Page 1438 - Williams Hematology ( PDFDrive )

1412 Part X: Malignant Myeloid Diseases Chapter 88: Acute Myelogenous Leukemia 1413

TABLE 88–11. Prognostic Factors in Acute Myelogenous Leukemia
Better prognosis than average of all patients hemopathy may relapse as a smoldering leukemia. It then
Early blast clearance during remission induction therapy 1167,1168 reverts to AML but can be treated with remissions lasting several
years
1199–1203
Leukemic cells contain t(8;21), t(15;17), inv(16) t(16;16), trisomy 9
21 282,284,1169 Higher white cell count: Count >30 × 10 /L or a blast cell count
1204–1206
9
>15 × 10 /L
CEBPA mutations in cytogenetically normal AML 1170 Very low platelet count (<30 × 10 /L) 1205
9
Absence of exaggerated dysmyelopoiesis 1170 High serum lactic dehydrogenase 1207
Residual normal metaphases admixed with clonal cytogenetic
abnormalities 1172 High stem cell mobilizing capacity during complete remission
predicts for relapse risk
1208
High telomerase activity levels 1173 Another medical disorder: extreme obesity, diabetes mellitus,
Low levels of TdT expression by flow cytometry (<5%) 1172 chronic renal disease.
High BAX expression 1175 and high BAX/BCL-2 ratios 1176 Low serum albumin or prealbumin
High expression of integrin CD11b 1177 Need for intubation or ventilator support during induction
Absence of VLA-4 expression on AML blast cells 1178 therapy 1209
High levels of soluble VCAM-1 binding to AML blast cells 1179 Autonomous clonal growth of leukemic blast cells 1210
High levels of caspase-3 1180 High BCL-2 expression 1211,1212
Mutant CEBPA expression 1181 High MCL-1 expression: Elevated at the time of leukemic relapse.
NPM1 gene expression in adults or children (usually present in Suggests prognostic importance or that chemotherapeutic reg-
cytogenetically normal cases) 1182 imen selects for leukemia cells with elevated levels of apoptosis
1213
Higher neutrophil and higher platelet counts at time of com- inhibitors 1214
plete remission 1183 Low expression of retinoblastoma gene
<5% blasts on day 14 marrow predicts for complete remission High levels of WAF/Cip1 protein: This is a regulator at the G 1
1215
but not for overall survival 1184 checkpoint of cell cycle
MiR-181a expression in NK AML 1185 High CD34 expression: High CD34 antigen expression often in
1216
High methylation levels of polycomb group genes 1186 AML subtypes M0, M1, and M4. Remission rate of 61% vs.
to 88% in AML not expressing CD34. Correlation is stronger
Poorer prognosis than average of all patients between high-intensity expression of CD34 and lower remission
rate. 1216–1217 CD34 expression in APL 1218
Older age: Age at the time of diagnosis has the greatest impact 1219
on the probability of remission and on duration of survival. Chil- GATA-1 expression
dren in the first 15 years of life, exclusive of the neonatal period, Neural cell adhesion molecule (CD56) expression 1220
have the highest rate of remission and longest relapse-free remis- Elevated soluble L-selectin: Seen especially in extramedullary
sion; patients older than age 60 years have only half the chance disease 1221
of a young adult to enter remission and less likelihood of a long 1222
relapse-free remission. 1137 There is a gradient of poor response to Higher expression of interleukin (IL)-1β gene
treatment through adulthood, with the largest decrease after the Low FMS expression 1222
sixth decade of life Expression of the thrombopoietin receptor (c-MPL) mRNA 1223
Unfavorable karyotypes: The cytogenetic pattern of leukemic FLT3 mutations 1224,1225
blast cells influences outcome, but the relationship is com- Increased angiogenesis/vascular endothelial growth factor
plex. 212–284 The presence of –5, –7, 5q–, 7q–, or of exaggerated levels 1226
hyperdiploidy (>47 chromosomes), trisomy 8, t(6;9), trisomy 11,
and multiple chromosomal abnormalities in leukemic cells are High β -microglobulin levels in adults younger than 60 years
2
poor prognostic signs. old 1227
Multidrug resistance phenotype: Leukemic cells expressing P- MN1 (meningioma 1) gene overexpression in AML patients with
glycoprotein, a unidirectional drug efflux pump, encoded by the normal cytogenetics 1228
MDR1. 1187 Expression of this gene product can result in decreased Young adults with the genotype WT1(mutation)/FLT3-ITD(pos-
accumulation of anthracyclines, amsacrine, mitoxantrone, and itive) have a lower complete remission rate and an inferior
etoposide. Expression of P-glycoprotein does not influence out- relapse-free and overall survival compared to those with the
come of treatment, but if rhodamine-123 efflux also is increased, genotype WT1(mutation)/FLT3-ITD(negative) 1229
relapse is more common. 1188–1191 Frequently observed in AML cells WT1 gene mutations in patients with AML and a normal
after relapse. Associated with CD34 expression and chromosome karyotype 1230,1231
7 abnormalities. 1190 Alternative non–MDR1-mediated drug efflux
mechanisms are important also. 1191–1194 MDR1 expression is low in Patients with AML with a large number of AML stem cells
favorable prognosis subtypes of AML 1195 Elevated expression of IL-3Rα 1232
Presence of mutated KIT with t(8;21): Associated with higher MLL tandem duplications 1233 and 11p23/MLL abnormalities 1234
relapse risk and poorer overall survival 1196 CD56 expression in APL. 1235 High incidence of CNS involvement,
Prior clonal hemopathy: Chemotherapy or radiotherapy remis- especially with CD7 expression. 1236 Also contributes to poorer
sion rates are one-third to one-half that of de novo AML in the outcomes in t(8;21) cases 1237
same age group. Remission duration is shorter with remissions P15 methylation 1238
>3 years very uncommon. 1197–1198 AML developing from the clonal
(continued)

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