scholarly journals Minimal Residual Disease Diagnostics and Chimerism in the Post-Transplant Period in Acute Myeloid Leukemia

2011 ◽  
Vol 11 ◽  
pp. 310-319 ◽  
Author(s):  
Ulrike Bacher ◽  
Torsten Haferlach ◽  
Boris Fehse ◽  
Susanne Schnittger ◽  
Nicolaus Kröger
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Minimal Residual Disease ◽  
Real Time Pcr ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Quantitative Real Time Pcr ◽  
Post Transplant ◽  
Minimal Residual ◽  
Acute Myeloid

In acute myeloid leukemia (AML), the selection of poor-risk patients for allogeneic hematopoietic stem cell transplantation (HSCT) is associated with rather high post-transplant relapse rates. As immunotherapeutic intervention is considered to be more effective before the cytomorphologic manifestation of relapse, post-transplant monitoring gains increasing attention in stem cell recipients with a previous diagnosis of AML. Different methods for detection of chimerism (e.g., microsatellite analysis or quantitative real-time PCR) are available to quantify the ratio of donor and recipient cells in the post-transplant period. Various studies demonstrated the potential use of mixed chimerism kinetics to predict relapse of the AML. CD34+-specific chimerism is associated with a higher specificity of chimerism analysis. Nevertheless, a decrease of donor cells can have other causes as well. Therefore, efforts continue to introduce minimal residual disease (MRD) monitoring based on molecular mutations in the post-transplant period. TheNPM1(nucleophosmin) mutations can be monitored by sensitive quantitative real-time PCR in subsets of stem cell recipients with AML, but for approximately 20% of patients, suitable molecular mutations for post-transplant MRD monitoring are not available so far. This emphasizes the need for an expansion of the panel of MRD markers in the transplant setting.

scholarly journals Monitoring of Post-Transplant MLL-PTD as Minimal Residual Disease Can Predict Relapse After Allogeneic HSCT in Patients With Acute Myeloid Leukemia and Myelodysplastic Syndrome

2021 ◽  
Author(s):  
Jun Kong ◽  
Meng-Ge Gao ◽  
Ya-Zhen Qin ◽  
Yu Wang ◽  
Chen-Hua Yan ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Significant Difference ◽  
Minimal Residual ◽  
Acute Myeloid

Abstract Background: MLL-PTD is a special MLL rearrangement gene that occurs in about 5-10% of acute myeloid leukemia (AML) with a normal karyotype and in 5-6% of myelodysplastic syndrome (MDS) patients. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently one of the curative therapies available for AML and MDS with excess blasts (MDS-EB). However, how the prognosis of patients with high levels of MLL-PTD after allo-HSCT, including AML and MDS, and whether MLL-PTD could be used as a reliable indicator for minimal residual disease (MRD) monitoring in transplant patients remains unknown. Our study purposed to analyze the dynamic changes of MLL-PTD peri-transplantation and the best threshold for predicting relapse after transplantation.Methods: We retrospectively collected the clinical data of 48 patients with MLL-PTD AML or MDS-EB who underwent allo-HSCT in Peking University People’s Hospital. The MLL-PTD was examined by real-time quantitative polymerase chain reaction (RQ-PCR) at the diagnosis, before transplantation and the fixed time points after transplantation. Detectable MLL-PTD/ABL>0.08% was defined as MLL-PTD positive in this study.Results: The 48 patients included 33 AML patients and 15 MDS-EB patients. The median follow-up time was 26(0.7-56) months after HSCT. In AML patients, 7 patients (21.2%) died of treatment-related mortality (TRM), 6 patients (18.2%) underwent hematological relapse and died ultimately. Of the 15 patients with MDS-EB, 2 patients (13.3%) died of infection. The 3-year cumulative incidence of relapse (CIR), overall survival (OS), disease-free survival (DFS) and TRM were 13.7%±5.2%, 67.8%±6.9%, 68.1%±6.8% and 20.3%±6.1%, respectively. ROC curve showed that post-transplant MLL-PTD≥1.0% was the optimal cut-off value for predicting hematological relapse after allo-HSCT. There was statistical difference between post-transplant MLL-PTD≥1.0% and MLL-PTD<1.0% groups (3-year CIR: 75%±15.3% vs. 0%, P<0.001; 3-year OS: 25.0±15.3% vs. 80.7%±6.6%, P<0.001; 3-year DFS: 25.0±15.3% vs. 80.7%±6.6%, P<0.001; 3-year TRM: 0 vs. 19.3±6.6%, P=0.277). However, whether MLL-PTD≥1% or MLL-PTD<1% before transplantation has no significant difference on the prognosis. Conclusions: Our study indicated that MLL-PTD had a certain stability and could effectively reflect the change of tumor burden. The expression level of MLL-PTD after transplantation can serve as an effective indicator for predicting relapse.

Optimal Post-Remission Therapy for Flow-Cytometry Minimal Residual Disease Positive Patients with Acute Myeloid Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 610-610
Author(s):  
Francesco Buccisano ◽  
Luca Maurillo ◽  
Valter Gattei ◽  
Giovanni Del Poeta ◽  
Maria Ilaria Del Principe ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Consolidation Therapy ◽  
Minimal Residual ◽  
Acute Myeloid

Abstract Autologous (AuSCT) and allogeneic stem cell transplantation (SCT) are well established post-remissional strategies for patients with Acute Myeloid Leukemia (AML). However, there is still a debate ongoing about the relative merit of each of these options in first CR. Minimal residual disease (MRD) may be a useful tool to stratify AML patients into categories of risk which can benefit from differentiated post-remissional approaches. To address this issue, we analysed retrospectively, a series of 123 patients affected with AML in whom flow-cytometry serial determinations of MRD were available, at established time-points (post-induction, post-consolidation, post-stem cell transplantation). All were entered into the EORTC/GIMEMA protocols AML10/AML12 (age &lt;61 yrs) or AML13 (age&gt;61 yrs), all consisting in intensive induction and consolidation cycles, and, for patients aged &lt;61 years, AuSCT or SCT. Median age was 52 years (range 18–78), no APL cases were included in the study. The “Maximally Selected Rank Statistic” analysis was used to select the MRD level and the time-point of analysis achieving the best prognostic significance in terms of overall survival (OS) and relapse free survival (RFS). This test was specifically developed to find out the optimal cut-off for a given biological variable correlating with clinical parameters of interest. This approach confirmed the threshold of 3.5x10−4 residual leukemic cells after consolidation therapy, as a discriminator between MRD− and MRD+ cases with different 5-years OS (64% vs. 14%, P&lt;.001) and RFS (68% vs. 13%, P&lt;.001). Therefore, among these 123 patients, we enucleated 2 groups of patients which underwent stem cell transplant procedure, 53 AuSCT and 11 SCT. The two subgroups were balanced in terms of FAB categories, WBC count, karyotype and expression of MDR-1 phenotype; 34/64 (53%) were MRD+ (9 SCT, 25 AuSCT) and 30/64 (47%) were MRD− (1 SCT, 28 AuSCT). Among the 53 patients submitted to AuSCT, MRD− had a significant better outcome than those MRD+, both in terms of 5-years OS (68% vs. 24%, P=0.003) and RFS (68% vs. 11%, P&lt;.001). In the SCT group the low numbers hampered any firm conclusion; however, when the category of post-consolidation MRD+ patients was separately analysed, the use of SCT was associated with a better RFS (49% vs. 11%, P=NS); we assume that the lack of statistical significance was merely due to the few cases in the SCT group. In conclusion, the threshold of 3.5x10−4 at post-consolidation check-point is critical to predict disease outcome; MRD− patients have an excellent outcome regardless of the post-consolidation therapy; in the MRD+ group, AuSCT seems not to improve the prognosis whereas the use of SCT is associated with a superior outcome, although a larger number of patients is required to confirm this assumption. Figure Figure

scholarly journals Monitoring of post-transplant MLL-PTD as minimal residual disease can predict relapse after allogeneic HSCT in patients with acute myeloid leukemia and myelodysplastic syndrome

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Jun Kong ◽  
Meng-Ge Gao ◽  
Ya-Zhen Qin ◽  
Yu Wang ◽  
Chen-Hua Yan ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Minimal Residual Disease ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Significant Difference ◽  
Minimal Residual ◽  
Acute Myeloid

Abstract Background The mixed-lineage leukemia (MLL) gene is located on chromosome 11q23. The MLL gene can be rearranged to generate partial tandem duplications (MLL-PTD), which occurs in about 5-10% of acute myeloid leukemia (AML) with a normal karyotype and in 5-6% of myelodysplastic syndrome (MDS) patients. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently one of the curative therapies available for AML and MDS with excess blasts (MDS-EB). However, how the prognosis of patients with high levels of MLL-PTD after allo-HSCT, and whether MLL-PTD could be used as a reliable indicator for minimal residual disease (MRD) monitoring in transplant patients remains unknown. Our study purposed to analyze the dynamic changes of MLL-PTD peri-transplantation and the best threshold for predicting relapse after transplantation. Methods We retrospectively collected the clinical data of 48 patients with MLL-PTD AML or MDS-EB who underwent allo-HSCT in Peking University People’s Hospital. The MLL-PTD was examined by real-time quantitative polymerase chain reaction (RQ-PCR) at the diagnosis, before transplantation and the fixed time points after transplantation. Detectable MLL-PTD/ABL > 0.08% was defined as MLL-PTD positive in this study. Results The 48 patients included 33 AML patients and 15 MDS-EB patients. The median follow-up time was 26(0.7-56) months after HSCT. In AML patients, 7 patients (21.2%) died of treatment-related mortality (TRM), 6 patients (18.2%) underwent hematological relapse and died ultimately. Of the 15 patients with MDS-EB, 2 patients (13.3%) died of infection. The 3-year cumulative incidence of relapse (CIR), overall survival (OS), disease-free survival (DFS) and TRM were 13.7 ± 5.2, 67.8 ± 6.9, 68.1 ± 6.8 and 20.3% ± 6.1%, respectively. ROC curve showed that post-transplant MLL-PTD ≥ 1.0% was the optimal cut-off value for predicting hematological relapse after allo-HSCT. There was statistical difference between post-transplant MLL-PTD ≥ 1.0% and MLL-PTD < 1.0% groups (3-year CIR: 75% ± 15.3% vs. 0%, P < 0.001; 3-year OS: 25.0 ± 15.3% vs. 80.7% ± 6.6%, P < 0.001; 3-year DFS: 25.0 ± 15.3% vs. 80.7 ± 6.6%, P < 0.001; 3-year TRM: 0 vs. 19.3 ± 6.6%, P = 0.277). However, whether MLL-PTD ≥ 1% or MLL-PTD < 1% before transplantation has no significant difference on the prognosis. Conclusions Our study indicated that MLL-PTD had a certain stability and could effectively reflect the change of tumor burden. The expression level of MLL-PTD after transplantation can serve as an effective indicator for predicting relapse.

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