Shakthi T Bhaskar, B. Dholaria, B. Savani, Olalekan O. Oluwole
Chimeric antigen receptor (CAR) T-cell therapy has gained wide used across an array of hematologic malignancies. Though CAR T therapy has changed outcomes in the treatment of many malignancies its administration can be complicated by delays related to patient-related factors, social barriers, or insurance issues. Because of the lengthy process required to treat a patient with CAR T-cells, bridging therapy (BT), administered after leukapheresis but prior to CAR T infusion, has become an important component of safely administering CAR T therapy. Here we review data supporting the use of BT, factors to consider in patient selection, and types of available BT and rationale for choosing amongst them.
嵌合抗原受体（CAR）T 细胞疗法已在一系列血液系统恶性肿瘤中得到广泛应用。尽管 CAR T 疗法改变了许多恶性肿瘤的治疗效果，但由于患者相关因素、社会障碍或保险问题导致治疗延迟，使治疗变得更加复杂。由于使用 CAR T 细胞治疗患者需要漫长的过程，因此在白细胞清除术后、CAR T 输注前进行的桥接疗法（BT）已成为安全使用 CAR T 疗法的重要组成部分。在此，我们回顾了支持使用桥接疗法的数据、选择患者时应考虑的因素、可用桥接疗法的类型以及选择这些疗法的理由。
{"title":"The Evolving Role of Bridging Therapy during CAR-T Therapy","authors":"Shakthi T Bhaskar, B. Dholaria, B. Savani, Olalekan O. Oluwole","doi":"10.46989/001c.116261","DOIUrl":"https://doi.org/10.46989/001c.116261","url":null,"abstract":"Chimeric antigen receptor (CAR) T-cell therapy has gained wide used across an array of hematologic malignancies. Though CAR T therapy has changed outcomes in the treatment of many malignancies its administration can be complicated by delays related to patient-related factors, social barriers, or insurance issues. Because of the lengthy process required to treat a patient with CAR T-cells, bridging therapy (BT), administered after leukapheresis but prior to CAR T infusion, has become an important component of safely administering CAR T therapy. Here we review data supporting the use of BT, factors to consider in patient selection, and types of available BT and rationale for choosing amongst them.","PeriodicalId":10368,"journal":{"name":"Clinical Hematology International","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Treatment algorithms differ for adult patients with Philadelphia-negative (Ph-) and Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). For Ph- ALL intensive induction-consolidation chemotherapy using “pediatric-inspired” protocols is a standard of care. Allogeneic hematopoietic cell transplantation (allo-HCT) from either an HLA-matched sibling, unrelated or haploidentical donor should be considered for patients with high estimated risk of relapse. Inadequate response at the level of measurable residual disease (MRD) is the strongest adverse prognostic factor. Patients with B-ALL and detectable MRD should be treated with blinatumomab. In the future, the use of blinatumomab and/or inotuzumab ozogamycin in addition to first-line chemotherapy may become a new standard of care reducing the role of allo-HCT. For patients with Ph+ ALL, tyrosine kinase inhibitors (TKI) are the most important components of treatment protocols, while the intensity of chemotherapy may be reduced. Allo-HCT is recommended for all patients treated with imatinib along with low-intensity chemotherapy. Results of phase-II studies using front-line dasatinib or ponatinib in sequence or in combination with blinatumomab are very promising. Such a strategy may allow the avoidance of systemic chemotherapy. The future role of allo-HCT in this context appears uncertain.
{"title":"How I treat newly diagnosed acute lymphoblastic leukemia","authors":"Giebel Sebastian","doi":"10.46989/001c.117026","DOIUrl":"https://doi.org/10.46989/001c.117026","url":null,"abstract":"Treatment algorithms differ for adult patients with Philadelphia-negative (Ph-) and Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). For Ph- ALL intensive induction-consolidation chemotherapy using “pediatric-inspired” protocols is a standard of care. Allogeneic hematopoietic cell transplantation (allo-HCT) from either an HLA-matched sibling, unrelated or haploidentical donor should be considered for patients with high estimated risk of relapse. Inadequate response at the level of measurable residual disease (MRD) is the strongest adverse prognostic factor. Patients with B-ALL and detectable MRD should be treated with blinatumomab. In the future, the use of blinatumomab and/or inotuzumab ozogamycin in addition to first-line chemotherapy may become a new standard of care reducing the role of allo-HCT. For patients with Ph+ ALL, tyrosine kinase inhibitors (TKI) are the most important components of treatment protocols, while the intensity of chemotherapy may be reduced. Allo-HCT is recommended for all patients treated with imatinib along with low-intensity chemotherapy. Results of phase-II studies using front-line dasatinib or ponatinib in sequence or in combination with blinatumomab are very promising. Such a strategy may allow the avoidance of systemic chemotherapy. The future role of allo-HCT in this context appears uncertain.","PeriodicalId":10368,"journal":{"name":"Clinical Hematology International","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140995705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zoé Van de Wyngaert, Irene Romera-Martinez, Céline Chedeville, Paolo Musiu, Souhila Ikhlef, Bénédicte Jonca, M. Mohty, F. Malard
We present the case of a dialyzed patient with relapsed IgA and lambda free light chain multiple myeloma treated with elranatamab. Despite end-stage renal impairment, the treatment with anti-B cell maturation antigen (BCMA)xCD3 bispecific antibody proved to be feasible, without unexpected side effects. Increased attention to infectious risk is crucial for these doubly fragile patients.
{"title":"Elranatamab treatment in a multiple myeloma patient undergoing renal dialysis","authors":"Zoé Van de Wyngaert, Irene Romera-Martinez, Céline Chedeville, Paolo Musiu, Souhila Ikhlef, Bénédicte Jonca, M. Mohty, F. Malard","doi":"10.46989/001c.116800","DOIUrl":"https://doi.org/10.46989/001c.116800","url":null,"abstract":"We present the case of a dialyzed patient with relapsed IgA and lambda free light chain multiple myeloma treated with elranatamab. Despite end-stage renal impairment, the treatment with anti-B cell maturation antigen (BCMA)xCD3 bispecific antibody proved to be feasible, without unexpected side effects. Increased attention to infectious risk is crucial for these doubly fragile patients.","PeriodicalId":10368,"journal":{"name":"Clinical Hematology International","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141007900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Rauf, I. Maghfoor, Muhammad Aseafan, Khadijah Al Shankati, Ali M. Alhanash, Faateh Sohail, Tusneem A. M. Elhassan, S. Akhtar
Rituximab with anthracycline-based combination frontline chemoimmunotherapy can cure 50–60% of patients with diffuse large B-cell lymphoma (DLBCL). However, studies on the outcomes of patients with DLBCL who experience partial response (PR), stable or progressive disease in response to frontline rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) therapy are limited, as are data on the outcomes of high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) in patients with primary refractory DLBCL who demonstrate chemosensitivity to salvage chemotherapy (SC). We assessed the latter among 184 patients, 144 of whom started SC, with 84 responding and 72 receiving HDC–ASCT. The 5-year survival rate was 58.9%; the median overall survival (OS) was not reached. The difference in response to SC (partial response versus complete response) was significant, with higher 2- and 5-year OS rates in patients with CR (78.1% and 74.9%, respectively) than in those with PR (55.3% and 47%, respectively). The median OS for the whole group was 15 months and particularly patients who had progressive disease after frontline R-CHOP had dismal outcomes. Our study suggests that in patients with primary refractory DLBCL without initial progressive disease after frontline R-CHOP, the depth of response to SC before HDC–ASCT is predictive of relapse.
{"title":"Outcomes of Autologous stem cell transplantation in patients with primary refractory Diffuse Large B-cell lymphoma who demonstrate chemosensitivity to salvage chemotherapy","authors":"M. Rauf, I. Maghfoor, Muhammad Aseafan, Khadijah Al Shankati, Ali M. Alhanash, Faateh Sohail, Tusneem A. M. Elhassan, S. Akhtar","doi":"10.46989/001c.115919","DOIUrl":"https://doi.org/10.46989/001c.115919","url":null,"abstract":"Rituximab with anthracycline-based combination frontline chemoimmunotherapy can cure 50–60% of patients with diffuse large B-cell lymphoma (DLBCL). However, studies on the outcomes of patients with DLBCL who experience partial response (PR), stable or progressive disease in response to frontline rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP) therapy are limited, as are data on the outcomes of high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) in patients with primary refractory DLBCL who demonstrate chemosensitivity to salvage chemotherapy (SC). We assessed the latter among 184 patients, 144 of whom started SC, with 84 responding and 72 receiving HDC–ASCT. The 5-year survival rate was 58.9%; the median overall survival (OS) was not reached. The difference in response to SC (partial response versus complete response) was significant, with higher 2- and 5-year OS rates in patients with CR (78.1% and 74.9%, respectively) than in those with PR (55.3% and 47%, respectively). The median OS for the whole group was 15 months and particularly patients who had progressive disease after frontline R-CHOP had dismal outcomes. Our study suggests that in patients with primary refractory DLBCL without initial progressive disease after frontline R-CHOP, the depth of response to SC before HDC–ASCT is predictive of relapse.","PeriodicalId":10368,"journal":{"name":"Clinical Hematology International","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140716485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katie S. Gatwood, Zahra Mahmoudjafari, Brittney Baer, Stacy Pak, Hoim Kim, Karin Abernathy, B. Dholaria, Olalekan Oluwole
Chimeric antigen receptor T-cell therapy (CAR-T) has altered the treatment landscape of several hematologic malignancies. Until recently, most CAR-T infusions have been administered in the inpatient setting, due to their toxicity profile. However, the advent of new product constructs, as well as improved detection and management of adverse effects, have greatly increased the safety in administering these therapies. CAR-T indications continue to expand, and inpatient administration is associated with increased healthcare resource utilization and overall cost. Therefore, transitioning CAR-T administration to the outpatient setting has been of great interest in an effort to improve access, reduce financial burden, and improve patient satisfaction. Establishment of a successful outpatient CAR-T requires several components, including a multidisciplinary cellular therapy team and an outpatient center with appropriate clinical space and personnel. Additionally, clear criteria for outpatient administration eligibility and for inpatient admission with pathways for prompt toxicity evaluation and admission, and toxicity management guidelines should be implemented. Education about CAR-T therapy and its associated toxicities is imperative for all clinical staff, as well as patients and their caregivers. Finally, rigorous financial planning and close collaboration with payers to ensure equitable access, while effectively managing cost, are essential to program success and sustainability. This review provides a summary of currently published experiences, as well as expert opinion regarding implementation of an outpatient CAR-T program.
{"title":"Outpatient CAR T-Cell Therapy as Standard of Care: Current Perspectives and Considerations","authors":"Katie S. Gatwood, Zahra Mahmoudjafari, Brittney Baer, Stacy Pak, Hoim Kim, Karin Abernathy, B. Dholaria, Olalekan Oluwole","doi":"10.46989/001c.115793","DOIUrl":"https://doi.org/10.46989/001c.115793","url":null,"abstract":"Chimeric antigen receptor T-cell therapy (CAR-T) has altered the treatment landscape of several hematologic malignancies. Until recently, most CAR-T infusions have been administered in the inpatient setting, due to their toxicity profile. However, the advent of new product constructs, as well as improved detection and management of adverse effects, have greatly increased the safety in administering these therapies. CAR-T indications continue to expand, and inpatient administration is associated with increased healthcare resource utilization and overall cost. Therefore, transitioning CAR-T administration to the outpatient setting has been of great interest in an effort to improve access, reduce financial burden, and improve patient satisfaction. Establishment of a successful outpatient CAR-T requires several components, including a multidisciplinary cellular therapy team and an outpatient center with appropriate clinical space and personnel. Additionally, clear criteria for outpatient administration eligibility and for inpatient admission with pathways for prompt toxicity evaluation and admission, and toxicity management guidelines should be implemented. Education about CAR-T therapy and its associated toxicities is imperative for all clinical staff, as well as patients and their caregivers. Finally, rigorous financial planning and close collaboration with payers to ensure equitable access, while effectively managing cost, are essential to program success and sustainability. This review provides a summary of currently published experiences, as well as expert opinion regarding implementation of an outpatient CAR-T program.","PeriodicalId":10368,"journal":{"name":"Clinical Hematology International","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140726005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jana Sawyer, Taylor Elliott, Lindsay Orton, Hunter Sowell, Katie S. Gatwood, Kendall Shultes
Hematopoietic stem cell transplantation (HSCT) remains the only curative option for several hematological malignancies. Its use has continued to grow, with an estimated 23,500 transplants performed annually in the United States alone. The acute toxicities that occur from conditioning chemotherapy can impact the peri-transplant period and have substantial implications on patients’ tolerability and outcomes, irrespective of the treatment of their disease. Chemotherapy-induced nausea vomiting (CINV), mucositis, transplant-associated thrombotic microangiopathy (TA-TMA), and sinusoidal obstruction syndrome, also known as a veno-occlusive disease (SOS/VOD) can all have significant implications for patients. These acute complications begin with the start of conditioning chemotherapy and add to potential toxicity for patients throughout the early post-transplant period, from Day +30 for CINV, mucositis, and SOS, and which can continue through at least Day +100 with the onset of TA-TMA. These toxicities must be prevented and managed appropriately. This review will summarize the literature surrounding them and guide their management.
造血干细胞移植（HSCT）仍然是治疗多种血液恶性肿瘤的唯一选择。造血干细胞移植的使用量持续增长，仅在美国，估计每年就有23,500例造血干细胞移植。无论治疗何种疾病，条件性化疗引起的急性毒性反应都会影响围移植期，并对患者的耐受性和治疗效果产生重大影响。化疗引起的恶心呕吐（CINV）、粘膜炎、移植相关性血栓性微血管病（TA-TMA）和窦性阻塞综合征（又称静脉闭塞症（SOS/VOD））都会对患者产生重大影响。这些急性并发症始于调理化疗，并在移植后早期增加了患者的潜在毒性，CINV、粘膜炎和 SOS 可从 +30 天开始，TA-TMA 可至少持续到 +100 天。必须预防和妥善处理这些毒性反应。本综述将总结有关这些毒性反应的文献，并对其管理提供指导。
{"title":"Prevention and management of acute toxicities from conditioning regimens during hematopoietic stem cell transplantation","authors":"Jana Sawyer, Taylor Elliott, Lindsay Orton, Hunter Sowell, Katie S. Gatwood, Kendall Shultes","doi":"10.46989/001c.94952","DOIUrl":"https://doi.org/10.46989/001c.94952","url":null,"abstract":"Hematopoietic stem cell transplantation (HSCT) remains the only curative option for several hematological malignancies. Its use has continued to grow, with an estimated 23,500 transplants performed annually in the United States alone. The acute toxicities that occur from conditioning chemotherapy can impact the peri-transplant period and have substantial implications on patients’ tolerability and outcomes, irrespective of the treatment of their disease. Chemotherapy-induced nausea vomiting (CINV), mucositis, transplant-associated thrombotic microangiopathy (TA-TMA), and sinusoidal obstruction syndrome, also known as a veno-occlusive disease (SOS/VOD) can all have significant implications for patients. These acute complications begin with the start of conditioning chemotherapy and add to potential toxicity for patients throughout the early post-transplant period, from Day +30 for CINV, mucositis, and SOS, and which can continue through at least Day +100 with the onset of TA-TMA. These toxicities must be prevented and managed appropriately. This review will summarize the literature surrounding them and guide their management.","PeriodicalId":10368,"journal":{"name":"Clinical Hematology International","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140747284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Tso, S. Acharyya, S. Z. Fong, L. Lee, S. V. Sreekanth, B. Fan, Seok W. S. Chan, K. Ong
Real-world data on the outcome of Asian patients with secondary hemophagocytic lymphohistiocytosis (HLH), especially on dengue-associated HLH, are limited to small case series. This is a retrospective records review of adult patients with secondary HLH between 2015 and 2020. Thirty-two adult patients were followed up for a median of 6.6 months (range 0.1 – 75 months). 15 had underlying lymphomas, and 12 had viral infections. Hemophagocytosis was seen in 28 of 29 patients with a bone marrow biopsy. 100% and 76.5% of patients with and without an underlying malignancy required HLH-directed therapy and blood product transfusion. 12 of 15 patients with lymphomas were treated with additional chemotherapy. Patients with malignancy-associated HLH had poorer survival than non-malignancy-associated HLH (median overall survival (OS) 1.5 months versus not reached, p-value 0.003). The 1-year survival rates of patients with malignancy-associated HLH, HLH with unknown etiologies, and infection-associated HLH were 0.133 (95% CI: 0.036 – 0.484), 0.400 (95% CI: 0.137 – 1.000) and 0.833 (95% CI: 0.647 – 1.000), respectively. Malignancy significantly increased the risk of death compared to infection-associated HLH (HR 9.37, p-value 0.003). Eight patients were diagnosed with dengue-associated HLH with a median HSCORE of 240 (98-99% probability of HLH). Their mean ferritin was 34,740 ng/mL. Three patients required blood product transfusion, 5 required corticosteroids and/or etoposide, with a median duration of treatment of 31 days. Their overall survival rate was 87.5%. Our study highlights the stark contrast in the survival of secondary HLH patients with and without an underlying malignancy. We also present one of the world’s most extensive case series of dengue-associated HLH.
{"title":"A Retrospective Review of Secondary Hemophagocytic Lymphohistiocytosis (HLH) and Dengue-associated HLH from a Teaching Hospital in Singapore.","authors":"A. Tso, S. Acharyya, S. Z. Fong, L. Lee, S. V. Sreekanth, B. Fan, Seok W. S. Chan, K. Ong","doi":"10.46989/001c.94954","DOIUrl":"https://doi.org/10.46989/001c.94954","url":null,"abstract":"Real-world data on the outcome of Asian patients with secondary hemophagocytic lymphohistiocytosis (HLH), especially on dengue-associated HLH, are limited to small case series. This is a retrospective records review of adult patients with secondary HLH between 2015 and 2020. Thirty-two adult patients were followed up for a median of 6.6 months (range 0.1 – 75 months). 15 had underlying lymphomas, and 12 had viral infections. Hemophagocytosis was seen in 28 of 29 patients with a bone marrow biopsy. 100% and 76.5% of patients with and without an underlying malignancy required HLH-directed therapy and blood product transfusion. 12 of 15 patients with lymphomas were treated with additional chemotherapy. Patients with malignancy-associated HLH had poorer survival than non-malignancy-associated HLH (median overall survival (OS) 1.5 months versus not reached, p-value 0.003). The 1-year survival rates of patients with malignancy-associated HLH, HLH with unknown etiologies, and infection-associated HLH were 0.133 (95% CI: 0.036 – 0.484), 0.400 (95% CI: 0.137 – 1.000) and 0.833 (95% CI: 0.647 – 1.000), respectively. Malignancy significantly increased the risk of death compared to infection-associated HLH (HR 9.37, p-value 0.003). Eight patients were diagnosed with dengue-associated HLH with a median HSCORE of 240 (98-99% probability of HLH). Their mean ferritin was 34,740 ng/mL. Three patients required blood product transfusion, 5 required corticosteroids and/or etoposide, with a median duration of treatment of 31 days. Their overall survival rate was 87.5%. Our study highlights the stark contrast in the survival of secondary HLH patients with and without an underlying malignancy. We also present one of the world’s most extensive case series of dengue-associated HLH.","PeriodicalId":10368,"journal":{"name":"Clinical Hematology International","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140232346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CD19-directed Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized the treatment of patients with B-cell acute lymphoblastic leukemia (B-ALL). Somewhat uniquely among oncologic clinical trials, early clinical development occurred simultaneously in both children and adults. In subsequent years however, the larger number of adult patients with relapsed/refractory (r/r) malignancies has led to accelerated development of multiple CAR T-cell products that target a variety of malignancies, resulting in six currently FDA-approved for adult patients. By comparison, only a single CAR-T cell therapy is approved by the FDA for pediatric patients: tisagenlecleucel, which is approved for patients 25 years with refractory B-cell precursor ALL, or B-cell ALL in second or later relapse. Tisagenlecleucel is also under evaluation in pediatric patients with relapsed/refractory B-cell non-Hodgkin lymphoma, but is not yet been approved for this indication. All the other FDA-approved CD19-directed CAR-T cell therapies available for adult patients (axicabtagene ciloleucel, brexucabtagene autoleucel, and lisocabtagene maraleucel) are currently under investigations among children, with preliminary results available in some cases. As the volume and complexity of data continue to grow, so too does the necessity of rapid assimilation and implementation of those data. This is particularly true when considering “atypical” situations, e.g. those arising when patients do not precisely conform to the profile of those included in pivotal clinical trials, or when alternative treatment options (e.g. hematopoietic stem cell transplantation (HSCT) or bispecific T-cell engagers (BITEs)) are also available. We have therefore developed a relevant summary of the currently available literature pertaining to the use of CD19-directed CAR-T cell therapies in pediatric patients, and sought to provide guidance for clinicians seeking additional data about specific clinical situations.
CD19 定向嵌合抗原受体（CAR）T 细胞疗法彻底改变了 B 细胞急性淋巴细胞白血病（B-ALL）患者的治疗。早期的临床试验同时在儿童和成人中进行，这在肿瘤临床试验中略显独特。然而，在随后的几年里，由于复发/难治性（r/r）恶性肿瘤的成年患者人数增多，导致针对各种恶性肿瘤的多种 CAR T 细胞产品加速开发，目前已有六种产品获得 FDA 批准用于成年患者。相比之下，只有一种 CAR-T 细胞疗法获 FDA 批准用于儿童患者：tisagenlecleucel，该疗法获准用于 25 岁的难治性 B 细胞前体 ALL 或第二次或以后复发的 B 细胞 ALL 患者。Tisagenlecleucel也正在接受复发/难治性B细胞非霍奇金淋巴瘤儿科患者的评估，但尚未获准用于这一适应症。目前，美国食品及药物管理局批准的所有其他用于成人患者的 CD19 导向 CAR-T 细胞疗法（axicabtagene ciloleucel、brexucabtagene autoleucel 和 lisocabtagene maraleucel）都在儿童患者中进行研究，部分病例已取得初步结果。随着数据量和复杂性的不断增加，快速吸收和实施这些数据的必要性也在不断增加。在考虑 "非典型 "情况时尤其如此，例如，当患者与关键临床试验中的患者情况不完全一致时，或当有其他治疗方案（如造血干细胞移植（HSCT）或双特异性 T 细胞诱导剂（BITEs））可供选择时。因此，我们编写了一份关于在儿科患者中使用 CD19 导向 CAR-T 细胞疗法的现有文献的相关摘要，并试图为临床医生寻求有关特定临床情况的更多数据提供指导。
{"title":"The Implementation of Chimeric Antigen Receptor (CAR) T-cell Therapy in Pediatric Patients: Where Did We Come From, Where Are We Now, and Where are We Going?","authors":"Tristan Knight E, Olalekan Oluwole, Carrie Kitko","doi":"10.46989/001c.94386","DOIUrl":"https://doi.org/10.46989/001c.94386","url":null,"abstract":"CD19-directed Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized the treatment of patients with B-cell acute lymphoblastic leukemia (B-ALL). Somewhat uniquely among oncologic clinical trials, early clinical development occurred simultaneously in both children and adults. In subsequent years however, the larger number of adult patients with relapsed/refractory (r/r) malignancies has led to accelerated development of multiple CAR T-cell products that target a variety of malignancies, resulting in six currently FDA-approved for adult patients. By comparison, only a single CAR-T cell therapy is approved by the FDA for pediatric patients: tisagenlecleucel, which is approved for patients 25 years with refractory B-cell precursor ALL, or B-cell ALL in second or later relapse. Tisagenlecleucel is also under evaluation in pediatric patients with relapsed/refractory B-cell non-Hodgkin lymphoma, but is not yet been approved for this indication. All the other FDA-approved CD19-directed CAR-T cell therapies available for adult patients (axicabtagene ciloleucel, brexucabtagene autoleucel, and lisocabtagene maraleucel) are currently under investigations among children, with preliminary results available in some cases. As the volume and complexity of data continue to grow, so too does the necessity of rapid assimilation and implementation of those data. This is particularly true when considering “atypical” situations, e.g. those arising when patients do not precisely conform to the profile of those included in pivotal clinical trials, or when alternative treatment options (e.g. hematopoietic stem cell transplantation (HSCT) or bispecific T-cell engagers (BITEs)) are also available. We have therefore developed a relevant summary of the currently available literature pertaining to the use of CD19-directed CAR-T cell therapies in pediatric patients, and sought to provide guidance for clinicians seeking additional data about specific clinical situations.","PeriodicalId":10368,"journal":{"name":"Clinical Hematology International","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140245148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kathryn Taberner, Andrew A. House, Aaron Haig, Cyrus C. Hsia
{"title":"A Case of Renal Iron Overload Associated with Cold Agglutinin Disease Successfully Managed by Rituximab","authors":"Kathryn Taberner, Andrew A. House, Aaron Haig, Cyrus C. Hsia","doi":"10.46989/001c.91478","DOIUrl":"https://doi.org/10.46989/001c.91478","url":null,"abstract":"","PeriodicalId":10368,"journal":{"name":"Clinical Hematology International","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139147776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Asparaginase-associated pancreatitis complicates 2-10% of patients treated for acute lymphoblastic leukemia, causing morbidity and discontinuation of asparaginase administration. Among acute complications, pancreatic fluid collections can be managed conservatively, but intervention is indicated when associated with persistent insulin therapy need and recurrent abdominal pain. Endoscopic treatment has become the standard approach in adult patients, with increasing favorable evidence in children. This work compares the characteristics of a pediatric oncology patient treated at our institution with reported literature experiences, showing feasibility, safety and effectiveness of endoscopic approach.
{"title":"Asparaginase-associated Pancreatitis Complicated by Pancreatic Fluid Collection Treated with Endoscopic Cistogastrostomy in Pediatric Acute Lymphoblastic Leukemia: A Case Report and Systematic Review of the Literature.","authors":"Giulia Fiumana, Alessia Pancaldi, Helga Bertani, Valentina Boarino, Monica Cellini, Lorenzo Iughetti","doi":"10.46989/001c.90958","DOIUrl":"https://doi.org/10.46989/001c.90958","url":null,"abstract":"Asparaginase-associated pancreatitis complicates 2-10% of patients treated for acute lymphoblastic leukemia, causing morbidity and discontinuation of asparaginase administration. Among acute complications, pancreatic fluid collections can be managed conservatively, but intervention is indicated when associated with persistent insulin therapy need and recurrent abdominal pain. Endoscopic treatment has become the standard approach in adult patients, with increasing favorable evidence in children. This work compares the characteristics of a pediatric oncology patient treated at our institution with reported literature experiences, showing feasibility, safety and effectiveness of endoscopic approach.","PeriodicalId":10368,"journal":{"name":"Clinical Hematology International","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138954036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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