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patients under the age of 60 years and 60 or above, respectively. These tables indicate that for every cytogenetic group, with the exception of inv(16)/t(8;21), and in both younger and older patients, the de novo patients have both higher CR rates and longer RFS. Figures 7.3 to 7.5 depict the effect of the de novo/sec-ondary distinction on survival. Goldstone et al. have also noted that secondary disease (an AHD or PCH) remains associated with a worse outcome after accounting for age and cytogenetics.8

There are three broad options for treatment of secondary AML/MDS: palliative care only, SCH, or inves-tigational therapy, preferably in the context of a clinical trial. As relapse rates begin to decline sharply once 2-3 years have elapsed from the CR date, patients alive in CR at these times can be considered "potentially cured."9 Multiplying CR rate by RFS probability indicates that only 10% of secondary cases are predicted to be alive in first CR at 2 years from treatment date if given SCH (Table 7.1). Under these circumstances, investigational therapy may be necessary at some point in the majority of patients with secondary AML/ MDS.

It is critical to ask whether there are groups of patients with secondary AML/MDS who should, or plausibly might, receive SCH, which in any event is intuitively preferred by patients and physicians, given the fewer number of unknowns involved. Tables 7.3

and 7.4 indicate that both older and younger patients with inv(16) or t(8;21) should receive SCH. As made clear by Beaumont et al.,10 standard treatment should also be recommended for patients with secondary acute promyelocytic leukemia (APL). Younger patients with secondary AML and a normal karyotype have a 20% likelihood of remaining alive in first CR at 2 years (a CR rate of 0.69 X an RFS of 0.29; Table 7.3). Whether this result is sufficiently high to justify the use of SCH, given that it is distinctly possible that investigational therapy could be considerably worse, is a subjective decision, except in cases where an internal tandem duplication or mutation of FLT311 is present and tips the scales to a recommendation for investigational therapy. In the other groups depicted in Tables 7.3 and 7.4, the results with SCH are so poor (less than or equal to 10% probability of potential cure) that investiga-tional therapy is preferred, given that even if it proves worse than SCH, it cannot be much worse. The recommendation that all patients with secondary AML with the exception of those with inv(16) or t(8;21) and, quite plausibly, those under age 60 with good performance status and a normal karyotype are candidates for investigational therapy is, in general, in accord with the recommendation of the National Comprehensive Cancer Network,12 a consortium of academic medical centers. In those older patients in whom this recommendation cannot be carried out, the option of

Figure 7.2 Survival probabilities when patients with PCH or AHD are considered as one group (secondary AML/MDS) and compared to de novo patients (neither AHD nor PCH)

Figure 7.1 Survival probabilities of M.D. Anderson patients according to AHD and PCH status

Figure 7.2 Survival probabilities when patients with PCH or AHD are considered as one group (secondary AML/MDS) and compared to de novo patients (neither AHD nor PCH)

Table 7.2 Associations with other covariates Predictors De novo cases Secondary cases

Median age

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