Table 3.
Standard risk stratification and outcome of children with HD ALL in contemporary treatment protocols.
| Study protocol | Age (years) | WBC ×109/L | CNS status | Treatment response | Genetic parameters | Outcome | Ref. | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Steroid responsea | Day 8 | Day 15 | End of induction | Later timepoints | |||||||
| AIEOP-BFM 2000 ALL | 1–17 | Any | Any | + | <1.000 blast/µl (PB) | n.a. | PCR MRD negative |
Day 78 PCR negative |
– |
Standard DI PII: 4-year OS 97.9% 8-year DFS 92% reduced intensity DI PIII: 4-year OS 93.4% 8-year DFS 90% |
[148, 149] |
| ALL IC-BFM | 1–6 | <20 | Any | + | <1.000 blast/µl (PB) | M1/M2 | – | – | – |
5-year EFS 81% 5-year OS 90% (all SR patients combined) |
[150] |
| CoALL 07–03 | <10 | <25 | Any | – | – | MRD <0.01% | MRD <0.01%b | – | – | Number of identified HD patients is too low | [151] |
| COG AALL 0331 LRS | 1–10 | <50 | CNS1 only | – | M1c | M1c | MRD <0.01%b | – | +4, +10, +17 |
6-year CCR 96.3% 6-year OS 99.4% |
[116, 118] |
| COG AALL 0932 LR-C | 1–10 | <50 | CNS1 only | – |
MRD <0.01% (PB) |
– | MRD <0.01%b | – | +4, +10 |
5-year EFS 98.8% 5-year OS 100% (all LR patients combined) |
[117] |
| COG AALL 0932 LR-M | 1–10 | <50 | CNS1 only | – |
MRD <0.01% (PB) |
– | MRD <0.01%b | – | +4, +10 |
5-year EFS 98.5% 5-year OS 100% (all LR patients combined) |
[117] |
| COG P9904 | 1–10 | <50 | No CNS3 | – | MRD <0.01% (PB) | MRD <0.01%b | – | +4, +10 |
5-year EFS 97% 5-year OS 98% (all LR patients combined) |
[117] | |
| RELLA05 | 1–9 | <50 | CNS1/CNS2 or traumatic LP | – | MRD <0.01%d | – | – | DNA index >1, 16 |
5-year EFS 92% 5-year OS 96% (LR group combined) |
[152] | |
| JACLS-ALL-02 | 1–9 | <10 | No CNS3 | + | <1.000 blast/µl (PB) | M1/M2 BM | M1 BM | – | – |
4-year EFS 89.4% 4-year OS 94.9% |
[153] |
| JACLS-ALL-02 SR | 1–9 | <10 | No CNS3 | + |
<1.000 blast/µl (PB) |
M1/M2 BM | M1 BM | – | – |
4-year EFS 100% (+4, +10, +17) 4-year EFS 88.2% (other HD) |
[93] |
| St. Jude Total XVI | 1–10 | <50 | Any | – | – | MRD <1% | D46 MRD <0.01% | – | DNA index >1, 16 |
5-year EFS 95.3% 5-year OS 99.4% |
[154, 155] |
| UKALL 2003 | 1–10 | <50 | Any | – | – | M1/M2 BM | MRD <0.01% | – | – |
10-year survival: all HD patients 90% EFS, 94% OS good risk HD 92% EFS 96% OS poor risk HD 81% EFS, 86% OS |
[120, 156] |
| UKALL 97/99 | 1–10 | <50 | Any | – | – | M1/M2 BM | – | – | – |
10-year survival: all HD patients 84% EFS, 93% OS good risk HD 86% EFS, 94% OS poor risk HD 71% EFS, 89% OS |
[120] |
| NOPHO ALL 1992/2000 |
2–10 (1992) 1–10 (2000) |
<10 | CNS1 | – | – | M1/M2 BM | M1 BM | – |
Karyotype (central review) |
5-year EFS 82% 10-year EFS 80% 5-year OS 91% 10-year OS 89% (both studies combined) |
[157, 158] |
| DCOG 10 | 1–18 | Any | CNS1 only | + |
<1.000 blast/µl (PB) |
– | PCR negative |
Day 80 PCR negative |
– |
5-year EFS 87.9%, 5-year OS 93.3% |
[159] |
| CCLG-ALL 2008 | 1–10 | <50 | No CNS3 | + | <1.000 blast/µl (PB) | M1/M2 BM | PCR negative or flow MRD <0.01% |
Week 12 PCR negative or flow MRD <0.01% |
– |
5-year EFS 81.6% 5-year OS 91.5% (SR group combined) |
[160] |
| TCCSG L04–16 | 1–6 | <20 | No CNS3 | + | <1.000 blast/µl (PB) | – |
Day 43 M1 |
– | – |
5-year EFS 85% 5-year OS 95.4% |
[161] |
CNS central nervous system involvement, PB peripheral blood, BM bone marrow, MRD measurable residual disease, DFS disease-free survival, ES event-free survival, OS overall survival, CCR continuous complete remission, PII/PIII protocol II or protocol III of AIEOP/BFM, respectively, DI delayed intensification.
aPatients were exposed for 1 week to prednisone monotherapy before chemotherapy on day 8 has been initiated. On day 0, one additional dose of methotrexate was given intrathecally. The presence of less or more than 1.000 blasts/μl PB on day 8 was defined as prednisone good or poor response, respectively.
bDay 29 responses.
cDay 8 or day 15 M1 bone marrow.
dDay 19 MRD <0.01%.
+ day 29 MRD detectable but <0.01% and undetectable before start of interim maintenance.