Acute Lymphoblastic Leukemia, the Most Common Childhood Cancer, Is Curable Without...

Acute Lymphoblastic Leukemia, the Most Common Childhood Cancer, Is Curable
Without Preventive Cranial Radiation

St. Jude study shows personalized chemotherapy can improve cure rate and avoid
the use of radiation in acute lymphoblastic leukemia treatment

MEMPHIS, Tenn., June 24 /PRNewswire-USNewswire/ -- Childhood acute
lymphoblastic leukemia (ALL) can be successfully treated using a carefully
personalized chemotherapy regimen without cranial radiation, investigators at
St. Jude Children's Research Hospital have found. Such radiation of the brain
was once a standard ALL treatment to prevent recurrence of the leukemia in the
central nervous system (CNS).

Despite radiation's success in treating ALL, it produces side effects that
include second cancers, stunted growth, hormone imbalances and cognitive
deficits. Optimized use of anticancer drugs, especially those instilled
directly into the spinal fluid, have enabled clinicians to reduce radiation
use, and only patients at highest risk for relapse have received cranial
radiation.

Now, St. Jude researchers have established that radiation can be safely
eliminated in all patients with the use of highly effective chemotherapy
regimens. The findings appear in the June 25, 2009, issue of the New England
Journal of Medicine.

"Cranial radiation was an invaluable treatment when it was introduced by St.
Jude oncologists in the mid-1960s," said Ching-Hon Pui, M.D., chair of the St.
Jude Department of Oncology and an American Cancer Society Professor. "It
controlled CNS leukemia and boosted the cure rate for ALL from only 4 percent
to 50 percent. But radiation's side effects led to the steady reduction of
dosages and limited use to the highest-risk patients." According to Pui, the
paper's lead author, 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, radiation continues to be used in the
majority of children with ALL.

"Over the years, St. Jude investigators have identified many important risk
factors for CNS relapse and optimized chemotherapy treatment, leading to
improved control of CNS relapse," Pui said. "Our success led us to believe
that we could safely eliminate the use of cranial irradiation in all patients,
and this study clearly demonstrates that to be true."

The study involved 498 patients treated for ALL at St. Jude and Cook
Children's Medical Center in Fort Worth, Texas, between 2000 and 2007. The
risk of relapse was determined by measurement of residual leukemia cells
(so-called minimal residual disease) that were present after remission
induction treatment. The measurement of minimal residual disease was used to
modify therapy based on the level of disease detected. This measurement is the
most important prognostic indicator, according to Dario Campana, M.D., Ph.D.,
vice chair for laboratory research in the St. Jude Department of Oncology and
a co-author of the paper. "The combined use of immunological and molecular
methods allows us to study 100 percent of the patients for levels of minimal
residual disease, an unprecedented rate of success," Campana said.

St. Jude investigators applied personalized therapy based on molecular
genetics of ALL, pharmacogenetic traits of patients and pharmacodynamic
principles. "We prospectively determined the activity of drug-metabolizing
enzymes of each patient and adjusted the dosage of chemotherapy accordingly,"
said Mary Relling, Pharm.D., chair of the St. Jude Department of
Pharmaceutical Sciences and senior author of the paper. "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 the patients, which is the best treatment result reported
to date. This cure rate serves as a benchmark for others in the field. To
assess whether cranial irradiation would have made a difference in CNS
relapse, they compared the outcomes of 71 patients whose leukemias would have
qualified them for irradiation with the outcomes of 56 patients who had
received such irradiation in the past. The researchers found that the 71
patients, in fact, had significantly better complete remission than the 56
patients who had been irradiated.

"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 will have a better quality of life because of the absence of its side
effects," Pui said.

"In a way, these findings represent coming full circle," said Dr. William
Evans, St. Jude director and CEO and a co-author of the paper. "St. Jude was
the first to introduce cranial radiation as a treatment strategy that advanced
the cure of childhood ALL to 50 percent. Now, St. Jude is the first to show
that we can successfully eliminate irradiation by optimizing chemotherapy."

Other authors of this paper include Deqing Pei, John Sandlund, Sue Kaste, Raul
Ribeiro, Jeffrey Rubnitz, Susana Raimondi, Mihaela Onciu, Elaine
Coustan-Smith, Larry Kun, Sima Jeha, Cheng Cheng, Scott Howard, Vickey
Simmons, Monika Metzger, James Boyett, Wing Leung and James Downing (St.
Jude); W. Paul Bowman and Amy Bayles (Cook Children's Medical Center); and
Rupert Handgretinger (formerly of St. Jude).

The research was supported in part by the National Institutes of Health, the
American Cancer Society F.M. Kirby Clinical Research Professorship and ALSAC.

St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is internationally recognized for its
pioneering work in finding cures and saving children with cancer and other
catastrophic diseases. Founded by late entertainer Danny Thomas and based in
Memphis, Tenn., St. Jude freely shares its discoveries with scientific and
medical communities around the world. No family ever pays for treatments not
covered by insurance, and families without insurance are never asked to pay.
St. Jude is financially supported by ALSAC, its fundraising organization. For
more information, please visit www.stjude.org.

SOURCE St. Jude Children's Research Hospital

Carrie Strehlau, +1-901-595-2295, carrie.strehlau@stjude.org; or Summer
Freeman, +1-901-595-3061, summer.freeman@stjude.org, both of St. Jude Public
Relations