Gene mutations and pretransplant minimal residual disease predict risk of relapse in adult patients after allogeneic hematopoietic stem-cell transplantation for T cell acute lymphoblastic leukemia

2019 ◽  
Vol 60 (11) ◽  
pp. 2744-2753 ◽  
Author(s):  
Mingzhu Xu ◽  
Hong Liu ◽  
Yuejun Liu ◽  
Xiao Ma ◽  
Huiying Qiu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Stem Cell Transplantation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Gene Mutations ◽  
Hematopoietic Stem ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Minimal Residual ◽  
Risk Of Relapse

Use of Allogeneic Hematopoietic Stem-Cell Transplantation Based on Minimal Residual Disease Response Improves Outcomes for Children With Relapsed Acute Lymphoblastic Leukemia in the Intermediate-Risk Group

2013 ◽  
Vol 31 (21) ◽  
pp. 2736-2742 ◽  
Author(s):  
Cornelia Eckert ◽  
Günter Henze ◽  
Karlheinz Seeger ◽  
Nikola Hagedorn ◽  
Georg Mann ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Stem Cell Transplantation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Intermediate Risk ◽  
Treatment Intensification ◽  
Hematopoietic Stem ◽  
Minimal Residual ◽  
Risk Of Relapse

Purpose In children with intermediate risk of relapse of acute lymphoblastic leukemia (ALL), it is essential to identify patients in need of treatment intensification. We hypothesized that the prognosis of patients with unsatisfactory reduction of minimal residual disease (MRD) can be improved by allogeneic hematopoietic stem-cell transplantation (HSCT). Patients and Methods In the Acute Lymphoblastic Leukemia–Relapse Study of the Berlin-Frankfurt-Münster Group (ALL-REZ BFM) 2002, patients with an MRD level of ≥ 10−3 (n = 99) at the end of induction therapy were allocated to HSCT, whereas those with an MRD level less than 10−3 (n = 109) continued to receive chemotherapy. MRD was quantified by real-time polymerase chain reaction for clone-specific T-cell receptor/immunoglobulin gene rearrangements. Results The probability of event-free survival for patients with MRD ≥ 10−3 was 64% ± 5% in ALL-REZ BFM 2002 compared with 18% ± 7% in the predecessor study ALL-REZ BFM P95/96 (P < .001). This was mainly achieved by reducing the cumulative incidence of subsequent relapse (CIR) at 8 years from 59% ± 9% to 27% ± 5% (P < .001). The favorable prognosis of patients with MRD less than 10−3 could be confirmed in those with a late combined or isolated bone marrow B-cell precursor (BCP) –ALL relapse (CIR, 20% ± 5%), whereas patients with an early combined BCP-ALL relapse had an unfavorable outcome (CIR, 63% ± 13%; P < .001). Conclusion Allogeneic HSCT markedly improved the prognosis of patients with intermediate risk of relapse of ALL and unsatisfactory MRD response. As a result, outcomes in this group approximated those of patients with favorable MRD response. Patients with early combined relapse require treatment intensification even in case of favorable MRD response, demonstrating the prognostic impact of time to relapse.

Allogeneic hematopoietic stem cell transplantation contributes to eradication of minimal residual disease in adult Philadelphia chromosome-positive acute lymphoblastic leukemia patients treated with dasatinib.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7024-7024
Author(s):  
Jeremy Chang ◽  
Mojtaba Akhtari
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Minimal Residual

7024 Background: Philadelphia Chromosome-Positive (Ph+) disease is associated with a poor prognosis in acute lymphoblastic leukemia (ALL). Recent studies have shown that the eradication of minimal residual disease (MRD) in this population leads to improved survival outcomes. While hematopoietic stem cell transplantation (HSCT) has demonstrated clinical benefits in Ph+ ALL patients treated with the tyrosine kinase inhibitor (TKI) imatinib, its role is less clear with the use of more potent, newer-generation TKIs such as dasatinib. Methods: This was a retrospective study analyzing the impact of allogeneic HSCT on MRD status in Ph+ ALL patients treated with dasatinib. Patients were divided into 2 groups: those treated with chemotherapy plus dasatinib followed by allogeneic HSCT and those who received chemotherapy plus dasatinib alone. All patients underwent bone marrow biopsy with MRD analysis following induction therapy and subsequent re-evaluation of MRD status at day 100 post-transplant in the HSCT group and after further cycles of chemotherapy plus dasatinib in the non-transplant group. MRD-negative disease was defined as the absence of a BCR-ABL1 transcript by real-time quantitative polymerase chain reaction (qRT-PCR) with a sensitivity of 0.01%. Results: A total of 51 adult Ph+ ALL patients with MRD-positive disease following induction therapy were included. Twenty-seven patients (53%) were male and the median age at time of diagnosis was 42 years (range 23-68). There were 29 patients in the transplant group and 22 patients in the non-transplant group. When analyzing rates of MRD eradication, 18 (62%) patients in the transplant group were found to have MRD-negative disease at day 100 post-transplant compared to 7 (32%) patients in the non-transplant group who only received further cycles of chemotherapy plus dasatinib (risk ratio 0.56, 95% confidence interval 0.32-0.96, p = 0.048). Conclusions: In the era of newer-generation TKIs, allogeneic HSCT continues to have notable benefits in Ph+ ALL such as a significantly higher rate of MRD eradication as demonstrated in this study.

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