By Christine Duncan, MD
2009-12-08
The story of acute lymphoblastic
leukemia (ALL) is a tale of two diseases. The continued success of ALL
treatment in pediatric patients, with enviable survival rates, contrasts with
much lower survival in adults and some children with high-risk disease.
However, the recent adaptation of pediatric regimens to adult protocols and
advances in the understanding of specific ALL subtypes may soon improve
survival of adult patients. Recent progress in the ALL therapy was presented
Monday morning in the ALL clinical trial Oral Session.
Researchers from the Italian
Association of Pediatric Hematology and Oncology (AIEOP), the Children’s Cancer
Group (CCG), and the Dana-Farber Cancer Institute (DFCI) ALL Consortium believe
that despite admirable outcomes overall, there is still work to be done in
pediatric ALL. As Dr. Lynda Vrooman of DFCI explains, “There has been great
success in the treatment of childhood ALL, but there is still the need to
improve the efficacy and minimize the toxicity therapy.”
Dr. Yousif Matloub of Rainbow
Babies and Children’s Hospital in Cleveland
began the session by presenting the results of molecular studies from the
Children’s Cancer Group CCG 1991 clinical trial. Samples from more than 1,300
patients with non-T-cell ALL were analyzed for trisomies 4 and 10 and for the
presence of TEL/AML1. Of the patients tested, 24 percent had at least one of
the trisomies, and 41 percent had TEL/AML. Patients in these groups had an
impressive overall survival rate of 97.8 percent.
The AIEOP group focused on
non-Philadelphia-positive high-risk disease in children, with HR defined as
either the presence of a t(4;11) translocation, poor response to prednisone,
failure to achieve a complete remission (CR) by day 33, or high minimal
residual disease burden at day 78. The event-free survival (EFS) and overall
survival rates for this group were 58.7 percent and 70.1 percent.
The DFCI trial found that patients
who received dexamethasone had significantly better EFS compared with patients
who received prednisone. However, the dexamethasone group had increased
skeletal toxicity. The DFCI 00-001 study also compared the standard
asparaginase dosing with individualized dosing, which was feasible, did not
show a difference in asparaginase toxicity, and resulted in improved EFS.
The Dutch-Belgian HOVON-70 trial
bridged pediatric and adult ALL therapy. Fifty-four adult patients up to the
age of 40 years were treated with a dose-intensified chemotherapy based on pediatric
regimens. The investigators found that the therapy was feasible in the study
population and are moving forward with a phase III trial.
The Spanish PETHEMA and the German Multicenter Study Group
for Adult ALL (GMALL) reported their findings related to two HR populations.
The PETHMA group differentiated therapy based on early marrow blast clearance
and MRD for patients with Philadelphia-negative HR leukemia. They were able to
successfully treat patients with early blast clearance and low post-consolidation
MRD without stem cell transplantation. Dr. Dieter Hoelzer from GMALL reported
the outcomes of three studies of subtype-oriented treatment strategies in adult
T-ALL. Patients were grouped by immunophenotyping as having either early T-ALL,
thymic T-ALL, or mature T-ALL. The
results were encouraging, and the group was able to improve survival by using
subtype directed therapy.
Dr. Duncan works in the same department as Dr. Lynda
Vrooman at Dana-Farber Cancer Institute.
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