Acute Leukemias - Republican Scientific Medical Library

a 4.2 · Prognostic Factors in Patients with Relapsed or Refractory AML 59
Fig. 4.2. Cumulative rates of overall survival among acute myeloid
leukemia patients in first relapse according to prognostic group.
Favorable risk group A contains patients with score of 1 to 6 points,
intermediate group B: 7 to 9 points, poor group C: 10 to 14 points.
P value was calculated with use of the log-rank test [10].
survival (OS) rates of 70% and 64% for the favorable
prognostic group, 49% and 38% for the intermediate
risk group, and 16% and 17% for the poor risk group.
Results from the Dutch-Belgian Hemato-Oncology
Group (HOVON) are shown in Fig. 4.2. The reproducibility
and simplicity of this stratification schema may
facilitate therapeutic decisions and the assessment of
novel treatment strategies for first salvage therapy.
In addition to improving outcomes in patients with
relapsed and refractory AML, efforts have been undertaken
to identify quantitative methods that predict for
relapse in patients who are in apparent morphologic
CR. For example, early intervention in this setting has
been beneficial in patients with APL where treatment
at the time of molecular relapse may be associated with
a better outcome than that observed with treatment only
after overt relapse demonstrated by morphology of the
bone marrow [12]. Furthermore, such efforts have pro-
vided important clues into the mechanisms by which
chemoresistance is mediated and may influence the design
of strategies for the prevention of relapsed disease.
As an example, a persistently abnormal karyotype in patients
in apparent CR by morphologic criteria predicts
for relapse [13].
4.2.1 Age
In virtually every study conducted to date, the CR rate
with conventional cytotoxic salvage chemotherapy is inversely
related to age (Table 4.1) [1, 9, 14–16]. In a retrospective
study by Rees and colleagues, which included a
large number of patients in each age subgroup, the CR2
rate among 375 patients was 33% for younger patients
compared to 19% among older patients [16]. Furthermore,
an analysis by the Eastern Cooperative Oncology
Group (ECOG) of the outcome of approximately 3000
newly diagnosed AML patients, demonstrated a poorer
5-year OS rate among 1000 older (> 55 years) patients
compared to 2 000 younger (< 55 years) patients [17].
In addition, several cooperative groups have shown an
improvement in CR1 rates, but not in OS in older adults
during the last two decades [17, 18]. Since AML is generally
a disease of older adults, with a median age of approximately
68 years, this observation carries important
implications. Patients with relapsed and refractory
AML, particularly older adults, are frequently encountered
and there is an urgent need for more effective
and less toxic therapy.
4.2.2 Duration of CR1 and Cytogenetics
The most important predictor of achieving a CR2 with
salvage chemotherapy appears to be the duration of
Table 4.1. Selected studies demonstrating the impact of age on achieving a second complete response
Study Age 60 years
CR2/total patients CR2 (%) CR2/total patients CR2 (%)
Rees, et al. 1986 [16] 124/375 33 21/110 19
Keating, et al. 1989 [9] 75/208 36 5/35 14
Hiddemann, et al. 1990 [1] 56/104 54 14/32 44
Kern, et al. 1998 [15] 67/138 49 21/48 44
Sternberg, et al. 2000 [14] 10/22 45 19/25 76