Table 1.
Survival Rate of Patients with Remission-Induction Failure, According to Presenting Features.*
| Baseline Characteristic | Patients (N = 1041) no./total no. (%) |
10-Year Survival Rate % |
P Value |
|---|---|---|---|
| All patients | |||
| t(9;22)(BCR-ABL1) status | <0.001 | ||
| Positive | 110/815 (13) | 11±3 | |
| Negative | 705/815 (87) | 35±2 | |
| No data | 226/1041 | 32±3 | |
| t(9;22)(BCR-ABL1)–negative patients | |||
| Sex | 0.08 | ||
| Male | 427/705 (61) | 32±2 | |
| Female | 278/705 (39) | 39±3 | |
| Age at diagnosis | <0.001 | ||
| <1 yr | 44/705 (6) | 29±7 | |
| 1–5 yr | 236/705 (33) | 52±3 | |
| 6–9 yr | 150/705 (21) | 33±4 | |
| 10–13 yr | 169/705 (24) | 25±3 | |
| 14–18 yr | 106/705 (15) | 16±5 | |
| Leukocyte count at diagnosis | <0.001 | ||
| <20 (×109/liter) | 215/704 (31) | 42±4 | |
| 20 to 49 (×109/liter) | 77/704 (11) | 38±6 | |
| 50 to 99 (×109/liter) | 113/704 (16) | 43±5 | |
| 100 to 199 (×109/liter) | 99/704 (14) | 33±5 | |
| ≥200 (×109/liter) | 200/704 (28) | 23±3 | |
| Cell lineage | <0.001 | ||
| B-cell | 387/628 (62) | 41±3 | |
| T-cell | 241/628 (38) | 28±3 | |
| NCI criteria† | <0.001 | ||
| B-cell lineage | |||
| Standard risk | 166/593 (28) | 60±4 | |
| High risk | 189/593 (32) | 26±3 | |
| T-cell lineage | |||
| Standard risk | 50/593 (8) | 30±7 | |
| High risk | 188/593 (32) | 27±3 | |
| CNS leukemia | 0.23 | ||
| Yes | 44/684 (6) | 32±7 | |
| No | 640/684 (94) | 35±2 | |
| Karyotype‡ | <0.001 | ||
| Normal | 159/514 (31) | 36±4 | |
| 11q23/MLL | 50/514 (10) | 16±5 | |
| High hyperdiploidy | 55/514 (11) | 71±6 | |
| Other | 250/514 (49) | 30±3 | |
| Bone marrow status at end of induction§ | <0.001 | ||
| M1 | 22/620 (4) | 45±11 | |
| M2 | 282/620 (45) | 41±3 | |
| M3 | 316/620 (51) | 26±3 | |
| Complete remission according to protocol criteria¶ | <0.001 | ||
| Yes | 389/520 (75) | 48±3 | |
| No | 131/520 (25) | 14±3 | |
| Period of diagnosis | 0.04 | ||
| 1985–1988 | 44/705 (6) | 27±7 | |
| 1989–1992 | 172/705 (24) | 28±3 | |
| 1993–1996 | 237/705 (34) | 38±3 | |
| 1997–2000 | 252/705 (36) | 39±3 |
Plus–minus values are 10-year survival estimates ±SE. For all 1041 patients, the 10-year survival rate was 32±1%, the median age at diagnosis was 8.1 years, and the median leukocyte count at the time of diagnosis was 42×109 per liter. P values were calculated with the use of the log-rank test. CNS denotes central nervous system.
According to National Cancer Institute (NCI) criteria, standard-risk patients were 1 to 9 years of age with a leukocyte count of less than 50×109 per liter; all other patients were high-risk.
Cytogenetic or molecular genetic information was available for 624 patients — initially in 608 patients and after additional analysis in the other 16 patients; BCR-ABL1 was found in 14 of these 16 patients and rearrangement of the mixed-lineage leukemia gene (MLL) was found in 2. T-cell ALL was diagnosed in 7 of the patients with BCR-ABL1 and in 12 of the patients with MLL rearrangement. The 110 patients with positive t(9;22)(BCR-ABL1) status were excluded from the analysis. High hyperdiploidy was defined by a modal chromosomal number (the most frequent count of chromosomes in a given patient) above 50.
Bone marrow status at the end of induction was defined by the study groups (Table 2 in the Supplementary Appendix) as follows: M1, less than 5% blasts; M2, 5 to 24% blasts; and M3, 25% or more blasts. The Pediatric Oncology Group (POG) had data on patients with M3 bone marrow status only. Exclusion of the POG data resulted in a total of only 546 patients with data: 22 patients (4%) had M1 status, 282 patients (52%) had M2 status, and 242 patients (44%) had M3 status. Survival estimates remained unchanged. The small percentage of patients with M1 marrow (4%) were considered to have had induction failure despite this “remission” status because persisting leukemic blasts were found at the other sites: mediastinal mass in 7 patients; CNS, lymph nodes, liver, kidney, spleen, or parotid glands in 12 patients; and peripheral blood in 3 patients.
Most study groups checked the remission status of patients again at predefined times after the end of induction. Exceptions were the Children’s Cancer Group (CCG), the POG, and the St. Jude Children’s Research Hospital study group, which evaluated remission only at the end of induction. Patients in these three studies, as well as patients in other studies with missing data, are excluded here.