Toward Optimization of Postremission Therapy for Residual Disease–Positive Patients With Acute Myeloid Leukemia

• Published in: Journal of clinical oncology Vol. 26; no. 30; pp. 4944 - 4951
• Main Authors: MAURILLO, Luca, BUCCISANO, Francesco, VENDITTI, Daniela, QUARESIMA, Micol, CERRETTI, Raffaella, RIZZO, Manuela, DE FABRITIIS, Paolo, LO COCO, Francesco, ARCESE, William, AMADORI, Sergio, VENDITTI, Adriano, ILARIA DEL PRINCIPE, Maria, DEL POETA, Giovanni, SPAGNOLI, Alessandra, PANETTA, Paola, AMMATUNA, Emanuele, NERI, Benedetta, OTTAVIANI, Licia, SARLO, Chiara
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 20.10.2008; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Anthracyclines - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Cytarabine - administration & dosage; Disease-Free Survival; Etoposide - administration & dosage; Female; Hematologic and hematopoietic diseases; Humans; Leukemia, Myeloid, Acute - therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Neoplasm, Residual; Prognosis; Remission Induction; Stem Cell Transplantation - methods; Transplantation, Autologous; Transplantation, Homologous; Treatment Outcome; Tumors; Human; Acute myelogenous leukemia; Cancerology; Minimal residual disease; Malignant hemopathy; Consolidation treatment; Optimization; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2007.15.9814

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