Article Figures & Data
Figures
- Figure 1.
AYA and children with ALL: 5-year relapse-free survival by age group.
- Figure 2.
Hazard of relapse in AYA and children with ALL. Smoothed plot of risk of relapse per month, stratified by age (AYA vs. child) for the following groups: A, Overall hazard of relapse from first CR1 to 10 years. B, Hazard of relapse during treatment from CR1. C, Hazard of relapse after completion of treatment (from date of last treatment). Shaded areas indicate confidence regions.
Tables
- Table 1.
Characteristics of children and AYA with ALL
Total Child: 1–14 y AYA: 15–39 y (n = 184) (n = 91) (n = 93) P Sociodemographics Age Median (interquartile range) 15 y (4.75–34 y) 4 y (3–10 y) 23 y (19–30 y) Gender Male 119 (64.7%) 56 (61.5%) 63 (67.7%) 0.4 Female 65 (35.3%) 35 (38.5%) 30 (32.3%) Race/ethnicity Non-Hispanic white 63 (34.2%) 30 (33.0%) 33 (35.5%) 0.1 African-American 1 (0.5%) 0 (0%) 1 (1.1%) Hispanic 99 (53.8%) 46 (50.6%) 53 (57.0%) Asian-Pacific Islander 21 (11.4%) 15 (16.5%) 6 (6.5%) Insurance Private 85 (46.2%) 48 (52.8%) 37 (39.8%) 0.2 Public 66 (35.9%) 30 (33.0%) 36(38.7%) No insurance/unknown 33 (17.9%) 13 (14.3%) 20 (21.5%) SES Low 32 (17.4%) 10 (11.0%) 22 (23.7%) 0.2 Mid-Low 36 (19.6%) 18 (19.8%) 18 (19.4%) Mid 39 (21.2%) 23 (25.3%) 16 (17.2%) Mid-High 39 (21.2%) 20 (22.0%) 19 (20.4%) High 38 (20.7%) 20 (22.0%) 18 (19.4%) Insurance + SES combined Private insurance + high SES 47 (25.5%) 26 (28.6%) 21 (22.6%) 0.3 Public/none + mid/low SES 69 (37.5%) 29 (31.9%) 40 (43.0%) Mixed profilea 68 (37.0%) 34 (31.9%) 32 (34.4%) Treatment variables Therapy Pediatric 102 (55.4%) 84 (92.3%) 18 (19.4%) <0.0001 Adult 65 (35.3%) 0 (0%) 65 (69.9%) Mixed 7 (3.8%) 0 (0%) 7 (7.5%) International 10 (5.4%) 7 (7.7%) 3 (3.2%) Oncology service Pediatric 101 (54.9%) 84 (92.3%) 17 (18.3%) <0.0001 Adult 71 (38.6%) 0 (0%) 71 (76.3%) Mixed 2 (1.1%) 0 (0%) 2 (2.2%) International 10 (5.4%) 7 (7.7%) 3 (3.2%) Oncology service + therapy Pediatric oncology/pediatric therapy 101 (54.9%) 84 (92.3%) 17 (18.3%) <0.0001 Adult oncology/adult therapy 65 (35.3%) 0 (0%) 65 (69.9%) Mixed oncology/mixed therapy 18 (9.8%) 7 (7.7%) 11 (11.8%) Duration of maintenance mean (SD) in months All patients 19 (11.2) 23.5 (8.5) 14.9 (12) <0.01 Patients who completed therapy 25.4 (6.8) 25.3 (6.5) 25.4 (7.3) 0.9 Duration of consolidation mean (SD) in months All patients 7.2 (3.6) 8.0 (3.6) 6.5 (3.5) <0.01 Patients who completed therapy 8.0 (3.5) 8.2 (3.6) 7.7 (3.4) 0.5 Clinical trial enrollment Enrolled on clinical trial 60 (32.6%) 39 (42.9%) 21 (22.6%) 0.003 Not enrolled on clinical trial 124 (67.4%) 52 (57.1%) 72 (77.4%) Clinical prognosticators White blood cell count at diagnosis WBC <50K 129 (70.1%) 67 (73.6%) 62 (66.7%) 0.3 WBC >50K 55 (29.9%) 24 (26.4%) 31 (33.3%) Response to therapy at the end of inductionb M1 marrow at end of Induction 139 (75.5%) 78 (85.7%) 61 (65.6%) <0.01 M2-M3 marrow at end of Induction 18 (9.8%) 4 (4.4%) 14 (15.1%) Other 27 (14.7%) 9 (9.9%) 18 (19.4%) Immunophenotype Precursor B-cell 149 (81%) 79 (86.8%) 70 (75.3%) 0.04 T-cell 35 (19%) 12 (13.2%) 23 (24.7%) High-risk cytogenetic profilec High-risk cytogenetic profile 18 (9.8%) 5 (5.5%) 13 (14.0%) 0.05 No presence of high-risk features 166 (90.2%) 86 (94.5%) 80 (86%) CNS disease Positive 6 (3.3%) 2 (2.2%) 4 (4.3%) 0.3 Negative 168 (91.3%) 86 (94.5%) 82 (88.2%) Unknown 10 (5.4%) 3 (3.3%) 7 (7.5%) ↵aMixed profile in this situation reflects a combination of either public or no insurance + high SES, or private insurance + low SES.
↵bResponse to therapy at the end of induction was grouped as follows: (i) patients with an M1 marrow (<5% blasts) at the end of induction; (ii) patients with an M2-M3 marrow (≥5% blasts) at the end of induction, but with M1 marrow on follow-up evaluation after additional therapy; (iii) patients who did not have a documented end of induction marrow, but the first marrow documented after initiation of treatment (>36 days) was M1 (“other”).
↵cHigh-risk cytogenetic profile indicates presence of either: Philadelphia chromosome, MLL rearrangement and/or hypodiploidy.
- Table 2.
Multivariable hazard of relapse in AYA and children
Relapse during therapya (all patients: n = 184) Relapse after completion of therapya (patients completed therapy: n = 119) HR (95% CI) P HR (95% CI) P Age group Child 1.0 (—) — 1.0 (—) — AYA 10.5 (2.1–52.5) 0.004 7.7 (2.5–23.9) <0.001 Duration of therapy Duration of maintenanceb 1.0 (0.8–1.3) 0.9 0.9 (0.8–0.9) <0.001 Duration of consolidationb 1.0 (0.8–1.3) 0.9 0.9 (0.8–1.0) 0.2 Oncology service and therapy types Pediatric oncology + pediatric therapy 1.0 (—) — 1.0 (—) — Adult oncology + adult therapy 2.5 (1.1–5.7) 0.03 0.6 (0.2–1.8) 0.3 Mixed oncology + mixed therapy 0.5 (0.2–1.8) 0.3 0.23 (0.04–1.0) 0.04 Insurance and SES Private insurance + high SES 1.0 (—) — 1.0 (—) — Public insurance + low SES 0.7 (0.3–1.5) 0.3 6.2 (1.8–21.9) 0.004 Mixed profile 0.9 (0.4–0.8) 0.7 2.1 (0.5–8.3) 0.3 Race/ethnicity Non-Hispanic white 1.0 (—) — 1.0 (—) — Nonwhite race/ethnicity 2.1 (1.1–4.0) 0.03 0.6 (0.2–1.5) 0.2 Clinical trial enrollment Enrolled on clinical trial 1.0 (—) — 1.0 (—) — Not enrolled on clinical trial 1.8 (0.9–3.5) 0.09 0.6 (0.3–1.5) 0.3 Gender Female 1.0 (—) — 1.0 (—) — Male 0.7 (0.4–1.3) 0.3 3.3 (1.3–8.5) 0.01 Time Time in monthsb 1.0 (0.8–1.3) 0.8 1.0 (0.9–1.0) <0.001 Clinical prognosticators WBC at diagnosis <50K 1.0 (—) — 1.0 (—) — WBC at diagnosis >50K 1.6 (1.0–3.0) 0.07 3.5 (1.4–8.8) 0.007 Precursor B-cell 1.0 (—) — 1.0 (—) — T-cell 1.1 (0.6–2.1) 0.8 0.2 (0.07–0.7) 0.007 No high-risk cytogenetics identified 1.0 (—) — 1.0 (—) — High-risk cytogenetic profile 1.1 (0.5–2.3) 0.8 0.5 (0.1–2.0) 0.3 M1 marrow at end of inductionc 1.0 (—) — 1.0 (—) — M2-M3 marrow at end of inductionc 1.8 (0.9–4.0) 0.1 2.0 (0.5–7.5) 0.3 CNS negative 1.0 (—) — CNS positive 4.9 (1.6–15.3) 0.006 ↵aAdjusted discrete time survival analysis, modeling hazard of relapse with death due to nonrelapse causes and date of last contact as censoring events. Bolded values represent statistically significant findings. On-therapy model adjusted for AYA*time interaction.
↵bThese variables were modeled as time-varying covariates. Months represents: (i) months from remission in the model calculating hazard of relapse on therapy; (ii) months from completion of therapy in the model calculating hazard of relapse after completing therapy. HRs represent each additional month of time from remission/completion of therapy, or each additional month of therapy.
↵cPatients with M2-M3 marrows (≥5% blasts) at the end of induction were compared with patients who either (i) had M1 marrows (<5% blasts) at the end of induction or (ii) did not have a documented end of induction marrow, but the first marrow documented after initiation of treatment (>36 days) was M1.
- Table 3.
Multivariable hazard of relapse in AYA by time of relapse
Relapse during therapya (all AYA: n = 93) Relapse after completion of therapya (AYA who completed therapy: n = 42) HR (95% CI) P HR (95% CI) P Duration of therapy Duration of maintenanceb 0.9 (0.7–1.2) 0.6 0.7 (0.6–0.8) <0.001 Duration of consolidationb 0.9 (0.7–1.2) 0.6 0.8 (0.6–1.0) 0.03 Oncology service and therapy types Pediatric oncology + pediatric therapy 1.0 (—) — 1.0 (—) — Adult oncology + adult therapy 1.9 (0.7–5.2) 0.2 0.8 (0.1–4.7) 0.8 Mixed oncology + mixed therapy 0.3 (0.1–1.5) 0.2 0.3 (0.04–1.9) 0.2 Insurance and SES Private insurance + high SES 1.0 (—) — 1.0 (—) — Public insurance + low SES 0.5 (0.2–1.4) 0.2 6.8 (0.8–60.8) 0.09 Mixed profile 0.6 (0.2–1.7) 0.4 1.2 (0.1–12.5) 0.9 Race and ethnicity Non-Hispanic white 1.0 (—) — 1.0 (—) — Nonwhite race/ethnicity 2.2 (1.0–4.8) 0.05 0.2 (0.03–1.9) 0.2 Clinical trial enrollment Enrolled on clinical trial 1.0 (—) — 1.0 (—) — Not enrolled on clinical trial 2.6 (1.0–6.3) 0.04 1.1 (0.2–6.0) 0.9 Gender Female 1.0 (—) — 1.0 (—) — Male 0.8 (0.4–1.7) 0.6 1.3 (0.3–5.1) 0.7 Age Age, y 1.00 (1.0–1.1) 0.5 1.0 (0.9–1.1) 1.0 Time Time in monthsb 1.1 (0.8–1.4) 0.7 0.98 (0.96–1.0) 0.03 Clinical prognosticators WBC <50K 1.0 (—) — 1.0 (—) — WBC >50K 1.6 (0.8–3.1) 0.2 7.9 (1.6–38.8) 0.01 Precursor B cell 1.0 (—) — 1.0 (—) — T cell 1.3 (0.6–2.6) 0.5 0.3 (0.04–1.6) 0.2 No high-risk cytogenetics identified 1.0 (—) — 1.0 (—) — High-risk cytogenetic profile 1.2 (0.6–2.6) 0.7 M1 marrow at end of inductionc 1.0 (—) — 1.0 (—) — M2-M3 marrow at end of inductionc 2.0 (0.9–4.9) 0.1 1.2 (0.2–6.6) 0.9 CNS negative 1.0 (—) — CNS positive 8.6 (2.1–35.0) 0.003 ↵aAdjusted discrete time survival analysis, modeling hazard of relapse with death due to nonrelapse causes and date of last contact as censoring events. Bolded values represent statistically significant findings. On-therapy model adjusted for AYA*time interaction.
↵bThese variables were modeled as time-varying covariates. Time at risk represents: (i) months from CR1 in the model calculating hazard of relapse on therapy; (ii) months from completion of therapy in the model calculating hazard of relapse after completing therapy. HRs represent each additional month of time from remission/completion of therapy, or each additional month of therapy.
↵cPatients with M2-M3 marrows at the end of induction were compared with patients who either (i) had M1 marrows at the end of induction or (ii) did not have a documented end of induction marrow, but the first marrow documented after initiation of treatment (>36 days) was M1.
Supplementary Data
- Supplementary Figure 1 - Consort Diagram of Final Evaluable Cohort
- Supplementary Table 1 - Univariable Hazard of Relapse in Adolescents and Young Adults (AYA) and Children
- Supplementary Figure 2 - Proportion of Patients per Age Group by Year at Diagnosis
Volume 27, Issue 10
