167© Springer International Publishing AG, part of Springer Nature 2018C.W. Penteado Schmidt, Chemotherapy in Neonates and Infants, https://doi.org/10.1007/978-3-319-70591-0

Appendix

Body Surface Area of Neonates and Infants

A nomogram for body calculation of neonates is needed. The formula by Meban (BSA m2 = 6.4954 × weight (g) 0.562 × height (cm) 0.320) is possibly the best to estimate the body surface of newborns, followed by the Mosteller (√[(height in cm × weight in kg)/3,600]) formula; however, the Boyd and Dubois formulas are not recommended for surface estimation of newborns for treatment, due to either overestimation or underestimation. A studie compared Meban, Moesteller, Boyd and Dubois formulas with a BSA-Mean (an arithmetic mean of these four formulas). The Meban formula is most similar to the BSA-Mean for-mula, with a mathematically perfect correlation and the least dissimilarity using Euclidean distance, followed by the Mosteller formula. The estimations by both Boyd and Dubois show about a 5% deviation above and below the BSA-Mean formula, respectively, with a consistent dissimi-larity using Euclidean distance regardless of the same goodness of fit. The degree of deviation increases with weight and decreases with height [33].

168

Acidity/Basicity of Chemotherapeutic Drugs

Table A.1 Acidity/basicity of chemotherapeutic drugsDrug Acidity/basicityAlkylating drug (cyclophosphamide) Weak acid [29]

Anthracycline drugs (daunorubicine, doxorubicin)

Weak bases [27, 29, 66]

Methotrexate Weak acid [28]

Mitoxantrone Weak base [66]

Platinum compounds (cisplatin, carboplatin)

Weak acids [29]

Vinka alkaloid drug (vincristine) Weak base [27, 29]

Before any of these drugs are prescribed for young children, they should be verified by the pharmacist and physician with regard to the ideal dose, dilution, protocol, and other specifications for each age group.

Appendix

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177© Springer International Publishing AG, part of Springer Nature 2018C.W. Penteado Schmidt, Chemotherapy in Neonates and Infants, https://doi.org/10.1007/978-3-319-70591-0

Index

AABC, see ATP-binding cassettes

(ABC)ABCA to ABCG, 143ABCB1, 144ABCC1, 144ABCC3, 144ABCC4, 144ABCC5, 144ABCC6, 144ABCG2, 144Abdomen, 14Abdominal cavity, 14Abdominal distension, 14Abdominal pain, 134Absolute neutrophil count, 40Absorption, 2, 77–79, 81, 103,

104, 121Absorption of oral drugs, 79Acetylation, 97Acid drugs, 79, 83, 84, 86, 88,

102, 146Acidification of urine, 102, 146Acid-labile drugs, 78, 79Acid pH, 79Acid protein, 83Acid uric, 147Acrolein, 97, 99Active tubular secretion, 100Acute and delayed nausea, 124Acute leukemia, 7, 151, 152Acute lymphoblastic leukemia,

18–55, 123, 157

Acute lymphoid leukemia (ALL), 5, 6, 12, 41

development, 152induction therapy, 153

Acute megakaryoblastic leukemia (AMKL), 7, 152, 153

Acute monoblastic (M4), 5Acute myeloid leukemia

(AML), 5, 6, 12, 56, 153, 157, 158

Acute pain, 117, 119–120Acute renal failure, 148Acyclovir, 164Additive effect, 134Additive toxic effects, 133Adenosine triphosphate (ATP),

90, 143, 144Adenoviruses, 166Adjustments, 20, 58, 59, 62Adjuvant drugs, 115Administration, 120Adrenal cortical, 84Adverse effects, 117, 123Adverse reactions, 139Affinity, 84African Americans, 143Age dependent, 93AIEOP 2001/02, 59–63AIEOP 2002/01, 42, 56–63AIEOP AML 2002/01 study, 158AIEOP study, 158AIEO study, 58

178

Akldo-keto reductase 1 (AKR1), 99

Alanine transaminase (ALT), 67, 69

Albumin, 69, 83, 84, 86–88, 126binding affinity, 88complex, 86–88concentrations, 126level, 67

Alcohol, 121, 139Aldehyde dehydrogenase

(ALDH), 99Aldoifosfamide, 99Aldophosphamide tautomer, 99Alimentation, 125, 126Alkaline phosphatase (ALP), 67Alkaline pH urine, 102Alkalinization, 148

of urine, 102, 146ALL, see Acute lymphoid

leukemia (ALL)Allergic reactions, 139, 141Allergy, 27, 34, 36Allogeneic bone marrow

transplantation, 157–158

Allogeneic hematopoietic SCT (allo-HSCT), 56–58

Allogeneic SCT, 56Allogeneic transplantation, 157Allograft, 57Allopurinol, 147α-acid glycoprotein, 83, 84, 86, 87,

89, 126α-1-Acid-glycoprotein, 86ALT, see Alanine transaminase

(ALT)Alternative donors, 57Amegakaryocytic

thrombocytopenia, 157Amikacin, 132Amino acids, 90, 91, 144Aminoglycosides, 132Aminotransferase levels, 40

AMKL, see Acute megakaryoblastic leukemia (AMKL)

AML1, 151Amniotic fluid, 78Amphotericin B, 135Ampicillin, 78Amputation, 13, 14Analgesia, 117–120Analgesics, 142–144Analogous nucleoside, 144Anaplastic astrocytoma, 11Anemia, 14, 72, 143Anion gap, 140Antenatal sonography, 13Anthracyclines, 58, 144Antibiotics, 132–135

derived from penicillin, 134not derived from penicillin,

134Antibody levels, 26, 27Antidiuretic hormone (ADH),

99Antiemetic, 132, 166Antifungals, 135, 166Antihuman T-lymphocyte

immunoglobulin, 165Antimicrobial, 133Antineoplastic drugs, 2, 97, 134,

136, 143Antineoplastic therapy, 143, 145Antioxidant, 137, 139, 141Apnea, 115, 124Aprepitant, 124, 132Aprepitant dose, 124Aprepitant oral suspension

doses, 124Arabs, 142Area under the curve (AUC), 71,

73–76, 109, 110, 119, 123, 163

Arrhythmias, 15, 124Asia, 6Asparaginase, 12, 27, 34, 36

Index

179

Aspergillus spp., 166AST, 69Astrocytoma, 10, 11

in pregnancy, 11ATA1, 91, 144ATP-binding cassettes (ABC), 90

expression, 90, 144family, 145genes, 143proteins, 143superfamily, 90transporters, 90, 144

Atria, 138AUC, see Area under the curve

(AUC)Audiologic evaluations, 65Autologous, 56, 157Autologous HSCT (auto-HSCT),

57Autologous SCT, 157Autologous transplantation, 157Availability, 161Avinza, 121Azithromycin, 133Azole antifungals, 135

BBacteria, 82Bacterial flora, 103Basic drugs, 79, 84, 87, 88, 126, 127B cells, 11Bcr-abl fusion, 19Benign, 4, 8, 15Benzoic acid, 138, 139, 141Benzyl alcohol, 138, 140Berlin–Frankfurt–Münster

(BFM), 18, 41–45BFM86/90, 19BFM95 protocol, 12, 41Bidirectional transporters, 90Bile, 80, 81, 102, 103Bile acid synthesis, 78Bile salts, 81, 82, 90

Bilirubin, 40, 69, 83, 84, 86–88, 99, 139, 142

Bilirubin–albumin, 88Bilirubin–albumin binding

affinity, 87Bilirubin level, 67Binding, 83, 84, 86, 88, 89

affinity, 88of albumin, 127of drugs, 86proteins, 77, 83–89site, 86and transport proteins,

126–130Bioactivation, 97Bioavailability, 80, 82, 91Biochemical examinations, 3Biopsy, 18Biotransformation, 77, 83, 97Biphenotypic leukemia, 18, 123Birth weight, 10, 102Blast cells, 7, 152Blasts, 11, 21, 43, 45, 153Bleeding, 9B-lineage ALL, 153Blood, 152

counts, 22, 65, 153flow, 15, 94flow to muscle, 79

Bloodstream, 97Body surface area, 24, 94, 113,

114Body surface area–to–weight

ratio, 79Body weight, 3, 85Bolus, 104Bone marrow, 21, 30, 43, 161

aspiration, 18examination, 43puncture, 21, 27, 30

Bound drug, 83Bound substrate molecules, 89Bovine milk, 125Bowman’s space, 100

Index

180

Boys, 4Bradycardia, 124Brain, 8, 11, 90, 92, 93Brainstem gliomas, 65Brain tumors, 63, 157Breakpoints as in B-ALL, 19Broad-spectrum antibiotics, 166Busulfan, 162–163Busulfan adjustment, 163

CCancer, 5, 6

cells, 91, 144drugs, 91therapy, 90

Capillaries, 101Carboplatin, 9, 10, 63, 66, 70–76,

85, 109, 110, 133clearance, 71concentrations, 110doses, 71, 109

Carboplatine, 66Carboxy-ifosfamide, 99Cardiac failure, 15Cardiac function, 158Cardiac QTc interval, 123Cardiac tumors, 15Cardiac vascular tumors, 15Cardiomyopathy, 112Cardiopulmonary tumors, 4, 8Cardiovascular, 138, 140, 158

accumulation, 140collapse, 139effects, 138

Carrier protein, 127Carriers, 143Carries, 90Caspofungin, 135Catabolic metabolism, 164Catabolized, 125Catalysis, 97Caucasians, 143CBFA2T3-GLIS2, 58CBFA2T3-GLIS2 gene fusion

transcripts, 58

CCG, 18CCG-1953 protocol, 12CCG-9921, 65, 66

protocol, 63–66study, 64

CD3+ cells, 161CD4+ cells, 161CD8+ cells, 161CD10-, 11CD10 expression, 19, 20CD19+ cells, 11CD34+ cells, 11, 161Ceftriaxone, 133Cell, 90, 92, 127Cell membranes, 89, 90Cellular drug efflux, 103Cellular uptake, 91Central depressive effects, 92Central nervous system

(CNS), 5, 26, 43, 46, 63dysfunction, 139infiltration, 11involvement, 20, 24leukemia, 26not evaluable, 23status, 20, 23, 24, 41toxicity, 34, 138, 140tumors, 4, 8, 10–11

Cesarean, 13Chemical characteristics of the

drug, 78Chemistry, 65Chemosensitivity, 13, 14Chemotherapeutic drugs, 126,

131, 132, 143Chemotherapy, 3, 8–13, 15, 20, 21,

45, 64–67, 69, 78–82, 89–91, 94–97, 103–125, 131–135, 137, 143, 147, 148, 151–155, 161–163

drugs, 58, 77, 92, 94, 95, 97in the plasma, 67protocols, 109resistance, 144

Childhood malignancies, 4Children’s Cancer Group, 12

Index

181

Children’s Hospital Los Angeles, 13

Children’s Hospital San Diego, 13

China, 153Chinese, 143Chloroacetaldehyde, 99Chromosome, 151Chromosome 21, 152Chronic granulomatous disease,

157Chronic pain, 117Circulation, 90, 127Circulatory problems, 14Cirrhosis, 123Cisplatin, 63, 65, 68–70, 85, 92, 93,

97, 110, 133, 135clearance, 69, 110dosage, 69in high doses, 124plasma concentration, 68

Clarithromycin, 133Clearance, 56, 71, 91, 100, 114,

131Clearance rates of morphine, 116Clinical condition, 21Clinical effect, 106Clinical importance, 93, 131Clinically, 92, 93Clinical pharmacological study,

70Clinical practice, 77, 106Clinical problems, 29Clinical response, 66Clinical significance, 84, 90, 125Clonazepam, 164Clotrimoxazole, 32CNS, see Central nervous system

(CNS)CNS 1, 23, 24CNS 2, 23, 24, 27CNS 3, 23, 24CNS+, 18, 27, 49Coagulation, 83Coagulopathy, 14Coating materials, 137

Cochrane, 117Codeine, 115, 142, 143Codification, 143Colonization of the

gastrointestinal tract, 82

Complete remission, 21, 45, 56–58, 61, 69, 72

Computed tomography (CT), 8, 15, 24

Concentration, 28, 46–48, 50, 52, 59, 61, 63, 69, 90–91, 94, 113

Concentration–effect curve, 106Concentration gradient, 90Conditioning, 164Conditioning therapy, 161, 163,

164Conditions, 94Conformational change, 89Congenital cellular mesoblastic

nephroma, 13, 14Congenital diseases, 151Congenital fibrosarcoma, 14Congenital fructose intolerance,

139, 141Congenital intracranial immature

teratoma, 8Congenital neuroblastoma, 148Congenital precursor B-cell

acute lymphoid leukemia (ALL), 148

Congenital tumors, 3, 4, 7–8, 95Conjugation, 97Conserving agents, 137Consistency improvers, 137Consolidation, 22, 41, 57, 58, 63,

154courses, 57phase I, 62phase II, 62therapy, 58, 153

Constipation, 134Continuous administration, 104Continuous intravenous

infusion, 118

Index

182

Continuous renal replacement therapy, 122

Contractile force, 138Copper transporters (CTRs), 91,

143Cord blood, 161Coronary flow, 138Corticosteroids, 12, 19, 136Cotransport, 91Cotrimoxazole, 40Countertransport, 91Cow’s milk, 125, 126CR1, 57Cranial nerve palsy, 9, 24Cranial radiation, 12Craniospinal irradiation, 64Craniospinal radiation therapy,

65Creatinine, 21, 69, 100

clearance, 100, 101, 109level, 67

Criteria, 45Criterion, 19Cryotherapy, 73Crystalline human serum

albumin, 86, 87Cerebrospinal fluid (CSF), 23, 24Cumulative area under the curve

(AUC) values, 71Cumulative busulfan, 163Cyanosis, 15Cyclophosfamide, 50, 51Cyclophosphamide, 22, 29, 38, 47,

51, 63, 65, 66, 85, 95–97, 111, 132

Cyclosporin, 165Cyclosporine, 165Cyclosporine A, 165CYP1A1, 94CYP2A1, 94CYP2A4, 135CYP2A6, 95, 131CYP2B6, 95, 131CYP2C, 94, 95CYP2C8, 132CYP2C9, 95, 131, 132, 135

CYP2C19, 132, 135CYP2CP, 135CYP2D6, 94, 95, 142, 143CYP2E1, 94, 95CYP3A4, 94, 95, 131–133, 135CYP3A7, 94Cystathionine β-synthase, 152Cystatin C, 101Cystic fibrosis, 143Cystitis, 51, 66Cytarabine, 21, 25, 26, 29–31, 34,

36–38, 40, 42, 47, 48, 50, 52, 54, 56, 59–61, 85, 111–112, 153

block, 38intrathecal, 28

Cytocentrifugation, 23Cytochemistry, 18Cytochrome P450 (CYP), 77, 97,

99, 135enzymes, 97, 99, 135system, 90, 127

Cytogenetic, 57Cytokine family 2–4, 151Cytolytic chemotherapy, 147Cytomegalovirus (CMV), 166

status, 161Cytoplasmic azurophilic

granules, 152Cytoplasmic blebs, 152Cytoplasms, 152Cytotoxic activity, 97

DDaily AUC, 71Daily practice, 105Daunorubicin, 26, 46, 54, 85, 92,

93, 97, 128, 153Death, 12, 141, 142, 147Death rate, 57Decreased cardiac function, 58Decreased cardiac output, 80Deficiency, 58Desmoplastic infantile

astrocytoma, 11

Index

183

Detoxification, 99Developing countries, 6Dexamethasone, 12, 25, 35, 49,

51–55, 124, 131, 132Dexrazoxane, 112Dextrose, 120Diagnose, 7, 13Diagnosis, 3, 5–7, 9, 15, 18, 20, 27,

45, 67Diagnostic surgery, 64Diarrhea, 72Died, 57, 148Digestive tract colonization, 81Dihydrofolate, 134Dihydrofolate reductase, 134Diluent, 31, 33, 37, 40, 46–50, 52, 54,

55, 59, 61, 63, 111, 113Dilution, 120Dimesna, 97Disease, 3–8, 12, 21, 57, 64, 65Disease-free survival, 158Disintegrating materials, 137Dispersing agent, 139, 141Dissolution rates, 80Distal tubular reabsorption, 100Distal tubules, 100Distribution, 2, 85, 89

by proteins, 83volume, 85–87

Disturbance of consciousness, 8Diuresis, 29, 148DNA mutation, 151Domperidone, 123, 124Donor, 57, 159–161, 166Donor priority, 160Dosage adjustments, 67Dosage effects, 106Dosage of cytotoxic drugs, 56Dosage of morphine, 120Dosage range, 106Dose adjustment, 12, 27, 39, 43,

62–63, 71, 77, 81, 95, 106, 122

of high-dose cytarabine, 61of high-dose cytarabine

administration, 60

Dose–effect curve, 106Dose monitoring, 110

by measurements, 68Dose reductions, 24, 30, 40, 42, 43,

46–50, 52, 54, 55Dose–response relationship, 105,

106Doses, 94Down syndrome, 7, 148, 151Doxorubicin, 49, 92, 93, 96, 112,

127, 132Drugs, 58, 84–86

absorption, 78, 81binding, 83–93clearance, 82, 102, 110depuration, 100disposition, 105, 110distribution, 83, 104efflux, 144excretion, 100–102filtration, 127is hydrophilic, 85interactions, 77, 90, 92,

104–105, 125–136mechanism of action, 106metabolism, 2–3monitoring, 27, 73–76, 110, 114in the plasma, 106resistance, 144therapy, 105transporters, 90uptake, 144

Drug’s link to a receptor, 106Ductus venosus, 94

EEarly B-lineage acute lymphoid

leukemia (ALL), 153Early neonatal period, 102East Asia, 6ECG, see Electrocardiograms

(ECGs)Echinocandin, 135Echocardiography, 15Edema, 109

Index

184

Effects, 106Efflux, 90, 93

morphine, 92time, 92transporter, 103

EGIL scoring, 18Electrocardiograms (ECGs), 12311q23 translocation, 11Elimination, 2, 90, 97, 102, 103,

110, 127, 146Embryonal tumor, 4Emetogenic chemotherapy, 123,

124Empty stomach, 30, 32, 39Emulgents, 137Emulsifier, 139, 141Endocrine, 158Endogenous compounds, 83Endogenous molecules, 99Endotracheal intubation, 119Enteral nutrition, 164Enterohepatic circulation, 103Enzymatic conditions, 95Enzymatic metabolism, 96, 97, 99Enzyme, 94, 97

complex, 94, 95, 134, 142concentrations, 94

Ependymoma, 63Epidermis, 79Epidural, 115Epipodophyllotoxins, 58, 144Epstein–Barr virus, 154, 166Equilibrium, 103Erwinia asparaginase, 27, 34, 36Erythrocyte concentrations, 108,

109Erythrocytes, 23Erythromycin, 133Escherichia coli asparaginase, 27Essential amino acids, 91Ester salt, 80Estimated creatinine clearance,

109Estrogenic activity, 142Ethanol, 139, 142Ethiopians, 142

Etoposide, 9, 10, 54, 57–59, 61, 63, 65, 66, 71, 72, 75, 76, 85, 92, 93, 95, 96, 112, 128, 132

ETV6-NTRK3 gene, 13, 14EUROCARE-5, 4, 6, 7Eurocord/EBMT, 158Europe, 6, 18European countries, 4European study, 18European Study of Neonatal

Excipient Exposure, 140

Event-free survival, 57, 58Excipients, 116, 137

of drugs, 137, 139Excision, 13Excretion, 3, 77, 82, 83, 102–103,

110of morphine, 116

Extemporaneous morphine solution, 121

Extemporaneous oral solution, 112

Extemporaneous preparation, 107, 108, 111, 121

Extracellular compartment, 103Extracellular water, 3Extracompartment maintenance

phase (M), 41, 44, 48Extracranial, 9Extracranial teratomas, 4, 8Extrahepatic metabolism,

122–123Extramedullary involvement, 5–6

FFAB M7-AMKL, 154Failure, 133Family donors, 57, 160Family history, 6Fatal, 143Fat digestion, 80, 81Fat-soluble compounds, 81Fat-soluble substances, 81

Index

185

Fat-soluble vitamins, 81Fatty acids, 86Feces, 102Feeding intolerance, 124Fetal albumin, 86, 88, 89Fetal brain, 92Fetal isoform CYP1A1, 95Fetal life, 82Fetal liver, 94Fetuses, 11, 13, 14, 94, 95Fever, 166Fibroma, 15Filgrastim, 65, 66First few weeks of life, 3First part of OCTADAD, 22, 35–37First-pass metabolism, 80First regimen (A) of induction, 64Fludarabine, 162–163Fluorescence in situ hybridization

(FISH), 20Folate deficiency, 152Folate metabolism, 151Folinic acid, 33, 114, 165Folinic acid doses, 33Food, 78, 121Food and Drug Administration

(FDA), 115, 133, 148Formula, 56, 59, 61, 62, 105Formulas (artificial milk), 82Foscarnet, 166FPDMM, 151Free bilirubin, 86, 87Free fatty, 86Free fatty acids, 84, 86–89French–American–British (FAB)

classification, 153Full term, 67, 82Full-term neonate, 3, 70, 78, 85Full-term newborns, 100Funnel, 122Furosemide, 29

GGabapentin, 91Ganciclovir, 166

Ganglioneuroblastoma, 4Gasping respirations, 139Gasping syndrome, 139Gastric acid secretions, 81Gastric acid secretory capacity,

78Gastric emptying, 82

time, 78, 81Gastric pH, 78, 79, 81Gastroesophageal reflux, 123, 124Gastrointestinal enzymatic

activity, 78Gastrointestinal motility, 82Gene, 11, 90, 143, 151Gene duplications, 142Generally Recognized as Safe

(GRAS), 137Genetic metabolic disorders, 157Genetics, 90, 143–145

disorders, 143localization, 90

Gentamicin, 132Germ cells, 4Germ layers, 4, 8Germline mutation, 6Gestation, 92Gestational age, 1, 2, 10, 70,

73–76, 88GFR, see Glomerular filtration

rate (GFR)Gilbert syndrome, 40Girls, 4Glioblastoma, 11Glioma, 135Globulin, 84, 87, 88Glomerular filtration, 100, 109Glomerular filtration rate

(GFR), 100, 101, 122, 148

Glomerulus, 101Glucocorticoids, 24Glucuronic acid, 99Glucuronidases, 99Glucuronidation, 97, 99Glutathione (GSH), 99Glutathione conjugation, 97

Index

186

Glycine, 139, 141Good prednisone response, 23Graft-versus-host disease

(GvHD), 164, 165Gram-negative sepsis, 57Granulocyte colony-stimulating

factor (G-CSF), 45, 161Granulocytes, 43GRF, 122Growth hormone, 84Guideline, 71GvHD, see Graft-versus-host

disease (GvHD)

HHalf-life, 103, 109, 116, 123, 126Harmful excipient, 139Head, 8Health Canada, 142Health problems, 106Hearing, 158

impairment, 76loss, 72

Heart, 14, 138Hemangioma, 13, 14Hematological effects, 134Hematological toxicities, 72Hematology disorders, 157Hematopoiesis, 21Hematopoietic SCT (HSCT), 57Hematuria, 29, 135Hemodynamic function, 15Hemoglobin levels, 164Hemophagocytic, 157Hemorrhage, 14, 166Hemorrhagic, 9Hemorrhagic cystitis, 97, 111Hepatic, 134Hepatic drug metabolism, 94Hepatic enzyme, 77Hepatic glucuronidation, 94Hepatic hemangiomas, 13Hepatic impairment, 122Hepatic malignancy, 14Hepatic metabolism, 94, 95

Hepatic oxygenation, 94Hepatic sulfation activity, 94Hepatic tumors, 4, 8, 13–14Hepatitis A, B, and C, 166Hepatoblastoma, 13, 14, 68–69,

110Hepatocytes, 84Hepatosplenomegaly, 5Hepatotoxins, 84Hereditary, 6Herpes simplex, 164Herpesviruses, 166High-dose cytarabine, 57, 58,

62–63High-dose intravenous

methotrexate, 33High-dose methotrexate, 32High dose of cytarabine, 22, 34,

56, 58High doses of methotrexate, 114High tumor burden, 149Hippuric acid, 138Hispanics, 143Histological, 4, 8, 9, 15Histopathological, 9HIV, see human

immunodeficiency virus (HIV)

Hofmann elimination, 97Hospital for Sick Children

(Toronto), 157HR protocol, 44Human immunodeficiency virus

(HIV), 151, 166Human leukocyte antigen

(HLA), 159Human leukocyte antigen typing,

159Human milk, 125, 126Human milk interactions, 125Human T-lymphotropic virus

(HTLV) 1+2, 166Hydration, 3, 29, 78, 102, 108, 146,

147, 164Hydrocephalus, 9, 10Hydrocodone, 143

Index

187

Hydrocortisone, 26, 30, 31, 33, 37, 40, 131

Hydrocortisone intrathecal, 28Hydrolysis, 82, 97Hydrolysis of ATP, 90Hydrophilic, 89Hydrophilic drugs, 87Hydrops, 14Hyperalbuminemia, 84, 127Hypercalcemia, 6, 147Hyperleukocytosis, 5, 11,

148, 149Hyperosmolarity, 138, 140Hyperphosphatemia, 147Hypertension, 6Hyperuricemia, 147Hypoalbuminemia, 84, 127Hypocalcemia, 147Hypoplastic bone marrow, 21Hypotension, 80, 138–140Hypothyroidism, 58, 158

IIB, 20, 21IB phase, 20, 21, 29–31ICE, 58, 61ICE 2 + 3+ 7, 58, 61ICE 3+ 5+ 10, 58, 61Idarubicin, 56, 59, 60, 85, 92, 93,

128IFNAR, 151IFN-α/β receptor, 151Ifosfamide, 53, 63, 66, 85, 95–97,

99, 111, 132Ifosfamide mustard, 99Ifosforamide mustard, 97Ileum, 81Imaging, 65

findings, 24of the neuroaxis, 65techniques, 15

Imatinib, 92, 93, 96, 136Immature teratoma, 9Immunobiological processes, 83immunoglobulins, 164

Immunophenotyping, 18Immunoreactivity, 93Impaired cognitive function,

58, 158Inactivation, 97Incidence, 152Increase/decrease, 84, 135Induce, 94, 136Inducer, 92, 93, 127, 130, 131Induces CYP3A4, 134Induction, 20, 21, 25–28, 41,

42, 56–58, 62, 64, 131, 153

Induction chemotherapy, 56, 63, 148

Induction phase, 20, 30, 58, 64–66

Induction phase A, 65Induction phase B, 66Induction phase I of protocol, 41Induction phase I of protocol I,

42, 46Induction therapy, 21Induction therapy ICE 3 + 5 +

10, 59Induction treatment, 154Infections, 21, 166Influx, 90Infratentorial tumors, 65Infusion, 120Inhibit, 134Inhibit enzymes, 136Inhibition, 133, 134Inhibitor, 96, 132, 135Injection, 104Inotropic effects, 139Insulin, 84Intensification, 12, 42Intensified consolidation, 42Interaction, 124, 126, 132–134Interfant-06, 18, 20–22, 24–30,

32–40, 123, 124, 132, 159–166

Interfant-99, 18, 19Intermediate-risk, 10Intermittent hemodialysis, 122

Index

188

International Collaborative Treatment Protocol For Infants Under One Year With Acute Lymphoblastic Or Biphenotypic Leukemia study, 18

Intestinal absorption, 103Intestinal GvHD, 164Intestinal microflora, 82Intestinal motility, 78, 82, 103Intestinal motility disorder, 124Intestinal surface area, 103Intestinal tract, 103Intestinal transit, 82, 103Intestine, 90, 102, 103Intoxication, 79, 92, 93, 95, 102,

121, 139, 142by an acid drug, 146

Intracellular, 103Intracerebral/meningeal mass, 24Intracranial cavity, 11Intracranial hemorrhage, 10, 138,

140Intracranial mass, 10Intracranial teratomas, 8, 9Intramuscular, 80, 81Intramuscular absorption, 79–81Intramuscular drug absorption,

80Intraoperative hemorrhage, 9Intrathecal, 24, 26, 28, 30, 31, 33,

37, 39, 40, 43, 46–50, 52, 54–56, 59, 61, 63, 111, 113, 115

Intrathecala, 37Intrathecal cytarabine, 26, 41, 62Intrathecal drugs, 112Intrathecal injection, 111Intrathecal methotrexate, 26, 33Intrathecal prednisolone, 26, 37Intrathecal therapy, 113Intrathecal use, 40, 52Intrauterine or neonatal onset

of childhood CNS tumors, 10

Intravenous, 29, 115Intravenous morphine, 115, 120Intraventricular hemorrhage, 117Intubation, 117Invasive cancer, 4Investigation, 10In vivo, 105Ionized, 102Ions, 90Irinotecan, 92, 93, 96, 129, 132,

136, 144Irradiation, 11, 41, 64Isoenzymes, 94Isoform, 91, 95Isoform 3A7, 95Isoniazid, 134Isophosphoramide mustard, 99Italian group protocol, 56

JJapan, 8Japanese, 143Jaw pain, 134JOE, 75Juvenile myelomonocytic

leukemia, 157

KKadian, 121, 122Kaposi’s sarcoma, 154Kidney, 90, 91, 97, 100, 102, 138

disease, 84, 127function, 110involvement, 147

LLaboratory, 69Laboratory monitoring, 166Lactate dehydrogenase (LDH)

levels, 69, 149Lactic acidosis, 138, 140LAM-92 article, 58LAM-92 protocol, 56, 59–63

Index

189

LAM-92 study, 58L-amino acid transporter, 91L-amino acid transports, 91Largeness for gestational age, 10Large-neutral amino acid

transporters (LATs), 91, 143–144

Laser treatment, 72, 73, 75L-asparaginase, 12, 46, 49, 52–54,

85Leaky tubules, 100Leiomyomas, 154Leiomyosarcomas, 154Leucocytes, 40Leucovorin, 114, 165Leukemia, 4, 5, 7, 8, 11–12, 26,

124, 132, 152, 153Leukemia cutis, 5Leukemic cells, 19, 23Leukemic infiltration, 18Leukemogenesis, 151Leukocoria, 7Leukocyte, 43, 45Leukocyte counts, 5Levels of cisplatin in plasma, 70Linker drug, 84Lipophilic, 89Lipophilic drugs, 86, 87, 97Lipoprotein, 84Liver, 80, 84, 90, 91, 94, 95, 99, 117,

138cirrhosis, 134disease, 84, 127function, 40, 67

Local excision, 14Located in the 11q23 band, 19Low-birth-weight infants, 141Low-grade astrocytoma, 11Low/intermediate-risk, 9Low-risk neuroblastoma, 10, 70Lumbar puncture, 27Lumen, 102, 146Lung cancer, 144Lungs, 14, 102Lymph nodes, 154, 155Lymphoid, 11

Lymphomas, 154Lymphoproliferative lesions, 154

MM7 AMKL, 153Macrocephaly, 10Macrolide antibiotics, 133MADIT, 52, 54, 55Magnetic resonance imaging

(MRI), 24of the heart, 15

Maintenance, 22, 44, 45, 65phase, 20, 39–42, 45,

64–66therapy, 22, 40, 55, 64

Malignancy, 5, 151, 154Malignant brain tumor, 63Malignant cells, 147Malignant neoplasm, 5Malignant rhabdoid tumor of

the kidney, 12Malignant tumors, 15Management of chemotherapy,

105MARMA, 20, 22MARMA phase, 20, 22, 32–33Marrow, 152Maternal milk, 82Maturation, 80Maturation process of organ

systems, 78Mature B-ALL without

MLL, 19Mature teratoma, 9Maximum concentrations, 104MD group, 165Measured creatinine clearance,

109Measurements, 71Mechanically ventilated

newborns, 117Mechanical ventilation, 117Mechanism of action, 77, 104Mechanism of activation, 97Mediastinal tumor, 43

Index

190

Medulloblastoma, 10, 11, 63Megakaryoblastic (M7)

leukemias, 5Membrane, 89Mercaptopurine, 47, 48, 50, 55,

107–108, 125, 126Mercaptorurine, 107–108Mesenchymal hamartoma, 13, 14Mesna, 29, 47, 51, 53, 66, 97, 111Mesna cystitis, 47, 50Mesoblastic nephroma, 6Metabisulfite, 116, 139, 141Metabolic abnormalities, 147Metabolic acidosis, 102, 138–141Metabolic activity, 97Metabolic derangements, 148Metabolic mechanisms, 90, 127Metabolic parameters, 149Metabolism, 2, 82, 95, 97, 132, 135

of bile salts, 81, 103Metabolites, 97, 99, 103, 108Metabolization, 42Metabolize, 127Metabolizers, 142Metachronous tumors, 12Metastases, 13, 14Metastatic disease, 14, 64Metastatic tumors, 15Methadone, 143Methotrexate, 26, 30–33, 39, 40,

46–55, 85, 92, 93, 102, 113, 129, 134, 135, 144, 146, 165

clearance, 114intrathecal, 28plasma level, 33

Methylation, 97, 151Methyltetrahydrofolate

reductase enzyme, 152Metoclopramide, 84, 123Micafungin, 135Microbial colonization, 82Mild liver disease, 122Milk, 30, 32, 126Milk products, 39Minimum residual disease, 20

Mitoxantrone, 57, 58, 62, 92, 93, 144

Mixed-lineage leukemia (MLL), 11, 19, 20

MLL gene, 19MLL gene (11q23)

rearrangements, 19MLL gene status, 20Modulation, 131Molecular genetics, 10Molecular weight, 80Molecule, 97Monitoring, 93, 106Monitoring of dosage, 3Morphine, 99, 115–123, 136, 142,

143Morphine half-life, 116Morphine-3-glucuronide, 117Morphine-6-glucuronide, 117Morphological grounds, 21Morphological verification, 18Mortality, 13, 82, 117MSD group, 165Mucosa, 164Mucosa-associated lymphoid

tissue (MALT) group, 154

Mucositis, 22, 32, 57, 134Murmurs, 15Muscle, 80

contractility, 80mass, 80, 100perfusion, 80

Muscular mass, 79Muscular perfusion, 80Muscular water content, 80Musculoskeletal, 158Mutations, 143, 152Myeloablative dose, 163Myeloablative preparation,

158Myelodysplastic disease, 4Myeloid, 11Myeloid blasts, 148Myelomonoblastic (M5), 5Myeloproliferative disease, 4

Index

191

Myelosuppression, 34, 134Myxoma, 15

NNarrow therapeutic index, 106,

126Nasogastric tube, 122, 164Nausea, 123–124Negative inotropic effects, 141Neoadjuvant, 8Neonatal abstinence syndrome,

121Neonatal death, 138Neonatal jaundice, 69Neonatal period, 95, 100Neonatal urinary tract infections

(UTIs), 132Neonates, 92, 132Neonate’s gastrointestinal tract,

82Neonatology, 92, 93, 115, 137Neoplasms, 4, 8, 11Nephrectomy, 67, 68Nephroblastoma, 6Nephrotic syndrome, 84, 127Nephrotoxic, 133, 135Nephrotoxic chemotherapy, 133Nephrotoxic drugs, 135Nephrotoxicity, 132, 133Nephroureterectomy, 12Neural compounds, 91Neuroaxis, 65Neuroblastoma, 4, 8–10, 76, 114,

157Neurodevelopmental, 117Neurological, 158Neurological disorders, 143Neurological sequelae, 12Neuronal effects, 139, 142Neurotoxic, 11Neurotoxicity, 135, 139, 141Neutral amino acids, 91Neutropenia, 72, 164Neutrophils, 20, 22, 35, 36, 38, 40

count, 21, 22, 164

recovery, 164Newborns, 94, 95, 100, 102, 138

with Down syndrome, 152NH

2 group, 97NH4

+ excretion, 102Nicotinamide adenine dinucleotide

(NADH), 125NK1 receptor antagonist, 124Noncongenital malignancy, 4Nonenzymatic degradation, 97Nonenzymatic elimination, 99Nonepithelial renal tumors, 6Non-Hodgkin’s lymphomas, 154Noninvasive diagnostic, 15Nonmetastatic tumors, 64Nonmyxomatous, benign cardiac

tumors, 15Nonopioid, 142Nonventilated infants, 119–120Nordic, 10Normal saline, 120North Africans, 142Nucleated cell, 161Nuclei, 152Nucleoli, 152Numbness, 134Nutrients, 91, 144Nutrient transport system, 91Nutrition, 84

OOCT-1, see Organic cation

transporter-1 (OCT-1)OCT1/SLC22A1, 91OCT2/SLC22A2, 91OCT3/SLC22A3, 91OCTADAD, 20, 22OCTADAD phase, 20, 22Off-label, 1, 2, 147-OH group, 97Ointment bases, 137Oncocytic cardiomyopathy, 15Oncology treatment, 2Ondansetron, 1231A1, 99, 134

Index

192

Operation, 9Opioids, 92, 117Oral, 115Oral drug absorption, 78, 81Oral drugs, 91, 111Oral morphine, 121–122Oral solution, 111, 121Organic anion transporters

(OATs), 91, 143Organic anion–transporting

polypeptides (OATPs), 91, 143

Organic cations, 91Organic cation transporter-1

(OCT-1), 91–93Organic cation transporters

(OCTs), 91, 143Organs, 92, 93Osmotic laxative effects,

139, 141Ototoxicity, 72, 132, 133, 138, 140Oxidase system, 97Oxidation, 97Oxidized, 97

PPacked red cells, 164Pain, 117, 134

control, 166management, 115–123, 136

Pancreas, 80Pancreatic fluid, 80, 81Paralytic ileus, 134Paraneoplastic syndromes, 6Parenteral nutrition, 164Partial remission, 58, 61Parvovirus, 166Passive diffusion, 90Peak serum concentrations, 80Pediatrics, 134Pediatric tumors, 3PEG-asparaginase, 34, 36PEG-L-asparaginase, 24, 26, 27Penicillin, 78, 134Peptides, 91, 144

Peptide transporters (PEPTs), 91, 143

Percutaneous absorption, 79Perinatal astrocytoma, 10Perinatal hepatic tumors, 13Perinatal period, 13Peripheral blast cells, 154Peripheral blasts, 153Peripheral blood, 45

examination, 18stem cells, 161

Peripheral nervous cell tumors, 4Peristalsis, 82Peritoneal dialysis, 122Periventricular leukomalacia, 117P-glycoprotein, 90, 92, 93, 103,

127, 131, 135expression, 103immunoreactivity, 92

pH, 78–81, 102, 146of the rectum, 80urinary, 102

Pharmacodynamic curves of the concentration–effect, 106

Pharmacodynamics, 2, 42, 77, 94, 104–106, 112, 116, 143

Pharmacokinetic analysis, 68, 163Pharmacokinetics, 2, 42, 66,

77–94, 99, 103–105, 112, 114, 116, 126, 135, 143, 163

Pharmacological dosage of the chemotherapy drugs in the blood, 67

Pharmacological predictions, 79Pharmacologic therapies, 1Pharmacology/pharmacological,

83, 87, 88, 106, 142Phase I clinical trial, 105Phase I of protocol I, 46Phase II of protocol, 41Phase II of protocol I, 44, 47Phase II of reinduction, 44Phase I reaction, 97Phase II reactions, 97

Index

193

Phase II reinduction, 45Phenotype, 142Phenylbutazone, 84Phosphoribosylglycinamide

formyltransferase, 151Phylogenetic classification, 143Physical examination, 13Physiochemical properties, 80Physiological changes, 94, 106Physiological processes, 2pKa, 83Placenta, 14Plasma, 83, 87, 106, 126, 147Plasma albumin, 84, 86, 87, 89, 127Plasma cisplatin levels, 68, 69, 110Plasma concentrations, 67, 69,

106, 110, 114, 143dosage, 3of vincristine, 66

Plasma creatinine, 100Plasma levels, 33Plasma membranes, 90, 91Plasma methotrexate levels, 33Plasma monitoring, 106Plasma proteins, 77, 83, 85, 126,

127, 134Plasma solids, 126Plasma uric, 147Plateau, 103, 104Platelets, 21, 22, 35, 36, 38, 166

concentrate, 164count, 22, 40, 43levels, 164–166

Platinum, 133Platinum compounds, 132, 133Pneumocystis carinii prophylaxis,

164POG 9421, 153Polar, 99Polymerase chain reaction

(PCR), 166Polymorphisms, 135, 142, 151Polyoxyethylene, 139Polyoxyethylene sorbitan fatty

acid ester, 139, 141Polysorbate, 138, 139

Polysorbate 80, 139, 141Polysorbates 20, 139, 141Poor prednisolone response, 45Poor prednisone response, 23Poor prognosis, 19Port end, 122Posterior fossa, 9, 65Postmenstrual age, 1, 2Postnatal, 100Postnatal age, 1, 2Postnatal maturation, 79, 92, 93Postnatal screening, 6Preoperative chemotherapy, 13Postoperative complications, 9Postremission therapy, 56Power for oral suspension, 124Precipitation, 102, 146Precursor B-lineage, 19Predicted serum creatinine, 101Prednisolone, 26, 28, 30, 31, 33, 37,

40, 84, 131Prednisolonea, 37Prednisolone intrathecal, 28Prednisone, 25, 27, 46, 131Prednisone response, 19, 20, 25,

27Pregnancy, 7, 11, 152Premature, 1, 100, 115

infants, 100, 102, 116, 123, 124neonate, 2, 3, 79, 86, 116

Prematurity, 6, 79Prenatal ultrasound, 13Preoperative chemotherapy, 13,

14Prescription/manipulation, 120Preservatives, 28, 31, 33, 37, 40,

46–50, 52, 54, 55, 59, 61, 63, 111, 113, 115, 137–140, 142

Preterm, 85, 101babies, 116infants, 117neonates, 70, 78, 100, 138

Primordial germ cells, 8Procedures, 120Prognoses, 15

Index

194

Prognosis, 6, 8, 9, 11–13, 58Prognostic, 19, 20Prophylaxis, 51Propylene glycol, 138, 140Propyl hydroxybenzoate,

139, 142Propylparaben, 139, 142Propyl parahydroxybenzoate,

139, 142Proteins, 83–86, 89, 126, 127, 131

binding, 83–85, 89, 116, 142binding sites, 139load, 102

Protein-bound, 87Protocol drugs, 67Protocol II/phase, 41Protocol II/phase II, 41Protocols, 3, 8, 10–12, 17–76, 92,

93, 104, 132, 153for morphine, 116–120

Proton pump inhibitors, 136Proximal tubular secretion, 100,

134Proximal tubules, 101Pulmonary, 158Pulmonary toxicity, 134Pulses, 42, 55

QQTc interval, 124

RRadiation, 10, 11Radiation therapy, 64Radiological diagnosis of a

brain tumor, 64Radiotherapy, 9–11, 15Randomizations, 21, 41–42Rasburicase, 147–149Reabsorption, 100Reabsorption of creatinine, 100Rearrangement, 19, 23Rectal absorption, 80Rectal area, 80

Rectal drug absorption in neonates, 80

Rectal route, 80Rectal vault, 80Rectal veins, 80Rectum, 80Recurrence, 64Reduce doses, 40Reduction, 56, 67, 97Reinduction, 41, 42, 44Reinduction phase, 41

protocol II/phase I, 42, 49, 50

protocol II/phase II, 42Relapse, 12, 57, 72Relapsed ALL, 19Relative to older children, 2Remission, 7, 21, 43, 45, 67, 72,

152–154Renal, 65, 76, 100–102Renal blood flow, 100Renal clearance, 82, 100, 109Renal elimination, 100Renal excretion, 99, 146Renal failure, 133, 147Renal function, 100, 109, 110, 148Renal impairment, 108, 122Renal insufficiency, 147Renal toxicity, 72Renal tubular precipitation, 147Renal tubular secretion, 134Renal tubules, 102, 146, 147Renal tumors, 4, 6, 8, 12–13Repeated administration,

103, 104Rescue with leucovorin, 48,

51, 53Research, 77, 92, 93, 105Researchers, 93, 95Resection, 8, 9Residual tumor, 64Resistance, 12, 90, 91, 143, 144Respiratory condition, 9Respiratory depression, 115,

142, 143Respiratory distress, 14, 15, 139

Index

195

Respiratory insufficiency, 138, 140

Response to prednisone, 19Retinal involvement, 24Retinoblastoma, 6, 7, 70–73, 75,

110, 114, 157Retinoblastoma gene, RB1, 6Retrodiffusion, 102Reverse transcriptase–

polymerase chain reaction, 14

Rhabdoid tumor, 63Rhabdomyoma, 15Rhabdomyosarcoma, 114, 157Rifampicin, 134Risk, 67, 148Risk groups, 20Routine measurements, 40

SSacrococcygeal region, 4, 8Screening for retinopathy, 6SCT, see Stem cell

transplantation (SCT)Second consolidation, 62Second malignancy, 7Second malignant neoplasms, 158Second MARMA phase, 34Second part of the OCTADAD

phase, 38Second phase of MARMA, 22Second regimen (B), 64Second surgery, 64Sedation in infants, 120Seizure prophylaxis, 164Seizures, 138, 140Sensorineural deafness, 72Sepsis, 80, 166Septic episode, 72Serum albumin, 86, 89Serum analysis, 110Serum concentrations, 123, 135

of morphine, 142Serum creatinine, 100, 109Serum dosage, 105

Serum urate, 1487p21, 14417q21.3, 144Severe aplastic anemia, 157Severe kidney disease, 127Sialic acid, 83Sibling donors, 160Silent inactivation of PEG-

asparaginase, 34, 36Silent inactivation of PEG-L-

asparaginase, 27Single-unit cord blood

transplantation, 15816-French gastrostomy tube, 1226-Mercaptopurine, 29, 30, 32, 39,

40, 85, 125, 12616p13.1, 1446-Thioguanine, 35, 386-thiouric acid, 1256-tioguanine nucleotides, 1096-year event-free survival, 19, 41Skeletal muscle, 100Skeletal muscle capillaries, 80Skin, 79Skin perfusion, 79Slow and continuous infusion,

104Small intestine, 91Smallness for gestational age, 10Sodium benzoate, 139, 141Sodium bicarbonate, 102,

146–148Soft tissue tumors, 4, 8Solid tumors, 7, 151Solubility, 80Solute carrier(s), 90–91, 143, 144

family, 89proteins, 90transporters, 144

Solvent, 138, 140Sorbitol, 139, 141Spontaneous regression, 9St. Jude Children’s Research

Hospital, 108, 109, 112, 113

STC, 12

Index

196

Stem cell, 57Stem cell source, 161Stem cell transplantation (SCT),

12, 20, 22, 56, 153, 157–166

Steroid, 90Steroidal anti-inflammatories, 131Stillbirth, 14Stimulated donors, 161Stomach, 78Stratification, 20, 41Stratum corneum, 79Subependymal giant cell

astrocytoma, 11Substrate, 90–92, 95–97, 127–132,

135, 143Sulfa drugs, 134Sulfamethoxazole, 134Sulfate, 99Sulfation, 97Supportive care, 12Supportive therapy, 164–166Supratentorial malignant

gliomas, 65Supratentorial primitive

neuroectodermal tumors (PNETs), 63, 64

Surface area, 24Surgeon, 11Surgery, 8–10, 13–15Surgical, 13, 14Surgical intervention, 10Surgical resection, 11, 14, 15, 69Surgical treatment, 9Survival, 12, 15Sweetening, 141Symptoms, 40, 153Systemic circulation, 80, 92, 102,

146Systemic clearance, 112, 113System L, 91

Tt(8;21), inv.(16) or t(16;16), 57, 58Tanzania, 155

Taste and smell improvers, 137Teratomas, 8–9, 15Term neonate, 2, 86Testicular biopsy, 27Testicular leukemia, 18Testis, 90Testosterone, 84Tetrahydrofolate, 134Texas Children’s Hospital, 6Theophylline, 82Therapeutic drug monitoring, 66,

71Therapeutic index, 105, 106Therapy, 9, 10Therapy I for high-risk patients

(HR-I), 42, 44, 51–52Therapy II for high-risk patients

(HR-II), 42, 44, 52–54Therapy III for high-risk patients

(HR-III), 42, 44, 52, 54–55

Thiol group, 97Thiotepa, 162–1633q27, 14413q deletion, 7213q32, 144Thrombocytes, 40Thyroid, 84Tioguanine, 108, 109Tissues, 4, 8, 10, 87, 89, 90,

127, 142compartments, 85repair, 83

TLP−, 23TLP+, 23, 27T lymphocytes, 45Tolerance, 117Topical drugs, 79Topotecan, 92, 93, 96, 144Total body water, 85, 87Total protein, 87Toxic, 88, 100, 115Toxic additive effects, 133Toxic dosage, 106Toxic effects, 34, 126, 132, 134,

140

Index

197

Toxicity(ies), 12, 32, 34, 57, 64, 67–69, 72, 76, 90, 91, 102, 105, 106, 112, 114, 132, 134, 137–146, 151

Toxic metabolites, 99Toxic renal, 134Toxic response, 87Toxoplasmosis, 166Tract colonization, 82Transcriptase–polymerase chain

reaction, 13Transdermally, 79Transient abnormal myelopoiesis,

153Transient leukemia, 7, 152, 153Transient myeloproliferative

disease, 153Transient myeloproliferative

disorder, 148Transit time, 78Translation of chromosomes

(8;14), 19Translocation, 11, 45Translocation of chromosomes

(9;22) (q34;q11), 19Translocations t(9;22) and

t(4;11), 45Transmembrane domains, 90Transplantation, 57, 63, 157–159,

161, 166Transplanted, 58Transplanted nucleated

cells, 161Transport, 90, 91Transporter, 90, 91Transporter proteins, 93Transport proteins, 77, 83, 89–93Transport systems, 82Traumatic lumbar puncture

(TLP), 20, 23Traumatic puncture, 23Treatment, 7, 9–13, 15, 17, 45, 67,

71, 76Treatment protocol, 18Treosulfan, 162Trimethoprim, 134

Trimethoprim–sulfamethoxazole, 164

Trisomy 21 mosaics, 151Trisomy of chromosome 21, 152Tuberculosis, 134Tumoral cells, 91–93Tumor lysis syndrome, 147–149Tumors, 3, 6–15, 64, 76

biopsy, 15bulk, 147cells in vitro, 105lysis, 25, 27, 147–149prognostic factor, 144

2A6, 1342B6, 1342C8, 1342C9, 1342C19, 134

UUmbilical blood supply, 94Umbilical cord blood, 161Unbound bilirubin, 86, 88Unbound fraction, 83

of drugs, 87Unconjugated bilirubin, 69, 86,

88, 89Unique transient leukemia, 152Unrelated donor, 57, 160Unresectable tumors, 14Uptake, 91Urate, 148Ureteral or bladder obstruction,

147Uric acid, 147, 148Uridine diphosphate

glucose (UDPG)-glucuronyltransferase activities, 99

Urinary alkalinization, 102, 146, 147

Urinary pH, 102, 146Urine, 110, 116Urotoxic metabolite, 97USA, 4, 5

Index

198

VVancomycin, 133Varicella, 166Vascular compartment, 83Vascular compromise, 14Vascularized, 80Vascular tumors, 15Vasodilator, 139, 141Vasomotor control, 79Ventilated neonates, 117Ventilation, 117Vertical flow, 107, 108, 111–113Vinblastine, 90, 93, 130, 132–134Vinblastinea, 53Vinca alkaloids, 135Vincristine, 10, 25, 35, 42, 46, 49,

51, 52, 55, 63, 65, 66, 68, 71, 72, 75, 85, 92, 93, 96, 97, 114, 129, 132–134, 136

clearance, 114concentrations, 67dose reduction, 67plasma concentrations, 67

Vinorelbine, 133Viral hepatitis, 40Viscosity-decreasing agent,

138, 140

Vision impairment, 158Vitamin D, 81Vitamin E, 81, 139, 141Vitamins, 90Vomiting, 8, 72, 124Vomiting management, 123Voriconazole, 135, 136

WWater, 79Water in body, 3, 89Water-soluble, 97, 99Water-soluble drugs, 80Weak acids, 102, 146Weak bases, 91, 102, 146White blood cell (WBC),

21–23, 27count, 20, 23, 27, 40

Wilms’ tumor, 6, 66–68, 114Wiskott–Aldrich syndrome, 157

XXanthine oxidase, 125, 126, 147

enzyme, 125

Index