MRD stratification for patients with B-lineage ALL in selected contemporary clinical trials
| Study . | MRD study . | MRD stratification . | ||||
|---|---|---|---|---|---|---|
| Time . | Site . | |||||
| Associazione Italiana Ematologia Oncologia Pediatrica Berlin-Frankfurt-Münster (AIEOP-BFM) ALL 20098,9 * | Day 15 Day 33 Day 78 | Bone marrow Bone marrow Bone marrow | SR No HR factors and day 33 and day 78 MRD negative by PCR, or PCR-MRD not available and day 15 <0.1% by FCM | MR Others | HR HR factors, or day 15 ≥10% by FCM or day 78 ≥0.05% by PCR, or for B-ALL only, day 33 ≥0.05% and day 78 positive <0.05% by PCR | |
| Children’s Oncology Group (COG) AALL 08B110 † | Day 8 Day 29 | Blood Bone marrow | LR NCI SR Favorable genetics; no unfavorable factors; day 8 <0.01%; day 29 <0.01% | AR NCI SR Favorable genetics; no unfavorable factors; day 8 ≥0.01%; day 29 <0.01%, or neutral genetics; no unfavorable factors; day 8 <1%; day 29 <0.01% | HR NCI SR Favorable genetics; no unfavorable factors; day 29 ≥0.01% NCI SR Neutral genetics; no unfavorable factors; day 8 ≥1%; day 29 <0.01% NCI HR Day 29 <0.01% | VHR NCI SR or HR Unfavorable factors NCI SR Neutral genetics; day 29 ≥0.01% NCI HR Day 29 ≥0.01%, or Age ≥13 y |
| Dutch Children’s Oncology Group (DCOG) ALL-1012 ‡ | Day 33 Day 79 | Bone marrow Bone marrow | SR No unfavorable factors; day 33 and day 79 undetectable by PCR | MR Others | HR Unfavorable factors; day 33 ≥0.05%; day 79 ≥0.05% | Induction failure Day 29 >5% |
| NCRI United Kingdom Acute Lymphoblastic Leukaemia (UKALL) 201113,14 § | Day 29 Week 14 | Bone marrow Bone marrow | LR Day 29 <0.005% | IR Unfavorable factors, or Day 29 <0.005%; and week 14 <0.5% | HR Week 14 ≥0.5% | |
| St. Jude Children’s Research Hospital (SJCRH) Total Therapy XVI17-19 || | Day 15 Day 42 Week 15 | Bone marrow Bone marrow Bone marrow if day 42 ≥0.01% | LR Favorable factors; day 15 <1%; day 42 <0.01% | SR Favorable factors; day 15 ≥1%; day 42 <1%, or Unfavorable factors; day 42 <1% | HR Day 42 ≥1%, or week 15 ≥0.1% | |
| Study . | MRD study . | MRD stratification . | ||||
|---|---|---|---|---|---|---|
| Time . | Site . | |||||
| Associazione Italiana Ematologia Oncologia Pediatrica Berlin-Frankfurt-Münster (AIEOP-BFM) ALL 20098,9 * | Day 15 Day 33 Day 78 | Bone marrow Bone marrow Bone marrow | SR No HR factors and day 33 and day 78 MRD negative by PCR, or PCR-MRD not available and day 15 <0.1% by FCM | MR Others | HR HR factors, or day 15 ≥10% by FCM or day 78 ≥0.05% by PCR, or for B-ALL only, day 33 ≥0.05% and day 78 positive <0.05% by PCR | |
| Children’s Oncology Group (COG) AALL 08B110 † | Day 8 Day 29 | Blood Bone marrow | LR NCI SR Favorable genetics; no unfavorable factors; day 8 <0.01%; day 29 <0.01% | AR NCI SR Favorable genetics; no unfavorable factors; day 8 ≥0.01%; day 29 <0.01%, or neutral genetics; no unfavorable factors; day 8 <1%; day 29 <0.01% | HR NCI SR Favorable genetics; no unfavorable factors; day 29 ≥0.01% NCI SR Neutral genetics; no unfavorable factors; day 8 ≥1%; day 29 <0.01% NCI HR Day 29 <0.01% | VHR NCI SR or HR Unfavorable factors NCI SR Neutral genetics; day 29 ≥0.01% NCI HR Day 29 ≥0.01%, or Age ≥13 y |
| Dutch Children’s Oncology Group (DCOG) ALL-1012 ‡ | Day 33 Day 79 | Bone marrow Bone marrow | SR No unfavorable factors; day 33 and day 79 undetectable by PCR | MR Others | HR Unfavorable factors; day 33 ≥0.05%; day 79 ≥0.05% | Induction failure Day 29 >5% |
| NCRI United Kingdom Acute Lymphoblastic Leukaemia (UKALL) 201113,14 § | Day 29 Week 14 | Bone marrow Bone marrow | LR Day 29 <0.005% | IR Unfavorable factors, or Day 29 <0.005%; and week 14 <0.5% | HR Week 14 ≥0.5% | |
| St. Jude Children’s Research Hospital (SJCRH) Total Therapy XVI17-19 || | Day 15 Day 42 Week 15 | Bone marrow Bone marrow Bone marrow if day 42 ≥0.01% | LR Favorable factors; day 15 <1%; day 42 <0.01% | SR Favorable factors; day 15 ≥1%; day 42 <1%, or Unfavorable factors; day 42 <1% | HR Day 42 ≥1%, or week 15 ≥0.1% | |
AIEOP, Associazione Italiana Ematologia Oncologia Pediatrica; AR, average risk; FM, Berlin-Frankfurt-Münster; COG, Children’s Oncology Group; DCOG, Dutch Children’s Oncology Group; FCM, flow cytometry; HR, high risk; IR, intermediate risk; LR, low risk; MR, medium risk; NCI, National Cancer Institute; SJCRH, St. Jude Children’s Research Hospital; SR, standard risk; UKALL, United Kingdom Acute Lymphoblastic Leukaemia; VHR, very high risk.
High-risk factors include prednisone poor response, nonremission on day 33, MLL-AF4 or t (4;11), hypodiploidy <45 chromosomes.
Favorable genetics include double trisomy 4 and 10 or ETV6-RUNX1, and unfavorable factors include central nervous system 3 (CNS3) status, testicular leukemia, hypodiploidy <44 chromosomes, DNA index <0.81, intrachromosomal amplification of chromosome 21, M3 marrow on day 29, MLL rearrangement, and BCR-ABL1. NCI HR indicates patients with B-lineage ALL with presenting leukocyte count ≥50 000/μL or age ≥10 y, and NCI SR indicates patients without these features.
Unfavorable factors include MLL-AF4, prednisone poor response, CNS3 status, testicular leukemia, and no complete remission on day 33.
Unfavorable factors include MLL rearrangement, near haploidy <30 chromosomes, low hypoploidy 30-39 chromosomes, t(17;19) (q23;p13) and intrachromosomal amplification of chromosome 21.
Favorable factors include NCI SR, ETV6-RUNX1, DNA index ≥1.16; unfavorable factors include CNS3 status, testicular leukemia, BCR-ABL1, E2A-PBX1, MLL rearrangement, and hypodiploidy <44 chromosomes.