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();,:

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Pretreatment detection of peripheral blood malignant circulating plasma cells (CPCs) has been shown to be of negative prognostic value in multiple myeloma (MM). We hypothesized that the assessment of CPC kinetics in response to one therapy cycle using six-color flow cytometry could be helpful in the early detection of MM refractoriness to treatment. Forty-two patients with refractory or relapsed (RR) MM were enrolled. Median time to tumor progression (TTP) of 51 days and median overall survival (OS) of 308 days was shortest in patients whose CPCs with aberrant phentoype (aCPCs) did not decrease after one therapy cycle compared to patients with decreasing (median TTP 258 days and OS 856 days) or undetectable (median TTP 581 days and OS 1006 days) aCPCs (p < 0.001 and p = 0.007 for TTP and OS, respectively). Non-reduction of aCPCs in patients with RR MM after the first cycle of therapy may be useful in early identification of patients resistant to a given therapy.

PCR of TCR/Ig gene rearrangements is considered the method of choice for minimal residual disease (MRD) quantification in BCP-ALL, but flow cytometry analysis of leukemia-associated immunophenotypes (FCM-MRD) is faster and biologically more informative. FCM-MRD performed in 18 laboratories across seven countries was used for risk stratification of 1487 patients with BCP-ALL enrolled in the NOPHO ALL2008 protocol. When no informative FCM-marker was available, risk stratification was based on real-time quantitative PCR. An informative FCM-marker was found in 96.2% and only two patients (0.14%) had non-informative FCM and non-informative PCR-markers. The overall 5-year event-free survival was 86.1% with a cumulative incidence of relapse (CIR5y) of 9.5%. FCM-MRD levels on days 15 (HzR 4.0, p < 0.0001), 29 (HzR 2.7, p < 0.0001), and 79 (HzR 3.5, p < 0.0001) associated with hazard of relapse adjusted for age, cytogenetics, and WBC. The early (day 15) response associated with CIR5y adjusted for day 29 FCM-MRD, with higher levels in adults (median 2.4 × 10−2 versus 5.2 × 10−3, p < 0.0001). Undetectable FCM- and/or PCR-MRD on day 29 identified patients with a very good outcome (CIR5y = 3.2%). For patients who did not undergo transplantation, day 79 FCM-MRD > 10−4 associated with a CIR5y = 22.1%. In conclusion, FCM-MRD performed in a multicenter setting is a clinically useful method for MRD-based treatment stratification in BCP-ALL.