Magician and illusionist Criss Angel recently posted some great news: His son Johnny Crisstopher, now 7 years old, has entered remission after a 6-year battle with B-cell acute lymphoblastic leukemia (ALL).
Johnny was first diagnosed in 2015. He underwent many rounds of chemotherapy and earlier entered a short period of remission. Angel told "" in an interview that in December 2019, he "noticed [Johnny's] testicle was swollen and that's one of the signs. Cancer in boys hides either in a testicle or in the head, so we're really aware of that."
Doctors confirmed that Johnny had relapsed, and he underwent many more rounds of chemotherapy.
In January 2022, Angel posted on a video of Johnny ringing a bell to celebrate his entry into remission. This time Angel is hoping that Johnny will "be in remission forever." In the Extra interview, Angel was asked what the hardest part of Johnny's cancer was for him as a father. Angel answered: "Seeing my kid, you know, going through hell. Not understanding what was going on."
In 2001, Angel began to work with organizations that serve sick children, such as the Make-A-Wish Foundation. He said he enjoyed entertaining the kids and making them smile. After Johnny's diagnosis, Angel's interest in helping sick children expanded. He said he now wants to raise awareness about pediatric cancer as well as raise money for pediatric cancer research and for assistance for families going through the same experience with their child. To this end, Angel posted a nearly 14-minute video, entitled "," representing the 1,095 chemotherapy sessions his son underwent to treat his leukemia.
Angel said he hopes the film will lead to the raising of "hundreds of millions of dollars" toward pediatric cancer awareness and research and that he would "rather be remembered for the work that I did with kids than the work that I did as a magician."
Childhood ALL
Pediatric ALL is a cancer of the blood and bone marrow, where too many stem cells become lymphoblasts, B lymphocytes, or T lymphocytes. These leukemia cells do not function like normal lymphocytes and are less able to fight off infection. The malignant cells can also crowd out white blood cells, red blood cells, and platelets, leading to infection, anemia, and bleeding.
ALL can spread to the lymph nodes, spleen, liver, central nervous system (CNS), testicles, and other organs. Without treatment, ALL usually progresses quickly.
Signs and symptoms of ALL may include the following:
- Weakness or fatigue
- Fever or night sweats
- Bruising or bleeding easily (i.e., bleeding gums, purplish patches in the skin, or petechiae)
- Shortness of breath
- Unexpected weight loss or anorexia
- Pain in the bones or joints
- Swollen usually painless lymph nodes, particularly in the neck, armpit, or groin
- Swelling or discomfort in the abdomen
- Frequent infections
Incidence and Survival
ALL is the most common cancer diagnosed in children and represents about 25% of cancer diagnosed in children under age 15. In the U.S., ALL occurs at an annual rate of approximately 41 cases per million in people ages 0 to 14 years and approximately 17 cases per million in those ages 15 to 19, according to the NCI's . There are approximately 3,100 children and adolescents younger than age 20 diagnosed with ALL each year in the U.S.
Dramatic improvements in survival have been achieved in children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%. For ALL, the 5-year survival rate increased over the same time from 60% to approximately 90% for children younger than 15 and from 28% to more than 75% for adolescents age 15 to 19.
Genomics
According to , the genomics of childhood ALL has been extensively investigated, and multiple distinctive subtypes have been defined on the basis of cytogenetic and molecular characterizations.
The genomic landscape of B-cell ALL is typified by a range of genomic alterations that disrupt normal B-cell development and, in some cases, by mutations in genes that provide a proliferation signal. Genomic alterations leading to blockage of B-cell development include translocations (e.g., TCF3-PBX1 and ETV6-RUNX1); point mutations (e.g., IKZF1 and PAX5); and intragenic/intergenic deletions (e.g., IKZF1, PAX5, EBF, and ERG).
High hyperdiploidy, which occurs in 20-25% of cases of B-cell ALL, is a chromosome number abnormality, defined as 51-65 chromosomes per cell. High hyperdiploidy generally occurs in cases with clinically favorable prognostic factors (patients age 1 to <10 years with a low white blood cell count) and is an independent favorable prognostic factor. Trisomies of chromosomes 4, 10, and 17 (triple trisomies) also tend to have a favorable outcome.
The most common form of chromosomal translocations in ALL is ETV6-RUNX1. Fusion of the ETV6 gene on chromosome 12 to the RUNX1 gene on chromosome 21 is present in 20-25% of all cases of B-cell ALL. This Ph chromosome t(9;22)(q34.1;q11.2) (also known as the Philadelphia chromosome) is present in approximately 3% of children with ALL and leads to production of a BCR-ABL1 fusion protein with tyrosine kinase activity. This subtype of ALL is more common in older children with B-cell ALL.
Treatment
Treatment for children with ALL is typically divided into the following phases:
1. Remission induction chemotherapy (at the time of diagnosis)
The goal of the first phase of therapy (remission induction) is to induce a complete remission (CR). This induction phase typically lasts 4 weeks. Overall, approximately 98% of patients with newly diagnosed B-cell ALL achieve CR by the end of this phase, with somewhat lower rates in infants and in non-infant patients with T-cell ALL or high presenting leukocyte counts.
Induction chemotherapy typically consists of the following drugs, with or without an anthracycline (either doxorubicin or daunorubicin): vincristine, corticosteroids (either prednisone or dexamethasone), L-asparaginase, intrathecal chemotherapy (i.e., administration via an injection into the spinal canal or the subarachnoid space so that the drug reaches the cerebrospinal fluid).
2. Postinduction, consolidation/intensification therapy (after achieving CR)
Once complete remission (CR) has been achieved, systemic treatment in conjunction with central nervous system (CNS)-directed therapy follows. The most commonly used intensification schema is the BFM (Berlin, Frankfurt, Muenster) backbone, which includes the following:
- Initial consolidation with cyclophosphamide, low-dose cytarabine, and mercaptopurine (6-MP)
- Interim maintenance phase, which includes four doses of high-dose methotrexate with leucovorin rescue
- Re-induction (or delayed intensification), which typically includes agents and schedules similar to those used during the induction and initial consolidation phases
- Maintenance, typically consisting of daily 6-MP, weekly low-dose methotrexate, and sometimes administration of vincristine and a corticosteroid, as well as continued intrathecal therapy; maintenance generally continues for 2-3 years of continuous CR -- in some studies, boys are treated longer than girls
Sanctuary Sites
Historically, certain extramedullary sites have been considered "sanctuary sites" (i.e., anatomic spaces that are poorly penetrated by many of the orally and intravenously administered chemotherapy agents typically used to treat ALL).
The two most important sanctuary sites in childhood ALL are the CNS and the testes. Successful treatment of ALL requires therapy that effectively addresses clinical or subclinical involvement of leukemia in these extramedullary sanctuary sites.
At diagnosis, approximately 3% of patients have CNS3 disease (defined as cerebrospinal fluid specimen with ≥5 white blood cells/μL with lymphoblasts and/or the presence of cranial nerve palsies). However, unless specific therapy is directed towards the CNS, most children with ALL will eventually develop overt CNS leukemia whether or not lymphoblasts were detected in the spinal fluid at initial diagnosis.
CNS-directed treatments include intrathecal chemotherapy, CNS-directed systemic chemotherapy, and cranial radiation; some or all of these are included in current regimens for ALL.
Overt testicular involvement at the time of diagnosis occurs in approximately 2% of boys. The role of radiation therapy for testicular involvement is also unclear. A study from St. Jude Children's Research Hospital suggests that a good outcome can be achieved with aggressive conventional chemotherapy without radiation. The Children's Oncology Group has also adopted this strategy for boys with testicular involvement that resolves completely during induction chemotherapy.
Late-term effects of cancer treatment include the following:
- Physical problems, including with the heart, blood vessels, liver, or bones, and fertility; when dexrazoxane is given with anthracyclines, the risk of late heart effects is lessened
- Changes in mood, feelings, thinking, learning, or memory; children younger than 4 years who have received radiation therapy to the brain have a higher risk of these effects
- Second cancers or other conditions, such as brain tumors, thyroid cancer, acute myeloid leukemia, and myelodysplastic syndrome
Michele R. Berman, MD, is a pediatrician-turned-medical journalist. She trained at Johns Hopkins, Washington University in St. Louis, and St. Louis Children's Hospital. Her mission is both journalistic and educational: to report on common diseases affecting uncommon people and summarize the evidence-based medicine behind the headlines.