Pub Date : 2025-12-01DOI: 10.1016/j.htct.2025.106168
Hüseyin Derya Dinçyürek , Birol Güvenç
<div><h3>Introduction</h3><div>Multiple myeloma (MM) in young adults is uncommon, and high-risk cytogenetics complicate standard pathways. We report a 31-year-old woman with IgA-κ MM, large sacral involvement, and adverse genetics, achieving a deep remission with daratumumab–lenalidomide–dexamethasone (DRd) plus focal radiotherapy (RT), electing to defer autologous transplant.</div></div><div><h3>Methods</h3><div>Single-patient case review from prospectively maintained records. Data included presenting features, MRI/PET-CT, serum/urine monoclonal studies, bone-marrow histology/flow, and plasma-cell FISH. Treatment, response, and tolerability were documented.</div></div><div><h3>Results</h3><div>A previously healthy 31-year-old presented with severe nocturnal lumbosacral pain and right-sciatic radiation. MRI revealed a left-lateral sacral mass (77 × 56 mm) with contrast enhancement; PET-CT demonstrated focal hypermetabolic lytic lesions in sacrum, L1, pubis, and scapula (SUVmax 5.4–5.9), with no visceral/extramedullary organ disease. Serum studies showed an IgA-κ M-component with elevated free light-chain ratio; β2-microglobulin was 4.2 mg/L (ISS stage II). Bone-marrow biopsy displayed intertrabecular plasma-cell infiltration; immunophenotype CD38+, CD56+, κ-restricted, CD19–; reticulin 0–1/4; amyloid negative. Plasma-cell FISH identified t(14;20)(IGH–MAFB) in ∼35% of cells, indicating high-risk disease.</div><div>She commenced DRd and received concurrent local RT to the sacrum (fractionated) for rapid pain control. Treatment was well tolerated, without renal or calcium derangements. Clinically, pain resolved; biochemically, the M-component cleared; radiologically, bone foci regressed with disappearance of pathologic uptake on interval imaging. Bone-marrow reassessment showed marked reduction of clonal plasma cells, consistent with deep response. Given age, recovery, and patient preference, autologous transplant was performed; she continued maintenance (daratumumab ± lenalidomide) with sustained remission on follow-up.</div></div><div><h3>Discussion</h3><div>This case underscores four practice points. (1) Aggressive osseous disease at young age can herald high-risk biology; early, integrated MRI/PET staging captures true burden and guides focal RT for symptom control while systemic therapy acts on disseminated marrow disease. (2) Immunophenotype and marrow context (CD38+/CD56+, κ-restriction; low reticulin) affirmed clonal plasmacytosis consistent with MM rather than solitary plasmacytoma or IgG4-related processes. (3) Cytogenetic risk—notably t(14;20)—supports intensified monoclonal-antibody–based induction (DRd) and vigilant surveillance, as this lesion associates with inferior outcomes on IMiD/PI-only backbones. (4) In select young patients achieving deep remission, deferring ASCT after robust daratumumab-based induction and consolidative RT can be reasonable when aligned with patient values and close monitoring—especially if toxicity, fertilit
{"title":"High-Risk IgA-κ Myeloma with Sacral Mass in a 31-Year-Old: Deep Response to Daratumumab–Lenalidomide–Dexamethasone plus Local RT without ASCT","authors":"Hüseyin Derya Dinçyürek , Birol Güvenç","doi":"10.1016/j.htct.2025.106168","DOIUrl":"10.1016/j.htct.2025.106168","url":null,"abstract":"<div><h3>Introduction</h3><div>Multiple myeloma (MM) in young adults is uncommon, and high-risk cytogenetics complicate standard pathways. We report a 31-year-old woman with IgA-κ MM, large sacral involvement, and adverse genetics, achieving a deep remission with daratumumab–lenalidomide–dexamethasone (DRd) plus focal radiotherapy (RT), electing to defer autologous transplant.</div></div><div><h3>Methods</h3><div>Single-patient case review from prospectively maintained records. Data included presenting features, MRI/PET-CT, serum/urine monoclonal studies, bone-marrow histology/flow, and plasma-cell FISH. Treatment, response, and tolerability were documented.</div></div><div><h3>Results</h3><div>A previously healthy 31-year-old presented with severe nocturnal lumbosacral pain and right-sciatic radiation. MRI revealed a left-lateral sacral mass (77 × 56 mm) with contrast enhancement; PET-CT demonstrated focal hypermetabolic lytic lesions in sacrum, L1, pubis, and scapula (SUVmax 5.4–5.9), with no visceral/extramedullary organ disease. Serum studies showed an IgA-κ M-component with elevated free light-chain ratio; β2-microglobulin was 4.2 mg/L (ISS stage II). Bone-marrow biopsy displayed intertrabecular plasma-cell infiltration; immunophenotype CD38+, CD56+, κ-restricted, CD19–; reticulin 0–1/4; amyloid negative. Plasma-cell FISH identified t(14;20)(IGH–MAFB) in ∼35% of cells, indicating high-risk disease.</div><div>She commenced DRd and received concurrent local RT to the sacrum (fractionated) for rapid pain control. Treatment was well tolerated, without renal or calcium derangements. Clinically, pain resolved; biochemically, the M-component cleared; radiologically, bone foci regressed with disappearance of pathologic uptake on interval imaging. Bone-marrow reassessment showed marked reduction of clonal plasma cells, consistent with deep response. Given age, recovery, and patient preference, autologous transplant was performed; she continued maintenance (daratumumab ± lenalidomide) with sustained remission on follow-up.</div></div><div><h3>Discussion</h3><div>This case underscores four practice points. (1) Aggressive osseous disease at young age can herald high-risk biology; early, integrated MRI/PET staging captures true burden and guides focal RT for symptom control while systemic therapy acts on disseminated marrow disease. (2) Immunophenotype and marrow context (CD38+/CD56+, κ-restriction; low reticulin) affirmed clonal plasmacytosis consistent with MM rather than solitary plasmacytoma or IgG4-related processes. (3) Cytogenetic risk—notably t(14;20)—supports intensified monoclonal-antibody–based induction (DRd) and vigilant surveillance, as this lesion associates with inferior outcomes on IMiD/PI-only backbones. (4) In select young patients achieving deep remission, deferring ASCT after robust daratumumab-based induction and consolidative RT can be reasonable when aligned with patient values and close monitoring—especially if toxicity, fertilit","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106168"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796516","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.2025.106131
Hüseyin Koçak, Esra Nur Saygeçitli, Ali Turunç, Birol Güvenç
Introduction
Histiocytic sarcoma (HS) is a rare, aggressive malignancy of monocyte–macrophage lineage, typically presenting with extranodal disease and lacking B- or T-cell markers [1]. Because of its rarity, there is no standard treatment, though salvage regimens such as ICE (ifosfamide, carboplatin, etoposide) have demonstrated some benefit. Ifosfamide, a DNA-alkylating prodrug metabolized by hepatic CYP3A4 and CYP2B6, is associated with central nervous system (CNS) toxicity in 10–30% of patients [2,3]. Encephalopathy is the most common presentation, while catatonia—characterized by stupor, mutism, negativism, posturing, and waxy flexibility—is rarely reported in oncology patients [4].
Case Presentation
A 27-year-old male with stage IV HS, confirmed by biopsy of an 80 × 70 mm terminal ileum mass, was admitted for ICE chemotherapy. On day three, he developed acute psychomotor symptoms including stupor, mutism, and negativism. The Bush–Francis Catatonia Rating Scale (score 7) and Kanner Catatonia Screening Instrument (score 4) confirmed retarded-type catatonia. Neurological evaluation (cranial CT, diffusion-weighted MRI) and laboratory studies were unremarkable. Vital signs remained stable. He was treated with intravenous diazepam 10 mg every 8 hours (two doses total), leading to full resolution of catatonic symptoms. The patient was discharged clinically stable.
Conclusion
Discussion Ifosfamide-induced neurotoxicity typically appears within 48–72 hours, mediated by toxic metabolites such as chloroacetaldehyde that disrupt mitochondrial function and neurotransmission [2,3]. While encephalopathy is well-documented, catatonia is extremely rare and underrecognized. In this case, the temporal relationship to ifosfamide, absence of structural CNS pathology, and rapid benzodiazepine response strongly support ifosfamide-induced catatonia. Similar observations have been described rarely; Gupta et al. [5] reported an analogous case in lymphoma. Benzodiazepines remain first-line therapy, often producing rapid resolution, even in drug-induced catatonia [6].Conclusion This case highlights catatonia as a rare neuropsychiatric complication of ifosfamide. Recognition of such unusual adverse effects is critical, as early diagnosis and benzodiazepine treatment can prevent delays in cancer therapy and improve outcomes.
{"title":"CATATONIA FOLLOWING IFOSFAMIDE CHEMOTHERAPY IN A PATIENT WITH HISTIOCYTIC SARCOMA: A RARE NEUROPSYCHIATRIC COMPLICATION","authors":"Hüseyin Koçak, Esra Nur Saygeçitli, Ali Turunç, Birol Güvenç","doi":"10.1016/j.htct.2025.106131","DOIUrl":"10.1016/j.htct.2025.106131","url":null,"abstract":"<div><h3>Introduction</h3><div>Histiocytic sarcoma (HS) is a rare, aggressive malignancy of monocyte–macrophage lineage, typically presenting with extranodal disease and lacking B- or T-cell markers [1]. Because of its rarity, there is no standard treatment, though salvage regimens such as ICE (ifosfamide, carboplatin, etoposide) have demonstrated some benefit. Ifosfamide, a DNA-alkylating prodrug metabolized by hepatic CYP3A4 and CYP2B6, is associated with central nervous system (CNS) toxicity in 10–30% of patients [2,3]. Encephalopathy is the most common presentation, while catatonia—characterized by stupor, mutism, negativism, posturing, and waxy flexibility—is rarely reported in oncology patients [4].</div></div><div><h3>Case Presentation</h3><div>A 27-year-old male with stage IV HS, confirmed by biopsy of an 80 × 70 mm terminal ileum mass, was admitted for ICE chemotherapy. On day three, he developed acute psychomotor symptoms including stupor, mutism, and negativism. The Bush–Francis Catatonia Rating Scale (score 7) and Kanner Catatonia Screening Instrument (score 4) confirmed retarded-type catatonia. Neurological evaluation (cranial CT, diffusion-weighted MRI) and laboratory studies were unremarkable. Vital signs remained stable. He was treated with intravenous diazepam 10 mg every 8 hours (two doses total), leading to full resolution of catatonic symptoms. The patient was discharged clinically stable.</div></div><div><h3>Conclusion</h3><div>Discussion Ifosfamide-induced neurotoxicity typically appears within 48–72 hours, mediated by toxic metabolites such as chloroacetaldehyde that disrupt mitochondrial function and neurotransmission [2,3]. While encephalopathy is well-documented, catatonia is extremely rare and underrecognized. In this case, the temporal relationship to ifosfamide, absence of structural CNS pathology, and rapid benzodiazepine response strongly support ifosfamide-induced catatonia. Similar observations have been described rarely; Gupta et al. [5] reported an analogous case in lymphoma. Benzodiazepines remain first-line therapy, often producing rapid resolution, even in drug-induced catatonia [6].Conclusion This case highlights catatonia as a rare neuropsychiatric complication of ifosfamide. Recognition of such unusual adverse effects is critical, as early diagnosis and benzodiazepine treatment can prevent delays in cancer therapy and improve outcomes.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106131"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796543","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.2025.106171
Abdi İbrahim Halil Sönmez
<div><div>A 37-year-old female patient with a diagnosis of thalassemia major was admitted to the emergency department with complaints of fatigue, nausea, vomiting, and abdominal pain. Laboratory tests revealed elevated liver enzymes and pancytopenia, prompting her hospitalization. It was noted that the patient had not received chelation therapy for the past three months and had a history of irregular use of chelating agents. Her laboratory values were as follows: WBC: 2,460/mm³, Neutrophils: 700/mm³, Hemoglobin: 5.2 g/dL, MCV: 62.8 fL, Platelets: 15,000/mm³. Due to her symptomatic presentation, the patient received cross-matched erythrocyte and platelet suspensions for transfusion. CRP was 0.8 mg/dL; coagulation and renal function tests were within normal limits. The patient had indirect hyperbilirubinemia, LDH: 984 U/L, vitamin B12: 467 pg/mL, folate: 9.53 pg/mL, and ferritin: 956 ng/mL. Both direct and indirect Coombs tests were initially negative. Tests for hepatitis markers, EBV, TORCH, and HIV were also negative. Parvovirus evaluation could not be performed. Peripheral blood smear revealed schistocytes, fragmented erythrocytes, and target cells, thrombocytopenia but no atypical cells. The patient underwent abdominal ultrasonography, which showed hepatosplenomegaly, with the spleen measuring 19 cm. Chest X-ray revealed pleural effusion, and thoracic and abdominal CT scans were planned. Thoracic CT revealed mass-like lesions in the vertebral area with unclear distinction, areas of pneumonic consolidation, and pleural effusion. Intravenous cephalosporin therapy was initiated for presumed pneumonia. ANA and anti-dsDNA tests were sent and returned negative. A PET-CT scan was planned. As the patient's cytopenias persisted despite ongoing transfusion needs, a bone marrow biopsy was performed. Bone marrow aspiration revealed increased cellularity and erythropoiesis without any abnormal findings. PET-CT demonstrated vertebral involvement attributed to extramedullary hematopoiesis; no malignant uptake was detected. Methylprednisolone was initiated at 1 mg/kg. Although platelet levels increased, anemia persisted. Repeated Coombs tests later returned strongly positive (+3) for both direct and indirect Coombs. Direct Coombs was positive for both IgG and C3. The patient had an elevated LDH (1200 U/L) and decreased haptoglobin levels. Due to steroid-refractory autoimmune hemolytic anemia, Rituximab 375 mg/week was administered for four doses, and the steroid dosage was tapered off. After two months, lab results showed WBC: 5,150/mm³, Hemoglobin: 9.2 g/dL, Platelets: 168,000/mm³. With a now negative direct Coombs test and a post-transfusion ferritin level of 2,322 ng/mL, chelation therapy was reinitiated. The patient, diagnosed with infection-related autoimmune hemolytic anemia, continues to receive monthly transfusions of cross-matched erythrocyte suspensions, Türkiye.</div><div>In this patient with thalassemia major who developed infection-associated auto
{"title":"A CASE OF THALASSEMIA DIAGNOSED WITH AUTOIMMUNE HEMOLYTIC ANEMIA","authors":"Abdi İbrahim Halil Sönmez","doi":"10.1016/j.htct.2025.106171","DOIUrl":"10.1016/j.htct.2025.106171","url":null,"abstract":"<div><div>A 37-year-old female patient with a diagnosis of thalassemia major was admitted to the emergency department with complaints of fatigue, nausea, vomiting, and abdominal pain. Laboratory tests revealed elevated liver enzymes and pancytopenia, prompting her hospitalization. It was noted that the patient had not received chelation therapy for the past three months and had a history of irregular use of chelating agents. Her laboratory values were as follows: WBC: 2,460/mm³, Neutrophils: 700/mm³, Hemoglobin: 5.2 g/dL, MCV: 62.8 fL, Platelets: 15,000/mm³. Due to her symptomatic presentation, the patient received cross-matched erythrocyte and platelet suspensions for transfusion. CRP was 0.8 mg/dL; coagulation and renal function tests were within normal limits. The patient had indirect hyperbilirubinemia, LDH: 984 U/L, vitamin B12: 467 pg/mL, folate: 9.53 pg/mL, and ferritin: 956 ng/mL. Both direct and indirect Coombs tests were initially negative. Tests for hepatitis markers, EBV, TORCH, and HIV were also negative. Parvovirus evaluation could not be performed. Peripheral blood smear revealed schistocytes, fragmented erythrocytes, and target cells, thrombocytopenia but no atypical cells. The patient underwent abdominal ultrasonography, which showed hepatosplenomegaly, with the spleen measuring 19 cm. Chest X-ray revealed pleural effusion, and thoracic and abdominal CT scans were planned. Thoracic CT revealed mass-like lesions in the vertebral area with unclear distinction, areas of pneumonic consolidation, and pleural effusion. Intravenous cephalosporin therapy was initiated for presumed pneumonia. ANA and anti-dsDNA tests were sent and returned negative. A PET-CT scan was planned. As the patient's cytopenias persisted despite ongoing transfusion needs, a bone marrow biopsy was performed. Bone marrow aspiration revealed increased cellularity and erythropoiesis without any abnormal findings. PET-CT demonstrated vertebral involvement attributed to extramedullary hematopoiesis; no malignant uptake was detected. Methylprednisolone was initiated at 1 mg/kg. Although platelet levels increased, anemia persisted. Repeated Coombs tests later returned strongly positive (+3) for both direct and indirect Coombs. Direct Coombs was positive for both IgG and C3. The patient had an elevated LDH (1200 U/L) and decreased haptoglobin levels. Due to steroid-refractory autoimmune hemolytic anemia, Rituximab 375 mg/week was administered for four doses, and the steroid dosage was tapered off. After two months, lab results showed WBC: 5,150/mm³, Hemoglobin: 9.2 g/dL, Platelets: 168,000/mm³. With a now negative direct Coombs test and a post-transfusion ferritin level of 2,322 ng/mL, chelation therapy was reinitiated. The patient, diagnosed with infection-related autoimmune hemolytic anemia, continues to receive monthly transfusions of cross-matched erythrocyte suspensions, Türkiye.</div><div>In this patient with thalassemia major who developed infection-associated auto","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106171"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796522","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.2025.106124
Naciye Nur Tozluklu, Birol Güvenç
<div><h3>Introduction</h3><div>Waldenström macroglobulinemia is a rare B-cell malignancy representing less than 2% of all hematologic malignancies, with an annual incidence of approximately 3-5 cases per million. The disease is characterized by lymphoplasmacytic lymphoma infiltrating bone marrow and lymphoid organs with concurrent IgM monoclonal protein secretion. Many patients are diagnosed asymptomatically through incidental laboratory findings, requiring careful evaluation to distinguish from other B-cell disorders and determine appropriate management strategies.</div></div><div><h3>Case Report</h3><div>A 54-year-old female was referred to hematology following discovery of a monoclonal spike on routine serum protein electrophoresis during routine health screening. The patient denied symptoms suggestive of hyperviscosity syndrome including headache, visual disturbances, epistaxis, or neurological complaints. She reported no B-symptoms (fever, night sweats, weight loss) and had no history of recurrent infections or bleeding tendencies.</div><div>Physical examination was unremarkable without palpable lymphadenopathy, hepatomegaly, or splenomegaly. The patient appeared well with stable vital signs and no evidence of hyperviscosity syndrome.</div><div>Laboratory evaluation revealed significant findings on protein studies. Serum protein electrophoresis showed increased gamma fraction (26.3%; normal: 10.7-20.3%) with relatively decreased albumin (47.9%; normal: 52-65%) and albumin/globulin ratio of 0.92. A sharp M-spike was evident in the gamma region. Immunofixation electrophoresis confirmed IgM-kappa monoclonal protein.</div><div>Quantitative immunoglobulins demonstrated markedly elevated IgM at 27.98 g/L with normal IgG (7.6 g/L) and IgA (2.4 g/L). Beta-2 microglobulin was normal (1.91 mg/L), indicating low tumor burden. Urine free light chain analysis showed normal kappa (3.78 mg/L) and lambda (0.73 mg/L) levels with elevated kappa/lambda ratio (5.18), consistent with kappa-predominant monoclonality.</div><div>Bone marrow examination revealed 40% cellularity with approximately 25% infiltration by small B-lymphocytes with plasmacytic differentiation organized in 4-5 intertrabecular lymphoid aggregates. Reticulin fibrosis was absent (grade 0/4), and amyloid staining was negative.</div><div>Immunohistochemistry demonstrated CD20+, CD38+, CD138+ cells with negative CD5, CD23, cyclin D1, LEF-1, and CD56, excluding chronic lymphocytic leukemia/small lymphocytic lymphoma and mantle cell lymphoma. Flow cytometry confirmed CD19+/CD20+/CD45+ clonal B-cell population with CD138+ plasmacytic subset showing intracytoplasmic kappa restriction and negative CD56, consistent with lymphoplasmacytic lymphoma rather than multiple myeloma.</div><div>Based on the constellation of findings including IgM-kappa monoclonal protein, characteristic bone marrow morphology and immunophenotype, the diagnosis of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia was estab
{"title":"Asymptomatic Waldenström Macroglobulinemia: A Case of Incidental Monoclonal Gammapathy Discovery","authors":"Naciye Nur Tozluklu, Birol Güvenç","doi":"10.1016/j.htct.2025.106124","DOIUrl":"10.1016/j.htct.2025.106124","url":null,"abstract":"<div><h3>Introduction</h3><div>Waldenström macroglobulinemia is a rare B-cell malignancy representing less than 2% of all hematologic malignancies, with an annual incidence of approximately 3-5 cases per million. The disease is characterized by lymphoplasmacytic lymphoma infiltrating bone marrow and lymphoid organs with concurrent IgM monoclonal protein secretion. Many patients are diagnosed asymptomatically through incidental laboratory findings, requiring careful evaluation to distinguish from other B-cell disorders and determine appropriate management strategies.</div></div><div><h3>Case Report</h3><div>A 54-year-old female was referred to hematology following discovery of a monoclonal spike on routine serum protein electrophoresis during routine health screening. The patient denied symptoms suggestive of hyperviscosity syndrome including headache, visual disturbances, epistaxis, or neurological complaints. She reported no B-symptoms (fever, night sweats, weight loss) and had no history of recurrent infections or bleeding tendencies.</div><div>Physical examination was unremarkable without palpable lymphadenopathy, hepatomegaly, or splenomegaly. The patient appeared well with stable vital signs and no evidence of hyperviscosity syndrome.</div><div>Laboratory evaluation revealed significant findings on protein studies. Serum protein electrophoresis showed increased gamma fraction (26.3%; normal: 10.7-20.3%) with relatively decreased albumin (47.9%; normal: 52-65%) and albumin/globulin ratio of 0.92. A sharp M-spike was evident in the gamma region. Immunofixation electrophoresis confirmed IgM-kappa monoclonal protein.</div><div>Quantitative immunoglobulins demonstrated markedly elevated IgM at 27.98 g/L with normal IgG (7.6 g/L) and IgA (2.4 g/L). Beta-2 microglobulin was normal (1.91 mg/L), indicating low tumor burden. Urine free light chain analysis showed normal kappa (3.78 mg/L) and lambda (0.73 mg/L) levels with elevated kappa/lambda ratio (5.18), consistent with kappa-predominant monoclonality.</div><div>Bone marrow examination revealed 40% cellularity with approximately 25% infiltration by small B-lymphocytes with plasmacytic differentiation organized in 4-5 intertrabecular lymphoid aggregates. Reticulin fibrosis was absent (grade 0/4), and amyloid staining was negative.</div><div>Immunohistochemistry demonstrated CD20+, CD38+, CD138+ cells with negative CD5, CD23, cyclin D1, LEF-1, and CD56, excluding chronic lymphocytic leukemia/small lymphocytic lymphoma and mantle cell lymphoma. Flow cytometry confirmed CD19+/CD20+/CD45+ clonal B-cell population with CD138+ plasmacytic subset showing intracytoplasmic kappa restriction and negative CD56, consistent with lymphoplasmacytic lymphoma rather than multiple myeloma.</div><div>Based on the constellation of findings including IgM-kappa monoclonal protein, characteristic bone marrow morphology and immunophenotype, the diagnosis of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia was estab","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106124"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796700","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.2025.106118
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.2025.106118","DOIUrl":"10.1016/j.htct.2025.106118","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 106118"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796704","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.2025.106120
Ali Turunç, Birol Güvenç
<div><h3>Introduction</h3><div>Castleman disease represents a rare, heterogeneous group of lymphoproliferative disorders, often categorized as unicentric or multicentric, with plasma-cell (PC), hyaline-vascular, or mixed histology. Idiopathic multicentric Castleman disease (iMCD) remains a diagnostic and therapeutic challenge, particularly in patients presenting with systemic inflammation and polyclonal plasmacytosis without overt clonal plasma cell disorder. We present the case of a patient with plasma-cell–predominant iMCD, successfully treated with IL-6 blockade, emphasizing the diagnostic pitfalls and the importance of early therapeutic intervention.</div></div><div><h3>Methods</h3><div>A male patient was admitted to the Department of Hematology, Çukurova University, with a 1-year history of progressive fatigue, weight loss, abdominal fullness, and generalized lymphadenopathy. Physical examination revealed widespread lymphadenopathy and splenomegaly. Laboratory tests demonstrated normocytic anemia, elevated CRP and ferritin, mildly increased IgG, and elevated β2-microglobulin. Excisional lymph node biopsy and splenectomy specimens were evaluated by histopathology and immunohistochemistry. Imaging studies included CT and PET-CT for staging., Türkiye</div></div><div><h3>Results</h3><div>Histopathology revealed follicular hyperplasia with regressed germinal centers and interfollicular plasmacytosis. Immunohistochemistry confirmed CD38+ and CD138+ plasma-cell infiltration, HHV-8 negativity, and a non-clonal kappa/lambda pattern. IgG4/IgG ratio was 22%. PET-CT demonstrated widespread FDG-avid lymphadenopathy (SUVmax 4–6) and splenomegaly, without extranodal organ involvement. Bone marrow evaluation was negative for clonal plasma cell infiltration. The case was classified as idiopathic multicentric Castleman disease, plasma-cell variant (iMCD-PC).</div><div>The patient was initiated on tocilizumab (anti-IL-6R) in combination with corticosteroids. Within 6 weeks, systemic symptoms and inflammatory markers improved significantly, with partial regression of lymphadenopathy on imaging. In the event of refractoriness, lenalidomide or sirolimus were considered as second-line options. Close follow-up with PET-CT and serum paraproteins was arranged to monitor potential clonal evolution into plasma cell neoplasia.</div></div><div><h3>Discussion</h3><div>This case illustrates the diagnostic complexity of iMCD-PC, which may mimic lymphoid malignancies and overlap with monoclonal gammopathies. The absence of monoclonality and CRAB criteria excluded multiple myeloma, while systemic inflammatory features and IL-6 axis dysregulation supported iMCD. Tocilizumab provided meaningful clinical and biochemical improvement. The case is valuable as an example of iMCD with strong plasmacytic component, highlighting the necessity of long-term surveillance due to the risk of clonal transformation.</div></div><div><h3>Conclusion</h3><div>Plasma-cell–predominant iMCD is a rar
{"title":"Plasma-Cell–Predominant Idiopathic Multicentric Castleman Disease: A Rare Diagnostic and Therapeutic Challenge","authors":"Ali Turunç, Birol Güvenç","doi":"10.1016/j.htct.2025.106120","DOIUrl":"10.1016/j.htct.2025.106120","url":null,"abstract":"<div><h3>Introduction</h3><div>Castleman disease represents a rare, heterogeneous group of lymphoproliferative disorders, often categorized as unicentric or multicentric, with plasma-cell (PC), hyaline-vascular, or mixed histology. Idiopathic multicentric Castleman disease (iMCD) remains a diagnostic and therapeutic challenge, particularly in patients presenting with systemic inflammation and polyclonal plasmacytosis without overt clonal plasma cell disorder. We present the case of a patient with plasma-cell–predominant iMCD, successfully treated with IL-6 blockade, emphasizing the diagnostic pitfalls and the importance of early therapeutic intervention.</div></div><div><h3>Methods</h3><div>A male patient was admitted to the Department of Hematology, Çukurova University, with a 1-year history of progressive fatigue, weight loss, abdominal fullness, and generalized lymphadenopathy. Physical examination revealed widespread lymphadenopathy and splenomegaly. Laboratory tests demonstrated normocytic anemia, elevated CRP and ferritin, mildly increased IgG, and elevated β2-microglobulin. Excisional lymph node biopsy and splenectomy specimens were evaluated by histopathology and immunohistochemistry. Imaging studies included CT and PET-CT for staging., Türkiye</div></div><div><h3>Results</h3><div>Histopathology revealed follicular hyperplasia with regressed germinal centers and interfollicular plasmacytosis. Immunohistochemistry confirmed CD38+ and CD138+ plasma-cell infiltration, HHV-8 negativity, and a non-clonal kappa/lambda pattern. IgG4/IgG ratio was 22%. PET-CT demonstrated widespread FDG-avid lymphadenopathy (SUVmax 4–6) and splenomegaly, without extranodal organ involvement. Bone marrow evaluation was negative for clonal plasma cell infiltration. The case was classified as idiopathic multicentric Castleman disease, plasma-cell variant (iMCD-PC).</div><div>The patient was initiated on tocilizumab (anti-IL-6R) in combination with corticosteroids. Within 6 weeks, systemic symptoms and inflammatory markers improved significantly, with partial regression of lymphadenopathy on imaging. In the event of refractoriness, lenalidomide or sirolimus were considered as second-line options. Close follow-up with PET-CT and serum paraproteins was arranged to monitor potential clonal evolution into plasma cell neoplasia.</div></div><div><h3>Discussion</h3><div>This case illustrates the diagnostic complexity of iMCD-PC, which may mimic lymphoid malignancies and overlap with monoclonal gammopathies. The absence of monoclonality and CRAB criteria excluded multiple myeloma, while systemic inflammatory features and IL-6 axis dysregulation supported iMCD. Tocilizumab provided meaningful clinical and biochemical improvement. The case is valuable as an example of iMCD with strong plasmacytic component, highlighting the necessity of long-term surveillance due to the risk of clonal transformation.</div></div><div><h3>Conclusion</h3><div>Plasma-cell–predominant iMCD is a rar","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106120"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796705","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.2025.106174
Birol Güvenç
<div><h3>Introduction</h3><div>Light-chain multiple myeloma (LCMM) accounts for a subset of myeloma cases characterized by the absence of an M-protein spike on serum protein electrophoresis. This diagnostic challenge often delays recognition and treatment. We present the case of a 75-year-old woman with kappa-dominant LCMM, where conventional marrow and serum studies were inconclusive, yet clinical and imaging findings confirmed active disease.</div></div><div><h3>Methods</h3><div>A comprehensive diagnostic evaluation was performed, including hematology and biochemistry profiles, serum protein electrophoresis, serum and urine immunofixation, serum free light chain (sFLC) quantification, bone marrow aspiration and biopsy with immunohistochemistry, and 18F-FDG PET-CT imaging.</div></div><div><h3>Results</h3><div>Gülüşen Kellesibüyük, a 75-year-old female, presented with fatigue, anemia, and back pain. Laboratory evaluation revealed hemoglobin of 9.7 g/dL, elevated inflammatory markers, and preserved renal and calcium levels. Serum protein electrophoresis demonstrated no monoclonal spike. Immunofixation of urine identified monoclonal kappa light chains. sFLC testing showed markedly increased kappa levels (121–270 mg/L) with a pathological κ/λ ratio between 3.9 and 4.2. Bone marrow aspirates revealed only 2–3% plasma cells with polytypic staining, and biopsies were normocellular without evidence of clonal infiltration. Despite these inconclusive marrow results, PET-CT demonstrated a metabolically active lytic lesion in the L4 vertebra (SUVmax 11.4) and multiple punctate cranial lytic lesions. The combination of anemia, abnormal light chain ratio, and PET-CT–confirmed bone lesions established the diagnosis of active LCMM.</div></div><div><h3>Discussion</h3><div>This case emphasizes the diagnostic complexity of LCMM, where reliance solely on serum electrophoresis or marrow histology may be misleading. The absence of an M spike, coupled with non-diagnostic marrow sampling, initially obscured the diagnosis. However, integration of sFLC analysis, urine immunofixation, and advanced imaging confirmed the presence of active myeloma. Elderly, transplant-ineligible patients such as this one benefit from modern therapeutic approaches that combine efficacy with tolerability. Triplet regimens including daratumumab with lenalidomide and dexamethasone or reduced-intensity bortezomib-based protocols are recommended as first-line options. For patients with limited access to hospital care, oral regimens may be considered, though efficacy is comparatively lower, Türkiye.</div></div><div><h3>Conclusion</h3><div>The case of demonstrates that light-chain multiple myeloma can be present despite normal serum electrophoresis and non-clonal marrow findings. Comprehensive evaluation with free light chain assays, urine studies, and PET-CT is essential to avoid underdiagnosis. This case highlights the importance of applying full diagnostic criteria to detect atypical myeloma pre
轻链多发性骨髓瘤（LCMM）是骨髓瘤病例的一个子集，其特征是血清蛋白电泳中没有m蛋白尖峰。这一诊断难题往往会延误识别和治疗。我们报告一例75岁女性kappa显性LCMM，常规骨髓和血清研究尚无定论，但临床和影像学结果证实为活动性疾病。方法采用血液学和生化、血清蛋白电泳、血清和尿液免疫固定、血清游离轻链（sFLC）定量、骨髓穿刺和活检免疫组化、18F-FDG PET-CT成像等方法进行综合诊断。结果g ll en kellesib y k， 75岁，女性，表现为疲劳、贫血和背部疼痛。实验室评估显示血红蛋白为9.7 g/dL，炎症标志物升高，肾脏和钙水平保持不变。血清蛋白电泳未见单克隆峰。尿免疫固定鉴定单克隆kappa轻链。sFLC检测显示kappa水平明显升高（121 ~ 270 mg/L），病理κ/λ比值在3.9 ~ 4.2之间。骨髓抽吸显示只有2-3%的浆细胞呈多型染色，活检为正常细胞，无克隆浸润的证据。尽管这些不确定的骨髓结果，PET-CT显示在L4椎体（SUVmax 11.4）有代谢活跃的溶解性病变和多个点状颅骨溶解性病变。结合贫血、异常轻链比和pet - ct证实的骨病变，确定活动性LCMM的诊断。本病例强调LCMM诊断的复杂性，单纯依靠血清电泳或骨髓组织学可能会产生误导。没有M尖峰，再加上非诊断性骨髓取样，最初使诊断模糊不清。然而，综合sFLC分析、尿液免疫固定和晚期影像学证实了活动性骨髓瘤的存在。像这样的老年人，不适合移植的患者受益于结合疗效和耐受性的现代治疗方法。建议将达拉单抗联合来那度胺和地塞米松或以硼替佐米为基础的低强度方案作为一线方案。对于获得医院护理机会有限的患者，可以考虑口服治疗方案，尽管疗效相对较低。结论该病例表明，尽管血清电泳和非克隆骨髓检查正常，轻链多发性骨髓瘤仍可存在。利用游离轻链试验、尿液研究和PET-CT进行综合评估对于避免漏诊是必不可少的。这个病例强调了应用完整的诊断标准及早发现非典型骨髓瘤的重要性，确保及时开始治疗并改善患者的预后。
{"title":"“Kappa Light-Chain Multiple Myeloma Without Serum M-Spike: A Diagnostic and Therapeutic Challenge in an Elderly Patient”","authors":"Birol Güvenç","doi":"10.1016/j.htct.2025.106174","DOIUrl":"10.1016/j.htct.2025.106174","url":null,"abstract":"<div><h3>Introduction</h3><div>Light-chain multiple myeloma (LCMM) accounts for a subset of myeloma cases characterized by the absence of an M-protein spike on serum protein electrophoresis. This diagnostic challenge often delays recognition and treatment. We present the case of a 75-year-old woman with kappa-dominant LCMM, where conventional marrow and serum studies were inconclusive, yet clinical and imaging findings confirmed active disease.</div></div><div><h3>Methods</h3><div>A comprehensive diagnostic evaluation was performed, including hematology and biochemistry profiles, serum protein electrophoresis, serum and urine immunofixation, serum free light chain (sFLC) quantification, bone marrow aspiration and biopsy with immunohistochemistry, and 18F-FDG PET-CT imaging.</div></div><div><h3>Results</h3><div>Gülüşen Kellesibüyük, a 75-year-old female, presented with fatigue, anemia, and back pain. Laboratory evaluation revealed hemoglobin of 9.7 g/dL, elevated inflammatory markers, and preserved renal and calcium levels. Serum protein electrophoresis demonstrated no monoclonal spike. Immunofixation of urine identified monoclonal kappa light chains. sFLC testing showed markedly increased kappa levels (121–270 mg/L) with a pathological κ/λ ratio between 3.9 and 4.2. Bone marrow aspirates revealed only 2–3% plasma cells with polytypic staining, and biopsies were normocellular without evidence of clonal infiltration. Despite these inconclusive marrow results, PET-CT demonstrated a metabolically active lytic lesion in the L4 vertebra (SUVmax 11.4) and multiple punctate cranial lytic lesions. The combination of anemia, abnormal light chain ratio, and PET-CT–confirmed bone lesions established the diagnosis of active LCMM.</div></div><div><h3>Discussion</h3><div>This case emphasizes the diagnostic complexity of LCMM, where reliance solely on serum electrophoresis or marrow histology may be misleading. The absence of an M spike, coupled with non-diagnostic marrow sampling, initially obscured the diagnosis. However, integration of sFLC analysis, urine immunofixation, and advanced imaging confirmed the presence of active myeloma. Elderly, transplant-ineligible patients such as this one benefit from modern therapeutic approaches that combine efficacy with tolerability. Triplet regimens including daratumumab with lenalidomide and dexamethasone or reduced-intensity bortezomib-based protocols are recommended as first-line options. For patients with limited access to hospital care, oral regimens may be considered, though efficacy is comparatively lower, Türkiye.</div></div><div><h3>Conclusion</h3><div>The case of demonstrates that light-chain multiple myeloma can be present despite normal serum electrophoresis and non-clonal marrow findings. Comprehensive evaluation with free light chain assays, urine studies, and PET-CT is essential to avoid underdiagnosis. This case highlights the importance of applying full diagnostic criteria to detect atypical myeloma pre","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106174"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796828","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.2025.106206
Demet Çekdemir
<div><div>Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is a high-risk subtype of ALL, historically associated with poor outcomes. The introduction of tyrosine kinase inhibitors (TKIs) has dramatically changed its therapeutic landscape. Current optimization strategies focus on integrating TKIs with chemotherapy, immunotherapy, and, in selected cases, allogeneic stem cell transplantation (allo-HSCT), while tailoring treatment according to minimal residual disease (MRD) status and patient characteristics.</div><div>Induction therapy now commonly consists of a TKI combined with corticosteroids and/or reduced-intensity chemotherapy, aiming to achieve remission with lower toxicity compared to traditional intensive regimens. Commonly used TKIs include imatinib, dasatinib, and ponatinib, with the latter being preferred in cases with the T315I mutation due to its broader activity.</div><div>Consolidation therapy is designed to eradicate residual disease. Achieving MRD negativity is the primary goal, as it strongly predicts long-term survival. Strategies include continued TKI administration combined with short chemotherapy blocks or novel agents such as blinatumomab, a CD19-targeted bispecific T-cell engager. Allo-HSCT remains an important option for younger, fit patients, especially those with persistent MRD or high relapse risk. However, accumulating evidence suggests that deep and durable remissions may be achievable without transplantation when combining TKIs with immunotherapies.</div><div>Maintenance therapy typically involves prolonged TKI treatment, often for at least two to three years, with ongoing MRD monitoring to guide adjustments.</div><div>In the relapsed or refractory setting, therapeutic options expand to include next-generation TKIs such as ponatinib, immunotherapies including blinatumomab and the CD22-targeted antibody-drug conjugate inotuzumab ozogamicin, and chimeric antigen receptor T-cell (CAR-T) therapies targeting CD19, which have shown promising results in heavily pretreated patients.</div><div>The core principles of treatment optimization in Ph+ ALL include:</div><div>1. MRD-directed decision-making, as MRD negativity is the strongest predictor of favorable outcomes.</div><div>2. Reducing treatment-related toxicity, particularly in elderly or frail patients, by minimizing intensive chemotherapy and incorporating TKIs with immunotherapy.</div><div>3. Individualizing the role of allo-HSCT, reserving it primarily for patients with persistent MRD, high-risk features, or early relapse.</div><div>4. Integrating novel agents such as blinatumomab, inotuzumab, and CAR-T therapies earlier in the treatment course to improve long-term survival and potentially reduce the need for transplantation.</div><div>In summary, modern management of Ph+ ALL emphasizes TKI-based regimens, MRD-guided therapeutic decisions, and the incorporation of targeted immunotherapies. While allo-HSCT remains relevant for selected patients,
{"title":"SUMMARY: OPTIMIZATION OF TREATMENT IN PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA (PH+ ALL)","authors":"Demet Çekdemir","doi":"10.1016/j.htct.2025.106206","DOIUrl":"10.1016/j.htct.2025.106206","url":null,"abstract":"<div><div>Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is a high-risk subtype of ALL, historically associated with poor outcomes. The introduction of tyrosine kinase inhibitors (TKIs) has dramatically changed its therapeutic landscape. Current optimization strategies focus on integrating TKIs with chemotherapy, immunotherapy, and, in selected cases, allogeneic stem cell transplantation (allo-HSCT), while tailoring treatment according to minimal residual disease (MRD) status and patient characteristics.</div><div>Induction therapy now commonly consists of a TKI combined with corticosteroids and/or reduced-intensity chemotherapy, aiming to achieve remission with lower toxicity compared to traditional intensive regimens. Commonly used TKIs include imatinib, dasatinib, and ponatinib, with the latter being preferred in cases with the T315I mutation due to its broader activity.</div><div>Consolidation therapy is designed to eradicate residual disease. Achieving MRD negativity is the primary goal, as it strongly predicts long-term survival. Strategies include continued TKI administration combined with short chemotherapy blocks or novel agents such as blinatumomab, a CD19-targeted bispecific T-cell engager. Allo-HSCT remains an important option for younger, fit patients, especially those with persistent MRD or high relapse risk. However, accumulating evidence suggests that deep and durable remissions may be achievable without transplantation when combining TKIs with immunotherapies.</div><div>Maintenance therapy typically involves prolonged TKI treatment, often for at least two to three years, with ongoing MRD monitoring to guide adjustments.</div><div>In the relapsed or refractory setting, therapeutic options expand to include next-generation TKIs such as ponatinib, immunotherapies including blinatumomab and the CD22-targeted antibody-drug conjugate inotuzumab ozogamicin, and chimeric antigen receptor T-cell (CAR-T) therapies targeting CD19, which have shown promising results in heavily pretreated patients.</div><div>The core principles of treatment optimization in Ph+ ALL include:</div><div>1. MRD-directed decision-making, as MRD negativity is the strongest predictor of favorable outcomes.</div><div>2. Reducing treatment-related toxicity, particularly in elderly or frail patients, by minimizing intensive chemotherapy and incorporating TKIs with immunotherapy.</div><div>3. Individualizing the role of allo-HSCT, reserving it primarily for patients with persistent MRD, high-risk features, or early relapse.</div><div>4. Integrating novel agents such as blinatumomab, inotuzumab, and CAR-T therapies earlier in the treatment course to improve long-term survival and potentially reduce the need for transplantation.</div><div>In summary, modern management of Ph+ ALL emphasizes TKI-based regimens, MRD-guided therapeutic decisions, and the incorporation of targeted immunotherapies. While allo-HSCT remains relevant for selected patients, ","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106206"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796837","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.2025.106207
Mehmet Gündüz
<div><div><strong>CRS (Cytokine Release Syndrome)</strong> CRS is an exaggerated systemic inflammatory response triggered by treatments such as Bispecific Antibodies (BsAb), which activate T cells and cause the release of inflammatory cytokines.</div><div>CRS symptoms range from mild flu-like symptoms to severe multiorgan failure.</div><div>Symptoms: Fever, hypotension, hypoxia, tachycardia, organ dysfunction.</div><div>Physical Examination - Temperature, blood pressure, pulse oximetry or arterial blood gas (or mixed venous blood gas/O2 saturation), skin, heart, and lung examination</div><div>Laboratory Tests - Complete blood count with differential diagnosis; Coagulation (PT/PTT, fibrinogen, fibrin D-dimer); Chemistry (serum electrolytes, kidney and liver function, uric acid, lactate, LDH; C-reactive protein and ferritin (inflammation); Microbiological tests, especially in neutropenic patients (blood and urine cultures); cardiac markers are clinically indicated. Do not await laboratory results.</div><div>Laboratory findings<strong>:</strong> Cytopenias, elevated creatinine, elevated liver enzymes, irregular coagulation parameters, elevated C-Reactive Protein</div><div>• Management of CRS (see Management Section below) does not require laboratory testing and should not be delayed pending laboratory results.</div><div><strong>Management by grade:</strong></div><div>• Grade 1: Support only (antipyretic, fluid support, close monitoring).</div><div>• Grade 2: Low-dose oxygen, IV fluids, low-dose vasopressors if necessary. Tocilizumab may be initiated.</div><div>• Grade ≥3: High-dose oxygen, intensive care support, vasopressor requirement.</div><div><strong>Medical Treatment:</strong></div><div>• First choice: Tocilizumab (anti-IL-6 monoclonal antibody)</div><div>• If no response: Corticosteroids (e.g., dexamethasone, methylprednisolone) are added.</div><div>• Other support: Antibiotic prophylaxis/treatment, electrolyte balance, close monitoring of organ functions.</div><div><strong>Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS):</strong></div><div>Neurological toxicity caused by the inflammatory effects of cytokines released after BsAb treatment results in disruption of the blood-brain barrier and accumulation of inflammatory cytokines in the central nervous system.</div><div>ICANS is a diagnosis of exclusion after other possibilities have been excluded. Neurological toxicity develops after immune activation.</div><div>Flu-like symptoms: Fever (≥38.0°C/<100.4°F) (unattributable to another cause); nausea; fatigue; headache; rash; diarrhea, arthralgia, myalgia</div><div>Hypotension</div><div>Systemic inflammatory response syndrome (circulatory collapse; vascular leakage; peripheral and/or pulmonary edema; renal failure; cardiac dysfunction; multiorgan failure)</div><div>Respiratory symptoms: cough; tachypnea; hypoxia, ARDS</div><div>Rash and Urticaria (allergic reaction)</div><div>Low-grade CRS is common and high-grade is rare</div><
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Pub Date : 2025-12-01DOI: 10.1016/j.htct.2025.106162
Birol Güvenç
<div><h3>Case Report</h3><div>A 53-year-old male from Samandağ presented in early 2024 with progressive anemia, fatigue, and splenomegaly. Laboratory evaluation revealed pancytopenia with atypical lymphoid cells on peripheral smear and mildly elevated LDH. Physical examination confirmed palpable splenomegaly without lymphadenopathy.</div><div>Bone marrow biopsy performed on August 5, 2024, demonstrated classic hairy cell leukemia with characteristic immunophenotype: CD20+, CD103+, CD25+, Annexin A1+, TRAP+ with negative CD3, CD5, CD23, and CD34. Flow cytometry confirmed 8-10% clonal B-cell population with CD103+, CD25+, CD11c+ expression and aberrant kappa/lambda ratio, establishing HCL diagnosis.</div><div>Treatment was initiated with rituximab plus cladribine combination therapy along with G-CSF support and prophylactic antifungal therapy. Post-treatment evaluation on September 17, 2024, demonstrated exceptional response with complete disappearance of all HCL-specific phenotypic markers (0% residual disease) and minimal CD20+ cells (1.8%) reflecting rituximab effect. Bone marrow biopsy confirmed morphologic remission. Imaging showed dramatic spleen size reduction from 22 cm to 14 cm with regression of retroperitoneal lymphadenopathy.</div><div>Eight months later, in April-May 2025, the patient developed B-symptoms including persistent fever, weight loss, and dyspnea. HRCT and PET-CT revealed concerning new findings: left lower lobe pulmonary lesion with intense metabolic activity (SUVmax: 34.07), mediastinal involvement (SUVmax: 16.13), and new abdominal lymphadenopathy (SUVmax: 7-10).</div><div>Lung biopsy performed on June 16, 2025, revealed diffuse large B-cell lymphoma with non-germinal center phenotype: CD20+, PAX5+, Bcl-6+, MUM1+ with extensive Bcl-2 expression (95%) and low c-Myc expression (10%), confirming systemic DLBCL diagnosis.</div><div>Standard R-CHOP chemotherapy (six cycles) was administered from July through November 2025. The patient tolerated treatment well with only mild neutropenia as significant toxicity. Post-treatment PET-CT demonstrated complete metabolic remission with disappearance of all metabolically active lesions, achieving Deauville score ≤2.</div><div>At current follow-up, the patient remains in complete remission from both malignancies with excellent performance status and no evidence of disease recurrence.</div></div><div><h3>Discussion</h3><div>This case represents a rare scenario of sequential B-cell malignancies with successful treatment outcomes for both conditions. The eight-month interval between HCL remission and DLBCL development, combined with distinct immunophenotypes, suggests either treatment-related secondary malignancy or activation of a dormant malignant clone rather than clonal evolution.</div><div>The non-germinal center DLBCL phenotype with high Bcl-2 expression indicates aggressive biology requiring prompt intervention. The excellent response to standard R-CHOP therapy demonstrates that DLB
{"title":"SEQUENTIAL DEVELOPMENT OF DIFFUSE LARGE B-CELL LYMPHOMA FOLLOWING SUCCESSFUL HAIRY CELL LEUKEMIA TREATMENT: A CASE REPORT WITH COMPLETE REMISSION","authors":"Birol Güvenç","doi":"10.1016/j.htct.2025.106162","DOIUrl":"10.1016/j.htct.2025.106162","url":null,"abstract":"<div><h3>Case Report</h3><div>A 53-year-old male from Samandağ presented in early 2024 with progressive anemia, fatigue, and splenomegaly. Laboratory evaluation revealed pancytopenia with atypical lymphoid cells on peripheral smear and mildly elevated LDH. Physical examination confirmed palpable splenomegaly without lymphadenopathy.</div><div>Bone marrow biopsy performed on August 5, 2024, demonstrated classic hairy cell leukemia with characteristic immunophenotype: CD20+, CD103+, CD25+, Annexin A1+, TRAP+ with negative CD3, CD5, CD23, and CD34. Flow cytometry confirmed 8-10% clonal B-cell population with CD103+, CD25+, CD11c+ expression and aberrant kappa/lambda ratio, establishing HCL diagnosis.</div><div>Treatment was initiated with rituximab plus cladribine combination therapy along with G-CSF support and prophylactic antifungal therapy. Post-treatment evaluation on September 17, 2024, demonstrated exceptional response with complete disappearance of all HCL-specific phenotypic markers (0% residual disease) and minimal CD20+ cells (1.8%) reflecting rituximab effect. Bone marrow biopsy confirmed morphologic remission. Imaging showed dramatic spleen size reduction from 22 cm to 14 cm with regression of retroperitoneal lymphadenopathy.</div><div>Eight months later, in April-May 2025, the patient developed B-symptoms including persistent fever, weight loss, and dyspnea. HRCT and PET-CT revealed concerning new findings: left lower lobe pulmonary lesion with intense metabolic activity (SUVmax: 34.07), mediastinal involvement (SUVmax: 16.13), and new abdominal lymphadenopathy (SUVmax: 7-10).</div><div>Lung biopsy performed on June 16, 2025, revealed diffuse large B-cell lymphoma with non-germinal center phenotype: CD20+, PAX5+, Bcl-6+, MUM1+ with extensive Bcl-2 expression (95%) and low c-Myc expression (10%), confirming systemic DLBCL diagnosis.</div><div>Standard R-CHOP chemotherapy (six cycles) was administered from July through November 2025. The patient tolerated treatment well with only mild neutropenia as significant toxicity. Post-treatment PET-CT demonstrated complete metabolic remission with disappearance of all metabolically active lesions, achieving Deauville score ≤2.</div><div>At current follow-up, the patient remains in complete remission from both malignancies with excellent performance status and no evidence of disease recurrence.</div></div><div><h3>Discussion</h3><div>This case represents a rare scenario of sequential B-cell malignancies with successful treatment outcomes for both conditions. The eight-month interval between HCL remission and DLBCL development, combined with distinct immunophenotypes, suggests either treatment-related secondary malignancy or activation of a dormant malignant clone rather than clonal evolution.</div><div>The non-germinal center DLBCL phenotype with high Bcl-2 expression indicates aggressive biology requiring prompt intervention. The excellent response to standard R-CHOP therapy demonstrates that DLB","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106162"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796759","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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