scholarly journals Description and prognostic significance of the kinetics of minimal residual disease status in adults with acute lymphoblastic leukemia treated with HyperCVAD

2018 ◽  
Vol 93 (4) ◽  
pp. 546-552 ◽  
Author(s):  
Ryan D. Cassaday ◽  
Philip A. Stevenson ◽  
Brent L. Wood ◽  
Pamela S. Becker ◽  
Paul C. Hendrie ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Disease Status ◽  
Kinetics Of ◽  
Minimal Residual

Minimal Residual Disease Status Is the Most Important Preditive Factor in Adults with Acute Lymphoblastic Leukemia. Prospective, Multicenter PALG 4-2002 MRD Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2821-2821 ◽  
Author(s):  
Jerzy Holowiecki ◽  
Malgorzata Krawczyk-Kulis ◽  
Sebastian Giebel ◽  
Krystyna Jagoda ◽  
Beata Stella-Holowiecka ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Hematopoietic Cell Transplantation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Disease Status ◽  
High Dose ◽  
Risk Criteria ◽  
Minimal Residual

Abstract Current therapeutic protocols for adult acute lymphoblastic leukemia (ALL) take into account the risk of relapse, in order adjust the treatment intensity to individual patient needs. It is postulated that in addition to “classical” risk criteria the status of minimal residual disease (MRD) should be considered for treatment decisions. The aim of this study was to prospectively evaluate the feasibility and prognostic significance of MRD detected with the use of immunophenotyping for outcome of ALL patients treated according to 4-2002 protocol of the Polish Adult Leukemia Group (PALG). Induction therapy included PDN, Asp and 4x epirubicin+VCR. Consolidation consisted of 2x high-dose AraC+Cy, 2x Mtx+Vep, 6MP, and CNS prophylaxis. Patients stratified to high risk (HR) group according to “classical” criteria based on those formerly developed by GMALL (bcr/abl(+), WBC>30 G/L, prepreB, early or mature T phenotype, age>35y, or prolonged time to achieve CR) were further referred for hematopoietic cell transplantation (HCT), whereas those assigned to standard risk (SR) group were treated with maintenance for 2 years. MRD was tested at the level of 0.1% after completion of induction and consolidation therapy in patients achieving CR, employing multicolor flow-cytometry, including a new “empty spaces” method taking into account an individual pattern of antigen expression on blast cells. 165 ALL pts (B-lineage 79%, T-lineage 21%), aged 29 y (17–60) were included. CR rate equaled 85,5%. 23% of CR pts were assigned to SR, 77%- to HR according to classical criteria. MRD evaluation was possible in all but 8 pts. After induction 37% of CR pts were found MRD(+). Among those who remained in CR, MRD after consolidation was detected in 26% of cases. 64% of patients were MRD(−) at both time-points, whereas in the remaining 36% of cases MRD was detected at least once. MRD status affected both relapse incidence (RI) and leukemia-free survival (LFS). After 3 years the RI was higher for pts with MRD(+) vs. MRD(−) if assessed after induction (82%vs.29%,p=0.00007) and after consolidation (62%vs.41%,p=0.05). For pts with MRD(−) at both study end-points the probability of LFS was 65% whereas for those with MRD(+) after either induction and/or consolidation − 26% (p=0.008). In the respective subgroups RI equaled 28% and 73% (p=0.004). The difference was observed for patients assigned to SR group (20%vs.92%,p=0.01) as well as to HR group (33%vs.70%,p=0.05). In a multivariate analysis including classical risk criteria the MRD status remained the only significant factor predictive for RI (HR: 2.5(1.3–4.8),p=0.006) and LFS (HR: 2.1(1.2–3.9),p=0.01). We conclude that immunophenotyping employing “empty spaces” method is feasible for MRD evaluation in adults with ALL. MRD stzatus after induction and consolidation is the most important predictive factor for RI and LFS. Based on our findings patients with MRD detected after induction and/or consolidation should be offered intensified treatment with the use of HCT irrespective of the absence of other risk factors.

scholarly journals PROGNOSTIC SIGNIFICANCE AND TREATMENT IMPLICATIONS OF MINIMAL RESIDUAL DISEASE STUDIES IN PHILADELPHIA-NEGATIVE ADULT ACUTE LYMPHOBLASTIC LEUKEMIA

2014 ◽  
Vol 6 (1) ◽  
pp. e2014062 ◽  
Author(s):  
Orietta Spinelli ◽  
Manuela Tosi ◽  
Barbara Peruta ◽  
Marie Lorena Guinea Montalvo ◽  
Elena Maino ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Adult Acute Lymphoblastic Leukemia ◽  
Cure Rates ◽  
Sensitive Individual ◽  
Minimal Residual ◽  
Risk Of Relapse

Acute lymphoblastic leukemia (ALL) is curable in about 40-50% of adult patients, however this is subject to ample variations owing to several host- and disease-related prognostic characteristics. Currently, the study of minimal residual disease (MRD) following induction and early consolidation therapy stands out as the most sensitive individual prognostic marker to define the risk of relapse following the achievement of remission, and ultimately that of treatment failure or success. Because substantial therapeutic advancement is now being achieved using intensified pediatric-type regimens, MRD analysis is especially useful to orientate stem cell transplantation choices. These strategic innovations are progressively leading to greater than 50% cure rates. 

scholarly journals DNA Methylation Adds Prognostic Value to Minimal Residual Disease Status in Pediatric T‐Cell Acute Lymphoblastic Leukemia

2016 ◽  
Vol 63 (7) ◽  
pp. 1185-1192 ◽  
Author(s):  
Magnus Borssén ◽  
Zahra Haider ◽  
Mattias Landfors ◽  
Ulrika Norén‐Nyström ◽  
Kjeld Schmiegelow ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Minimal Residual Disease ◽  
Prognostic Value ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Status ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Minimal Residual

Importance of Minimal Residual Disease Testing During the Second Year of Therapy for Children With Acute Lymphoblastic Leukemia

2003 ◽  
Vol 21 (4) ◽  
pp. 704-709 ◽  
Author(s):  
Glenn M. Marshall ◽  
Michelle Haber ◽  
Edward Kwan ◽  
Ling Zhu ◽  
Daniella Ferrara ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Maintenance Chemotherapy ◽  
Childhood All ◽  
Second Year ◽  
Minimal Residual

Purpose: A high level of minimal residual disease (MRD) after induction chemotherapy in children with acute lymphoblastic leukemia (ALL) is an indicator of relative chemotherapy resistance and a risk factor for relapse. However, the significance of MRD in the second year of therapy is unclear. Moreover, it is unknown whether treatment intervention can alter outcome in patients with detectable MRD. Patients and Methods: We assessed the prognostic value of MRD testing in bone marrow samples from 85 children at 1, 12, and 24 months from diagnosis using clone-specific polymerase chain reaction primers designed to detect clonal antigen receptor gene rearrangements. These children were part of a multicenter, randomized clinical trial, which, in the second year of treatment, compared a 2-month reinduction-reintensification followed by maintenance chemotherapy with standard maintenance chemotherapy alone. Results: MRD was detected in 69% of patients at 1 month, 25% at 12 months, and 28% at 24 months from diagnosis. By univariate analysis, high levels of MRD at 1 month, or the presence of any detectable MRD at 12 or 24 months from diagnosis, were highly predictive of relapse. Multivariate analysis showed that MRD testing at 1 and 24 months each had independent prognostic significance. Intensified therapy at 12 months from diagnosis did not improve prognosis in those patients who were MRD positive at 12 months from diagnosis. Conclusion: Clinical outcome in childhood ALL can be predicted with high accuracy by combining the results of MRD testing at 1 and 24 months from diagnosis.

scholarly journals Prognostic significance of minimal residual disease in infants with acute lymphoblastic leukemia treated within the Interfant-99 protocol

Leukemia ◽  
2009 ◽  
Vol 23 (6) ◽  
pp. 1073-1079 ◽  
Author(s):  
V H J Van der Velden ◽  
L Corral ◽  
M G Valsecchi ◽  
M W J C Jansen ◽  
P De Lorenzo ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Minimal Residual

Prognostic Significance of Minimal Residual Disease in Adult Patients with B-Lineage Acute Lymphoblastic Leukemia by 8-Color Flow Cytometry

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4789-4789
Author(s):  
Xiang-Qin Weng ◽  
Yang Shen ◽  
Yan Sheng ◽  
Bing Chen ◽  
Jing-han Wang ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Lymphoblastic Leukemia ◽  
Treatment Response ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Color Flow ◽  
B Lineage ◽  
Minimal Residual

Abstract Abstract 4789 Monitoring of minimal residual disease (MRD) in patients with acute lymphoblastic leukemia (ALL) by immunophenotyping and/or molecular techniques provides a way to precisely evaluate early treatment response and predict relapse. In this study, we have investigated the prognostic significance of MRD in adult patients with B-lineage acute lymphoblastic leukemia (B-ALL) by 8-color flow cytometry. A cohort of 106 patients with B-ALL who had achieved a complete remission (CR) and at least 1 LAIP characteristics were enrolled to perform MRD assessment at the end of induction and 1 cycle of consolidation. LAIPs were identifiable in 96% of the patients by 8-color flow cytometric assay, in which, most cases (90.6%) containing 2 or more LAIPs had a sensitivity as high as identifying 1 leukemic blast among 1×105 BM nucleated cells. MRD negative status could clearly predict a favorable 1 year relapse free survival (RFS) and 2 year overall survival (OS) when a cut-off level of 0.01% was used to define MRD positivity at the point of achieving CR (P=0.000 and 0.000, respectively) and after 1 cycle of consolidation (P=0.000 and 0.000, respectively), respectively. In multivariate analysis including cytogenetic abnormalities, clinical factors and MRD status, late CR (P=0.046), MRD status at the points of obtaining CR (P=0.016) and 1 consolidation (P=0.007) were associated with RFS independently, while only MRD status after 1 course of consolidation was independent prognostic factor for OS (P=0.000). Of note, in exploring the fewer patients with MRD negative status experienced recent relapse, we have identified that most of such patients had a MRD level of 10−4−10−5 comparing to undetectable MRD level. Furthermore, our evidences showed that MRD assessed by flow cytometry and by RQ-PCR assay targeting to BCR-ABL fusion gene yielded concordant results in the vast majority of cases (90%). In conclusion, immunophenotypic evaluation of MRD by 8-color flow cytometry could work as an important tool to assess the treatment response and prognosis precisely in adult B-ALL. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document