Abstract Haematologica 1998; 83:627-635 original paper Outcome assessment of age group-specific (±50 years) post-remission consolidation with high-dose cytarabine or bone marrow autograft for adult acute myelogenous leukemia RENATO BASSAN, ROBERTO RAIMONDI,* TERESA LEREDE, ANNA D’EMILIO,* MAURIZIO BUELLI, GIANMARIA BORLERI, ALBERTO PERSONENI,° PIERO BELLAVITA, # FRANCESCO RODEGHIERO,* TIZIANO BARBUI Divisions of Hematology, °Radiotherapy, and # Transfusion Service, Ospedali Riuniti, Bergamo;*Division of Hematology, Ospedale Civile San Bortolo, Vicenza, Italy Correspondence: Renato Bassan, MD, Divisione di Ematologia, Ospedali Riuniti, Largo Barozzi 1, 24100 Bergamo, Italy. Phone: inter- national + 39-035-269491 • Fax: international + 39-035-269667. Background and Objective. To assess outcome of an age-adapted post-remission strategy for adult patients with acute myelogenous leukemia (AML, FAB-M3 excluded), including autologous bone mar- row transplantation (ABMT) or high-dose cytarabine (HiDAC) consolidation. Design and Methods. AML patients in first complete remission (CR) after doxorubicin-cytarabine-thiogua- nine (DoxAT) chemotherapy were scheduled to receive two identical early consolidation courses fol- lowed by HiDAC (1 g/m 2 /bd for 6 days), if aged > 50 years, or HiDAC plus total body irradiation (TBI) plus ABMT if aged < 50 years, the bone marrow being har- vested prior to the HiDAC/TBI regimen and unpurged. Results were examined by treatment intention and in actual treatment groups, by selected pretreatment and therapy-related variables, and compared with age and disease matched historical patients treated with DoxAT consolidation without additional HiDAC or ABMT. Results. One-hundred and eight (70%) of 153 patients achieved a response and were evaluable after a follow-up of 3.3-8.8 years. According to treat- ment intention, long-term relapse-free survival (RFS) was significantly improved in both age groups com- pared with controls (< 50 years: 41% vs 15%, p<0.05; > 50 years: 33% vs 22%, p<0.005). Actually, 41 patients proceeded to ABMT and 24 to the HiDAC cycle (including 5 aged < 50 years), 23 had early con- solidation only (1: refusal; 1: inadequate marrow har- vest; 21: complications), 10 relapsed and 2 died very early into remission, 7 were submitted to an allo- geneic BMT, and one denied any post-remission ther- apy. The long-term RFS rates for ABMT and HiDAC groups were 53% and 54% (47% for 19 patients aged > 50), respectively, significantly better than for his- torical patients or those unable to go beyond early consolidation (p<0.005, adjusted for early adverse events). Overall 5-year survival rate was 40% (p<0.0001), 54% for CR patients, 60% after ABMT, and 65% after HiDAC. Relative to the ABMT and HiDAC intensive treatment groups, only the presence of hepatosplenomegaly at diagnosis was associated with a significantly worse outcome like that of the control study. Interpretation and Conclusions. This age-adapted double post-remission consolidation strategy with ABMT (allo-BMT) or HiDAC was applicable to only about two thirds of responders and was effective in about half these cases, regardless of patient age or specific treatment modality. While the loss of CR patients from treatment realization was unrelated to the study design and depended mainly on recurrence of AML and toxic complications, the exact place of ABMT vs HiDAC consolidation remains unsettled, calling for a new study in comparable patient and risk groups. ©1998, Ferrata Storti Foundation Key words: adult AML, high-dose cytarabine, ABMT S everal recent phase II and phase III clinical tri- als addressed the issue of post-remission con- solidation therapy in adults with acute myel- ogenous leukemia (AML) in first complete remission (CR). These trials confirmed the therapeutic superi- ority, over conventional-dose treatments, of high- dose cytarabine (HiDAC), autologous bone marrow transplantation (ABMT), and allogeneic bone mar- row transplantation (allo-BMT). Reported relapse- free survival (RFS) rates were 35%-63% with ABMT, 1- 6 31%-66% with allo-BMT. 2,3,6-11 and 27%-52% with HiDAC. 3,7,12-19 In some but not all these studies, exclusion rates from the programmed consolidation phases were reported, ranging from 10%-20%, 13,16,19 to 20%-30%, 5,12 to >30%. 2,3,6,15 This observation alone suggests that the applicability of newer treatment modalities may be even more difficult outside the highly controlled circumstances of clinical trials, especially when high-dose treatments are to be administered to unselected and sometimes critically ill patients. While the real incidence of this insidious phenomenon and its final prognostic implications are undetermined, it is intuitively important to know to what extent innovative study results are repro- ducible in common clinical practice. A study conducted from 1984-1987 at Bergamo and Vicenza Hospitals (B/VH, Italy) on a series of un- selected, consecutive patients with AML aged 15-60 years showed that, with a short-term therapy (STT) ©Ferrata Storti Foundation