MINIMAL RESIDUAL DISEASE MONITORING: SWISS MED. WEEKLY www.smw.ch

Published 22 January 2014, doi:10.4414/smw.2014.13907 Cite this as: Swiss Med Wkly. 2014;144:w13907 Minimal residual disease monitoring: the new standard for treatment evaluation of haematological malignancies? Mathieu Hauwel, Thomas Matthes Swiss Flow Cytometry School, Haematology Service and Clinical Pathology Service, Geneva University Hospital, Switzerland SUMMARY of on-line paper. Abbreviations ALL acute lymphoblastic leukaemia AML acute myeloid leukaemia ASO-PCR allele-specific oligonucleotide-PCR BCR B-cell receptor CLL chronic lymphocytic lymphoma CML chronic myeloid leukaemia CR complete remission cytoCR flow cytometry CR DNA deoxyribonucleic acid FISH fluorescent in-situ hybridisation FL follicular lymphoma iCR immunofixation CR IgH immunoglobulin heavy chain LAIP leukaemia-associated immunophenotype LSCs leukaemic stem cells MCFC multicolour flow cytometry MRD minimal residual disease mRNA messenger RNA NGS new generation sequencing NMR nuclear magnetic resonance PCR polymerase chain-reaction PET positron emission tomography PFS progression-free survival Ph Philadelphia chromosome RNA ribonucleic acid RT-PCR reverse transcriptase-PCR sCR serum free light chain ratio CR TCR T-cell receptor Minimal residual disease (MRD) refers to the small number of malignant cells that remain after therapy when the patient is in remission and shows no symptoms or overt signs of disease. Current treatment protocols for haematological malignancies allow most patients to obtain some form of MRD state, but cure seldom follows and in most cases fatal relapses occur sooner or later, leaving a bitter impression of having won a battle yet lost the war. MRD detection and quantification are used for evaluation of treatment efficiency, patient risk stratification and long-term outcome prediction. Whereas multicolour flow cytometry (MCFC) and polymerase chain reaction (PCR) based methods constitute the two most commonly used techniques for MRD detection, next generation sequencing will certainly be widely employed in the future. As MRD reflects the nature of the malignant disease itself, including its sensitivity to the drug regimens applied, it constitutes the ideal method for surveillance and patient follow-up. The morphological examination of peripheral blood or bone marrow smears, although still an indispensable part of routine laboratory testing, is clearly insufficient for patient management, and clinicians should not ask themselves whether to look for MRD or not, but how and when. Key words: minimal residual disease; flow cytometry, next generation sequencing; PCR; acute lymphoblastic leukaemia; acute myeloid leukaemia; chronic myeloid leukaemia; multiple myeloma, lymphoid neoplasm