scholarly journals PCN75 COST-EFFECTIVENESS OF BLINATUMOMAB VERSUS CHEMOTHERAPY IN ADULT PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA IN FIRST HEMATOLOGICAL COMPLETE REMISSION WITH MINIMAL RESIDUAL DISEASE USING A MARKOV COHORT APPROACH

2020 ◽  
Vol 23 ◽  
pp. S36-S37
Author(s):  
T.E. Delea ◽  
N. Despiegel ◽  
D. Boyko ◽  
F. Dirnberger ◽  
S. Tiwana ◽  
...  
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.


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.


2021 ◽  
Vol 6 (1) ◽  
pp. 56-64
Author(s):  
O. A. Vynnytska ◽  
◽  
O. I. Dorosh ◽  
L. Ya. Dubey ◽  
N. V. Dubey

Immunophenotyping of leukemia cells was studied in this work; minimal residual disease was monitored among children with acute lymphoblastic leukemia under conditions of relapse and complete remission after the application of ALLIC-BFM 2009 cytostatic therapy. The study showed that after application of ALLIC-BFM 2009 therapy, 88% of children had complete remission, and 12% had relapses. Among patients with relapses, the number of blast cells in the bone marrow was at a high level (more than 6%). Monitoring of patients during therapy established an increase in the minimal residual disease level of more than 1% after treatment in patients with recurrent disease. Immunophenotyping of blast cells among patients with relapse showed the expression of linear independent antigens HLA (93%), Auti-TdT (91%), CD10 (78%), CD38 (91%) and CD34 (57%) and B-linear antigens: CD19, CD22, CD58, CD79a, the highest expression was found for the CD19 antigen. A low level of expression of CD45 (28%) was recorded with relapses of acute lymphoblastic leukemia and high (89%) level was with complete remission of the disease. We did not detect expression of antigens characteristic of T-cell acute lymphoblastic leukemia in bone marrow of patients with acute lymphoblastic leukemia, both with relapses and with remission. At the same time, the expression of myeloid antigens (CD33 and CD13) was noted among acute lymphoblastic leukemia patients. Among patients, the incidence of acute lymphoblastic leukemia was the most pronounced in children aged from 3 to 6 years – 37 patients (35.2%) and aged from 6 to 9 years – 26 (24.8%) patients. The highest accidence was found among patients with chromosomal translocation TEL / AML – 22 (21%) patients with a median age 5 years. In second place, the frequency of mutations is the translocation of E2A / PBX1. BCR / ABL translocation was less common. It was noted in 1.9% of patients, but the expression of this gene indicated a bad course of the disease, as patients after cytostatic therapy under the ALLIC BFM 2009 program had a recurrence. Recurrence was also observed in patients with TEL/AML chromosomal translocation. Determination of minimal residual disease showed its increased level in patients with chromosomal aberrations BCR / ABL and TEL/AML throughout the treatment phase. In addition, patients in these groups were diagnosed with initial leukocytosis followed by leukopenia after a course of chemotherapy. Patients of all groups showed a decrease in hemoglobin. The biggest changes in clinical and laboratory parameters were found between patients with chromosomal translocations BCR/ABL and TEL/AML, as evidenced by the development of relapses in patients of these groups. The low level of association between karyotype disorders, with the formation of AF4/MLL and E2A/PBX1, and clinical and laboratory parameters in patients with acute lymphoblastic leukemia may indicate that the isolated clonal disorders are independent prognostic factors for the course of the disease


Blood ◽  
2018 ◽  
Vol 131 (14) ◽  
pp. 1522-1531 ◽  
Author(s):  
Nicola Gökbuget ◽  
Hervé Dombret ◽  
Massimiliano Bonifacio ◽  
Albrecht Reichle ◽  
Carlos Graux ◽  
...  

Abstract Approximately 30% to 50% of adults with acute lymphoblastic leukemia (ALL) in hematologic complete remission after multiagent therapy exhibit minimal residual disease (MRD) by reverse transcriptase–polymerase chain reaction or flow cytometry. MRD is the strongest predictor of relapse in ALL. In this open-label, single-arm study, adults with B-cell precursor ALL in hematologic complete remission with MRD (≥10−3) received blinatumomab 15 µg/m2 per day by continuous IV infusion for up to 4 cycles. Patients could undergo allogeneic hematopoietic stem-cell transplantation any time after cycle 1. The primary end point was complete MRD response status after 1 cycle of blinatumomab. One hundred sixteen patients received blinatumomab. Eighty-eight (78%) of 113 evaluable patients achieved a complete MRD response. In the subgroup of 110 patients with Ph-negative ALL in hematologic remission, the Kaplan-Meier estimate of relapse-free survival (RFS) at 18 months was 54%. Median overall survival (OS) was 36.5 months. In landmark analyses, complete MRD responders had longer RFS (23.6 vs 5.7 months; P = .002) and OS (38.9 vs 12.5 months; P = .002) compared with MRD nonresponders. Adverse events were consistent with previous studies of blinatumomab. Twelve (10%) and 3 patients (3%) had grade 3 or 4 neurologic events, respectively. Four patients (3%) had cytokine release syndrome grade 1, n = 2; grade 3, n = 2), all during cycle 1. After treatment with blinatumomab in a population of patients with MRD-positive B-cell precursor ALL, a majority achieved a complete MRD response, which was associated with significantly longer RFS and OS compared with MRD nonresponders. This study is registered at www.clinicaltrials.gov as #NCT01207388.


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 ◽  
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.


Sign in / Sign up

Export Citation Format

Share Document