VOD

2
3
4

Injury to the hepatic venous endotheliumEndothelial cell injury is seen in sinusoidal

endothelial cells and hepatocytes in zone 3 of the liver acinusDeposition of fibrinogen
and factor VIII within the venular walls and liver sinusoidsVenular
occlusionWidespread zonal liver disruption and centrilobular hemorrhagic necrosis,
post-sinusoidal obstruction and portal hypertension
Weight gain, jaundice, peripheral edema, ascites, AMS/confusion, bleeding, renal
failure, cardiopulmonary failure, hyperbilirubinemia, transaminitis, decreased synthetic
function (albumin, INR, etc)
Heparin 4units/kg/hr D0D+30 or D/C, Ursodiol 12mg/kg/day/BID D-7 to D+30
Supportive care (minimize renal/hepatotoxic exposures, Na/fluid restriction, diuretics,
HD for renal failure, intubation/mechanical ventilation for respiratory failure),
prostaglandin E, glutamine, vitamin E, alteplase, defibrotide,

GvHD
1. Activation, proliferation and migration of donor T cells targeting non-self MHC
antigens on recipient tissues leading to immune tissue destruction
2. Acute GvHD is defined as symptoms developing within +100 days post BMT
which are mainly localized to the skin, GI tract and liver. Chronic GvHD occurs
after D+100 and can manifest as skin, liver, GI, respiratory, intraarticular or
immune disease
3. Risk factors for GvHD include: older donor/recipient age, HLA mismatch, acute
GvHD, unrelated or cord donor, viral reactivation, splenectomy, PBSC transplant
4. Clinical manifestations of GvHD include: maculopapular rash, alopecia,
arthralgia, arteritis, transaminitis, increased bilirubin, cirrhosis, dysphagia,
abdominal pain, diarrhea, bronchiolitis obliterans, cytopenias, pericarditis,
pleural effusion
5. Tapering glucocorticoids is important to prevent adrenal crisis secondary to
steroid HPA axis inhibition
6. Treatment for disease refractory to steroids after 3-5 days include: MMF,
sirolimus, ATG, infliximab, thalidomide, photopheresis
mAbs
1. An ideal mAb is specific against 1 target, interacts with the target leading to target
cytotoxicity (ADCC, CDC, apoptosis, immune destruction), should not be immunogenic and
should only require single administration
2. Mechanisms of action for mAbs include: ADCC, CDC, apoptosis-induction, and introduction
of radioactive cytotoxic entities
3. Naming: murine =-mo-, chimeric=-xi-, humanized=-zu-, human=-mu4. mAbs are advantageous over traditional chemotherapy because they target a specific
antigen, have cytotoxic effects at only the antigenic site, and are associated with fewer
AEs
5. Targets of current mAbs include: CD20, CD52, CD33, HER2, VEGFR, EGFR/HER1/ErbB
MTX/LCV
1. DHFR inhibition leading to prevention of thymidine synthesis
2. Mucositis, n/v/d, BMS, reash, alopecia, renal dysfunction, hepatoxicityfibrosis/cirrhosis
3. HD-MTX improves drug distribution into larger solid tumors and sanctuary sites (CNS,
testes), over and prevents MTX resistant clones

4. Given IT for CNS disease in leukemia, better CSF concentrations are achieved with a longer
half-life; all while decreasing systemic MTX exposure
5. LCV works as MTX rescue by providing a reduced folic acid source to restore nucleotide
synthesis in non-malignant cells arrested by MTX administration. Additionally it competes
with MTX for active membrane transport
6. LCV should start 24-48 hours after HD-MTX administration and continue until serum MTX
level is <0.1 or per protocol
7. Methotrexate should be administered 10 days after peg-asparaginase to prevent
pharmacological antagonism due to decreased rate of DNA replication following pegasparaginase administration
Carboplatin Dosing
1. The DLT of carboplatin BMS; primarily thrombocytopenia
2. Children require a modified formula since they have greater weight variation, a larger
variation in tissue compartment and body size preventing assumption of constant nonrenal clearance, the adult AUC formula under predict AUC in children by up to 41%
3. AUC is preferred over BSA due to more consistent exposure with PK-based dosing which
ultimately increases response, AUC dose escalation has shown better responses in
relapsed pediatric solid tumor patients, and decreased risk toxicity
4. Schwartz formula should be used to calculate CrCl in pediatric patients but is inaccurate in
children <6 mo old
5. Corrected GFR is adjusted to reflect the GFR as based on the size of the average adult BSA
(1.73m2) while uncorrected GFR is the GFR based on the patients actual BSA
6. The three pediatric derived formulas are the Newell, Mann/Pein and Marina formula
TLS
1. TLS is caused by the rapid lysis of cells following chemotherapy administration which leads
to the spillage of intracellular uric acid, potassium and phosphorus into the plasma
causing uric acid nephropathy, secondary hypocalcemia and subsequent nephrolithiasis
and arrhythmias.
2. Hyperkalemia, hyperphosphatemic, hyperuricemia and hypocalcemia
3. Risk indicators for higher-risk disease include: Bulky disease or large tumor burden
sensitive to chemotherapy or rapidly proliferating disease (eg Burkitts), LDH >2x UNL,
WBC >100K
4. Management for low-risk patients is monitoring or based on clinical judgement.
Intermediate-risk patients require hydration at 1.5-2x MIVF with or without urine
Alkalinization with sodium bicarbonate and allopurinol. High-risk patients should receive
hydration plus rasburicase.
5. Uric acid samples following rasburicase administration must be immediately placed on ice
Aplastic Anemia
1. Aplastic anemia is pancytopenia secondary to hypoplasticity or aplasticity of the bone
marrow
2. Medications implicating in causing aplastic anemia include: alkylating agents,
antimetabolites, Anthracyclines, carbamazepine, phenytoin, chloramphenicol, quinacrine,
sulfonamides and acetazolamide
3. Most commonly presents as anemia with fatigue and pallor, neutropenia and
thrombocytopenia with visual disturbances secondary to retinal hemorrhage
4. New diagnosis patients may benefit from ATG, CSA, and steroids while severe aplastic
anemia requires BMT

5. Unrelated donor BMT patients also receive fludarabine, TBI, and a second dose of
thymoglobulin (6mg/kg total vs. 4mg/kg)
6. Fludarabine can cause neurotoxicity, tachypnea and visual disturbances
Intrathecal Chemotherapy
1. Factors influencing drug BBB permeability include: lipophilicity, unionized state, lower MW,
limited PPB, and high affinity for CNS protein carriers
2. Advantages to IT chemotherapy administration include higher CSF concentration,
minimization of systemic toxicity, and longer elimination half-lives
3. Disadvantages include: the need for and risk of LP, volume must match !0% of the
patients CSF volume, and risk of chemical arachnoidosis, leukoencephalopathy, subacute
myelopathy and cognitive/learning disabilities.
4. Dosing is based on age rather than weight or BSA due to the necessity that the volume of
IT administred must correlate with the CSF volumeof the patient
5. Toxicities associated with IT methotrexate include chemical arachnoidosis,
leukoencephalopathy, subacute myelopathy and cognitive/learning disabilities
6. Methotrexate, cytarabine and hydrocortisone are drugs that are currently administered IT
Long-Term Complications of Chemo
1. Treatment strategies for pediatric malignancies include chemotherapy, radition and
combinations of the two.
2. Endocrine reproductive effects include delayed/arrested puberty, hypogonadism,
premature menopause
3. Agents with higher incidences of cognitive dysfunction include IT therapy, cytarabine,
methotrexate, cranial irraditation
4. Anthracyclines and high-dose cyclophosphamide are associated with cardiac toxicity
5. Strategies for prevention of cardiotoxicity include limiting total exposure to <300mg/m 2,
dexrazoxane administration, screening/ECHO or MUGA/EKG prior to each cycle and on an
ongoing basis, avoidance of QT prolonging drugs, heart healthy lifestyle modifications