scholarly journals Allogeneic Transplantation for Ph+ Acute Lymphoblastic Leukemia (ALL): Impact of Conditioning Intensity, Tyrosine Kinase Inhibitors (TKI) and Minimal Residual Disease (MRD)

2013 ◽  
Vol 19 (2) ◽  
pp. S223
Author(s):  
Veronika Bachanova ◽  
David Marks ◽  
Mei-Jie Zhang ◽  
Hailin Wang ◽  
Daniel J. Weisdorf
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Minimal Residual Disease ◽  
Kinase Inhibitors ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Transplantation ◽  
Conditioning Intensity ◽  
Minimal Residual

scholarly journals Outcomes of Children With BCR-ABL1–Like Acute Lymphoblastic Leukemia Treated With Risk-Directed Therapy Based on the Levels of Minimal Residual Disease

2014 ◽  
Vol 32 (27) ◽  
pp. 3012-3020 ◽  
Author(s):  
Kathryn G. Roberts ◽  
Deqing Pei ◽  
Dario Campana ◽  
Debbie Payne-Turner ◽  
Yongjin Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Kinase Inhibitors ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Ras Signaling ◽  
Abl Tyrosine Kinase ◽  
Minimal Residual

Purpose BCR-ABL1–like acute lymphoblastic leukemia (ALL) is a recently identified B-cell ALL (B-ALL) subtype with poor outcome that exhibits a gene expression profile similar to BCR-ABL1-positive ALL but lacks the BCR-ABL1 fusion protein. We examined the outcome of children with BCR-ABL1–like ALL treated with risk-directed therapy based on minimal residual disease (MRD) levels during remission induction. Patients and Methods Among 422 patients with B-ALL enrolled onto the Total Therapy XV study between 2000 and 2007, 344 had adequate samples for gene expression profiling. Next-generation sequencing and/or analysis of genes known to be altered in B-ALL were performed in patients with BCR-ABL1–like ALL who had available material. Outcome was compared between patients with and those without BCR-ABL1–like ALL. Results Forty (11.6%) of the 344 patients had BCR-ABL1–like ALL. They were significantly more likely to be male, have Down syndrome, and have higher MRD levels on day 19 and at the end of induction than did other patients with B-ALL. Among 25 patients comprehensively studied for genetic abnormalities, 11 harbored a genomic rearrangement of CRLF2, six had fusion transcripts responsive to ABL tyrosine kinase inhibitors or JAK inhibitors, and seven had mutations involving the Ras signaling pathway. There were no significant differences in event-free survival (90.0% ± 4.7% [SE] v 88.4% ± 1.9% at 5 years; P = .41) or in overall survival (92.5% ± 4.2% v 95.1% ± 1.3% at 5 years; P = .41) between patients with and without BCR-ABL1–like ALL. Conclusion Patients who have BCR-ABL1–like ALL with poor initial treatment response can be salvaged with MRD-based risk-directed therapy and may benefit from identification of kinase-activating lesions for targeted therapies.

scholarly journals Minimal Residual Disease Assessment and Allogeneic Transplantation As Consolidation Therapy in Acute Lymphoblastic Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-8
Author(s):  
Jf Combariza ◽  
Leonardo Bautista Toloza ◽  
M Arango ◽  
L Diaz ◽  
Claudia Agudelo Lopez ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
De Novo ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Transplantation ◽  
Disease Assessment ◽  
Negative Group ◽  
First Remission ◽  
Minimal Residual

Minimal Residual Disease Assessment and Allogeneic Transplantation as Consolidation Therapy in Acute Lymphoblastic Leukemia Abstract Introduction: Detectable minimal residual disease (MRD) after therapy for acute lymphoblastic leukemia (ALL) is the strongest predictor of hematologic relapse (1-4). Colombian reports of adults with ALL showed poor survival rates, the median OS was 12 months and the median PFS was only 7 months (5,6). Most reports from Colombia as well as Latin America did not include patients that had a transplant as an initial consolidation strategy and used MRD as prognostic factor. (7-9). The objective of the study was to assess progression free survival (PFS) and overall survival (OS) of patients with ALL according with MRD status at end of induction therapy. Methods: A retrospective cohort comparing PFS and OS in adults with de novo ALL, according to the MRD status at the end of induction chemotherapy, and the type of post-induction consolidation strategy used. This research work had the endorsement of the ethics and research committees of the institutions where it was carried out. Results: Were included 165 adults with ALL in the MRD investigational group, the basal characteristics of the population are described in table 1.There were 73 patients in the MDR negative group and 92 in the MDR positive group. Median PFS for the MRD positive group was 11 months (CI 95% 11.7 - 22.2), and not reached for the MRD negative group (p<0.001). At three-years PFS was 18% and 55 %, respectively (p<0,001). Fig 1. The median OS for MRD positive patients was 16 months (CI 95%, 8.8 - 23.15) and was not reached in the MRD negative group. At three-years, OS was 26 % and 51 % for the former and latter group, respectively. Fig 2. Among subjects that were not transplanted, median PFS was 21 months for MRD negative and 9 months MRD positive patients (p<0.001). Fig 3A. Median of PFS was not reached in either group, whereas 3-year PFS was 64% for MRD negative and 70% for MRD positive patients when transplantation in first remission was used (p=0.861). Fig 3B. For the patients with only chemotherapy for consolidation treatment, the median OS were 16 months (IC 95% 11.32 to 20.67) for MRD positive, and 27 months IC 95% (20.91 to 33.09) in negative MRD. (p=0.004). The 3-year OS 34% for MRD negative and 22% for MRD positive patients. Fig 4A. The individuals with allogeneic transplantation during first remission overcome de risk of death in the positive MRD status. The median OS were 16 months for positive MRD and transplantation and not reached in negative MRD group, The 3 year OS were 74% for MRD negative and 49% for MRD positive patients. (p=0.187). Fig 4B. Multivariate analysis At multivariate analysis, the Negative MRD status and transplantation in first remission were associated with better PFS and OS, in these patients with ALL de novo, Table 2. Conclusion: MRD status at end of induction is an independent prognostic factor for PFS and OS in adult ALL. Allogeneic transplantation in first remission may overcome the adverse prognostic impact MRD. This is the first report that verifies the impact of MRD, on progression free survival and overall survival in the Colombian population. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document