A clinical study found that the combination of all-trans retinoic acid, a metabolite of vitamin A,

and arsenic trioxide is very effective in children with standard and high-risk acute promyelocytic
leukemia, or APL. Almost all patients in the study survived for two years without relapse. None
of the children at standard risk of APL required conventional chemotherapy, and children at
high risk of APL received only four doses of the chemotherapeutic idarubicin (Idamycin PFS).
The results of a study conducted by the Children's Oncology Group and funded by the National
Cancer Institute, part of the National Institutes of Health, were published on November 11,
2021 in JAMA Oncology.

"It's a great success and it will be a new standard of care," said Malcolm A. Smith, M.D., Ph.D.,
from the National Cancer Institute's cancer treatment evaluation program, which funded a
multi-institutional, non-randomized, co-operative phase 3 group study. Twenty years ago, these
patients were treated with intensive chemotherapy, including drugs that led In contrast, all-
trans retinoic acid and arsenious oxide have less acute or long-term side effects.

"As a pediatrician and oncologist, I have to have difficult conversations with families about what
their children are going through and what therapy they have to go through to improve," said
Matthew Kutny, M.D., Children of Alabama and University. from Alabama, Birmingham,
principal investigator. "Therefore, offering a therapy that is less stringent and has few side
effects, but also has a surprisingly high survival rate, is a good feeling."

APL accounts for 5 to 10% of diagnoses of acute myeloid leukemia in children and adolescents.
Symptoms of this blood and bone marrow cancer include excessive bleeding, a fast heartbeat,
low red blood cell counts, fever and tiredness. Previously, treatment of children with APL
included anthracyclines that could damage the heart.

An earlier study by the Pediatric Oncology Group found that children with APL treated with
arsenious oxide and all-trans retinoic acid in combination with anthracycline-containing
chemotherapeutic drugs had a high incidence of two years. survival and low risk of relapse.
Incident-free survival is the time after primary treatment during which the patient remains free
of debilitating disease, relapse, or death.

The combination of all-trans retinoic acid and arsenic trioxide is currently preferred as the first-
line treatment in adults with a standard risk of APL. Adult patients with high-risk APL will also
receive some chemotherapy, such as maintenance therapy (additional treatment to prevent
recurrence of leukemia). In a study in the Pediatric Oncology Group (AAML1331;
NCT02339740), 154 children aged 1 to 22 years with newly diagnosed standard or high-risk APL
received all-trans retinoic acid orally with intravenous arsenic trioxide daily for at least 28 days.
Children at high risk for APL also received four doses of the anthracycline idarubicin in the first
phase of treatment. High-risk patients were defined as patients with a white blood cell count
greater than 10,000 / μl. Higher white blood cell counts have historically predicted worse
outcomes in children with APL.
However, in this study, children with standard and high-risk APL had overall overall survival
rates of 99% and 100%, respectively. The 2-year event-free survival rates were 98% and 96%,
respectively. One child with standard-risk APL died at the beginning of treatment and three
children (one with standard-risk APL and two with high-risk APL) relapsed.

Less than 10% of children have serious side effects that only occur in the initial phase of
treatment. Side effects include increased blood sugar, liver irritation and bleeding. Some
patients with high-risk APL have developed oral lesions as a result of treatment with idarubicin.
A serious complication of APL is the differentiation syndrome, which can cause life-threatening
inflammation. Physician support and health care strategies are offered to help participants
manage these and other side effects.

Founded by Dr. Kutný stated that due to the fact that maintenance therapy is no longer
needed, the duration of treatment in children was reduced from more than two years to about
nine months. Further monitoring is needed, he said, to determine the long-term effect of
treating children with all-trans retinoic acid and arsenious oxide.

"Arsenic is often associated with poisoning, but it can also be a powerful drug," says Dr. Kutny.
"Arsenic trioxide has been used in traditional Chinese medicine for millennia. The difference
between a drug and a poison is more than just a dose. Over time, we know the exact dose that
can be effective in killing these types of leukemia. -Cells that damage other healthy non-paper
towels.

Arsenic trioxide interacts with all-trans retinoic acid and blocks the action of the egg proteins
that leukemic cells need to survive and grow. The doctor noticed. Kutný said that the Children's
Oncology Group is currently researching ways to supply arsenic trioxide in oral form, which will
make it easier for children to use it.

The St. The Baldrick Foundation in Monrovia, California, a major funding fund for childhood
cancer research, also provides support to members of the Children's Oncology Group in
conducting study AAML1331.