Table 2.
Outcome of patients with high hyperdiploid acute lymphoblastic leukaemia treated in UKALL2003 stratified by UKALL high hyperdiploid risk profile, end of induction minimal residual disease, and UKALL copy number alteration profile
|
Number of cases |
Relapse rate |
Event-free survival |
Overall survival |
||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Total | UKALL-HeH good risk | UKALL-HeH poor risk | Total | UKALL-HeH good risk | UKALL-HeH poor risk | p value | Total | UKALL-HeH good risk | UKALL-HeH poor risk | p value | Total | UKALL-HeH good risk | UKALL-HeH poor risk | p value | |||
| All patients with high hyperdiploidy | 725 (100%) | 579 (100%) | 146 (100%) | 7% (5–9) | 5% (3–7) | 16% (10–23) | 0·0030 | 90% (87–92) | 92% (90–94) | 81% (73–86) | 0·0010 | 94% (92–95) | 96% (94–97) | 86% (79–91) | <0·0001 | ||
| MRD data available | 632 (87%) | 510 (88%) | 122 (84%) | 7% (5–9) | 5% (3–7) | 16% (10–24) | <0·0001 | 91% (88–93) | 93% (90–95) | 81% (73–87) | <0·0001 | 95% (93–96) | 97% (95–98) | 86% (78–92) | <0·0001 | ||
| MRD data not available | 93 (13%) | 69 (12%) | 24 (16%) | 6% (3–15) | 4% (1–13) | 14% (5–37) | 0·079 | 84% (74–90) | 85% (74–92) | 79% (57–91) | 0·53 | 87% (78–92) | 88% (78–94) | 83% (61–93) | 0·59 | ||
| MRD levels, % | |||||||||||||||||
| 0 | 174 (27%) | 145 (28%) | 29 (24%) | 4% (2–9) | 3% (1–9) | 7% (2–26) | 0·19 | 95% (91–98) | 97% (91–99) | 89% (71–96) | 0·037 | 98% (95–99) | 100% | 89% (71–96) | <0·0001 | ||
| 0 to <0·01 | 196 (31%) | 158 (31%) | 38 (31%) | 6% (3–10) | 4% (2–9) | 15% (6–32) | 0·0030 | 92% (87–95) | 94% (89–97) | 81% (63–90) | 0·0020 | 95% (91–98) | 98% (94–99) | 85% (66–93) | 0·0020 | ||
| 0·01 to <0·1 | 154 (24%) | 126 (25%) | 28 (23%) | 7% (4–12) | 3% (1–9) | 23% (11–44) | <0·0001 | 91% (86–95) | 94% (89–97) | 77% (56–89) | 0·0070 | 95% (89–98) | 95% (89–98) | 92% (73–98) | 0·45 | ||
| 0·1 to <1·0 | 73 (12%) | 54 (11%) | 19 (16%) | 11% (6–22) | 12% (5–24) | 11% (3–38) | 0·92 | 84% (73–90) | 83% (70–91) | 84% (59–95) | 0·91 | 93% (84–97) | 94% (84–98) | 89% (64–97) | 0·45 | ||
| ≥1·0 | 35 (6%) | 27 (5%) | 8 (7%) | 19% (9–38) | 12% (4–34) | 42% (16–82) | 0·048 | 76% (58–87) | 81% (60–92) | 58% (18–84) | 0·20 | 79% (61–89) | 85% (65–94) | 57% (17–84) | 0·10 | ||
| Original MRD risk group, % | |||||||||||||||||
| <0·01 | 370 (59%) | 303 (59%) | 67 (55%) | 5% (3–8) | 4% (2–7) | 11% (6–23) | 0·0010 | 93% (90–96) | 95% (92–97) | 84% (73–91) | <0·00001 | 97% (94–98) | 99% (97–100) | 86% (73–93) | <0·0001 | ||
| ≥0·01 | 262 (41%) | 207 (41%) | 55 (45%) | 10% (7–14) | 7% (4–11) | 21% (12–35) | 0·0020 | 87% (82–91) | 90% (85–93) | 77% (63–86) | 0·023 | 92% (88–95) | 94% (89–96) | 87% (74–93) | 0·076 | ||
| Optimal MRD threshold, % | |||||||||||||||||
| <0·03 | 462 (73%) | 377 (74%) | 85 (70%) | 5% (3–8) | 4% (2–6) | 11% (6–21) | 0·0010 | 93% (90–95) | 95% (92–97) | 85% (76–91) | <0·0001 | 96% (94–98) | 98% (96–99) | 88% (77–94) | <0·0001 | ||
| ≥0·03 | 170 (27%) | 133 (26%) | 37 (30%) | 12% (8–18) | 8% (4–14) | 27% (15–45) | 0·0030 | 84% (78–89) | 88% (81–92) | 71% (53–84) | 0·024 | 90% (85–94) | 92% (86–96) | 83% (65–92) | 0·064 | ||
| Slow early responder* | |||||||||||||||||
| Yes | 68 (9%) | 53 (9%) | 15 (10%) | 19% (11–32) | 12% (5–26) | 46% (24–75) | 0·0010 | 76% (63–85) | 83% (69–91) | 50% (23–72) | 0·0040 | 86% (76–93) | 94% (83–98) | 57% (29–78) | <0·0001 | ||
| No | 657 (91%) | 526 (91%) | 131 (90%) | 6% (4–8) | 4% (3–6) | 12% (8–20) | <0·0001 | 91% (89–93) | 93% (90–95) | 84% (77–90) | 0·0010 | 95% (92–96) | 96% (94–97) | 89% (82–94) | 0·0040 | ||
| Treatment pathways† | |||||||||||||||||
| MRD <0·01% and regimen A or B | 346 | 287 | 59 | 5% (3–8) | 4% (2–7) | 9% (4–21) | 0·014 | 94% (90–96) | 95% (92–97) | 86% (74–93) | 0·0010 | 97% (94–98) | 99% (96–100) | 88% (74–95) | <0·0001 | ||
| One delayed intensification block | 158 (46%) | 133 (46%) | 25 (42%) | 95% (89–98) | 95% (89–98) | 92% (71–98) | 0·31 | 5% (2–10) | 5% (2–11) | 4% (1–27) | 0·90 | 97% (90–99) | 99% (92–100) | 85% (48–97) | 0·011 | ||
| Two delayed intensification blocks | 188 (54%) | 154 (54%) | 34 (57%) | 92% (88–95) | 95% (90–97) | 82% (64–91) | 0·0020 | 5% (3–9) | 3% (1–8) | 13% (5–30) | 0·0040 | 97% (93–99) | 99% (95–100) | 88% (71–95) | 0·0020 | ||
| MRD ≥0·01% and regimen A or B | 143 | 113 | 30 | 8% (5–14) | 6% (3–13) | 15% (6–35) | 0·17 | 90% (84–94) | 92% (85–96) | 82% (62–92) | 0·14 | 94% (88–97) | 94% (87–97) | 93% (75–98) | 0·69 | ||
| MRD ≥0·01% and regimen C | 151 | 116 | 35 | 11% (7–18) | 7% (3–14) | 27% (15–46) | 0·0010 | 84% (77–89) | 88% (80–92) | 71% (52–83) | 0·021 | 90% (84–94) | 94% (88–97) | 76% (58–87) | 0·0040 | ||
| UKALL copy number alteration profile‡ | |||||||||||||||||
| Total | 239 (100%) | 189 (100%) | 50 (100%) | 10% (7–15) | 6% (3–11) | 27% (16–42) | <0·0001 | 86% (81–90) | 90% (85–94) | 69% (53–80) | <0·0001 | 92% (87–95) | 94% (90–97) | 81% (66–90) | 0·0020 | ||
| Good risk | 182 (76%) | 147 (78%) | 35 (70%) | 9% (5–14) | 5% (2–10) | 25% (13–44) | <0·0001 | 88% (82–92) | 92% (87–96) | 68% (50–81) | <0·0001 | 94% (89–96) | 96% (91–98) | 83% (65–92) | 0·0020 | ||
| Intermediate or poor risk | 57 (24%) | 42 (22%) | 15 (30%) | 15% (8–28) | 10% (4–25) | 29% (12–61) | 0·090 | 80% (67–89) | 83% (68–92) | 71% (39–88) | 0·37 | 85% (73–92) | 88% (74–95) | 75% (41–91) | 0·40 | ||
Data are n (%), rates at 10 years (95% CI), or n, unless otherwise indicated. HeH=high hyperdiploid. MRD=minimal residual disease. NCI=US National Cancer Institute.
*
Slow early responders were patients who had ≥25% marrow blasts at day 15 (NCI standard risk) or day 8 (NCI high risk).
†
Most patients followed one of these three main treatment pathways; the remaining patients have been excluded from this section for clarity. Details of treatment pathways can be found in the appendix (p 22).
‡
Only 239 patients were tested by multiplex ligation-dependent probe amplification to determine the UKALL copy number alteration profile.