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As the number and type of regulatory authority-approved cellular therapies grow, clinical treatment centers face a heavy burden of duplicative documentation around initial qualification, ongoing auditing, and reporting, with overlapping requirements from each manufacturer to ensure safe use of their specific product, which in the United States are stipulated under individual Food and Drug Administration (FDA) Biologic License Applications. The American Society for Transplantation and Cellular Therapy (ASTCT) convened the 80/20 Task Force to consider challenges and potential solutions to these issues. The Task Force proposed that 80% of manufacturers' requirements for onboarding and ongoing operations of commercially available products could be standardized and streamlined. Task Force members interviewed dozens of stakeholders, including clinicians at large academic medical centers already using commercial and investigational immune effector cell (IEC) products, regulators, members of accrediting bodies and professional cellular therapy societies, and manufacturers of IEC therapies for oncologic indications. In November 2021, the Task Force organized and led virtual discussions in a public forum and at a private ASTCT 80/20 Workshop at the online AcCELLerate Forum, a cellular-therapy stakeholders' meeting organized by the ASTCT, National Marrow Donor Program (NMDP), and Center for International Blood and Marrow Transplant Research (CIBMTR). At the workshop, approximately 60 stakeholders worked to identify and prioritize common challenges in onboarding and maintenance of operations at clinical sites for commercial FDA-approved and future IEC therapies and ways to streamline the process. It was agreed that standardization would improve efficiency of onboarding, allowing more cost-effective, sustainable growth of approved IEC therapies at treatment centers, and facilitate wider access while maintaining safety and clinical success. This early but extensive survey of stakeholders resulted in 5 overarching suggestions for both established and emerging treatment centers: (1) eliminate duplication in accreditation and auditing of clinical sites; (2) define expectations for the education about and management of CAR-T therapy toxicities to potentially replace product-specific REMS programs; (3) streamline current REMS education, testing, and data reporting; (4) standardize information technology (IT) platforms supporting enrollment, clinical site-manufacturer communication, and logistics of maintaining chain of identity/chain of custody across multiple transportation steps; and (5) encourage the use of universal nomenclature by cell therapy manufacturers. Future discussions need to engage a broader range of stakeholders, including administrators, pharmacists, nurses, data coordinators, surgeons, pathologists, and those developing promising cellular therapies for solid tumors, as well as teams from smaller academic or community cancer center settings. Continued collaboration with stakeholders outside of clinical sites will include accrediting bodies/auditors, established and emerging cell therapy companies, software developers, professional societies, and the patients who receive these therapies. Active dialog with government regulators remains essential. Such joint efforts are critical as the number of IEC therapies for myriad oncologic and nononcologic indications grows., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

The role of hematopoietic cell transplantation (HCT) in adults with acute lymphoblastic leukemia (ALL) is reviewed and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the recommendations. A panel of ALL experts developed consensus on the treatment recommendations based on the evidence. Allogeneic HCT offers a survival benefit in selected patients with ALL, and this review summarizes the standard indications as well as the areas of controversy. There is now greater experience with pediatric-inspired chemotherapy regimens that has transformed upfront therapy for adult ALL, resulting in higher remission rates and overall survival. This in turn has increased the equipoise around decision making for ALL in first complete remission (CR1) when there is no measurable residual disease (MRD) at the end of induction and/or consolidation. Randomized studies are needed for adults with ALL to compare allogeneic HCT in CR1 with pediatric-inspired chemotherapy alone. Indications for transplantation in the evolving landscape of MRD assessments and novel targeted and immune therapeutics remain important areas of investigation., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

On August 30, 2017 the US Food and Drug Administration approved tisagenlecleucel (Kymriah; Novartis, Basel, Switzerland), a synthetic bioimmune product of anti-CD19 chimeric antigen receptor T cells (CAR-T), for the treatment of children and young adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL). With this new era of personalized cancer immunotherapy, multiple challenges are present, ranging from implementation of a CAR-T program to safe delivery of the drug, long-term toxicity monitoring, and disease assessments. To address these issues experts representing the American Society for Blood and Marrow Transplant, the European Society for Blood and Marrow Transplantation, the International Society of Cell and Gene Therapy, and the Foundation for the Accreditation of Cellular Therapy formed a global CAR-T task force to identify and address key questions pertinent for hematologists and transplant physicians regarding the clinical use of anti CD19 CAR-T therapy in patients with B-ALL. This article presents an initial roadmap for navigating common clinical practice scenarios that will become more prevalent now that the first commercially available CAR-T product for B-ALL has been approved., (Copyright © 2018 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: The outlook for patients with refractory and relapsed acute lymphocytic leukaemia (ALL) is poor. CD22 is highly expressed in patients with ALL. Inotuzumab ozogamicin is a CD22 monoclonal antibody conjugated to the toxin calecheamicin. We did a phase 2 study to assess the efficacy of this antibody., Methods: We recruited patients at the MD Anderson Cancer Center, Houston, TX, USA, between June, 2010, and March, 2011. Adults and children with refractory and relapsed ALL were eligible. Ten adults were treated before enrolment of children started. Patients were given 1·8 mg/m(2) inotuzumab ozogamicin intravenously over 1 h every 3-4 weeks (the first three adults and three children received 1·3 mg/m(2) in the first course). The primary endpoint was overall response (complete response or marrow complete response with no recovery of platelet count or incomplete recovery of neutrophil and platelet counts). Analysis was done by intention to treat. This study is registered, number NCT01134575., Findings: 49 patients were enrolled and treated. Median age was 36 years (range 6-80). CD22 was expressed in more than 50% of blasts in all patients. The median number of courses was two (range one to five) and the median time between courses was 3 weeks (range 3-6). Nine (18%) patients had complete response, 19 (39%) had marrow complete response, 19 (39%) had resistant disease, and two (4%) died within 4 weeks of starting treatment. The overall response rate was 57% (95% CI 42-71). The most frequent adverse events during course one of treatment were fever (grade 1-2 in 20 patients, grade 3-4 in nine), hypotension (grade 1-2 in 12 patients, grade 3 in one), and liver-related toxic effects (bilirubin: grade 1-2 in 12 patients, grade 3 in two; raised aminotransferase concentration: grade 1-2 in 27 patients, grade 3 in one)., Interpretation: Inotuzumab ozogamicin shows promise as a treatment for refractory and relapsed ALL., Funding: Pfizer., (Copyright © 2012 Elsevier Ltd. All rights reserved.)