Page 1436 - Williams Hematology ( PDFDrive )

1410 Part X: Malignant Myeloid Diseases Chapter 88: Acute Myelogenous Leukemia 1411

Fertility and Gonadal Function cytogenetic abnormalities at morphologic remission after induction
Patients treated for AML, especially patients undergoing condition- therapy predicts for a significantly shorter relapse-free survival and
ing for allogeneic stem cell transplantation, have decreased gonadal overall survival, for example. 1135
function. 1121–1123 Men may develop oligospermia. Women may develop
ovarian dysfunction and very high gonadotropin levels. 1124 Men recover Rates of Remission
gonadal function more often and sooner than do women. Recovery of Remission rates have improved dramatically in the last 60 years, but
ovarian function in women is partly dependent on a younger age at the remission, relative 5-year survival, and cure rates are most dependent
time of treatment. In survivors of childhood AML treated only with on the patient’s age when AML occurs. 1136,1137 Initial remission rates now
chemotherapy and not transplantation, normal pubertal development approach 90 percent in children, 70 percent in young adults, 60 percent
and fertility are found, but antimüllerian hormone was low in some in middle-aged patients, and 40 percent in older patients. Within age
women. 1125 Women in remission following treatment for AML with groups, remission is related to other variables such as cytogenetic risk
allogeneic transplantation can become pregnant and deliver healthy category and expression of MDR genes in leukemic cells, but these vari-
infants 1126,1127 ; however, this preservation of fertility is rare. 1128 Histologic ables also are correlated with age at onset. For example, the more favor-
studies of the testes show marked suppression of spermatogenesis as a able cytogenetic patterns t(8;21), t(15;17), inv16, or t(16;16) are present
function of duration of treatment for AML and not of the specific agents in approximately 30 percent of patients between 10 and 39 years old,
used or the patient’s age. Residual spermatogenesis in intensively treated 15 percent of patients between 40 and 59 years old, and 5 percent of
patients enables recovery of reproductive function in males. 1129 Males patients 60 to 90 years old (Table 88–9). 1137 Other factors, such as AML
receiving intensive daunorubicin, cytosine arabinoside, or 6-thiogua- evolving from a prior clonal myeloid disease or developing as a result
nine treatment for AML have conceived children during therapy. 1130 of cytotoxic treatment for another cancer or immune disorder, can
Banking of sperm should be offered, and cryopreservation of ova can decrease the expected remission and survival rates for the age group. In
be attempted prior to institution of cytotoxic therapy, but often nei- one study, treatment-related AML was an adverse prognostic factor for
ther is logistically possible or successful in patients with AML who are death in remission for younger patients and for relapse in remission in
acutely ill at presentation and require urgent chemotherapy. 1121 Banking older patients. 1138 Age-related comorbid conditions may limit the appro-
of sperm or ova-ovarian tissue should be considered before myeloabla- priateness or tolerance of intensive therapy, decreasing the opportunity
tive conditioning regimens for transplantation are administered. Many for remission. The expected increase in the proportion of old and old-
AML survivors report they were not, or not fully, informed about fertility- old individuals in the population may decrease remission rates and their
related issues. 1131 duration unless counteracting improvements in treatment approaches
are developed. In one study of 1069 consecutive AML patients in first
COURSE AND PROGNOSIS CR treated between 1991 and 2003, the yearly risk of treatment failure
was 69.1 in the first year, 37.7 in the second year, 17 in the third year,
RESULTS OF TREATMENT 7.6 in the fourth year, and 6.6 in the fifth year. The effects of cytogenetics
remained constant during the first 3 years, but the effect of age increased
Definition of Remission with time. The probability of relapse-free survival at 6 years was 84 percent
Complete remission (CR) after AML therapy is defined as neu- for those in remission at 3 years, but for the group older than 60 years
trophil count greater than 1000/μL and platelet count greater than old, it was only 56 percent, suggesting that different variables contribute
100,000/μL 1132 with less than 5 percent blasts morphologically in mar- differently over time to overall outcomes. 1139
row and the absence of extramedullary AML, although this definition Early death can occur during induction chemotherapy, and per-
has been called into question. 1133 Remission with incomplete platelet formance status and age are the most important predictors of treatment
recovery CR platelets (CRp) has all these requirements but the platelet related mortality. Age may be primarily a surrogate for other factors
count does not reach 100 × 10 /L. In a large cooperative group study, which also predict treatment related mortality. 1140
9
at least 94 percent of patients receiving cytarabine-based therapy who
survived more than 3 or 5 years achieved a remission. Three- and 5-year Clonal Remissions
survivals with CRp were less frequent. 1134 With residual leukemic cell A small proportion of patients who enter remission have apparently
detection now possible by flow cytometry, cytogenetic, and molecular normal hematopoiesis supported by a single clone rather than the
methodologies, definitions of remission may change. Persistence of expected polyclonal hematopoiesis. Evidence points to this clone being

TABLE 88–9. Frequency of Cytogenetic Findings with a More Favorable Prognosis by Age Group
Favorable
No. of Cases t(8;21) (No. of t(15;17) (No. of Inv16/t(16;16) Total (No. of Karyotypes (% of
Age (Years) Studied Cases) Cases) (No. of Cases) Cases) All Cases)
10–39 307 27 38 33 98 32
40–59 584 36 28 28 92 16
60–69 579 18 24 21 63 11
70–79 381 5 7 5 17 4.5
>80 45 1 2 0 3 6.6
Total 1896 87 99 87 273 22
These observations were made in Germany by Claudia Schoch and colleagues and kindly provided to the authors. (See also Schoch C, Kern W,
Krawitz P, et al: Dependence of age-specific incidence of acute myeloid leukemia on karyotype. Blood 98:3500, 2001.)

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