Gustav Hedberg, Qi Chen, Tadepally Lakshmikanth, Nikolas Herold, Per Kogner, Petter Brodin, Linda Ljungblad
Background
Paediatric classical Hodgkin lymphoma (cHL) is the most common malignancy in adolescents, and despite excellent survival, a subset of patients experiences treatment failure or severe long-term toxicity, underscoring the need for improved risk stratification. Early response assessment is particularly important, as it guides decisions on radiotherapy, where overtreatment can lead to substantial late effects.
Methods
In the context of a large-scale systems-level immunomonitoring initiative, we specifically examined paediatric cHL and profiled their systemic immunology alongside children with intra- and extracranial solid tumours and other lymphomas. Through longitudinal sampling before and after treatment, we aimed to identify diagnostic and prognostic biomarkers relating immune profiles to early treatment response and risk of developing neutropenic fever.
Results
Plasma CCL17 and MCP-4 were markedly elevated in cHL compared with other paediatric lymphomas and other solid tumours, with distinct immune cell compositions, particularly between cHL and extracranial tumours. CCL17 and MCP-4 negatively correlated with age in extracranial and intracranial tumours but not in cHL, indicating disease-specific regulation. Chemotherapy induced consistent protein changes in cHL and eliminated CCL17 and MCP-4 differences between cHL and other lymphomas. Lower baseline MCP-4 and greater CCL17 reduction after chemotherapy were associated with favourable early response, while lower granzyme levels identified patients at higher neutropenic fever risk.
Conclusion
Together, these exploratory findings highlight clinically relevant biomarkers in a paediatric oncology context, with the potential to enhance diagnostic precision, guide response-adapted therapy and effectively allocate supportive care, thereby improving outcomes for children with cHL.
Trial Registration
The authors have confirmed clinical trial registration is not needed for this submission
{"title":"Systemic Immune Alterations in Paediatric Classical Hodgkin Lymphoma With CCL17 and MCP-4 as Diagnostic and Predictive Biomarkers","authors":"Gustav Hedberg, Qi Chen, Tadepally Lakshmikanth, Nikolas Herold, Per Kogner, Petter Brodin, Linda Ljungblad","doi":"10.1002/jha2.70228","DOIUrl":"10.1002/jha2.70228","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Paediatric classical Hodgkin lymphoma (cHL) is the most common malignancy in adolescents, and despite excellent survival, a subset of patients experiences treatment failure or severe long-term toxicity, underscoring the need for improved risk stratification. Early response assessment is particularly important, as it guides decisions on radiotherapy, where overtreatment can lead to substantial late effects.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In the context of a large-scale systems-level immunomonitoring initiative, we specifically examined paediatric cHL and profiled their systemic immunology alongside children with intra- and extracranial solid tumours and other lymphomas. Through longitudinal sampling before and after treatment, we aimed to identify diagnostic and prognostic biomarkers relating immune profiles to early treatment response and risk of developing neutropenic fever.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Plasma CCL17 and MCP-4 were markedly elevated in cHL compared with other paediatric lymphomas and other solid tumours, with distinct immune cell compositions, particularly between cHL and extracranial tumours. CCL17 and MCP-4 negatively correlated with age in extracranial and intracranial tumours but not in cHL, indicating disease-specific regulation. Chemotherapy induced consistent protein changes in cHL and eliminated CCL17 and MCP-4 differences between cHL and other lymphomas. Lower baseline MCP-4 and greater CCL17 reduction after chemotherapy were associated with favourable early response, while lower granzyme levels identified patients at higher neutropenic fever risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Together, these exploratory findings highlight clinically relevant biomarkers in a paediatric oncology context, with the potential to enhance diagnostic precision, guide response-adapted therapy and effectively allocate supportive care, thereby improving outcomes for children with cHL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>The authors have confirmed clinical trial registration is not needed for this submission</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"7 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12849930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146088194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>A 70-year-old woman diagnosed with nodal T follicular helper cell lymphoma, angioimmunoblastic type (nTFHL-AI), was treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Approximately 2 weeks after the fifth cycle of CHOP, the patient developed difficulty in keeping her right eye open. Simultaneously, cervical lymphadenopathy was observed. Eye examination revealed solid subconjunctival tissue, chemosis, conjunctival hyperemia, eyelid redness/swelling, and diplopia (Figure A,B). Magnetic resonance imaging revealed contrast enhancement in the soft tissue surrounding the right eyeball (Figure C). Positron emission tomography revealed hypermetabolic masses on the right eyelid and eyeball (Figure D). Conjunctival biopsy was performed, and tissue samples were obtained from the inferonasal and inferotemporal conjunctiva. Hematoxylin and eosin-stained sections demonstrated the infiltration of small- to medium-sized lymphoid cells into the lamina propria (Figure E). Immunohistochemical analysis revealed that the lymphoid cells were positive for CD3, CD4, CD5, BCL-6, PD-1, ICOS, and CXCL-13 (Figure F–H) and negative for CD8, CD20, CD30, and EBER, which were matched as the IHC profile of nTFHL-AI. Based on these findings, the conjunctival lesion was diagnosed as an nTFHL-AI relapse. Cervical lymph node biopsy also confirmed nTFHL-AI relapse and identified clonal T-cell receptor-β gene rearrangement. The patient received salvage chemotherapy with ifosfamide, carboplatin, and etoposide, which proved ineffective. In contrast, the patient responded to involved-site radiation therapy of the right eye combined with tucidinostat, an oral histone deacetylase inhibitor.</p><p>Ocular adnexal lymphoma accounts for 1%–2% of all non-Hodgkin lymphomas, most of which are of the B-cell lineage [<span>1</span>]. Conjunctival T-cell lymphoma is rare, with conjunctival nTFHL-AI being extremely uncommon [<span>2, 3</span>]. Conjunctival lymphomas exhibit distinct ocular features by subtype and are particularly useful for diagnosing common B-cell lymphomas [<span>2</span>]. Conversely, ocular manifestations are often insufficiently described in T-cell lymphomas, which are rare subtypes of conjunctival lymphomas [<span>3-7</span>]. In a previously reported case of nTFHL-AI, the ocular findings comprised two pink, discrete, non-tender bulbar conjunctival masses [<span>3</span>]. In our case, in addition to a solid conjunctival mass, we observed chemosis, conjunctival hyperemia, eyelid redness and swelling, and diplopia. Our case presents a rare manifestation of ocular involvement of nTFHL-AI and provides insights into the differential diagnosis of a red eye, which includes both benign and serious conditions requiring ophthalmologic evaluation, including infections, rheumatologic disorders, thyroid diseases, sarcoidosis, orbital myositis, and, rarely, malignancies.</p><p>The authors have nothing to report.</p><p>The authors have nothing to report.</p><
{"title":"Ocular Involvement of Relapsed Nodal T Follicular Helper Cell Lymphoma, Angioimmunoblastic Type","authors":"Seiya Bamba, Masashi Nishikubo, Shin-Ichiro Ito, Junnosuke Yamakawa, Shigeo Hara, Ryusuke Yamamoto","doi":"10.1002/jha2.70229","DOIUrl":"10.1002/jha2.70229","url":null,"abstract":"<p>A 70-year-old woman diagnosed with nodal T follicular helper cell lymphoma, angioimmunoblastic type (nTFHL-AI), was treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Approximately 2 weeks after the fifth cycle of CHOP, the patient developed difficulty in keeping her right eye open. Simultaneously, cervical lymphadenopathy was observed. Eye examination revealed solid subconjunctival tissue, chemosis, conjunctival hyperemia, eyelid redness/swelling, and diplopia (Figure A,B). Magnetic resonance imaging revealed contrast enhancement in the soft tissue surrounding the right eyeball (Figure C). Positron emission tomography revealed hypermetabolic masses on the right eyelid and eyeball (Figure D). Conjunctival biopsy was performed, and tissue samples were obtained from the inferonasal and inferotemporal conjunctiva. Hematoxylin and eosin-stained sections demonstrated the infiltration of small- to medium-sized lymphoid cells into the lamina propria (Figure E). Immunohistochemical analysis revealed that the lymphoid cells were positive for CD3, CD4, CD5, BCL-6, PD-1, ICOS, and CXCL-13 (Figure F–H) and negative for CD8, CD20, CD30, and EBER, which were matched as the IHC profile of nTFHL-AI. Based on these findings, the conjunctival lesion was diagnosed as an nTFHL-AI relapse. Cervical lymph node biopsy also confirmed nTFHL-AI relapse and identified clonal T-cell receptor-β gene rearrangement. The patient received salvage chemotherapy with ifosfamide, carboplatin, and etoposide, which proved ineffective. In contrast, the patient responded to involved-site radiation therapy of the right eye combined with tucidinostat, an oral histone deacetylase inhibitor.</p><p>Ocular adnexal lymphoma accounts for 1%–2% of all non-Hodgkin lymphomas, most of which are of the B-cell lineage [<span>1</span>]. Conjunctival T-cell lymphoma is rare, with conjunctival nTFHL-AI being extremely uncommon [<span>2, 3</span>]. Conjunctival lymphomas exhibit distinct ocular features by subtype and are particularly useful for diagnosing common B-cell lymphomas [<span>2</span>]. Conversely, ocular manifestations are often insufficiently described in T-cell lymphomas, which are rare subtypes of conjunctival lymphomas [<span>3-7</span>]. In a previously reported case of nTFHL-AI, the ocular findings comprised two pink, discrete, non-tender bulbar conjunctival masses [<span>3</span>]. In our case, in addition to a solid conjunctival mass, we observed chemosis, conjunctival hyperemia, eyelid redness and swelling, and diplopia. Our case presents a rare manifestation of ocular involvement of nTFHL-AI and provides insights into the differential diagnosis of a red eye, which includes both benign and serious conditions requiring ophthalmologic evaluation, including infections, rheumatologic disorders, thyroid diseases, sarcoidosis, orbital myositis, and, rarely, malignancies.</p><p>The authors have nothing to report.</p><p>The authors have nothing to report.</p><","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"7 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12834508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146069314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Madalena Correia Pires, Ana Costa e Castro, Filipa Marujo, Rita Valsassina, Joana Patena Forte, Joana de Pais de Faria
<p>A 5-year-old male with Trisomy 21, presented 7 days after varicella-zoster virus (VZV) infection with rapidly progressive purpura on the lower limbs and gluteal region (Figure 1A).</p><p>Labs showed thrombocytopenia (64,000/µL), elevated CRP (83.8 mg/L, NR < 5 mg/L), prolonged INR, unmeasurable fibrinogen, and markedly elevated D-dimers (> 150,000 ng/mL, NR < 500 ug/L). Clinical suspicion of disseminated intravascular coagulation (DIC) complicating purpura fulminans (PF) was considered. The patient received IVIG, fibrinogen concentrate, and fresh frozen plasma (FFP), but deteriorated with hypotension, anuria, and progression of skin lesions, requiring PICU admission.</p><p>Upon PICU admission, severe anemia (Hb 4 g/dL), persistent thrombocytopenia, low fibrinogen (1.2 g/L, NR 1.5–4 g/L), and protein S (< 7.3%, NR 74%–146%) were documented, with no apparent source of bleeding. Protein C and Antithrombin III levels were initially low, consistent with DIC and consumption coagulopathy, but normalized following plasmapheresis. Immunologic workup showed positive anticardiolipin IgG/IgM (76.5/36.8 UQ, NR < 20), and anti-β2-glycoprotein I IgG/IgM (660.1/66.3 UQ, NR < 20), with negativation at 12 weeks follow-up. VVZ PCR in blood was positive, while blood cultures and the remaining etiologic workup, including CMV and HHV-6 PCR, were negative. Treatment included IVIG (Days 1–7), plasmapheresis (Days 1–5), unfractionated heparin (Days 1–11, aPTT-adjusted), later switched to enoxaparin (until Day 42), FFP (Days 5–9 and every 48 h thereafter), and high-dose methylprednisolone with taper over 12 weeks. Protein S levels increased to 41% by PICU discharge on Day 13. Additional therapy included packed red blood cells and platelet transfusions, pain management, nutritional support, and antimicrobials for secondary infections. Complications included bacterial sepsis, fungemia, and iatrogenic adrenal insufficiency.</p><p>Extensive necrotic skin lesions evolved into full-thickness tissue loss requiring surgical debridement and skin grafting (Figure 1B,C). After 98 days, the patient was discharged, maintained on gabapentin for pain control and corticosteroid taper.</p><p>PF is a rare thrombotic disorder, typically associated with bacterial sepsis (e.g., pneumococcus, meningococcus, <i>Staphylococcus</i>) or congenital anticoagulant deficiencies. Post-infectious PF, especially following VZV infection, is increasingly recognized in children, and is believed to involve autoimmune mechanisms, with early descriptions demonstrating anti–protein S autoantibodies reducing protein S levels, with spontaneous recovery over weeks to months [<span>1, 2</span>].</p><p>More recent reports link post-viral PF with transient antiphospholipid antibodies, which do not appear to correlate with severity, but may exacerbate endothelial injury or coagulopathy in an already primed prothrombotic milieu [<span>3</span>].</p><p>This case was severe, requiring PICU admission
一名患有21三体的5岁男性，在感染水痘带状疱疹病毒（VZV） 7天后出现下肢和臀区迅速进行性紫癜（图1A）。实验室显示血小板减少（64,000/µL）， CRP升高（83.8 mg/L, NR < 5 mg/L）， INR延长，纤维蛋白原无法测量，d -二聚体明显升高（150,000 ng/mL, NR < 500 ug/L）。临床怀疑弥散性血管内凝血（DIC）合并暴发性紫癜（PF）。患者接受IVIG、纤维蛋白原浓缩物和新鲜冷冻血浆（FFP）治疗，但病情恶化，出现低血压、无尿和皮肤病变进展，需要入院PICU。在PICU入院时，记录了严重贫血（Hb 4 g/dL），持续性血小板减少，低纤维蛋白原（1.2 g/L, NR 1.5-4 g/L）和蛋白S (< 7.3%, NR 74%-146%)，无明显出血来源。蛋白C和抗凝血酶III水平最初较低，符合DIC和消耗性凝血功能障碍，但血浆置换后恢复正常。免疫检查显示抗心磷脂IgG/IgM阳性（76.5/36.8 UQ, NR < 20），抗β2-糖蛋白I IgG/IgM阳性（660.1/66.3 UQ, NR < 20），随访12周均为阴性。血液中VVZ PCR阳性，而血液培养和其他病原学检查（包括CMV和HHV-6 PCR）均为阴性。治疗包括IVIG（第1-7天），血浆置换（第1-5天），未分级肝素（第1-11天，aptt调整），随后切换到依诺肝素（直到第42天），FFP（第5-9天，此后每48小时）和大剂量甲基强的松龙，并在12周内逐渐减少。第13天PICU出院时，蛋白S水平升高至41%。其他治疗包括填充红细胞和血小板输注、疼痛管理、营养支持和抗菌素治疗继发感染。并发症包括细菌性败血症、真菌血症和医源性肾上腺功能不全。大面积坏死的皮肤病变演变为全层组织损失，需要手术清创和植皮（图1B，C）。98天后，患者出院，继续使用加巴喷丁控制疼痛并逐渐减少皮质类固醇的使用。PF是一种罕见的血栓性疾病，通常与细菌性败血症（如肺炎球菌、脑膜炎球菌、葡萄球菌）或先天性抗凝血缺乏有关。感染后PF，特别是在VZV感染后，越来越多地在儿童中被认识到，并且被认为与自身免疫机制有关，早期的描述显示抗蛋白S自身抗体降低蛋白S水平，在数周到数月的时间内自然恢复[1,2]。最近的报道将病毒后PF与短暂性抗磷脂抗体联系起来，这似乎与严重程度无关，但可能加剧内皮损伤或血栓形成前环境中的凝血功能障碍。该病例病情严重，由于DIC引起的失血性休克，需要入院PICU。患有21三体的儿童对免疫失调的易感性增加，在病毒感染后可能容易发生严重的内皮损伤或凝血功能障碍。蛋白质S缺乏的短暂性与文献中描述的获得性、非遗传性PF形式一致[5,6]。及时识别和处理——包括FFP、抗凝、免疫调节治疗，必要时进行血浆置换——对于限制血栓和坏死的进展至关重要[1,5,6]。包括血液学、传染病、重症监护和儿科外科在内的多学科方法对改善结果至关重要。准备并撰写手稿。所有其他作者审查了图像和手稿，并作出了重要的修订。作者没有什么可报告的。作者没有什么可报告的。临床细节和照片的公布已获得患者法定监护人的书面知情同意。作者声明无利益冲突。支持本研究结果的数据可向通讯作者索取。由于隐私或道德限制，这些数据不会公开。
{"title":"Post-Varicella Purpura Fulminans With Extensive Skin Necrosis in a Child","authors":"Madalena Correia Pires, Ana Costa e Castro, Filipa Marujo, Rita Valsassina, Joana Patena Forte, Joana de Pais de Faria","doi":"10.1002/jha2.70230","DOIUrl":"10.1002/jha2.70230","url":null,"abstract":"<p>A 5-year-old male with Trisomy 21, presented 7 days after varicella-zoster virus (VZV) infection with rapidly progressive purpura on the lower limbs and gluteal region (Figure 1A).</p><p>Labs showed thrombocytopenia (64,000/µL), elevated CRP (83.8 mg/L, NR < 5 mg/L), prolonged INR, unmeasurable fibrinogen, and markedly elevated D-dimers (> 150,000 ng/mL, NR < 500 ug/L). Clinical suspicion of disseminated intravascular coagulation (DIC) complicating purpura fulminans (PF) was considered. The patient received IVIG, fibrinogen concentrate, and fresh frozen plasma (FFP), but deteriorated with hypotension, anuria, and progression of skin lesions, requiring PICU admission.</p><p>Upon PICU admission, severe anemia (Hb 4 g/dL), persistent thrombocytopenia, low fibrinogen (1.2 g/L, NR 1.5–4 g/L), and protein S (< 7.3%, NR 74%–146%) were documented, with no apparent source of bleeding. Protein C and Antithrombin III levels were initially low, consistent with DIC and consumption coagulopathy, but normalized following plasmapheresis. Immunologic workup showed positive anticardiolipin IgG/IgM (76.5/36.8 UQ, NR < 20), and anti-β2-glycoprotein I IgG/IgM (660.1/66.3 UQ, NR < 20), with negativation at 12 weeks follow-up. VVZ PCR in blood was positive, while blood cultures and the remaining etiologic workup, including CMV and HHV-6 PCR, were negative. Treatment included IVIG (Days 1–7), plasmapheresis (Days 1–5), unfractionated heparin (Days 1–11, aPTT-adjusted), later switched to enoxaparin (until Day 42), FFP (Days 5–9 and every 48 h thereafter), and high-dose methylprednisolone with taper over 12 weeks. Protein S levels increased to 41% by PICU discharge on Day 13. Additional therapy included packed red blood cells and platelet transfusions, pain management, nutritional support, and antimicrobials for secondary infections. Complications included bacterial sepsis, fungemia, and iatrogenic adrenal insufficiency.</p><p>Extensive necrotic skin lesions evolved into full-thickness tissue loss requiring surgical debridement and skin grafting (Figure 1B,C). After 98 days, the patient was discharged, maintained on gabapentin for pain control and corticosteroid taper.</p><p>PF is a rare thrombotic disorder, typically associated with bacterial sepsis (e.g., pneumococcus, meningococcus, <i>Staphylococcus</i>) or congenital anticoagulant deficiencies. Post-infectious PF, especially following VZV infection, is increasingly recognized in children, and is believed to involve autoimmune mechanisms, with early descriptions demonstrating anti–protein S autoantibodies reducing protein S levels, with spontaneous recovery over weeks to months [<span>1, 2</span>].</p><p>More recent reports link post-viral PF with transient antiphospholipid antibodies, which do not appear to correlate with severity, but may exacerbate endothelial injury or coagulopathy in an already primed prothrombotic milieu [<span>3</span>].</p><p>This case was severe, requiring PICU admission ","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"7 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12834503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146069245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PICALM::MLLT10-positive T-ALL is rare and associated with poor prognosis. Lineage switch to AML is exceptionally uncommon, particularly after long-term remission.
Case Presentation
We report an adolescent PICALM::MLLT10-positive T-ALL with a cortical thymocyte, non-ETP phenotype. The patient achieved complete remission but relapsed as AML 6 years later. Cytogenetics revealed del(5q), del(17p), and 17q gain. Mutational profiling demonstrated mutations with LOH in NF1 and EZH2, a hemizygous SMC1A mutation, and a hemizygous PHF6 mutation detected only after subsequent therapy.
Conclusion
This case illustrates that therapy-resistant PICALM::MLLT10 progenitors can persist during remission and re-emerge as AML through lineage switch. The sequential acquisition of cooperating genetic lesions supports clonal evolution and highlights the need for molecular monitoring and novel therapeutic strategies.
Trial Registration
The authors have confirmed clinical trial registration is not needed for this submission.
{"title":"Clonal Evolution and Lineage Switch from T-Cell Acute Lymphoblastic Leukemia to Acute Myeloid Leukemia in Therapy-Resistant PICALM::MLLT10 Leukemia","authors":"Machiko Kawamura, Daichi Sadato, Masayuki Haruta, Nobuko Kubota, Yuka Harada, Takeshi Kobayashi, Noriko Doki, Fumio Kasai, Yu Nishimura, Hirofumi Kobayashi, Nobuo Maseki","doi":"10.1002/jha2.70217","DOIUrl":"10.1002/jha2.70217","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p><i>PICALM::MLLT10</i>-positive T-ALL is rare and associated with poor prognosis. Lineage switch to AML is exceptionally uncommon, particularly after long-term remission.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Case Presentation</h3>\u0000 \u0000 <p>We report an adolescent <i>PICALM::MLLT10</i>-positive T-ALL with a cortical thymocyte, non-ETP phenotype. The patient achieved complete remission but relapsed as AML 6 years later. Cytogenetics revealed del(5q), del(17p), and 17q gain. Mutational profiling demonstrated mutations with LOH in <i>NF1</i> and <i>EZH2</i>, a hemizygous <i>SMC1A</i> mutation, and a hemizygous <i>PHF6</i> mutation detected only after subsequent therapy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This case illustrates that therapy-resistant <i>PICALM::MLLT10</i> progenitors can persist during remission and re-emerge as AML through lineage switch. The sequential acquisition of cooperating genetic lesions supports clonal evolution and highlights the need for molecular monitoring and novel therapeutic strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>The authors have confirmed clinical trial registration is not needed for this submission.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"7 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146055156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carla Romagnoli, Alexandra Lyubimova, Leily Santos-Carrion, Ferial Alloush, Vathany Sriganeshan, Andrea Noboa, Jacqueline C. Barrientos
Hemophagocytic lymphohistiocytosis (HLH) is an immune disorder causing excessive inflammation and tissue damage. Lymphoma, especially T-cell lymphoma, is the most common cause of HLH, while Multiple Myeloma (MM) is rarely associated. We present a 61-year-old man with spiking fevers, fatigue, and unintentional weight loss. The HLH was driven by two distinct malignant clones in his bone marrow: plasma cell neoplasm and B-cell lymphoma. Patient failed initial therapy with steroids, anakinra, and chemotherapy. Tocilizumab use, on the other hand, led to an excellent clinical and laboratory response immediately. This is the first reported case of HLH associated with two hematological malignancies.
Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission
{"title":"Hemophagocytic Lymphohistiocytosis as First Manifestation of Dual B-Cell Neoplasms: A Case Report of Co-Existing Multiple Myeloma and B-Cell Lymphoma","authors":"Carla Romagnoli, Alexandra Lyubimova, Leily Santos-Carrion, Ferial Alloush, Vathany Sriganeshan, Andrea Noboa, Jacqueline C. Barrientos","doi":"10.1002/jha2.70210","DOIUrl":"10.1002/jha2.70210","url":null,"abstract":"<p>Hemophagocytic lymphohistiocytosis (HLH) is an immune disorder causing excessive inflammation and tissue damage. Lymphoma, especially T-cell lymphoma, is the most common cause of HLH, while Multiple Myeloma (MM) is rarely associated. We present a 61-year-old man with spiking fevers, fatigue, and unintentional weight loss. The HLH was driven by two distinct malignant clones in his bone marrow: plasma cell neoplasm and B-cell lymphoma. Patient failed initial therapy with steroids, anakinra, and chemotherapy. Tocilizumab use, on the other hand, led to an excellent clinical and laboratory response immediately. This is the first reported case of HLH associated with two hematological malignancies.</p><p><b>Trial Registration</b>: The authors have confirmed clinical trial registration is not needed for this submission</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"7 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146047528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Liya Ma, Yaojia Shen, Jie Chang, Shanshan Suo, Lu Wang, Weifang Zhu, Jianjun Qiao, Hongyan Tong
We report a 69-year-old man diagnosed as myelodysplastic syndrome and administrated with azacitidine and selinexor treatment. Then he was revealed high fever and multiple tender erythematous papules involving his mouth, back, upper and lower extremities, which were diagnosed as Sweet's syndrome by skin biopsy. He was administrated with adalimumab and his rashes gradually disappeared after adalimumab treatment. But he had secondary disseminated fungal infections. Finally, he died of heart failure and severe infection.
Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission
{"title":"Successful Treatment of Refractory Sweet's Syndrome With Adalimumab in a Myelodysplastic Syndrome Patient","authors":"Liya Ma, Yaojia Shen, Jie Chang, Shanshan Suo, Lu Wang, Weifang Zhu, Jianjun Qiao, Hongyan Tong","doi":"10.1002/jha2.70218","DOIUrl":"10.1002/jha2.70218","url":null,"abstract":"<p>We report a 69-year-old man diagnosed as myelodysplastic syndrome and administrated with azacitidine and selinexor treatment. Then he was revealed high fever and multiple tender erythematous papules involving his mouth, back, upper and lower extremities, which were diagnosed as Sweet's syndrome by skin biopsy. He was administrated with adalimumab and his rashes gradually disappeared after adalimumab treatment. But he had secondary disseminated fungal infections. Finally, he died of heart failure and severe infection.</p><p>Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"7 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12826987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146055268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Edwin U. Suárez, Teresa Arquero-Portero, Pilar Llamas-Sillero
Since the original description of VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome, several atypical manifestations of this unusual disease have been reported, providing further insight into the condition [1].
A 66-year-old male patient presented with multiple episodes of ear chondritis and panniculitis over the past 2 years (Figure 1: Panel A and B). Laboratory tests revealed mild macrocytic anemia, and biopsy of the skin lesions (Figure 1: Panel B) showed neutrophilic panniculitis. A bone marrow biopsy was performed, revealing dysplastic features in the myeloid and erythroid series. He was diagnosed with VEXAS syndrome (UBA1 [Met41Thr] mutation using the Sanger method). Concurrently, the presence of low-level biclonal IgG lambda and IgM lambda components, a low-proportion lymphoplasmacytic infiltrate as determined by flow cytometry, and mutated MYD88 was identified. In addition, in next-generation sequencing, DNMT3A mutated with a variant allele frequency of 28%, and normal cytogenetics was observed. The patient was diagnosed with Waldenström macroglobulinemia (smoldering) and low-risk myelodysplastic syndrome. He was treated with 5-azacitidine, and on Day 29 of the first cycle, he reported experiencing dysesthesia in the left hemilingual area, with no other notable findings on physical examination. A second cycle of 5-azacitidine was initiated, and on Day 3, the lingual symptoms persisted, accompanied by significant swelling of the left side of the tongue (Figure 1: Panel C). This condition improved after brief treatment with corticosteroids, and the patient had no further symptoms. He was re-administered 5-azacitidine until the cycle was completed, with no further angioedema observed. Conventional laboratory tests for angioedema revealed no discernible cause. Following the fourth cycle of hypomethylating therapy, the patient continues to show a clinical response, with an improvement in all symptoms and a disappearance of the UBA1 mutation in the bone marrow, as determined using the same technique.
A deliberative exchange with the medical community was deemed essential to establish a comprehensive understanding framework in the event of the emergence of additional cases involving this entity.
All authors participated in the preparation of every component of the article.
The authors have nothing to report.
Informed consent has been obtained. All authors had access to the data and a role in writing this manuscript.
The authors declare no conflicts of interest.
The data that support the findings of this study are available on request from the corresponding author.
{"title":"Hemi-Orolingual Angioedema in a Patient With VEXAS Syndrome","authors":"Edwin U. Suárez, Teresa Arquero-Portero, Pilar Llamas-Sillero","doi":"10.1002/jha2.70207","DOIUrl":"10.1002/jha2.70207","url":null,"abstract":"<p>Since the original description of VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome, several atypical manifestations of this unusual disease have been reported, providing further insight into the condition [<span>1</span>].</p><p>A 66-year-old male patient presented with multiple episodes of ear chondritis and panniculitis over the past 2 years (Figure 1: Panel A and B). Laboratory tests revealed mild macrocytic anemia, and biopsy of the skin lesions (Figure 1: Panel B) showed neutrophilic panniculitis. A bone marrow biopsy was performed, revealing dysplastic features in the myeloid and erythroid series. He was diagnosed with VEXAS syndrome (<i>UBA1</i> [Met41Thr] mutation using the Sanger method). Concurrently, the presence of low-level biclonal IgG lambda and IgM lambda components, a low-proportion lymphoplasmacytic infiltrate as determined by flow cytometry, and mutated <i>MYD88</i> was identified. In addition, in next-generation sequencing, <i>DNMT3A</i> mutated with a variant allele frequency of 28%, and normal cytogenetics was observed. The patient was diagnosed with Waldenström macroglobulinemia (smoldering) and low-risk myelodysplastic syndrome. He was treated with 5-azacitidine, and on Day 29 of the first cycle, he reported experiencing dysesthesia in the left hemilingual area, with no other notable findings on physical examination. A second cycle of 5-azacitidine was initiated, and on Day 3, the lingual symptoms persisted, accompanied by significant swelling of the left side of the tongue (Figure 1: Panel C). This condition improved after brief treatment with corticosteroids, and the patient had no further symptoms. He was re-administered 5-azacitidine until the cycle was completed, with no further angioedema observed. Conventional laboratory tests for angioedema revealed no discernible cause. Following the fourth cycle of hypomethylating therapy, the patient continues to show a clinical response, with an improvement in all symptoms and a disappearance of the <i>UBA1</i> mutation in the bone marrow, as determined using the same technique.</p><p>A deliberative exchange with the medical community was deemed essential to establish a comprehensive understanding framework in the event of the emergence of additional cases involving this entity.</p><p>All authors participated in the preparation of every component of the article.</p><p>The authors have nothing to report.</p><p>Informed consent has been obtained. All authors had access to the data and a role in writing this manuscript.</p><p>The authors declare no conflicts of interest.</p><p>The data that support the findings of this study are available on request from the corresponding author.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"7 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12822429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146031858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>A 58-year-old male presented with acute kidney injury and hypercalcaemia. The blood work showed haemoglobin 124 g/L, white blood cells 9.44 × 10<sup>9</sup>/L (neutrophil 2.99 × 10<sup>9</sup>/L, lymphocytes 3.35 × 10<sup>9</sup>/L) and platelets 79 × 10<sup>9</sup>/L. Corrected calcium 3.51 mmol/L (normal range 2.2–2.6 mmol/L), creatinine 308 µmol/L, LDH 383 IU/L (normal range 135–225 IU/L), β2-microglobulin 12.8 mg/L (normal range 0–2.3 mg/L). There was clear evidence of immunoparesis (IgA 0.21, IgG 3.64 and IgM 0.2 g/L), but paraprotein was undetectable by serum protein electrophoresis and immunofixation. Urine immunofixation was negative for monoclonal protein. Serum-free kappa chain level was normal, with a normal kappa/lambda light chain ratio. The blood film showed circulating plasma cells with plasmablast morphology (Figure 1A). By flow cytometry, these cells were negative for CD45, CD5, CD10, CD19, CD20, CD56, CD33, CD23, and immunoglobulin (Figure 1C). The bone marrow aspirate showed background staining and 90% plasma cells with atypical binucleated forms (Figure 1B). CD138-cell FISH showed a gain at 1q21 (69%), deletion of the <i>TP53</i> gene at 17p13 (10%), and no evidence of immunoglobulin rearrangement. Trephine biopsy showed 80%–90% plasma cells, which were positive for CD138, cyclin D1, MUM1, and negative for kappa and lambda staining (Figure 2). The PET/CT showed multifocal avid bone disease. He was diagnosed with non-secretory multiple myeloma (NSMM) (stage ISS 3, R-ISS 3), non-producing phenotype, and primary plasma cell leukaemia. He had a poor response to multiple lines of treatment (bortezomib/ cyclophosphamide/ lenalidomide/ dexamethasone (VCRD), VRD-PACE (cisplatin/ doxorubicin/ cyclophosphamide/ etoposide), melphalan autograft transplantation, carfilzomib/ lenalidomide/ dexamethasone (KRD), isatuximab/ pomalidomide/ dexamethasone and teclistamab) and sadly passed away within 3 years of diagnosis.</p><p>NSMM is a rare subtype of myeloma accounting for 1%–3% of all myeloma cases, in which there is no detectable monoclonal protein secretion by neoplastic plasma cells [<span>1</span>]. Non-secretors can produce but have defects in secreting immunoglobulins. Non-producers are unable to synthesize immunoglobulins, and no light-chain-restricted plasma cells are detectable by immunohistochemistry, flow cytometry, or in situ hybridization. It is a challenge to detect disease early at the asymptomatic (smouldering myeloma) or MGUS stage. Whole-body functional imaging (PET/CT, MRI) is essential in identifying myeloma-defining lesions, risk stratification and assessing treatment response by monitoring the reduction in metabolic activity or changes in diffusion properties. B-cell maturation antigen (BCMA) is highly expressed on plasma cells. Soluble BCMA, a blood marker, correlates strongly with the total amount of bone marrow plasma cells [<span>2</span>]. The novel soluble BCMA assay could be an essential tool for monitoring tre
{"title":"Non-Secretory Myeloma With Non-Producing Phenotype Presented as Plasma Cell Leukaemia With Plasmablast Morphology","authors":"Ke Xu, Ian Proctor","doi":"10.1002/jha2.70224","DOIUrl":"10.1002/jha2.70224","url":null,"abstract":"<p>A 58-year-old male presented with acute kidney injury and hypercalcaemia. The blood work showed haemoglobin 124 g/L, white blood cells 9.44 × 10<sup>9</sup>/L (neutrophil 2.99 × 10<sup>9</sup>/L, lymphocytes 3.35 × 10<sup>9</sup>/L) and platelets 79 × 10<sup>9</sup>/L. Corrected calcium 3.51 mmol/L (normal range 2.2–2.6 mmol/L), creatinine 308 µmol/L, LDH 383 IU/L (normal range 135–225 IU/L), β2-microglobulin 12.8 mg/L (normal range 0–2.3 mg/L). There was clear evidence of immunoparesis (IgA 0.21, IgG 3.64 and IgM 0.2 g/L), but paraprotein was undetectable by serum protein electrophoresis and immunofixation. Urine immunofixation was negative for monoclonal protein. Serum-free kappa chain level was normal, with a normal kappa/lambda light chain ratio. The blood film showed circulating plasma cells with plasmablast morphology (Figure 1A). By flow cytometry, these cells were negative for CD45, CD5, CD10, CD19, CD20, CD56, CD33, CD23, and immunoglobulin (Figure 1C). The bone marrow aspirate showed background staining and 90% plasma cells with atypical binucleated forms (Figure 1B). CD138-cell FISH showed a gain at 1q21 (69%), deletion of the <i>TP53</i> gene at 17p13 (10%), and no evidence of immunoglobulin rearrangement. Trephine biopsy showed 80%–90% plasma cells, which were positive for CD138, cyclin D1, MUM1, and negative for kappa and lambda staining (Figure 2). The PET/CT showed multifocal avid bone disease. He was diagnosed with non-secretory multiple myeloma (NSMM) (stage ISS 3, R-ISS 3), non-producing phenotype, and primary plasma cell leukaemia. He had a poor response to multiple lines of treatment (bortezomib/ cyclophosphamide/ lenalidomide/ dexamethasone (VCRD), VRD-PACE (cisplatin/ doxorubicin/ cyclophosphamide/ etoposide), melphalan autograft transplantation, carfilzomib/ lenalidomide/ dexamethasone (KRD), isatuximab/ pomalidomide/ dexamethasone and teclistamab) and sadly passed away within 3 years of diagnosis.</p><p>NSMM is a rare subtype of myeloma accounting for 1%–3% of all myeloma cases, in which there is no detectable monoclonal protein secretion by neoplastic plasma cells [<span>1</span>]. Non-secretors can produce but have defects in secreting immunoglobulins. Non-producers are unable to synthesize immunoglobulins, and no light-chain-restricted plasma cells are detectable by immunohistochemistry, flow cytometry, or in situ hybridization. It is a challenge to detect disease early at the asymptomatic (smouldering myeloma) or MGUS stage. Whole-body functional imaging (PET/CT, MRI) is essential in identifying myeloma-defining lesions, risk stratification and assessing treatment response by monitoring the reduction in metabolic activity or changes in diffusion properties. B-cell maturation antigen (BCMA) is highly expressed on plasma cells. Soluble BCMA, a blood marker, correlates strongly with the total amount of bone marrow plasma cells [<span>2</span>]. The novel soluble BCMA assay could be an essential tool for monitoring tre","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"7 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12817461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>A 57-year-old female with a reported history of isolated neutropenia presented with 3 years of progressive bilateral vision loss and 4 months of a rapidly growing plaque on her left eyelid (Figure 1A). MRI of the orbits revealed a 1.4 cm left superomedial preseptal mass with retroseptal extension (Figure 1B). On pathological analysis after left anterior orbitotomy, biopsy samples demonstrated subepithelial histiocytic inflammation with band-like zones of necrobiosis comprised of xanthic epithelioid histiocytes, including multinucleated giant cells. Such histological features resembled those conveyed in Figures 3 and 5 of the report published by Wood et al. [<span>1</span>] and were consistent with necrobiotic xanthogranuloma (NXG). NXG is a rare and chronic type of non-Langerhans cell histiocytosis commonly associated with paraproteinemia in up to 80% of patients, representing monoclonal gammopathy of clinical significance [<span>2</span>]. Figure 1</p><p>Laboratory evaluation was notable for an IgG lambda M-spike. Bone marrow biopsy revealed a lambda-restricted plasma cell population. Imaging and biopsies of her liver and left lower extremity skin lesions confirmed further involvement of NXG (Figure 1C). The patient went on to receive numerous treatment regimens, including oral steroids (a 5-week taper of prednisone 60 mg), IVIG (4 monthly treatments), rituximab (4 weekly treatments), and orbital radiation (24 gray/12 fractions). None of these therapies induced a clinical response, and so plasma cell-directed therapy was attempted.</p><p>She subsequently received monthly cycles of daratumumab (1800 mg monthly), lenalidomide (25 mg Days 1–21), and dexamethasone (20 mg weekly that was then tapered) (DRd). After 10 months of DRd/DR therapy, the patient's M-spike has decreased, her cutaneous lesions have improved, and no focal orbital masses were identified on repeat MRI (Figure 1D). To our knowledge, this is the first reported response of NXG to a daratumumab-containing regimen. As the granulomatous pathophysiology of NXG may be driven by the presence of a concurrent monoclonal paraprotein, plasma cell-directed therapies should be considered in cases refractory to conventional treatment options like alkylating agents, steroids, or IVIG [<span>3</span>].</p><p>A.T., A.-R.J., and A.G. all cared for the patient and assisted with data collection. A.T. wrote the manuscript and prepared the images. A.-R.J. and A.G. reviewed the manuscript.</p><p>The authors have nothing to report.</p><p>The authors declare no conflicts of interest.</p><p>This case report was conducted in accordance with the Declaration of Helsinki. The collection and evaluation of all protected health information was performed in a Health Insurance Portability and Accountability Act (HIPAA)-compliant manner.</p><p>Written informed consent was obtained from the patient, including permission for publication of images.</p><p>The data that support the findings of this study are available
{"title":"Refractory Periorbital Necrobiotic Xanthogranuloma Treated With Plasma Cell-Directed Therapy","authors":"Aaron Trando, Ah-Reum Jeong, Aaron M. Goodman","doi":"10.1002/jha2.70223","DOIUrl":"https://doi.org/10.1002/jha2.70223","url":null,"abstract":"<p>A 57-year-old female with a reported history of isolated neutropenia presented with 3 years of progressive bilateral vision loss and 4 months of a rapidly growing plaque on her left eyelid (Figure 1A). MRI of the orbits revealed a 1.4 cm left superomedial preseptal mass with retroseptal extension (Figure 1B). On pathological analysis after left anterior orbitotomy, biopsy samples demonstrated subepithelial histiocytic inflammation with band-like zones of necrobiosis comprised of xanthic epithelioid histiocytes, including multinucleated giant cells. Such histological features resembled those conveyed in Figures 3 and 5 of the report published by Wood et al. [<span>1</span>] and were consistent with necrobiotic xanthogranuloma (NXG). NXG is a rare and chronic type of non-Langerhans cell histiocytosis commonly associated with paraproteinemia in up to 80% of patients, representing monoclonal gammopathy of clinical significance [<span>2</span>]. Figure 1</p><p>Laboratory evaluation was notable for an IgG lambda M-spike. Bone marrow biopsy revealed a lambda-restricted plasma cell population. Imaging and biopsies of her liver and left lower extremity skin lesions confirmed further involvement of NXG (Figure 1C). The patient went on to receive numerous treatment regimens, including oral steroids (a 5-week taper of prednisone 60 mg), IVIG (4 monthly treatments), rituximab (4 weekly treatments), and orbital radiation (24 gray/12 fractions). None of these therapies induced a clinical response, and so plasma cell-directed therapy was attempted.</p><p>She subsequently received monthly cycles of daratumumab (1800 mg monthly), lenalidomide (25 mg Days 1–21), and dexamethasone (20 mg weekly that was then tapered) (DRd). After 10 months of DRd/DR therapy, the patient's M-spike has decreased, her cutaneous lesions have improved, and no focal orbital masses were identified on repeat MRI (Figure 1D). To our knowledge, this is the first reported response of NXG to a daratumumab-containing regimen. As the granulomatous pathophysiology of NXG may be driven by the presence of a concurrent monoclonal paraprotein, plasma cell-directed therapies should be considered in cases refractory to conventional treatment options like alkylating agents, steroids, or IVIG [<span>3</span>].</p><p>A.T., A.-R.J., and A.G. all cared for the patient and assisted with data collection. A.T. wrote the manuscript and prepared the images. A.-R.J. and A.G. reviewed the manuscript.</p><p>The authors have nothing to report.</p><p>The authors declare no conflicts of interest.</p><p>This case report was conducted in accordance with the Declaration of Helsinki. The collection and evaluation of all protected health information was performed in a Health Insurance Portability and Accountability Act (HIPAA)-compliant manner.</p><p>Written informed consent was obtained from the patient, including permission for publication of images.</p><p>The data that support the findings of this study are available ","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"7 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70223","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146007840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rosa María González Arreola, María Teresa Magaña Torres, Ma. Guadalupe Domínguez Quezada, Janet Margarita Soto Padilla, José Luis Toro Castro, Beatriz Kazuko De la Herrán Arita, Alicia Gutiérrez Méndez, Hugo Antonio Romo Rubio, Juan Ramón González García
Introduction
In Mexico, the 5-year overall survival (OS) rate for pediatric acute lymphoblastic leukemia (ALL) ranges from 45% to 85%, markedly lower than the ∼90% reported in high-income countries, where cytogenomic testing is essential for accurate risk stratification and therapeutic decision-making. The few available data for Mexican cohorts derive from studies conducted in Mexico City using conventional karyotyping, DNA index analysis, and RT-PCR targeting only four gene fusions. Broader cytogenomic characterization is needed to identify additional prognostic alterations.
Methods
We analyzed 170 pediatric ALL cases (150 B-Cell lineage, 10 T-Cell lineage, and 10 mixed phenotype) using fluorescence in situ hybridization (FISH) with a panel of 11 probe sets targeting recurrent cytogenomic abnormalities. All patients were treated according to the Total XV protocol.
Results
Among 150 B-Cell ALL cases, recurrent cytogenomic abnormalities included ETV6::RUNX1 (n = 19), TCF3::PBX1 (n = 7), BCR::ABL1 (n = 5), KMT2A::V (n = 10), IGH::V (n = 7), V::CRLF2 (n = 11), iAMP21 (n = 8), and deletions involving CDKN2A/B (n = 38), TP53 (n = 7), RB1 (8), ATM (n = 1), and ETV6 (n = 15). Hypodiploidy (n = 2), high-hyperdiploidy (n = 38), low-hyperdiploidy (n = 16), and 1q gain (n = 14) were also identified.
Conclusions
Our findings reveal a cytogenomic landscape characterized by a predominance of high-risk abnormalities such as iAMP21 and KMT2A::V, together with a lower frequency of low-risk alterations like ETV6::RUNX1. The frequent coexistence of secondary abnormalities further supports the relevance of comprehensive cytogenomic profiling for accurate risk assessment. The high diagnostic coverage and rapid turnaround of the FISH-based approach underscore its value as a reliable and efficient diagnostic tool in newly diagnosed ALL.
Trial Registration
The authors have confirmed clinical trial registration is not needed for this submission
{"title":"Cytogenomic Abnormalities in Children With Acute Lymphoblastic Leukemia From Western Mexico: A Single-Center Fluorescence In Situ Hybridization-Based Study","authors":"Rosa María González Arreola, María Teresa Magaña Torres, Ma. Guadalupe Domínguez Quezada, Janet Margarita Soto Padilla, José Luis Toro Castro, Beatriz Kazuko De la Herrán Arita, Alicia Gutiérrez Méndez, Hugo Antonio Romo Rubio, Juan Ramón González García","doi":"10.1002/jha2.70220","DOIUrl":"10.1002/jha2.70220","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>In Mexico, the 5-year overall survival (OS) rate for pediatric acute lymphoblastic leukemia (ALL) ranges from 45% to 85%, markedly lower than the ∼90% reported in high-income countries, where cytogenomic testing is essential for accurate risk stratification and therapeutic decision-making. The few available data for Mexican cohorts derive from studies conducted in Mexico City using conventional karyotyping, DNA index analysis, and RT-PCR targeting only four gene fusions. Broader cytogenomic characterization is needed to identify additional prognostic alterations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analyzed 170 pediatric ALL cases (150 B-Cell lineage, 10 T-Cell lineage, and 10 mixed phenotype) using fluorescence in situ hybridization (FISH) with a panel of 11 probe sets targeting recurrent cytogenomic abnormalities. All patients were treated according to the Total XV protocol.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among 150 B-Cell ALL cases, recurrent cytogenomic abnormalities included ETV6<i>::RUNX1</i> (<i>n</i> = 19), <i>TCF3::PBX1</i> (<i>n</i> = 7), <i>BCR::ABL1</i> (<i>n</i> = 5), <i>KMT2A</i>::V (<i>n</i> = 10), <i>IGH</i>::V (<i>n</i> = 7), V::<i>CRLF2</i> (<i>n</i> = 11), iAMP21 (<i>n</i> = 8), and deletions involving <i>CDKN2A/B</i> (<i>n</i> = 38), <i>TP53</i> (<i>n</i> = 7), <i>RB1</i> (8), <i>ATM</i> (<i>n</i> = 1), and <i>ETV6</i> (<i>n</i> = 15). Hypodiploidy (<i>n</i> = 2), high-hyperdiploidy (<i>n</i> = 38), low-hyperdiploidy (<i>n</i> = 16), and 1q gain (<i>n</i> = 14) were also identified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings reveal a cytogenomic landscape characterized by a predominance of high-risk abnormalities such as iAMP21 and <i>KMT2A</i>::V, together with a lower frequency of low-risk alterations like <i>ETV6::RUNX1</i>. The frequent coexistence of secondary abnormalities further supports the relevance of comprehensive cytogenomic profiling for accurate risk assessment. The high diagnostic coverage and rapid turnaround of the FISH-based approach underscore its value as a reliable and efficient diagnostic tool in newly diagnosed ALL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>The authors have confirmed clinical trial registration is not needed for this submission</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"7 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12814622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146013444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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