Abstract
Abstract 2573
In adult Ph- ALL two major risk groups are generally identified on account of patient age, presentation white blood cell (WBC) count, disease immunophenotype and genetics/cytogenetics, with 5-year overall and disease-free survival (OS, DFS) rates of approximately 50% in standard-risk (SR) and 30% in high-risk (HR) patients, respectively. Although the difference is significant, this classification reflects a static risk assessment and does not recognize increasingly important factors such as individual response dynamics (complete remission [CR] vs induction failure or early relapse; MRD course) and risk-oriented treatment decisions with or without stem-cell transplantation (SCT).
To evaluate dynamic risk factors in association with adherence to risk-oriented therapy as major determinants of outcome.
OS and DFS rates were reanalyzed according to MRD-related risk definitions and risk-oriented treatment steps in a prospective clinical trial (Bassan et al, Blood 2009;113:4153). Different risk and treatment subsets were identified according to (i) achievement of CR vs early failure due to induction death, early relapse or toxicity precluding the application of MRD/risk-oriented therapy according to trial design, and (ii) adherence to planned MRD/risk-oriented chemotherapy or SCT vs non-adherence unrelated to early failure. Outcome results were compared with those obtained using traditional SR and HR definitions.
Three-hundred and four patients with Ph- ALL were treated (age range 16–68 years, median 35 years; male 57%), of whom 258 (85%) entered CR and 18 and 28 proved refractory or died early, respectively. Among CR patients, 78 did not complete early consolidation and MRD study (50 relapse, 9 toxicity and 19 very HR to early SCT), while 144 did it and were allocated to MRD-oriented therapy and 36 without a sensitive probe for MRD analysis were allocated according to clinical risk class. Six-year OS and DFS were 44% (n=138) and 43% (n=122) in SR vs 28% (n=166) and 28% (n=136) in HR, respectively (P=0.0009). Instead, OS and DFS results according to early treatment response, completion of MRD study for risk re-stratification and adherence to MRD/risk-oriented therapy identified several distinct prognostic categories, in which survival, largely unrelated to age and clinical risk class, ranged from 0% at 2.8 mos. (early deaths) to 73% at 6–10 years (MRD-negative), as detailed in the table and figure.
In this study, long-term survival rates were about 50% in SR patients (MRD unknown), 70% in MRD-negative ones receiving chemotherapy, and 40%–50% in all those proceeding to allogeneic SCT because very HR, HR MRD unknown or MRD-positive. Therefore, using a risk/MRD-oriented strategy, the adherence to protocol design concurs to identify the patient subsets with the highest probability of cure.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
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