Pros and cons of the 2 promising different haploidentical HCT approaches
| . | Haploidentical nonmyeloablative, T-cell–replete, bone marrow transplant with thiotepa and PTCy18,33,34 . | Haploidentical myeloablative, ex vivo T-cell–deplete PBSC transplant using advanced-technology graft manipulation19-21,42 . |
|---|---|---|
| Pros | • Nonmyeloablative • >90% donor availability • Most adults can tolerate the conditioning regimen • Good rates of engraftment • Multicenter trial completed in middle- to high-income settings • Event-free survival: >90% in adults • Overall 2-year survival: >90% • Low rates of acute and chronic GvHD • Typically, discontinuation of immunosuppressive therapy in 1 year • Protocols easily replicable at different institutions and relatively inexpensive | • >90% donor availability • Event-free survival: >80% • Overall survival: 80%-90% • Low rates of acute and chronic GvHD • Prevents EBV-PTLD by removing CD19+ cells ex vivo • Reduced need for posttransplant immune-suppressive medications |
| Cons | • Late health effects are not well established • Graft rejection (~12.5% in <18 years) • Increased risk of viral reactivations • May be prohibitive to patients with significant chronic kidney disease stage 4 or 5 • Limited insurance coverage, donor eligibility, and a high rate of DSAs may limit access • Late health effects on fertility are not well described, expected, or studied systematically | • Limited to single-center experiences • Expensive and labor-intensive • Variability in quality of cells depending on the source • Limited follow-up • Late health effects are not well established • May be prohibitive to patients with significant chronic kidney disease stage 4 or 5 • Specialized expertise required • Delayed immune reconstitution • Increased risk of viral reactivations • Graft rejection (0%-14%) • Fertility in women is likely to be low, not studied systematically |
| . | Haploidentical nonmyeloablative, T-cell–replete, bone marrow transplant with thiotepa and PTCy18,33,34 . | Haploidentical myeloablative, ex vivo T-cell–deplete PBSC transplant using advanced-technology graft manipulation19-21,42 . |
|---|---|---|
| Pros | • Nonmyeloablative • >90% donor availability • Most adults can tolerate the conditioning regimen • Good rates of engraftment • Multicenter trial completed in middle- to high-income settings • Event-free survival: >90% in adults • Overall 2-year survival: >90% • Low rates of acute and chronic GvHD • Typically, discontinuation of immunosuppressive therapy in 1 year • Protocols easily replicable at different institutions and relatively inexpensive | • >90% donor availability • Event-free survival: >80% • Overall survival: 80%-90% • Low rates of acute and chronic GvHD • Prevents EBV-PTLD by removing CD19+ cells ex vivo • Reduced need for posttransplant immune-suppressive medications |
| Cons | • Late health effects are not well established • Graft rejection (~12.5% in <18 years) • Increased risk of viral reactivations • May be prohibitive to patients with significant chronic kidney disease stage 4 or 5 • Limited insurance coverage, donor eligibility, and a high rate of DSAs may limit access • Late health effects on fertility are not well described, expected, or studied systematically | • Limited to single-center experiences • Expensive and labor-intensive • Variability in quality of cells depending on the source • Limited follow-up • Late health effects are not well established • May be prohibitive to patients with significant chronic kidney disease stage 4 or 5 • Specialized expertise required • Delayed immune reconstitution • Increased risk of viral reactivations • Graft rejection (0%-14%) • Fertility in women is likely to be low, not studied systematically |
The third haploidentical transplant protocol is no longer open at the National Institutes of Health clinical center: nonmyeloablative, in vivo T-cell depletion with alemtuzumab using PBSC transplant.35,37
DSA, donor-specific antibody; EBV, Epstein-Barr virus.