Questions and Answers
What chemotherapy drugs should SW receive as part of her ALL induction therapy?
What is the recommended starting dose for mercaptopurine (6MP) for SW based on her pharmacogenetic testing?
What is the role of the Drug TPMT in the metabolism of mercaptopurine?
TPMT catabolizes 6-MP and thioguanine to inactive metabolites.
Patients with T-cell ALL are typically classified as standard risk.
Signup and view all the answers
The critical assessment point for B-cell ALL patients is at the end of _____ phase.
Signup and view all the answers
Match the following ALL risk groups with their defining characteristics:
Signup and view all the answers
Which of the following characteristics classifies SC as standard-risk disease?
Signup and view all the answers
Cranial radiation is currently used in the treatment of CNS disease.
Signup and view all the answers
What is the recommended treatment for low-risk Group A patients with completely resected stage I disease?
Signup and view all the answers
Relapses for patients typically occur within __ to __ months post-treatment.
Signup and view all the answers
Match the treatment regimens with their corresponding risk groups:
Signup and view all the answers
What are the primary agents used in chemotherapy for Wilms tumor?
Signup and view all the answers
What is the recommended starting dose for patients with homozygous wild-type TPMT genotype?
Signup and view all the answers
What is the recommended starting dose for patients with homozygous deficient NUDT15 genotype?
Signup and view all the answers
What percentage of children with ALL is likely to relapse?
Signup and view all the answers
Extramedullary relapse is the most common type of relapse in children with ALL.
Signup and view all the answers
Which of the following is typically NOT recommended for patients who do not reach complete morphologic remission?
Signup and view all the answers
Patients with T-cell immunophenotype account for approximately ___% of relapses.
Signup and view all the answers
What is the goal of surgery in treating children with high-risk medulloblastoma?
Signup and view all the answers
What is the treatment strategy for children under 3 years of age with high-risk conditions?
Signup and view all the answers
Pediatric diffuse high-grade gliomas have a 5-year overall survival rate greater than 20%.
Signup and view all the answers
What is the common location for pilocytic astrocytoma?
Signup and view all the answers
What treatment is often utilized for relapsed pediatric astrocytomas?
Signup and view all the answers
Which tumor DNA content is considered a favorable prognostic indicator?
Signup and view all the answers
Delayed primary (second look) surgery is used to determine response and remove residual disease in high-risk patients.
Signup and view all the answers
What is the primary goal of surgery in tumor treatment?
Signup and view all the answers
In children with neuroblastoma, the treatment modality primarily used is _____
Signup and view all the answers
Match the treatment phase with its purpose for high-risk neuroblastoma:
Signup and view all the answers
What is the most common agent used in the induction phase for high-risk neuroblastoma?
Signup and view all the answers
Corticosteroids are recommended during dinutuximab therapy.
Signup and view all the answers
What is the goal of maintenance therapy in high-risk neuroblastoma?
Signup and view all the answers
Which of the following medication classes would be contraindicated concurrently with dinutuximab?
Signup and view all the answers
A favorable prognostic factor in neuroblastoma includes hyperdiploidy and _____ tumor histology.
Signup and view all the answers
What is the expected 5-year survival rate for infants with low-risk neuroblastoma?
Signup and view all the answers
What is the most common translocation associated with Burkitt lymphoma?
Signup and view all the answers
What is the recommended first-line chemotherapy treatment for Burkitt lymphoma?
Signup and view all the answers
What are the commonly used agents in local chemotherapy for retinoblastoma?
Signup and view all the answers
Intra-arterial chemotherapy can penetrate to the retina and vitreous space effectively.
Signup and view all the answers
What is the overall effectiveness of intra-arterial chemotherapy in preventing enucleation?
Signup and view all the answers
Which of the following conditions may require systemic chemotherapy?
Signup and view all the answers
Neoadjuvant chemotherapy, delayed enucleation, adjuvant chemotherapy and ____________ are part of the treatment for orbital locoregional disease.
Signup and view all the answers
What percentage of patients can achieve a cure for extraocular disease?
Signup and view all the answers
What is the incidence of secondary malignancy in children who survive retinoblastoma?
Signup and view all the answers
Metastatic disease without CNS involvement is common in developed countries.
Signup and view all the answers
Which of the following are effective agents in systemic chemotherapy?
Signup and view all the answers
What is the dosage of Dactinomycin for a child weighing more than 30 kg in the 4A regimen?
Signup and view all the answers
The overall prognosis for localized Wilms Tumor is approximately 90%.
Signup and view all the answers
Which of the following is a poor prognostic factor for Wilms Tumor?
Signup and view all the answers
What combination of drugs is prescribed for Ewing Sarcoma treatment every two weeks?
Signup and view all the answers
What is the 5-year overall survival rate for localized disease at diagnosis in Ewing Sarcoma?
Signup and view all the answers
Which gene mutation is linked to hereditary retinoblastoma?
Signup and view all the answers
What is the most appropriate treatment for a child diagnosed with unilateral retinoblastoma and vitreous seeding?
Signup and view all the answers
Study Notes
Learning Objectives
- Develop patient-specific treatment and monitoring plans for pediatric cancer based on clinical trials and guidelines.
- Evaluate the impact of cancer-related molecular biology tests on prognosis.
- Communicate treatment goals effectively with patients and caregivers, addressing both short- and long-term considerations.
- Understand ethical and regulatory issues in research, including informed consent and patient confidentiality.
Pediatric Acute Lymphoblastic Leukemia (ALL)
- Patient case example features a 5-year-old girl diagnosed with precursor B-cell ALL after presenting with symptoms such as anemia and high WBC count.
- Treatment options for induction therapy include dexamethasone, vincristine, calaspargase, and daunorubicin (correct answer).
Risk Stratification in Pediatric ALL
- NCI classifies B-cell ALL into Standard Risk and High Risk based on age and initial WBC count:
- Standard Risk: Age 1-9.99 years and WBC < 50,000 cells/mm³.
- High Risk: Age < 1 year or ≥ 10 years or WBC ≥ 50,000 cells/mm³.
- Additional risk factors include immunophenotype (B-cell vs. T-cell), CNS disease, testicular involvement, and genetic features.
- Steroid pre-treatment may falsely lower WBC counts, leading to possible up-stratification to high risk.
Treatment Phases for ALL
- Three phases of therapy are standard: Induction, Consolidation, and Maintenance.
-
Induction
- Goal: Achieve complete morphologic remission (90-95% success rate).
- High-risk patients receive a 4-drug induction regimen (including daunorubicin).
-
Consolidation
- Duration: 6-9 months, focuses on eradicating residual disease with drugs like vincristine and mercaptopurine.
- T-cell ALL patients may require intensified regimens.
-
Maintenance
- Duration: 2 years from the start of interim maintenance.
- Standard regimen includes daily mercaptopurine and weekly methotrexate.
Minimal Residual Disease (MRD)
- Critical marker for prognosis assessed at end of induction; MRD ≤ 0.01% strongly predicts event-free survival (EFS).
Pharmacogenetic Considerations
- TPMT and NUDT15 enzymes influence the metabolism of mercaptopurine (6-MP), affecting dose adjustments:
- Poor metabolizers of TPMT require reduced doses due to increased toxicity risk.
- NUDT15's role in converting toxic metabolites should also be considered.
Additional Treatment Considerations
- Philadelphia chromosome-positive (Ph+) ALL patients require tyrosine kinase inhibitors alongside their chemotherapy.
- Calaspargase pegol-mknl (Asparlas®) is a newer asparaginase product with distinct pharmacokinetic properties over previous versions.
- Monitor for toxicities including hypersensitivity, pancreatitis, and clotting disorders when administering asparaginase.
Patient Case #1 Highlights
- Correct answer for induction therapy regimen is D (Dexamethasone, vincristine, calaspargase, and daunorubicin).
- SW classified as high risk due to elevated WBC at presentation.
- Recommended starting dose of mercaptopurine for SW, testing reveals poor metabolizer status, requiring dose reduction.### Dosing Recommendations Based on TPMT Genotype
- TPMT Genotype: Homozygous wild-type (90% of patients): Normal starting dose recommended, classified as "Normal metabolizer."
- TPMT Genotype: Heterozygous (10% of patients): Start at 30-80% of full dose, termed "Intermediate metabolizer."
- TPMT Genotype: Homozygous deficient (0.3% of patients): Initiate at 10% of full dose, administer 3 times per week, recognized as "Poor metabolizer."
Dosing Recommendations Based on NUDT15 Genotype
- NUDT15 Genotype: Homozygous wild-type: Normal starting dose advised, identified as "Normal metabolizer."
- NUDT15 Genotype: Heterozygous: Recommended starting dose is 30-80% of full.
- NUDT15 Genotype: Homozygous deficient: Specific doses for 6-MP are 10 mg/m²/day and for 6-TG, 25% dosing, categorized as "Poor metabolizer."
Relapsed Acute Lymphoblastic Leukemia (ALL)
- 15-20% of children with ALL experience relapse; isolated bone marrow (BM) relapse occurs in 50-60% of cases.
- Extramedullary relapse includes isolated (with <5% leukemic cells in BM) and combined (with >5% leukemic cells in BM).
- Common sites for extramedullary relapse are the CNS and testicles; risk is elevated for patients with t(1;19), large leukemic burdens, and T-cell lineage.
Prognostic Factors for Relapsed ALL
-
Time to Relapse:
- Early: Relapse within 36 months (BM) or 18 months (extramedullary).
- Late: Relapse after 36 months (BM) or 18 months (extramedullary).
- Site of Relapse: Isolated extramedullary and combined relapse have a better prognosis than isolated BM relapse.
- Immunophenotype: T-cell accounted for approximately 15% of relapses.
Treatment of Relapsed ALL
- Re-induction therapy can involve repeating original therapy if the relapse is late.
- Consider clinical trials or novel chemotherapy agents not previously used.
- Targeted therapies include Blinatumomab and Tisagenlecleucel (indicated for relapsed or refractory ALL in patients up to 25 years).
- CNS relapse may require cranial irradiation, while allogeneic hematopoietic stem cell transplantation (HSCT) can improve survival in high-risk populations.
Treatment Strategies Based on Complete Remission Status
- CR1: Recommended for primary induction failure, consider for T-ALL, hypodiploid ALL, or persistent MRD positivity.
- CR2: Recommended for Pre-B ALL with early BM relapse, T-ALL with BM relapse, or ALL with multiple relapses.
Treatment Approaches for Medulloblastoma in High-Risk Children ≥3 Years Old
- Treatment includes surgery, standard dose radiation therapy, and chemotherapy, or high-dose chemotherapy with autologous stem cell rescue.
- Surgery aims for gross total resection; standard dose radiation begins after surgical resection.
Chemotherapy Regimen
- During radiotherapy: Vincristine at 1.5 mg/m² weekly for 6-8 weeks.
- After radiation: Vincristine at 1.5 mg/m² weekly for 3 weeks, Lomustine 100 mg/m² on day 1, and Prednisone at 40 mg/m² over 14 days.
Treatment for Children <3 Years of Age
- Surgery and aggressive multi-agent adjuvant therapy are preferred; radiation is avoided to limit neurocognitive impairments.
- Various chemotherapy regimens include cyclophosphamide, cisplatin, and vincristine.
Prognosis for Medulloblastoma
- Aggressive treatments provide approximately 60-80% survival; overall outcomes vary by age group with higher risk exhibiting lower EFS rates.
- Desmoplastic/nodular histology generally leads to a superior prognosis; treatment-related morbidity needs consideration.
Pediatric Diffuse High-Grade Glioma
- Rare, aggressive tumors with <20% 5-year overall survival; incidence is 1.8 per 100,000 children.
- Risk factors include inherited syndromes and prior cranial radiation exposure.
Treatment and Prognosis
- Treatments may include surgery, radiation, and chemotherapy; children <3 years should avoid radiation due to long-term risks.
- Targeted therapies are available for recurrent disease based on specific mutations.
Astrocytomas
- Slow-growing, indolent tumors that rarely transform malignantly.
- Surgery is the mainstay treatment, achieving gross total resection in 60-80% of cases.
Chemotherapy Regimen for Astrocytomas
- Carboplatin combined with vincristine is commonly employed after surgery; multi-agent regimens (TPCV) may also be used based on individual patient factors.
Prognosis for Low-Grade Astrocytomas
- Excellent long-term survival rates exceed 85%, with surgical excision providing cure in many cases; recurrences are generally manageable.### Neuroblastoma Overview
- Resistance to chemotherapy poses a significant obstacle to improving survival rates for high-risk neuroblastoma patients.
- Increasing dosage intensity of chemotherapy regimens is necessary to combat this resistance.
Risk Stratification
- Low Risk: Localized tumors may be cured with surgery; hyperdiploidy and favorable histology.
- Intermediate Risk: Includes young patients with metastatic disease or large, unresectable tumors; no standard chemotherapy regimen exists.
- High Risk: Characterized by metastases and MYCN amplification; requires aggressive multimodal treatment and immunotherapy.
- MS Stage: Patients exhibit metastases limited to the skin, liver, or bone marrow and may undergo spontaneous regression.
Treatment Strategies by Risk Group
-
Low Risk:
- INSS Stage 1: Surgery alone yields a 99% overall survival (OS) rate.
- INSS Stage 2: Surgery alone yields a 96% 5-year OS rate.
- Intermediate Risk: Multimodal treatment tailored to the individual; no defined standard chemotherapy.
-
High Risk:
- Induction involves chemotherapy combinations (e.g., Cyclophosphamide, Doxorubicin, Vincristine, Cisplatin, Etoposide) to reduce tumor size.
- Dose-intensity methods aim to overcome resistance.
- Consolidation includes intensive chemotherapy or myeloablative therapy with autologous stem cell rescue.
Induction Treatment for High Risk
- Cycles 1, 3, 4, 5: Various chemotherapy combinations (CAV and P-VP) administered.
- Local control through debulking surgery after initial chemotherapy cycles is vital.
- Radiation therapy may be needed to eliminate residual disease post-surgery.
Maintenance Therapy
- Aims to eradicate remaining tumor and prevent relapse, utilizing:
- Isotretinoin: Promotes differentiation and decreases neuroblastoma cell proliferation.
- Immunotherapy: Mainly targeting GD2 surface glycolipid with anti-GD2 (Dinutuximab), combined with GM-CSF.
- Supportive care is crucial, incorporating hydration and pre-medications to reduce hypersensitivity risks.
Specific Considerations for Dinutuximab
- Administered as an IV infusion over several days.
- Concurrent corticosteroids are contraindicated due to their immunosuppressive effects on T-cells and NK cells.
Prognosis and Survival Rates
- Positive prognostic factors include younger age at diagnosis, locoregional disease, and complete surgery.
- Survival rates vary significantly by risk group:
- Low Risk: ~95%
- Intermediate Risk: 80-90%
- High Risk: <50%
- 5-year survival for infants: ~90% and ~55% for older children.
Non-Hodgkin Lymphoma Overview
- Pediatric non-Hodgkin lymphoma (NHL) often presents as high-grade and bears resemblance to leukemias in its systemic nature and treatment approach.
Burkitt Lymphoma Characteristics
- Involves a translocation of the C-MYC oncogene and is prone to tumor lysis syndrome due to rapid growth rates.
- Treatment typically involves reduction chemotherapy followed by intensive multi-agent regimens.
Treatment Approaches for Burkitt Lymphoma
- Low-risk patients (resected stage I or abdominal stage II) may not require systemic chemotherapy.
- Intermediate-risk patients utilize reduced chemotherapy regimens.
- High-risk patients receive intensified chemotherapy, possibly including maintenance.
CNS Considerations
- CNS-directed therapy is often necessary in cases with central nervous system involvement, ensuring both high-dose systemic and intrathecal treatment are employed.
Key Considerations in Pediatric Cancer Treatment
- Early intervention, dose intensity, and careful monitoring for side effects like renal failure and infections are paramount.
- Maintenance therapies are critical in enhancing long-term survival outcomes in high-risk pediatric populations.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Description
This quiz explores the critical aspects of pediatric malignancies and the supportive care required for affected children. Participants will review key concepts presented by Jennifer Young, PharmD, and apply their knowledge in a clinical context. Enhance your understanding of pediatric hematology and oncology through this focused quiz.
