scholarly journals Prognostic value of minimal residual disease before allogeneic hematopoietic stem cell transplantation in patients with acute leukemia

2021 ◽  
Vol 66 (4) ◽  
pp. 539-555
Author(s):  
Z. V. Konova ◽  
E. N. Parovichnikova ◽  
I. V. Galtseva ◽  
M. Yu. Drokov ◽  
Yu. O. Davydova ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Minimal Residual Disease ◽  
Prognostic Value ◽  
Residual Disease ◽  
Disease Status ◽  
Long Term Results ◽  
Disease Relapse ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Minimal Residual

Introduction. One of the main causes of treatment failure after allogeneic hematopoietic stem cells transplantation (alloHSCT) for acute leukemia (AL) is disease relapse. In recent years, multiparameter fl ow cytometry (MPC) has been widely used to detect minimal residual disease (MRD) because of its capacity to identify patients with a high risk of relapse due to availability and the ability to obtain results in a timely manner.Aim — to evaluate the prognostic value of MRD status before allo-HSCT and the effect of donor type and conditioning intensity on long-term results of allo-HSCT of MOB-positive patients.Patients and methods. The analysis included 107 patients with acute myeloid leukemia (AML) and 63 patients with acute lymphoblastic leukemia (ALL) who underwent allo-HSCT between September 2015 and June 2020. All patients were in complete morphological remission before allo-HSCT. At the time of allo-HSCT 91 patients with AML and 37 patients with ALL were in the first complete remission (CR), in their second and more than two CRs were 16 and 26 patients, respectively. The median follow-up was 18 (1.5–48) months for AML and 14 (1.8–60.1) months for ALL. Immunophenotypic study was performed before allo-HSCT. MRD was detected using a combination of the “different from normal” method and the search for cells with a leukemia-associated immunophenotype.Results. The disease status at the time of transplantation and the presence of MRD before allo-HSCT were independent factors infl uencing the probability of relapse (disease status: HR = 2.911, 95% CI: 1.328–6.379; MRD before allo-HSCT: HR = 7.667, 95% CI: 3.606–16.304) and post-transplant mortality (disease status: HR = 2.911, 95% CI: 1.328–6.379; MRD before allo-HSCT: HR = 7.667, 95% CI: 3.606–16.304). In univariate analysis, the relapse-free survival of MRD+ patients with AL in the first CR was significantly worse than in MRD– (AML: 23 % versus 57 %, p < 0.0001, ALL: 34 % versus 61.7 %, p = 0.0484), and the probability of relapse in MRD+ patients was significantly higher (AML: 75 % versus 12 %, p < 0.0001, ALL: 57 % versus 7 %, p = 0.0072). Pre-transplant MRD status was not prognostically significant for AL-patients in the second and third remission. The development of chronic GVHD reduces post-transplant mortality if it does not require systemic therapy with glucocorticosteroids (HR = 0.006, 95% CI: 0.008–0.446).Conclusion. Testing for MRD of patients with AL in the first CR before allo-HSCT is necessary for risk stratification and identification of patients who will need preventive post-transplant therapy in order to prevent disease relapse.

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

Early lymphocyte recovery (ELR) impact on disease outcome following autologous hematopoietic stem cell transplantation (HDT/ASCT) for multiple myeloma (MM) in the era of novel agents.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19539-e19539
Author(s):  
Jeremy Scott McDuffie ◽  
Bipin N. Savani ◽  
Wichai Chinratanalab ◽  
Stacey Goodman ◽  
John P. Greer ◽  
...  
Keyword(s):  
Minimal Residual Disease ◽  
Residual Disease ◽  
Disease Status ◽  
Novel Agents ◽  
Disease Outcome ◽  
Disease Stage ◽  
Response Criteria ◽  
Hematopoietic Stem ◽  
Significant Difference ◽  
Minimal Residual

e19539 Background: Absolute lymphocyte count (ALC) > 500 cells/ µL on day 15 (ELR+) after HDT/ASCT, has been reported to be an independent prognostic indicator, for improved OS and PFS in patients with MM. Novel agents (immunomodulatory drugs (IMiDs) and proteasome inhibitors), mediate there effect through T-cell stimulation, NK cell activation, anti-proliferation, and are now main stay of therapy for MM. We sought to determine their effects on ELR, and correlated to disease outcome. Methods: A retrospective review of all MM patients seen at our institution undergoing HDT/ASCT from January 2008 to December 2012 was performed. Patients were identified from our CIBMTR database. ALC was determined pre-HDT/ASCT (T1), on day15 (T2) and d30 (T3) post-HDC/ASCT. No restrictions on inclusion were made based upon the International Myeloma Working Group response criteria. All had novel agents as part of their initial induction regimen. Disease response was determined by standard clinical and laboratory CIBMTR response criteria, and minimal residual disease status (MRD) by multiparameter flow cytometry. Results: In our study (n= 184), 52/184 patients had ELR+ while 132/184 had ALC < 500 cells/mL (ELR-) at T2. 21% received IMiDs, 33% proteasome inhibitor and 46% combination therapies. 52% of the ELR+ patients were MRD negative (-) at T1, and improved to 74% and 89% at D100, and 1 year post-HDC/ASCT respectively. Similarly 63%, 70%, and 80% of the ELR- patients, were MRD (-) at similar time-points. Chi squared analysis showed no significant difference in rates of MRD (-) based on ELR. ELR also had no impact on disease status as determined by CIBMTR response criteria, or 1 year PFS and OS (p = 0.383), (p = 0.577) respectively. Multivariate analyses, using cox-regression showed no impact of ALC at T1, T2, T3, age, sex, race, cytogenetic risk, or disease stage on disease outcome. Conclusions: Novel agents improve disease control independent of ELR following HDC/ASCT. Understanding their biologic effect on immune-reconstitution will provide a platform for adoptive immunotherapy to better target minimal residual disease.

scholarly journals The Clinical Significance of Minimal Residual Disease Detected By Multiparametric Flow Cytometry in Acute Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5261-5261
Author(s):  
Fen Huang ◽  
Hui Jing ◽  
Zhengshan Yi ◽  
Xiaolei Wei ◽  
Zhongxin Zheng ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Acute Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Intensive Therapy ◽  
Remission Induction ◽  
Hematopoietic Stem ◽  
Multiparametric Flow Cytometry ◽  
The Relationship ◽  
Minimal Residual

Abstract Purpose Minimal residual disease (MRD) detected by multiparametric flow cytometry is an important method for predicting relapse. According to the dynamic changes of MRD, through the first clinical treatment to prevent relapse in patients with elevated MRD levels. Method We retrospectively analyze dynamic level of MRD of 75 patients with acute leukemia in our department of hematology from January 2011 to June 2013. According to the retrospective data, to analyze the expression of LAIP and discuss the relationship between changes of MRD and prognosis. Result In this study there were 75 patients, including 20 patients with acute lymphocytic leukemia (ALL) and 55 patients with acute myeloid leukemia (AML). The specific LAIP were detected in 49 patients with AML, and the cross lineage and non-synchronous expression were majority. In cross lineage expression, detected frequency of CD45/CD34/CD33/CD13/CD56 was highest, accounted for 67.3% (33/49). In non-synchronous expression, CD45/CD34/CD117/CD33/CD64 accounted for 57.1% (28/49). In 20 patients with ALL, there were 16 patients with B-ALL and 4 patients with T-ALL. The specific LAIP were detected in all of the patients. In patients with B-ALL, detected frequency of CD45/CD19/CD22/CD10/CD13 was highest, accounting for 43.8% (7/16). In abnormal quantity of antigens, CD45/CD19/CD22/CD10/CD38 was the most common type, accounting for 50%. The abnormal expression of CD7/TDT was detected in four patients with T-ALL. In monitoring period 7 patients relapsed. We analyzed the relationship between the clinical data and replase. The results showed that level of peripheral hemoglobin at diagnosis and the times of remission induction were significantly associated with replase (P=0.021 and P=0.017, respectively). To analyze the relationship between change of MRD and prognosis, the results showed that 0.05% as the threshold was significantly related with recurrence. 20 patients of persistent MRD≥0.05% had significant differences with 28 patients of persistent MRD<0.05% in replase free survival (P=0.005). Conclusion It has important significance to predict relapse in patients with acute leukemia by detecting minimal residual disease. Patients of MRD ≥ 0.05% should receive early intensive therapy or hematopoietic stem cell transplantation. Even patients without relapse, it should be closely monitor dynamic levels of MRD and highly vigilant extramedullary relapse. Disclosures No relevant conflicts of interest to declare.

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.

Minimal Residual Disease Quantification in Ovarian Tissue Collected in Patients in Complete Remission of Acute Leukemia

Blood ◽  
2020 ◽  
Author(s):  
Florian Chevillon ◽  
Emmanuelle Clappier ◽  
Chloe Arfeuille ◽  
Jean-Michel Cayuela ◽  
Jean-Hugues Dalle ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Complete Remission ◽  
Acute Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Ovarian Tissue ◽  
Ovarian Tissue Cryopreservation ◽  
Hematopoietic Stem ◽  
Leukemic Infiltration ◽  
Minimal Residual

Ovarian tissue cryopreservation (OTC) is offered to women treated for acute leukemia to preserve their fertility before hematopoietic stem cell transplantation. The risk of leukemic infiltration in ovarian samples harvested before administration of chemotherapy limits ovarian tissue transplantations. We assessed the minimal residual disease (MRD) by sensitive quantitative polymerase chain reaction in cryopreserved ovarian cortex and medulla samples harvested from 30 patients in complete remission of acute leukemia, including 60 % with negative bone marrow MRD at the time of OTC. Ovarian MRD was undetectable in 21 patients (70%), detectable below 10-4 in 8 patients (27%) and between 10-3 and 10-4 in 1 patient (3%). Twenty patients (67%) had concordant MRD between bone marrow and ovarian samples. Interestingly 4 patients had positive MRD in ovarian samples while undetectable in bone marrow. Our results underline the importance of reaching the best control of the disease with undetectable or low MRD levels before OTC to minimize the risk of ovarian leukemic infiltration. The discordant results between ovarian samples and bone marrow require to test the more ovarian samples available before considering ovarian tissue transplantation.

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