1.
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.
2.
Impact of T-cell dose on the outcome of T-cell replete HLA matched allogeneic peripheral blood stem cell transplantation
Saad, A., Lamb, L., Wang, T., Hemmer, M. T., Spellman, S., Couriel, D., Alousi, A., Pidala, J., Abdel-Azim, H., Agrawal, V., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
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Abstract
BACKGROUND Data on whether T-cell dose of allogeneic peripheral blood stem cell (PBSC) product influences transplant outcome are conflicting. METHODS Using CIBMTR database, we identified 2,736 adult patients who underwent first allogeneic peripheral blood stem cell (PBSC) transplant for acute leukemia (AML, ALL) or myelodysplastic syndrome (MDS) between 2008-2014 using an HLA-matched sibling donor (MSD) or 8/8-matched unrelated donor (MUD). We excluded ex-vivo and in-vivo T-cell depleted transplants. Correlative analysis was performed between CD3+ T-cell dose and risk of graft-versus-host-disease (GVHD), relapse, non-relapse mortality (NRM), disease free survival (DFS) and overall survival (OS). RESULTS Using maximum likelihood estimation method, we identified CD3+ T-cell cell dose cutoff that separated risk of acute GVHD (aGVHD) grade II-IV in both MSD and MUD groups. A CD3+ T-cell dose cutoff of 14x10(7) cells/kg identified MSD/low CD3+ (n=223) and MSD/high CD3+ (n=1214), and a dose of 15x10(7) cells/kg identified MUD/low CD3+ (n=197) and MUD/high CD3+ (n=1102). With univariate analysis, MSD/high CD3+ group had higher cumulative incidence of day 100 aGVHD grade II-IV of 33% vs 25% when compared to MSD/low CD3+ group (P value =0.009). There was no other difference between both groups in engraftment rate, risk of aGVHD grade III-IV or chronic GVHD (cGVHD), NRM, relapse, DFS, or OS. MUD/high CD3+ group had higher cumulative incidence of day 100 aGVHD grade II-IV of 49% vs 41% when compared to MUD/low CD3+ group (P value =0.04). There was no other difference between both groups in engraftment rate, risk of severe aGVHD or cGVHD, NRM, relapse, DFS, or OS. Multivariate analysis of MSD and MUD groups failed to show an association between CD3+ T-cell dose and risk of either aGVHD grade II-IV (p value =0.1 and 0.07 respectively) or cGVHD (p value=0.8 and 0.3 respectively). Sub-analysis of CD4, CD8 and CD4/CD8 ratio failed to identify cutoff values predictive of transplant outcome. Using log-rank test, the sample size was, however, suboptimal to identify difference at these cutoff cell dose. CONCLUSION In this registry study, CD3+ T-cell dose of PBSCT product did not influence risk of aGVHD or cGVHD or other transplant outcomes when using HLA-matched sibling or 8/8 unrelated donors. Subset analysis of CD4+ and CD8+ T-cell dose was not possible for small sample size.
PICO Summary
Population
Patients reported to CIBMTR database with acute leukaemia (ALL or AML) or myelodysplastic syndrome between 2008-2014 (n=2736)
Intervention
First allogeneic peripheral blood stem cell using an HLA-matched sibling donor (MSD)
Comparison
8/8-matched unrelated donor (MUD)
Outcome
Using maximum likelihood estimation method, we identified CD3+ T-cell cell dose cutoff that separated risk of acute GVHD (aGVHD) grade II-IV in both MSD and MUD groups. A CD3+ T-cell dose cutoff of 14x10(7) cells/kg identified MSD/low CD3+ (n=223) and MSD/high CD3+ (n=1214), and a dose of 15x10(7) cells/kg identified MUD/low CD3+ (n=197) and MUD/high CD3+ (n=1102). With univariate analysis, MSD/high CD3+ group had higher cumulative incidence of day 100 aGVHD grade II-IV of 33% vs 25% when compared to MSD/low CD3+ group. MUD/high CD3+ group had higher cumulative incidence of day 100 aGVHD grade II-IV of 49% vs 41% when compared to MUD/low CD3+ group. Multivariate analysis of MSD and MUD groups failed to show an association between CD3+ T-cell dose and risk of either aGVHD grade II-IV or cGVHD. Sub-analysis of CD4, CD8 and CD4/CD8 ratio failed to identify cutoff values predictive of transplant outcome.