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();,:
Summary
Previously, we have shown that patients with diffuse large B‐cell lymphoma (DLBCL) transplanted with contaminated bone marrow (BM) generally have a poor outcome. Whether this is also the case when peripheral blood progenitor cell (PBPC) grafts are used is not known. Forty‐three patients with chemosensitive DLBCL or follicular lymphoma grade 3 (FLgr3) were treated with high‐dose therapy (HDT) and autologous stem cell support. Nine patients received purged grafts. Quantitative real‐time polymerase chain reaction (QRT‐PCR) for either the BCL2/IgH translocation or allele specific oligonucleotide (ASO) QRT‐PCR for the immunoglobulin heavy chain (IgH) complementarity‐determining region 3 were used. Nine of 25 (36%) PBPC grafts contained tumour cells as tested by QRT‐PCR, including two grafts purged by CD34+ cell enrichment combined with B‐cell depletion. The level of contamination of the PBPC/CD34+ cells ranged from 0 to 8·28%. No relationship could be shown between the total number of tumour cells infused and relapse. Patients receiving PCR‐positive or PCR‐negative PBPC grafts had similar progression‐free survival (PFS) (P = 0·49). However, a significant difference was seen in PFS and overall survival (OS) for the patients given ≥6·1 × 106 CD34+ cells/kg compared with those given <6·1 × 106 CD34+ cells/kg (P = 0·01 and P < 0·05 respectively).
Peripheral T-cell lymphoma (PTCL) with a nodular architecture is rare. Recently, two variants have been described with infiltration of the B-cell follicle, one variant that localizes to the marginal zone with a so-called perifollicular growth pattern, and a variant that localizes to the germinal center. These lymphomas have a CD4+ phenotype and may express Bcl-6. We have studied five similar cases of PTCL with involvement of the B-cell follicle. However, our cases differ from the cases previously described by their predominant and frequently patchy involvement of the expanded mantle zone of the B-cell follicle at onset. Later biopsies in three of the cases show diffuse infiltration of the lymph node, without features of angioimmunoblastic TCL (AILT). All cases expressed Bcl-6 in addition to CD4. Cytogenetics was available in four of the cases but revealed no recurrent chromosomal aberrations or changes associated with other types of PTCL. No mutations of the BCL-6 gene were observed. Together, the cases seem to have an intermediately aggressive clinical behavior. Whether our cases are part of a spectrum of PTCLs that encompasses previously described variants with predominant marginal zone or germinal center infiltration or they represent a separate T-cell lymphoma type remains to be demonstrated by a study of more of such cases.
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word count: 199 Abstract Minimal residual disease (MRD) is a powerful prognostic factor in acute lymphoblastic leukemia (ALL) and is used for patient stratification and treatment decisions, but its precise role in Philadelphia chromosome positive ALL is less clear.This uncertainty results largely from methodological differences relating to the use of real-time quantitative PCR (qRT-PCR) to measure BCR-ABL1 transcript levels for MRD analysis. We here describe the first results by the EURO-MRD consortium on standardization of qRT-PCR for the e1a2 BCR-ABL1 transcript in Ph+ALL, designed to overcome the lack of standardisation of laboratory procedures and data interpretation. Standardised use of EAC primer/probe sets and of centrally prepared plasmid standards had the greatest impact on reducing interlaboratory variability. In QC1 the proportion of analyses with BCR-ABL1/ABL1 ratios within half a log difference were 40/67 (60%) and 52/67 (78%) at 10 -3 and 36/67 (53%) and 53/67 (79%) at 10 -4 BCR-ABL1/ABL1. Standardized RNA extraction, cDNA synthesis and cycler platforms did not improve results further, whereas stringent application of technical criteria for assay quality and uniform criteria for data interpretation and reporting were essential. We provide detailed laboratory recommendations for the standardized MRD analysis in routine diagnostic settings and in multicenter clinical trials for Ph+ALL.
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