ABSTRACT
Measurable residual disease (MRD) is a well-known independent prognostic factor in acute leukemias, and multicolor flow cytometry (MFC) is widely used to detect MRD. MFC is able not only to enumerate MRD accurately but also to describe an antigen expression profile of residual blast cells. However, the relationship between MRD immunophenotype and patient survival probability has not yet been studied. We determined the prognostic impact of MRD immunophenotype in adults with B-cell acute lymphoblastic leukemia (B-ALL). In a multicenter study RALL-2016 (NCT03462095), 267 patients were enrolled from 2016 to 2022. MRD was assessed at the end of induction (day 70) in 94 patients with B-ALL by six- or 10-color flow cytometry in the bone marrow specimens. The 4 year relapse-free survival (RFS) was lower in MRD-positive B-ALL patients [37% vs. 78% (p < 0.0001)]. The absence of CD10, positive expression of CD38, and high expression of CD58 on MRD cells worsened the 4 year RFS [19% vs. 51% (p = 0.004), 0% vs. 51% (p < 0.0001), and 21% vs. 40% (p = 0.02), respectively]. The MRD immunophenotype is associated with RFS and could be an additional prognostic factor for B-ALL patients.
ABSTRACT
Introduction: Waldenström macroglobulinemia is an incurable disease, despite advances in the use of targeted therapy. Aim: To assess the effectiveness of intensive induction immunochemotherapy and its combination with targeted drugs and subsequent autologous stem cell transplantation (auto-SCT). Materials and Methods: Twenty-one patients were selected. Four and 17 patients were in the medium- and high-risk groups, respectively. Twelve patients (57%) had hyperviscosity syndrome, 21 (100%) had anemia, 4 (19%) had platelets <100, 4 had hemolysis, 4 (19%) had cryoglobulinemia, 13 (62%) had lymphadenopathy and splenomegaly, 12 had B-symptoms, 11 had LDH >250 U/L, 6 had albumin <30 g/L, and 11 had β-2-microglobulin >4 mg/L. The mean PIgM was 45.3 g/L and Hb was 82 g/L. Sixteen patients (76%) had an L265P mutation in MYD 88 and 2 patients had del -17p. Results: The mean age of the patients was 51.4 years (33–66 years), with 8 women. Four patients underwent 4 courses - R-EPOCH\R - BAC, 17 patients had the R -EPOCH\R - BAC + ibrutinib, and 15 patients had auto-SCT. BEAM was received by 6 patients. BEAM + daratumumab was received by 9 patients. The overall response was 100%, partial response was 100%, very good partial response was 71%, and CR was 32%. At a median follow-up of 44 months, 5-year overall survival was 93% and 5-year progression-free survival was 87%. After 28 months of observation, progression was observed in 1 patient. One patient died in CR from Covid-19 pneumonia. In the group of patients who received immunochemotherapy with ibrutinib and subsequent high-dose consolidation under the Dara - BEAM program, there was a trend towards an increase in the frequency of CR compared with the rest of the patients: 59% and 18%, respectively. Conclusions: R-EPOCH\ R-BAC + ibrutinib + high-dose consolidation + auto-SCT led to deep responses in 71% of patients. Primary intensification makes it possible to implement the concept of “stop” therapy, which makes it cost-effective. The use of high-dose consolidation according to the Dara-BEAM program increases the effectiveness of treatment. We are continuing the study, which will increase the reliability of the results.