High CR-Rate after Intensive Chemotherapy but Disappointing Results after Palliative Treatment in Patients with Acute Myeloid Leukemia Above the Age of 60 Years: An Analysis of the AML97#38 Study of the East German Hematology and Oncology Study Group (OSHO).

The incidence of AML increases with age. More than half of the patients (pts) are over 60 years (y) at time of diagnosis. On the other hand, elderly pts are clearly under-represented in the literature. The AML 97 study was designed to register all pts aged 60 and more with newly diagnosed AML. Subsequently, pts were allocated to one of the 3 parts of protocol dependent on Karnofsky’s index (KI).

Methods: Since March 1998 to October 2005 a total of 644 pts were enrolled in the study, 496 (77%) pts were allocated to the curative, 115 (18%) to the palliative and 33 (5%) to the supportive part of the protocol. Pts characteristics between the 3 groups differed significant in respect to age (p<10⁻⁶) and KI (p<10⁻⁶). Median age of pts was 66 y (range 60–88 y), 76 y (range 64–90 y) and 77 y (range 63–97 y) for the curative, palliative and supportive protocol respectively. Curative treatment consisted of one (in case of PR of two) courses of induction (AraC 2 g/m² iv day 1,3,5,7 in combination with Mitoxantrone 10 mg/m² iv day 1–3) followed by 2 consolidation courses (AraC 240 mg/m² iv day 1–5 combined with Mitoxantrone 10 mg/m² iv day 1–2). Palliative treatment consisted of Idarubicin 10 mg po day 1 in combination with either Thioguanine 40 mg po day 1–5, or AraC 80 mg sc day 1–5 or Etoposide 100 mg po day 1–5. As supportive treatment only transfusions were applied.

Results: The present analysis based on 550 eligible and evaluable pts, 420 after curative, 98 after palliative and 32 after supportive treatment. After intensive chemotherapy, 100%, 74,5%, 65,4% and 52,2% pts achieved CR with favourable, normal, other or unfavourable karyotype, respectively. The high CR rate was accompanied by an acceptable early death (ED) rate of 17% for all intensive treated patients. The actually event free survival (EFS) after 4y is 0,45 (±0,11), 0,12 (±0,03), 0,11 (±0,05) and 0,05 (±0,03) for favourable, normal, other and unfavourable cytogenetics, respectively. The median overall survival (OS) is actually not reached for the favourable karyotype (range 4–87 months), amount to 13 months (m) for normal (range 1–105 m) and other (range 4–88 m) karyotype and 7 months (range 1–88 m) for unfavourable karyotype. In a multivariate analysis, cytogenetics at diagnosis were the most important and powerful prognostic factor for CR (p=0,002), EFS (p=10⁻⁶) and OS (p=10⁻⁵). The results of pts after palliative or supportive therapy were clearly inferior with median OS of 54 and 11 days, respectively.

Conclusion: Our registration study shows that CR can be induced in a high proportion of elderly AML pts with acceptable ED rates in the curative arm. Despite high CR rates, quality of CR was not reached for improving EFS and OS. So a new protocol with the option of allogeneic PBCST after reduced conditioning was successfully started. The results after palliative therapy are disappointing. New strategies like demethylation or targeted therapy are necessary for these elderly pts not eligible for intensive chemotherapy.