Impact of complete molecular response on survival in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.

Abstract

The impact of achieving complete molecular response (CMR) in Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) remains undefined. We evaluated the impact of CMR on outcomes among 85 patients with Ph(+) ALL who received first-line hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine plus a tyrosine kinase inhibitor, had minimal residual disease (MRD) assessments for BCR-ABL1 by quantitative polymerase chain reaction at complete remission (CR) and at 3-month time points, and did not undergo allogeneic stem cell transplantation (SCT). MRD status at 3 months had better discrimination for overall survival (OS; P = .005) and relapse-free survival (RFS; P = .002) than did MRD status at CR (P = .11 and P = .04, respectively). At 3 months, achievement of CMR vs response less than CMR was associated with longer median OS (127 vs 38 months, respectively; P = .009) and RFS (126 vs 18 months, respectively; P = .007). By multivariate analysis, only CMR at 3 months was prognostic for OS (hazard ratio, 0.42; 95% confidence interval, 0.21-0.82; P = .01). Patients with Ph(+) ALL who achieve CMR at 3 months have superior survival compared with those with lesser molecular responses and have excellent long-term outcomes even without SCT.

• Authors: Nicholas J Short, Elias Jabbour, Koji Sasaki, Keyur Patel, Susan M O'Brien, Jorge E Cortes, Rebecca Garris, Ghayas C Issa, Guillermo Garcia-Manero, Rajyalakshmi Luthra, Deborah Thomas, Hagop Kantarjian, Farhad Ravandi
• Journal: Blood (Blood) Vol. 128 Issue 4 Pg. 504-7 (07 28 2016) ISSN: 1528-0020 [Electronic] United States
• PMID: 27235138 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2016 by The American Society of Hematology.

Chemical References

• BCR-ABL1 fusion protein, human
• Cytarabine
• Vincristine
• Dexamethasone
• Cyclophosphamide
• Fusion Proteins, bcr-abl
• Methotrexate

Topics

• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Cyclophosphamide (administration & dosage, adverse effects)
• Cytarabine (administration & dosage, adverse effects)
• Dexamethasone (administration & dosage, adverse effects)
• Disease-Free Survival
• Female
• Follow-Up Studies
• Fusion Proteins, bcr-abl (blood)
• Humans
• Infant
• Male
• Methotrexate (administration & dosage, adverse effects)
• Neoplasm, Residual
• Philadelphia Chromosome
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (blood, drug therapy, mortality)
• Survival Rate
• Vincristine (administration & dosage, adverse effects)