Flow cytometric detection of minimal residual disease in B-lineage acute lymphoblastic leukemia by using “MRD lite” panel

Abstract

IntroductionMinimal residual disease (MRD) refers to the presence of recalcitrant leukemic blasts in the peripheral blood or bone marrow, which is beyond the lower limit of morphologic detection by light microscopy and can only be detected by highly sensitive assays, be it polymerase chain reaction based or flow cytometry based. 1 PCR-based and flow cytometric MRD technologies have been developed over the past two decades with their inherent advantages and disadvantages. 2-9 Detection of MRD would aid in the patient management by either intensifying therapy in MRD positive cases or de-intensifying and thereby reducing treatment-related mortality and morbidity in MRD negative cases. Prospective studies in large series of patients have demonstrated a strong correlation between MRD levels during clinical remission and treatment outcome. 10,11 For MRD studies, leukemia-associated immunophenotypes (LAIP)m e d i c a l j o u r n a l a r m e d f o r c e s i n d i a 7 3 ( 2 0 1 7 ) 5 4 -5 7

Flow Cytometry in Pediatric Malignancies

“…The MRD lite analysis is based on the fact that on Day 19, not >0.01% precursor B cells (hematogones) are present in the bone marrow. And thus presence of >0.01% CD19 positive B cells which coexpress either CD34 and/or CD10 would be residual blasts, and not hematogones (which are also CD19+ with CD34 and/or CD10) [13,14]. This methodology has its disadvantages as (a) it cannot be used to evaluate MRD on Day 28-33 after completion of induction therapy which has better prognostication than MRD done on day 19; (b) not using LAIPs to differentiate residual blasts from precursor B cells may give false positive results, and (c) the limit of detection is 0.01%, which is one log lower than the one with advanced flow cytometry.…”

Pediatric acute lymphoblastic leukemia treatment protocols improvement: emphasis on minimal residual disease

“…Большой интерес представляют работы, указыва ющие на внутриутробное происхождение ОЛЛ у детей [2][3][4][5][6][7]. Косвенные данные, подтверждающие этот факт, получены в исследованиях ОЛЛ близнецов раннего возраста, у которых конкордантность составила более 50 %, что позволяет предположить наличие первично го генетического события, произошедшего внутри утробно и не связанного с наследственной предраспо ложенностью [4,8].…”