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Pretransplant minimal residual disease level predicts clinical outcome in patients with acute myeloid leukemia receiving high-dose chemotherapy and autologous stem cell transplantation.

Author(s): Venditti A, Maurillo L, Buccisano F, Del Poeta G, Mazzone C, Tamburini A, Del Principe MI, Consalvo MI, De Fabritiis P, Cudillo L, Picardi A, Franchi A, Lo-Coco F, Amadori S

Affiliation(s): Cattedra di Ematologia, Divisione di Ematologia, Universita di Roma Tor Vergata, Rome, Italy.

Publication date & source: 2003-11, Leukemia., 17(11):2178-82.

Publication type: Clinical Trial; Randomized Controlled Trial

A total of 31 adult patients with AML entered in the EORTC/GIMEMA AML-10 trial, who received autologous stem cell transplantation (ASCT) after induction and consolidation chemotherapy, were prospectively evaluated for minimal residual disease (MRD) by multidimensional flow cytometry (MFC). Using a cutoff level of 3.5 x 10(-4) leukemic cells pre-ASCT, 12 patients (39%) were stratified to MRD high-risk group and 19 (61%) into MRD low-risk group. During follow-up, all patients who were in the high-risk group relapsed at a median time of 7 months; in the low-risk group, five patients relapsed at a median time of 11 months and 14 remained in remission for 56 (range 7-80) months (P=0.00004). Longitudinal MFC determinations post-ASCT showed increased MRD levels in three of the five patients who underwent subsequent relapse, while disease recurrence was unpredicted in the remaining two cases. The pre-ASCT MRD status was the factor most strongly associated with relapse risk in the multivariate analysis (P=0.0014). We conclude that: (1) pre-ASCT MRD status predicts successful outcome in patients receiving ASCT; (2) high-dose chemotherapy conditioning regimen followed by ASCT has no impact on the unfavorable prognostic value of high pre-ASCT MRD level; and (3) sequential MRD monitoring post-ASCT may allow the prediction of impending relapse.

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