American Society of Hematology 2003 Coverage
Please use for reference only.
Julia Draznin Maltzman, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: December 15, 2003
The American Society of Hematology (ASH) meeting took place December 7-10, 2003 in San Diego, California. The most important and noteworthy findings were presented at the plenary session held on Sun December 8, 2003. The abstracts related to cancer are listed and explained in this weeks news flash.
Identification, Validation, and Cloning of a Novel Gene (OPAL1) and Associated Genes Highly Predictive of Outcome in Pediatric Acute Lymphoblastic Leukemia Using Gene Expression Profiling
Presenter: Monica Mosquera-Caro
Affiliation: University of New Mexico
Childhood Acute Lymphoblastic Leukemia (ALL) has a long-term remission rate of 75%. Unfortunately, 25% of these kids will relapse and develop resistant disease. Furthermore, about 25% of all patients have the potential to be cured with less intensive chemotherapy. Knowing which patients are likely to respond to treatment before initiating therapy would be a major advantage for physicians and patients alike. Due to the relative heterogeneity of the disease and the intensity of treatment, it would be a tremendous advantage if physicians could tailor therapy to each individual patient. To this end, a group of investigators has set out to identify genes that may help in predicting outcome in this patient population.
Using gene expression profiling technology, a novel gene was identified and cloned. The gene was called Outcome Predictor in Acute Leukemia 1 (OPAL1). Of all the genes evaluated, OPAL1 conferred the strongest predictive power to treatment outcome. High OPAL1 expression was associated with a good chance of long-term remission (87%), as opposed to low OPAL1 expression, which showed only a 32% chance of long-term remission. Low OPAL1 was in fact, found to be associated with induction failure. OPAL1 was predictive of a good outcome also in T cell ALL and infant ALL.
Investigators of this study concluded that the use of gene expression profiling could be used to find novel genes that may in turn, be used to classify risk and predict outcome in ALL patients.
Novel Chemically-Stabilized Helices of the BCL-2 Family Induce Apoptosis of Leukemia Cells
Presenter: Loren D. Walensky Affiliation: Johns Hopkins University
Apoptosis is a very stoically regulated pathway by pro and anti apoptosis proteins. It is the delicate balance of these proteins within the cell that maintain homeostasis. When the balance is disturbed; regulation is lost. BCL2, a well know survival, anti-apoptosis protein is thought to be overexpressed in a number of cancers including follicular lymphoma. When BCL2 is overproduced, it immortalizes a cell that should have been destroyed under normal, physiologic conditions.
These investigators describe in detail how they successfully generated specific and stable pro-apoptosis proteins and inserted them into a cell overexpressing BCL2. Using this new technique, the group was indeed able to activate apoptosis in cultured T and B leukemic cells.
These exciting data indicate that this mechanism may be used as a tool to better understand and manipulate the apoptotic pathways in both normal and malignant cells.
Efficacy and Safety of the Oral Direct Thrombin Inhibitor Ximelagatran Compared with Current Standard Therapy for Acute, Symptomatic Deep Vein Thrombosis, with or without Pulmonary Embolism: The THRIVE Treatment Study
Presenter: Charles W. Francis
Affiliation: University of Rochester
This study evaluated the efficacy and safely of Ximelagtran (Exanta, AstraZeneca), a new oral thrombin inhibitor. Current treatment for acute venous clots consists of unfractionated heparin or low molecular weight heparin followed by a vitamin antagonist such as warfarin. Warfarin requires monitoring by frequent blood draws and dose adjustments. It also has multiple food and drug interactions of which patients must be weary. Ximelagtran, requires no blood work for monitoring purposes. It has very predictable pharmacokinetics without drug or food interactions.
These investigators presented results from an international, randomized, double blind, double dummy trial that included 2,489 patients with deep vein thrombi. (37% of these patients had known pulmonary emboli). They were randomized to receive either oral Ximlagtran or sub-cutaneous Enoxaparin followed by Warfarin.
For six months of treatment, Ximlagtran was found to be as good as Enoxaparin followed by Warfarin without the need for coagulation monitoring. This trial may well change the current treatment of deep vein thrombi.
Phase III Trial of Rituximab-CHOP (R-CHOP) vs. CHOP with a Second Randomization to Maintenance Rituximab (MR) or Observation in Patients 60 years of Age and Older with Diffuse Large B-Cell Lymphoma (DLBCL)
Presenter: Thomas M. Habermann
Affiliation: Mayo Clinic
632 patients over the age of 60 with DLBCL were randomized to receive wither R-CHOP or CHOP alone. A second randomization occurred following induction therapy to either MR or observation alone. The overall response rate for both regimens was comparable: R-CHOP was 77% and 76% for CHOP alone. Progressive disease occurred in 6.5% of patients who received R-CHOP and 10.5% of those who got CHOP. In a almost three year follow up, the time to treatment failure favored the R-CHOP group but overall survival was equivalent in both groups.
In the R-CHOP group there was no difference seen between MR and observation alone in regards to time to treatment failure and overall survival. CHOP patients, however, had a statistically significant longer time to treatment failure if they received MR. Despite this, however, there was no difference in overall survival in the two groups.
Investigators caution that when interpreting these results, we should keep in mind that this study was not designed to directly compare R-CHOP to CHOP alone.
The investigators concluded that the addition of Rituximab to CHOP did not change overall response rate but did produce a longer time to treatment failure. MR also did improve time to treatment failure but only in those patients who were treated with CHOP alone as induction therapy. No overall survival differences have been seen to this point. The significance of this trial is that Rituxan when given for DLBCL offers an advantage in regards to time to treatment failure. It is still unclear what is the best way to give Rituxan – concurrently with CHOP or as maintenance.