Transplant outcomes from published studies using haploidentical HCT with PTCy for SCD
| Characteristic . | Bolanos-Meade et al16 . | De la Fuente et al33 . | Fitzhugh et al35 . | Saraf et al39 . | Pawlowska et al41 . |
|---|---|---|---|---|---|
| Protocol | Phase 1/2, single center | Phase 2, multicenter | Phase 1/2, single center | Phase 2 single center | Phase 2 single center |
| Goal | Full donor chimerism | Full donor chimerism | Stable mixed donor-recipient chimerism | Full donor chimerism | Full donor chimerism (PTIS-HCT approach) |
| Stem cell source | Bone marrow* | Bone marrow* | Peripheral blood | Peripheral blood | Bone marrow (3) Peripheral blood (1) |
| Donor type | Haploidentical | Haploidentical | Haploidentical | Haploidentical | Haploidentical |
| Donor availability† | 100% | >90% | 100% | 90% | 100% |
| Number of patients | 14 | 18 | 23 (21-SCD) | 8 | 4 |
| Age, median (range), y | 30 (15-46) | 20.9 (12.1-26) | 36 (20-56) | 29 (20-38) | 18.5 (13 to 23) |
| Type of conditioning | Nonmyeloablative | Nonmyeloablative | Nonmyeloablative | Nonmyeloablative | Reduced toxicity |
| Conditioning | ATG, fludarabine, cyclophosphamide, TBI (200 cGy) | ATG, fludarabine, cyclophosphamide, thiotepa, TBI (200 cGy) | Alemtuzumab, TBI (400 cGy) | ATG, fludarabine, cyclophosphamide, TBI (300 cGy) | PTIS: fludarabine and dexamethasone × 2 courses; then ATG, busulfan, fludarabine |
| GvHD prophylaxis | PTCy, tacrolimus, sirolimus, MMF | PTCy, sirolimus, MMF | PTCy,‡ sirolimus | PTCy, sirolimus, MMF | PTCy, tacrolimus, MMF |
| Median follow-up, mo | 23.4 (minimal 6.9) | 13.3 (IQR, 3.8-23.1) | 38 (range, 8-74) | 17 (range, 12-30) | 5-11 |
| Engraftment rate | 57% (8/14) | 83% (15/18) | Cohort 1: 33% (1/3) Cohort 2: 63% (5/8) Cohort 3: 83% (10/12) | ≥95% (7/8) | 100% |
| Mixed chimerism | 25% (2/8) at 6 months | None | 100% (16/16) | 13% (1/8) | None |
| EFS | NA | 93% | NA | 75% (6/8) | NA |
| OS | 100% | 100% | 87% (11/12) | 88% (7/8) | 100% |
| Graft failure | 43% (1 primary; 5 secondary) | 6% (1/15)# | 65% (7 primary; 8 secondary); 50% in Cohort 3 | 12.5% (1/8) | 0% |
| TRM | 0% | 0% | 9.5% (2/21) | 13% (1/8) | 0% |
| Acute GvHD >2 | 0% | 13% (2/16) | 0% | 25% (2/8) | 25% (1/4) |
| Chronic GvHD (moderate-severe) | 0% | 6% (1/16) | 0% | 13% (1/8) | 75% (3/4) |
| Immunosuppression duration (IST) | 14.2% (2/14) still on at publication | 85% (6/7) off at 1 year | Continuing | 3/6 on IST | 1/4 on IST |
| Complications | PRES (3), viral reactivations | PRES (1), viral reactivations, VOD (1) with second transplant | Viral reactivation, CMV colitis, PTLD (1), MDS after graft failure (2) | SAH (2), viral reactivations, | Viral reactivations |
| Protocol status | Completed | Completed | Abandoned | unknown | unknown |
| Characteristic . | Bolanos-Meade et al16 . | De la Fuente et al33 . | Fitzhugh et al35 . | Saraf et al39 . | Pawlowska et al41 . |
|---|---|---|---|---|---|
| Protocol | Phase 1/2, single center | Phase 2, multicenter | Phase 1/2, single center | Phase 2 single center | Phase 2 single center |
| Goal | Full donor chimerism | Full donor chimerism | Stable mixed donor-recipient chimerism | Full donor chimerism | Full donor chimerism (PTIS-HCT approach) |
| Stem cell source | Bone marrow* | Bone marrow* | Peripheral blood | Peripheral blood | Bone marrow (3) Peripheral blood (1) |
| Donor type | Haploidentical | Haploidentical | Haploidentical | Haploidentical | Haploidentical |
| Donor availability† | 100% | >90% | 100% | 90% | 100% |
| Number of patients | 14 | 18 | 23 (21-SCD) | 8 | 4 |
| Age, median (range), y | 30 (15-46) | 20.9 (12.1-26) | 36 (20-56) | 29 (20-38) | 18.5 (13 to 23) |
| Type of conditioning | Nonmyeloablative | Nonmyeloablative | Nonmyeloablative | Nonmyeloablative | Reduced toxicity |
| Conditioning | ATG, fludarabine, cyclophosphamide, TBI (200 cGy) | ATG, fludarabine, cyclophosphamide, thiotepa, TBI (200 cGy) | Alemtuzumab, TBI (400 cGy) | ATG, fludarabine, cyclophosphamide, TBI (300 cGy) | PTIS: fludarabine and dexamethasone × 2 courses; then ATG, busulfan, fludarabine |
| GvHD prophylaxis | PTCy, tacrolimus, sirolimus, MMF | PTCy, sirolimus, MMF | PTCy,‡ sirolimus | PTCy, sirolimus, MMF | PTCy, tacrolimus, MMF |
| Median follow-up, mo | 23.4 (minimal 6.9) | 13.3 (IQR, 3.8-23.1) | 38 (range, 8-74) | 17 (range, 12-30) | 5-11 |
| Engraftment rate | 57% (8/14) | 83% (15/18) | Cohort 1: 33% (1/3) Cohort 2: 63% (5/8) Cohort 3: 83% (10/12) | ≥95% (7/8) | 100% |
| Mixed chimerism | 25% (2/8) at 6 months | None | 100% (16/16) | 13% (1/8) | None |
| EFS | NA | 93% | NA | 75% (6/8) | NA |
| OS | 100% | 100% | 87% (11/12) | 88% (7/8) | 100% |
| Graft failure | 43% (1 primary; 5 secondary) | 6% (1/15)# | 65% (7 primary; 8 secondary); 50% in Cohort 3 | 12.5% (1/8) | 0% |
| TRM | 0% | 0% | 9.5% (2/21) | 13% (1/8) | 0% |
| Acute GvHD >2 | 0% | 13% (2/16) | 0% | 25% (2/8) | 25% (1/4) |
| Chronic GvHD (moderate-severe) | 0% | 6% (1/16) | 0% | 13% (1/8) | 75% (3/4) |
| Immunosuppression duration (IST) | 14.2% (2/14) still on at publication | 85% (6/7) off at 1 year | Continuing | 3/6 on IST | 1/4 on IST |
| Complications | PRES (3), viral reactivations | PRES (1), viral reactivations, VOD (1) with second transplant | Viral reactivation, CMV colitis, PTLD (1), MDS after graft failure (2) | SAH (2), viral reactivations, | Viral reactivations |
| Protocol status | Completed | Completed | Abandoned | unknown | unknown |
ATG, antithymocyte globulin; CMV, cytomegalovirus; IQR, interquartile range; IST, immunosuppression therapy; MMF, mycophenolate mofetil; NA, not available; PRES, posterior reversible encephalopathy/neurological complications (means peripheral neuropathy, neuralgia); PTIS, pretransplant immunosuppressive therapy; PTLD, posttransplant lymphoproliferative disorder; SAH, sub-arachnoid hemorrhage; TRM, transplant-related mortality; VOD, veno-occlusive disease.
Three patients received granulocyte colony-stimulating factor–primed bone marrow.
Patient who had IST stopped due to severe reaction and PRES.
Escalating doses of PTCy: 0 mg/kg in cohort 1, 50 mg/kg in cohort 2, and 100 mg/kg in cohort 3.