Toward optimization of postremission therapy for residual disease-positive patients with acute myeloid leukemia.
OBJECTIVE
Despite the identification of several baseline prognostic indicators, the outcome of patients with acute myeloid leukemia (AML) is generally heterogeneous. The effects of autologous (AuSCT) or allogeneic stem-cell transplantation (SCT) are still under evaluation. Minimal residual disease (MRD) states may be essential for assigning patients to therapy-dependent risk categories.


METHODS
By multiparametric flow cytometry, we assessed the levels of MRD in 142 patients with AML who achieved complete remission after intensive chemotherapy.


RESULTS
A level of 3.5 x 10(-4) residual leukemia cells (RLCs) after consolidation therapy was established to identify MRD-negative and MRD-positive cases, with 5-year relapse-free survival (RFS) rates of 60% and 16%, respectively (P < .0001) and overall survival (OS) rates of 62% and 23%, respectively (P = .0001). Of patients (n = 77) who underwent a transplantation procedure (56 AuSCT and 21 SCT procedures); 42 patients (55%) were MRD positive (28 patients who underwent AuSCT and 14 patients who underwent SCT) and 35 patients (45%) were MRD negative (28 patients who underwent AuSCT and seven who underwent SCT). MRD-negative patients had a favorable prognosis, with only eight (22%) of 35 patients experiencing relapse, whereas 29 (69%) of 42 MRD-positive patients experienced relapse (P < .0001). In this high-risk group of 42 patients, we observed that 23 (82%) of 28 of those who underwent AuSCT experienced relapse, whereas six (43%) of 14 who underwent SCT experienced relapse (P = .014). Patients who underwent SCT also had a higher likelihood of RFS (47% v 14%).


CONCLUSIONS
A threshold of 3.5 x 10(-4) RLCs postconsolidation is critical for predicting disease outcome. MRD-negative patients have a good outcome regardless of the type of transplant they receive. In the MRD-positive group, AuSCT does not improve prognosis and SCT represents the primary option.
Maurillo
Luca
L
Hematology, Policlinico Tor Vergata and Ospedale S Eugenio, Rome, Italy.
Buccisano
Francesco
F
Del Principe
Maria Ilaria
MI
Del Poeta
Giovanni
G
Spagnoli
Alessandra
A
Panetta
Paola
P
Ammatuna
Emanuele
E
Neri
Benedetta
B
Ottaviani
Licia
L
Sarlo
Chiara
C
Venditti
Daniela
D
Quaresima
Micol
M
Cerretti
Raffaella
R
Rizzo
Manuela
M
de Fabritiis
Paolo
P
Lo Coco
Francesco
F
Arcese
William
W
Amadori
Sergio
S
Venditti
Adriano
A
D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D011379:Prognosis; D012074:Remission Induction; D033581:Stem Cell Transplantation / Q000379:methods*; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D018943:Anthracyclines; D003561:Cytarabine; D005047:Etoposide