Double induction strategy including high dose cytarabine in combination with all-trans retinoic acid: effects in patients with newly diagnosed acute promyelocytic leukemia

Abstract

A prospective multicenter study was performed to investigate the clinical and molecular results of intensified double induction therapy including high-dose cytarabine (ara-C) in combination with ATRA in newly diagnosed acute promyelocytic leukemia (APL), followed by consolidation and 3 years maintenance therapy.

High dose ara-C in the treatment of newly diagnosed acute promyelocytic leukemia: long-term results of the German AMLCG

“…The long-term data confirm and extend initial results on 51 patients published earlier. 19 The relapse rate of 11.4% after 10 years is less than half compared with the data of the literature for high risk APL treated without HD ara-C. 2,6,8,9 Figure 3 Relapse free survival. (a) Of all patients (n ¼ 131), who entered remission and (b) according to initial white blood cell count o or X10 Â 10 9 /l (P ¼ 0.83).…”

How to manage acute promyelocytic leukemia

“…4 However, for high-risk (WBC count410 Â 10 9 /l) patients, large doses of Ara-C could act better. 2,4,56 Although ATRA plus chemotherapy gained great effects, there are still problems such as relapse, severe side effects of chemotherapy and so on. The 5-year relapse-free survival and overall survival (OS) from SIH were only around 34.0 and 52%.…”

Reply to Sanz et al

“…After combined double induction including high-dose ara-C and ATRA, there are no hematologic or clinical relapses until 3. years. 1 This is confirmed in the recent update of November 2000 with a longer follow-up (median 33 months) and a higher number of patients (n = 73). The rate of hematologic remission is 93%.…”

“…8 (5) Since the kinetics of molecular remission was identified as one of two prognostic factors in APL in the British trials, 6 the rapid achievement of molecular remission reported by us 1 again suggests an improvement of poor prognosis. (6) The low relapse rate in the AMLCG study 1 is not explained by a comparatively high cumulative anthracycline dosage. Given the dose equivalents used by the EORTC 9 as daunorubicin (DNR) 50 mg = mitoxantrone 12 mg = idarubicin 10 mg, the cumulative DNR equivalent of 485 mg/m 2 given during induction and consolidation in the AMLCG study remains within the dose ranges of the other trials, 4,6,7 even if maintenance treatment is included in the calculation.…”

“…5 (4) WBC count as a risk factor of relapse 3,4,6,7 has not been reproduced in the current trial of the AMLCG. 1 Even in patients with WBC count у5000/ l, there was no hematologic relapse until 3. years ( Figure 1). Intensive chemotherapy including high dose ara-C may thus improve poor prognosis in APL as it does in other subtypes of AML.…”