EsPhALL (EsPhALL2004 and EsPhALL2010)
EsPhALL is the European intergroup study that brought the leukaemia pill imatinib into treatment for children with Philadelphia-positive acute lymphoblastic leukaemia; the first version gave it in short bursts after induction and the second gave it continuously, and together they set the chemotherapy backbone that the standard of care still uses.
Overview
EsPhALL was an intergroup study across ten European groups, Chile and Hong Kong for children with Philadelphia chromosome-positive acute lymphoblastic leukaemia identified on national front-line trials. In EsPhALL2004 (2004 to 2009) good-risk patients, defined by early response, were randomised to post-induction imatinib with chemotherapy or chemotherapy alone, and all poor-risk patients received imatinib; the backbone was a Berlin-Frankfurt-Munster high-risk regimen with transplant after four post-induction blocks. Four-year disease-free survival in good-risk patients was 72.9 percent with imatinib against 61.7 percent without, a difference that was not statistically significant in the intention-to-treat analysis, and four-year event-free survival in poor-risk patients was 53.5 percent.
EsPhALL2010 (2010 to 2014) gave imatinib continuously from day 15 of induction and through chemotherapy, with transplant reserved for poor early responders: 155 patients had five-year event-free survival of 57.0 percent and overall survival of 71.8 percent, similar to EsPhALL2004 despite transplanting fewer patients, at the cost of more toxicity during intensive blocks. The paediatric Philadelphia-positive leukaemia page describes imatinib given through induction and continued throughout EsPhALL-type chemotherapy on this evidence.
- 72.9 vs 61.7 out of 100 alive without the cancer coming back at 4 years with Post-induction imatinib + chemotherapy compared with Chemotherapy alone; 11.2 more per 100.
- Roughly one extra person helped for every 9 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- Put another way, the treated group had about 37 percent lower chance of the event at any given time (hazard ratio 0.63, likely range 0.28 to 1.41).
- The likely range for the hazard ratio crosses 1, so the difference could be due to chance.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- 53.5 out of 100 people free of a major event at 4 years with Post-induction imatinib + chemotherapy.
- There was no comparison group, so this number cannot tell you how much of the effect is due to the treatment.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- 57 out of 100 people free of a major event at 5 years with Imatinib from day 15 of induction + chemotherapy.
- There was no comparison group, so this number cannot tell you how much of the effect is due to the treatment.
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- 71.8 out of 100 people alive at 5 years with Imatinib from day 15 of induction + chemotherapy.
- There was no comparison group, so this number cannot tell you how much of the effect is due to the treatment.
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- These results apply to the people the trial enrolled: Children and adolescents aged 1 to 17 with Philadelphia chromosome-positive acute lymphoblastic leukaemia treated on national front-line trials: imatinib with a BFM high-risk chemotherapy backbone and transplant for the higher-risk, first as short discontinuous courses after induction (EsPhALL2004, randomised in good-risk patients) and then continuously from day 15 of induction (EsPhALL2010, single arm). People in a different situation may not see the same effect.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
178 registered.
95% CI 56.1 to 84.1 · 95% CI 45.0 to 74.7
Source95% CI 40.4 to 65.0
Source95% CI 48.5 to 64.6; 38% transplanted in first remission
Source95% CI 63.5 to 78.5
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Disease-free survival at 4 years, good-risk patients (EsPhALL2004)primary | Post-induction imatinib + chemotherapy | 46 | 72.9% | 0.63 (0.28 to 1.41) | 0.24 | link |
| Chemotherapy alone | 44 | 61.7% | ||||
| Event-free survival at 4 years, poor-risk patients (EsPhALL2004, all given imatinib)primary | Post-induction imatinib + chemotherapy | 70 | 53.5% | - | - | link |
| Event-free survival at 5 years (EsPhALL2010, continuous imatinib)primary | Imatinib from day 15 of induction + chemotherapy | 155 | 57% | - | - | link |
| Overall survival at 5 years (EsPhALL2010, continuous imatinib)primary | Imatinib from day 15 of induction + chemotherapy | 155 | 71.8% | - | - | link |
Continuous imatinib from induction lets many children with Philadelphia-positive ALL avoid transplant, but the intensive BFM backbone is toxic; later trials reduced chemotherapy intensity under tyrosine kinase inhibitor cover.
Together with AALL0031, EsPhALL established kinase inhibitor plus chemotherapy as standard for paediatric Ph-positive ALL, with later trials giving imatinib continuously and reducing transplant.
Similar pages
not linked directly; found by shared links- TrialAALL1521
Shares Leukaemia (all types), Acute lymphoblastic leukaemia, Cytotoxic chemotherapy, Small-molecule kinase inhibitors and the tag soc-trials.
- TrialGRAALL-2005
Shares Leukaemia (all types), Acute lymphoblastic leukaemia, Cytotoxic chemotherapy and the tag soc-trials.
- TrialIntReALL SR 2010
Shares Leukaemia (all types), Acute lymphoblastic leukaemia, Cytotoxic chemotherapy and the tag soc-trials.
- TrialMORPHO
Shares Leukaemia (all types), Allogeneic stem cell transplantation, Small-molecule kinase inhibitors and the tag soc-trials.
- TrialAALL1231
Shares Leukaemia (all types), Acute lymphoblastic leukaemia, Cytotoxic chemotherapy and the tag soc-trials.
- TrialAALL0232
Shares Leukaemia (all types), Acute lymphoblastic leukaemia, Cytotoxic chemotherapy and the tag soc-trials.
- TrialALL R3 (UKALLR3)
Shares Leukaemia (all types), Acute lymphoblastic leukaemia, Cytotoxic chemotherapy and the tag soc-trials.
- TrialAAML1031
Shares Leukaemia (all types), Cytotoxic chemotherapy, Small-molecule kinase inhibitors and the tag soc-trials.