eMedicine Specialties > Pediatrics: General Medicine > Oncology

Hepatoblastoma: Treatment & Medication

Author: Jennifer R Willert, MD, Assistant Clinical Professor of Pediatrics, University of California at San Diego; Consulting Staff, Department of Pediatrics, Division of Hematology, Oncology and Bone Marrow Transplant, San Diego Children's Hospital; Member, Rebecca Moore's Cancer Center, Translational Oncology, University of California San Diego Medical Center
Coauthor(s): Gary Dahl, MD, Professor, Department of Pediatrics, Division of Hematology/Oncology, Stanford University School of Medicine
Contributor Information and Disclosures

Updated: Jan 14, 2008

Treatment

Medical Care

European groups, such as the International Society for Paediatric Oncology (SIOP), and groups in the United Kingdom and Australia, have been instrumental in demonstrating a role for preoperative adjuvant chemotherapy in improving surgical and overall outcomes. The European cooperative groups have also been very influential in encouraging a role for liver transplantation in patients with tumors deemed nonresectable. They have also developed criteria that can be used to determine which patients will benefit most from preoperative adjuvant chemotherapy as well as which patients should be referred early on for consideration for liver transplantation.

  • Chemotherapy
    • The most important advance in the care of children with hepatoblastoma has been the discovery of effective chemotherapy. Initial reports showed the efficacy of vincristine (VCR), cyclophosphamide (CPM), and doxorubicin with 5-fluorouracil (5-FU). This regimen was based on reports that suggested the efficacy of these agents in children and adults with liver tumors.
    • Cisplatin is the most active single agent used to treat hepatoblastoma. Doxorubicin is active as well. These agents are currently being combined in clinical trials. Attempts to reduce the ototoxic effects of cisplatin have led to the use of carboplatin; however, whether this agent will be as effective as cisplatin against hepatoblastoma remains to be seen. No direct randomized control trial has addressed this question to date.
    • The Intergroup Liver Tumor study showed similar efficacy of the cisplatin/5-FU/VCR regimen and the cisplatin plus doxorubicin regimen.26 Because the latter regimen was more toxic, the cisplatin/5-FU/VCR combination is regarded as standard in hepatoblastoma. The Intergroup Liver Tumor study demonstrated that intensification of therapy by alternating platinum analogs increased the risk of adverse outcome in children with unresectable or metastatic hepatoblastoma. The cisplatin/5-FU/VCR regimen was shown to be superior in this trial. Early referral for evaluation for liver transplantation is encouraged in these patients.
    • Preoperative chemotherapy can completely eradicate metastatic pulmonary disease and multinodular liver disease. Some authors recommend that all patients undergo preoperative chemotherapy, although patients may present in a setting in which resection occurs first. 
    • Chemotherapy is usually started approximately 4 weeks after surgery to allow liver regeneration. A minimum of 2 weeks should pass after surgery before administration of cytotoxic agents. 
    • Recent international data continue to support the role of neoadjuvant preoperative chemotherapy with improvements in survival. Data from Italy in a cohort of 13 children with hepatoblastoma also support a role for etoposide and epirubicin when combined with cisplatin, with EFS and overall survival rates at 5 years of 84% and 88%, respectively.27  
    • Treatment usually consists of 6 cycles of chemotherapy administered every 2-4 weeks; AFP levels are used as a guide to determine response to therapy. 
    • In addition to the drugs discussed above, carboplatin and etoposide have been used along with liver transplantation for advanced or recurrent disease with some success. Paclitaxel is also used in patients with extremely high-risk disease.
    • Use of neoadjuvant (preoperative) chemotherapy can often render a previously inoperable tumor more easily resectable. Some data from tumor xenografts suggest that these tumors may respond to irinotecan. Irinotecan has indeed shown activity in relapsed or refractory hepatoblastoma but has not yet been used for front-line therapy. 
    • Gemcitabine has been used with some partial responses in phase II trials. Combination therapy with other agents may improve outcomes in patients with relapsed/recurrent disease, perhaps providing decreased time to progression.
    • An approach with limited pediatric application is hepatic artery chemoembolization (HACE), which has been used successfully in some liver tumors in adults.
    • Promising studies performed in mice suggest a role for antiangiogenic agents, such as vascular endothelial growth factor (VEGF), in suppressing tumor growth in hepatoblastoma.28 A considerable amount of preclinical data have also demonstrated a role for multidrug resistance 1 (MDR1) inhibition as potentially leading to an improved response to chemotherapy in tumors that have otherwise become refractory to treatment because of a drug resistance mechanism.29,30
    • A few isolated studies have reported patients receiving only chemotherapy with survival at greater than 5 years.31
  • Radiotherapy
    • Doses used for treatment of hepatoblastoma are usually 1200-2000 centigray (cGy). These dose limits are based on the liver's limited ability to regenerate after radiation.
    • Radiotherapy may be used when microscopic disease is seen at the resection margins; in general, preoperative chemotherapy should minimize this.
    • Adjuvant radiotherapy may have a role in the treatment of chemoresistant pulmonary metastases.

Surgical Care

  • Because of the rarity of this disease and to optimize results, children with extensive hepatoblastoma should be managed and treated in centers affiliated with experienced liver transplant teams and with surgeons familiar with this diagnosis and familiar with complex decisions regarding planning for resection. These surgical and liver transplant teams work closely with oncologists, pathologists, and radiologists to provide optimal outcomes.
  • The hepatoblastoma can be completely resected at diagnosis in approximately one third of patients, those who have stage I or II disease. In 60% of patients, hepatoblastomas are localized but are unresectable at diagnosis. Approximately 10% of patients have metastases at diagnosis, most commonly to the lungs. These figures vary depending on the age of the patient at diagnosis, the size of the tumor, and the expertise of the surgical staff available for the procedure. Heroic efforts to resect tumors "up front" should be avoided, and adjuvant chemotherapy should be strongly considered when subtotal resection with microscopic margins is possible or when surgical morbidity is expected to be high.
  • Initial resection of operable primary tumors by lobectomy is the standard of care. Occasionally, pulmonary lesions are resected. This can occur after chemotherapy as well, with the ultimate goal for negative surgical margins for all disease. 
  • The following cases warrant early referral to a transplant surgeon:
    • Multifocal or large solitary lesions
    • Tumors involving all 4 sectors of the liver
    • Unifocal, centrally located tumors that involve the main hilar structures or main hepatic veins
  • Second-look laparotomy is warranted if AFP levels remain elevated following resection. Local porta hepatis nodal sampling is performed rather than true nodal dissection because nodal involvement is rare.
  • The most frequent complication of surgery is intraoperative hemorrhage; loss of the entire blood volume is not uncommon. 
  • In cases involving a substantial portion of the liver, particularly when diaphragmatic extension precludes complete surgical resection, liver transplantation has been advocated. Liver transplantation has also been considered in the presence of unresectable disease following neoadjuvant (preoperative) or adjuvant (postoperative) chemotherapy. Living related-donor transplantation may be considered in some situations as well. Early involvement of the liver transplant team and the hepatology team is essential because delays can adversely affect outcomes. 
  • Results from numerous cooperative international large group studies on hepatoblastoma continue to support a role for preoperative adjuvant chemotherapy in those tumors not easily respectable up front.4,32,33,34,22 Some authors advocate using adjuvant chemotherapy preoperatively, even when resection may be successful up front. The controversy over this is considerable,35 but all are in agreement that complete resection with no residual disease is ultimately the most important prognostic factor for improved survival results in hepatoblastoma. Hence, any treatment, medical or surgical, that leads to an improvement in gross total resection is the goal.
  • Increasing evidence suggests that arterial chemoembolization is feasible in patients with unresectable hepatoblastoma, patients who are not candidates for liver transplant, or both.
  • Liver transplantation has an increasing role in children with nonresectable tumors or in those who show chemotherapy resistance. Overall 5-year survival is as high as 70-89% in some series. Early referral and collaboration with liver transplant centers is encouraged. Whether posttransplant chemotherapy is indicated is controversial.
  • Thoracotomy and resection of pulmonary metastases also have a role, with some patients having long-term disease-free survival when aggressive attempts are made to surgically eradicate all areas of disease.

Consultations

A multidisciplinary approach in children with malignancy is necessary to ensure that appropriate care is safely administered with minimal toxicity. The team usually consists of specialized pediatric nurses, pediatric surgeons, pharmacologists with expertise in dealing with chemotherapy in children, nutritionists, social workers, child life specialists, and subspecialists in areas such as pediatric gastroenterology, neurology, cardiology, and infectious diseases. Early referral to liver transplant centers is encouraged for nonresectable tumors or those that show chemotherapy resistance. Referral to a radiation oncologist with pediatric experience may also be indicated.

Diet

Adequate nutrition is necessary for childhood growth and development. Maintaining adequate nutritional status is also important to maximize response to therapy. Many of the treatments may result in compromised nutritional status. Children undergoing radiotherapy or chemotherapy, particularly children younger than 5 years, typically require enteral or parenteral supplementation, often with electrolyte supplementation as well. Occupational therapists and child life specialists may be consulted to help with behavioral issues related to feeding, particularly in infants and toddlers.

Activity

Specific postoperative limitations on activity may be necessary, and, occasionally, some activities are limited because of central line placement or severe immunosuppression and myelosuppression associated with therapy; otherwise, no specific limitations are placed on activity. Most children are encouraged to attend daycare or school and participate in normal play essential to childhood development. Contact sports should be avoided during therapy, especially during periods of thrombocytopenia.

Medication

All chemotherapy orders are written and countersigned by pediatric oncologists. Most children are treated according to clinical protocols used in multiple institutions. For patients with refractory disease, a phase I or II trial is usually considered. Information on clinical trials is usually accessible through the National Cancer Institute (NCI) Web site and linked sites. The resources presented below should serve as guidelines only.

Antineoplastic agents have a narrow therapeutic index, and effective doses usually cause significant toxic effects. Any physician or other practitioner caring for children with cancer must be familiar with the indications, appropriate dosages, and toxic effects of the chemotherapy agents prescribed. They must also be familiar with any special considerations regarding age, weight, pharmacokinetic variations (ie, drug absorption, distribution, metabolism, excretion), coexisting medical problems, or possible pharmacokinetic interactions. To minimize risk to the patient, only practitioners familiar with the toxic effects and potential complications should prescribe antineoplastic agents.

Full discussion of the agents typically used in treating hepatoblastoma is beyond the scope of this article, but brief summaries of the drugs most commonly used are provided below.

Antineoplastic agents, alkylating agents, metal salts

The mechanism of action is similar to that of alkylating agents, namely, binding and cross-linking DNA strands.


Carboplatin (Paraplatin)

Similar to cisplatin, produces DNA cross-links that are predominantly interstrand. Effect is cell cycle nonspecific.

Adult

Pediatric

500 mg/m2/d IV for 2 d; may use Calvert formula to calculate dose: Total dose (mg) = target AUC X (GFR + 25)
Requires prehydration and should be administered with 0.45% NaCl, potassium chloride, and mannitol

Nephrotoxicity increases with aminoglycosides and other nephrotoxic drugs; reacts with aluminum, thus, must not come into contact with aluminum

Documented hypersensitivity; contraindicated in significant renal compromise; must evaluate risks versus benefits of use in setting of bone marrow depression, hearing impairment, renal function impairment, and infection

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

History of anaphylaxis warrants significant premedication (ie, corticosteroids, antihistamines, H2 blockers) and close monitoring if future doses are mandatory; may produce significant nephrotoxicity or ototoxicity; CrCl and audiologic evaluation must be performed at baseline and during therapy to monitor renal and hearing functions; incidence of neurotoxicity and nephrotoxicity is higher with previous use of cisplatin
Primary toxic effects are myelosuppression, emesis, anaphylaxis (rare), ototoxicity, renal toxicity, hypomagnesemia, electrolyte disturbances, and alopecia; rarer effects include metallic taste, peripheral neuropathy, hepatotoxicity, and secondary leukemia; myelosuppression usually lasts longer with carboplatin than with cisplatin, occasionally taking as long as 6 wk for counts to recover to levels adequate to proceed with next cycle of therapy; in particular, thrombocytopenia can persist for weeks and result in increased need for transfusion; close monitoring of CBC counts and platelets is necessary
Patients should avoid exposure to ill contacts, seek care for fever or bleeding, and avoid contact sports


Cisplatin (Platinol)

Binds and cross-links DNA strands, disrupting cell function. Usually combined with etoposide or doxorubicin.

Adult

Pediatric

20-40 mg/m2/d IV for 5 d
Alternative: 90-100 mg/m2 IV as single dose
Requires prehydration and should be administered with 0.45% NaCl, potassium chloride, and mannitol

Increased risk of ototoxicity when administered with aminoglycosides; increased risk of uric acid nephropathy when administered with probenecid or sulfinpyrazone

Documented hypersensitivity; contraindicated in significant renal compromise; must evaluate risks versus benefits in patients with hearing impairment

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May produce significant nephrotoxicity and ototoxicity (more than carboplatin); CrCl and audiologic evaluation must be performed at baseline and during therapy to monitor renal function and hearing; other primary toxic effects include nausea, vomiting (highly emetogenic), myelosuppression, and electrolyte disturbances; rare toxic effects include metallic taste, peripheral neuropathy, hepatotoxicity, and secondary leukemia; close monitoring of CBC counts and platelets is necessary; patients must avoid exposure to ill contacts, seek care for fever or bleeding, and avoid contact sports


Cyclophosphamide (Cytoxan, Neosar)

After metabolism by hepatic microsomal enzymes, produces active alkylating metabolites that probably damage DNA. Usually administered with doxorubicin and VCR or doxorubicin and cisplatin. Also an immunosuppressant.
Administered with mesna to prevent urotoxicity (ie, hemorrhagic cystitis).

Adult

Pediatric

1000-2000 mg/m2/d IV for 2 d
Marrow ablation: 60 mg/kg (ideal body weight)
Requires hydration before and during infusion

Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones
Chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity; increased risk of cardiomyopathy when administered at higher doses and combined with radiotherapy

Documented hypersensitivity; hematuria

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Must administer adequate hydration before and during infusion to prevent hemorrhagic cystitis; common toxic effects include anorexia, nausea, vomiting, myelosuppression, alopecia, immunosuppression, gonadal dysfunction, and sterility; occasional toxic effects include metallic taste, SIADH, and hemorrhagic cystitis; rare toxic effects include transient blurred vision, arrhythmias and myocardial necrosis (high dose), pulmonary fibrosis, secondary malignancy, and bladder fibrosis; close monitoring of CBC counts and platelets is necessary; patients should avoid exposure to ill contacts, seek care for fever or bleeding, and avoid contact sports

Antitumor antibiotics, natural products

These agents are usually derived from microorganisms and have various antitumor mechanisms. All interfere with the DNA structure or the breakage-resealing process.


Doxorubicin (Adriamycin)

Causes DNA strand breakage mediated by effects on topoisomerase II. Intercalates into DNA and inhibits DNA polymerase. Usually combined with VCR and CPM or with cisplatin.

Adult

Pediatric

30-75 mg/m2/d IV as single dose, slow push or continuous infusion
Alternative: 20 mg/m2/d IV qd for 4 d
For very small infants and children, consider dosing based on weight in kg rather than BSA

May decrease phenytoin and digoxin plasma levels; phenobarbital may decrease plasma levels of doxorubicin; cyclosporine may induce coma or seizures; mercaptopurine increases toxicity of doxorubicin; cyclophosphamide increases cardiac toxicity of doxorubicin

Documented hypersensitivity; severe heart failure, cardiomyopathy, and impaired cardiac function; preexisting myelosuppression

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Must document adequate baseline cardiac function and monitor cardiac function during treatment, especially if cumulative dose >450 mg/m2; doxorubicin is sclerosing agent (vesicant) and must be administered IV with free-flowing catheter to avoid extravasation; may cause local ulceration or severe burning and tissue damage; common toxic effects include cardiac arrhythmias (rarely clinically significant), nausea, vomiting, worsened adverse effects of radiation, pink or red color to urine, myelosuppression, alopecia, and immunosuppression; occasional toxic effects include stomatitis, hepatotoxicity, mucositis, and cardiomyopathy (cumulative and dependent on dose; risk increases when cumulative dose exceeds 450 mg/m2); rare toxic effects include palmoplantar erythrodysesthesia, anaphylaxis, allergic reactions, rash, and secondary malignancy; close monitoring of CBC counts and platelets is necessary; patients must avoid exposure to ill contacts and seek care for fever or bleeding

Topoisomerase II inhibitors, natural products

These plant alkaloids inhibit the topoisomerases that interfere with the normal DNA breakage-resealing reaction and cause single-strand breaks in DNA.


Etoposide (Toposar, VePesid)

Interacts with topoisomerase II and produces single-strand breaks in DNA. Arrests cells in late S phase or G2 phase. Typically combined with ifosfamide, cisplatin, or carboplatin.

Adult

Pediatric

75-150 mg/m2/d IV for 3-5 d
For very small infants and children, consider dosing based on weight in kg rather than BSA

May prolong effects of warfarin and increase clearance of methotrexate; cyclosporine and etoposide have additive effects in cytotoxicity of tumor cells

Documented hypersensitivity; consider using etoposide phosphate (Etopophos) in such patients

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

At high doses, hypotension is common and responds to fluid boluses or low-dose pressors; in patients sensitive to etoposide, use prophylaxis to avoid allergic reactions; common toxic effects include nausea, vomiting, and myelosuppression; occasional toxic effects include alopecia, worsened radiation damage, and diarrhea; rare toxic effects include hypotension, anaphylaxis, skin rash, peripheral neuropathy, stomatitis, and secondary malignancy; close monitoring of CBC counts is necessary; patients must avoid exposure to ill contacts and seek care for fever or bleeding

Antineoplastic antimetabolites

These agents are close structural analogs of vital intermediates in the biosynthetic pathways of nucleic acids and proteins. They either inhibit synthesis of cellular macromolecules and their building blocks or are incorporated into the macromolecules, resulting in a defective product.


5-Fluorouracil (Adrucil)

Prodrug that inhibits thymidine synthesis and is incorporated into RNA and DNA.
Specific to the S phase of the cell cycle.

Adult

Pediatric

500 mg/m2 IV push as single dose or qd for 5 d
800-1200 mg/m2 continuous IV infusion over 24-120 h
No guidelines available for modifying dose in patients with hepatic or renal dysfunction

Increased risk of bleeding with anticoagulants, NSAIDs, platelet inhibitors, and thrombolytic agents; enhanced bone marrow toxicity with other immunosuppressive agents; clearance delayed and toxicity increased by thymidine competing for enzyme that catabolizes 5-FU; intracellular activation and incorporation into RNA increased by methotrexate

Documented hypersensitivity; inherited deficiency of catabolic enzyme dihydropyrimidine dehydrogenase (associated with severe 5-FU toxicity)

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Toxic effects exacerbated by impairments in liver function; dose-limiting toxic effects include leukopenia, thrombocytopenia, severe diarrhea, stomatitis, and dysphagia; local ulceration if extravasation occurs; other common toxic effects include proctitis, nausea and vomiting, partial loss of nails, hypopigmentation, and immunosuppression; severe mucositis can lead to infection, dehydration, and poor nutritional status; close monitoring of CBC counts is necessary; patients must avoid exposure to ill contacts and seek care for fever or bleeding

Mitotic inhibitors, natural products

These plant alkaloids bind to microtubular proteins, inhibiting RNA synthesis by disrupting DNA formation.


Vincristine (Oncovin, Vincasar PFS)

Binds tubulin, leading to its depolymerization, which results in mitotic inhibition and metaphase arrest. Specific to S and M phases of the cell cycle. Used in combination with doxorubicin and CPM.

Adult

Pediatric

1-2 mg/m2 IV push; not to exceed 2 mg/dose
For very small infants and children, consider dosing based on weight in kg rather than BSA

Increased neurotoxicity when combined with radiotherapy; increased myelosuppression when administered with doxorubicin; interacts with probenecid and sulfinpyrazone

Documented hypersensitivity; neuromuscular disease; intrathecal administration universally causes death

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Adjust dose in hyperbilirubinemia (to avoid potential neurotoxicity), ileus, and severe neuropathy; VCR is sclerosing agent (vesicant) must be administered IV with free-flowing catheter to avoid extravasation; may cause local ulceration or severe burning and tissue damage; common toxic effects include hair loss and loss of deep tendon reflexes; occasional toxic effects include jaw pain, weakness, constipation, numbness, tingling, and clumsiness; rare toxic effects include paralytic ileus, ptosis, vocal cord paralysis, myelosuppression, CNS depression, SIADH, and seizures

Colony-stimulating factors

These agents promote growth and differentiation of myeloid progenitor cells. They may improve survival and function of granulocytes.


Filgrastim (Neupogen)

G-CSF Used to combat neutropenia, particularly in patients receiving myelosuppressive therapy. Produced recombinantly in Escherichia coli for clinical use.

Adult

Pediatric

5-10 mcg/kg/d SC for 10-14 d; initiate 24-26 h after last dose of chemotherapy; continue until ANC recovers to >1500-5000/mL
Under certain circumstances, with proper precautions, can be administered as slow IV infusion but dose must be higher (10 mcg/kg) and adverse reactions have been reported

Sensitivity to yeast- or E coli– derived proteins

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Occasional adverse effects include local irritation at injection site, medullary bone pain, increased alkaline phosphatase, LDH, and uric acid levels, or thrombocytopenia; rare adverse effects include allergies, low-grade fever, subclinical splenomegaly, exacerbation of preexisting skin rashes, alopecia, and cutaneous vasculitis; patients should seek medical care for fever, pain, or redness at injection site and avoid ill contacts; monitor blood counts to determine end of therapy

More on Hepatoblastoma

Overview: Hepatoblastoma
Differential Diagnoses & Workup: Hepatoblastoma
Treatment & Medication: Hepatoblastoma
Follow-up: Hepatoblastoma
Multimedia: Hepatoblastoma
References
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Further Reading

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Keywords

hepatoblastoma, embryonal hepatic tumor, hepatic neoplasms in children, liver tumor, liver cancer, pediatric cancer, pediatric neoplasm, childhood hepatic tumor, Beckwith-Wiedemann syndrome, BWS, pulmonary metastases, hemihypertrophy, trisomy 20, epithelial hepatoblastoma, familial adenomatous polyposis, FAP, colonic polyps, adenocarcinoma, Wnt pathway, low birth weight infants, very low birth weight infants, anorexia, osteopenia, acute abdomen, chronic hepatitis B infection, isosexual precocity, talipes equinovarus, persistent ductus arteriosus, tetralogy of Fallot, extrahepatic biliary atresia, dysplastic kidney, horseshoe kidney, cleft palate, Goldenhar syndrome, Prader-Willi syndrome, Meckel diverticulum, Simpson-Golabi-Behmel syndrome, fetal alcohol syndrome, neurofibromatosis type 1, NF1, Li-Fraumeni syndrome

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Contributor Information and Disclosures

Author

Jennifer R Willert, MD, Assistant Clinical Professor of Pediatrics, University of California at San Diego; Consulting Staff, Department of Pediatrics, Division of Hematology, Oncology and Bone Marrow Transplant, San Diego Children's Hospital; Member, Rebecca Moore's Cancer Center, Translational Oncology, University of California San Diego Medical Center
Jennifer R Willert, MD is a member of the following medical societies: American Academy of Pediatrics, American Society for Blood and Marrow Transplantation, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Children's Oncology Group
Disclosure: Nothing to disclose.

Coauthor(s)

Gary Dahl, MD, Professor, Department of Pediatrics, Division of Hematology/Oncology, Stanford University School of Medicine
Gary Dahl, MD is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

Medical Editor

Stephan A Grupp, MD, PhD, Director, Stem Cell Biology Program, Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia; Associate Professor of Pediatrics, University of Pennsylvania
Stephan A Grupp, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Steven K Bergstrom, MD, Assistant to the Chairman, Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland
Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and International Society for Experimental Hematology
Disclosure: Nothing to disclose.

CME Editor

Helen SL Chan, MBBS, FRCP(C), FAAP, Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada
Helen SL Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Clinical Oncology, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA, Executive Director, Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, DC; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Clinical Oncology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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