Page 1434 - Williams Hematology ( PDFDrive )

1408 Part X: Malignant Myeloid Diseases Chapter 88: Acute Myelogenous Leukemia 1409

standard induction chemotherapy is unacceptable given the less than newborn usually is normal after intensive chemotherapy for AML dur-
1 year median survival expected. 1063 Lower-dose regimens can also be ing pregnancy, if therapy is started after the first trimester. 1072,1077,1078
toxic and can lead to severe cytopenias. Use of colony-stimulating fac- Vaginal delivery should be used whenever possible. Pregnant women
tor permits older patients to tolerate full-dose induction therapy. The with AML who enter remission have little difficulty with childbirth or
Medical Research Council of the United Kingdom observed remis- postparturition. The remission rates of AML are approximately the rates
sion rates of 80 percent in children, 70 percent in adults younger than expected for the age group, and long-term remissions can occur with
50 years of age, 68 percent in adults 50 to 59 years old, 53 percent in current therapy. Leukemic infiltrates can be found on the maternal side
adults 60 to 69 years old, 39 percent in adults 70 to 75 years old, and of the placenta, but usually not in the villi. One case of maternal-to-fetal
22 percent in adults older than 75 years of age. 1064 In one study of transmission of AML has been documented. 1080 Transmission of AML
patients older than 60 years of age, the 2-, 5-, and 10-year survivals were from one identical twin to another through a shared placental circula-
22, 11, and 8 percent, respectively. 1065,1066 The older patients who remain tion accounts for the dual occurrence in twins in the first several years
177
free of leukemia beyond 1 year have a reasonable quality of life. 1067,1068 of life. There are reports of the use of ATRA for APL treatment during
The National Cancer Institute 5-year relative survival rates for patients pregnancy, but use during the first trimester is discouraged, and data
with AML are 11 percent for adults ages 65 to 74 years and 1.8 percent are sparse. 941,1081,1082
for adults ages 75 years and older. 1069
Even though t(8;21) and inversion 16 are rare in older AML
patients, remission rates are high with these favorable prognostic chro- TREATMENT OF CHILDREN
mosome changes, so induction chemotherapy is often recommended, AML represents approximately 15 percent of the acute leukemias in
although rates of relapse remain high. 1070 In parallel, elderly patients children (younger than 20 years of age) in the United States. APL is
with unfavorable cytogenetics have a dismal prognosis, and those who treated as in adults, with ATRA and an anthracycline antibiotic. In other
have a monosomal karyotype have low complete remission and overall phenotypes of AML, intensive treatment—including initial therapy
survival rates; 37 versus 64 percent and 8 versus 28 percent, respectively, with cytarabine and daunomycin or doxorubicin and a third drug such
in those with and without monosomal karyotype. 1071 as mitoxantrone or 6-thioguanine, followed by intensive multidrug con-
solidation therapy including additional agents such as etoposide, and
intrathecal cytarabine—has resulted in remission in approximately 80
TREATMENT OF PREGNANT PATIENTS percent of children and 5-year relapse-free remissions in approximately
Leukemia (AML, ALL, CML) is the second most common malignancy 50 percent of treated children. 1083–1086 Most of the children in long-term
of women in the childbearing age group and is expected to occur in remission are considered cured.
9
approximately 1 in 75,000 to 100,000 pregnancies. 1072,1073 No systematic Monocytic leukemia and hyperleukocytic (>100 × 10 /L) myel-
studies of the (1) effects of leukemia on pregnancy or delivery, (2) effects ogenous leukemia are unfavorable phenotypes. In children, FLT3-ITD
of the leukemia or its treatment on the fetus, or (3) postnatal devel- mutations are approximately half as common (15 percent) as in adults
opment of the offspring exposed to maternal chemotherapy in utero (30 percent), but are a very poor prognostic indicator. 1087 Therapy can
have been performed. A recent literature review led to the conclusion be adjusted for children based on the presence of poor prognostic vari-
that treatment during the second and third trimesters resulted in fewer ables, which include age younger than 2 years or older than 10 years;
complications to the fetus, but delaying treatment adversely affected the abnormalities of chromosome 3, 5, or 7, complex karyotypes, FLT3
outcome of mothers. Remission rates were comparable to that of non- mutations, elevated white cell count of 50 × 10 /L or greater, male gen-
9
pregnant patients. 1074 Folic acid inhibitors, purine, pyrimidine, or retin- der; and, perhaps, most importantly, because it reflects the effect of all
oid analogues given during the first trimester of pregnancy increase the factors, the presence of greater than 15 percent blast cells in the marrow
probability of major congenital malformations. In a French study of 37 examined 14 days after onset of treatment. 1088,1089 The presence of resid-
patients with acute leukemia during pregnancy, 34 patients achieved ual blast cells detected by flow cytometry after induction therapy is a
remission, and disease-free survival appeared equivalent to that of very poor prognostic finding. 1090 The duration of first remission predicts
patients who were not treated during pregnancy. 1075 In another study the subsequent remission rate and long-term survival in children with
from Saudi Arabia, of 21 pregnant patients with acute leukemia, 10 were relapse.
given chemotherapy with seven livebirths and three spontaneous abor- Translocations 8;21, 15;17, or inv16 are good prognostic markers.
tions without any teratogenetic or congenital malformations. In the 11 Loss of a sex chromosome in the t(8;21) group is especially favorable.
not given chemotherapy until after 34 weeks of gestation, three had nor- Monosomy 7 and abnormalities of chromosomes 3 or 5 are poor prog-
mal births and eight had an abortion before starting chemotherapy. 1076 nostic features. 1091 Pediatric AML with t(8;16)(p11;p13) has been found
If the pregnancy is not terminated, leukapheresis might be use- to be a distinct clinical entity, and in a subset of neonatal cases, spon-
ful in the first trimester, when chemotherapy poses a high risk to the taneous remissions can occur. 1092 In childhood 11p23/MLL AML, there
embryo. Intensive chemotherapy given to women in the second and are large differences in outcome based on translocation partners that
third trimesters of pregnancy does not present an inordinate risk to are independent prognostic markers as assessed in a large international
fetal or neonatal development, 1077,1078 although an increased frequency study. 1093 When gene mutations were examined in childhood leukemia,
of premature delivery, higher perinatal mortality, and lower birthwei- FLT3-ITD was most frequent, and 29 percent had more than one gene
ght for gestational age are observed, especially if the fetus is exposed to mutation. Mutated epigenetic regulators were less than in adults, but
chemotherapy. were often seen with other mutations. 1094
Cytarabine is highly teratogenic in animal models and malfor- In the United Kingdom Medical Research Council Trial 12,
mations have been described in women who were treated in the first completed in 2002, using daunorubicin, mitoxantrone cytarabine,
trimester of pregnancy. Doxorubicin is the preferred anthracycline etoposide, and asparaginase in different combinations, approximately
antibiotic to treat pregnant women as it has lower transplacental trans- 90 percent of children with AML had a remission, 60 percent of chil-
fer. Doxorubicin is considered relatively safe when used in pregnant dren had a 5-year disease-free survival, and most were considered
women. 1079 Newborn infants may be transiently cytopenic if the mother cured. 1091 Approximately 4 percent of children are drug resistant with
receives chemotherapy near the time of delivery. Development of the this program and approximately 4 percent die during induction and

Kaushansky_chapter 88_p1373-1436.indd 1409 9/21/15 11:02 AM