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Improved risk classification for risk-specific therapy based on the molecular study of minimal residual disease (MRD) in adult acute lymphoblastic leukemia (ALL)
- Publication Year :
- 2009
-
Abstract
- Clinical risk classification is inaccurate in predicting relapse in adult patients with acute lymphoblastic leukemia, sometimes resulting in patients receiving inappropriate chemotherapy or stem cell transplantation (SCT). We studied minimal residual disease (MRD) as a predictive factor for recurrence and as a decisional tool for postconsolidation maintenance (in MRDneg) or SCT (in MRDpos). MRD was tested at weeks 10, 16, and 22 using real-time quantitative polymerase chain reaction with 1 or more sensitive probes. Only patients with t(9;22) or t(4;11) were immediately eligible for allogeneic SCT. Of 280 registered patients (236 in remission), 34 underwent an early SCT, 60 suffered from relapse or severe toxicity, and 142 were evaluable for MRD at the end of consolidation. Of these, 58 were MRDneg, 54 MRDpos, and 30 were not assessable. Five-year overall survival/disease-free survival rates were 0.75/0.72 in the MRDneg group compared with 0.33/0.14 in MRDpos (P = .001), regardless of the clinical risk class. MRD was the most significant risk factor for relapse (hazard ratio, 5.22). MRD results at weeks 16 to 22 correlated strongly with the earlier time point (P = .001) using a level of 10−4 or higher to define persistent disease. MRD analysis during early postremission therapy improves risk definitions and bolsters risk-oriented strategies. ClinicalTrials.gov identifier: NCT00358072.
- Subjects :
- Oncology
Male
Neoplasm, Residual
Transplantation Conditioning
Oncogene Proteins, Fusion
medicine.medical_treatment
Biochemistry
Translocation, Genetic
Risk Factors
MED/15 - MALATTIE DEL SANGUE
hemic and lymphatic diseases
Antineoplastic Combined Chemotherapy Protocols
Prospective Studies
Transplantation, Homologou
Hematology
Hazard ratio
Middle Aged
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prognosis
Chemotherapy regimen
Combined Modality Therapy
Survival Rate
Treatment Outcome
Female
Human
Adult
medicine.medical_specialty
Adolescent
Prognosi
Immunology
Young Adult
Acute lymphocytic leukemia
Internal medicine
medicine
Humans
Transplantation, Homologous
Aged
Chemotherapy
Antineoplastic Combined Chemotherapy Protocol
business.industry
Risk Factor
Cell Biology
medicine.disease
Minimal residual disease
Surgery
Transplantation
Prospective Studie
Adult Acute Lymphoblastic Leukemia
business
Stem Cell Transplantation
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....7003b58fd3f02e6be8cbc58ba8b9a14d