Young adult patients entered on the CCG 1961 study had 5-year event-free survival rate of 71.5% (95% CI, 64.4% to 78.6%). In our previous cohort of young adult patients, the 5-year event-free survival rate was 64%.8
Age more than 15 years has historically been a strong adverse prognostic factor on clinical trials for children and adolescents with ALL. This is no longer the case with contemporary trials. The Dana-Farber Cancer Consortium recently reported that a small group of patients 15 to 18 years of age at diagnosis (n = 51) had a 5-year event-free survival rate of 78%, as compared with 85% for those 1 to 10 years of age and 77% for those 10 to 15 years of age.9
Among all patients enrolled onto CCG 1961, RER patients who were randomly assigned to augmented-intensity therapy had a significantly better event-free survival and overall survival (81% and 89%) compared with patients receiving standard-intensity therapy (72% and 83%). There was no benefit to a second delayed intensification phase. Young adult RER patients also had better outcomes with augmented- versus standard-intensity therapy for both event-free (81.8% v 66.9%, P = .07) and overall survival (83.2% v 75.6%, P = .14). Although these differences did not reach conventional levels of statistical significance among the young adult patients, they are quite similar in magnitude to the differences observed in the entire study population. This study was not powered to adequately assess an event-free survival difference among young adult patients by treatment regimen.
Thus we conclude that augmented-intensity therapy improves outcome for young adult RER patients. Event-free survival is similar for the first 2 years for patients receiving standard- or increased-intensity postinduction treatment. However, beyond 2 years, the benefit of increased-intensity postinduction treatment is apparent. This finding was also seen in our prior CCG 1882 study and in the overall RER population in this study.
SER patients had a 5-year EFS rate of 70.7%. The results of the idarubicin versus doxorubicin randomization have not yet been reported.
Young adult patients had a higher incidence of induction death and death in remission compared with younger patients. These patients also had a higher incidence of avascular necrosis and corticosteroid-induced hyperglycemia.
Young adult patients with B-precursor ALL and a presenting WBC count more than 50,000/μL had a worse prognosis compared with patients with WBCs less than 50,000/μL.
In reports published to date, young adult patients treated by pediatric oncologists have a better outcome compared with similar patients treated by medical oncologists.10–13
The event-free survival advantage is substantial, with a 20% to 30% absolute improvement observed in most comparisons. Whether the difference in outcome is due to physician compliance, patient compliance, protocol differences, or other differences is not easily ascertained. More 16- and 17-year-old patients are treated in pediatric centers, whereas more 18- to 21-year-old patients are treated in adult centers. There are no demographic differences between the 16- and 17-year-old patients compared with the 18- to 21-year-old patients, but there could be psychosocial factors that differ between the two populations. Pediatric and adult protocols differ significantly in the drugs used. Compared with adult protocols, pediatric protocols feature significantly more nonmyelosuppressive therapy (vincristine, corticosteroids, L-asparaginase) elements and more intensive early CNS-directed therapy.
The Medical Research Council (MRC) and the Eastern Cooperative Oncology Group (ECOG) conducted a joint study for adult patients 15 to 59 years of age with ALL between 1993 and 2006. Patients enrolled onto this trial received two phases of induction therapy and then underwent an allogeneic stem-cell transplantation if a matched sibling donor was available. Other patients were randomlyassigned to receive continuation chemotherapy or autologous stem-cell transplantation. The overall survival among 234 Ph-negative patients younger than 20 years of age was only 43%.14
Adult patients in the MRC/ECOG study considered standard risk (age < 35 years; no t(9; 22); B precursor and WBCs < 100,000/μL, T cell and WBCs < 30,000/μL) showed a significant 5-year survival benefit if they had a matched sibling donor available. Five-year survival was 62% for patients with a donor (n = 239) compared with 52% for patients without a donor (n = 323; P
We determined outcome for patients 16 to 21 years of age enrolled onto CCG 1961 meeting the MRC/ECOG criteria for “standard” risk. Five-year event-free and overall survival rates were 72.6% and 80.3%, respectively, markedly better than that observed in the adult trial. One could argue that the outcome for patients 22 to 30 years of age might be worse than for patients 16 to 21 years of age. However, a report from Ribera et al15
showed that for patients treated on a pediatric-type treatment regimen, there was no difference in outcome for patients 15 to 18 years of age (n = 35) and those 19 to 30 years of age (n = 46). This result needs to be confirmed in trials with larger patient numbers. There was also no difference in outcome in our study for patients 16 to 17 years of age versus those 18 to 21 years of age, although the numbers in the older age group were small.
Our results establish that young adult patients with ALL who do not have the t(9;22) or other high-risk features such as induction failure or hypodiploidy with less than 44 chromosomes have an event-free survival rate greater than 70% with chemotherapy alone and therefore do not meet criteria generally used to select patients for allogeneic stem-cell transplantation in first remission. This study was not designed to test the hypothesis that routine use of allogeneic stem-cell transplantation in first remission might improve outcome for young adult patients with ALL. Because of concerns regarding early mortality and both early and late morbidity, we generally consider patients candidates for allogeneic stem-cell transplantation in first remission only if they have an expected event-free survival rate of less than 50%.
Whether adult centers can attain outcomes similar to those obtained in pediatric centers is being explored in a current study conducted by the major adult cooperative groups in the United States. This trial uses one of the established arms of the current Children's Oncology Group high-risk, B-precursor ALL trial used for young adult patients.
We believe that young adult patients with ALL between the ages of 16 and 21 years should either be enrolled onto a clinical trial that is studying a pediatric-type treatment regimen or should be referred to a pediatric center for treatment. When a pediatric-type treatment regimen is used, routine use of stem-cell transplantation in first remission for this patient population seems unwarranted.