Minimal residual disease quantification by flow cytometry provides reliable risk stratification in T-cell acute lymphoblastic leukemia

Abstract

Since the publication of the original paper, the authors realized in the analyses of day 15 MRD <25% and day 29 MRD data and outcome, three patients were misclassified due to non-censoring of event after HSCT. All three were stratified concordantly by FCM and PCR, two above (one relapse and one non-relapse related death) and one (relapse) below the cutoff level of 10 −3 . There is no change in the conclusions of the paper. An additional seven were misclassified but had day 15 MRD levels >0.25 and thus did not affect further analyses.The original article can be found online at https://doi.org/10.1038/ s41375-018-0307-6. 1234567890();,:1234567890();,:

Highly sensitive chimerism detection in blood is associated with increased risk of relapse after allogeneic hematopoietic cell transplantation in childhood leukemia

“…A subset of children had bone marrow samples analyzed for MRD concurrently with chimerism analysis in peripheral blood. MRD was analyzed by RQ‐PCR according to the EuroMRD guidelines or by multicolor flow cytometry as described in the NOPHO ALL2008 guidelines . MRD results were categorized as either negative or positive < 10 −4 ; positive ≥ 10 −4 but <10 −3 ; positive ≥ 10 −3 ; or positive but below a quantitative range of 10 −3 …”

Minimal residual disease monitoring cannot fully replace bone marrow morphology in assessing disease status in pediatric acute lymphoblastic leukemia

“…MRD monitoring has redefined the concept of remission in pediatric ALL providing a reliable measurement of the drug sensitivity of leukemic lymphoblasts guiding better risk-directed therapy. Several studies have demonstrated a strong association between MRD levels and treatment outcome in childhood ALL (1,2,4). Accordingly, MRD techniques are currently utilized during and after induction therapy and for post remission monitoring to assess the response to therapy and to provide important information on the depth of post induction remission in essentially all major pediatric ALL protocols (6).…”

“…PCR-MRD monitoring was performed in parallel from day 29 according to the pre-T phenotype and protocol. Cytogenetic analysis revealed a clone with t(5;14) as the only aberration (46,XY,t(5;14)(q15; q32) [13]/46,XY [2]) confirmed by FISH to not involve TLX3. Multiplex PCR was negative for all 28 investigated translocations (8).…”

“…Samples for morphological evaluation and cytogenetics were drawn after repuncture in another area of the medulla, and finally, trephine biopsies were taken after the third repuncture of the iliac crest. MRD was measured at the Department of Clinical Immunology (NOPHO National Danish MRD laboratory), Rigshospitalet, Copenhagen, Denmark, either by RQ-PCR based techniques using patientspecific clonal Ig/TCR gene rearrangements according to the BIOMED-2 guidelines (14,15) and/or flow cytometry using protocol-defined six to eight color MRD panels for identification and monitoring of leukemia-associated immunophenotypes according to the NOPHO ALL-2008 guidelines (2,16). According to the protocol, BCP-ALL should primary be stratified using MRD flow and T-ALL primary using PCR-MRD if informative markers are available.…”

“…Minimal residual disease (MRD) monitoring during therapy has become the most important independent prognostic factor in childhood acute lymphoblastic leukemia (ALL) (1,2). In childhood, ALL MRD monitoring is done by multiparameter flow cytometry, quantitative polymerase chain reaction (PCR) of clonal rearrangements in immunoglobulin and/or T-cell receptor genes (IG/ TCR), or reverse transcriptase quantitative PCR (qRT-PCR) of leukemic fusion transcripts (1,3,4).…”