Overview of studies evaluating preemptive DLI
| Reference . | Study design . | Disease . | Graft type, conditioning regimen, donor source, GvHD prophylaxis . | Trigger . | Cell dose . | Study arms compared . | Efficacy outcomes . | Grade III/IV GvHD . |
|---|---|---|---|---|---|---|---|---|
| 20 | Prospective, nonrandomized | AML (n = 36), ALL (n = 44) | NR | MRD | Starting CD3 dose Matched related: 1 × 106/kg MUD/MMUD: 1 × 105/kg | Preemptive DLI vs no DLI | CIR: 6% 3-y OS: 80% —— CIR: 63% 3-y OS: 26% | NR |
| 21 | Case report | AML (n = 1) | NR | MRD, MC | Not reported | Single case report | Conversion to MRD negativity | NR |
| 22 | Prospective, nonrandomized | AML (n = 61) ALL (n = 38) MDS (n = 6) Total n = 105 | T cell-replete MAC-BM/PBSC-alloHSCT Conditioning regimens/donor source: matched related (n = 40): Bu/Cy or Cy/TBI Haplo (n = 53) and MUD (n = 12): Bu/Cy + ATG or Cy/TBI + ATG GvHD prophylaxis: CSA, MMF, MTX (± ATG) | MRD | Median CD3 dose: 3.8 × 107/kg | Preemptive DLI (n = 56) vs IL-2 (n = 49) | CIR: 28% 3-y OS: 58% 3-y DFS: 56% —— CIR: 64% 3-y OS: 28% 3-y DFS: 24% | 8% (P = .471) —— 4% |
| 30 | Retrospective | AML (n = 14) ALL (n = 11) CML (n = 2) | T cell-replete MAC-PBSC-alloHSCT Conditioning regimens/donor source: matched related (n = 14): Bu/Cy Haplo (n = 2) and MUD (n = 11): Bu/Cy + ATG + cytarabine GvHD prophylaxis: CSA, MMF, MTX (± ATG) | MRD | Median CD3 dose: 5.51 × 107/kg | Preemptive DLI vs Therapeutic DLI | 1-y OS: 94% —— 1-y OS: 27% | 6% —— 9% |
| 24 | Prospective, nonrandomized phase 2 trial | AML (n = 14) MDS (n = 4) MPN (n = 2) Others (n = 16) | T cell-replete low-dose alemtuzumab RIC-PBSC-alloHSCT Conditioning regimens: Myeloid: Flu/Bu Lymphoid: Flu/Cy (± rituximab) Donor source: MUD: 33 MMUD: 3 GvHD prophylaxis: Tacrolimus, MTX, alemtuzumab | MC (<50% at d+60) | Starting CD3 dose: 0.5–1.0 × 107/kg | Preemptive DLI | 2-y OS: 57%; 2-y DFS: 38%; 1-y NRM: 14% | 0% |
| 25 | Retrospective | AML (n = 16) NHL (n = 6) HL (n = 5) MM (n = 4) ALL (n = 3) Others (n = 6) | T cell-replete HLA-haplo-BM-alloHSCT Conditioning regimens: MAC (n = 6): Bu/Cy RIC (n = 34): Flu/Cy/TBI Donor source: Haplo (n = 40) GvHD prophylaxis: Tacrolimus, MMF, PTCy | MRD, LOC | Starting CD3 dose 1 × 105/kg-1 × 106/kg | Preemptive DLI (n = 5) vs Therapeutic DLI (n = 35) | ORR: 60% —— ORR: 26% | NR |
| 23 | Prospective, nonrandomized | AML (n = 17) | T cell-replete BM/PBSC-MAC-alloHSCT Conditioning regimens/donor source: matched related (n = 43): Bu/Cy or Cy/TBI Haplo (n = 44) and MUD (n = 5): Bu/Cy + ATG or Cy/TBI + ATG GvHD prophylaxis: CSA, MMF, MTX (± ATG) | MRD | NR | Preemptive DLI vs No DLI | 2-y CIR: 24% 2-y OS: 64% —— 2-y CIR: 84% 2-y OS: 0% | NR |
| 26 | Retrospective | AML (n = 22) ALL (n = 9) MM (n = 1) | T cell-replete HLA-haplo-MAC-BM-alloHSCT Conditioning regimens: Flu/Bu/TT Flu/TBI Donor source: Haplo (n = 32) GvHD prophylaxis: CSA, MMF, PTCy | MRD | Starting CD3 dose 1 × 104/kg-1 × 105/kg | Preemptive DLI vs Therapeutic DLI | ORR: 45% 2-y OS: 43% —— ORR: 33% 2-y OS: 19% | 5% —— 8% |
| 35 | Retrospective | AML (n = 207) | T cell-replete MAC-BM/PBSC/CB-alloHSCT Conditioning regimens: Bu/Flu (+TT), Bu/Cy, Cy/Mel/TT Cy/TT, Cy/TBI Donor source: Matched related (n = 82) MUD (n = 66) Haplo (n = 59) GvHD prophylaxis: CSA, MTX | MRD | Starting CD3 dose: Matched-sibling: 1 × 106/kg MUD: 1 × 105/kg; HaploDLI: 1 × 104/kg | WT1 100 copies/104 ABL vs WT1 180 copies/104 ABL | CIR: 29% 4-y LFS 74% —— CIR: 76% 4-y LFS: 23% | 0% 0% |
| 31 | Retrospective | AML (n = 31) NHL (n = 19) MDS (n = 8) Others (n = 28) | T cell-replete BM/PBSC-MAC/RIC-alloHSCT Conditioning regimens: RIC (n = 60): Flu, Mel, Alemtuzumab MAC (n = 26): Bu/Cy, Bu/Flu, TBI/Cy, TBI/Cy/VP Donor sources: Matched related (n = 53) MUD (n = 25) MMUD (n = 8) GvHD prophylaxis: Not reported for MAC; alemtuzumab for RIC | MC | Starting CD3 dose: Matched-sibling: 3 × 106-1 × 107/kg MUD: 1-3 × 106/kg | Preemptive DLI vs Therapeutic DLI | 5-y OS: 69% 5-y PFS: 71% —— 5-y OS: 28% 5-y PFS: 18% | 26% —— 31% |
| 28 | Retrospective | AML (n = 14) MDS (n = 20 ALL/NHL (n = 5) CML (n = 2) | T-cell replete PB-haploHCT Conditioning regimens: MAC (n = 8) RIC (n = 13) Donor source: Haplo (n = 21) GvHD prophylaxis: tacrolimus, MMF/ sirolimus, MMF, PTCy | MC | Most common starting CD3 dose: 1 × 106/kg | Preemptive DLI (n = 2) vs Therapeutic DLI (n = 12) | 120-d OS: 100% —— 120-d OS: 29% | NR |
| 27 | Retrospective, matched-pair analysis | AML, MDS, ALL (n = 20) | T cell-replete BM/PBSC-MAC-alloHSCT Conditioning regimens/donor source: matched related (n = 8): Bu/Cy Haplo (n = 12): Bu/Cy + cytarabine + ATG GvHD prophylaxis: CSA, MMF, MTX | MRD | Median CD3 dose: 2.5 × 107/kg | No control | MRD conversion: 75%; 2-y CIR 31%; 2-y OS 69% | Grade II-IV aGvHD: 4 (20%) |
| 29 | Retrospective single-center landmark analysis | AML (n = 42) | T cell-replete PBSC-MAC/RIC-alloHSCT Conditioning regimens: MAC (n = 12): Bu/Cy, TT/Bu/Flu RIC (n = 30): Flu/BCNU/Mel, Flu/TT Donor source: matched related (n = 11) MUD (n = 23) MMUD (n = 7) Haplo (n = 1) GvHD prophylaxis: CSA/Alemtuzumab, CSA/MMF, MTX ± ATG | MRD (n = 18) MC (n = 24) | Median starting CD3 dose: 0.69 × 106/kg | Preemptive DLI vs Therapeutic DLI | 5-y OS: 43% —— 5-y OS: 10% | 7% —— 6% |
| 34 | Retrospective registry study | AML (n = 153) ALL (n = 39) | BM/PBSC-MAC /RIC-alloHSCT with (n = 149) and without (n = 42) T-cell depletion Conditioning regimens: MAC (n = 74) RIC (n = 107) Donor source: Matched related (n = 129) MUD (n = 63) GvHD prophylaxis: No IST regimens reported | MRD (n = 23) MC (n = 169) | Median starting CD3 dose: 1 × 106/kg | Preemptive DLI for MRD (n = 23) Preemptive DLI for MC (n = 169) | Decreasing MRD/improving peripheral blood counts: 71% (16/21); 5-y NRM: 9% 5-y CIR: 44% 5-y LFS: 47% 5-y OS: 51% —— Improving MC: 70% (110/158); 5-y NRM: 15% 5-y CIR: 28% 5-y LFS: 57% 5-y OS: 63% | 7% (18/248 patients from entire cohort including preemptive DLI for MRD/MC and prophylactic DLI) |
| Reference . | Study design . | Disease . | Graft type, conditioning regimen, donor source, GvHD prophylaxis . | Trigger . | Cell dose . | Study arms compared . | Efficacy outcomes . | Grade III/IV GvHD . |
|---|---|---|---|---|---|---|---|---|
| 20 | Prospective, nonrandomized | AML (n = 36), ALL (n = 44) | NR | MRD | Starting CD3 dose Matched related: 1 × 106/kg MUD/MMUD: 1 × 105/kg | Preemptive DLI vs no DLI | CIR: 6% 3-y OS: 80% —— CIR: 63% 3-y OS: 26% | NR |
| 21 | Case report | AML (n = 1) | NR | MRD, MC | Not reported | Single case report | Conversion to MRD negativity | NR |
| 22 | Prospective, nonrandomized | AML (n = 61) ALL (n = 38) MDS (n = 6) Total n = 105 | T cell-replete MAC-BM/PBSC-alloHSCT Conditioning regimens/donor source: matched related (n = 40): Bu/Cy or Cy/TBI Haplo (n = 53) and MUD (n = 12): Bu/Cy + ATG or Cy/TBI + ATG GvHD prophylaxis: CSA, MMF, MTX (± ATG) | MRD | Median CD3 dose: 3.8 × 107/kg | Preemptive DLI (n = 56) vs IL-2 (n = 49) | CIR: 28% 3-y OS: 58% 3-y DFS: 56% —— CIR: 64% 3-y OS: 28% 3-y DFS: 24% | 8% (P = .471) —— 4% |
| 30 | Retrospective | AML (n = 14) ALL (n = 11) CML (n = 2) | T cell-replete MAC-PBSC-alloHSCT Conditioning regimens/donor source: matched related (n = 14): Bu/Cy Haplo (n = 2) and MUD (n = 11): Bu/Cy + ATG + cytarabine GvHD prophylaxis: CSA, MMF, MTX (± ATG) | MRD | Median CD3 dose: 5.51 × 107/kg | Preemptive DLI vs Therapeutic DLI | 1-y OS: 94% —— 1-y OS: 27% | 6% —— 9% |
| 24 | Prospective, nonrandomized phase 2 trial | AML (n = 14) MDS (n = 4) MPN (n = 2) Others (n = 16) | T cell-replete low-dose alemtuzumab RIC-PBSC-alloHSCT Conditioning regimens: Myeloid: Flu/Bu Lymphoid: Flu/Cy (± rituximab) Donor source: MUD: 33 MMUD: 3 GvHD prophylaxis: Tacrolimus, MTX, alemtuzumab | MC (<50% at d+60) | Starting CD3 dose: 0.5–1.0 × 107/kg | Preemptive DLI | 2-y OS: 57%; 2-y DFS: 38%; 1-y NRM: 14% | 0% |
| 25 | Retrospective | AML (n = 16) NHL (n = 6) HL (n = 5) MM (n = 4) ALL (n = 3) Others (n = 6) | T cell-replete HLA-haplo-BM-alloHSCT Conditioning regimens: MAC (n = 6): Bu/Cy RIC (n = 34): Flu/Cy/TBI Donor source: Haplo (n = 40) GvHD prophylaxis: Tacrolimus, MMF, PTCy | MRD, LOC | Starting CD3 dose 1 × 105/kg-1 × 106/kg | Preemptive DLI (n = 5) vs Therapeutic DLI (n = 35) | ORR: 60% —— ORR: 26% | NR |
| 23 | Prospective, nonrandomized | AML (n = 17) | T cell-replete BM/PBSC-MAC-alloHSCT Conditioning regimens/donor source: matched related (n = 43): Bu/Cy or Cy/TBI Haplo (n = 44) and MUD (n = 5): Bu/Cy + ATG or Cy/TBI + ATG GvHD prophylaxis: CSA, MMF, MTX (± ATG) | MRD | NR | Preemptive DLI vs No DLI | 2-y CIR: 24% 2-y OS: 64% —— 2-y CIR: 84% 2-y OS: 0% | NR |
| 26 | Retrospective | AML (n = 22) ALL (n = 9) MM (n = 1) | T cell-replete HLA-haplo-MAC-BM-alloHSCT Conditioning regimens: Flu/Bu/TT Flu/TBI Donor source: Haplo (n = 32) GvHD prophylaxis: CSA, MMF, PTCy | MRD | Starting CD3 dose 1 × 104/kg-1 × 105/kg | Preemptive DLI vs Therapeutic DLI | ORR: 45% 2-y OS: 43% —— ORR: 33% 2-y OS: 19% | 5% —— 8% |
| 35 | Retrospective | AML (n = 207) | T cell-replete MAC-BM/PBSC/CB-alloHSCT Conditioning regimens: Bu/Flu (+TT), Bu/Cy, Cy/Mel/TT Cy/TT, Cy/TBI Donor source: Matched related (n = 82) MUD (n = 66) Haplo (n = 59) GvHD prophylaxis: CSA, MTX | MRD | Starting CD3 dose: Matched-sibling: 1 × 106/kg MUD: 1 × 105/kg; HaploDLI: 1 × 104/kg | WT1 100 copies/104 ABL vs WT1 180 copies/104 ABL | CIR: 29% 4-y LFS 74% —— CIR: 76% 4-y LFS: 23% | 0% 0% |
| 31 | Retrospective | AML (n = 31) NHL (n = 19) MDS (n = 8) Others (n = 28) | T cell-replete BM/PBSC-MAC/RIC-alloHSCT Conditioning regimens: RIC (n = 60): Flu, Mel, Alemtuzumab MAC (n = 26): Bu/Cy, Bu/Flu, TBI/Cy, TBI/Cy/VP Donor sources: Matched related (n = 53) MUD (n = 25) MMUD (n = 8) GvHD prophylaxis: Not reported for MAC; alemtuzumab for RIC | MC | Starting CD3 dose: Matched-sibling: 3 × 106-1 × 107/kg MUD: 1-3 × 106/kg | Preemptive DLI vs Therapeutic DLI | 5-y OS: 69% 5-y PFS: 71% —— 5-y OS: 28% 5-y PFS: 18% | 26% —— 31% |
| 28 | Retrospective | AML (n = 14) MDS (n = 20 ALL/NHL (n = 5) CML (n = 2) | T-cell replete PB-haploHCT Conditioning regimens: MAC (n = 8) RIC (n = 13) Donor source: Haplo (n = 21) GvHD prophylaxis: tacrolimus, MMF/ sirolimus, MMF, PTCy | MC | Most common starting CD3 dose: 1 × 106/kg | Preemptive DLI (n = 2) vs Therapeutic DLI (n = 12) | 120-d OS: 100% —— 120-d OS: 29% | NR |
| 27 | Retrospective, matched-pair analysis | AML, MDS, ALL (n = 20) | T cell-replete BM/PBSC-MAC-alloHSCT Conditioning regimens/donor source: matched related (n = 8): Bu/Cy Haplo (n = 12): Bu/Cy + cytarabine + ATG GvHD prophylaxis: CSA, MMF, MTX | MRD | Median CD3 dose: 2.5 × 107/kg | No control | MRD conversion: 75%; 2-y CIR 31%; 2-y OS 69% | Grade II-IV aGvHD: 4 (20%) |
| 29 | Retrospective single-center landmark analysis | AML (n = 42) | T cell-replete PBSC-MAC/RIC-alloHSCT Conditioning regimens: MAC (n = 12): Bu/Cy, TT/Bu/Flu RIC (n = 30): Flu/BCNU/Mel, Flu/TT Donor source: matched related (n = 11) MUD (n = 23) MMUD (n = 7) Haplo (n = 1) GvHD prophylaxis: CSA/Alemtuzumab, CSA/MMF, MTX ± ATG | MRD (n = 18) MC (n = 24) | Median starting CD3 dose: 0.69 × 106/kg | Preemptive DLI vs Therapeutic DLI | 5-y OS: 43% —— 5-y OS: 10% | 7% —— 6% |
| 34 | Retrospective registry study | AML (n = 153) ALL (n = 39) | BM/PBSC-MAC /RIC-alloHSCT with (n = 149) and without (n = 42) T-cell depletion Conditioning regimens: MAC (n = 74) RIC (n = 107) Donor source: Matched related (n = 129) MUD (n = 63) GvHD prophylaxis: No IST regimens reported | MRD (n = 23) MC (n = 169) | Median starting CD3 dose: 1 × 106/kg | Preemptive DLI for MRD (n = 23) Preemptive DLI for MC (n = 169) | Decreasing MRD/improving peripheral blood counts: 71% (16/21); 5-y NRM: 9% 5-y CIR: 44% 5-y LFS: 47% 5-y OS: 51% —— Improving MC: 70% (110/158); 5-y NRM: 15% 5-y CIR: 28% 5-y LFS: 57% 5-y OS: 63% | 7% (18/248 patients from entire cohort including preemptive DLI for MRD/MC and prophylactic DLI) |
aGvHD, acute graft-versus-host disease; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; ATG, antithymocyte globulin; BCNU, carmustine; Bu, busulfan; CIR, cumulative incidence of relapse; CSA, cyclosporine A; Cy, cyclophosphamide; DFS, disease-free survival; DLI, donor lymphocyte infusion; Flu, fludarabine; Haplo, HLA-haploidentical donor; LFS, leukemia-free survival; MAC, myeloablative conditioning; MC, mixed chimerism; MDS, myelodysplastic syndrome; Mel, melphalan; MMUD, mismatched unrelated donor; MMF, mycophenolate mofetil; MRD, measurable residual disease; MTX, methotrexate; MUD, matched unrelated donor; NR, not reported; NRM, nonrelapse mortality; ORR, overall response rate; OS, overall survival; PTCy, posttransplant cyclophosphamide; RIC, reduced-intensity conditioning; TBI, total body irradiation; TT, thiotepa; VP, etoposide.