospective design, and demographic factors.Th","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106121"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796706","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}
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