Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL) is a rare subtype of the most common childhood cancer, acute lymphoblastic leukemia (ALL).
Ph+ ALL, like ALL, is a cancer of lymphocytes, a kind of white blood cell. It differs from ordinary ALL in that it has a well-known mutation in its genetic code that fuses two genes that do not ordinarily fuse together (the BCR and ABL genes). The BCR-ABL gene, often known as the Philadelphia Chromosome, has the potential to cause cancer in white blood cells.
While this Philadelphia chromosome is rare in pediatric ALL, it is much more common in adult ALL. It’s also the main cause of another much more common adult leukemia called chronic myelogenous leukemia (CML).
Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Symptoms
Ph+ ALL has the same signs and symptoms as regular ALL, including liver or spleen enlargement, enlarged lymph nodes, paleness, fevers, bruises, weight loss, bone pain, and abnormal blood cell counts. These symptoms are generic and can occur in a variety of viral infections. Patients with mononucleosis, for example, can have many of the same symptoms, and it can be difficult to tell the two diseases apart without specialized testing.
Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Risk Factors
The well-known risk variables that affect outcomes in children with this disease are age, white blood cell (WBC) count upon diagnosis, minimal residual disease (MRD), and complex cytogenetics. With a high WBC count and an age of over ten years, chemotherapy had a dismal prognosis.
How Is Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia Diagnosed?
When a patient is diagnosed with ALL, specialized tests are undertaken to examine the cancer cells’ unique genes inside. These tests are used to see whether there are any alterations in the cancer that could make it more or less responsive to cancer-fighting medications. One of the many genetic alterations that these diagnostic tests can detect is the Philadelphia Chromosome. Patients usually don’t find out they have the Ph+ ALL subtype until a week or two after they’ve been diagnosed with ALL and have undergone more extensive testing.
What are the Treatment Options for Philadelphia Chromosome Positive ALL?
Pediatric Ph+ ALL patients have historically been difficult to treat with conventional chemotherapy. Most pediatric ALL patients have a survival rate of more than 85 percent, while survival rates for these individuals were just about 30 percent. Survival rates have lately doubled to around 70 percent, because of the development of a new class of medications that directly target the Philadelphia Chromosome.
Tyrosine kinase inhibitors are the name for these medications. Imatinib is the most well-known medication in this class (or Gleevec). For children with Ph+ ALL, imatinib in conjunction with chemotherapy has become the accepted standard of care. In fact, imatinib will be used in combination with chemotherapy in the next significant US clinical trial aimed at improving outcomes in children with Ph+ ALL.
Philadelphia Chromosome Positive ALL Clinical Trials
The cure rate for Ph+ ALL is improving, although it still lags behind the majority of pediatric patients with ALL. Some of the science is focused on the development of new types of medications that target the Philadelphia Chromosome directly. Other studies are attempting to employ other medications to treat the 30 percent of patients who do not react to imatinib (or comparable drugs in its class) treatment — a particularly tough group of patients to treat.
Researchers are trying to figure out why certain juvenile Ph+ ALL patients relapse or don’t react to imatinib, and how we can utilize a different class of drug in combination with imatinib to increase cure rates.
Clinical trials are recruiting right now for improved outcomes and finding new targeted therapies for Philadelphia Chromosome Positive ALL.