Treatment of elderly patients (≥60 years) with newly diagnosed acute promyelocytic leukemia. Results of the Italian multicenter group GIMEMA with ATRA and idarubicin (AIDA) protocols

Abstract

In all, 134 elderly patients (median age 66 years, range 60-75 years) with newly diagnosed acute promyelocytic leukemia (APL) were enrolled in two successive protocols of the Italian multicenter group GIMEMA. All patients received an identical induction with all-trans retinoic acid and idarubicin; 116 (86%) entered complete remission (CR), two (2%) were resistant and 16 (12%) died during induction. After CR, 106 patients received further therapy whereas 10 did not, because of refusal (n ¼ 5) or toxicity (n ¼ 5). Consolidation consisted of three chemotherapy courses in the AIDA protocol (AIDA, 67 patients) or, since 1997, of an amended protocol including only the first cycle (amended AIDA, aAIDA, 39 patients). In the AIDA group, 43 patients (64%) completed consolidation, while seven (11%) and 17 (25%) patients were withdrawn after first and second courses, respectively; nine patients (13%) died in CR and 12 (18%) relapsed. In the aAIDA group, all patients received the assigned treatment; two patients (5%) died in CR and six (15%) relapsed. In the AIDA and aAIDA series, the 3-year overall and discasefree survival rates were 81 and 83% (P ¼ NS), 73 and 72% (P ¼ NS), respectively. We highlight here the frequency and severity of complications linked to intensive chemotherapy in this clinical setting and suggest that, in APL of the elderly, less intensive postremission therapy allows significant reduction of severe treatment-related toxicity and may be equally effective.

Outcome of acute promyelocytic leukemia treated with all trans retinoic acid and chemotherapy in elderly patients: the European group experience

“…Similar findings were made by the Italian GIMEMA study, where 86% of the patients older than 60 years with newly diagnosed APL treated with ATRA and idarubicin achieved complete remission and 12% died during induction, mainly from hemorrhage, ATRA syndrome, sepsis or heart failure. 8 A lower CR rate in elderly patients was also found by the Spanish PETHEMA and the Japanese groups with ATRA combined to or followed by chemotherapy, but data in those two studies were only available for patients older than 70 3-5 ( Table 2). As in the present study, the difference with younger adults was due to a higher incidence of early deaths, generally secondary to bleeding or sepsis.…”

“…For example in the GIMEMA study, a 13% incidence of deaths in CR were seen in patients who received three consolidation chemotherapy courses vs 5% in patient who received one consolidation course. 8 Reduction in mortality can also be obtained by avoiding the use of Ara C in the chemotherapy regimen, as shown by the Spanish PETHEMA group 4,5 and also by other studies. 14 Early introduction of arsenical compounds like As 3 O 3 15 or As 4 S 4 , 16 which have no myelosuppressive effect, during induction or consolidation treatment, could also allow reduction of the total amount of chemotherapy administered in elderly APL patients.…”

“…The mean lower WBC count we observed in elderly patients had not been found in the Italian GIMEMA experience, where other pretreatment parameters were also similar in elderly patients and younger adults. 8 The use of heparin, tranexamic acid and fresh frozen plasma transfusion did not differ statistically according to the age group (data not shown).…”

“…[2][3][4][5][6] To our knowledge, two studies have specifically analyzed the impact of ATRA on the outcome of elderly APL patients. 5,8 In this study, we report our experience of newly diagnosed APL in patients older than 60 years treated with ATRA and intensive chemotherapy. Our data show that APL in elderly patients is as sensitive to ATRA-Chemotherapy regimens as APL in younger patients, but we observed a less favorable outcome, mainly due to a higher incidence of early deaths and to myelotoxicity of consolidation chemotherapy.…”

Curative Strategies in Acute Promyelocytic Leukemia

“…It has been suggested that a reduction in the intensity of consolidation in older adults may be beneficial. 25 …”