From OncoLog, July/August 2007, Vol. 52, No. 7-8

In Brief

Lymphocyte Count Predicts Outcomes in Young Patients with Acute Leukemias

Researchers from the Children’s Cancer Hospital at M. D. Anderson have found that absolute lymphocyte counts (ALCs) measured 15 days after chemotherapy are a simple but powerful predictor of relapse and survival in children and young adults with acute myelogenous leukemia (AML) or acute lymphocytic leukemia (ALL).

ALC, a measure of normal immune cells, is found on routine complete blood count (CBC) reports but is not currently used to guide therapy.

“This is a simple measurement from the CBC, and what it may provide is information that is critical to early and accurate risk stratification,” said Patrick Zweidler-McKay, M.D., Ph.D., assistant professor of pediatrics at M. D. Anderson.

Improvements in risk stratification based on the ALC information would allow physicians to alter treatment and potentially improve remission durability and cure rates, said Guillermo De Angulo, M.D., a Children’s Cancer Hospital researcher and fellow. “The ALC test can help us identify patients who might need more or could benefit from less chemotherapy very early in their treatment,” he said.

The researchers’ findings were presented at the American Society of Pediatric Hematology/Oncology’s annual meeting, held in May. The study, which involved multiple analyses of patient outcomes, ALCs, and other potential indicators, included 171 patients with AML or ALL, age 21 years or younger, who had begun treatment at M. D. Anderson between 1995 and 2005.

“An important aspect of what we found is that ALC measurements from different days can be used to stratify high- and low-risk groups,” said Dr. Zweidler-McKay, the study’s senior author. For example, in patients with AML, the patients with an ALC lower than 350 cells/μL on day 28 of treatment had a dismal five-year overall survival rate of 10%; in contrast, the five-year overall survival rate was 85% when the ALC was 350 cells/μL or higher on day 15.

The findings were similar for patients with ALL, the most common form of childhood leukemia, with six-year overall survival rates of 55% versus 87% for low and high ALCs—a smaller difference but highly significant. “ALL therapy already benefits from a successful risk-stratification approach; however, currently at least half of patients who do not survive are thought to be standard risk, and this is where ALC may help,” Dr. Zweidler-McKay said.

In addition to acute leukemias, the M. D. Anderson team has found that ALC is associated with survival in pediatric patients with non-Hodgkin’s lymphoma and Ewing’s sarcoma, and other investigators have demonstrated that ALC predicts outcome in adults with AML and patients who have undergone stem cell transplants for various malignancies.

“All these findings from different sources seem to imply that a generalized post-therapy ALC phenomenon exists,” Dr. Zweidler-McKay said. “If so, it would be relevant to the way we treat a wide range of malignancies and ages, and the fact that a CBC is a universal, inexpensive test is key. It means that physicians all over the world, even in developing countries, could use ALCs to help determine what treatments their patients really need, very early on in treatment.”

Gefitinib Under Study for Squamous Cell Carcinoma of the Skin

Although most cases of squamous cell carcinoma of the skin are successfully treated by aggressive surgery, sometimes followed by radiation, researchers at M. D. Anderson have identified certain factors that predict a poor outcome for squamous cell carcinoma patients. Among these factors are large tumor size (4 cm or more in diameter), lymph node metastasis, perineural invasion, and deep invasion into underlying tissue. According to Randal Weber, M.D., professor in and chair of the Department of Head and Neck Surgery, “Up to 40% of patients with these factors will die of their disease, so it’s not just an innocuous skin cancer that’s easily managed. It has a significant mortality rate.”

Squamous cell carcinoma cells overexpress the epidermal growth factor receptor. Activation of that receptor promotes cell proliferation, invasion, angiogenesis, and cell motility. However, these tumor cell actions can be diminished if the receptor is blocked. Dr. Weber and colleagues are hoping that gefitinib (ZD1839), a small-molecule tyrosine kinase inhibitor that binds to the epidermal growth factor receptor, will block the receptor’s activation and thus inhibit or even reverse tumor growth.

So far, 15 squamous cell carcinoma patients have been treated in an ongoing phase II clinical study of gefitinib being conducted at M. D. Anderson (protocol 2004-0204). “In three patients, we’ve seen a complete disappearance of the tumor on clinical exam. In one of those patients, after we excised the tumor site, there was no residual cancer. In several other patients, their disease either regressed partially or showed no growth,” said Dr. Weber. “These preliminary results are pretty remarkable.”

Gefitinib is given daily for two periods of 30 days each (60 days total) before patients undergo surgery. Some patients, but not all, also undergo radiation therapy, depending on tumor size and other factors.

For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789.

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