Page 1437 - Williams Hematology ( PDFDrive )

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

a preleukemic cell rather than a normal stem cell. 1141–1144 This finding groups, and the proportion of AML patients receiving transplantation
is in keeping with previous hypotheses about the possible patterns of is very small. 1136,1158–1161 Abnormalities of chromosomes 17p and –5/5q–
remission and relapse in AML 1145–1148 and has implications for minimal have negative impact on outcomes after allogeneic transplant. 1162,1163
residual disease detection. In contrast to other AML subtypes, APL has had an increased
incidence as well as improved survival since the introduction of ATRA.
Spontaneous Remissions In one large study, relative survival rates were 0.18 for the period 1975
Spontaneous disappearance of AML has been reported for more than to 1990, with increase to 0.64 from 2000 to 2008. Age did remain an
100 years; however, most cases reported before 1960 had poor doc- important predictor of survival; 0.38 in those older than age 60 years
umentation of the diagnosis. Bona fide cases of AML patients who and 0.73 for those 20 to 29 years old. 1164
entered CR, usually after or concurrent with an infection, occur but are Relapse (or a new leukemic event) in long-term survivors occur-
very rare. 1148–1151 The occurrence of spontaneous remission with infec- ring as late as 8 years after remission has been reported in adults 1153,1154
tion is consistent with the observation that the antibody response to and after more than 16 years in children. 1153,1154 Relapse in long-term
Pseudomonas vaccine 1152 correlates with improved probability of che- survivors nearly always occurs in the marrow in adults and usually in the
motherapy-induced remission. Spontaneous remissions often are short marrow in children, with occasional childhood cases of CNS or gonadal
lived but have lasted up to 3 years in adults and more than 9 years in relapses occurring initially, followed by relapse in the marrow. 1159 Stud-
children. 1153 A particularly notable case of remission for more than 60 ies of long-term survivors of AML show that most can return to work
years has been documented following “treatment” prior to the intro- and that, at a median followup of 9 years, no increased risk of secondary
duction of chemotherapeutic drugs. The regimen included arsenic. 1154 invasive cancer or secondary AML had occurred. 1160,1161 An exception
to this finding is the occasional report of myelodysplasia or presumably
LONG-TERM SURVIVAL secondary AML in long-term survivors of APL. Health-related quality
Prior to the introduction of chemotherapy for AML 60 years ago, the of life in long-term survivors appears to recover completely as related to
physical, psychological, and emotional well-being, but continued sexual
median survival of patients was approximately 6 weeks, 1155 the 1-year dysfunction has been reported. 1165 The quality of life at the time of diag-
survival was approximately 3 percent, and longer survival occurred nosis and during the course of therapy usually is poor. 1165,1166
in less than 1 percent of patients. Five-year relative survival rates of
patients in the United States from 2004 to 2010, based on the Surveil-
lance, Epidemiology, and End Results Program of the National Can- FEATURES INFLUENCING OUTCOME OF
cer Institute, are 56 percent for patients younger than age 45 years, THERAPY IN ACUTE MYELOGENOUS LEUKEMIA
39 percent for patients 45 to 54 years old, 27 percent for patients 55
to 64 years old, 11 percent for patients 65 to 74 years old, and 1.8 Numerous features are related to outcome of AML treatment. Older
percent for patients older than age 75 years at the time of diagnosis age and less-favorable cytogenetic risk group are the two most com-
(Table 88–10). 1069 Considering that the median age at disease onset is pelling determinants of a poor outcome. Even with multivariate anal-
approximately 70 years and that 75 percent of patients are older than 45 ysis, dissecting which other features are themselves important or are
years, the overall median survival is approximately 12 months. A study associations that segregate with another prognostic factor is difficult
of the cost of care of older AML patients using Medicare data found that (Table 88–11). 1167–1264 As noted previously, prognostic models of AML
in adults older than age 65 years who were diagnosed between 1991 and that rely solely on molecular mutations have been proposed. 105
1996, the median survival was 2 months and the 2-year survival was Determining useful prognostic variables in patients with AML is
6 percent. 1156 Very similar results were found in a study of nearly 10,000 imprecise because negative prognostic factors may be eliminated by
patients in Sweden. 1157 Better survival has been reported for younger better treatment protocols. Moreover, several prognostic factors are
patients who have received allogeneic stem cell transplantation in first significant only when AML is stratified by age or by morphologic phe-
remission, but the confidence limits for remission duration and survival notype. Conflicting findings are common among studies. In addition,
are overlapping for drug-treated and drug- and transplantation-treated although a prognostic variable may be correlated significantly with a
favorable outcome, the lack of a very strong statistical correlation with
the outcome of treatment makes the variable’s presence or absence of
TABLE 88–10. Acute Myelogenous Leukemia: Five-Year little prognostic value in an individual patient. If a stem cell donor is
Percent Relative Survival Rates (2004–2010) available, unfavorable prognostic factors could influence the therapist to
use allogeneic stem cell transplantation as a means of remission main-
Acute Myelogenous tenance in patients entering remission. The impact of prognostic factors
Age (Years) Leukemia* may change in patients treated with allogeneic stem cell transplantation
<45 56 compared with conventional cytotoxic treatment. 1265,1266
45–54 39
55–64 27 DETECTION OF MINIMAL RESIDUAL DISEASE
65–74 11 General Considerations
The tumor cell burden in acute leukemia at presentation is approx-
>75 1.8
imately one trillion (10 ) cells. Apparent marrow aplasia followed by
12
<65 43 restitution of normal hematopoiesis can occur with at least a three-log
>65 6.0 reduction in leukemic cell numbers, which represents a residual tumor
cell burden of approximately one billion cells. Intensification therapy is
*Percent rounded to nearest integer. intended to decrease further the residual cell numbers. With the advent
Data from SEER Cancer Statistics. Table 13.6. National Cancer Institute, of specific monoclonal antibodies for leukemic cell antigens and FISH
Washington, DC. Available at: http://seer.cancer.gov/csr/1975_2011/ coupled with flow cytometry and DNA amplification by PCR, resid-
browse_csr.php?sectionSEL=13&pageSEL=sect_13_table.16.html ual leukemic cell populations at or below the level of one billion cells,

Kaushansky_chapter 88_p1373-1436.indd 1412 9/21/15 11:02 AM