Genetic Profiles Linked to Hematologic Outcomes

February 2012 Vol 5, No 1, Special Issue - Conference Highlights ASH
Caroline Helwick
Caroline Helwick

Hematologic malignancies are characterized by genetic subtypes with varying prognoses. Analysis of these subtypes is beginning to make a difference in the clinic.

“Researchers are finding that genetic determinants are important causes of treatment failure,” said Kathryn Roberts, MD, who presented the findings from St. Jude Children’s Research Hospital in Memphis.

“But it is currently not possible to increase the dose or intensity of current therapies because of toxicity,” Dr Roberts said.

The findings support the screening of all patients newly diagnosed with acute lymphocytic leukemia (ALL) for the presence of high-risk subtypes. Identifying these patients should help characterize the genetic abnormalities that underlie a unique subtype of high-risk B-cell ALL and also help select candidates for targeted therapies.

Dr Roberts and her colleagues have identified a unique subtype of BCR-ABL–negative, high-risk B-cell ALL, with a deletion or mutation of IKZF1, which confers a poor outcome. They refer to this new subtype as “Ph [Philadelphia chromosome]-like ALL.” Up to 15% of pediatric ALL cases can be classified as Ph-like, and previous trials have shown that the outcome of these cases can be improved when tyrosine kinase inhibitors such as imatinib are added to chemotherapy regimens.

“This study represents potential changes in care,” said Martin S. Tallman, MD, Chief of Leukemia Services, Memorial Sloan-Kettering Cancer Center, New York, who moderated a press briefing. “This study provides further evidence that we can target specific leukemias with directed therapy, rather than just continue to give relatively indiscriminate chemotherapy.”

For Lymphoma, Genetic Risk Score Predicts Outcome
In patients with diffuse large B-cell lymphoma (DLBCL), a genetic risk score based on the expression of a small number of genes was able to predict clinical outcomes related to specific treatments, investigators from the Eastern Cooperative Oncology Group (ECOG) and Southwest Oncol­ogy Group reported.

Using tissue from 183 DLBCL patients in the ECOG E4494 phase 3 trial, researchers were able to construct a 5-gene predictor model that identified outcomes of patients treated with CHOP (cyclophosphamide/ doxorubicin/vincristine/prednisolone) and a 6-gene model that was predictive in patients treated with R-CHOP (CHOP plus rituximab). High-versus-low genetic risk scores significantly predicted clinical outcomes at a median follow-up of 9.4 years, reported Jane Winter, MD, of the Lymphoma Committee, ECOG, Chicago, IL.

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Last modified: March 16, 2012
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