Adam Lamble, MD, Attending Physician, Cancer and Blood Disorders Center, Seattle Children’s Hospital, discusses a recent study that lists six high-risk alterations of acute myeloid leukemia (AML) that ought to be included in Children's Oncology Group’s (COG) contemporary risk classification system. These findings were recently presented at this year’s American Society of Hematology Meeting & Exposition (ASH 2022).

AML is a rare progressing blood cancer that most often occurs in people over the age of 40 years but it can occur in children as well. Signs and symptoms can vary but for many patients, the cancer can be very aggressive and may require intensive treatment.

As Dr. Lamble explains, diagnostic specimens from 2 sequential COG phase 3 trials for pediatric AML (AAML0531 and AAML1031) were retrospectively tested with next generation sequencing. This data was combined with a central review of structural and molecular alterations to identify candidates for risk adjustment (i.e., 5-year event-free survival (EFS) inferior to similarly treated patients with noninformative cytomolecular genetics with and/or without censoring for stem cell transplant in first complete remission.) Candidate alterations were then incorporated into an updated risk classification which was retrospectively applied to assess impact on treatment allocation.

Of 1944 patients in , 137 (7%) patients with 1 of 6 newly defined alterations met the predefined criteria for risk adjustment. These included:
• CEBPA co-occurring with CSF3R (n=18, EFS: 33%),
• CREBBP mutations (n=40, EFS: 18%),
• TP53 mutations (n=20, EFS: 0%),
• KMT2A-partial tandem duplications (n=21, EFS: 43%),
• IDH1/2 mutations in the absence of NPM1 (n=36, EFS: 31%), and
• Fusions involving the ETS family, excluding previously high-risk defined members (n=13, EFS: 43%).

As a group, patients with these alterations had an EFS of 28% and relapse risk of 70%, which were worse than contemporarily defined standard-risk patients and analogous to contemporarily defined high-risk patients.

The study concluded that “before these alterations can be considered high-risk, further investigation is required, including corroboration from other large pediatric and adult consortium trials and the benefit of this re-allocation will need to be validated prospectively.”

To learn more about AML and other rare cancers, visit checkrare.com/diseases/cancers/

Dr. Mangesh P Kamath | Appointment booking no: 9900587736, 9900613143
Website: drmangeshkamathcancercare.com
Senior Consultant & Medical Director | Medical and HematoOncologist, BMT Physician,
Healius Cancer & Hematology Clinic, Banashankari Stage II, Bengaluru
It is unfortunate that blood cancers in children can occur as early in infancy and it can occur at any age of the child. Childhood leukemia can be divided into acute myeloid leukemia and acute lymphoblastic leukemia. Compared to adult cancers the childhood cancers and more so the childhood blood cancers are far more curable there is a wealth of evidence to show that children not only tolerate blood cancer much better but also have significantly higher cure rates from blood cancer than adults. Most of the childhood cancers including blood cancers are due to certain genetic abnormalities. These genetic abnormalities themselves provide an opportunity for oncologist targeted certain weak points of the blood cancer so that the cancer can be defeated not all the childhood cancers are treated in the same way. Lymphoblastic Leukemia are of two types Low Risk Leukemia High Risk Leukemia. The Low Risk Leukemia in certain scenario do not need to undergo Bone Marrow Transplantation after having undergone intense chemotherapy for the time of diagnosis. High Risk Leukemia will need to undergo Bone Marrow Transplantation from a healthy donor, maybe the child’s brother sister or from the parents so that the cancer can be truly eliminated and be replaced by a healthy bone marrow. Many cancers in children are treated with the most intense of protocols and the childhood cancers are treated with intense protocols. The intense protocols are very well tolerated by children and the cure rates are exemplary with the latest of protocols. In today’s era long term toxicity is minimized due to treatment of Childhood leukemia. So even after they complete treatment and they are cure of the blood they are able to lead a healthy life
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Despite allogeneic hematopoietic cell transplantation the survival chances in pediatric AML are 50% only. With the developed adjuvant WT1 Cord Blood Derived Dendritic Cell Vaccine the survival chances may increase. The clinical study will start early 2017.
PIs: Dr Jaap Jan Boelens (clinical / translational) and Dr Stefan Nierkens (lab / translational)