Multiple Choice Questions

1. Age at relapse
   
2. Duration of CR1
   
3. Cytogenetics at diagnosis
   
4. All of the above

As has become clear, a substantial number of patients may not benefit from intensive re-induction chemotherapy and a search for investigational therapies (i.e., a clinical trial is more appropriate). Yet, on the other hand, a small group of patients may indeed benefit from attempts at intensive re-induction therapy and carry an altogether more favorable prognosis. Several prognostic indices have been devised to more accurately predict outcome for patients in first relapse. In a study by Breems et al. (2005) of 667 patients with AML in first relapse, four clinical parameters determined outcome: duration of CR1, cytogenetics at diagnosis, age at relapse, and whether or not previous HPCT was performed. Using a stratification system, three risk groups were identified with OS rates ranging from 46% at 5 years in the best prognosis group to 4% in the worst prognosis group (Table 12.2), which included the majority (almost 70%) of the patients. The GOELAMS group presented a simplified prognostic score based on a multivariate analysis of 138 patients with relapsed or refractory AML, which was then validated in an independent cohort of 111 patients. The three strongest independent adverse prognostic factors for OS included disease status (relapse within the first 12 months or later), FLT3–ITD-positive status, and high-risk cytogenetics. Accordingly, patients with no adverse factors had an OS of 58%, whereas patients in the highest risk group (two or more adverse factors) had an OS of 12% at 2 years. Applying these scores to the described patient, the 5-year OS is 4% and the 2-year OS is 12% in the study by Breems et al. (2005) and the GOELAMS group, respectively.

1. True
   
2. False

Although the 7 + 3 combination consisting of standard doses of cytarabine (100 to 200 mg/m²/dose) is the most widely used induction therapy, there is some evidence that higher doses of cytarabine during induction benefit younger adults (patients <60 years) and especially those patients <45 years of age. The question arises whether patients who fail to respond to higher-intensity induction regimens fare differently from those who relapse after a more standard and less intensive induction regimen. In a study of 1597 patients with AML between the ages of 18 and 85 years, 285 patients were refractory to HiDAC-based induction therapy. These patients on average tended to be older and were more likely to have a history of an antecedent hematologic disorder, blasts with unfavorable cytogenetics, and a higher WBC count at presentation. Only 43 patients (22%) responded to salvage therapy, and with a median follow-up of 72 months, only 11 patients stayed alive, mostly those who underwent an HPCT. The median survival of these patients was only 3.8 months, and among the patients who achieved remission, the median remission duration was only 9.1 months.