A Benchmark in the Treatment of Acute Lymphoblastic Leukemia

Childhood acute lymphoblastic leukemia can be successfully treated without cranial radiation through a carefully personalized chemotherapy regimen, according to investigators from St. Jude Children's Research Hospital. Radiation of the brain was once the standard method of treatment for ALL to prevent the recurrence of the disease in the central nervous system.

Despite the success in treating ALL with radiation, the range of side effects include second cancers, stunted growth, hormone imbalances and cognitive deficits. Optimization of anticancer drugs, especially those delivered directly into the spinal fluid, has enabled clinicians to reduce radiation use. Only patients with the highest occurrence of relapse continue to receive cranial radiation.

According to Ching-Hon Pui, M.D., chair of the St. Jude Department of Oncology, “Cranial radiation was an invaluable treatment when it was introduced by St. Jude oncologists in the mid 1960’s. It controlled central nervous system leukemia and boosted the cure rate for ALL from only 4 percent to 50 percent. But the radiation’s side effects led to the stead reduction of dosages and limited use to the highest risk patients.” According to Pui, about 20 percent of the approximately 3,400 cases of childhood ALL diagnosed in the U.S. each year are still treated with radiation. In some developing countries, the majority of children with ALL are treated with radiation.

 The study involved nearly 500 patients treated for ALL at St Jude and Cook Children’s Medical Center in Fort Worth, Texas, between 2000 and 2007. Residual leukemia cells present after remission induction treatment were measured to determine the risk of relapse. This measurement was then used to modify therapy according to the amount of these cells detected.

Study investigators used the molecular genetics of ALL, pharmocogenetic traits of patients, and pharmocodynamic principles to apply personalized therapy to patients. Mary Relling, Pharm. D., chair of the St. Jude Department of Pharmaceutical Sciences said, “We prospectively determined the activity of drug-metabolizing enzymes of each patient and adjusted the dosage of chemotherapy accordingly. Personalized therapy that we use avoids over- or under-treatment to maximize the cure rate while preventing excessive toxicity.”

The researchers reported that this therapy produced a projected cure rate of 90 percent for all patients; the best treatment results reported to date. This cure rate is a new benchmark for all others in the field. To determine whether cranial irradiation would have made a difference in central nervous system relapse, they compared the outcomes of 71 patients who would have qualified for irradiation with the outcomes of 56 patients who received irradiation in the past. The researchers found that the 71 patients treated with this personalized therapy had significantly better complete remission than the 56 patients who had been irradiated.

Pui concludes, “The bottom line is that not only did we get outstanding treatment responses in these patients, many of whom would have otherwise received irradiation, but they have a better quality of life because of the absence of its side effects.”


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