Evangeline Y. Wong, Cameron Wellard, Jun Yen Ng, Eliza Chung, Zoe K. McQuilten, Stephen Opat, Erica M. Wood, Dipti Talaulikar
Introduction
Lymphoma is a common malignancy among adolescents and young adults (AYAs) which is generally defined as 15–39 years. Relative to other age groups, lymphoma in AYAs remains understudied with heterogeneous treatment options.
Methods
We performed a retrospective review of patients aged 18–60 years in the Australasian Lymphoma and Related Diseases Registry (LaRDR) with new diagnoses of the common subtypes of lymphoma in AYAs between January 2016 and April 2023. The subtypes are classic Hodgkin lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL) and Burkitt lymphoma (BL). Patient demographics, disease characteristics, treatment and outcome data were collected, and comparisons were made between AYAs (18–39 years) and older adults (OAs) (aged 40–60).
Results
AYAs had higher rates of cHL and PMBCL whereas OAs presented more frequently with DLBCL. AYAs with cHL and PMBCL had higher rates of early-stage and low-risk disease than OAs. In contrast, both AYAs and OAs were more likely to present with advanced-stage DLBCL and BL. AYAs with cHL were more likely to be treated with BEACOPP as compared to OAs who were more commonly treated with ABVD. There was no significant difference in treatment regimens for DLBCL, PMBCL or BL between AYAs and OAs. AYAs with cHL had better overall survival (OS) compared to OAs; specifically, cHL AYAs had better OS and DLBCL AYAs had better progression-free survival (PFS) and OS compared to OAs.
Conclusion
The study provides valuable data on patient and disease characteristics, treatments used and outcomes in AYA compared to OA aged 40–60 years. Registry data such as from LaRDR can help improve treatment standardisation and AYA patient outcomes.
Trial Registration
The authors have confirmed clinical trial registration is not needed for this submission
{"title":"Real-World Data on Lymphoma in Adolescents and Young Adults (AYA)—Report From the Lymphoma and Related Diseases Registry (LaRDR)","authors":"Evangeline Y. Wong, Cameron Wellard, Jun Yen Ng, Eliza Chung, Zoe K. McQuilten, Stephen Opat, Erica M. Wood, Dipti Talaulikar","doi":"10.1002/jha2.1096","DOIUrl":"10.1002/jha2.1096","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Lymphoma is a common malignancy among adolescents and young adults (AYAs) which is generally defined as 15–39 years. Relative to other age groups, lymphoma in AYAs remains understudied with heterogeneous treatment options.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed a retrospective review of patients aged 18–60 years in the Australasian Lymphoma and Related Diseases Registry (LaRDR) with new diagnoses of the common subtypes of lymphoma in AYAs between January 2016 and April 2023. The subtypes are classic Hodgkin lymphoma (cHL), diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL) and Burkitt lymphoma (BL). Patient demographics, disease characteristics, treatment and outcome data were collected, and comparisons were made between AYAs (18–39 years) and older adults (OAs) (aged 40–60).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>AYAs had higher rates of cHL and PMBCL whereas OAs presented more frequently with DLBCL. AYAs with cHL and PMBCL had higher rates of early-stage and low-risk disease than OAs. In contrast, both AYAs and OAs were more likely to present with advanced-stage DLBCL and BL. AYAs with cHL were more likely to be treated with BEACOPP as compared to OAs who were more commonly treated with ABVD. There was no significant difference in treatment regimens for DLBCL, PMBCL or BL between AYAs and OAs. AYAs with cHL had better overall survival (OS) compared to OAs; specifically, cHL AYAs had better OS and DLBCL AYAs had better progression-free survival (PFS) and OS compared to OAs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The study provides valuable data on patient and disease characteristics, treatments used and outcomes in AYA compared to OA aged 40–60 years. Registry data such as from LaRDR can help improve treatment standardisation and AYA patient outcomes.</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":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070036","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}
Adults with relapsed or refractory Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukaemia (R/R Ph+ BCP-ALL) have a dismal outcome. Blinatumomab as a single agent has shown activity in R/R Ph- BCP-ALL, and second or third-generation tyrosine kinase inhibitors (TKIs) can produce high remission rates in Ph+ leukaemias. We aimed to assess the activity of blinatumomab and TKI in combination with intensive chemotherapy in the relapsed or refractory setting.
Methods
Ten patients with R/R Ph+ BCP-ALL were treated with the combination of a modified hyper-CVAD (mHCVAD) regimen (cyclophosphamide, vincristine, adriamycin, dexamethasone), blinatumomab and TKI (mainly ponatinib).
Results
Complete remission (CR) was achieved in 10/10 patients, with deep molecular responses, and 6/10 were alive in remission after a median follow-up of 19.4 months. Three major cardiovascular events were noted.
Conclusion
These preliminary data, suggest that the mHCVAD-blinatumomab-TKI (mainly ponatinib) regimen may achieve a high rate of CR with undetectable measurable residual disease in adults with R/R Ph+ BCP-ALL and could be proposed to such patients, but cardiovascular or infectious complications should be warning, especially in older or frail patients.
{"title":"Relapsed Philadelphia chromosome-positive B-cell acute lymphoblastic leukaemia responds well to a combination of modified hyper-CVAD, blinatumomab and tyrosine kinase inhibitor","authors":"Gaétan Basile, Jean Galtier, Titouan Cazaubiel, Edouard Forcade, Emilie Klein, Audrey Bidet, Carmen Botella-Garcia, Clémence Mediavilla, Laurence Clement, Pierre-Yves Dumas, Arnaud Pigneux, Thibaut Leguay","doi":"10.1002/jha2.1064","DOIUrl":"10.1002/jha2.1064","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Adults with relapsed or refractory Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukaemia (R/R Ph+ BCP-ALL) have a dismal outcome. Blinatumomab as a single agent has shown activity in R/R Ph- BCP-ALL, and second or third-generation tyrosine kinase inhibitors (TKIs) can produce high remission rates in Ph+ leukaemias. We aimed to assess the activity of blinatumomab and TKI in combination with intensive chemotherapy in the relapsed or refractory setting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Ten patients with R/R Ph+ BCP-ALL were treated with the combination of a modified hyper-CVAD (mHCVAD) regimen (cyclophosphamide, vincristine, adriamycin, dexamethasone), blinatumomab and TKI (mainly ponatinib).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Complete remission (CR) was achieved in 10/10 patients, with deep molecular responses, and 6/10 were alive in remission after a median follow-up of 19.4 months. Three major cardiovascular events were noted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These preliminary data, suggest that the mHCVAD-blinatumomab-TKI (mainly ponatinib) regimen may achieve a high rate of CR with undetectable measurable residual disease in adults with R/R Ph+ BCP-ALL and could be proposed to such patients, but cardiovascular or infectious complications should be warning, especially in older or frail patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061505","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}
Xiaoxian Zhao, Deepa Jagadeesh, Juraj Bodo, Lisa Durkin, Daniel J. Lindner, Sarah L. Ondrejka, Eric D. Hsi
Introduction
Angioimmunoblastic T-cell lymphoma (AITL) is a rare and aggressive lymphoma with a poor prognosis. AITL is associated with Epstein–Barr virus (EBV)-positive B cells in most cases, suggesting a possible role for the virus in the pathobiology of AITL. Cell lines from AITL patients do not exist and models of human AITL are needed. We aim to establish such a model and use it for preclinical therapeutic evaluation.
Methods
Primary lymph node tissue from an AITL patient was used for tumor cell isolation and injection to NSG mice. The established patient-derived xenograft (PDX) model was characterized by immunophenotyping, whole-exome sequencing (WES), and T/B-cell receptor gene rearrangement studies. In vivo AITL PDX trials were performed with elotuzumab, romidepsin, and rituximab.
Results
An AITL PDX mouse model that includes a coexisting EBV+ B-cell proliferation was established. We confirmed clonal identity of the engrafted T cells with the primary T-lymphoma cells. WES on DNA from xenografted sorted T and B cells identified eight and three mutations previously reported in the COSMIC database, respectively. Primary tumor cells could be passaged serially in NSG mice with an increasing percentage of monoclonal B cells that mimic the human condition in which the clonal B-cell component in some cases may mask an underling T-cell lymphoma. In this PDX mouse study, single agent elotuzumab or rituximab significantly improved mice survival. Survival was further improved when elotuzumab or romidepsin was combined with rituximab.
Conclusion
To our knowledge, this is the first molecular characterization of AITL model coexisting with associated EBV+ B cells, and use of such a PDX model for therapeutic evaluation of agents targeting both malignant T cells and B cells simultaneously.
{"title":"Angioimmunoblastic T-cell lymphoma: Characterization of clonal T and B cells and a patient-derived xenograft study of coexisting T- and B-cell proliferation","authors":"Xiaoxian Zhao, Deepa Jagadeesh, Juraj Bodo, Lisa Durkin, Daniel J. Lindner, Sarah L. Ondrejka, Eric D. Hsi","doi":"10.1002/jha2.1080","DOIUrl":"10.1002/jha2.1080","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Angioimmunoblastic T-cell lymphoma (AITL) is a rare and aggressive lymphoma with a poor prognosis. AITL is associated with Epstein–Barr virus (EBV)-positive B cells in most cases, suggesting a possible role for the virus in the pathobiology of AITL. Cell lines from AITL patients do not exist and models of human AITL are needed. We aim to establish such a model and use it for preclinical therapeutic evaluation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Primary lymph node tissue from an AITL patient was used for tumor cell isolation and injection to NSG mice. The established patient-derived xenograft (PDX) model was characterized by immunophenotyping, whole-exome sequencing (WES), and T/B-cell receptor gene rearrangement studies. In vivo AITL PDX trials were performed with elotuzumab, romidepsin, and rituximab.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>An AITL PDX mouse model that includes a coexisting EBV+ B-cell proliferation was established. We confirmed clonal identity of the engrafted T cells with the primary T-lymphoma cells. WES on DNA from xenografted sorted T and B cells identified eight and three mutations previously reported in the COSMIC database, respectively. Primary tumor cells could be passaged serially in NSG mice with an increasing percentage of monoclonal B cells that mimic the human condition in which the clonal B-cell component in some cases may mask an underling T-cell lymphoma. In this PDX mouse study, single agent elotuzumab or rituximab significantly improved mice survival. Survival was further improved when elotuzumab or romidepsin was combined with rituximab.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>To our knowledge, this is the first molecular characterization of AITL model coexisting with associated EBV+ B cells, and use of such a PDX model for therapeutic evaluation of agents targeting both malignant T cells and B cells simultaneously.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061575","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}
Shannon Ugarte, Talia Gebhard, David R. Cornblath, Steven S. Scherer, Daria V. Babushok
Intravenous immunoglobulin (IVIG) is an immunomodulatory therapy derived from pooled donor immunoglobulins and used for treatment of various autoimmune conditions. Here we report the diagnosis and management of IVIG-induced chronic severe neutropenia with absolute neutrophil count <0.5×103/µL in a patient with multifocal motor neuropathy. Serial blood count showed a cyclical pattern of neutropenia: worsening 24–48 h post-IVIG, then gradually improving before the next infusion. IVIG-induced neutropenia is rare, with previous reports of predominantly mild transient neutropenia. Our case describes chronic severe neutropenia that developed years after starting IVIG. We summarize available evidence and management strategies for IVIG-associated neutropenia.
{"title":"Chronic Severe Neutropenia Associated With Intravenous Immunoglobulin for Multifocal Motor Neuropathy","authors":"Shannon Ugarte, Talia Gebhard, David R. Cornblath, Steven S. Scherer, Daria V. Babushok","doi":"10.1002/jha2.1102","DOIUrl":"10.1002/jha2.1102","url":null,"abstract":"<p>Intravenous immunoglobulin (IVIG) is an immunomodulatory therapy derived from pooled donor immunoglobulins and used for treatment of various autoimmune conditions. Here we report the diagnosis and management of IVIG-induced chronic severe neutropenia with absolute neutrophil count <0.5×10<sup>3</sup>/µL in a patient with multifocal motor neuropathy. Serial blood count showed a cyclical pattern of neutropenia: worsening 24–48 h post-IVIG, then gradually improving before the next infusion. IVIG-induced neutropenia is rare, with previous reports of predominantly mild transient neutropenia. Our case describes chronic severe neutropenia that developed years after starting IVIG. We summarize available evidence and management strategies for IVIG-associated neutropenia.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11771351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054436","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}
Hem Prajapati, Yash M. Patel, Ajay C. Parmar, Sahaj Y. Patel, Tasin Mohammedyakub Shaikhjiwala
A previously healthy 30-year-old woman experienced worsening back pain, fatigue, weakness, loss of appetite, and facial puffiness. After 18 months of these symptoms, she was diagnosed with multiple myeloma, which was also damaging her kidneys. The treatment involved a combination of medications and blood transfusions, leading to improved kidney function. Despite the challenges of managing her condition as a mother of young children, she remains hopeful. This case emphasizes the need for awareness of multiple myeloma in younger patients and the importance of early diagnosis and multidisciplinary care for managing this chronic illness.
Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission
{"title":"A Complex Presentation of Multiple Myeloma With Renal Complications in a Young Female: Diagnostic Challenges and Treatment Approach","authors":"Hem Prajapati, Yash M. Patel, Ajay C. Parmar, Sahaj Y. Patel, Tasin Mohammedyakub Shaikhjiwala","doi":"10.1002/jha2.1093","DOIUrl":"10.1002/jha2.1093","url":null,"abstract":"<p>A previously healthy 30-year-old woman experienced worsening back pain, fatigue, weakness, loss of appetite, and facial puffiness. After 18 months of these symptoms, she was diagnosed with multiple myeloma, which was also damaging her kidneys. The treatment involved a combination of medications and blood transfusions, leading to improved kidney function. Despite the challenges of managing her condition as a mother of young children, she remains hopeful. This case emphasizes the need for awareness of multiple myeloma in younger patients and the importance of early diagnosis and multidisciplinary care for managing this chronic illness.</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":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048771","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}
Vahid Pazhakh, Lucy C. Fox, Nicole Den Elzen, Matthew R. Emerson, Scott B. Cohen, Tracy M. Bryan, Kevin Norris, Duncan M. Baird, Tara Cochrane, John Mackintosh, Ashleigh Scott, Piers Blombery
Telomere biology disorders (TBDs) are inherited conditions associated with multisystem manifestations. We describe clinical and functional characterisation of a novel TERT variant. Whole-genome sequencing was performed along with single telomere length analysis (STELA). Telomerase activity and processivity were assessed. A novel TERT variant (K710R) was detected in a patient with classic TBD features showing reduced telomerase activity and processivity. Despite clinical and functional evidence, the variant was classified as a variant of uncertain significance. We have described a novel TERT variant and highlighted the need for further refinement of variant classification specific for TBDs.
{"title":"A novel TERT variant associated with a telomere biology disorder and challenges in variant classification","authors":"Vahid Pazhakh, Lucy C. Fox, Nicole Den Elzen, Matthew R. Emerson, Scott B. Cohen, Tracy M. Bryan, Kevin Norris, Duncan M. Baird, Tara Cochrane, John Mackintosh, Ashleigh Scott, Piers Blombery","doi":"10.1002/jha2.1066","DOIUrl":"10.1002/jha2.1066","url":null,"abstract":"<p>Telomere biology disorders (TBDs) are inherited conditions associated with multisystem manifestations. We describe clinical and functional characterisation of a novel TERT variant. Whole-genome sequencing was performed along with single <i>telomere</i> length analysis (<i>STELA</i>). Telomerase activity and processivity were assessed. A novel TERT variant (K710R) was detected in a patient with classic TBD features showing reduced telomerase activity and processivity. Despite clinical and functional evidence, the variant was classified as a variant of uncertain significance. We have described a novel TERT variant and highlighted the need for further refinement of variant classification specific for TBDs.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048778","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}
Tobias S. Slørdahl, Frida Bugge Askeland, Margrete Sofie Sætre Hanssen, Håkon Hov, Stine Marie Sundt-Hansen, Sofia Lindahl, Nils Tore Vethe, Henrik Hjorth-Hansen, Mona H. Fenstad, Anders Waage, Øyvind Hjertner, Fredrik Schjesvold, Anders Sundan
Multiple myeloma is characterized by malignant cells which produce high amounts of monoclonal immunoglobulin. Myeloma cells are, therefore, dependent on effective protein degradation. Proteasomal protein degradation is targeted by proteasome inhibitors in routine care. Autophagic protein degradation is currently not targeted in myeloma treatment. This Phase I trial showed that the combination of the proteasome inhibitor carfilzomib and the autophagy inhibitor hydroxychloroquine was well tolerated in patients with relapsed/refractory multiple myeloma. Adverse events were mostly Grades 1 and 2. An overall response rate of 44% indicates a meaningful clinical efficacy of this combination.
Trial Registration: The study was registered at clinicaltrials.gov # NCT04163107.
{"title":"Combined Proteasome and Autophagy Inhibition in Relapsed/Refractory Multiple Myeloma—A Phase I Trial of Hydroxychloroquine, Carfilzomib, and Dexamethasone","authors":"Tobias S. Slørdahl, Frida Bugge Askeland, Margrete Sofie Sætre Hanssen, Håkon Hov, Stine Marie Sundt-Hansen, Sofia Lindahl, Nils Tore Vethe, Henrik Hjorth-Hansen, Mona H. Fenstad, Anders Waage, Øyvind Hjertner, Fredrik Schjesvold, Anders Sundan","doi":"10.1002/jha2.1091","DOIUrl":"10.1002/jha2.1091","url":null,"abstract":"<p>Multiple myeloma is characterized by malignant cells which produce high amounts of monoclonal immunoglobulin. Myeloma cells are, therefore, dependent on effective protein degradation. Proteasomal protein degradation is targeted by proteasome inhibitors in routine care. Autophagic protein degradation is currently not targeted in myeloma treatment. This Phase I trial showed that the combination of the proteasome inhibitor carfilzomib and the autophagy inhibitor hydroxychloroquine was well tolerated in patients with relapsed/refractory multiple myeloma. Adverse events were mostly Grades 1 and 2. An overall response rate of 44% indicates a meaningful clinical efficacy of this combination.</p><p><b>Trial Registration</b>: The study was registered at clinicaltrials.gov # NCT04163107.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756982/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048748","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}
Katharina Kleinschmidt, Anja Troeger, Jürgen Föll, Tarek Hanafee-Alali, Marcus Jakob, Sonja Kramer, Silke Kietz, Selim Corbacioglu
Introduction
Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening condition characterised by obstruction of the small veins of the liver. Although typically associated with haematopoietic stem cell transplantation, VOD/SOS may also occur following intensive multimodal chemotherapy regimens. In children, symptoms of VOD/SOS are refractory thrombocytopaenia, weight gain, hepatomegaly, ascites and fluid retention, hyperbilirubinaemia and sometimes right upper quadrant pain.
Methods
Here, we present a case series of six paediatric patients with acute lymphoblastic leukaemia who developed severe VOD/SOS while receiving standard AIEOP-BFM ALL protocol treatment.
Results/Conclusions
All patients responded promptly to defibrotide treatment and exhibited favourable clinical outcomes.
Trial Registration
The authors have confirmed clinical trial registration is not needed for this submission
{"title":"Defibrotide for the Treatment of Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome in Paediatric Patients Who Did Not Receive Haematopoietic Stem Cell Transplantation: Case Reports of Patients From a German Academic Hospital","authors":"Katharina Kleinschmidt, Anja Troeger, Jürgen Föll, Tarek Hanafee-Alali, Marcus Jakob, Sonja Kramer, Silke Kietz, Selim Corbacioglu","doi":"10.1002/jha2.1094","DOIUrl":"10.1002/jha2.1094","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening condition characterised by obstruction of the small veins of the liver. Although typically associated with haematopoietic stem cell transplantation, VOD/SOS may also occur following intensive multimodal chemotherapy regimens. In children, symptoms of VOD/SOS are refractory thrombocytopaenia, weight gain, hepatomegaly, ascites and fluid retention, hyperbilirubinaemia and sometimes right upper quadrant pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we present a case series of six paediatric patients with acute lymphoblastic leukaemia who developed severe VOD/SOS while receiving standard AIEOP-BFM ALL protocol treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results/Conclusions</h3>\u0000 \u0000 <p>All patients responded promptly to defibrotide treatment and exhibited favourable clinical outcomes.</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":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048751","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 60-year-old man presented with worsening right-sided facial paresthesia and persistent chin numbness, along with general deterioration and confusion for 3 weeks.</p><p>Laboratory investigations revealed hypercalcemia (3.5 mmol/L; normal: 2.2‒2.7 mmol/L) and elevated creatinine (330 µmol/L; normal: 65‒119 µmol/L). Serum protein electrophoresis showed no monoclonal band, while light chain analysis indicated free kappa light chains at 6.2 mg/L (normal: 3.3‒19.4 mg/L) and free lambda light chains at 8260 mg/L (normal: 5.7‒26 mg/L). Additionally, anemia (60 g/L) and thrombocytopenia (100 × 10⁹/L) were observed, with no abnormal circulating cells.</p><p>A whole-body computed tomography scan revealed a mass in the right infratemporal fossa (Figure 1A, upper panel, asterisk) extending into the right maxillary sinus, causing lysis of its lateral wall and continuing into the pterygopalatine fossa, with potential involvement of the maxillary (V2) and mandibular (V3) nerves. A mass in the left cheek caused minimal lysis of the left maxilla (Figure 1A, bottom panel, asterisk). No other lytic lesions were observed.</p><p>Involvement of cerebrospinal fluid was absent. Bone marrow aspirate exhibited large to giant atypical cells (averaging 60‒70 µm in diameter) with a polymorphic nuclear pattern (abnormally lobated or multinucleated), prominent nucleoli, and abundant deeply bluish, occasionally vacuolated cytoplasm (Figure 1B,C). Flow cytometry of the bone marrow aspirate showed no conclusive results; however, the morphological aspect suggested a rare variant of neoplastic plasma cells—megakaryocytoid—where the cells exhibited markedly increased size, similar to that of a megakaryocyte.</p><p>Furthermore, the bone marrow biopsy confirmed the diagnosis of multiple myeloma, with immunohistochemistry demonstrating the presence of lambda monoclonal plasma cells (CD38+, CD138+, CD56‒, and CD117+). The left cheek mass was also found to be infiltrated by plasma cells, which exhibited the same megakaryocytoid morphology. Epstein‒Barr encoding region in situ hybridization was negative. No expression of LMP1 EBNA1 or EBNA2 was detected. HHV8 staining was negative. No biopsy of the cranial mass was performed.</p><p>Fluorescence in situ hybridization on selected plasma cells detected a gain of the <i>IgH</i> (14q32) locus with variant rearrangement as the sole anomaly. Three years post-diagnosis, the patient shows myeloma progression and myeloma cast nephropathy despite partial response to multiple therapies, including ongoing treatment with carfilzomib, dexamethasone, and pomalidomide.</p><p>This case underscores the heterogeneous nature of neoplastic plasma cells, which can present with features resembling a wide range of hematologic and non-hematologic disorders, thus posing significant diagnostic challenges [<span>1</span>]. In this case, the cells exhibit large, atypical morphology with markedly pleomorphic nuclei, resembling dysplastic megakaryocytes.</p><p>Radu
{"title":"Multiple myeloma: A closer look at one of its faces","authors":"Radu Chiriac, Zofia Gross","doi":"10.1002/jha2.1098","DOIUrl":"10.1002/jha2.1098","url":null,"abstract":"<p>A 60-year-old man presented with worsening right-sided facial paresthesia and persistent chin numbness, along with general deterioration and confusion for 3 weeks.</p><p>Laboratory investigations revealed hypercalcemia (3.5 mmol/L; normal: 2.2‒2.7 mmol/L) and elevated creatinine (330 µmol/L; normal: 65‒119 µmol/L). Serum protein electrophoresis showed no monoclonal band, while light chain analysis indicated free kappa light chains at 6.2 mg/L (normal: 3.3‒19.4 mg/L) and free lambda light chains at 8260 mg/L (normal: 5.7‒26 mg/L). Additionally, anemia (60 g/L) and thrombocytopenia (100 × 10⁹/L) were observed, with no abnormal circulating cells.</p><p>A whole-body computed tomography scan revealed a mass in the right infratemporal fossa (Figure 1A, upper panel, asterisk) extending into the right maxillary sinus, causing lysis of its lateral wall and continuing into the pterygopalatine fossa, with potential involvement of the maxillary (V2) and mandibular (V3) nerves. A mass in the left cheek caused minimal lysis of the left maxilla (Figure 1A, bottom panel, asterisk). No other lytic lesions were observed.</p><p>Involvement of cerebrospinal fluid was absent. Bone marrow aspirate exhibited large to giant atypical cells (averaging 60‒70 µm in diameter) with a polymorphic nuclear pattern (abnormally lobated or multinucleated), prominent nucleoli, and abundant deeply bluish, occasionally vacuolated cytoplasm (Figure 1B,C). Flow cytometry of the bone marrow aspirate showed no conclusive results; however, the morphological aspect suggested a rare variant of neoplastic plasma cells—megakaryocytoid—where the cells exhibited markedly increased size, similar to that of a megakaryocyte.</p><p>Furthermore, the bone marrow biopsy confirmed the diagnosis of multiple myeloma, with immunohistochemistry demonstrating the presence of lambda monoclonal plasma cells (CD38+, CD138+, CD56‒, and CD117+). The left cheek mass was also found to be infiltrated by plasma cells, which exhibited the same megakaryocytoid morphology. Epstein‒Barr encoding region in situ hybridization was negative. No expression of LMP1 EBNA1 or EBNA2 was detected. HHV8 staining was negative. No biopsy of the cranial mass was performed.</p><p>Fluorescence in situ hybridization on selected plasma cells detected a gain of the <i>IgH</i> (14q32) locus with variant rearrangement as the sole anomaly. Three years post-diagnosis, the patient shows myeloma progression and myeloma cast nephropathy despite partial response to multiple therapies, including ongoing treatment with carfilzomib, dexamethasone, and pomalidomide.</p><p>This case underscores the heterogeneous nature of neoplastic plasma cells, which can present with features resembling a wide range of hematologic and non-hematologic disorders, thus posing significant diagnostic challenges [<span>1</span>]. In this case, the cells exhibit large, atypical morphology with markedly pleomorphic nuclei, resembling dysplastic megakaryocytes.</p><p>Radu ","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048906","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}
Ke Zhang, John Bliamptis, Janice Park, Patricia Kopko, Amber P. Sanchez, Srila Gopal
Hemoglobin H (HbH) disease is associated with anemia, ineffective erythropoiesis, and iron overload. We report a case of a patient with HbH/Hb Constant Spring disease, who was maintained on chronic transfusions as an adult due to symptomatic anemia. Over time, he developed iron overload and was started on chelation therapy but did not have an adequate response to chelation. We then added erythrocytapheresis to chelation therapy and were able to successfully decrease his iron burden while managing his anemia. Therapeutic erythrocytapheresis may be an effective treatment strategy for iron overload in HbH disease that is refractory to chelation.
{"title":"Erythrocytapheresis as a strategy to manage anemia and iron overload in nondeletional hemoglobin H disease","authors":"Ke Zhang, John Bliamptis, Janice Park, Patricia Kopko, Amber P. Sanchez, Srila Gopal","doi":"10.1002/jha2.1089","DOIUrl":"10.1002/jha2.1089","url":null,"abstract":"<p>Hemoglobin H (HbH) disease is associated with anemia, ineffective erythropoiesis, and iron overload. We report a case of a patient with HbH/Hb Constant Spring disease, who was maintained on chronic transfusions as an adult due to symptomatic anemia. Over time, he developed iron overload and was started on chelation therapy but did not have an adequate response to chelation. We then added erythrocytapheresis to chelation therapy and were able to successfully decrease his iron burden while managing his anemia. Therapeutic erythrocytapheresis may be an effective treatment strategy for iron overload in HbH disease that is refractory to chelation.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11756960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048811","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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