Is minimal residual disease monitoring a useful tool in acute lymphoblastic leukemia?
Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer and advances in its clinical and laboratory biology have grown exponentially over the last few decades. Treatment outcome has improved steadily with over 90% of patients surviving 5 years from initial diagnosis. This success can …
What is minimal residual disease (MRD)?
Jul 15, 2020 · Minimal residual disease is a small number of cancer cells left in the body after treatment. These cells have the potential to come back and cause relapse in our patients. In leukemia, for example, we look for response after chemotherapy treatment by looking under the microscope for cancer cells present in a bone marrow biopsy. When there are ...
What is the PMID for minimal/measurable residual disease in AML?
Nowadays, minimal residual disease (MRD) is accepted as the strongest independent prognostic factor in acute lymphoblastic leukemia (ALL). It can be detected by molecular methods that use leukemia-specific or patient-specific molecular markers (fusion gene transcripts, or immunoglobulin/T-cell receptor [IG/TR] gene rearrangements), and by multi-parametric flow …
What is minimal residual disease direct risk stratification?
The Role of Minimal Residual Disease (MRD) Assessment in Patient Care After treating cancer, any remaining cancer cells in the body can become active and start to multiply, causing a relapse of the disease. Detecting MRD may indicate that the treatment was not completely effective or that the treatment was incomplete. Minimal residual disease may
What is minimal residual disease in leukemia?
How is minimal residual disease measured?
What does residual disease mean in cancer?
Is residual disease curable?
What does minimal disease mean?
How do you assess MRD in all?
What does residual mean in medical terms?
(Entry 1 of 2) 1 : of, relating to, or being something that remains: as. a : remaining after a disease or operation residual paralysis. b : remaining in a body cavity after maximum normal expulsion has occurred residual urine — see residual volume.Apr 29, 2022
What does residual condition mean?
Which is the most sensitive method of minimal residual disease testing in chronic myelogenous leukemia?
What is MRD transplant?
What is minimal residual disease in multiple myeloma?
In multiple myeloma, MRD refers to myeloma cells that are present in the bone marrow after a clinical response has been measured and the patient is in remission. These residual myeloma cells are clinically relevant, as they may lead to disease progression and relapse.
What is MRD in medical terms?
However, there is a different phrase that can be somewhat confusing to patients – minimal residual disease (MRD). This term is used often by physicians when treating patients with blood cancers, such as leukemia, lymphoma or multiple myeloma. MRD refers to cancer cells remaining after treatment that can’t be detected by those same scans or tests.
What is minimal residual disease?
Minimal residual disease is a small number of cancer cells left in the body after treatment. These cells have the potential to come back and cause relapse in our patients. In leukemia, for example, we look for response after chemotherapy treatment by looking under the microscope for cancer cells present in a bone marrow biopsy. ...
What does MRD mean in medical terms?
Minimal residual disease (MRD) is a term used to describe the small number of cancer cells in the body after cancer treatment. An MRD positive test result means that disease was still detected after treatment. An MRD negative result means that no disease was detected after treatment.
How does MRD testing affect treatment?
Testing for MRD can help the treatment team distinguish between patients who need additional (or different) treatment from those who do not. This knowledge can also potentially guide treatment decisions and improve patient outcomes.
What is the LLS?
LLS is the world’s largest voluntary health organization dedicated to funding blood cancer research, education and patient services. LLS has chapters throughout the United States and in Canada. To find the chapter nearest to you, visit our Web site at www.LLS.org/ChapterFind or contact: The Leukemia & Lymphoma Society 3 International Drive, Suite 200 Rye Brook, NY 10573Call an Information Specialist at (800) 955-4572 Email: [email protected] LLS offers free information and services for patients and families touched by blood cancers. The following entries list various resources available to you. Use this information to learn more, to ask questions and to make the most of your healthcare team.
What is MRD in all?
MRD is defined as any approach—including cytogenetics, flow cytometry, PCR-based tools, and high throughput sequencing methods— aimed at detecting and possibly quantifying residual tumor cells beyond the sensitivity level of cytomorphology. To be informative, MRD assays for ALL should allow to detect one leukemic cell among 10,000 normal cells or more in virtually all patients. Currently, the most standardized methods to study MRD in ALL are: multi-parametric flow cytometry (MFC) of leukemia-associated immunophenotypes (LAIP) and, more so, polymerase chain reaction (PCR) amplification-based methods that use leukemia-specific (fusion gene transcripts) or patient-specific (immunoglobulin/T-cell receptor (IG/TR) gene rearrangements) molecular markers ( 15 – 20 ).
What is the molecular study of antigen receptor gene rearrangements?
The most commonly used technique is the molecular study based of antigen-receptor gene rearrangements. Immunoglobulin and T-cell receptor (IG/TR) gene rearrangements are physiological events not directly linked to the pathogenesis of the leukemia. During B- and T-lymphocytes ontogeny, the IG and TR genes are assembled by a somatic rearrangement process. The separated gene segments encoding the V, D, J regions are combined to form a single exon encoding the variable region. In this process, some nucleotides are randomly deleted or inserted at junctional sites of each segment, leading to final receptor sequences unique to each B or T lymphocytes ( 36 ). In the case of a neoplastic transformation of a single lymphoid cell, all leukemic cells will contain the same rearranged clonal IG and/or TR genes; this approach can also be exploited to detect a low number of ALL cells among a large number of normal lymphoid cells expressing gene rearrangements with different sequences. The study of these rearrangements has become the most sensitive method to assess the clonality of a lymphoid expansion. Although IG rearrangements are mostly found in B cells and TR rearrangements in T- lymphocytes, both B-lineage and T-lineage leukemic cells can display cross-lineage rearrangements, which can be used for MRD evaluation ( 37, 38 ): up to 90% of precursor B-ALL may express TR gene rearrangements ( 38) whereas a lower proportion of T-ALL (20%) shows IG rearrangements ( 39 ). To identify these molecular markers at diagnosis, genomic DNA derived from leukemic cells need to undergoes a PCR amplification process and the positive PCR products are then analyzed by heteroduplex or gene scan ( 40, 41) to establish clonality. Subsequently, clonal PCR fragments undergo Sanger sequencing to define the junctional regions and obtain complementary allele-specific oligonucleotide (ASO)-primers for MRD monitoring, mostly performed by real-time quantitative PCR (RQ-PCR). Amplification conditions and sensitivity testing for each ASO-primer are established on the diagnostic material serially diluted in normal mononuclear cells. This RQ-PCR protocol combined with fluorescently labeled probes allows the detection of up to 1 leukemic cell in 100,000 (10 −5) normal lymphoid cells and leukemia cell dilutions are therefore used to quantify MRD in bone marrow samples collected during treatment ( 42) ( Table 1 and Figure 2 ). This technology can generate at least one single sensitive molecular probe suitable for MRD analysis in over 90% of pediatric ( 18) and adult ( 43, 44) ALL patients.
Is MRD a prognostic factor?
The clinical impact of MRD is now widely accepted and is regarded today as the most important prognostic factor in the state-of-the-art management of ALL. MRD can provide different information, according to the timing in which it is performed (very early during treatment, after induction/consolidation, before and after SCT) and, more recently, it can be refined by the evaluation of additional genomic markers.
What is blinatumomab used for?
Blinatumomab is the first antibody approved for treatment of refractory ALL and, more recently, for the treatment of MRD+ patients. In relapsed/refractory ALL, blinatumomab has led to morphologic responses ranging from 43 to 69% of patients ( 135, 136) with 76 to 88% of responding patients being MRD negative. Patients who achieved a negative molecular MRD status had a longer survival than patients who remained MRD positive ( 137, 138 ). In MRD+ patients, blinatumomab induced a complete MRD response in 78% of cases and, as expected, MRD responders has a longer RFS than non-responders. A small fraction of complete MRD responders did not undergo transplant and is still in continuous CR ( 139, 140 ).
What are car T cells?
CAR-T cells are patient or, less frequently, donor-derived normal T cells molecularly engineered to express a T-cell receptor mediating cytotoxicity toward anti-CD19 (in most cases). After CAR-T cells are infused into a patient, they act as a “living drug” against cancer cells: they bind to the target, become activated, proliferate and exert their cytotoxic activity. Several groups have shown that most of the responding patients (both children and adults) become MRD negative (at least by FCM) ( 143 – 145) and maintain this status for several months or years ( 146, 147 ). Data on the prognostic value of MRD in this setting are still preliminary. However, differently from first-line chemotherapeutic approaches, relapse is observed also in patients reaching a MRD negativity, mostly because of the loss of CD19. Therefore, MRD response in this setting seems to be an essential but not sufficient criterion for the definition of long-term remissions. Higher sensitivities or earlier MRD assessments might be necessary to identify a subgroup of patients with a particularly rapid and deep MRD response and a better prognosis.
Is MRD a predictor of outcome?
MRD is a powerful and independent predictor of outcome in both children and adult ALL, during treatment, in the pre- and post-SCT settings , with different prognostic meanings on the base of the clinical context.
What is the name of the cancer that affects the white blood cells?
Acute lymphoblastic leukemia (ALL) is a type of cancer of the blood and bone marrow that affects white blood cells. These white blood cells are important to your immune system because they play a role in helping your body fight infection and disease. But when you have ALL, the bone marrow makes too many of these white blood cells ...
Why are white blood cells important?
These white blood cells are important to your immune system because they play a role in helping your body fight infection and disease. But when you have ALL, the bone marrow makes too many of these white blood cells and they do not work properly. 1,2. Remission means that your body is free of signs and symptoms of cancer.
Is remission a good thing?
Remission is a great achievement, but it does not always mean the cancer has been cured. 1. Along with the news that your ALL is in remission, your doctor may have talked to you about testing for remaining traces of ALL. Or you may have already been tested but wonder what it’s all about.
What does MRD mean in medical terms?
Any remaining traces of detectable cancer (MRD) can possibly cause a relapse, which is the return of a disease or the signs and symptoms of a disease after a period of improvement.
What is blincyto used for?
BLINCYTO ® (blinatumomab) is a prescription medicine used to treat B-cell precursor acute lymphoblastic leukemia (ALL) in patients who still have detectable traces of cancer after chemotherapy. The approval of BLINCYTO ® in these patients is based on a study that measured response rate and duration of response.
What is MRD in pediatrics?
Several studies have demonstrated that monitoring of minimal residual disease (MRD) in childhood and adult acute lymphoblastic leukemia (ALL) significantly correlates with clinical outcome. MRD detection is particularly useful for evaluation of early treatment response and consequently for improved front-line therapy stratification. MRD information is also significant for children undergoing allogeneic hematopoietic stem cell transplantation and those with relapsed ALL. Currently, three highly specific and sensitive methodologies for MRD detection are available, namely multiparameter flow cytometric immunophenotyping, real-time quantitative polymerase chain reaction (RQ-PCR)-based detection of fusion gene transcripts or breakpoints, and RQ-PCR-based detection of clonal immunoglobulin and T-cell receptor gene rearrangements. In this review, characteristics, pitfalls, advantages and disadvantages of each MRD technique are critically discussed. The special emphasis is put on interlaboratory standardization, especially in view of the results obtained within the European collaborative BIOMED-1, BIOMED-2, and Europe Against Cancer projects and recent developments by European Study Group on MRD detection in ALL and EuroFlow Consortium. Standardized MRD techniques form the basis for stratification of patients into the risk groups in new treatment protocols mainly in childhood ALL. Only the results of these studies can answer the question whether MRD-based treatment intervention is associated with improved outcome.
What is minimal residual disease?
The concept of minimal residual disease (MRD) detection in acute lymphoblastic leukemias (ALL) is inherently associated with the progress in treatment of these malignancies. 1 More than 80% of childhood and 35% of adult ALL patients can be cured with modern chemotherapy supplemented with hematopoietic stem cell transplantation (HSCT) in high risk patients (reviewed by Hoelzer et al. 2 ). Still, a substantial number of ALL patients relapse and the prediction of relapse with conventional prognostic factors such as age, blast count at diagnosis, immunophenotype at diagnosis, presence of chromosome aberrations, response to steroid prophase and classical clinical risk group assignment is far from optimal. Also microarray-based gene expression profiling could not identify gene signatures, typically associated with high risk of relapse. Tracing residual leukemic cells during early phases of treatment provides prognostic information superior to all known classical prognostic factors. Several prospective studies in childhood ALL demonstrated that the most relevant information comes from detection of MRD in bone marrow at the early phases of treatment, particularly at the end of induction treatment (reviewed by Szczepański et al. 3 and Cazzaniga and Biondi 4 ). Children with undetectable MRD at the end of induction have an excellent prognosis and are good candidates for treatment de-intensification or at least should not be subjected to further treatment intensification, particularly not to HSCT. 5, 6, 7, 8, 9 In childhood ALL, a group of ultrafast responders could be identified with successful clearance of MRD in bone marrow even within first 2 weeks of the induction. 10, 11 In contrast, children with high MRD levels at the end of induction treatment are in urgent need for treatment intensification or even for novel treatment approaches, particularly when such high MRD levels persist into the consolidation treatment. 5, 6, 7, 8, 9 Children with high-risk primary ALL and children with relapsed ALL planned for allogeneic HSCT can also profit from MRD monitoring. 12, 13, 14, 15, 16, 17 It is now generally accepted that one of the prerequisites for successful allo-HSCT is maximal reduction of MRD before start of the transplant procedure. Patients with high pretransplant MRD levels are at very high risk for ALL relapse. 12, 14, 15 Currently, the ongoing studies aim at assessment of possible approaches to lower pretransplant MRD levels and/or attune graft-versus-host reaction according to post-transplant MRD levels by modifying the immunosuppression to improve the outcome after HSCT. Finally, it was recently demonstrated that treatment stratification of standard risk adult ALL patients can be substantially improved when including MRD information. 18
What is RQ-PCR in MRD?
RQ-PCR-based detection and quantification of junctional regions of clonal Ig and TCR gene rearrangements is by far the most widely employed strategy of MRD monitoring in ALL. Although this MRD strategy is the most laborious, expensive and time consuming, it is the most reproducible approach not only within the same laboratory but also between different laboratories. The junctional regions of clonal Ig and TCR gene rearrangements are fingerprint-like sequences for each lymphoid malignancy and can be identified in the vast majority of ALL patients using the standardized primer sets established through the European collaboration within the BIOMED-1 and -2 frameworks. 35, 36, 37 The immunobiologic studies identified and characterized oligoclonality and clonal evolution of Ig/TCR gene rearrangements between diagnosis and relapse. 38, 39, 40, 41, 42 Therefore, it is widely accepted that preferably at least two Ig/TCR targets should be followed per patient.