Select trials that have compared pediatric-inspired regimens to allo-HSCT for ALL, some with MRD risk stratificationa
| . | Group Study . | |||||
|---|---|---|---|---|---|---|
| . | DFCI – CIBMTR44 . | CALGB 10403 – CIBMTR45 . | GRAALL 2003/200546 . | PETHEMA ALL-AR-0347 . | PETHEMA ALL-HR-1148 . | NILG ALL 10/0749 . |
| Analysis | Retrospective | Retrospective | Retrospective | Phase 2, prospective | Phase 2, prospective | Phase 2, prospective |
| Study period (date range) | 2002-2011 | 2002-2012 | 2003-2011 | 2003-2012 | 2011-2019 | 2008-2012 |
| Age range, years | 18-50 | 16-39 | 15-55 | 15-60 | 15-60 | 18-65 |
| No. of patients | 108 (chemo) vs 422 (HSCT) | 217 (chemo) vs 263 (HSCT) | 240 (chemo) vs 282 (HSCT) | 108 (chemo) vs 71 (HSCT) | 218 (chemo) vs 106 (HSCT) | 203 |
| Patient risk category | Standard and high risk | Standard and high risk | High risk | High risk | High risk | Standard risk, high risk, very high risk |
| No. of T-ALL patients | 24 (chemo) vs 61 (HSCT) | 65 (chemo) vs 43 (HSCT) | 80 (chemo) vs 99 (HSCT) | 29 (chemo) vs 27 (HSCT) | 71 (chemo) vs 32 (HSCT) | 11 (chemo) vs 33 (HSCT) |
| T-ALL subgroup analysis* | No | No | Yes | No | No | Yes |
| MRD analysis used to assign risk/postremission therapy | No | No | Yes (<1 × 10−4) | Yes (< 5 × 10−4 at EOC) | Yes (<0.1% EOI, <0.01% EOC) | Yes, (>10−4 at week 10 of therapy) |
| Outcome measure for whole series | 4-y DFS, OS, TRM | 3- and 5-y DFS, OS, NRM, CIR | 3-y CIR, NRM, RFS, OS for allo-HSCT; effect of allo-HSCT by MRD levels | DFS, OS, impact of MRD on DFS and OS | OS, rates of morphologic and MRD response, EFS, and CIR | 5-y RFS, OS, CIR, TRM |
| Chemo as postremission therapy (whole series) | 4-y DFS: 71%; 4-y OS: 73%; TRM: 6% | 5-y DFS: 58%; 5-y OS: 66%; 5-y NRM: 8%; 5-y CIR: 34% | Not reported in manuscript, but no significant difference observed between chemo and allo-HSCT | 5-y DFS 55%, 5-y OS 59% | 5-y OS 59%, 5-y CIR 45% | 5-y OS 71%, 5-y RFS 58%, TRM 6%, relapse risk 34% |
| Allo-HSCT as postremission therapy (whole series) | 4-y DFS: 40%; 4-y OS: 45%; TRM: 37% | 3-y DFS: 50%; 3-y OS: 53%; 3-y NRM: 24%; 5-y DFS: 44%; 5-y OS: 47%; 5-y NRM: 29%; 5-y CIR: 23% | 3-y CIR: 18.5%; 3-y NRM: 13.3%; 3-y RFS: 68.1%; 3-y OS: 72.5% | 5-y DFS 32%; 5-y OS 37% | 5-y OS 38%, 5-y CIR 40% | 5-y OS 54%, 5-y RFS 53% The 5-y CIR 36% TRM was 18% |
| Conclusion | Chemotherapy without allo-HSCT favored | Chemotherapy without allo-HSCT favored even though relapse risk was higher in chemotherapy cohort. | No significant effect of allo-HSCT on RFS or OS in entire study population. Allo-HSCT favored for patients with detectable MRD. | MRD clearance after induction and early consolidation is the only prognostic factor for DFS and OS. Allo-HSCT could be avoided for patients with good early cytologic response and MRD <5 × 10−4. | Patients with adequate MRD response after induction and consolidation do well with chemotherapy without allo-HSCT. B- and T-cell patients had similar outcomes, but ETP-ALL had inferior outcomes. | MRD clearance and age ≤55 y were the most favorable independent prognostic factors. Entire cohort of T-ALL patients: 5-y OS 73%, 5-y RFS 60%, CIR 30%. |
| . | Group Study . | |||||
|---|---|---|---|---|---|---|
| . | DFCI – CIBMTR44 . | CALGB 10403 – CIBMTR45 . | GRAALL 2003/200546 . | PETHEMA ALL-AR-0347 . | PETHEMA ALL-HR-1148 . | NILG ALL 10/0749 . |
| Analysis | Retrospective | Retrospective | Retrospective | Phase 2, prospective | Phase 2, prospective | Phase 2, prospective |
| Study period (date range) | 2002-2011 | 2002-2012 | 2003-2011 | 2003-2012 | 2011-2019 | 2008-2012 |
| Age range, years | 18-50 | 16-39 | 15-55 | 15-60 | 15-60 | 18-65 |
| No. of patients | 108 (chemo) vs 422 (HSCT) | 217 (chemo) vs 263 (HSCT) | 240 (chemo) vs 282 (HSCT) | 108 (chemo) vs 71 (HSCT) | 218 (chemo) vs 106 (HSCT) | 203 |
| Patient risk category | Standard and high risk | Standard and high risk | High risk | High risk | High risk | Standard risk, high risk, very high risk |
| No. of T-ALL patients | 24 (chemo) vs 61 (HSCT) | 65 (chemo) vs 43 (HSCT) | 80 (chemo) vs 99 (HSCT) | 29 (chemo) vs 27 (HSCT) | 71 (chemo) vs 32 (HSCT) | 11 (chemo) vs 33 (HSCT) |
| T-ALL subgroup analysis* | No | No | Yes | No | No | Yes |
| MRD analysis used to assign risk/postremission therapy | No | No | Yes (<1 × 10−4) | Yes (< 5 × 10−4 at EOC) | Yes (<0.1% EOI, <0.01% EOC) | Yes, (>10−4 at week 10 of therapy) |
| Outcome measure for whole series | 4-y DFS, OS, TRM | 3- and 5-y DFS, OS, NRM, CIR | 3-y CIR, NRM, RFS, OS for allo-HSCT; effect of allo-HSCT by MRD levels | DFS, OS, impact of MRD on DFS and OS | OS, rates of morphologic and MRD response, EFS, and CIR | 5-y RFS, OS, CIR, TRM |
| Chemo as postremission therapy (whole series) | 4-y DFS: 71%; 4-y OS: 73%; TRM: 6% | 5-y DFS: 58%; 5-y OS: 66%; 5-y NRM: 8%; 5-y CIR: 34% | Not reported in manuscript, but no significant difference observed between chemo and allo-HSCT | 5-y DFS 55%, 5-y OS 59% | 5-y OS 59%, 5-y CIR 45% | 5-y OS 71%, 5-y RFS 58%, TRM 6%, relapse risk 34% |
| Allo-HSCT as postremission therapy (whole series) | 4-y DFS: 40%; 4-y OS: 45%; TRM: 37% | 3-y DFS: 50%; 3-y OS: 53%; 3-y NRM: 24%; 5-y DFS: 44%; 5-y OS: 47%; 5-y NRM: 29%; 5-y CIR: 23% | 3-y CIR: 18.5%; 3-y NRM: 13.3%; 3-y RFS: 68.1%; 3-y OS: 72.5% | 5-y DFS 32%; 5-y OS 37% | 5-y OS 38%, 5-y CIR 40% | 5-y OS 54%, 5-y RFS 53% The 5-y CIR 36% TRM was 18% |
| Conclusion | Chemotherapy without allo-HSCT favored | Chemotherapy without allo-HSCT favored even though relapse risk was higher in chemotherapy cohort. | No significant effect of allo-HSCT on RFS or OS in entire study population. Allo-HSCT favored for patients with detectable MRD. | MRD clearance after induction and early consolidation is the only prognostic factor for DFS and OS. Allo-HSCT could be avoided for patients with good early cytologic response and MRD <5 × 10−4. | Patients with adequate MRD response after induction and consolidation do well with chemotherapy without allo-HSCT. B- and T-cell patients had similar outcomes, but ETP-ALL had inferior outcomes. | MRD clearance and age ≤55 y were the most favorable independent prognostic factors. Entire cohort of T-ALL patients: 5-y OS 73%, 5-y RFS 60%, CIR 30%. |
Data for T-ALL outcomes embedded within the report of the entire cohort of ALL patients, the majority of which is B-ALL.
CIR, cumulative incidence of relapse; EOC, end of consolidation; EOI, end of induction; LFS, leukemia free survival; NRM, nonrelapse mortality; RFS, relapse-free survival; TRM, treatment-related mortality.