Acute Leukemias - Republican Scientific Medical Library

More documents

Recommendations

Info

a 5.3 · Etiology 83 5.3.1.2 Cytogenetic Abnormalities Cytogenetic abnormalities frequently found in ALL cases include germ-line karyotypic abnormalities, somatic karotypic abnormalities, translocations, and deletions. The germ-line abnormalities associated with childhood leukemia include Down syndrome (trisomy 21) [64, 118, 144], Bloom syndrome [64], Fanconi anemia, Klinefelter syndrome, and ataxia-telangiectasia [37]. The somatic abnormalities associated with childhood leukemia include aneuploidy (in one form or another in 92% of childhood ALL cases), pseudodiploidy (in 41.5% of ALL cases) and hyperdiploidy (in 20–30% of pre-B ALL and about 90% of early pre-B ALL) [108, 127]. Translocations frequently found in ALL cases include the TEL-AML1 translocation (found in about 20–25% of B-lineage childhood ALLs) [11, 34, 91, 95, 125]; MLL translocations (found in about 70–80% of infant leukemias [16, 53, 94, 109, 126], but less commonly in other leukemias, both childhood and adult); MLL- AF4 gene fusion (very common in infant ALL and also found in ALL of older children); and other translocations occurring in childhood ALL including t(9, 11)(p22;q23) [16, 53] and t(11, 19) [46], and CDK6-MLL [112]. TEL-AML1 is found in about 1% of cord blood specimens, yet only about 1% of those with this translocation will develop ALL in childhood. Deletion of 6q occurs in 11% of childhood ALL cases [108]. Among childhood ALL cases with t(12, 21), 77% also have 12p12–13 deletions [15]. In short, the chromosomes that are known to be involved in karyotypic abnormalities found in childhood ALL are 1, 4, 6–9, 11, 12, 14, 19, 21, and 22. Neither X nor Y is known to be involved with childhood ALL. Translocations are especially common in childhood ALL. Triggers for molecular anomalies may be inherited during pregnancy, and may develop during infancy or early childhood [13]. 5.3.1.3 Infectious Etiology The most widely accepted current theory of causation of childhood ALL is based on an infectious etiology associated with decreased immune function. Three variations on this theme of the “infection” that have been put forward are (1) exposure to a specific infectious agent postnatally, proposed by Kinlen [56], (2) exposure to a specific infectious agent prenatally or around the time of birth, proposed by Smith [137], or (3) a delay in the initial exposure to infectious agents in general beyond the first year of life, proposed by Greaves [39]. A recent review of this topic is provided by McNally and Eden [88], but does not resolve the controversy. We provide a brief review of some of the literature supporting each of these hypotheses. 5.3.1.4 Postnatal Infection by a Specific Leukemogenic Pathogen According to Kinlen’s hypothesis [56, 57], “outbreaks” of ALL follow epidemics of some common (and perhaps subclinical) infection, of which ALL is a rare outcome. These outbreaks tend to occur when infectious and susceptible populations come into close proximity or intermingle (“population mixing”), thus facilitating the spread of the pathogen. In relatively rural, isolated populations it is more likely that a sizeable portion of the population has not previously been exposed to the infectious agent, and thus is susceptible. Kinlen and colleagues have published many studies that are consistent with this theory. For example, he has documented high rates of leukemia mortality among preschool children in Kirkcaldy, following a rapid population increase due to the construction of the new town of Glenrothes [56], and excess leukemia mortality in five rural British New Towns founded between 1946 and 1950, which brought together new residents from a variety of isolated (i.e., low-density) rural settings. The statistically significant excess leukemia mortality was seen in rural towns for the time period 1946–1965 but not 1966–1985, consistent with the population mixing hypothesis. The excess leukemia mortality was not seen in overspill towns, which were less rural and had smaller rates of in-migration, also supporting the population mixing hypothesis. The relationship between population influx and childhood ALL received further support from a Cumbria-based study of children of “incomers” (both parents born outside Cumbria), who were at higher risk of common ALL than children of “local residents” (at least one parent born inside Cumbria) [21]. Studies in other countries found similar effects, such as extraordinarily high childhood leukemia mortality rates in Italy and Greece during 1958–1987, which have been attributed to high levels of population mixing associated with massive rural-to-urban migration in the years following World War II [59]; a study in Hong Kong
84 Chapter 5 · <strong>Acute</strong> Lymphoblastic Leukemia: Epidemiology and Etiology that showed evidence of statistically significant clustering of ALL in preschool children in small geographic regions (TPUs) in the highest decile of population growth during 1981–1991 [5]; a Canadian study in which leukemia incidence among children under 5 years of age was higher than expected in rural areas where the population grew, and lower than expected in growing urban areas [62]; and a US study using data from the SEER program that showed that rural counties with the greatest increase in population from 1980–1989 had the highest childhood leukemia incidence rates [153]. In contrast, in a study conducted in France, leukemia mortality rates were average among preschool children who resided in 43 rapidly-growing French administrative units (communes) [69]. 5.3.1.5 Prenatal Infection by a Specific Leukemogenic Pathogen According to Smith’s hypothesis [136, 137], high rates of ALL are attributable to in utero exposures to infections that result mainly in cases of precursor B-cell ALL. To investigate this hypothesis, several studies have compared ALL rates among children of mothers who reported infections during pregnancy to children of mothers who did not report infections during pregnancy. Early studies have been reviewed by Little [78] and show equivocal results. For example, the Oxford Survey of Childhood Cancers, a matched case-control study in England and Wales, found that children of mothers ill with an infective disease during pregnancy had increased rates of childhood malignancies (13 cases among mothers with infections during pregnancy versus 1 case among control mothers) [144]. However, in a more recent and more focused matched case-control study in Scotland, infection (any, respiratory tract, viral, genitourinary, or fungal) during pregnancy did not statistically significantly affect the risk of ALL in children ages 0 to 14 [85]. Similarly, a study by Infante-Rivard et al. looking at recurrent maternal infections did not find a statistically significant association with ALL in children [47]. However, a study of maternal lower genital tract infection reported a statistically significant association [99], as did a study of mothers with Epstein-Barr virus (EBV) [72]. 5.3.1.6 Delayed Exposure to Pathogens in General Greaves’ hypothesis is that secondary mutations and/or proliferation due to early exposure to general infectious agents transmitted from parents, siblings, and other contacts early in life will tend to reduce the risk of childhood ALL. This is because he believes that ALL is a consequence of two independent mutations: the first occurring in utero or shortly after birth, and the second occurring between 2 and 6 years of age that may be triggered by infection [35, 38]. Supporting this theory is the observation that the majority of childhood ALL cases diagnosed between ages 2 and 6 have the TEL/AML1 mutation. For example, in one study, eight of 12 children ages 2 to 5 recently diagnosed with TEL-AML1-positive ALL, including a pair of twins, were found to have TEL-AML1 fusion in the neonatal blood spots on their Guthrie cards, and the twins shared the same TEL- AML1 sequence (Wiemels et al. 1999 a). This is interpreted to be the first of the two mutations in Greaves’ theory. His theory supposes that a second mutation occurs in early childhood, causing ALL. The second mutation may be promoted by common infections. Further, relative isolation, as in Kinlen’s hypothesis, may delay exposures to common infections, enabling the susceptible preleukemic cells to multiply, increases the likelihood of occurrence of the second mutation. Various sources of childhood infection, or protection from infection, have been considered in light of this hypothesis. Breast feeding, an opportunity for infectious exposure after birth, tends to show decreased risk of ALL, although this effect may be confounded by SES, according to McNally [88], as cases in these studies tended to have lower SES. As a counter example, researchers have shown that attendance at a day care facility increases a child’s risk of infection, and thus should increase their risk of ALL according to this theory, but was found to be protective. However, as with breast feeding, SES may be a confounder as cases tended to have lower SES. Other sources of infectious exposures, such as older siblings, parents with occupations that bring them into contact with many people, and migration, also tend to be protective [88]. Studies have also found associations of allergies and asthma with ALL [139, 154]. Finally, seasonality may suggest an infectious etiology. Various authors have examined the seasonal pat-
Page 1 and 2:
E.H. Estey · S.H. Faderl · H. M.
Page 3 and 4:
E. H. Estey Department of Leukemia
Page 5 and 6:
VI Table of Contents 14 Philadelphi
Page 7 and 8:
VIII Contributors S. H. Faderl Depa
Page 9 and 10:
X Contributors D. Wartenberg Depart
Page 11 and 12:
Therapy of AML Elihu Estey Contents
Page 13 and 14:
a 1.2 · Standard Therapy 3 Table 1
Page 15 and 16:
a 1.2 · Standard Therapy 5 Table 1
Page 17 and 18: a 1.2 · Standard Therapy 7 tween G
Page 19 and 20: a 1.2 · Standard Therapy 9 Fig. 1.
Page 21 and 22: a 1.2 · Standard Therapy 11 of tre
Page 23 and 24: a 1.2 · Standard Therapy 13 Table
Page 25 and 26: a 1.2 · Standard Therapy 15 permit
Page 27 and 28: a References 17 19. Care RS, Valk P
Page 29 and 30: a References 19 6-thioguanine in th
Page 31 and 32: Acute Myeloid Leukemia: Epidemiolog
Page 33 and 34: a 3.1 · Epidemiology 49 3.1.4 Gend
Page 35 and 36: a 3.2 · Etiology 51 part of the in
Page 37 and 38: a 3.2 · Etiology 53 for the develo
Page 39 and 40: a References 55 38. Crane MM, Stom
Page 41 and 42: Relapsed and Refractory Acute Myelo
Page 43 and 44: a 4.2 · Prognostic Factors in Pati
Page 45 and 46: a 4.3 · Treatment of Relapsed and
Page 47 and 48: a 4.4 · Hematopoietic Stem Cell Tr
Page 49 and 50: a 4.6 · Gemtuzumab Ozogamicin 65 T
Page 51 and 52: a 4.7 · Relapsed and Refractory Ac
Page 53 and 54: a 4.7 · Relapsed and Refractory Ac
Page 55 and 56: a References 71 The ability of immu
Page 57 and 58: a References 73 39. Vogler WR, McCa
Page 59 and 60: a References 75 95. Sievers EL, Lar
Page 61 and 62: Part II - Acute Lymphoblastic Leuke
Page 63 and 64: 78 Chapter 5 · Acute Lymphoblastic
Page 67: 82 Chapter 5 · Acute Lymphoblastic
Page 79 and 80: Molecular Biology and Genetics Meir
Page 81 and 82: a 6.3 · Structural Aberrations 97
Page 83 and 84: a 6.3 · Structural Aberrations 99
Page 85 and 86: a 6.5 · Molecular Aberrations 101
Page 87 and 88: a References 103 clear that homozyg
Page 89 and 90: a References 105 53. Chim CS, Tam C
Page 91 and 92: a References 107 122. Lennard L, Li
Page 93 and 94: Diagnosis of Acute Lymphoblastic Le
Page 95 and 96: a 8.3 · Cytochemistry and Immunoph
Page 97 and 98: a 8.5 · Cytogenetic and Molecular
Page 99 and 100: a 8.5 · Cytogenetic and Molecular
Page 101 and 102: a References 127 including the reti
Page 103 and 104: a References 129 47. Kita K, Shirak
Page 105 and 106: Acute Lymphoblastic Leukemia: Clini
Page 107 and 108: a 7.3 · Diagnosis 111 or neoplasti
Page 109 and 110: a 7.3 · Diagnosis 113 Fig. 7.2. Hi
Page 111 and 112: a 7.3 · Diagnosis 115 The vast maj
Page 113 and 114: a References 117 dren: Biologic bas
Page 115 and 116: General Approach to the Therapy of
Page 117 and 118: a 9.3 · New Agents 133 dose methot
Page 119 and 120:
a References 135 4. Gökbuget N, Ho
Page 121 and 122:
138 Chapter 10 · Recent Clinical T
Page 123 and 124:
Page 125 and 126:
Page 127 and 128:
Page 129 and 130:
146 Chapter 11 · Conventional Ther
Page 131 and 132:
Page 133 and 134:
Page 135 and 136:
Page 137 and 138:
Page 139 and 140:
Page 141 and 142:
Page 143 and 144:
ALL Therapy: Review of the MD Ander
Page 145 and 146:
a 12.2 · The Hyper-CVAD Regimen in
Page 147 and 148:
a 12.3 · Subset-Specific Approache
Page 149 and 150:
Treatment of Adult ALL According to
Page 151 and 152:
a 13.2 · Therapy for Younger (15-6
Page 153 and 154:
a 13.3 · Therapy of Ph/BCR-ABL-Pos
Page 155 and 156:
a 13.5 · Prognostic Factors 173 13
Page 157 and 158:
a References 175 Only patients with
Page 159 and 160:
Philadelphia Chromosome-Positive Ac
Page 161 and 162:
a 14.2 · Molecular Biology of the
Page 163 and 164:
a 14.3 · Treatment of Ph+ ALL 181
Page 165 and 166:
a 14.4 · Hematopoietic Stem Cell T
Page 167 and 168:
a References 185 2. Kurzrock R, Sht
Page 169 and 170:
a References 187 56. Mori T, Manabe
Page 171 and 172:
a References 189 acute lymphoblasti
Page 173 and 174:
192 Chapter 15 · Burkitt’s Acute
Page 175 and 176:
Page 177 and 178:
Page 179 and 180:
Page 181 and 182:
Page 183 and 184:
Page 185 and 186:
204 Chapter 16 · Treatment of Lymp
Page 187 and 188:
Page 189 and 190:
Page 191 and 192:
Page 193 and 194:
Page 195 and 196:
Page 197 and 198:
216 Chapter 17 · The Role of Allog
Page 199 and 200:
Page 201 and 202:
Page 203 and 204:
Page 205 and 206:
Page 207 and 208:
Page 209 and 210:
Page 211 and 212:
230 Chapter 18 · The Role of Autol
Page 213 and 214:
Page 215 and 216:
Page 217 and 218:
Page 219 and 220:
238 Chapter 19 · Novel Therapies i
Page 221 and 222:
Page 223 and 224:
Page 225 and 226:
Page 227 and 228:
Page 229 and 230:
248 Chapter 20 · Minimal Residual
Page 231 and 232:
Page 233 and 234:
Page 235 and 236:
Page 237 and 238:
Page 239 and 240:
Page 241 and 242:
Page 243 and 244:
Page 245 and 246:
264 Chapter 21 · Central Nervous S
Page 247 and 248:
Page 249 and 250:
Page 251 and 252:
Page 253 and 254:
Page 255 and 256:
Page 257 and 258:
276 Chapter 22 · Relapsed Acute Ly
Page 259 and 260:
278 Chapter 22 · Relapsed Acute Ly
Page 261 and 262:
Emergencies in Acute Lymphoblastic
Page 263 and 264:
a 23.5 · Hyperleukocytosis 283 LA
Page 265 and 266:
a 23.9 · Neurological Complication
Page 267 and 268:
a References 287 29. Hingorani AD,
Page 269 and 270:
Subject Index A aberrant methylatio
Page 271 and 272:
a Subject Index 291 CREB, see enhan
Page 273 and 274:
a Subject Index 293 MUD, see matche
show all

Acute Leukemias - Republican Scientific Medical Library

Create successful ePaper yourself

Delete template?

Save as template?