Acute Lymphoblastic Leukemia in Adolescents and Young Adults in Finland.

Abstract

Background: Long-term survival in pediatric acute lymphoblastic leukemia has dramatically improved during the past three decades through intensification of therapy. Progress has also been made regarding therapy of adult ALL. Recent reports in the literature suggest better outcome on pediatric protocols, as compared with adult ones. In pediatric ALL, age over 10 years is a high-risk factor in many protocols. The arbitrary age limit of 16 years may not truly reflect the biologic differences in ALL between adolescents vs. young adults. The purpose of the present work was to evaluate the outcome of adolescents with ALL in Finland, treated on pediatric vs. adult ALL protocols. Materials and methods: All patients aged 10–25 years diagnosed with ALL during 1990–2005 in Finland were included. There were 120 patients (aged 10–16 yrs) treated on pediatric common Nordic (NOPHO) protocols with a total duration of 2 yrs, and 100 patients (aged 17–25 yrs) treated on Finnish National ALL adult protocols with a total duration of 3.5 yrs. In total 15 underwent allo-SCT in first remission. Data had been collected to the pediatric Nordic NOPHO database, as well as to the Finnish Leukemia Group ALL database. Events were defined as death, relapse, or second malignancy. Results: The 5-year EFS was 68 % for children (n=62) and 55% for adults (n=72) (p=0.04), and the 5-year OS was 75 % for children and 68 % for adults (p=0.075), respectively. When only patients treated with conventional chemotherapy were included (stem cell transplant recipients in 1CR excluded), the 5-year EFS was 65 % for children (n=53) and 55 % for adults (n=66) (p=0.09), and the 5-year OS was 80 % for children and 65 % for adults (p=0.09), respectively. Regardless of protocol, EFS in the age group of 10–15 years was 74 % and in the group 15–25 years 57 % (p=0,06). Conclusions: EFS regarding all patients was better on pediatric than on adult protocols. All the other comparisons reached statistically only a trend level. The difference in outcome between pediatric and adult protocols in Finland is less clear than reported elsewhere. Age seems to be a prognostic factor also in the adolescent age groups. The non-transplanted patients seemed to have a better outcome, suggesting that those with higher risk probably ended up with transplant. Although therapy is an important risk factor, our further analysis of cytogenetic features including CGH array may reveal other risk factors that may turn out to be even more powerful. EFS, pediatric vs. adult treatment group EFS, pediatric vs. adult treatment group

The inferior prognosis of adolescents with acute lymphoblastic leukaemia (ALL) is caused by a higher rate of treatment‐related mortality and not an increased relapse rate – a population‐based analysis of 25 years of the Austrian ALL‐BFM (Berlin‐Frankfurt‐Münster) Study Group

“…We confirm previous findings that adolescents are more likely to present with T cell ALL and less likely to have prognostically favourable genetic features, such as high-hyperdiploid karyotypes or ETV6/RUNX1 fusion genes (Plasschaert et al, 2004;Usvasalo et al, 2008;Pui et al, 2011). Intriguingly, the incidence of Ph+ patients was not different between the two age groups.…”

Adolescents and young adults with acute lymphoblastic leukemia have a better outcome when treated with pediatric‐inspired regimens: Systematic review and meta‐analysis

“…The literature search identified 2002 publications. Seventeen potentially relevant full text articles were retrieved for further evaluation [11–27]. Of these, nine were excluded [19–27].…”

“…Eleven studies published between 2003 and 2009 reporting on 2,489 patients, met inclusion criteria for systematic reviews [11–18, 28–30]. None of the studies was a randomized controlled trial.…”

“…Regimens of both pediatric‐inspired and conventional adult protocols were different between the studies. Eight nonrandomized studies compared patients given pediatric‐inspired regimens with those given conventional adult regimens at the same time period [11–13, 15, 16, 18, 28, 30]. Two studies included patients given pediatric‐inspired regimens that were compared with historical controls in which conventional adult protocols were given [17, 29].…”

Is the cancer survival improvement in European and American adolescent and young adults still lagging behind that in children?

“…For ALL, multiple comparisons have indicated pediatric treatment regimens are more effective than adult treatment protocols . In Europe, the pediatric regimen has been applied to adult ALL patients in Spain, France, Germany, the Netherlands, Sweden, Finland, Denmark, Italy, the United Kingdom, the Czech Republic . Because Europe has applied pediatric treatment approach to AYAs more widely than done by the USA, the greater rate of progress in young adults in Europe is likely be due to treatment differences, as well as a greater collaboration between pediatric and medical oncologists.…”