Pub Date : 2025-12-01DOI: 10.1016/j.htct.2025.106169
Ali Turunç, Birol Güvenç
Introduction
Multiple myeloma (MM) is a malignant plasma cell disorder that typically occurs sporadically. Familial clustering is rare, with only a limited number of cases reported worldwide. Such familial presentations suggest a possible hereditary predisposition or shared environmental risk factors contributing to disease development [1,2]. Here, we present two siblings with distinct plasma cell neoplasms: one with recurrent extramedullary plasmacytoma and the other with multiple myeloma.
Case Presentation
The first case was a 69-year-old woman who underwent surgery in 2017 for a proximal femoral mass, diagnosed as plasmacytoma. In 2024, she presented with a cervical swelling; excisional biopsy of a right level-5 lymph node again revealed plasmacytoma. Bone marrow biopsies performed at that time did not show features of multiple myeloma.
Her brother, one year older, was diagnosed with multiple myeloma in June 2025. PET-CT revealed lytic lesions in the axial skeleton, and systemic therapy was initiated.
Discussion
Familial occurrence of plasma cell neoplasms is exceedingly uncommon. Reported cases often involve either multiple relatives with MM or, less frequently, different manifestations of plasma cell disorders within the same family [3,4]. The present siblings illustrate divergent clinical phenotypes: persistent extramedullary plasmacytoma without myeloma progression in the sister, versus classical MM with lytic bone disease in the brother. This highlights the potential role of shared genetic background with variable penetrance and expression.
Genetic susceptibility loci, immune dysregulation, and epigenetic mechanisms have all been proposed as contributors to familial myeloma [5]. Recognizing such familial patterns may have implications for surveillance strategies in high-risk relatives.
Conclusion
We report a rare familial clustering of plasma cell neoplasms in siblings, underlining the importance of considering hereditary predisposition in plasma cell disorders. Further genetic and epidemiological studies are warranted to elucidate the underlying mechanisms.
{"title":"FAMILIAL MULTIPLE MYELOMA: SIBLING CASES WITH DISTINCT CLINICAL MANIFESTATIONS","authors":"Ali Turunç, Birol Güvenç","doi":"10.1016/j.htct.2025.106169","DOIUrl":"10.1016/j.htct.2025.106169","url":null,"abstract":"<div><h3>Introduction</h3><div>Multiple myeloma (MM) is a malignant plasma cell disorder that typically occurs sporadically. Familial clustering is rare, with only a limited number of cases reported worldwide. Such familial presentations suggest a possible hereditary predisposition or shared environmental risk factors contributing to disease development [1,2]. Here, we present two siblings with distinct plasma cell neoplasms: one with recurrent extramedullary plasmacytoma and the other with multiple myeloma.</div></div><div><h3>Case Presentation</h3><div>The first case was a 69-year-old woman who underwent surgery in 2017 for a proximal femoral mass, diagnosed as plasmacytoma. In 2024, she presented with a cervical swelling; excisional biopsy of a right level-5 lymph node again revealed plasmacytoma. Bone marrow biopsies performed at that time did not show features of multiple myeloma.</div><div>Her brother, one year older, was diagnosed with multiple myeloma in June 2025. PET-CT revealed lytic lesions in the axial skeleton, and systemic therapy was initiated.</div></div><div><h3>Discussion</h3><div>Familial occurrence of plasma cell neoplasms is exceedingly uncommon. Reported cases often involve either multiple relatives with MM or, less frequently, different manifestations of plasma cell disorders within the same family [3,4]. The present siblings illustrate divergent clinical phenotypes: persistent extramedullary plasmacytoma without myeloma progression in the sister, versus classical MM with lytic bone disease in the brother. This highlights the potential role of shared genetic background with variable penetrance and expression.</div><div>Genetic susceptibility loci, immune dysregulation, and epigenetic mechanisms have all been proposed as contributors to familial myeloma [5]. Recognizing such familial patterns may have implications for surveillance strategies in high-risk relatives.</div></div><div><h3>Conclusion</h3><div>We report a rare familial clustering of plasma cell neoplasms in siblings, underlining the importance of considering hereditary predisposition in plasma cell disorders. Further genetic and epidemiological studies are warranted to elucidate the underlying mechanisms.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106169"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796517","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.2025.106151
Birol Güvenç
<div><div>Case 1: A 25-year-old female (born 1993) presented in 2018 with fatigue, anemia, and pancytopenia. Bone marrow biopsy revealed high blast count with flow cytometry showing CD33 (94%), CD117 (73%), MPO (98%) positivity, and limited CD34 (3-4%) expression. Cytogenetic analysis was negative for t(8;21), inv(16), t(15;17), and BCR-ABL, classifying the case as cytogenetically normal intermediate-risk AML.</div><div>Brain MRI revealed meningeal involvement at diagnosis. The patient received standard 7+3 induction (cytarabine + idarubicin) achieving complete hematologic remission. Due to absence of suitable donor, autologous stem cell transplantation was performed. Despite achieving complete remission and remaining asymptomatic, prophylactic intrathecal methotrexate and cytarabine was initiated every 6 months for CNS protection.</div><div>Serial CSF examinations from 2019-2024 showed no blast cells. Bone marrow biopsies consistently demonstrated hypocellular marrow without blasts, with negative CD34 and CD117. The patient has maintained complete remission for 7 years without neurological symptoms or complications.</div><div>Case 2: A 46-year-old male (born 1973) presented in 2019 with anemia, thrombocytopenia, and fatigue. Bone marrow analysis confirmed AML with flow cytometry showing CD33 (99%), MPO (98%), high HLA-DR expression, but negative CD34 and CD117, consistent with aggressive AML phenotype.</div><div>CSF examination at diagnosis confirmed CNS involvement. After achieving complete remission with standard 7+3 induction (cytarabine + daunorubicin), the patient underwent allogeneic stem cell transplantation. Similar to Case 1, prophylactic intrathecal methotrexate and cytarabine was administered every 6 months despite clinical remission.</div><div>Follow-up from 2020-2023 showed consistently negative CSF examinations and stable bone marrow remission with <5% blasts. The patient has maintained complete remission for 6 years without transplant complications or neurological sequelae.</div><div>Discussion: These cases demonstrate several important clinical principles in managing AML with CNS involvement. First, both patients achieved sustained remission despite CNS involvement at diagnosis, traditionally associated with poor prognosis. The combination of intensive systemic therapy, stem cell transplantation, and prolonged prophylactic intrathecal therapy appears crucial for success.</div><div>The extended prophylactic intrathecal therapy regimen (6-7 years) far exceeds standard recommendations but proved remarkably safe and effective. The 6-monthly interval appears optimal, providing adequate CNS protection while minimizing procedure-related risks and patient burden compared to more frequent administration.</div><div>The contrasting transplant approaches (autologous vs. allogeneic) achieved similar outcomes, suggesting that the prophylactic intrathecal strategy may be more important than transplant type for CNS disease control. Both patie
{"title":"Long-term Success of Prophylactic Intrathecal Therapy in AML Patients with CNS Involvement: Two Cases with Extended Remission Following Stem Cell Transplantation","authors":"Birol Güvenç","doi":"10.1016/j.htct.2025.106151","DOIUrl":"10.1016/j.htct.2025.106151","url":null,"abstract":"<div><div>Case 1: A 25-year-old female (born 1993) presented in 2018 with fatigue, anemia, and pancytopenia. Bone marrow biopsy revealed high blast count with flow cytometry showing CD33 (94%), CD117 (73%), MPO (98%) positivity, and limited CD34 (3-4%) expression. Cytogenetic analysis was negative for t(8;21), inv(16), t(15;17), and BCR-ABL, classifying the case as cytogenetically normal intermediate-risk AML.</div><div>Brain MRI revealed meningeal involvement at diagnosis. The patient received standard 7+3 induction (cytarabine + idarubicin) achieving complete hematologic remission. Due to absence of suitable donor, autologous stem cell transplantation was performed. Despite achieving complete remission and remaining asymptomatic, prophylactic intrathecal methotrexate and cytarabine was initiated every 6 months for CNS protection.</div><div>Serial CSF examinations from 2019-2024 showed no blast cells. Bone marrow biopsies consistently demonstrated hypocellular marrow without blasts, with negative CD34 and CD117. The patient has maintained complete remission for 7 years without neurological symptoms or complications.</div><div>Case 2: A 46-year-old male (born 1973) presented in 2019 with anemia, thrombocytopenia, and fatigue. Bone marrow analysis confirmed AML with flow cytometry showing CD33 (99%), MPO (98%), high HLA-DR expression, but negative CD34 and CD117, consistent with aggressive AML phenotype.</div><div>CSF examination at diagnosis confirmed CNS involvement. After achieving complete remission with standard 7+3 induction (cytarabine + daunorubicin), the patient underwent allogeneic stem cell transplantation. Similar to Case 1, prophylactic intrathecal methotrexate and cytarabine was administered every 6 months despite clinical remission.</div><div>Follow-up from 2020-2023 showed consistently negative CSF examinations and stable bone marrow remission with <5% blasts. The patient has maintained complete remission for 6 years without transplant complications or neurological sequelae.</div><div>Discussion: These cases demonstrate several important clinical principles in managing AML with CNS involvement. First, both patients achieved sustained remission despite CNS involvement at diagnosis, traditionally associated with poor prognosis. The combination of intensive systemic therapy, stem cell transplantation, and prolonged prophylactic intrathecal therapy appears crucial for success.</div><div>The extended prophylactic intrathecal therapy regimen (6-7 years) far exceeds standard recommendations but proved remarkably safe and effective. The 6-monthly interval appears optimal, providing adequate CNS protection while minimizing procedure-related risks and patient burden compared to more frequent administration.</div><div>The contrasting transplant approaches (autologous vs. allogeneic) achieved similar outcomes, suggesting that the prophylactic intrathecal strategy may be more important than transplant type for CNS disease control. Both patie","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106151"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796519","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.2025.106163
Elif Vuslat Yımaz, Hüseyin Koçak, Birol Güvenç
<div><div>Case Report: A 53-year-old female presented with a 2-month history of progressive, painless left axillary mass without B-symptoms (fever, night sweats, weight loss). Medical history was unremarkable without chronic diseases, previous malignancy, or family history of cancer.</div><div>Physical examination revealed good general condition with stable vital signs. A 3-cm, rubbery, mobile lymph node was palpated in the left axilla without other palpable lymphadenopathy. Abdominal examination demonstrated mild hepatomegaly (2 cm below costal margin) without splenomegaly.</div><div>Laboratory evaluation showed normal complete blood count (Hb: 12.5 g/dL, WBC: 6.3 × 10⁹/L, PLT: 220 × 10⁹/L) with mildly elevated LDH (270 U/L). Renal and hepatic function tests were normal, and viral serologies were negative.</div><div>PET-CT imaging revealed significant findings: left axillary lymphadenopathy (30 × 22 mm) with SUVmax 9.12, mediastinal involvement in para-aortic and aortopulmonary regions (SUVmax: 5.89), bilateral apical pulmonary nodules (7.5 mm) with low FDG uptake, and a hypodense hepatic lesion (15 × 12 mm) with mild FDG uptake. No splenic involvement or bone metastases were detected.</div><div>Excisional biopsy of the left axillary lymph node confirmed follicular lymphoma, grade 1-2 according to WHO 2016 criteria. Immunohistochemistry demonstrated CD20(+), CD23(+), with negative CD5 and cyclin D1, consistent with follicular lymphoma. Critically, Ki-67 proliferation index was only 10%, indicating low proliferative activity.</div><div>Bone marrow examination showed normal hematopoiesis with reticulin grade 0/4, negative amyloid staining, and no evidence of lymphomatous infiltration.</div><div>Based on Lugano criteria, the patient was staged as advanced disease (stage IIIA-IIIB) due to mediastinal involvement and hepatomegaly.</div><div>Discussion: This case presents a striking clinico-radiologic discordance between low-grade histological features and high metabolic activity. The SUVmax of 9.12 is unusually high for grade 1-2 follicular lymphoma, typically associated with more aggressive histologies or transformed lymphomas.</div><div>Several mechanisms may explain this phenomenon. First, inflammatory microenvironment within lymph nodes can increase FDG uptake independent of tumor grade. Second, early transformation to diffuse large B-cell lymphoma may be focal and missed on single biopsy sampling. Third, some low-grade lymphomas may exhibit metabolically active behavior without histological transformation.</div><div>The management approach requires careful consideration. While current guidelines recommend "watch and wait" for asymptomatic, low tumor burden indolent FL, the high metabolic activity and advanced stage disease create uncertainty. Options include close surveillance with repeat biopsy if progression occurs, rituximab monotherapy, or combination therapy with R-CHOP or R-bendamustine for bulky/symptomatic disease.</div><div>The hepatome
{"title":"High FDG Uptake in Low-Grade Follicular Lymphoma: A Clinico-Radiologic Discordance Case","authors":"Elif Vuslat Yımaz, Hüseyin Koçak, Birol Güvenç","doi":"10.1016/j.htct.2025.106163","DOIUrl":"10.1016/j.htct.2025.106163","url":null,"abstract":"<div><div>Case Report: A 53-year-old female presented with a 2-month history of progressive, painless left axillary mass without B-symptoms (fever, night sweats, weight loss). Medical history was unremarkable without chronic diseases, previous malignancy, or family history of cancer.</div><div>Physical examination revealed good general condition with stable vital signs. A 3-cm, rubbery, mobile lymph node was palpated in the left axilla without other palpable lymphadenopathy. Abdominal examination demonstrated mild hepatomegaly (2 cm below costal margin) without splenomegaly.</div><div>Laboratory evaluation showed normal complete blood count (Hb: 12.5 g/dL, WBC: 6.3 × 10⁹/L, PLT: 220 × 10⁹/L) with mildly elevated LDH (270 U/L). Renal and hepatic function tests were normal, and viral serologies were negative.</div><div>PET-CT imaging revealed significant findings: left axillary lymphadenopathy (30 × 22 mm) with SUVmax 9.12, mediastinal involvement in para-aortic and aortopulmonary regions (SUVmax: 5.89), bilateral apical pulmonary nodules (7.5 mm) with low FDG uptake, and a hypodense hepatic lesion (15 × 12 mm) with mild FDG uptake. No splenic involvement or bone metastases were detected.</div><div>Excisional biopsy of the left axillary lymph node confirmed follicular lymphoma, grade 1-2 according to WHO 2016 criteria. Immunohistochemistry demonstrated CD20(+), CD23(+), with negative CD5 and cyclin D1, consistent with follicular lymphoma. Critically, Ki-67 proliferation index was only 10%, indicating low proliferative activity.</div><div>Bone marrow examination showed normal hematopoiesis with reticulin grade 0/4, negative amyloid staining, and no evidence of lymphomatous infiltration.</div><div>Based on Lugano criteria, the patient was staged as advanced disease (stage IIIA-IIIB) due to mediastinal involvement and hepatomegaly.</div><div>Discussion: This case presents a striking clinico-radiologic discordance between low-grade histological features and high metabolic activity. The SUVmax of 9.12 is unusually high for grade 1-2 follicular lymphoma, typically associated with more aggressive histologies or transformed lymphomas.</div><div>Several mechanisms may explain this phenomenon. First, inflammatory microenvironment within lymph nodes can increase FDG uptake independent of tumor grade. Second, early transformation to diffuse large B-cell lymphoma may be focal and missed on single biopsy sampling. Third, some low-grade lymphomas may exhibit metabolically active behavior without histological transformation.</div><div>The management approach requires careful consideration. While current guidelines recommend \"watch and wait\" for asymptomatic, low tumor burden indolent FL, the high metabolic activity and advanced stage disease create uncertainty. Options include close surveillance with repeat biopsy if progression occurs, rituximab monotherapy, or combination therapy with R-CHOP or R-bendamustine for bulky/symptomatic disease.</div><div>The hepatome","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106163"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796525","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.2025.106192
Sultan Okur Acar
<div><div>Abstract</div><div>Central nervous system (CNS) involvement is an important prognostic factor in acute lymphoblastic leukemia (ALL). Both primary and secondary CNS disease are associated with increased relapse risk and inferior survival. In adults, CNS involvement at diagnosis occurs in 5–10% of cases, with relapse rates of 4–15%. Before the introduction of prophylaxis in the 1980s, CNS relapse rates were as high as 30–40%.</div><div>The pathophysiology of CNS involvement in ALL is complex, involving early migration of leukemic blasts across the blood–brain barrier, facilitated by adhesion molecules, integrins, and vascular endothelial growth factor (VEGF). VEGF-mediated endothelial disruption increases vascular permeability and plays a pivotal role in the development of posterior reversible encephalopathy syndrome (PRES). Targeting VEGF with monoclonal antibodies has been shown to reduce CNS leukemic burden, suggesting a promising future strategy in both pediatric and adult ALL. The immune-privileged microenvironment of the CNS provides a sanctuary for leukemic cells, supporting their persistence and relapse risk.</div><div>Traditionally, cerebrospinal fluid (CSF) cytomorphology has been considered the gold standard for assessing CNS involvement. However, this method has low sensitivity and specificity, particularly in samples with low cell counts or technical artifacts. In recent years, flow cytometric immunophenotyping of CSF has demonstrated superior sensitivity, identifying CNS disease more frequently and serving as a strong biomarker for relapse prediction. Minimal CNS involvement not only increases the risk of relapse but is also associated with treatment-related neurotoxicities. Data from the NOPHO group indicate that minimal CNS involvement in pediatric ALL is linked to higher rates of seizures and PRES.</div><div>Standard treatment approaches continue to rely on intrathecal chemotherapy (methotrexate, cytarabine, corticosteroids) and high-dose systemic agents. However, repeated intrathecal administration and cranial irradiation carry substantial risks of long-term neurotoxicity, highlighting the need for more selective and less toxic strategies. Radiation therapy may still be considered in selected cases, particularly in the context of hematopoietic stem cell transplantation (HSCT). HSCT remains a potentially curative option, especially when preceded by effective cytoreduction with immunotherapy.</div><div>In conclusion, CNS involvement in ALL represents a biologically and clinically distinct entity requiring tailored management. Primary involvement demands sensitive diagnostics and a careful balance between efficacy and neurotoxicity, while secondary CNS relapse necessitates aggressive multimodal therapy, often incorporating novel immunotherapies and HSCT. Advances in CNS-directed diagnostics and therapeutics are expected to further individualize treatment, aiming to reduce relapse risk while minimizing late toxicities.</div>
{"title":"CNS INVOLVEMENT IN PRIMARY AND SECONDARY ALL AND TREATMENT STRATEGIES","authors":"Sultan Okur Acar","doi":"10.1016/j.htct.2025.106192","DOIUrl":"10.1016/j.htct.2025.106192","url":null,"abstract":"<div><div>Abstract</div><div>Central nervous system (CNS) involvement is an important prognostic factor in acute lymphoblastic leukemia (ALL). Both primary and secondary CNS disease are associated with increased relapse risk and inferior survival. In adults, CNS involvement at diagnosis occurs in 5–10% of cases, with relapse rates of 4–15%. Before the introduction of prophylaxis in the 1980s, CNS relapse rates were as high as 30–40%.</div><div>The pathophysiology of CNS involvement in ALL is complex, involving early migration of leukemic blasts across the blood–brain barrier, facilitated by adhesion molecules, integrins, and vascular endothelial growth factor (VEGF). VEGF-mediated endothelial disruption increases vascular permeability and plays a pivotal role in the development of posterior reversible encephalopathy syndrome (PRES). Targeting VEGF with monoclonal antibodies has been shown to reduce CNS leukemic burden, suggesting a promising future strategy in both pediatric and adult ALL. The immune-privileged microenvironment of the CNS provides a sanctuary for leukemic cells, supporting their persistence and relapse risk.</div><div>Traditionally, cerebrospinal fluid (CSF) cytomorphology has been considered the gold standard for assessing CNS involvement. However, this method has low sensitivity and specificity, particularly in samples with low cell counts or technical artifacts. In recent years, flow cytometric immunophenotyping of CSF has demonstrated superior sensitivity, identifying CNS disease more frequently and serving as a strong biomarker for relapse prediction. Minimal CNS involvement not only increases the risk of relapse but is also associated with treatment-related neurotoxicities. Data from the NOPHO group indicate that minimal CNS involvement in pediatric ALL is linked to higher rates of seizures and PRES.</div><div>Standard treatment approaches continue to rely on intrathecal chemotherapy (methotrexate, cytarabine, corticosteroids) and high-dose systemic agents. However, repeated intrathecal administration and cranial irradiation carry substantial risks of long-term neurotoxicity, highlighting the need for more selective and less toxic strategies. Radiation therapy may still be considered in selected cases, particularly in the context of hematopoietic stem cell transplantation (HSCT). HSCT remains a potentially curative option, especially when preceded by effective cytoreduction with immunotherapy.</div><div>In conclusion, CNS involvement in ALL represents a biologically and clinically distinct entity requiring tailored management. Primary involvement demands sensitive diagnostics and a careful balance between efficacy and neurotoxicity, while secondary CNS relapse necessitates aggressive multimodal therapy, often incorporating novel immunotherapies and HSCT. Advances in CNS-directed diagnostics and therapeutics are expected to further individualize treatment, aiming to reduce relapse risk while minimizing late toxicities.</div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106192"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796696","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.2025.106128
Elif Vuslat Yımaz, Birol Güvenç
<div><div>We report a 51-year-old male with IgA-lambda multiple myeloma who developed severe cutaneous drug eruption following bortezomib treatment. Despite treatment modification to daratumumab-based regimen, the patient achieved complete remission, demonstrating successful management of therapy-related adverse events in CD56-negative myeloma phenotype.</div><div>Introduction: Multiple myeloma represents approximately 10% of hematologic malignancies, with CD56-negative variants comprising a rare subset associated with distinct clinical characteristics. Bortezomib-containing regimens remain first-line therapy; however, cutaneous adverse reactions can necessitate treatment modifications. We present a case of successful alternative therapy following severe bortezomib-induced skin toxicity.</div><div>Methods/Case Presentation: A 51-year-old male presented with fatigue and back pain. Laboratory investigations revealed IgA elevation (6.8 g/L) with lambda light chain restriction. Serum protein electrophoresis showed decreased albumin (51.6%) and elevated beta fractions. Bone marrow flow cytometry demonstrated plasma cell population: CD38/CD138 100%, CD45 100%, CD117 79.8%, CD56 7.5% (negative), with 96.7% lambda clonality, confirming IgA-lambda multiple myeloma with CD56-negative phenotype.</div><div>Staging revealed elevated β2-microglobulin (2.75 mg/L). PET/CT identified metabolically active lytic lesions in T3 vertebra (SUVmax 6.35) and right lumbosacral region (SUVmax 13.41), indicating metabolic progression without hepatosplenomegaly.</div><div>Initial treatment commenced with VRD (bortezomib, lenalidomide, dexamethasone). After cycle 1, mild erythematous pruritic rash appeared. Following cycle 2, extensive cutaneous eruptions developed. Skin biopsy revealed upper dermal eosinophil-associated perivascular infiltration with erythrocyte extravasation; direct immunofluorescence was negative, consistent with drug-induced eruption.</div><div>Bortezomib was discontinued, and treatment switched to DRd (daratumumab, lenalidomide, dexamethasone). After 2 DRd cycles, M-protein disappeared, serum and urine immunofixation became negative, and hematologic parameters normalized. Follow-up PET/CT showed no active myeloma lesions, confirming complete remission.</div><div>Results: The patient achieved biochemical and radiological complete remission within 2 cycles of daratumumab-based therapy following bortezomib-induced severe cutaneous reaction. No significant toxicities were observed with the modified regimen.</div><div>Discussion: CD56-negative multiple myeloma represents a rare phenotype with potentially different therapeutic responses. This case demonstrates that severe bortezomib-related cutaneous toxicity can be successfully managed through immediate drug discontinuation and regimen modification. Daratumumab-based therapy proved highly effective, achieving rapid complete remission despite treatment change.</div><div>The CD38-targeting monoclonal antibody d
{"title":"CD56-Negative IgA-Lambda Multiple Myeloma with Bortezomib-Induced Severe Cutaneous Reaction: A Case Report","authors":"Elif Vuslat Yımaz, Birol Güvenç","doi":"10.1016/j.htct.2025.106128","DOIUrl":"10.1016/j.htct.2025.106128","url":null,"abstract":"<div><div>We report a 51-year-old male with IgA-lambda multiple myeloma who developed severe cutaneous drug eruption following bortezomib treatment. Despite treatment modification to daratumumab-based regimen, the patient achieved complete remission, demonstrating successful management of therapy-related adverse events in CD56-negative myeloma phenotype.</div><div>Introduction: Multiple myeloma represents approximately 10% of hematologic malignancies, with CD56-negative variants comprising a rare subset associated with distinct clinical characteristics. Bortezomib-containing regimens remain first-line therapy; however, cutaneous adverse reactions can necessitate treatment modifications. We present a case of successful alternative therapy following severe bortezomib-induced skin toxicity.</div><div>Methods/Case Presentation: A 51-year-old male presented with fatigue and back pain. Laboratory investigations revealed IgA elevation (6.8 g/L) with lambda light chain restriction. Serum protein electrophoresis showed decreased albumin (51.6%) and elevated beta fractions. Bone marrow flow cytometry demonstrated plasma cell population: CD38/CD138 100%, CD45 100%, CD117 79.8%, CD56 7.5% (negative), with 96.7% lambda clonality, confirming IgA-lambda multiple myeloma with CD56-negative phenotype.</div><div>Staging revealed elevated β2-microglobulin (2.75 mg/L). PET/CT identified metabolically active lytic lesions in T3 vertebra (SUVmax 6.35) and right lumbosacral region (SUVmax 13.41), indicating metabolic progression without hepatosplenomegaly.</div><div>Initial treatment commenced with VRD (bortezomib, lenalidomide, dexamethasone). After cycle 1, mild erythematous pruritic rash appeared. Following cycle 2, extensive cutaneous eruptions developed. Skin biopsy revealed upper dermal eosinophil-associated perivascular infiltration with erythrocyte extravasation; direct immunofluorescence was negative, consistent with drug-induced eruption.</div><div>Bortezomib was discontinued, and treatment switched to DRd (daratumumab, lenalidomide, dexamethasone). After 2 DRd cycles, M-protein disappeared, serum and urine immunofixation became negative, and hematologic parameters normalized. Follow-up PET/CT showed no active myeloma lesions, confirming complete remission.</div><div>Results: The patient achieved biochemical and radiological complete remission within 2 cycles of daratumumab-based therapy following bortezomib-induced severe cutaneous reaction. No significant toxicities were observed with the modified regimen.</div><div>Discussion: CD56-negative multiple myeloma represents a rare phenotype with potentially different therapeutic responses. This case demonstrates that severe bortezomib-related cutaneous toxicity can be successfully managed through immediate drug discontinuation and regimen modification. Daratumumab-based therapy proved highly effective, achieving rapid complete remission despite treatment change.</div><div>The CD38-targeting monoclonal antibody d","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106128"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796703","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.2025.106189
Yunus Çatma
<div><h3>Background</h3><div>The advent of tyrosine kinase inhibitors (TKIs) has revolutionized the management of chronic myeloid leukemia (CML), transforming it into a chronic condition with near-normal life expectancy. In this context, treatment-free remission (TFR)—defined as the maintenance of deep molecular response after discontinuation of TKIs—has emerged as a new therapeutic milestone beyond survival and disease control. While multiple clinical trials and real-world cohorts have demonstrated the feasibility and safety of TFR, several biological, molecular, and clinical factors continue to shape patient selection and long-term outcomes.</div></div><div><h3>Content</h3><div>This presentation synthesizes evidence from pivotal discontinuation trials (STIM, EURO-SKI, ENESTfreedom, ENESTop, DASFREE, DESTINY) as well as real-world studies from Europe, Asia, and North America. Updated recommendations from international guidelines (ELN 2020/2025, NCCN 2025) are reviewed alongside emerging biological insights, including immune surveillance, transcript types, and microenvironmental regulation of leukemia stem cells. Novel approaches such as dose de-escalation, immunotherapy combinations, and predictive modeling are critically examined to delineate future directions in TFR research.</div></div><div><h3>Results</h3><div>Clinical evidence consistently shows that sustained TFR is achievable in approximately <strong>40–60%</strong> of patients after ≥3 years of TKI therapy and ≥2 years of stable deep molecular response (DMR). Higher success rates have been reported in Japanese cohorts (up to 63%), underscoring the influence of patient selection and monitoring intensity.</div><div> <!-->1. <strong>Relapse dynamics:</strong> Most relapses occur within the first 6–12 months, with >95% of patients regaining major molecular response (MMR) after restarting TKIs. Late relapses are rare but underscore the necessity of lifelong molecular monitoring.</div><div> <!-->2. <strong>Predictors of success:</strong> Longer TKI duration (≥5 years), sustained MR4.5, and the e14a2 transcript type are consistently associated with improved outcomes. Immunological parameters, particularly increased NK cell activity and reduced regulatory T-cell frequencies, also correlate with durable remission.</div><div> <!-->3. <strong>Therapeutic strategies:</strong> Dose de-escalation (e.g., DESTINY trial) has been shown to reduce relapse risk and mitigate withdrawal symptoms. Second TFR attempts, as demonstrated in DAstop2, are feasible and safe for selected patients.</div><div> <!-->4. <strong>Adverse effects:</strong> Approximately 30–40% of patients experience musculoskeletal discomfort—termed “TKI withdrawal syndrome”—which is typically mild and self-limiting.</div></div><div><h3>Discussion</h3><div>TFR represents a paradigm shift in CML care, reflecting both biological disease control and patient-centered goals such as quality of life and long-term safety. While most relapses are
{"title":"TREATMENT-FREE REMISSION IN CHRONIC MYELOID LEUKEMIA: CURRENT EVIDENCE, PREDICTORS, AND FUTURE DIRECTIONS","authors":"Yunus Çatma","doi":"10.1016/j.htct.2025.106189","DOIUrl":"10.1016/j.htct.2025.106189","url":null,"abstract":"<div><h3>Background</h3><div>The advent of tyrosine kinase inhibitors (TKIs) has revolutionized the management of chronic myeloid leukemia (CML), transforming it into a chronic condition with near-normal life expectancy. In this context, treatment-free remission (TFR)—defined as the maintenance of deep molecular response after discontinuation of TKIs—has emerged as a new therapeutic milestone beyond survival and disease control. While multiple clinical trials and real-world cohorts have demonstrated the feasibility and safety of TFR, several biological, molecular, and clinical factors continue to shape patient selection and long-term outcomes.</div></div><div><h3>Content</h3><div>This presentation synthesizes evidence from pivotal discontinuation trials (STIM, EURO-SKI, ENESTfreedom, ENESTop, DASFREE, DESTINY) as well as real-world studies from Europe, Asia, and North America. Updated recommendations from international guidelines (ELN 2020/2025, NCCN 2025) are reviewed alongside emerging biological insights, including immune surveillance, transcript types, and microenvironmental regulation of leukemia stem cells. Novel approaches such as dose de-escalation, immunotherapy combinations, and predictive modeling are critically examined to delineate future directions in TFR research.</div></div><div><h3>Results</h3><div>Clinical evidence consistently shows that sustained TFR is achievable in approximately <strong>40–60%</strong> of patients after ≥3 years of TKI therapy and ≥2 years of stable deep molecular response (DMR). Higher success rates have been reported in Japanese cohorts (up to 63%), underscoring the influence of patient selection and monitoring intensity.</div><div> <!-->1. <strong>Relapse dynamics:</strong> Most relapses occur within the first 6–12 months, with >95% of patients regaining major molecular response (MMR) after restarting TKIs. Late relapses are rare but underscore the necessity of lifelong molecular monitoring.</div><div> <!-->2. <strong>Predictors of success:</strong> Longer TKI duration (≥5 years), sustained MR4.5, and the e14a2 transcript type are consistently associated with improved outcomes. Immunological parameters, particularly increased NK cell activity and reduced regulatory T-cell frequencies, also correlate with durable remission.</div><div> <!-->3. <strong>Therapeutic strategies:</strong> Dose de-escalation (e.g., DESTINY trial) has been shown to reduce relapse risk and mitigate withdrawal symptoms. Second TFR attempts, as demonstrated in DAstop2, are feasible and safe for selected patients.</div><div> <!-->4. <strong>Adverse effects:</strong> Approximately 30–40% of patients experience musculoskeletal discomfort—termed “TKI withdrawal syndrome”—which is typically mild and self-limiting.</div></div><div><h3>Discussion</h3><div>TFR represents a paradigm shift in CML care, reflecting both biological disease control and patient-centered goals such as quality of life and long-term safety. While most relapses are ","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106189"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796833","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.2025.106141
Songül Beskisiz Dönen , Miray Nilgün Yazok , Vehbi Demircan , Abdullah Karakuş , Mehmet Orhan Ayyıldız
<div><h3>INTRODUCTION</h3><div>Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the BCR-ABL1 fusion gene and accounts for approximately 15–20% of all leukemias. While the majority of cases harbor the p210 (major) transcript, the p190 (minor, e1a2) transcript is exceedingly rare, representing only about 1–2% of CML cases. This subtype may exhibit distinct hematologic features compared to p210-positive cases, particularly peripheral monocytosis and marked splenomegaly. In the literature, responses to tyrosine kinase inhibitor (TKI) therapy in p190-positive CML have been reported to be variable, and long-term outcomes are described only in limited case reports. Therefore, presenting the clinical and laboratory features of this uncommon subtype is of particular importance.</div></div><div><h3>CASE PRESENTATION</h3><div>A 23-year-old female patient presented with complaints of fatigue and dyspeptic symptoms. Complete blood count revealed WBC: 70 × 10³/µL, neutrophils: 58.5 × 10³/µL, monocytes: 7.38 × 10³/µL, hemoglobin: 10.4 g/dL, and platelets: 871 × 10³/µL. Abdominal ultrasonography demonstrated splenomegaly with a longitudinal diameter of 175 mm. Peripheral blood smear and bone marrow aspiration-biopsy findings were consistent with chronic myeloid leukemia, with blasts reported as <5%, and the overall evaluation was described as a “myeloproliferative neoplasm.”</div><div>Molecular testing showed negative results for the major BCR-ABL1 transcript, whereas the minor BCR-ABL1 (e1a2) transcript was detected at 3.4%. The patient was started on first-line therapy with imatinib. At the third month of treatment, BCR-ABL1 (minor) was 10.51%, although hematologic parameters had improved. With continuation of imatinib, the sixth-month evaluation showed a decrease in BCR-ABL1 (minor) to 1.56%, with a normalized blood count (WBC: 5.31 × 10³/µL, Hb: 10.6 g/dL, platelets: 226 × 10³/µL). The patient’s clinical symptoms had resolved, and she remains on imatinib therapy with ongoing follow-up.</div></div><div><h3>DISCUSSION AND CONCLUSION</h3><div>While the p210 (major) transcript is the most frequently detected form in chronic myeloid leukemia (CML), the p190 (minor, e1a2) transcript is exceedingly rare, occurring in only about 1–2% of cases. In the literature, this subtype has been associated with peripheral monocytosis and marked splenomegaly, and responses to tyrosine kinase inhibitors (TKIs) have been reported as variable. In some patients, imatinib therapy may not achieve sufficient molecular response, whereas deeper responses have been described with second-generation TKIs.</div><div>In our patient, early hematologic response was achieved with imatinib, and by the sixth month a marked molecular reduction was observed. Through this case, we aim to highlight the clinical and laboratory characteristics of p190-positive CML and to emphasize the importance of close molecular monitoring and careful evaluation of treatment response
{"title":"BCR-ABL1 MINOR (P190, E1A2) POSITIVE CHRONIC MYELOID LEUKEMIA: A RARE CASE REPORT","authors":"Songül Beskisiz Dönen , Miray Nilgün Yazok , Vehbi Demircan , Abdullah Karakuş , Mehmet Orhan Ayyıldız","doi":"10.1016/j.htct.2025.106141","DOIUrl":"10.1016/j.htct.2025.106141","url":null,"abstract":"<div><h3>INTRODUCTION</h3><div>Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the BCR-ABL1 fusion gene and accounts for approximately 15–20% of all leukemias. While the majority of cases harbor the p210 (major) transcript, the p190 (minor, e1a2) transcript is exceedingly rare, representing only about 1–2% of CML cases. This subtype may exhibit distinct hematologic features compared to p210-positive cases, particularly peripheral monocytosis and marked splenomegaly. In the literature, responses to tyrosine kinase inhibitor (TKI) therapy in p190-positive CML have been reported to be variable, and long-term outcomes are described only in limited case reports. Therefore, presenting the clinical and laboratory features of this uncommon subtype is of particular importance.</div></div><div><h3>CASE PRESENTATION</h3><div>A 23-year-old female patient presented with complaints of fatigue and dyspeptic symptoms. Complete blood count revealed WBC: 70 × 10³/µL, neutrophils: 58.5 × 10³/µL, monocytes: 7.38 × 10³/µL, hemoglobin: 10.4 g/dL, and platelets: 871 × 10³/µL. Abdominal ultrasonography demonstrated splenomegaly with a longitudinal diameter of 175 mm. Peripheral blood smear and bone marrow aspiration-biopsy findings were consistent with chronic myeloid leukemia, with blasts reported as <5%, and the overall evaluation was described as a “myeloproliferative neoplasm.”</div><div>Molecular testing showed negative results for the major BCR-ABL1 transcript, whereas the minor BCR-ABL1 (e1a2) transcript was detected at 3.4%. The patient was started on first-line therapy with imatinib. At the third month of treatment, BCR-ABL1 (minor) was 10.51%, although hematologic parameters had improved. With continuation of imatinib, the sixth-month evaluation showed a decrease in BCR-ABL1 (minor) to 1.56%, with a normalized blood count (WBC: 5.31 × 10³/µL, Hb: 10.6 g/dL, platelets: 226 × 10³/µL). The patient’s clinical symptoms had resolved, and she remains on imatinib therapy with ongoing follow-up.</div></div><div><h3>DISCUSSION AND CONCLUSION</h3><div>While the p210 (major) transcript is the most frequently detected form in chronic myeloid leukemia (CML), the p190 (minor, e1a2) transcript is exceedingly rare, occurring in only about 1–2% of cases. In the literature, this subtype has been associated with peripheral monocytosis and marked splenomegaly, and responses to tyrosine kinase inhibitors (TKIs) have been reported as variable. In some patients, imatinib therapy may not achieve sufficient molecular response, whereas deeper responses have been described with second-generation TKIs.</div><div>In our patient, early hematologic response was achieved with imatinib, and by the sixth month a marked molecular reduction was observed. Through this case, we aim to highlight the clinical and laboratory characteristics of p190-positive CML and to emphasize the importance of close molecular monitoring and careful evaluation of treatment response","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106141"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796971","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.2025.106180
Bariş Yılmaz
<div><div>Hemophilia is an X-linked recessive hereditary coagulation disorder characterized by a deficiency of factor VIII (hemophilia A) or factor IX (hemophilia B). Beginning in childhood, it constitutes a lifelong global health problem, associated with substantial morbidity, mortality, and treatment costs. While novel approaches—including gene therapies and non-factor-based biologic agents—are reshaping therapeutic strategies, factor replacement therapies remain the indispensable cornerstone of hemophilia management due to persistent clinical, biological, and economic limitations.</div></div><div><h3>Gene Therapy</h3><div>Gene transfer techniques utilizing adeno-associated virus (AAV) vectors (e.g., valoctocogene roxaparvovec, etranacogene dezaparvovec) have shown promise in maintaining sustained factor levels in adults. However, in pediatric populations, hepatocyte proliferation inevitably leads to loss of transgene expression. In addition, immune responses, hepatotoxicity, and the inability to administer repeat dosing represent major barriers to safety and efficacy in children. Ethical concerns further complicate implementation. For these reasons, gene therapy does not appear to be a feasible treatment option for pediatric hemophilia in the near future.</div></div><div><h3>Non–Factor-Based Agents</h3><div>Emicizumab, a bispecific antibody that mimics the bridging function of factor VIII, has significantly reduced bleeding frequency and revolutionized care, particularly in hemophilia A patients with inhibitors. Its subcutaneous administration enhances treatment adherence. Nevertheless, its inability to rapidly increase factor levels in emergencies such as major surgery or trauma is a critical limitation. Likewise, RNA interference (RNAi) therapies such as fitusiran and tissue factor pathway inhibitor (TFPI) inhibitors (concizumab, marstacimab) have shown encouraging results in clinical trials. However, thrombotic risks and uncertainties surrounding long-term safety restrict their use in pediatric populations.</div></div><div><h3>Factor Replacement Therapy</h3><div>Standard and extended half-life (EHL) FVIII/FIX concentrates, supported by more than four decades of safety data, continue to form the foundation of prophylaxis in childhood. EHL products have reduced treatment burden with once- or twice-weekly dosing, while playing a vital role in maintaining joint health and preventing trauma-related bleeding episodes. Factor replacement therapy remains the gold standard for the management of acute bleeding.</div></div><div><h3>Global Access and Health Economics</h3><div>Gene therapies and biologic agents are accessible almost exclusively in high-income countries due to their prohibitive costs (USD 2–3 million per treatment; emicizumab approximately USD 400,000 annually). In contrast, in low- and middle-income countries, factor replacement remains the only feasible option, in line with World Federation of Hemophilia (WFH) recommendations.</div></d
{"title":"OLD TRADITIONS IN A NEW VILLAGE*… WHY ARE FACTORS STILL NECESSARY? CONTEMPORARY PARADİGMS İN HEMOPHILIA MANAGEMENT AND THE IRREPLACEABLE ROLE OF FACTOR REPLACEMENT","authors":"Bariş Yılmaz","doi":"10.1016/j.htct.2025.106180","DOIUrl":"10.1016/j.htct.2025.106180","url":null,"abstract":"<div><div>Hemophilia is an X-linked recessive hereditary coagulation disorder characterized by a deficiency of factor VIII (hemophilia A) or factor IX (hemophilia B). Beginning in childhood, it constitutes a lifelong global health problem, associated with substantial morbidity, mortality, and treatment costs. While novel approaches—including gene therapies and non-factor-based biologic agents—are reshaping therapeutic strategies, factor replacement therapies remain the indispensable cornerstone of hemophilia management due to persistent clinical, biological, and economic limitations.</div></div><div><h3>Gene Therapy</h3><div>Gene transfer techniques utilizing adeno-associated virus (AAV) vectors (e.g., valoctocogene roxaparvovec, etranacogene dezaparvovec) have shown promise in maintaining sustained factor levels in adults. However, in pediatric populations, hepatocyte proliferation inevitably leads to loss of transgene expression. In addition, immune responses, hepatotoxicity, and the inability to administer repeat dosing represent major barriers to safety and efficacy in children. Ethical concerns further complicate implementation. For these reasons, gene therapy does not appear to be a feasible treatment option for pediatric hemophilia in the near future.</div></div><div><h3>Non–Factor-Based Agents</h3><div>Emicizumab, a bispecific antibody that mimics the bridging function of factor VIII, has significantly reduced bleeding frequency and revolutionized care, particularly in hemophilia A patients with inhibitors. Its subcutaneous administration enhances treatment adherence. Nevertheless, its inability to rapidly increase factor levels in emergencies such as major surgery or trauma is a critical limitation. Likewise, RNA interference (RNAi) therapies such as fitusiran and tissue factor pathway inhibitor (TFPI) inhibitors (concizumab, marstacimab) have shown encouraging results in clinical trials. However, thrombotic risks and uncertainties surrounding long-term safety restrict their use in pediatric populations.</div></div><div><h3>Factor Replacement Therapy</h3><div>Standard and extended half-life (EHL) FVIII/FIX concentrates, supported by more than four decades of safety data, continue to form the foundation of prophylaxis in childhood. EHL products have reduced treatment burden with once- or twice-weekly dosing, while playing a vital role in maintaining joint health and preventing trauma-related bleeding episodes. Factor replacement therapy remains the gold standard for the management of acute bleeding.</div></div><div><h3>Global Access and Health Economics</h3><div>Gene therapies and biologic agents are accessible almost exclusively in high-income countries due to their prohibitive costs (USD 2–3 million per treatment; emicizumab approximately USD 400,000 annually). In contrast, in low- and middle-income countries, factor replacement remains the only feasible option, in line with World Federation of Hemophilia (WFH) recommendations.</div></d","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106180"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796980","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.2025.106201
Gülsüm Akgün Çağlıyan
In autologous HSCT, stem cells are collected from the patient following prior exposure to chemotherapy. The standard mobilization approach is granulocyte colony-stimulating factor (G-CSF) alone or in combination with chemotherapy, such as cyclophosphamide. While chemotherapy-based mobilization may increase CD34+ yields and contribute to disease cytoreduction, it is associated with increased infectious and hematologic complications. Plerixafor, a CXCR4 antagonist, has emerged as a highly effective adjunct in patients with poor mobilization, particularly those heavily pretreated or with impaired marrow reserve. Predictors of mobilization failure include advanced age, extensive prior therapy, and low baseline blood counts.
In allogeneic HSCT, stem cells are obtained from healthy donors. G-CSF administration for 4–5 days remains the standard strategy, providing sufficient peripheral blood stem cell (PBSC) yields and enabling rapid hematopoietic recovery. Compared with bone marrow harvest, PBSC collection is less invasive and results in higher CD34+ cell counts, but is associated with an increased incidence of chronic graft-versus-host disease. Plerixafor has been investigated as an alternative or adjunct in specific donor populations with inadequate mobilization, though its use remains limited. Donor safety, tolerability of mobilization agents, and long-term health implications are major considerations in the allogeneic context.
Despite distinct indications, both autologous and allogeneic mobilization share key challenges: ensuring adequate stem cell yield, minimizing toxicity, and reducing the need for multiple apheresis procedures. Recent advances have improved mobilization outcomes, yet the problem of poor mobilizers persists. Novel mobilizing agents, optimization of dosing schedules, and risk-adapted strategies are under evaluation to enhance efficiency and safety.
Stem cell mobilization remains a critical determinant of HSCT success. Autologous mobilization is challenged by prior therapy and patient-related factors, whereas allogeneic mobilization prioritizes donor safety and graft quality. The incorporation of agents such as plerixafor has significantly expanded the mobilization armamentarium. Future directions include individualized mobilization protocols, novel pharmacologic combinations, and strategies aimed at improving long-term transplant outcomes.
{"title":"STEM CELL MOBILIZATION: AUTOLOGOUS AND ALLOGENEIC","authors":"Gülsüm Akgün Çağlıyan","doi":"10.1016/j.htct.2025.106201","DOIUrl":"10.1016/j.htct.2025.106201","url":null,"abstract":"<div><div>In autologous HSCT, stem cells are collected from the patient following prior exposure to chemotherapy. The standard mobilization approach is granulocyte colony-stimulating factor (G-CSF) alone or in combination with chemotherapy, such as cyclophosphamide. While chemotherapy-based mobilization may increase CD34+ yields and contribute to disease cytoreduction, it is associated with increased infectious and hematologic complications. Plerixafor, a CXCR4 antagonist, has emerged as a highly effective adjunct in patients with poor mobilization, particularly those heavily pretreated or with impaired marrow reserve. Predictors of mobilization failure include advanced age, extensive prior therapy, and low baseline blood counts.</div><div>In allogeneic HSCT, stem cells are obtained from healthy donors. G-CSF administration for 4–5 days remains the standard strategy, providing sufficient peripheral blood stem cell (PBSC) yields and enabling rapid hematopoietic recovery. Compared with bone marrow harvest, PBSC collection is less invasive and results in higher CD34+ cell counts, but is associated with an increased incidence of chronic graft-versus-host disease. Plerixafor has been investigated as an alternative or adjunct in specific donor populations with inadequate mobilization, though its use remains limited. Donor safety, tolerability of mobilization agents, and long-term health implications are major considerations in the allogeneic context.</div><div>Despite distinct indications, both autologous and allogeneic mobilization share key challenges: ensuring adequate stem cell yield, minimizing toxicity, and reducing the need for multiple apheresis procedures. Recent advances have improved mobilization outcomes, yet the problem of poor mobilizers persists. Novel mobilizing agents, optimization of dosing schedules, and risk-adapted strategies are under evaluation to enhance efficiency and safety.</div><div>Stem cell mobilization remains a critical determinant of HSCT success. Autologous mobilization is challenged by prior therapy and patient-related factors, whereas allogeneic mobilization prioritizes donor safety and graft quality. The incorporation of agents such as plerixafor has significantly expanded the mobilization armamentarium. Future directions include individualized mobilization protocols, novel pharmacologic combinations, and strategies aimed at improving long-term transplant outcomes.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106201"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796989","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.2025.106145
Zekeriya AKSÖZ, Ayşe UYSAL, Kübra ORAL
<div><h3>INTRODUCTION</h3><div>Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of non-Hodgkin lymphoma (NHL) and accounts for approximately one-quarter of NHL cases. Patients typically present with enlarged lymph nodes in the neck or abdomen. DLBCL’s first-line immunochemotherapy such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, Oncovin and prednisone) curing approximately two-thirds of patients. The prognosis is poor for DLBCL patients who receive first-line chemoimmunotherapy but develop early relapse or refractoriness. Treatment options for refractory patients include salvage chemoimmunotherapy, monoclonal antibodies, CAR-T or autologous stem cell transplantation. We will present a case of primary refractory DLBCL.</div></div><div><h3>CASE</h3><div>A 57-year-old male patient with no chronic illness presented to the internal medicine outpatient clinic complaining of abdominal pain and was referred to us due to the detection of conglomerate lymphadenopathy (LAP) in the abdomen on imaging. Positron Emission Tomography (PET-CT) revealed multiple LAP’s within the abdomen, the largest measuring 80 mm in diameter and with an SUV(max) value of 21.8. A tru-cut biopsy was performed from the large intra-abdominal LAP. The results were DLBCL with Bcl-2 (+), Bcl-6 (+), and Ki-67 85-90%. Myc could not be tested for technical reasons. No infiltration was detected in the bone marrow biopsy. The patient received 3 cycles of R-CHOP chemotherapy protocol, and a PET-CT scan was performed for interim evaluation. The PET-CT scan showed persistent conglomerate LAP’s with an SUV(max) value of 27.02 and a maximum diameter of 58 mm. The patient, considered refractory, received two cycles of R-DHAP (Rituximab-Dexamethasone, Cytarabine Cisplatin) chemotherapy protocol and a PET-CT scan was performed for response evaluation. The PET-CT scan showed multiple LAPs, the largest of which was 83 mm in diameter and had an SUV(max) of 31.45. A tru-cut biopsy was performed again from the largest intra-abdominal lymph node for confirmation of the diagnosis. Pathology was similar to the previous biopsy and c-myc was weak (+) (10-15%). The patient received two cycles of the R-GemOX (rituximab, gemcitabine, oxaliplatin) protocol. Only abdominal CT was scanned and no reduction in the mass was observed. Glofitamab therapy was initiated with off-label consent. The first and second cycle was completed. The patient did not develop cytokine release syndrome or neuropathy. A PET-CT scan was scheduled for 3 weeks later for response evaluation. The PET-CT scan showed that the intra-abdominal mass had regressed to 8 mm and the SUV(max) value to 3.44. The patient, who responded to glofitamab treatment, was offered autologous stem cell transplantation or CAR-T (Chimeric Antigen Receptor T-cell) therapy options. The patient requested to be referred to a center where CAR-T therapy could be performed. The patient is currently awaiting CAR-T therapy.</div></div><
{"title":"A CASE REPORT OF PRIMER REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA","authors":"Zekeriya AKSÖZ, Ayşe UYSAL, Kübra ORAL","doi":"10.1016/j.htct.2025.106145","DOIUrl":"10.1016/j.htct.2025.106145","url":null,"abstract":"<div><h3>INTRODUCTION</h3><div>Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of non-Hodgkin lymphoma (NHL) and accounts for approximately one-quarter of NHL cases. Patients typically present with enlarged lymph nodes in the neck or abdomen. DLBCL’s first-line immunochemotherapy such as R-CHOP (rituximab, cyclophosphamide, doxorubicin, Oncovin and prednisone) curing approximately two-thirds of patients. The prognosis is poor for DLBCL patients who receive first-line chemoimmunotherapy but develop early relapse or refractoriness. Treatment options for refractory patients include salvage chemoimmunotherapy, monoclonal antibodies, CAR-T or autologous stem cell transplantation. We will present a case of primary refractory DLBCL.</div></div><div><h3>CASE</h3><div>A 57-year-old male patient with no chronic illness presented to the internal medicine outpatient clinic complaining of abdominal pain and was referred to us due to the detection of conglomerate lymphadenopathy (LAP) in the abdomen on imaging. Positron Emission Tomography (PET-CT) revealed multiple LAP’s within the abdomen, the largest measuring 80 mm in diameter and with an SUV(max) value of 21.8. A tru-cut biopsy was performed from the large intra-abdominal LAP. The results were DLBCL with Bcl-2 (+), Bcl-6 (+), and Ki-67 85-90%. Myc could not be tested for technical reasons. No infiltration was detected in the bone marrow biopsy. The patient received 3 cycles of R-CHOP chemotherapy protocol, and a PET-CT scan was performed for interim evaluation. The PET-CT scan showed persistent conglomerate LAP’s with an SUV(max) value of 27.02 and a maximum diameter of 58 mm. The patient, considered refractory, received two cycles of R-DHAP (Rituximab-Dexamethasone, Cytarabine Cisplatin) chemotherapy protocol and a PET-CT scan was performed for response evaluation. The PET-CT scan showed multiple LAPs, the largest of which was 83 mm in diameter and had an SUV(max) of 31.45. A tru-cut biopsy was performed again from the largest intra-abdominal lymph node for confirmation of the diagnosis. Pathology was similar to the previous biopsy and c-myc was weak (+) (10-15%). The patient received two cycles of the R-GemOX (rituximab, gemcitabine, oxaliplatin) protocol. Only abdominal CT was scanned and no reduction in the mass was observed. Glofitamab therapy was initiated with off-label consent. The first and second cycle was completed. The patient did not develop cytokine release syndrome or neuropathy. A PET-CT scan was scheduled for 3 weeks later for response evaluation. The PET-CT scan showed that the intra-abdominal mass had regressed to 8 mm and the SUV(max) value to 3.44. The patient, who responded to glofitamab treatment, was offered autologous stem cell transplantation or CAR-T (Chimeric Antigen Receptor T-cell) therapy options. The patient requested to be referred to a center where CAR-T therapy could be performed. The patient is currently awaiting CAR-T therapy.</div></div><","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"47 ","pages":"Article 106145"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145797059","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号