Nathan and Oski's Hematology and Oncology of Infancy and Childhood

1. Introduction - p. 101 2. Bilirubin Metabolism - p. 101 3. Diagnosis of Hyperbilirubinemia - p. 107 4. Toxicity of Unconjugated Hyperbilirubinemia - p. 109 5. Nonpathologic Unconjugated Hyperbilirubinemia - p. 110 6. Disorders of Pathologic Unconjugated Hyperbilirubinemia - p. 111 7. Management and Treatment of Unconjugated Hyperbilirubinemia - p. 118 8. Disorders of Conjugated Hyperbilirubinemia - p. 123 9. References - p. 125 10. Chapter 5 Hemostasis in the Newborn and Infant - p. 128 11. Ontogeny of the Human Hemostatic System - p. 128 12. Clinical Aspects of Developmental Hemostasis - p. 133 13. Conclusion - p. 148 14. Acknowledgment - p. 148 15. References - p. 148 16. Appendix Normal Ranges of Hemostasis Laboratory Tests for Term and Preterm Infants - p. 150.e11 17. Section II Bone Marrow Failure - p. 157 18. Chapter 6 Acquired Aplastic Anemia and Pure Red Cell Aplasia - p. 161 19. Chapter 7 Inherited Bone Marrow Failure Syndromes - p. 182 20. Inherited Bone Marrow Failure Syndromes Associated with Pancytopenia - p. 187 21. Inherited Bone Marrow Failure Syndromes Associated with Isolated Cytopenias - p. 229 22. Acknowledgment - p. 251 23. References - p. 251 24. Chapter 8 Principles of Bone Marrow and Stem Cell Transplantation - p. 254 25. History and Overview - p. 254 26. Conditioning Regimens - p. 256 27. Sources of Stem Cells - p. 258 28. Peritransplant Supportive Care - p. 262 29. Infection Prophylaxis and Treatment - p. 263 30. Immune Reconstitution - p. 265 31. Graft Rejection - p. 265 32. Graft-Versus-Host Disease - p. 266 33. Global Health and Hematopoietic Stem Cell Transplantation - p. 287 34. References - p. 288 35. Section III Disorders of Erythrocyte Production - p. 290.e23 36. Chapter 9 Diagnostic Approach to the Anemic Patient - p. 293 37. Chapter 10 Megaloblastic Anemia - p. 308 38. Definitions - p. 309 39. History - p. 309 40. Folate - p. 309 41. Cobalamin (Vitamin B12) - p. 314 42. Manifestations of Deficiency - p. 319 43. Diagnosis of Deficiency - p. 323 44. Acquired Causes of Cobalamin Deficiency - p. 327 45. Diagnostic Approach to Acquired Causes of Cobalamin Deficiency - p. 332 46. Acquired Causes of Folate Deficiency - p. 332 47. Diagnostic Approach to Acquired Causes of Folate Deficiency - p. 334 48. Treatment of Acquired Deficiencies - p. 334 49. Genetic Disorders Causing Megaloblastic Anemia - p. 336 50. References - p. 342 51. Chapter 11 Disorders of Iron and Copper Metabolism, the Sideroblastic Anemias, and Lead Toxicity - p. 344 52. Physiologic Chemistry of Iron - p. 344 53. Acquisition and Distribution of Iron - p. 346 54. Role of Iron in Cell Proliferation and Differentiation - p. 351 55. Regulation of Proteins of Iron Metabolism - p. 352 56. Extremes of Iron Balance - p. 355 57. Disorders of Iron Utilization - p. 370 58. Sideroblastic Anemias - p. 370 59. Copper Metabolism - p. 375 60. Lead Toxicity - p. 377 61. References - p. 380 62. Chapter 12 Porphyrias - p. 382 63. Formation of the Pyrrole - p. 383 64. Assembly of the Tetrapyrrole - p. 388 65. Modification of the Tetrapyrrole Sidechains - p. 395 66. Enzymatic Oxidation of Protoporphyrinogen IX to Protoporphyrin IX and Insertion of Iron - p. 402 67. References - p. 406 68. Section IV Hemolytic Anemias - p. 408.e10 69. Chapter 13 Autoimmune Hemolytic Anemia - p. 411 70. Chapter 14 Paroxysmal Nocturnal Hemoglobinuria - p. 431 71. Chapter 15 Red Cell Membrane - p. 455 72. Membrane Lipids - p. 455 73. Membrane Proteins - p. 462 74. Integral Membrane Proteins - p. 466 75. Membrane Skeleton Proteins - p. 479 76. Organization of the Membrane Skeleton - p. 498 77. Red Cell Membrane Deformability and Stability - p. 505 78. Membrane Permeability - p. 507 79. Membrane Changes Associated with Aging and Senescence of Red Cells - p. 509 80. References - p. 511 81. Chapter 16 Disorders of the Red Cell Membrane - p. 515 82. Hereditary Spherocytosis - p. 515 83. Hereditary Elliptocytosis and Hereditary Pyropoikilocytosis - p. 548 84. Southeast Asian Ovalocytosis - p. 559 85. Stomatocytosis, Cryohydrocytosis, and Xerocytosis - p. 560 86. Acquired Disorders of Red Cell Membrane Lipids - p. 573 87. References - p. 576 88. Chapter 17 Pyruvate Kinase Deficiency and Disorders of Glycolysis - p. 580 89. Hexokinase Deficiency - p. 582 90. Glucose Phosphate Isomerase Deficiency - p. 585 91. Phosphofructokinase Deficiency - p. 588 92. Aldolase Deficiency - p. 590 93. Triose Phosphate Isomerase Deficiency - p. 591 94. Glyceraldehyde-3-Phosphate Dehydrogenase Deficiency - p. 593 95. Phosphoglycerate Kinase Deficiency - p. 593 96. 2,3-Bisphosphoglycerate Mutase Deficiency - p. 595 97. Monophosphoglycerate Mutase Deficiency - p. 596 98. Enolase Deficiency - p. 596 99. Pyruvate Kinase Deficiency - p. 596 100. Lactate Dehydrogenase Deficiency - p. 603 101. Abnormalities of Erythrocyte Nucleotide Metabolism - p. 603 102. Acquired Disorders of Erythrocyte Glycolysis - p. 606 103. References - p. 606 104. Chapter 18 Glucose-6-Phosphate Dehydrogenase Deficiency - p. 609 105. Chapter 19 Normal and Abnormal Hemoglobins - p. 630 106. Hemoglobin Structure and Function - p. 630 107. Abnormal Hemoglobins - p. 652 108. Conclusion - p. 671 109. Acknowledgements - p. 671 110. References - p. 671 111. Section V Disorders of Hemoglobin - p. 672.e10 112. Chapter 20 Sickle Cell Disease - p. 675 113. Pathophysiology - p. 675 114. Diagnosis - p. 684 115. Clinical Manifestations - p. 685 116. Mortality - p. 702 117. Approaches to Therapy - p. 703 118. Other Sickle Syndromes - p. 711 119. References - p. 713 120. Chapter 21 Thalassemias - p. 715 121. Human Hemoglobins: Composition and Genetics - p. 715 122. Classification of the Thalassemias - p. 722 123. Clinical Heterogeneity of Thalassemia Secondary to Diversity of Mutations - p. 745 124. Prenatal Diagnosis of Thalassemia - p. 767 125. References - p. 768 126. Section VI Phagocyte System - p. 769.e19 127. Chapter 22 Phagocyte System and Disorders of Granulopoiesis and Granulocyte Function - p. 773 128. Definition and Classification of Phagocytes - p. 773 129. Phagocyte Distribution and Structure - p. 773 130. Function of Phagocytes - p. 782 131. Quantitative Granulocyte and Mononuclear Phagocyte Disorders - p. 800 132. Disorders of Granulocyte and Mononuclear Phagocyte Function - p. 819 133. References - p. 845 134. Section VII Immune System - p. 847.e29 135. Chapter 23 Immune Response - p. 851 136. Lymphocyte Development - p. 852 137. Lymphocyte Specificity - p. 853 138. B-Cell Ontogeny - p. 853 139. T-Cell Ontogeny - p. 857 140. The Spleen - p. 862 141. B-Cell Activation and Function - p. 867 142. T-Cell Activation and Function - p. 871 143. Peripheral T-Cell Maturation - p. 878 144. Nonconventional T-Cell Subtypes - p. 881 145. Development and Function of T-Cell Receptor γδ T Cells - p. 882 146. Natural Killer Cell Development and Function - p. 882 147. Conclusions - p. 883 148. References - p. 883 149. Chapter 24 Primary Immunodeficiency Diseases - p. 886 150. Combined Immunodeficiencies - p. 887 151. Management of Combined Immunodeficiency - p. 896 152. Immunodeficiency Syndromes - p. 898 153. Other Immunodeficiencies Associated with Defective Mechanisms of DNA Repair - p. 901 154. Immunodeficiencies with Chromosomal Instability - p. 901 155. Pigmentary Dilution Disorders - p. 901 156. Mutations of the Nuclear Factor κ-B Pathway - p. 902 157. Defects of Toll-Like Receptor Signaling - p. 902 158. The Syndrome of Warts, Hypogammaglobulinemia, Infections, and Myelokathexis - p. 902 159. Hyperimmunoglobulin E Syndrome Caused by STAT3 Mutations - p. 903 160. Autosomal Recessive Hyper-Immunoglobulin E Syndrome Caused by TYK2 Mutations - p. 903 161. Chronic Mucocutaneous Candidiasis - p. 903 162. Immunodeficiencies with Skeletal Abnormalities - p. 903 163. Immunodeficiencies Associated with Disorders of Folate and Cobalamin Metabolism - p. 904 164. GATA2 Deficiency - p. 904 165. Immunodeficiencies with Immune Dysregulation - p. 904 166. Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy Syndrome - p. 904 167. Immune Dysregulation Polyendocrinopathy Enteropathy X-Linked Syndrome - p. 905 168. Defects of IL-2–Mediated Signaling - p. 905 169. Autoimmune Lymphoproliferative Syndrome - p. 905 170. ITCH Deficiency - p. 906 171. Immunodeficiencies with Impaired Cell-Mediated Cytotoxicity - p. 906 172. Familial Hemophagocytic Lymphohistiocytosis - p. 906 173. X-Linked Lymphoproliferative Disease - p. 906 174. IL-2 Inducible Tyrosine Kinase Deficiency - p. 907 175. CD27 Deficiency - p. 907 176. CD16 Deficiency - p. 907 177. Immunodeficiencies with Selective Predisposition to Pathogens - p. 907 178. Humoral Immunodeficiency - p. 908 179. Complement Deficiencies - p. 916 180. References - p. 920 181. Section VIII Storage Diseases - p. 921.e14 182. Chapter 25 Lysosomal Storage Diseases - p. 925 183. Section IX Hemostasis - p. 947.e5 184. Chapter 26 Platelets and the Vessel Wall - p. 951 185. Chapter 27 Blood Coagulation - p. 964 186. Chapter 28 Molecular Basis of Fibrinolysis - p. 984 187. Chapter 29 Approach to the Child with a Suspected Bleeding Disorder - p. 999 188. Chapter 30 Inherited Platelet Disorders - p. 1010 189. Chapter 31 Hemophilia and von Willebrand Disease - p. 1028 190. Hemophilia A and Hemophilia B - p. 1028 191. Von Willebrand Disease - p. 1039 192. References - p. 1053 193. Chapter 32 Rare Hereditary Coagulation Factor Abnormalities - p. 1055 194. Chapter 33 Inherited Disorders of Thrombosis and Fibrinolysis - p. 1062 195. Chapter 34 Acquired Platelet Defects - p. 1076 196. Quantitative Platelet Abnormalities - p. 1076 197. Acquired Defects in Platelet Function - p. 1099 198. References - p. 1101 199. Chapter 35 Acquired Disorders of Hemostasis - p. 1103 200. Section X Supportive Therapy - p. 1124.e6 201. Chapter 36 Transfusion Medicine* - p. 1127 202. Red Blood Cell Transfusions - p. 1127 203. Platelet Transfusions - p. 1142 204. Granulocyte Transfusions - p. 1149 205. Principles of Hematopoietic Cellular Therapy - p. 1149 206. Apheresis - p. 1153 207. Erythrocytapheresis (Red Blood Cell Exchange) for Sickle Cell Disease - p. 1158 208. Leukapheresis - p. 1159 209. Peripheral Blood Progenitor Cells - p. 1160 210. Extracorporeal Photopheresis - p. 1160 211. Plasma Exchange - p. 1160 212. Conclusion - p. 1163 213. References - p. 1163 214. Section XI Hematologic Manifestations of Systemic Diseases - p. 1164.e10 215. Chapter 37 Hematologic Manifestations of Systemic Diseases* - p. 1167 216. Collagen Disorders - p. 1168 217. Infectious Diseases - p. 1170 218. Cardiac Disease - p. 1182 219. Pulmonary Disease - p. 1184 220. Renal Disease - p. 1185 221. Gastrointestinal Disease - p. 1187 222. Endocrine Disorders - p. 1190 223. Metabolic Diseases - p. 1192 224. Neurologic and Psychiatric Disorders - p. 1194 225. Cutaneous Diseases - p. 1196 226. Pregnancy - p. 1197 227. Toxins and Other Insults - p. 1199 228. References - p. 1201 229. Chapter 38 Hematologic Manifestations of Systemic Diseases in Children of the Developing World - p. 1203 230. Volume II - p. 1225.e5 231. Section XII Biology of Cancer - p. 1225.e5 232. Chapter 39 Origins and Evolution of Pediatric Cancers - p. 1229 233. Chapter 40 Epidemiology of Leukemia in Childhood - p. 1239 234. Chapter 41 Informatics - p. 1257 235. Chapter 42 Genetic Predisposition to Cancer - p. 1270 236. Chapter 43 Genetics and Epigenetics of Childhood Cancers - p. 1294 237. Chapter 44 Targeted Therapies in Oncology - p. 1302 238. Traditional Chemotherapy - p. 1302 239. Introduction to Targeted Therapy - p. 1304 240. New and Emerging Opportunities in Pediatric Cancer - p. 1320 241. Conclusions - p. 1334 242. References - p. 1335 243. Chapter 45 Cytogenetic and Molecular Pathology of Pediatric Cancer - p. 1337 244. Cytogenetic and Molecular Methodologies - p. 1344 245. Genomic Mechanisms in Pediatric Tumors - p. 1355 246. Biologic Consequences of Chromosomal Translocation - p. 1358 247. Biologic Basis for Specificity of Balanced Chromosomal Rearrangements: Diagnostic Relevance - p. 1363 248. Cytogenetic and Molecular Pathology: Major Tumor Types - p. 1364 249. Conclusion - p. 1400 250. References - p. 1400 251. Section XIII Pediatric Cancer Therapeutics - p. 1401.e20 252. Chapter 46 Cancer Chemotherapy for Pediatric Patients - p. 1405 253. Chemotherapeutic Agents - p. 1405 254. Clinical Application of Chemotherapy - p. 1413 255. Chemotherapy in Children - p. 1414 256. Pharmacokinetic Changes during Childhood - p. 1414 257. Drug Interactions - p. 1420 258. Pharmacogenetics and Pharmacogenomics of Chemotherapeutic Agents in Children - p. 1423 259. New Drug Development - p. 1435 260. Strategies to Improve the Therapeutic Index - p. 1439 261. Conclusion and Perspectives - p. 1443 262. References - p. 1443 263. Chapter 47 Immunotherapy of Cancer - p. 1446 264. Chapter 48 Pediatric Radiation Oncology - p. 1474 265. Chapter 49 Pediatric Surgical Oncology - p. 1489 266. Section XIV Hematologic Malignancy - p. 1523.e7 267. Chapter 50 Acute Lymphoblastic Leukemia - p. 1527 268. Classification - p. 1527 269. Molecular Pathogenesis - p. 1531 270. Clinical Manifestations - p. 1535 271. Differential Diagnosis and Prognosis - p. 1537 272. Therapy - p. 1541 273. Complications of Treatment - p. 1547 274. Relapsed Acute Lymphoblastic Leukemia - p. 1550 275. Future Directions - p. 1552 276. References - p. 1552 277. Chapter 51 Pediatric Myeloid Leukemia, Myelodysplasia, and Myeloproliferative Disease - p. 1555 278. Acute Myelogenous Leukemia - p. 1555 279. Acute Promyelocytic Leukemia - p. 1590 280. Down Syndrome with Transient Disorder and Acute Myelogenous Leukemia - p. 1594 281. Myelodysplastic Syndromes - p. 1597 282. Myeloproliferative Disorders - p. 1602 283. Conclusion - p. 1611 284. References - p. 1612 285. Chapter 52 Infant Leukemias - p. 1614 286. Chapter 53 Pediatric Lymphoma - p. 1626 287. Lymphadenopathy - p. 1626 288. Emergencies in Patients with Newly Diagnosed Lymphoma - p. 1627 289. Hodgkin Lymphoma - p. 1628 290. Non-Hodgkin Lymphoma - p. 1648 291. Posttransplantation Lymphoproliferative Disease - p. 1668 292. Conclusion and Future Directions in Pediatric Lymphoma - p. 1670 293. References - p. 1672 294. Section XV Solid Tumors - p. 1672.e15 295. Chapter 54 Neuroblastoma - p. 1675 296. Epidemiology - p. 1675 297. Pathogenesis - p. 1676 298. Pathology - p. 1689 299. Clinical Presentation - p. 1691 300. Diagnosis and Evaluation - p. 1693 301. Risk Stratification - p. 1695 302. Approach to Treatment - p. 1698 303. Novel Therapies - p. 1706 304. Conclusions and Future Directions - p. 1712 305. References - p. 1712 306. Chapter 55 Pediatric Renal Tumors - p. 1714 307. Pathology of Pediatric Renal Tumors - p. 1714 308. Wilms Tumor (Nephroblastoma) - p. 1726 309. Clear Cell Sarcoma of the Kidney - p. 1738 310. Malignant Rhabdoid Tumor - p. 1739 311. Renal Cell Carcinoma - p. 1741 312. Congenital Mesoblastic Nephroma - p. 1743 313. Future Directions - p. 1744 314. References - p. 1744 315. Chapter 56 Retinoblastoma - p. 1747 316. Epidemiology - p. 1747 317. Biology of Retinoblastoma - p. 1748 318. Genetic Counseling for Families with Retinoblastoma - p. 1753 319. Pathology of Retinoblastoma - p. 1753 320. Clinical Manifestations of Retinoblastoma - p. 1754 321. Diagnosis and Extent of Disease Evaluations in Retinoblastoma - p. 1757 322. Staging of Retinoblastoma - p. 1757 323. Principles of Treatment of Retinoblastoma - p. 1759 324. Treatment of Intraocular Retinoblastoma - p. 1766 325. Treatment of Extraocular Retinoblastoma - p. 1770 326. Long-Term Effects of Retinoblastoma and Its Treatment - p. 1772 327. Other Long-Term Effects - p. 1776 328. References - p. 1777 329. Chapter 57 Tumors of the Brain and Spinal Cord - p. 1779 330. Epidemiology - p. 1780 331. Neurodevelopment - p. 1782 332. Conceptual Organization of Pediatric Brain Tumors - p. 1789 333. Imaging Studies - p. 1792 334. Neuropathology - p. 1796 335. Treatment Strategies - p. 1798 336. Pediatric Brain Tumors - p. 1806 337. Late Effects of Treatment - p. 1880 338. Palliative Care - p. 1885 339. References - p. 1885 340. Chapter 58 Hepatoblastoma and Other Liver Tumors in Children - p. 1886 341. Chapter 59 Rhabdomyosarcoma - p. 1906 342. Pathologic Classification of Rhabdomyosarcoma - p. 1906 343. Rhabdomyosarcoma in Cancer Predisposition Syndromes - p. 1908 344. Genetics of Sporadic Rhabdomyosarcoma - p. 1909 345. Applications of Molecular Genetic Approaches to Diagnosis and Prognosis - p. 1915 346. Molecular and Cellular Biology of Rhabdomyosarcoma - p. 1917 347. Preclinical Investigation of Emerging Drug Targets for Rhabdomyosarcoma - p. 1923 348. Clinical Research on Rhabdomyosarcoma - p. 1926 349. Incidence and Epidemiology - p. 1927 350. Clinical Presentation and Evaluation - p. 1927 351. Risk Group Classification - p. 1929 352. Treatment - p. 1931 353. Follow-Up after Treatment - p. 1942 354. Future Directions - p. 1943 355. References - p. 1944 356. Chapter 60 Nonrhabdomyosarcoma Soft Tissue Sarcomas and Other Soft Tissue Tumors - p. 1946 357. Epidemiology - p. 1949 358. Presentation and Evaluation - p. 1950 359. Staging and Grading - p. 1951 360. Treatment - p. 1954 361. General Biologic Features - p. 1955 362. Adipocytic Tumors - p. 1955 363. Fibroblastic and Myofibroblastic Tumors - p. 1956 364. So-Called Fibrohistiocytic Tumors - p. 1963 365. Smooth Muscle Tumors - p. 1964 366. Vascular Tumors - p. 1965 367. Chondroosseous Tumors - p. 1968 368. Tumors of Uncertain Differentiation - p. 1970 369. Neuroectodermal Tumors - p. 1978 370. Undifferentiated Tumors - p. 1980 371. References - p. 1981 372. Chapter 61 Ewing Sarcoma - p. 1983 373. Epidemiology - p. 1983 374. Biologic Features - p. 1985 375. Clinical Presentation and Diagnosis - p. 1993 376. Prognostic Factors - p. 1997 377. Treatment of Patients with Nonmetastatic Ewing Sarcoma - p. 2000 378. Treatment of Patients with Metastatic Ewing Sarcoma - p. 2009 379. Recurrent Ewing Sarcoma - p. 2012 380. Late Effects in Patients Treated for Ewing Sarcoma - p. 2014 381. Future Directions - p. 2015 382. References - p. 2015 383. Chapter 62 Osteosarcoma - p. 2018 384. Epidemiology - p. 2018 385. Etiology - p. 2020 386. Clinical Presentation and Evaluation - p. 2022 387. Pathology and Staging - p. 2026 388. Natural History and Prognosis - p. 2029 389. Biology - p. 2031 390. Treatment - p. 2043 391. Conclusion and Future Directions - p. 2053 392. References - p. 2054 393. Chapter 63 Pediatric Germ Cell Tumors - p. 2056 394. Development of the Germline - p. 2057 395. Histopathology of Germ Cell Tumors - p. 2059 396. Teratoma - p. 2061 397. Yolk Sac Tumor - p. 2063 398. Seminoma and Dysgerminoma - p. 2064 399. Embryonal Carcinoma - p. 2065 400. Choriocarcinoma - p. 2065 401. Mixed Ovarian Germ Cell Tumor - p. 2066 402. Summary of Pathology - p. 2066 403. Epidemiology of Pediatric Germ Cell Tumors - p. 2066 404. Molecular Biology of Germ Cell Tumors - p. 2069 405. Diagnosis and Staging of Pediatric Germ Cell Tumors - p. 2073 406. Surgery and Germ Cell Tumor - p. 2078 407. Prognostic Factors at Diagnosis of Pediatric Germ Cell Tumors - p. 2081 408. Treatment - p. 2081 409. Treatment of Stage I Malignant Nonseminomatous Germ Cell Tumors - p. 2083 410. Relapse and Salvage Therapy - p. 2093 411. Late Effects - p. 2096 412. Conclusions - p. 2098 413. References - p. 2098 414. Chapter 64 Histiocytoses - p. 2100 415. Chapter 65 Rare Tumors of Childhood - p. 2123 416. Chapter 66 Imaging in the Evaluation and Management of Childhood Cancer - p. 2146 417. Technical Considerations - p. 2147 418. Staging Considerations - p. 2154 419. Central Nervous System Tumors - p. 2154 420. Pulmonary and Intrathoracic Tumors - p. 2166 421. Gastrointestinal Tumors - p. 2182 422. Genitourinary Tumors - p. 2196 423. Adrenal/Suprarenal Tumors - p. 2204 424. Germ-Cell Tumors - p. 2211 425. Musculoskeletal Neoplasms - p. 2216 426. Lymphoproliferative Neoplasms - p. 2224 427. Imaging Treatment Complications - p. 2236 428. Interventional Radiology in Pediatric Oncology - p. 2238 429. New Imaging Techniques - p. 2248 430. Surveillance Imaging - p. 2251 431. Conclusion - p. 2252 432. References - p. 2252 433. Section XVI Supportive Care - p. 2254.e11 434. Chapter 67 Infectious Disease in the Pediatric Cancer Patient - p. 2257 435. Chapter 68 Oncologic Emergencies - p. 2267 436. Chapter 69 Nursing Care of Patients with Childhood Cancer - p. 2292 437. History of Pediatric Oncology Nursing - p. 2292 438. Overview of the Pediatric Oncology Nurse's Role - p. 2293 439. Caring for Patients and Families during the Diagnostic Phase - p. 2296 440. Nursing Implications of Pediatric Cancer Treatment - p. 2297 441. Pharmaceutical Advances - p. 2308 442. Supporting Patients and Families at the End of Treatment - p. 2308 443. Nursing Care of Childhood Cancer Survivors - p. 2309 444. Supporting Patients and Families during Relapse and Recurrence - p. 2311 445. Nursing Care of Children at the End of Life - p. 2312 446. Ethical Nursing Practice - p. 2315 447. Future Trends in Oncology Nursing - p. 2316 448. References - p. 2318 449. Chapter 70 Palliative Care in Pediatric Oncology - p. 2321 450. Chapter 71 Symptom Management in Children with Cancer - p. 2349 451. Pain - p. 2350 452. Nausea and Vomiting - p. 2369 453. Other Gastrointestinal Symptoms - p. 2381 454. Dyspnea - p. 2384 455. Cough - p. 2386 456. Fatigue - p. 2386 457. Pruritus - p. 2391 458. Mood Disorders and Mental Status Changes - p. 2393 459. References - p. 2394 460. Chapter 72 Childhood Cancer Survivorship - p. 2397 461. History and Overview - p. 2397 462. Second Cancers - p. 2403 463. Hematologic Malignancies - p. 2409 464. Organ System Late Effects - p. 2410 465. Other Late Effects - p. 2423 466. Special Considerations for the Hematopoietic Stem Cell Transplant Survivor - p. 2424 467. Follow-Up Care of Childhood Cancer Survivors - p. 2424 468. Future Directions - p. 2431 469. References - p. 2432 470. Chapter 73 Psychosocial Care of the Child and Family - p. 2435 471. Chapter 74 Ethical Considerations in Pediatric Oncology Clinical Trials - p. 2460 472. Appendices Reference Values in Infancy and Childhood - p. 2484 473. Index - p. I1