Concerns about the efficacy of high-dose methotrexate (HD-MTX) in preventing CNS recurrence in large B-cell lymphomas (LBCL) are based on studies with interpretation biases and incomplete information about HD-MTX dosing schedule and CNS events. We evaluated a pharmacokinetic-informed, CNS-directed HD-MTX protocol (3 g/m2 over 3 h, preceded by a bolus) in 336 LBCL patients achieving CMR after RCHOP or derivatives. HD-MTX use was based on institutional risk scores. In this study, CNS risk was reassessed using updated criteria: CNS-IPI ≥ 4, ≥ 3 extranodal sites, or involvement of testis, kidney, adrenal gland, uterus, or breast. According to these criteria, risk was low in 228 (68%) patients and high in 108 (32%); HD-MTX was given to 20 (9%) and 49 (45%), respectively. HD-MTX was well tolerated: 96% completed therapy. After a median follow-up of 77 months, 13 (4%) patients experienced CNS relapse, always as isolated events. Among high-risk patients, CNS relapse occurred in 19% (11/59) without HD-MTX versus 0% (0/49) with HD-MTX (p = 0.0009); significant reductions were seen in patients with high-risk organ involvement (32% to 0%, p = 0.002) or ≥ 3 extranodal sites (18% to 0%, p = 0.04). HD-MTX was independently associated with improved PFS and OS in high-risk patients, likely due to reduced CNS relapses (0% vs. 19%; p = 0.0009), whereas rates of unrelated deaths (8% vs. 15%; p = 0.26) and systemic relapses (18% vs. 22%; p = 0.81) were similar. In conclusion, HD-MTX, administered via a pharmacokinetic-informed, CNS-directed schedule, with or without intrathecal chemotherapy, significantly reduces CNS relapses and improves outcomes in high-risk LBCL patients in CMR. Trial Registration: ClinicalTrials.gov Identifier: NCT07181785.
{"title":"Three-Hour Infusion of Methotrexate at 3 g/m2 With or Without Intrathecal Chemotherapy Significantly Reduces CNS Relapses and Improves Survival in Patients With Large B-Cell Lymphomas at Increased CNS Risk.","authors":"Andrés J M Ferreri,Federico Erbella,Piera Angelillo,Lorenza Pecciarini,Lucia Bongiovanni,Alessandro Nonis,Maria Giulia Cangi,Maddalena V Ponti,Luca Saliani,Paolo Fiore,Marta Bruno-Ventre,Stefania Girlanda,Fabrizio Marino,Elena Flospergher,Giulio Cassanello,Fanny Palumbo,Teresa Calimeri,Maurilio Ponzoni","doi":"10.1002/ajh.70283","DOIUrl":"https://doi.org/10.1002/ajh.70283","url":null,"abstract":"Concerns about the efficacy of high-dose methotrexate (HD-MTX) in preventing CNS recurrence in large B-cell lymphomas (LBCL) are based on studies with interpretation biases and incomplete information about HD-MTX dosing schedule and CNS events. We evaluated a pharmacokinetic-informed, CNS-directed HD-MTX protocol (3 g/m2 over 3 h, preceded by a bolus) in 336 LBCL patients achieving CMR after RCHOP or derivatives. HD-MTX use was based on institutional risk scores. In this study, CNS risk was reassessed using updated criteria: CNS-IPI ≥ 4, ≥ 3 extranodal sites, or involvement of testis, kidney, adrenal gland, uterus, or breast. According to these criteria, risk was low in 228 (68%) patients and high in 108 (32%); HD-MTX was given to 20 (9%) and 49 (45%), respectively. HD-MTX was well tolerated: 96% completed therapy. After a median follow-up of 77 months, 13 (4%) patients experienced CNS relapse, always as isolated events. Among high-risk patients, CNS relapse occurred in 19% (11/59) without HD-MTX versus 0% (0/49) with HD-MTX (p = 0.0009); significant reductions were seen in patients with high-risk organ involvement (32% to 0%, p = 0.002) or ≥ 3 extranodal sites (18% to 0%, p = 0.04). HD-MTX was independently associated with improved PFS and OS in high-risk patients, likely due to reduced CNS relapses (0% vs. 19%; p = 0.0009), whereas rates of unrelated deaths (8% vs. 15%; p = 0.26) and systemic relapses (18% vs. 22%; p = 0.81) were similar. In conclusion, HD-MTX, administered via a pharmacokinetic-informed, CNS-directed schedule, with or without intrathecal chemotherapy, significantly reduces CNS relapses and improves outcomes in high-risk LBCL patients in CMR. Trial Registration: ClinicalTrials.gov Identifier: NCT07181785.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"2 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jorge J. Castillo, Andrew R. Branagan, Alberto Guijosa, Gottfried von Keudell, Andres Ramirez‐Gamero, Hannah Chory, Margaret Kobs, Nina Budano, Julia Nguyen, Alexandra Eurell, Courtney Boyajian, Kirsten Meid, Maria Luisa Guerrera, Amanda Kofides, Shirong Liu, Xia Liu, Nicholas Tsakmaklis, Zachary R. Hunter, Christopher J. Patterson, Steven P. Treon, Shayna Sarosiek
The BTK inhibitor ibrutinib and the BCL‐2 antagonist venetoclax are active therapies as single agents in Waldenström macroglobulinemia (WM). In this phase 2 study, we sought to investigate the combination of ibrutinib and venetoclax as a 2‐year fixed‐duration, oral‐based, chemotherapy‐free regimen in symptomatic, treatment‐naive WM patients. All patients had MYD88 mutations, 17 (38%) had CXCR4 mutations, and 4 (9%) had TP53 alterations. Following enrollment of 45 patients, treatment and enrollment were stopped due to the occurrence of ventricular arrhythmias in 4 (9%), which included two grade 5 events. The median treatment time was 10 cycles, each lasting 28 days. Follow‐up continued after protocol treatment was terminated. The very good partial response/complete response (VGPR/CR) rate was 42%, and it was lower in patients with CXCR4 (29% vs. 50%) or TP53 (25% vs. 44%) mutations. With a median follow‐up of 49 months, the median progression‐free survival (PFS) was 36 months (range 28–42). The median treatment‐free survival (TFS) and overall survival (OS) were not reached, and the 4‐year TFS and OS rates were 73% and 91%, respectively. The median PFS after end of therapy (PFS‐EOT) was 29 months. TP53 mutations were associated with inferior PFS, TFS, and PFS‐EOT, while CXCR4 mutations did not adversely impact these outcomes. Given the deep and durable responses seen in this study, concurrent BTK and BCL‐2 inhibition warrants further development in WM. TP53 mutations emerged as an adverse factor in WM in this combination study.
{"title":"Final Report of a Phase II Study of Ibrutinib and Venetoclax in Previously Untreated Waldenström Macroglobulinemia","authors":"Jorge J. Castillo, Andrew R. Branagan, Alberto Guijosa, Gottfried von Keudell, Andres Ramirez‐Gamero, Hannah Chory, Margaret Kobs, Nina Budano, Julia Nguyen, Alexandra Eurell, Courtney Boyajian, Kirsten Meid, Maria Luisa Guerrera, Amanda Kofides, Shirong Liu, Xia Liu, Nicholas Tsakmaklis, Zachary R. Hunter, Christopher J. Patterson, Steven P. Treon, Shayna Sarosiek","doi":"10.1002/ajh.70285","DOIUrl":"https://doi.org/10.1002/ajh.70285","url":null,"abstract":"The BTK inhibitor ibrutinib and the BCL‐2 antagonist venetoclax are active therapies as single agents in Waldenström macroglobulinemia (WM). In this phase 2 study, we sought to investigate the combination of ibrutinib and venetoclax as a 2‐year fixed‐duration, oral‐based, chemotherapy‐free regimen in symptomatic, treatment‐naive WM patients. All patients had <jats:italic>MYD88</jats:italic> mutations, 17 (38%) had <jats:italic>CXCR4</jats:italic> mutations, and 4 (9%) had <jats:italic>TP53</jats:italic> alterations. Following enrollment of 45 patients, treatment and enrollment were stopped due to the occurrence of ventricular arrhythmias in 4 (9%), which included two grade 5 events. The median treatment time was 10 cycles, each lasting 28 days. Follow‐up continued after protocol treatment was terminated. The very good partial response/complete response (VGPR/CR) rate was 42%, and it was lower in patients with <jats:italic>CXCR4</jats:italic> (29% vs. 50%) or <jats:italic>TP53</jats:italic> (25% vs. 44%) mutations. With a median follow‐up of 49 months, the median progression‐free survival (PFS) was 36 months (range 28–42). The median treatment‐free survival (TFS) and overall survival (OS) were not reached, and the 4‐year TFS and OS rates were 73% and 91%, respectively. The median PFS after end of therapy (PFS‐EOT) was 29 months. <jats:italic>TP53</jats:italic> mutations were associated with inferior PFS, TFS, and PFS‐EOT, while <jats:italic>CXCR4</jats:italic> mutations did not adversely impact these outcomes. Given the deep and durable responses seen in this study, concurrent BTK and BCL‐2 inhibition warrants further development in WM. <jats:italic>TP53</jats:italic> mutations emerged as an adverse factor in WM in this combination study.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"2 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147454684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Adetola A. Kassim, Alexis A. Thompson, Punam Malik
The practical aspects of developing curative treatments for sickle cell disease (SCD) in Africa, such as gene therapy and hematopoietic stem cell transplantation, involve strengthening healthcare infrastructure, training healthcare professionals, establishing regional treatment centers, and creating national SCD programs. The costs associated with gene therapy and stem cell transplants can be prohibitive, especially in low‐ and middle‐income countries. Strategies to address affordability, including local manufacturing, government funding, and partnerships with global health agencies, are essential to ensure equitable access. Establishing ethical and regulatory guidelines while raising awareness among patients and communities is critical. Early diagnosis through newborn screening and adequate clinical care programs are vital for identifying individuals with SCD who could benefit from curative therapies and other interventions. Addressing cultural beliefs and promoting positive attitudes toward SCD and its management is essential. While curative therapies offer hope, hydroxyurea and other disease‐modifying therapies with established clinical benefits are more accessible in many settings. Prioritizing these medications ensures that patients with SCD are medically prepared to receive curative therapies while simultaneously building capacity for advanced treatments, thus creating a pragmatic approach. Lastly, international collaboration and partnerships among researchers, global health agencies, and local organizations are vital for sharing knowledge, resources, and best practices in SCD management.
{"title":"Exploring Affordable Curative Therapy for Sickle Cell Disease in Africa: A Comprehensive Overview","authors":"Adetola A. Kassim, Alexis A. Thompson, Punam Malik","doi":"10.1002/ajh.70221","DOIUrl":"https://doi.org/10.1002/ajh.70221","url":null,"abstract":"The practical aspects of developing curative treatments for sickle cell disease (SCD) in Africa, such as gene therapy and hematopoietic stem cell transplantation, involve strengthening healthcare infrastructure, training healthcare professionals, establishing regional treatment centers, and creating national SCD programs. The costs associated with gene therapy and stem cell transplants can be prohibitive, especially in low‐ and middle‐income countries. Strategies to address affordability, including local manufacturing, government funding, and partnerships with global health agencies, are essential to ensure equitable access. Establishing ethical and regulatory guidelines while raising awareness among patients and communities is critical. Early diagnosis through newborn screening and adequate clinical care programs are vital for identifying individuals with SCD who could benefit from curative therapies and other interventions. Addressing cultural beliefs and promoting positive attitudes toward SCD and its management is essential. While curative therapies offer hope, hydroxyurea and other disease‐modifying therapies with established clinical benefits are more accessible in many settings. Prioritizing these medications ensures that patients with SCD are medically prepared to receive curative therapies while simultaneously building capacity for advanced treatments, thus creating a pragmatic approach. Lastly, international collaboration and partnerships among researchers, global health agencies, and local organizations are vital for sharing knowledge, resources, and best practices in SCD management.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"8 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147447217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R.E.W. has received research donations from Bristol-Myers Squibb, Theravia, and Hemex Health; is an advisor to Nova Laboratories, Theravia, and Octapharma; serves on a DSMB for NHLBI and Vaxart Inc.
{"title":"Sickle Cell Disease in Sub‐Saharan Africa: Progress and Potential","authors":"Russell E. Ware","doi":"10.1002/ajh.70242","DOIUrl":"https://doi.org/10.1002/ajh.70242","url":null,"abstract":"<h2> Conflicts of Interest</h2>\u0000<p>R.E.W. has received research donations from Bristol-Myers Squibb, Theravia, and Hemex Health; is an advisor to Nova Laboratories, Theravia, and Octapharma; serves on a DSMB for NHLBI and Vaxart Inc.</p>","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"21 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147447218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yvonne Dei‐Adomakoh, Emmanuela E. Ambrose, Alexandra Power‐Hays
Sickle cell disease (SCD) is a major individual and public health challenge in sub‐Saharan Africa, where over 5 million affected individuals live and where access to disease‐modifying treatment is limited. Despite established safety and efficacy of hydroxyurea, its use is limited across the region due to inconsistent healthcare infrastructure, high medication and laboratory costs, inadequate clinician training, and persistent disease stigma. Practical hydroxyurea dosing strategies, integration into national health plans, and a stronger supply chain are necessary to improve access to this life‐saving medication. Newly approved medications, such as L‐glutamine and crizanlizumab, may provide additional benefits to select patients, but are expensive and unavailable. The increased mortality observed in people on voxelotor in Africa highlights the need to ensure the safety of any new medication in varied settings through high‐quality research conducted on the continent. Overall, holistic strategies are needed to improve SCD care in Africa, such as universal screening with connection to comprehensive care that includes disease‐modifying treatment, community and healthcare worker education, centers of excellence, and capacity building. SCD management in Africa can be transformed by addressing systemic barriers and leveraging collaborative partnerships, leading to reduced mortality and alleviation of the individual and economic burdens of the disease. It is a moral and economic imperative to prioritize access to SCD treatment in Africa, the region with the greatest disease burden globally.
{"title":"Advancing Sickle Cell Disease Treatment in Sub‐Saharan Africa: Challenges and Opportunities for Disease Modifying Therapies","authors":"Yvonne Dei‐Adomakoh, Emmanuela E. Ambrose, Alexandra Power‐Hays","doi":"10.1002/ajh.70226","DOIUrl":"https://doi.org/10.1002/ajh.70226","url":null,"abstract":"Sickle cell disease (SCD) is a major individual and public health challenge in sub‐Saharan Africa, where over 5 million affected individuals live and where access to disease‐modifying treatment is limited. Despite established safety and efficacy of hydroxyurea, its use is limited across the region due to inconsistent healthcare infrastructure, high medication and laboratory costs, inadequate clinician training, and persistent disease stigma. Practical hydroxyurea dosing strategies, integration into national health plans, and a stronger supply chain are necessary to improve access to this life‐saving medication. Newly approved medications, such as L‐glutamine and crizanlizumab, may provide additional benefits to select patients, but are expensive and unavailable. The increased mortality observed in people on voxelotor in Africa highlights the need to ensure the safety of any new medication in varied settings through high‐quality research conducted on the continent. Overall, holistic strategies are needed to improve SCD care in Africa, such as universal screening with connection to comprehensive care that includes disease‐modifying treatment, community and healthcare worker education, centers of excellence, and capacity building. SCD management in Africa can be transformed by addressing systemic barriers and leveraging collaborative partnerships, leading to reduced mortality and alleviation of the individual and economic burdens of the disease. It is a moral and economic imperative to prioritize access to SCD treatment in Africa, the region with the greatest disease burden globally.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"17 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147447221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Many of the children with sickle cell disease born in sub‐Saharan Africa remain undiagnosed and untreated. Increasing capacity and infrastructure to support diagnostic and screening programs in high income countries have enabled near universal survival into adulthood. Early diagnosis and treatment are achievable goals that enjoy widespread consensus in sub‐Saharan Africa but may require a variety of individualized approaches that are specific to each country. A clear understanding of the issues that influence program building is required before identifying solutions adapted to the diverse health care settings in Africa and responsive to the challenges observed during pilot programs.
{"title":"Creative and Adaptive Solutions for Early Diagnosis of Sickle Cell Disease in Sub‐Saharan Africa","authors":"Luke R. Smart, Catherine I. Segbefia, Isaac Odame","doi":"10.1002/ajh.70210","DOIUrl":"https://doi.org/10.1002/ajh.70210","url":null,"abstract":"Many of the children with sickle cell disease born in sub‐Saharan Africa remain undiagnosed and untreated. Increasing capacity and infrastructure to support diagnostic and screening programs in high income countries have enabled near universal survival into adulthood. Early diagnosis and treatment are achievable goals that enjoy widespread consensus in sub‐Saharan Africa but may require a variety of individualized approaches that are specific to each country. A clear understanding of the issues that influence program building is required before identifying solutions adapted to the diverse health care settings in Africa and responsive to the challenges observed during pilot programs.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"93 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147447219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brigitte Ranque, Leon Tshilolo, Thomas N. Williams
Sickle Cell Disease (SCD) is highly prevalent in sub‐Saharan Africa. Epidemiological data remain sparse, but regional screening and research initiatives are expanding. Due to genetic, environmental, and socioeconomic factors, the disease course differs markedly from that in high‐income countries. Although mortality is improving and can be further lowered with simple interventions, it remains high, especially among undiagnosed children. Genetic factors, poor healthcare infrastructure, and poverty contribute to disease severity. While recent collaborative programs like SickleInAfrica offer hope, national policies that foster the training of healthcare workers, newborn screening, and access to treatment are crucial to reducing the burden of SCD across the region.
{"title":"The Epidemiology of Sickle Cell Disease in Sub‐Saharan Africa: Current Knowledge and Gaps to be Filled","authors":"Brigitte Ranque, Leon Tshilolo, Thomas N. Williams","doi":"10.1002/ajh.70212","DOIUrl":"https://doi.org/10.1002/ajh.70212","url":null,"abstract":"Sickle Cell Disease (SCD) is highly prevalent in sub‐Saharan Africa. Epidemiological data remain sparse, but regional screening and research initiatives are expanding. Due to genetic, environmental, and socioeconomic factors, the disease course differs markedly from that in high‐income countries. Although mortality is improving and can be further lowered with simple interventions, it remains high, especially among undiagnosed children. Genetic factors, poor healthcare infrastructure, and poverty contribute to disease severity. While recent collaborative programs like SickleInAfrica offer hope, national policies that foster the training of healthcare workers, newborn screening, and access to treatment are crucial to reducing the burden of SCD across the region.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"412 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147447220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Advanced genomic technologies are revolutionizing our ability to understand complex diseases. Large‐scale population studies are needed to realize the potential of using individual genetic information to personalize treatments for better patient outcomes for chronic non‐communicable diseases, such as sickle cell disease (SCD). SCD is recognized as a benchmark genetic disorder for study both in Africa and globally due to its unmet health burden and the potential utilization of genomic knowledge for improving the health outcomes for individuals living with the disease. Over the past two decades, groundbreaking genomic research in SCD has led to the discovery, fine mapping, and validation of genetic and epigenetic variants of importance for SCD. These include variants in genes such as BCL11A , HBG , MYB , KLF1, and FLT1, which are all associated with fetal hemoglobin expression, a major modifier of disease severity in SCD. There has also been increased genomic knowledge of other SCD modifiers, including the distribution of alpha‐ and beta‐thalassemia variants in Africa, and infectious disease related markers such as APOL1 . Pioneering pharmacogenomics studies for hydroxyurea are promising and have unveiled the importance of the implementation of such studies for all SCD therapeutics, including small molecules and recent gene‐based therapies. Genomic research for the development of personalized medicine for SCD must involve countries in Africa due to the high prevalence of the disease in these countries, the high African genetic diversity that influences disease progression, and the potential to follow treatment outcomes in large cohorts of patients. These findings hold great promise to lead to a better understanding of SCD biology and treatment responses, the discovery of new therapies, and informing the design and execution of much needed clinical trials.
{"title":"Genetics and Genomics in Sickle Cell Disease in Africa","authors":"Siana Nkya, Julie Makani, Jonathan M. Flanagan","doi":"10.1002/ajh.70220","DOIUrl":"https://doi.org/10.1002/ajh.70220","url":null,"abstract":"Advanced genomic technologies are revolutionizing our ability to understand complex diseases. Large‐scale population studies are needed to realize the potential of using individual genetic information to personalize treatments for better patient outcomes for chronic non‐communicable diseases, such as sickle cell disease (SCD). SCD is recognized as a benchmark genetic disorder for study both in Africa and globally due to its unmet health burden and the potential utilization of genomic knowledge for improving the health outcomes for individuals living with the disease. Over the past two decades, groundbreaking genomic research in SCD has led to the discovery, fine mapping, and validation of genetic and epigenetic variants of importance for SCD. These include variants in genes such as <jats:italic>BCL11A</jats:italic> , <jats:italic>HBG</jats:italic> , <jats:italic>MYB</jats:italic> , <jats:italic>KLF1,</jats:italic> and <jats:italic>FLT1,</jats:italic> which are all associated with fetal hemoglobin expression, a major modifier of disease severity in SCD. There has also been increased genomic knowledge of other SCD modifiers, including the distribution of alpha‐ and beta‐thalassemia variants in Africa, and infectious disease related markers such as <jats:italic>APOL1</jats:italic> . Pioneering pharmacogenomics studies for hydroxyurea are promising and have unveiled the importance of the implementation of such studies for all SCD therapeutics, including small molecules and recent gene‐based therapies. Genomic research for the development of personalized medicine for SCD must involve countries in Africa due to the high prevalence of the disease in these countries, the high African genetic diversity that influences disease progression, and the potential to follow treatment outcomes in large cohorts of patients. These findings hold great promise to lead to a better understanding of SCD biology and treatment responses, the discovery of new therapies, and informing the design and execution of much needed clinical trials.","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":"59 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147447358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francesco Pegoraro, Irene Ferri, Aurora Chinnici, Linda Beneforti, Irene Trambusti, Simona Gobbi, Rosa Maria Daniele, Rosamaria Mura, Elena Palmisani, Marco Zecca, Giulia Albrici, Alessandra Todesco, Carmela De Fusco, Samuele Naviglio, Veronica Barat, Fabio Timeus, Marta Pillon, Carmelo Rizzari, Annalisa Tondo, Maria Luisa Coniglio, Elena Sieni
{"title":"Encouraging Outcomes in Pediatric Malignancy-Associated Hemophagocytic Lymphohistiocytosis: Results From the Italian HLH Registry.","authors":"Francesco Pegoraro, Irene Ferri, Aurora Chinnici, Linda Beneforti, Irene Trambusti, Simona Gobbi, Rosa Maria Daniele, Rosamaria Mura, Elena Palmisani, Marco Zecca, Giulia Albrici, Alessandra Todesco, Carmela De Fusco, Samuele Naviglio, Veronica Barat, Fabio Timeus, Marta Pillon, Carmelo Rizzari, Annalisa Tondo, Maria Luisa Coniglio, Elena Sieni","doi":"10.1002/ajh.70259","DOIUrl":"https://doi.org/10.1002/ajh.70259","url":null,"abstract":"","PeriodicalId":7724,"journal":{"name":"American Journal of Hematology","volume":" ","pages":""},"PeriodicalIF":9.9,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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