Transplant outcomes from competing strategies using T-cell deplete haploidentical HCT for SCD
| Characteristic . | Foell et al19 . | Gilman et al42 . | Gaziev et al20 . | Cairo et al18 . |
|---|---|---|---|---|
| Protocol | Phase 2 trial (single center) | Phase 2 trial (single center) | Phase 2 trial (single center) | Phase 2 trial (multicenter) |
| Goal | Full-donor chimerism | Full-donor chimerism | Full-donor chimerism | Full-donor chimerism |
| Stem cell source | Peripheral blood | Peripheral blood | Peripheral blood | Peripheral blood |
| Donor type | Haploidentical | Haploidentical | Haploidentical | Haploidentical |
| Donor availability | 100% | 100% | 100% | 100% |
| Number of patients | 25 | 10 | 14 (3 SCD; 11 TDT) | 19 |
| Graft manipulation (T-cell depletion strategies) | CD3/CD19 T-cell depletion (19) or TCRαβ+/CD19+ depletion (6) | CD34+ cell-selected, T-cell–depleted (8 Haplo; 2 MUD) | TCR αβ+/CD19+– depleted grafts | CD34+ enrichment and mononuclear cell add-back |
| Age, median (range), mo | 13 (3-31) | 49 (14-60) | 47 (6-62) | 46 (1.9-76) |
| Type of conditioning | Myeloablative | Reduced intensity | Myeloablative | Myeloimmunoablative |
| Conditioning | ATG, fludarabine, thiotepa, treosulfan | Melphalan, thiotepa, fludarabine, and rabbit ATG + rituximab | PTIS: fludarabine, hydroxyurea, and azathioprine; then busulfan, thiotepa, cyclophosphamide, and ATG | PTIS: hydroxyurea and azathioprine; then fludarabine, busulfan, thiotepa, cyclophosphamide, total lymphocyte irradiation, and rabbit ATG |
| GvHD prophylaxis | Cyclosporine, MMF | DLI + methotrexate | Cyclosporine and methylprednisolone or MMF | None |
| Follow-up, median (range) | 22 mo | 49 (14-60) mo | 3.9 (0.5-5.2) y | 1409 (59-2330) d |
| Stable engraftment | 84% | 70% | 93% | 97.1% |
| Mixed chimerism | 16% (4/25) | 30%* | None | None |
| EFS | 88% (22/28) | 80% | 69% | 84% |
| OS | 88% (22/25) | 90% | 84% | 84% |
| Graft failure | 0% | 10% | 14% | 0% |
| TRM | 12% (3/25) | 10% (1/10) | 14.2% (2/14) | 15.7% (3/19) |
| Acute GvHD | Grades 1-2: 28% (7/25) Grades 3-4: 0% | Grades 2-4: 20% (2/10) | Grades 2-4: 28% | Grades 2-4: 6.2% |
| Chronic GvHD | Mild/moderate 14% Severe 0% (4/25) | Extensive skin (1/10) | Extensive 21% | Moderate-severe 6.7% |
| Immunosuppression duration | Off by 18 mo in patients with GvHD | Unknown | Unknown | Unknown |
| Complications | PRES (5), seizures (1), VOD (1), TAM/MAS (1). Viral reactivations 13 (52%) | PTLD (3), engraftment syndrome (2), PRES (2), viral reactivations | PTLD (3), DLBCL, viral reactivations (64%), AIHA (3), ITP (1); delayed immune reconstitution | Death from VOD (1), 1 each of acute and chronic GvHD |
| Protocol status | Ongoing | Ongoing | Ongoing | Completed |
| Characteristic . | Foell et al19 . | Gilman et al42 . | Gaziev et al20 . | Cairo et al18 . |
|---|---|---|---|---|
| Protocol | Phase 2 trial (single center) | Phase 2 trial (single center) | Phase 2 trial (single center) | Phase 2 trial (multicenter) |
| Goal | Full-donor chimerism | Full-donor chimerism | Full-donor chimerism | Full-donor chimerism |
| Stem cell source | Peripheral blood | Peripheral blood | Peripheral blood | Peripheral blood |
| Donor type | Haploidentical | Haploidentical | Haploidentical | Haploidentical |
| Donor availability | 100% | 100% | 100% | 100% |
| Number of patients | 25 | 10 | 14 (3 SCD; 11 TDT) | 19 |
| Graft manipulation (T-cell depletion strategies) | CD3/CD19 T-cell depletion (19) or TCRαβ+/CD19+ depletion (6) | CD34+ cell-selected, T-cell–depleted (8 Haplo; 2 MUD) | TCR αβ+/CD19+– depleted grafts | CD34+ enrichment and mononuclear cell add-back |
| Age, median (range), mo | 13 (3-31) | 49 (14-60) | 47 (6-62) | 46 (1.9-76) |
| Type of conditioning | Myeloablative | Reduced intensity | Myeloablative | Myeloimmunoablative |
| Conditioning | ATG, fludarabine, thiotepa, treosulfan | Melphalan, thiotepa, fludarabine, and rabbit ATG + rituximab | PTIS: fludarabine, hydroxyurea, and azathioprine; then busulfan, thiotepa, cyclophosphamide, and ATG | PTIS: hydroxyurea and azathioprine; then fludarabine, busulfan, thiotepa, cyclophosphamide, total lymphocyte irradiation, and rabbit ATG |
| GvHD prophylaxis | Cyclosporine, MMF | DLI + methotrexate | Cyclosporine and methylprednisolone or MMF | None |
| Follow-up, median (range) | 22 mo | 49 (14-60) mo | 3.9 (0.5-5.2) y | 1409 (59-2330) d |
| Stable engraftment | 84% | 70% | 93% | 97.1% |
| Mixed chimerism | 16% (4/25) | 30%* | None | None |
| EFS | 88% (22/28) | 80% | 69% | 84% |
| OS | 88% (22/25) | 90% | 84% | 84% |
| Graft failure | 0% | 10% | 14% | 0% |
| TRM | 12% (3/25) | 10% (1/10) | 14.2% (2/14) | 15.7% (3/19) |
| Acute GvHD | Grades 1-2: 28% (7/25) Grades 3-4: 0% | Grades 2-4: 20% (2/10) | Grades 2-4: 28% | Grades 2-4: 6.2% |
| Chronic GvHD | Mild/moderate 14% Severe 0% (4/25) | Extensive skin (1/10) | Extensive 21% | Moderate-severe 6.7% |
| Immunosuppression duration | Off by 18 mo in patients with GvHD | Unknown | Unknown | Unknown |
| Complications | PRES (5), seizures (1), VOD (1), TAM/MAS (1). Viral reactivations 13 (52%) | PTLD (3), engraftment syndrome (2), PRES (2), viral reactivations | PTLD (3), DLBCL, viral reactivations (64%), AIHA (3), ITP (1); delayed immune reconstitution | Death from VOD (1), 1 each of acute and chronic GvHD |
| Protocol status | Ongoing | Ongoing | Ongoing | Completed |
Viral reactivation indicates patients with reactivation of cytomegalovirus, herpes virus, Epstein-Barr virus, rotavirus, or polyomavirus.
AIHA, auto-immune hemolytic anemia; DLBCL, diffuse large B-cell lymphoma; DLI, donor lymphocyte infusion; ITP, immune thrombocytopenia; MAS, macrophage activation syndrome; MUD, matched unrelated donor; TAM, tumor-associated macrophages; TDT, transfusion dependent thalassemia.
Received prophylactic DLI or second transplant.