Oncogenetics and minimal residual disease are independent outcome predictors in adult patients with acute lymphoblastic leukemia

Blood ◽  
2014 ◽  
Vol 123 (24) ◽  
pp. 3739-3749 ◽  
Author(s):  
Kheira Beldjord ◽  
Sylvie Chevret ◽  
Vahid Asnafi ◽  
Françoise Huguet ◽  
Marie-Laure Boulland ◽  
...  

Key Points In adult ALL, oncogenetic markers and minimal residual disease levels are independent outcome predictors. Both factors should be used for individual treatment stratification.

Blood ◽  
2006 ◽  
Vol 107 (3) ◽  
pp. 1116-1123 ◽  
Author(s):  
Monika Brüggemann ◽  
Thorsten Raff ◽  
Thomas Flohr ◽  
Nicola Gökbuget ◽  
Makoto Nakao ◽  
...  

AbstractAdult patients with acute lymphoblastic leukemia (ALL) who are stratified into the standard-risk (SR) group due to the absence of adverse prognostic factors relapse in 40% to 55% of the cases. To identify complementary markers suitable for further treatment stratification in SR ALL, we evaluated the predictive value of minimal residual disease (MRD) and prospectively monitored MRD in 196 strictly defined SR ALL patients at up to 9 time points in the first year of treatment by quantitative polymerase chain reaction (PCR). Frequency of MRD positivity decreased from 88% during early induction to 13% at week 52. MRD was predictive for relapse at various follow-up time points. Combined MRD information from different time points allowed definition of 3 risk groups (P < .001): 10% of patients with a rapid MRD decline to lower than 10-4 or below detection limit at day 11 and day 24 were classified as low risk and had a 3-year relapse rate (RR) of 0%. A subset of 23% with an MRD of 10-4 or higher until week 16 formed the high-risk group, with a 3-year RR of 94% (95% confidence interval [CI] 83%-100%). The remaining patients whose RR was 47% (31%-63%) represented the intermediate-risk group. Thus, MRD quantification during treatment identified prognostic subgroups within the otherwise homogeneous SR ALL population who may benefit from individualized treatment.


Blood ◽  
2014 ◽  
Vol 124 (26) ◽  
pp. 3932-3938 ◽  
Author(s):  
Etan Orgel ◽  
Jonathan Tucci ◽  
Waseem Alhushki ◽  
Jemily Malvar ◽  
Richard Sposto ◽  
...  

Key Points Obesity is associated with increased risk for persistent minimal residual disease after induction therapy for pediatric BP-ALL.


2002 ◽  
Vol 20 (4) ◽  
pp. 1094-1104 ◽  
Author(s):  
Forida Y. Mortuza ◽  
Mary Papaioannou ◽  
Ilidia M. Moreira ◽  
Luke A. Coyle ◽  
Paula Gameiro ◽  
...  

PURPOSE: Investigation of minimal residual disease (MRD) in childhood acute lymphoblastic leukemia (ALL) using molecular markers has proven superior to other standard criteria (age, sex, and WBC) in distinguishing patients at high, intermediate, and low risk of relapse. The aim of our study was to determine whether MRD investigation is valuable in predicting outcome in Philadelphia-negative adult patients with ALL. PATIENTS AND METHODS: MRD was assessed in 85 adult patients with B-lineage ALL by semiquantitative immunoglobulin H gene analysis on bone marrow samples collected during four time bands in the first 24 months of treatment. Fifty patients received chemotherapy only and 35 patients received allogeneic (n = 19) or autologous (n = 16) bone marrow transplantation (BMT) in first clinical remission. The relationship between MRD status and clinical outcome was investigated and compared with age, sex, immunophenotype, and presenting WBC count. RESULTS: Fisher’s exact test established a statistically significant concordance between MRD results and clinical outcome at all times. Disease-free survival (DFS) rates for MRD-positive and -negative patients and log-rank testing established that MRD positivity was associated with increased relapse rates at all times (P < .05) but was most significant at 3 to 5 months after induction and beyond. MRD status after allogeneic BMT rather than before was found to be an important predictor of outcome in 19 adult patients with ALL tested. In patients receiving autologous BMT (n = 16), the MRD status before BMT was more significant (P = .005). CONCLUSION: The association of MRD test results and DFS was independent of and greater than other standard predictors of outcome and is therefore important in determining treatment for individual patients.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5123-5123
Author(s):  
Stephane Lepretre ◽  
Chantal Touboul ◽  
Alain Flinois ◽  
Lucie Kutikova ◽  
Kahina Makhloufi ◽  
...  

Introduction: In adult patients with acute lymphoblastic leukemia (ALL), the presence of a minimal residual disease (MRD+), defined as the persistence of tumoral cells at a submicroscopic level, is widely recognized as the most sensitive prognostic factor for relapse and death regardless of treatment choice and risk classification. Although ALL specific treatment guidelines and protocols recommend MRD testing, there is little published literature on how the MRD status would impact on the quality of life (QoL) of adult patients with ALL. This research study aims to describe and assess the impact of MRD status on QoL of different subgroup of adult patients with ALL. Methods: In this French, multi-center, non-interventional, cross-sectional study, a retrospective section consisted of collecting sociodemographic and clinical data extracted from patient medical records of enrolled patients, and a prospective section comprised the following 3 patient reported outcome (PRO) questionnaires that patients completed: the "EuroQol-five-dimensions-3 levels" questionnaire (EQ-5D-3L, a generic PRO from the European Quality-of-life [EuroQol] group), the "Quality of Life Questionnaire - Core 30" (QLQ-C30 , a cancer-specific PRO from the European Organization for Research and Treatment of Cancer [EORTC]), and the "Functional Assessment of Cancer Therapy-Leukemia" questionnaire (FACT-Leu, a leukemia-specific PRO from the Functional Assessment of Chronic Illness Therapy [FACIT]). Adult patients with ALL seen during the inclusion period, regardless of treatment setting and status were enrolled in this Study through hematologists who participated in the study. Results: The study enrolled 221 patients and the analysis was performed on 151 patients who have data on last MRD status. Only 28 patients were MRD+. Median age at the time of inclusion was 57 years (range: 21-83) for MRD+ patients and 53 years (range:19-79) for MRD- patients, 61% and 62% were male, respectively. Median time from diagnosis was 0.5 years and 2.2 years and median age at diagnosis was 53.0 years (range: 5-83) and 48.8 years (range: 5-79), respectively. Less than 40% of the patients received a HSCT prior to inclusion. Most patients (91.9%) who were MRD- at the last testing had an ECOG score 0-1, compared with 71.4% MRD+ patients. More MRD- than MRD+ patients were receiving a frontline therapy (82.1% vs 60.7%) and nearly all (98.4%) MRD- patients had reached a CR at the time of inclusion in this study (vs 50.0% MRD+ patients). Results on all PROs (EQ-5D-3L, QLQ-C30 and FACT-Leu questionnaires) were consistent, showing a lower QoL score in MRD+ patients compared with MRD- patients (Table 1) Using EQ-5D-3L, a higher proportion of patients with MRD+ reported at least one problem that impacted "usual activities", "pain/discomfort" and "selfcare" dimensions; no differences were seen between MRD+ and MRD- patients on "mobility" and "anxiety/depression" dimensions. Using QLQ-C30, symptoms scales and 3 single items ("dyspnea", "insomnia" and "appetite loss") were higher in patients with MRD+ at the last testing than in patients with MRD-, representing a higher level of symptomatology/problems in this group. Using FACT-Leu, all primary QoL domains (except for "social/family well-being" domain) were lower in patients with MRD+ than in patients with MRD-. Conclusions: This study shows that QoL is impaired in patients with MRD+. Disclosures Kutikova: Amgen: Employment. Makhloufi:Amgen (France) SAS: Employment. Chauny:Amgen (France) SAS: Employment. Désaméricq:Amgen (France) SAS: Employment.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4114-4114
Author(s):  
Veronika Bachanova ◽  
Michael J Burke ◽  
Claudio Brunstein ◽  
Michael R Verneris ◽  
Qing Cao ◽  
...  

Abstract Abstract 4114 Background: Umbilical cord blood (UCB) has become a valuable alternative source of stem cells for patients with high risk acute lymphoblastic leukemia (ALL) lacking a matched sibling donor. Data on the efficacy of transplant outcomes after UCB in ALL are limited, particularly for the adult population. Methods: We report the outcomes of 143 patients (74 children <18 years and 68 adults) with ALL who received UCBT at University of Minnesota between 1999–2010. Most had precursor-B ALL (n=87 [61%]), Philadelphia positive ALL (Ph+; n=41 [29%] and T cell ALL (n=15 [10%]). All except 7 patients were in complete remission (CR1: n=59 [41%] or CR2/CR3: n=77 [54%]). Most adults received double UCB grafts (adult =90% vs. children =27%, p=0.01) with HLA locus matching of 4/6 and 5/6 in 65% and 28% of adults vs. 29% and 53% of children (p=0.01). 86 had an assessment of Minimal Residual Disease (MRD) prior to UCBT using 4 to 6 color flow-cytometric analysis and MRD was based on prior (diagnostic) immunophenotype and according to published standards. Ten patients had MRD detected immediately prior to UCBT (2 patients were in CR1, 7 in CR2, 1 in CR3) and 76 patients were MRD-negative. Most patients (82%) received myeloablative conditioning (cyclophosphamide 120 mg/kg, fludarabine 75mg/m2 and total body irradiation (TBI) 1200–1320cGy). Non-myeloablative conditioning (cyclophosphamide 50mg/kg, fludarabine 200mg/m2 and TBI 200cGy was given to patients above 45 years (n=18 [13%]) and in those with poor fitness (n=8 [5%]). All patients received cyclosporine (day −3 to day +180) and mycophenolate mofetil ( day −3 to day +45) post-HCT. Results: The cumulative incidence of neutrophil engraftment by day 42 was 97% (95%CI 92–99%). Six months platelet engraftment was 71% (95%CI 67–85%), 48% (95% CI 32–64%) and 84% (95%CI 58–100%); p<0.01) for patients ≤18 years, 19–45 and >45 years of age, respectively. With a median follow-up of 3.9 years (0.5–11.8 years), the 3-year leukemia-free survival (LFS) and overall survival (OS) was 47% (95%CI 38–55%) and 49% (95%CI 40–57%) with trend to better OS in children (Table). Cumulative incidence of relapse at 1 year was 17% (95%CI 11–23%) and the relative risk tended to lower rates in adults following MA vs NMA conditioning (7% [95%CI 0–14% vs 21% [95%CI 5–37%]; p=0.19). In univariate analysis age, disease status (CR1 vs CR2/CR3 vs. non CR), disease group (pre-B ALL, Ph+ALL, T-ALL) or time to transplant had no impact on relapse rate. Treatment-related mortality at 1 year was higher in adult patients aged 18–45 years (46% [95%CI 31–61%]) compared to children (19% [95%CI 10–28%]) or older patients who received NMA conditioning regimen (TRM 5% [95%CI 0–15%]; p<0.01). Patients with MRD detected immediately prior to UCBT had a higher relative risk of relapse at 2 years (30% [95%CI 4–56%]) and lower LFS (30% [95%CI 7–58%]) compared to MRD- group (16% [95%CI 8–25%]; p=0.05 and 61% [95%CI 49–70%]; p=0.05); respectively. Conclusion: UCBT expands the options for patients with ALL and offers potent protection from post-transplant relapse. Our results indicate that novel strategies in UCB HCT for ALL should focus on decreasing TRM in adult patients receiving myeloablative conditioning and improving leukemia control to induce a MRD- state pre- transplant. Disclosures: No relevant conflicts of interest to declare.


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