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.