Pretransplant minimal residual disease level predicts clinical outcome in patients with acute myeloid leukemia receiving high-dose chemotherapy and autologous stem cell transplantation.
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.
Cattedra di Ematologia, Divisione di Ematologia, Università di Roma Tor Vergata, Rome, Italy.
A
A
Venditti
L
L
Maurillo
F
F
Buccisano
G
G
Del Poeta
C
C
Mazzone
A
A
Tamburini
M I
MI
Del Principe
M I
MI
Consalvo
P
P
De Fabritiis
L
L
Cudillo
A
A
Picardi
A
A
Franchi
F
F
Lo-Coco
S
S
Amadori
F L
FL
Coco
D000208:Acute Disease; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D016130:Immunophenotyping; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D007958:Leukocyte Count; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D018365:Neoplasm, Residual / Q000175:diagnosis*; D011237:Predictive Value of Tests; D011336:Probability; D012008:Recurrence; D018570:Risk Assessment; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D005047:Etoposide; D008942:Mitoxantrone; D015255:Idarubicin