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.

Early Molecular Response of Marrow Disease to Biologic Therapy Is Highly Prognostic in Neuroblastoma

2003 ◽  
Vol 21 (20) ◽  
pp. 3853-3858 ◽  
Author(s):  
Irene Y. Cheung ◽  
M. Serena Lo Piccolo ◽  
Brian H. Kushner ◽  
Nai-Kong V. Cheung
Keyword(s):  
Bone Marrow ◽  
Complete Remission ◽  
Minimal Residual Disease ◽  
Partial Remission ◽  
Progressive Disease ◽  
Residual Disease ◽  
Gm Csf ◽  
Stage 4 ◽  
Secondary Refractory ◽  
Minimal Residual

Purpose: A promising treatment strategy for stage 4 neuroblastoma patients is the repeated application of anti-GD2 immunotherapy after activating myeloid effectors with granulocyte-macrophage colony-stimulating factor (GM-CSF). To use early marrow response as a prognostic marker is particularly relevant for patients not likely to benefit from this therapy. Patients and Methods: Eighty-six stage 4 neuroblastoma patients older than 1 year at diagnosis were classified in four clinical groups on protocol entry: complete remission or very good partial remission (n = 33), primary refractory (n = 33), secondary refractory (n = 10), and progressive disease (n = 10). Bone marrow samples collected before and following treatment were assayed for GD2 synthase mRNA by real-time reverse transcriptase polymerase chain reaction. Response and survival analyses were performed on posttreatment samples before the third cycle at 1.8 months from protocol entry. Results: GD2 synthase mRNA was evident in pretreatment marrow samples of the four clinical groups (42%, 52%, 60%, and 80% of samples, respectively), with median transcript level of 10.0, 16.6, 26.5, and 87.2, respectively. This marker became negative following antibody plus GM-CSF in 77% of complete remission or very good partial remission, 45% of primary refractory, 25% of secondary refractory, and 0% of progressive disease group. Progression-free survival was statistically different between responder and nonresponder groups (P < .0001). Among patients with minimal residual disease, molecular responders had a significantly lower risk of disease progression at a median follow-up of 29.8 months (P = .0001). Conclusion: GD2 synthase mRNA is a sensitive response marker of neuroblastoma in the bone marrow. It is particularly useful for minimal residual disease evaluation and may potentially be useful as an early predictor of resistance to antibody plus GM-CSF immunotherapy.

High Efficacy and Good Tolerability with Rituximab In Vivo Purging Followed by High Dose Chemotheraphy and Autologous Peripheral Blood Stem Cell Transplantation (APBSCT) in Non-Hodgkin’s Lymphoma (NHL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4626-4626
Author(s):  
Yuankai Shi ◽  
Sheng Yang ◽  
Xiaohong Han ◽  
Peng Liu ◽  
Xiaohui He ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Complete Remission ◽  
Minimal Residual Disease ◽  
Median Time ◽  
Residual Disease ◽  
High Dose ◽  
Platelet Recovery ◽  
Minimal Residual

Abstract Purpose: High-dose chemotherapy (HDC) supported by APBSCT has been shown to be superior to standard therapy in NHL. However, many patients relapse due to minimal residual disease (MRD) in vivo or in the graft. Rituximab has the potential to clear both blood and bone marrow of malignant CD20+ cells, prompting this multicenter trial of in vivo purging with rituximab and HDC with APBSCT in China. Methods: Cyclophosphamide 4g/m2 was used as the mobilization regimen, CY/TBI, BEAM or CBV could be used as HDC at the discretion of the institution. Four infusions of rituximab (375 mg/m2) were given: one day before mobilization, one day before harvesting, one day before transplantation and on day 8 after transplantation. BCL-2/Ig-H translocation was measured as a marker of minimal residual disease in blood or bone marrow before mobilization and during transplantation using real-time quantitative PCR. Results: Thirty-one patients from 12 centers with histologically proven CD20+ NHL (28 aggressive, 3 indolent NHL) were enrolled. Twenty-four patients were previously untreated, and 7 patients had relapsed disease. Median yields of CD34+ cells and mononuclear cells were 5.9×106/kg and 4.4×108 /kg respectively. Median time to recovery of WBC >1.5×109/L, ANC >0.5×109/L and platelets >20×109/L after APBSCT was 10 days in each case. Median time to platelet recovery >50×109/L was 13 days. Generally, this therapeutic strategy was well tolerated with few side effects attribute to rituximab. All patients achieved a complete remission after APBSCT. At a median-follow-up of 12 months, overall survival and progression-free survival (PFS) are 87% and 73% respectively for all patients. In patients with aggressive NHL, overall survival and PFS are 85% and 73% respectively and in indolent NHL are 100% and 67% respectively. PFS and overall survival were slightly higher in previously untreated compared with relapsed patients (88% vs. 83% for PFS, 73% vs. 69% for overall survival). One of five 5 patients who were initially found to be PCR-positive and achieved PCR-negative status subsequently experienced progression accompanied by a return to PCR positivity. The remaining four patients are still in complete remission and are PCR negative. Conclusion: These results suggest that the regimen of rituximab combined with HDCT and APBSCT is effective and well tolerated for the treatment of patients with NHL.

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 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 Immunophenotypic Profile of Blast Cells as a Marker for Diagnosis of Relapsed Children Acute Lymphoblastic Leukemia

2021 ◽  
Vol 6 (1) ◽  
pp. 56-64
Author(s):  
O. A. Vynnytska ◽  
◽  
O. I. Dorosh ◽  
L. Ya. Dubey ◽  
N. V. Dubey
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Chromosomal Translocation ◽  
Cytostatic Therapy ◽  
Blast Cells ◽  
Minimal Residual

Immunophenotyping of leukemia cells was studied in this work; minimal residual disease was monitored among children with acute lymphoblastic leukemia under conditions of relapse and complete remission after the application of ALLIC-BFM 2009 cytostatic therapy. The study showed that after application of ALLIC-BFM 2009 therapy, 88% of children had complete remission, and 12% had relapses. Among patients with relapses, the number of blast cells in the bone marrow was at a high level (more than 6%). Monitoring of patients during therapy established an increase in the minimal residual disease level of more than 1% after treatment in patients with recurrent disease. Immunophenotyping of blast cells among patients with relapse showed the expression of linear independent antigens HLA (93%), Auti-TdT (91%), CD10 (78%), CD38 (91%) and CD34 (57%) and B-linear antigens: CD19, CD22, CD58, CD79a, the highest expression was found for the CD19 antigen. A low level of expression of CD45 (28%) was recorded with relapses of acute lymphoblastic leukemia and high (89%) level was with complete remission of the disease. We did not detect expression of antigens characteristic of T-cell acute lymphoblastic leukemia in bone marrow of patients with acute lymphoblastic leukemia, both with relapses and with remission. At the same time, the expression of myeloid antigens (CD33 and CD13) was noted among acute lymphoblastic leukemia patients. Among patients, the incidence of acute lymphoblastic leukemia was the most pronounced in children aged from 3 to 6 years – 37 patients (35.2%) and aged from 6 to 9 years – 26 (24.8%) patients. The highest accidence was found among patients with chromosomal translocation TEL / AML – 22 (21%) patients with a median age 5 years. In second place, the frequency of mutations is the translocation of E2A / PBX1. BCR / ABL translocation was less common. It was noted in 1.9% of patients, but the expression of this gene indicated a bad course of the disease, as patients after cytostatic therapy under the ALLIC BFM 2009 program had a recurrence. Recurrence was also observed in patients with TEL/AML chromosomal translocation. Determination of minimal residual disease showed its increased level in patients with chromosomal aberrations BCR / ABL and TEL/AML throughout the treatment phase. In addition, patients in these groups were diagnosed with initial leukocytosis followed by leukopenia after a course of chemotherapy. Patients of all groups showed a decrease in hemoglobin. The biggest changes in clinical and laboratory parameters were found between patients with chromosomal translocations BCR/ABL and TEL/AML, as evidenced by the development of relapses in patients of these groups. The low level of association between karyotype disorders, with the formation of AF4/MLL and E2A/PBX1, and clinical and laboratory parameters in patients with acute lymphoblastic leukemia may indicate that the isolated clonal disorders are independent prognostic factors for the course of the disease

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