scholarly journals Use of polymerase chain reactions to monitor minimal residual disease in acute lymphoblastic leukemia patients

Blood ◽  
1991 ◽  
Vol 77 (2) ◽  
pp. 331-339 ◽  
Author(s):  
S Yokota ◽  
TE Hansen-Hagge ◽  
WD Ludwig ◽  
A Reiter ◽  
A Raghavachar ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Clinical Remission ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Remission Induction ◽  
Clinical Relapse ◽  
Polymerase Chain ◽  
Minimal Residual

Abstract T-cell receptor (TCR) delta gene rearrangements are observed in more than 80% of acute lymphoblastic leukemia (ALL) patients. Moreover, a preferential usage of specific genetic elements has been shown in different ALL subtypes: V delta 1 DJ delta 1 rearrangements predominate in T-ALL, while most B-precursor ALLs show a recombination of V delta 2 to D delta 3. Recently we have proposed a strategy for the detection of minimal residual disease (MRD) based on the isolation of clonospecific probes following the in vitro amplification of V delta 1 DJ delta 1 junctions by polymerase chain reaction (PCR) and now have adapted this method to the preparation of specific V delta 2 D delta 3 fragments. In the present study, clonospecific probes were generated from 11 T-ALL and 16 cALL patients (21 children, 6 adults). The sensitivity of these 27 probes in detecting residual leukemia cells varied between 10(-4) to 10(-6) as determined by semiquantitative evaluation of dilution experiments. PCR analysis of 55 bone marrow (BM) and peripheral blood (PB) samples obtained from the 27 patients during complete clinical remission showed the following results: (1) Evidence for MRD was obtained in the BM of all patients (eight of eight) investigated 2 to 6 months after remission induction and also in 6 of 11 cases on maintenance therapy 7 to 19 months after diagnosis. (2) In contrast, all patients but one (10 of 11) analyzed 6 to 41 months after the termination of treatment lacked apparent evidence for leukemia DNA; the exception was a girl exhibiting 10(-4) to 10(-5) residual cells in her PB 5.5 years after diagnosis. (3) Longitudinal analysis in nine patients disclosed marked individual differences in the intervals between achievement of clinical remission and complete eradication of the leukemia cell clone. (4) Differences in the duration of MRD were not associated with distinct clinical-hematologic features. (5) Detection of residual disease by PCR proceeded clinical relapse in two cases.

scholarly journals Use of polymerase chain reactions to monitor minimal residual disease in acute lymphoblastic leukemia patients

Blood ◽  
1991 ◽  
Vol 77 (2) ◽  
pp. 331-339 ◽  
Author(s):  
S Yokota ◽  
TE Hansen-Hagge ◽  
WD Ludwig ◽  
A Reiter ◽  
A Raghavachar ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Clinical Remission ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Leukemia Cell ◽  
Remission Induction ◽  
Clinical Relapse ◽  
Polymerase Chain ◽  
Minimal Residual

T-cell receptor (TCR) delta gene rearrangements are observed in more than 80% of acute lymphoblastic leukemia (ALL) patients. Moreover, a preferential usage of specific genetic elements has been shown in different ALL subtypes: V delta 1 DJ delta 1 rearrangements predominate in T-ALL, while most B-precursor ALLs show a recombination of V delta 2 to D delta 3. Recently we have proposed a strategy for the detection of minimal residual disease (MRD) based on the isolation of clonospecific probes following the in vitro amplification of V delta 1 DJ delta 1 junctions by polymerase chain reaction (PCR) and now have adapted this method to the preparation of specific V delta 2 D delta 3 fragments. In the present study, clonospecific probes were generated from 11 T-ALL and 16 cALL patients (21 children, 6 adults). The sensitivity of these 27 probes in detecting residual leukemia cells varied between 10(-4) to 10(-6) as determined by semiquantitative evaluation of dilution experiments. PCR analysis of 55 bone marrow (BM) and peripheral blood (PB) samples obtained from the 27 patients during complete clinical remission showed the following results: (1) Evidence for MRD was obtained in the BM of all patients (eight of eight) investigated 2 to 6 months after remission induction and also in 6 of 11 cases on maintenance therapy 7 to 19 months after diagnosis. (2) In contrast, all patients but one (10 of 11) analyzed 6 to 41 months after the termination of treatment lacked apparent evidence for leukemia DNA; the exception was a girl exhibiting 10(-4) to 10(-5) residual cells in her PB 5.5 years after diagnosis. (3) Longitudinal analysis in nine patients disclosed marked individual differences in the intervals between achievement of clinical remission and complete eradication of the leukemia cell clone. (4) Differences in the duration of MRD were not associated with distinct clinical-hematologic features. (5) Detection of residual disease by PCR proceeded clinical relapse in two cases.

scholarly journals Detection of Philadelphia chromosome-positive acute lymphoblastic leukemia by polymerase chain reaction: possible eradication of minimal residual disease by marrow transplantation

Blood ◽  
1992 ◽  
Vol 79 (5) ◽  
pp. 1366-1370 ◽  
Author(s):  
K Miyamura ◽  
M Tanimoto ◽  
Y Morishima ◽  
K Horibe ◽  
K Yamamoto ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Marrow Transplantation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Minimal Residual

Abstract Minimal residual disease (MRD) in patients with Philadelphia chromosome- positive acute lymphoblastic leukemia (Ph1 ALL) who received allogeneic (n = 9) or autologous (n = 6) bone marrow transplantation (BMT) was evaluated by the polymerase chain reaction (PCR) for the bcr-abl transcript. Twelve patients received BMT at the time of hematologic and cytogenetic remission. However, MRD was detected in 8 of 10 patients evaluated. Seven patients, including three who had MRD before BMT, continue to have a disease-free survival 5 to 64 months after BMT. Twenty-one specimens obtained from these patients at various times after BMT did not show MRD. In three patients, MRD detected just before BMT seems to be eradicated by BMT protocol. The other eight patients developed cytogenetic or hematologic relapses 2 to 8 months after BMT. Seven of 14 samples from these patients demonstrated MRD, which preceded clinical relapse by 3 to 9 weeks. Thus, this technique for the detection of MRD appears to be useful for the more precise assessment of various antileukemia therapies and for early detection of leukemia recurrence.

Minimal residual disease by flow cytometry at the end of chemotherapy for remission induction in pediatric patients with acute lymphoblastic leukemia: Experience from a center in a low-income country.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 9554-9554
Author(s):  
Eloy Perez ◽  
Primo Cruz-Borja ◽  
Silvia Chavez-Gallegos
Keyword(s):  
Flow Cytometry ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Remission Induction ◽  
Response To Chemotherapy ◽  
Increased Risk ◽  
Cure Rates ◽  
Minimal Residual

9554 Background: The presence of minimal residual disease (MDR) following therapy for acute lymphoblastic leukemia (ALL) has been shown to be an important prognostic marker in many studies. MRD is typically detected either by polymerase chain reaction amplification or by flow cytometry. Flow-based MRD assessment has the potential for rapidly identifying patients at increased risk of relapsed, allowing for prompt changes in therapy, including earlier intensification. There are not many information about the response by MRD in countries with limited resources. Methods: The patients included were 90 ALL patients treated at the Hospital Infantil de Morelia from June 1, 2009 to January 5, 2012. MRD positivity (+) was defined as >0.01% of the gated population. Results: MRD was obtained in 90 patients, 38 males and 36 females. The median age was 7 years (10 months to 15 years). The levels of MRD were: <0.01, 74 (82.2%), 0.01-1%, 9 (10%), ≥1%, 7 (7.7%). There was not a statistically significant association between the most important ALL prognostic factors (Gender, Age at diagnosis, White blood cell count at diagnosis, Central Nervous System disease, Prednisone response, DNA Index, Immunophenotype). Conclusions: The good response found is similar to that reported by international groups, a situation which suggests that the response to chemotherapy is appropriate. However, cure rates are still not equal making it necessary to review institutional treatment protocols and social characteristics of the population to achieve cure rates reported by international groups.

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 Prognostic significance of bi/oligoclonality in childhood acute lymphoblastic leukemia as determined by polymerase chain reaction

2001 ◽  
Vol 119 (5) ◽  
pp. 175-180 ◽  
Author(s):  
Carlos Alberto Scrideli ◽  
Ricardo Defavery ◽  
José Eduardo Bernardes ◽  
Luíz Gonzaga Tone
Keyword(s):  
Polymerase Chain Reaction ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Chain Reaction ◽  
Significant Difference ◽  
Polymerase Chain ◽  
Minimal Residual

CONTEXT: The CDR-3 region of heavy-chain immunoglobulin has been used as a clonal marker in the study of minimal residual disease in children with acute lymphoblastic leukemia. Southern blot and polymerase chain reaction studies have demonstrated the occurrence of bi/oligoclonality in a variable number of cases of B-lineage acute lymphoblastic leukemia, a fact that may strongly interfere with the detection of minimal residual disease. Oligoclonality has also been associated with a poorer prognosis and a higher chance of relapse. OBJECTIVES: To correlate bi/oligoclonality, detected by polymerase chain reaction in Brazilian children with B-lineage acute lymphoblastic leukemia with a chance of relapse, with immunophenotype, risk group, and disease-free survival. DESIGN: Prospective study of patients’ outcome. SETTING: Pediatric Oncology Unit of the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo. PARTICIPANTS: 47 children with acute lymphoblastic leukemia DIAGNOSTIC TEST: Polymerase chain reaction using consensus primers for the CDR-3 region of heavy chain immunoglobulin (FR3A, LJH and VLJH) for the detection of clonality. RESULTS: Bi/oligoclonality was detected in 15 patients (31.9%). There was no significant difference between the groups with monoclonality and biclonality in terms of the occurrence of a relapse (28.1% versus 26.1%), presence of CALLA+ (81.2% versus 80%) or risk group (62.5% versus 60%). Disease-free survival was similar in both groups, with no significant difference (p: 0.7695). CONCLUSIONS: We conclude that bi/oligoclonality was not associated with the factors investigated in the present study and that its detection in 31.9% of the patients may be important for the study and monitoring of minimal residual disease.

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