Abstract
The optimal post remission treatment of AML patients(pts) > 60 y is controversial and disappointing with less than 20 % of pts cured. High dose of alkylating agents (BuMel-CyTBI)with peripheral blood stem cell support (PBSC) is recognized as a standard consolidation therapy for pts in AML CR1 younger than 60 y. Moreover, high dose Melphalan (HDMel)is reported as safe and efficient in patients with myeloma up to 75 y.The objective of the IPC-AML2000 study is to assess the feasability of HdMEL and PBSC support for AML CR1 patients > 60 y. From 01/2000 to 06/2004, 74/142 pts obtained CR1 after DNR/ARAC induction. They were offered a 1st consolidation with reduced DNR/ARAC dose and a 2nd consolidation (priming course) with Cyclophosphamide 3000mg/m2, VP16 300mg/m2 followed by lenograstim 263mcg/d and PBSC collection then a final intensification with HDMel 140 mg/m2.
Median age of the 74 pts was 67 y(61–79).There were 37m/37f; 17 pts (23%) had secondary leukemia following antecedent of hematologic disorder(n=12) or exposure to radiochemotherapy for cancer(n=5),30% had leucocytosis>30.10*9/ at diagnosis. Cytogenetic analysis revealed favorable risk karyotype in 10% of the pts, intermediate risk in 73% and unfavorable risk in 16%.Thirty four pts(46%)underwent a med of 2 (2–5) apheresis in a med of 15(10–36) days after the priming course, for a med of 8(2,5–23) 10*6/kg CD34+ cells collected. All the 34 patients collected underwent HDMel in a med of 2,5(2–5) months after CR1. Reasons for not receiving HDMel in 40 pts were equally divided in: refusal(27%,n=11)early relapse(25%,n=10)contra indication because of organ dysfonction or poor performance status(27%,n=11) or low CD34 counts (17%,n=7) The med age of the transplanted pts was 67 years(61–71);78% of de novo leukemia pts underwent HDMel compared to 22% of secondary leukemia pts (p=0,02) Following reinfusion of cryopreserved PBSC at Day0 and lenograstim 263mcg/day begining at Day 4,neutrophil reconstitution>0,5 and 1 .10*9/l was observed at Day 11(9–15) and Day12(9–18) respectively.Platelet reconstitution > 25,50,100.10*9/l was observed at Day 13(8–20),Day 14(11–35)and Day 19(13–100) respectively; med platelet and red blood cell transfusion were 0 unit(0–2) and 2 units (0–6) respectively;67% and 32% of the patients did not received any platelet or red blood cell transfusion respectively;20% of patients did not received antibiotherapy. Extra hematological toxicity was limited to mucositis (grade 0/1=57%,gr 2=12%,gr 3=26%,gr 4=5%) Median Day of hospital discharge was Day 14(0–24).No toxic death was observed. With a med follow up of 30(14–68) mths for pts alive, 2 year disease free survival of the 74CR patients and the 34 who received HDMel is 20%[12–31] and 25%[14–42] respectively with a med CR duration of 8 mths(2–68). DFS risk factor analysis for the transplanted pts did not show impact of age, secondary leukemia,hyperleucocytosis,caryotype,but a trend(p=0,003)for shorter DFS in pts receiving high doses of CD34 + cells (<=9.10*6/kg:14 mths,>9:6 mths)These data suggest that consolidation with HDMel and PBSC support is feasible in half of the AML pts > 60 y and can be incorporated safely in the treatment stategy of such pts. Giving the high relapse rate observed, alternative treatment should be considered.
A randomized placebo-controlled phase II study of clarithromycin or placebo combined with VCD induction therapy prior to high-dose melphalan with stem cell support in patients with newly diagnosed multiple myeloma