MINIMAL RESIDUAL DISEASE

Minimal Residual Disease: 
Definition: Submicroscopic disease, that remains undetected within the patient even after chemotherapy or bone marrow transplantation, and later can lead to relapse of disease.
Disease is minimal - no signs and symptoms are the disease are present in the patient.

Two types:
Molecular MRD: Detected by PCR only.

  • Real time quantitative PCR is used (RT-PCR)
  • Very sensitive.
  • Can detect 1 leukemic cell in 1000 - 1000 lakh normal cells
  • Detection of fusion transcripts (PML-RARA) or mutations (NPM) or gene overexpressions etc


Immunophenotypic MRD: Detected by flow cytometry

  • Uses multiparameter flow cytometry 
  • Principle: Leukemic cells express an antigen profile different from those observed on normal hematopoietic precursor cells 
  • MRD expression of markers is compared to the markers expressed in the original disease at diagnosis
  • Relies on Leukemia Associated immunophenotypes (LAIP) for diagnosis
  • Advantages: Rapid process, widely applicable

Applications:

  • Used in AML, ALL, CML, B cell NHL and myeloma
  • MRD monitoring is mainly used after induction chemotherapy, post-consolidation, pre-transplant and during CR
  • Predicting early relapse, prognostic significance and for therapy decisions
  • Risk adjusted therapy:
    • 1. To sparse those patients with no residual disease from additional chemotherapy
    • 2. To intensify the treatment or consider other options of treatment for those with MRD to avoid relapse.


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