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Are Alternative Donors Now Mainstream in Allogeneic Transplant?

Program: Education Program
Hematology Disease Topics & Pathways:
Research, Biological therapies, Lymphoid Leukemias, Acute Myeloid Malignancies, ALL, Hodgkin lymphoma, AML, clinical trials, Clinical Practice (Health Services and Quality), Lymphomas, non-Hodgkin lymphoma, Workforce, Plasma Cell Disorders, Clinical Research, health disparities research, Diversity, Equity, and Inclusion (DEI) , Chronic Myeloid Malignancies, Diseases, Therapies, real-world evidence, Lymphoid Malignancies, registries, Myeloid Malignancies, Study Population, Human, Transplantation
Saturday, December 10, 2022: 4:00 PM-5:15 PM
Great Hall BC (Ernest N. Morial Convention Center)

Description:
Hematopoietic cell transplantation (HCT) is the only potential curative treatment for most of malignant and some of the non-malignant hematological disorders. Recent studies comparing donor to no donor treatment in transplant eligible patients have shown better outcomes in patients undergoing HCT. Donor availability has been one of the important access obstacles to this curative therapy since matched sibling donor availability has been reported to be only ~30%. Matched unrelated donor (MUD) availability is in the 20-40% range for African- and Hispanic- Americans and donor availability is even lower in mixed race and ethnicity which has not been accurately estimated in published data. These estimates are even lower counting to HLA typing, medical deferrals, and suitability related issues. In the absence of a MSD or MUD, alternative donor choices including: haploidentical related (HAPLO), mismatched unrelated (MMUD) and umbilical cord blood (UCB) all have contributed to improve access and outcome of patients who are otherwise eligible for HCT.

Dr. Stephen Spellman will discuss HLA matching and impact on HCT outcomes. He will use a case-based approach focusing on the likelihood of availability by donor type by patient ethnic background considering matched sibling donors and alternative donors, including matched and mismatched unrelated, cord blood and haploidentical related donors. His talk will address complete HLA match by donor type, discussion of areas with limited data available and current controversies warranting future research. 

Dr. Monzr Al Malki will discuss the rapid growth on the use of alternative donors in HCT; specifically, in MMUD setting, including historical data and outcome analysis using conventional calcineurin inhibitor (CNI)-based graft-versus-host disease (GvHD) prophylaxis, optimal choice among multiple MMUDs available using different mis/matching criteria, and the importance of avoiding donor-specific HLA antibodies (DSA) in mitigating the risk of graft rejection. Dr. Al Malki later described current novel approaches to improve outcomes in MMUD HCT including post-transplant cyclophosphamide (PTCy) and Abatacept (ABA), discussing some of the main differences between these novel approaches and active clinical trial.

Dr. Arnon Nagler will debate the HAPLO donor vs UCB as graft source options based on the currently available data. This discussion should give some guidance and help the transplant physician to choose among a haploidentical versus a cord blood donor.  Although the number of HAPLO transplants (mainly non-T cell-depleted haplo transplants with post-transplant cyclophosphamide) is increasing while UCB is decreasing worldwide, recent developments in UCB and especially cord blood expansion and other strategies to improve engraftment and immune reconstitution post-UCB make UCB as a valuable option. Given the limited numbers of published or ongoing well-designed randomized controlled trials, the decision to perform haplo transplant or CBT in each patient depends not only on the patient, disease and donor characteristics and availability (although most if not all patients should have in principle an alternative donor) but also on the transplant physician discretion and most importantly center experience, preference and center’s ongoing clinical trials and strategies.

Chair:
Monzr M. Al Malki, MD, City of Hope National Medical Center
Disclosures:
Al Malki: Hasna Biopharma: Membership on an entity's Board of Directors or advisory committees; NexImmune: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Miltenyi Biotec: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; CareDx: Consultancy, Research Funding.
Hematopoietic cell transplantation (HCT) is the only potential curative treatment for most of malignant and some of the non-malignant hematological disorders. Recent studies comparing donor to no donor treatment in transplant eligible patients have shown better outcomes in patients undergoing HCT. Donor availability has been one of the important access obstacles to this curative therapy since matched sibling donor availability has been reported to be only ~30%. Matched unrelated donor (MUD) availability is in the 20-40% range for African- and Hispanic- Americans and donor availability is even lower in mixed race and ethnicity which has not been accurately estimated in published data. These estimates are even lower counting to HLA typing, medical deferrals, and suitability related issues. In the absence of a MSD or MUD, alternative donor choices including: haploidentical related (HAPLO), mismatched unrelated (MMUD) and umbilical cord blood (UCB) all have contributed to improve access and outcome of patients who are otherwise eligible for HCT.

Dr. Stephen Spellman will discuss HLA matching and impact on HCT outcomes. He will use a case-based approach focusing on the likelihood of availability by donor type by patient ethnic background considering matched sibling donors and alternative donors, including matched and mismatched unrelated, cord blood and haploidentical related donors. His talk will address complete HLA match by donor type, discussion of areas with limited data available and current controversies warranting future research. 

Dr. Monzr Al Malki will discuss the rapid growth on the use of alternative donors in HCT; specifically, in MMUD setting, including historical data and outcome analysis using conventional calcineurin inhibitor (CNI)-based graft-versus-host disease (GvHD) prophylaxis, optimal choice among multiple MMUDs available using different mis/matching criteria, and the importance of avoiding donor-specific HLA antibodies (DSA) in mitigating the risk of graft rejection. Dr. Al Malki later described current novel approaches to improve outcomes in MMUD HCT including post-transplant cyclophosphamide (PTCy) and Abatacept (ABA), discussing some of the main differences between these novel approaches and active clinical trial.

Dr. Arnon Nagler will debate the HAPLO donor vs UCB as graft source options based on the currently available data. This discussion should give some guidance and help the transplant physician to choose among a haploidentical versus a cord blood donor.  Although the number of HAPLO transplants (mainly non-T cell-depleted haplo transplants with post-transplant cyclophosphamide) is increasing while UCB is decreasing worldwide, recent developments in UCB and especially cord blood expansion and other strategies to improve engraftment and immune reconstitution post-UCB make UCB as a valuable option. Given the limited numbers of published or ongoing well-designed randomized controlled trials, the decision to perform haplo transplant or CBT in each patient depends not only on the patient, disease and donor characteristics and availability (although most if not all patients should have in principle an alternative donor) but also on the transplant physician discretion and most importantly center experience, preference and center’s ongoing clinical trials and strategies.

Monzr M. Al Malki, MD

Department of Hematology/HCT, City of Hope National Medical Center, Duarte, CA

Stephen R. Spellman

National Marrow Donor Program, Minneapolis, MN; CIBMTR® (Center for International Blood and Marrow Transplant Research), National Marrow Donor Program/Be The Match, Minneapolis, MN

Arnon Nagler, MD

Hematology Division, Chaim Sheba Medical Center, Tel Hashomer, Israel

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