Sarah K. Tasian, MD, an attending physician and assistant professor of pediatrics in the Division of Oncology at Children’s Hospital of Philadelphia, discusses the heterogeneity of pediatric Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL).

Tasian says that what is most striking about that subset of patients with ALL is how heterogeneous the disease is. Ph-like and Ph-positive ALL have similar kinase activated gene expression profiles, but different underlying genetic lesions, and new fusions are constantly being discovered. Moving forward, Tasian believes that the best way to find treatments for this disease is through timely diagnostic interventions and subsequent enrollment on clinical trials.

Patients with Ph-like ALL are generally subtyped by 2 pathways—either the ABL-class or CRLF2/JAK pathway. Tasian says that she hopes that they can be targeted similarly, but it remains an active area of clinical investigation. She is hopeful that it will be able to be answered through trials. There is currently no frontline standard of care for patients with this subtype of ALL.

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Sarah K. Tasian, MD, an attending physician and assistant professor of pediatrics in the Division of Oncology at Children’s Hospital of Philadelphia, discusses the heterogeneity of pediatric Philadelphia (Ph)-like acute lymphoblastic leukemia.

Dr. Tasian on the Heterogeneity of Ph-Like ALL in Pediatric Patients

Sarah K. Tasian, MD, an attending physician and assistant professor of pediatrics in the Division of Oncology at Children’s Hospital of Philadelphia (CHOP), discusses frontline therapy for pediatric patients with Ph-like acute lymphoblastic leukemia (ALL).

In pediatric oncology, physicians tend to enroll most patients on trials, explains Tasian. Patients who have Ph-like ALL with ABL-class lesions are assigned to dasatinib (Sprycel) on a separate arm of the frontline phase III trial at CHOP because they have a high risk of relapse and poor survival on regular chemotherapy, states Tasian.

For patients who have CRLF2 or JAK pathway alterations, physicians have a separate phase II clinical trial that is testing ruxolitinib (Jakafi) for second-line treatment of these patients. Physicians do not yet know whether this targeted agent is going to be effective in that patient subset, though. In the adult arena, there are ongoing clinical trials and FDA-approved medications, notes Tasian.

Dr. Tasian on Frontline Therapy for Pediatric Patients With Ph-Like ALL

Sarah K. Tasian, MD, an attending physician and assistant professor of pediatrics in the Division of Oncology at Children’s Hospital of Philadelphia, discusses genetic testing in pediatric acute lymphoblastic leukemia (ALL).

A complicated tiered genetic testing algorithm is used in children, different than what is used in adults, Tasian explains. All patients with high-risk ALL being treated on frontline Children’s Oncology Group phase III trials undergo this testing. Each newly-diagnosed patient is tested with a gene expressing screening called a low-density microarray, which identifies patients who do not have Philadelphia chromosome (Ph)-like ALL. If the patient does not have Ph-like ALL, they do not need to undergo further testing.

Identifying patients who have Ph-like ALL through the low-density microarray aids in arranging the downstream molecular testing. Tasian says that the most commonly used tests are fusion-based platforms like the Archer next-generation sequencing test. This helps identify which kinase fusions patients have, which can point to what tyrosine kinase inhibitor to give, or what clinical trial to enroll the patient in.

Sarah K. Tasian, MD, an attending physician and assistant professor of pediatrics in the Division of Oncology at Children’s Hospital of Philadelphia, discusses genetic testing in pediatric acute lymphoblastic leukemia.

Dr. Tasian on Genetic Testing in Pediatric ALL

Sarah K. Tasian, MD, an attending physician and assistant professor of pediatrics in the Division of Oncology at Children’s Hospital of Philadelphia, discusses the challenges in treating pediatric patients with Philadelphia chromosome (Ph)-like acute lymphoblastic leukemia (ALL).

One of the first hurdles in the treatment paradigm is genetic diagnostics, explains Tasian. Physicians have to be able to identify these patients relatively quickly. Induction therapy, which consists of 1 month of chemotherapy, is never altered for patients, states Tasian. Nonetheless, physicians have to be able to identify these patients before the end of induction therapy in order to introduce other therapeutic agents. Currently used therapies include tyrosine kinase inhibitors (TKIs).

Another challenge in pediatric oncology as a whole, says Tasian, is access to novel therapies. Recently, more pharmaceutical companies have shown interest in partnering with physicians to facilitate access to novel therapies like TKIs for patients, says Tasian.

Sarah K. Tasian, MD

Articles

Dr. Tasian on the Heterogeneity of Ph-Like ALL in Pediatric Patients

Dr. Tasian on Frontline Therapy for Pediatric Patients With Ph-Like ALL

Dr. Tasian on Genetic Testing in Pediatric ALL

Dr. Tasian on Challenges in Treating Pediatric Patients With Ph-Like ALL