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1.
ASTCT Clinical practice recommendations for transplant and cellular therapies in diffuse large B-cell lymphoma
Epperla, N., Kumar, A., Abutalib, S. A., Awan, F. T., Chen, Y. B., Gopal, A. K., Holter-Chakrabarty, J., Kekre, N., Lee, C. J., Lekakis, L., et al
Transplantation and cellular therapy. 2023
Abstract
Autologous hematopoietic cell transplantation (auto-HCT) has long remained the standard approach for patients with relapsed/refractory (R/R) chemosensitive diffuse large B-cell lymphoma (DLBCL). However, the advent of chimeric antigen receptor (CAR) T-cell therapy has caused a paradigm shift in the management of R/R DLBCL patients, especially with the recent approval of CD19-directed CAR T-cell therapy in the second line setting in high-risk groups (primary refractory and early relapse [≤12 months]). Consensus on the contemporary role, optimal timing, and sequencing of HCT and cellular therapies in DLBCL is lacking. Therefore, the American Society of Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines undertook this project to formulate consensus recommendations to address this unmet need. The RAND-modified Delphi method was used to generate 20 consensus statements with a few key statements as follows: 1) in the first-line setting, there is no role of auto-HCT consolidation for those achieving complete remission (CR) following R-CHOP or similar therapy in non-double hit/triple hit cases (DHL/THL) and in DHL/THL cases receiving intensive induction therapies, but auto-HCT may be considered in eligible patients receiving R-CHOP or similar therapies in DHL/THL cases. 2) Auto-HCT consolidation with thiotepa-based conditioning is standard-of-care for eligible patients with primary central nervous system achieving CR with first-line therapy. 3) In the primary refractory and early relapse setting, the preferred option is CAR T-cell therapy, while in late relapse (>12 months), consolidation with auto-HCT is recommended in those achieving chemosensitivity to salvage therapy (CR or partial response), and CAR T-cell therapy is recommended in those not achieving remission. These clinical practice recommendations will serve as a tool to guide clinicians managing patients with newly diagnosed and R/R DLBCL.
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2.
Updated Indications for Immune Effector Cell Therapy: 2023 Guidelines from the American Society for Transplantation and Cellular Therapy
Kanate, A. S., Majhail, N., DeFilipp, Z. M., Dhakal, B., Dholaria, B., Hamilton, B., Herrera, A. F., Inamoto, Y., Jain, T., Perales, M. A., et al
Transplantation and cellular therapy. 2023
Abstract
The American Society for Transplantation and Cellular Therapy (ASTCT) published its guidelines on indications for autologous and allogeneic hematopoietic cell transplantation (HCT) and immune effector cell therapy (IECT) in 2020. Since then we have witnessed rapid advancements in the field of IECT, resulting in several new chimeric antigen receptor T-cell (CAR-T) products and disease indications being approved by the U.S. Food and Drug Administration (FDA). To keep abreast of these practice changes, the ASTCT Committee on Practice Guidelines commissioned a focused update covering CAR-T therapy indications. This brief manuscript presents updated ASTCT recommendations on indications for CAR-T therapy. Only FDA approved indications for CAR-T were recommended and categorized as "standard of care" (S), where indication is well defined and supported by evidence. The ASTCT will continue to periodically review these guidelines and update them as new evidence becomes available.
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3.
Hematopoietic Cell Transplantation in the Management of Myelodysplastic Syndrome: An Evidence-Based Review from the American Society for Transplantation and Cellular Therapy Committee on Practice Guidelines
DeFilipp, Z., Ciurea, S. O., Cutler, C., Robin, M., Warlick, E. D., Nakamura, R., Brunner, A. M., Dholaria, B., Walker, A. R., Kröger, N., et al
Transplantation and Cellular Therapy. 2023;29(2):71-81
Abstract
The sole curative therapy for myelodysplastic syndrome (MDS) is allogeneic hematopoietic cell transplantation (HCT). Here this therapeutic modality is reviewed and critically evaluated in the context of the evidence. 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 MDS experts comprising transplantation and nontransplantation physicians developed consensus treatment recommendations. This review summarizes the standard MDS indications for HCT and addresses areas of controversy. Recent prospective trials have confirmed that allogeneic HCT confers survival benefits in patients with advanced or high-risk MDS compared with nontransplantation approaches, and the use of HCT is increasing in older patients with good performance status. However, patients with high-risk cytogenetic or molecular mutations remain at high risk for relapse. It is unknown whether administration of novel therapies before or after transplantation may decrease the risk of disease relapse in selected populations. Ongoing and future studies will investigate revised approaches to disease risk stratification, patient selection, and post-transplantation approaches to optimize allogeneic HCT outcomes for patients with MDS.
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4.
Evaluation of children with malignancies for blood and marrow transplantation: A report from the ASTCT Committee on Practice Guidelines
Fraint, E., Abdel-Azim, H., Bhatt, N. S., Broglie, L., Chattha, A., Kohorst, M., Ktena, Y. P., Lee, M. A., Long, S., Qayed, M., et al
Transplantation and cellular therapy. 2023
Abstract
Evaluation of a candidate for hematopoietic cell transplant (HCT) is a complex process with substantial inter-center variability. Although literature providing guidance for evaluating the eligibility of adults is well established, similar guidance for children is lacking. To address gaps between adult recommendations and the specific needs of children, we convened a panel of pediatric HCT experts from a wide geographic range of American Society of Transplantation and Cellular Therapy (ASTCT) member institutions to offer pediatric-focused pre-HCT evaluation recommendations. In this report from the ASTCT Committee on Practice Guidelines, we present a practical framework for evaluating children with malignancies who are candidates for HCT. We also highlight key differences from adults and emphasize areas of unmet need that require additional research to delineate best practices.
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5.
ASTCT Committee on Practice Guidelines Survey on Evaluation & Management of Diffuse Large B-cell Lymphoma after failure of Chimeric antigen receptor T cell therapy (CAR-T) therapy
Ahmed, N., Kumar, A., Kharfan-Dabaja, M. A., DeFilipp, Z., Herrera, A., Hashmi, S., Dholaria, B., Perales, M. A., Carpenter, P. A., Hamadani, M.
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Chimeric antigen receptor T cell therapy (CAR-T) is a major advance in managing aggressive relapsed and/or refractory B-cell lymphomas; however, relapses are frequent and pose a major therapeutic challenge. There is substantial variability across transplant and cellular therapy programs in assessing and managing post-CAR-T failures. METHODS The American Society for Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines conducted an online cross-sectional survey between August 2021 and October 2021, to determine the U.S. lymphoma and transplant and cellular therapy physicians' practice patterns for the detection and diagnosis of CAR-T failure, and management strategies for diffuse large B cell lymphoma (DLBCL) in this particular setting. RESULTS Email surveys were sent to 901 potential participants, of which 174 (19%) completed the survey. Responders were mainly White (51.2%), male (70.7%), and with >10 years of practice experience (51.2%). 87% of the responders were affiliated with university/teaching centers; 54.6% had general oncology practices and 45.4% had lymphoma-focused transplant/cellular therapy practices. The most common periods to perform surveillance scans were at 3 months and 12 months after CAR-T infusion. 88.5% of responders would often or always consider a biopsy to confirm relapse and 89% would routinely check for the persistence of the antigen targeted by the CAR (e.g. CD19 in the case of CD19 CAR-T). The most popular first salvage regimen for relapse or progression was an alternate CAR-T therapy (dual or alternate target) regardless of CD19 positivity. 27% of responders chose this regimen for CD19 positive relapse, while 31% of responders did so for CD19 negative relapse. 88.5% of responders favored consolidative allogeneic hematopoietic cell transplantation (alloHCT) after response to salvage, whereas 51.2% of physicians would consider autologous hematopoietic cell transplant (AHCT) in transplant naïve patients. CONCLUSIONS There is substantial cross-center variation in surveillance, diagnosis, and management of CAR-T failure. Prospective clinical trials evaluating novel agents in this setting are urgently needed to identify best management strategies.
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6.
ASTCT Clinical Practice recommendations for transplant and cellular therapies in multiple myeloma
Dhakal, B., Shah, N., Kansagra, A., Kumar, A., Lonial, S., Garfall, A., Cowan, A., Poudyal, B. S., Costello, C., Gay, F., et al
Transplantation and cellular therapy. 2022
Abstract
Over the past decade, therapeutic options in multiple myeloma (MM) have changed dramatically. Given the unprecedented efficacy of novel agents, the role of hematopoietic cell transplantation (HCT) in MM remains under scrutiny. Rapid advances in myeloma immunotherapy including the recent approval of chimeric antigen receptor (CAR) T-cell therapy will impact the MM therapeutic landscape. The American Society for Transplantation and Cellular Therapy (ASTCT) convened an expert panel to formulate clinical practice recommendations for role, timing, and sequencing of autologous (auto-HCT), allogeneic (allo-HCT) and CAR T-cell therapy for patients with newly diagnosed (NDMM) and relapsed/refractory MM (RRMM). The RAND-modified Delphi method was used to generate consensus statements. Twenty consensus statements were generated. The panel endorsed continued use of auto-HCT consolidation for patients with NDMM as a standard-of-care option, whereas in the front line allo-HCT and CAR-T were not recommended outside the setting of clinical trial. For patients not undergoing auto-HCT upfront, the panel recommended its use in first relapse. Lenalidomide as a single agent was recommended for maintenance especially for standard risk patients. In the RRMM setting, the panel recommended the use of CAR-T in patients with 4 or more prior lines of therapy. The panel encouraged allo-HCT in RRMM setting only in the context of clinical trial. The panel found RAND-modified Delphi methodology effective in providing a formal framework for developing consensus recommendations for the timing and sequence of cellular therapies for MM.
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7.
ASTCT, CIBMTR, and EBMT clinical practice recommendations for transplant and cellular therapies in mantle cell lymphoma
Munshi, P. N., Hamadani, M., Kumar, A., Dreger, P., Friedberg, J. W., Dreyling, M., Kahl, B., Jerkeman, M., Kharfan-Dabaja, M. A., Locke, F. L., et al
Bone marrow transplantation. 2021
Abstract
Autologous (auto-) or allogeneic (allo-) hematopoietic cell transplantation (HCT) are accepted treatment modalities for mantle cell lymphoma (MCL). Recently, chimeric antigen receptor (CAR) T-cell therapy received approval for MCL; however, its exact place and sequence in relation to HCT is unclear. The ASTCT, CIBMTR, and the EBMT, jointly convened an expert panel to formulate consensus recommendations for role, timing, and sequencing of auto-, allo-HCT, and CAR T-cell therapy for patients with newly diagnosed and relapsed/refractory (R/R) MCL. The RAND-modified Delphi method was used to generate consensus statements. Seventeen consensus statements were generated; in the first-line setting auto-HCT consolidation represents standard-of-care in eligible patients, whereas there is no clear role of allo-HCT or CAR T-cell therapy, outside of a clinical trial. In the R/R setting, the preferential option is CAR T-cell therapy especially in MCL failing or intolerant to at least one Bruton's tyrosine kinase inhibitor, while allo-HCT is recommended if CAR T-cell therapy has failed or is not feasible. In the absence of contemporary evidence-based data, the panel found RAND-modified Delphi methodology effective in providing a formal framework for developing consensus recommendations for the timing and sequence of cellular therapies for MCL.
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8.
Indications for Hematopoietic Cell Transplantation and Immune Effector Cell Therapy: Guidelines from the American Society for Transplantation and Cellular Therapy: Guidelines for Hematopoietic Transplantation and Cellular Therapy
Kanate, A. S., Majhail, N. S., Savani, B. N., Bredeson, C., Champlin, R. E., Crawford, S., Giralt, S. A., LeMaistre, C. F., Marks, D. I., Omel, J. L., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Abstract
The American Society for Transplantation and Cellular Therapy (ASTCT) published its first white paper on indications for autologous and allogeneic hematopoietic cell transplantation (HCT) in 2015. It was identified at the time that periodic updates of indications would be required to stay abreast with state of the art and emerging indications and therapy. In recent years, the field has not only seen an improvement in transplantation technology thus widening the therapeutic scope of HCT, but additionally a whole new treatment strategy using modified immune effector cells including chimeric antigen receptor T-cell (CART-cell) and T-cell receptors (TCRs) has emerged. The guidelines review committee of the ASTCT deemed it optimal to update the ASTCT recommendations for indications for HCT to include new data and to incorporate indications for immune effector cell therapy (IECT) where appropriate. The guidelines committee established multi-stakeholder task force consisting of transplant experts, payer representatives and a patient advocate to provide guidance on indications for HCT and IECT. This manuscript presents the updated recommendations from the ASTCT on indications for HCT and IECT. Indications for HCT/IECT were categorized as (1) Standard of care, where indication is well defined and supported by evidence, (2) Standard of care, clinical evidence available, where large clinical trials and observational studies are not available but has been shown to be effective therapy, (3) Standard of care, rare indication, for rare diseases where demonstrated effectiveness exist but large clinical trials and observational studies are not feasible, (4) Developmental, for diseases where pre-clinical and/or early phase clinical studies show HCT/IECT to be a promising treatment option, and (5) Not generally recommended, where available evidence does not support the routine use of HCT/IECT. The ASTCT will continue to periodically review these guidelines and update them as new evidence becomes available.
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Hematopoietic Cell Transplantation in the Treatment of Newly Diagnosed Adult Acute Myeloid Leukemia: An Evidence-Based Review from the American Society of Transplantation and Cellular Therapy
Dholaria, B., Savani, B. N., Hamilton, B. K., Oran, B., Liu, H. D., Tallman, M. S., Ciurea, S. O., Holtzman, N. G., Ii, G. L. P., Devine, S. M., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2020
Abstract
The role of hematopoietic cell transplantation (HCT) in the management of newly diagnosed adult acute myeloid leukemia (AML) is reviewed and critically evaluated in this evidence-based review. An AML expert panel, consistent of both transplant and non-transplant experts was invited to develop clinically relevant frequently asked questions covering disease- and HCT-related topics. A systematic literature review was conducted to generate core recommendations that were graded based on the quality and strength of underlying evidence based on the standardized criteria established by American Society of Transplantation and Cellular Therapy Steering Committee for evidence-based reviews. Allogeneic HCT offers a survival benefit in patients with intermediate and high-risk AML and is currently a part of standard clinical care. We recommend the preferential use of myeloablative conditioning in eligible patients. A haploidentical related donor marrow graft is preferred over a cord blood unit in the absence of a fully HLA-matched donor. The evolving role of allogeneic HCT in the context of measurable residual disease monitoring and recent therapeutic advances in AML with regards to maintenance therapy after HCT are also discussed.
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10.
Maintenance Therapies for Hodgkin and Non-Hodgkin Lymphomas After Autologous Transplantation: A Consensus Project of ASBMT, CIBMTR, and the Lymphoma Working Party of EBMT
Kanate, A. S., Kumar, A., Dreger, P., Dreyling, M., Le Gouill, S., Corradini, P., Bredeson, C., Fenske, T. S., Smith, S. M., Sureda, A., et al
JAMA oncology. 2019
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Abstract
Importance: Maintenance therapies are often considered as a therapeutic strategy in patients with lymphoma following autologous hematopoietic cell transplantation (auto-HCT) to mitigate the risk of disease relapse. With an evolving therapeutic landscape, where novel drugs are moving earlier in therapy lines, evidence relevant to contemporary practice is increasingly limited. The American Society for Blood and Marrow Transplantation (ASBMT), Center for International Blood and Marrow Transplant Research (CIBMTR), and European Society for Blood and Marrow Transplantation (EBMT) jointly convened an expert panel with diverse expertise and geographical representation to formulate consensus recommendations regarding the use of maintenance and/or consolidation therapies after auto-HCT in patients with lymphoma. Observations: The RAND-modified Delphi method was used to generate consensus statements where at least 75% vote in favor of a recommendation was considered as consensus. The process included 3 online surveys moderated by an independent methodological expert to ensure anonymity and an in-person meeting. The panel recommended restricting the histologic categories covered in this project to Hodgkin lymphoma (HL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and follicular lymphoma. On completion of the voting process, the panel generated 22 consensus statements regarding post auto-HCT maintenance and/or consolidation therapies. The grade A recommendations included endorsement of: (1) brentuximab vedotin (BV) maintenance and/or consolidation in BV-naive high-risk HL, (2) rituximab maintenance in MCL undergoing auto-HCT after first-line therapy, (3) rituximab maintenance in rituximab-naive FL, and (4) No post auto-HCT maintenance was recommended in DLBCL. The panel also developed consensus statements for important real-world clinical scenarios, where randomized data are lacking to guide clinical practice. Conclusions and Relevance: In the absence of contemporary evidence-based data, the panel found RAND-modified Delphi methodology effective in providing a rigorous framework for developing consensus recommendations for post auto-HCT maintenance and/or consolidation therapies in lymphoma.