Table 2.
CNS status at diagnosis, use of prophylactic cranial radiotherapy and outcomes in selected childhood ALL trials [8, 22, 23, 34, 37, 132–145].
| CNS status at diagnosis, % | 5-year cumulative incidence of CNS relapse, % | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Study | Recruitment period | Patients, n | CNS1 | CNS2 | CNS3 | TLP+ | CNS positive [definition where available] | Indication for prophylactic cranial irradiation | Isolated | Combined | 5-year EFS, % |
| AIEOP-BFM ALL2000 [34, 132, 133] | 2000–2006 | 3720 | n/a | n/a | n/a | n/a | 2.5 | MRD levels ≥10 − 3 at day 78, no CR at day 33, t(4;11) translocation, and poor prednisolone response | 1.5 | 1.2 | 82.2 |
| CCG 1991§ [134] | 2000–2005 | 1769 | 92.1 | 3.8 | 2.0 | 2.1 | No | 1.8 | 0.7 | 90.7 | |
| COALL 07–03 [135] | 2003–2010 | 763 | n/a | n/a | n/a | n/a | 2.6 [non-traumatic LP with leukocytes >5/uL in CSF] | B-precursor ALL and an initial WBC count of >200/nL or 100 to 200/nL and >1 × 109/L leukemic blasts in the peripheral blood at day 8, and patients with T-ALL with a WBC count of ≥50/nL | 1.4 | 2.1 | 84.3 |
| COG AALL 0232 [37] | 2004–2011 | 2914 | 85.9 | 14.1 | n/a | n/a | BM D15 M2 or M3, or D29 MRD > 0.1% | n/a | n/a | 75.3 | |
| COG AALL 0331 [23, 136] | 2005–2010 | 5299 | 91.0 | 8.0 | 1.0 | n/a | No | 2.0‡ | 0.8‡ | 89.0‡ | |
| DCOG ALL9 [137] | 1997–2004 | 859 | n/a | n/a | n/a | n/a | 2.4 [CNS3 (>5 cells/uL + blasts with <15 RBC/uL) or CT/MRI features] | No | 2.6 | 0.8 | 83.3 |
| DCOG ALL10 [138] | 2004–2012 | 778 | 42.4 | 42.2 | 1.0 | 10.3 | Patients aged >3 years on non-transplant protocol with TP1 MRD level of ≥5 × 10 − 4 or unknown and TP2 MRD level of ≥5 × 10 − 4, MLL-AF4 rearrangements, poor prednisone response, or no CR day 33 | 1.4 | 0.9 | 88.7 | |
| DFCI 00–01 [22] | 2000–2004 | 487 | 84.2 | 12.3 | 3.5 | n/a | WBC ≥ 50,000/μL, non-B-precursor phenotype, or prescence of mediastinal mass | 1.5 | 2.7 | 80.0 | |
| JACLS ALL-02 [139] | 2002–2008 | 1047 | 90.6 | 2.6 | 2.2 | 0.6 | No | 0.8† | 0.6† | 85.4† | |
| NOPHO ALL2000 [140, 141] | 2002–2007 | 1020 | 97.1* | n/a | 2.9 | n/a | Any age and WBC ≥ 200 × 109 l–1, BM D29 M3, t(9;22)(q34;q11), t(4;11)(q21;q23), or low hypodiploidy. And ≥5 years WBC 100—200 × 109 l–1 or T-ALL and mediastinal mass | 2.7 | 2.1 | 79.4 | |
| SJCRH total thearpy 15 [8] | 2000–2007 | 498 | 72.1 | 20.5 | 1.8 | 5.6 | No | 2.7 | 0.8 | 85.6 | |
| SJCRH total thearpy 16 [142] | 2007–2017 | 598 | 57.4 | 33.4 | 3.5 | 5.7 | No | 1.2 | 0.3 | 88.2 | |
| TCCSG L99-15 [143] | 1999–2003 | 754 | n/a | n/a | n/a | n/a | 2.9 [CNS-1s, CNS-2, CNS-3, TPL+ blasts] | WBC ≥ 100 | 1.6† | 1.5† | 78.2† |
| UKALL2003 [144, 145] | 2003–2011 | 3113 | 93.8 | 5.1 | 1.1 | n/a | n/a | CNS3 until August 2009 | 1.9 | 1.1 | 87.2 |
ALL acute lymphoblastic leukemia, BM bone marrow, CNS central nervous system, CR complete remission, CSF cerebrospinal fluid, CT computed tomography, EFS event free survival, M2 bone marrow has 5–25% leukemic blasts, M3 bone marrow has >25% leukemic blasts, MRD minimal residual disease, MRI magnetic resonance imaging, RBC red blood cells, TLP+ traumatic lumbar puncture with blasts present on cytospin, WBC white blood cells.
AIEOP-BFM l’Associazione Italiana di Ematologia e Oncologia Pediatrica – Berlin Frankfurt Münter, CCG Children’s Cancer Group, COALL Cooperative Acute Lymphoblastic Leukemia Study Group, COG ALL Children’s Oncology Group Acute Lymphoblastic Leukemia, DCOG Dutch Childhood Oncology Group, DFCI Dana-Farber Cancer Institute. JACLS Japan Childhood Leukemia Study Group. NOPHO Nordic Society of Paediatric Haematology and Oncology. SJCRH St. Jude Children’s Research Hospital. TCCSG Tokyo Children’s Cancer Study Group. UKALL United Kingdom Medical Research Council Acute Lymphoblastic Leukaemia.
*Combined CNS1 and CNS2.
†4-year EFS.
‡6-year EFS.
§Derived from methotrexate randomization data.