Another Reason Not to "Supersize" It

Obesity is an epidemic in the United States. It contributes substantially to poor cardiovascular health in adults. Presented at this meeting are results indicating that obese pre-adolescents and teenagers with acute lymphoblastic leukemia have a significantly higher risk of relapse compared to non-obese youths. In this project, outcomes from five sequential CCG studies were analyzed. In a poster session on Saturday, Dr. Anna Butturini reported the results of a total of 4356 patients included in this retrospective review. Obesity was defined as a body mass index of greater than the 95th percentile. There was no outcome effect for obesity in children less than ten years old. However, in the 1026 youths aged ten to 20, obesity independently predicted for increased risk of leukemia relapse, with a hazard ratio of 1.5.

The CCG also presents data from their 1961 study. Dr. Nachman and colleagues analyzed data for young adults between the ages of 16 and 21. It has been shown previously that individuals in this age group typically do better when included on children’s cooperative studies as opposed to studies designed for adults. This presentation reports the results on 262 patients. Patients were triaged depending upon the results of the day 7 restaging marrow into a rapid early response (RER) group or a slow early response (SER) group. The SER group did not have an improved outcome when pulsed idarubicin/cytoxan was added to augmented BFM, compared to augmented BFM alone. However, in the RER group, outcomes were improved when augmented BFM was administered compared to a standard BFM regimen (five years EFS 83 percent vs. 61 percent).

In other childhood ALL news, Dr. Lewis Silverman presents the results of Dana-Farber Cancer Institute Consortium Protocol 95-01. This was a protocol designed to minimize therapy-related morbidity without compromising efficacy. Between 1996 and 2000, 491 children between the ages of 0 and 18 were enrolled in this trial. With 4.6 years of follow-up, the estimated five-year EFS is 81 percent (86 percent for standard risk and 76 percent for high risk disease). Three major conclusions can be drawn from this trial. It was apparent that erwinia asparaginase was less toxic but also less efficacious. Also, cranial radiation was not required in standard risk disease as long as adequate intrathecal prophylaxis was administered, and dexrazoxane did not interfere with doxorubicin’s antileukemia effect.

Another significant study in childhood ALL was presented by Dr. Stella Davies and colleagues. They examined the relationship between nine different host germline pharmacogenetic polymorphisms and the presence of minimal residual disease in the bone marrow at day eight and day 28 of induction therapy. Two polymorphims were found to be more likely associated with MRD in the day 28 bone marrow. For the MTHFR A1298C polymorphism, MRD was detected in 31 percent of individuals with A/A or A/C genotypes compared to 19 percent of individuals with the CC genotype. For the MDR1 2677 polymorphism, MRD was detected in 39 percent of individuals with CG genotypes compared to 25 percent with other genotypes at that locus. None of the other seven pharmacogenetic polymorphisms were associated with an increased probability of having MRD.