Minimal residual disease (MRD) levels were determined by multi-parameter flow cytometry in 45 younger adult patients ( pound60 years old) with acute myeloid leukemia (AML) in complete remission. Data were collected after induction (MRD1; n=43) and/or at the end of post-remission chemotherapy or before stem cell transplantation (SCT)(MRD2; n=31). Patients with detectable MRD2 who underwent allogeneic or autologous SCT had significantly better 5-year relapse-free survival than patients not transplanted (80%, 53% and 0%, respectively p=0.003). Therefore allogeneic SCT should be considered in younger adult AML patients with detectable MRD at the end of post-remission chemotherapy. Autologous SCT may be an alternative for patients not eligible for allogeneic SCT.
Summary. Measurement of the soluble form of CD8 antigen (sCD8), a surface membrane component of suppressor/cytotoxic T cells, has yielded useful information relevant to prognosis in children with acute lymphoblastic leukaemia and Hodgkin's disease (HD). An ELISA technique was used to measure the amount of sCD8 in sera from 123 adults with untreated HD. Significantly higher mean sCD8 levels were found in patients with advanced disease (stage III‐IV; P < 0·001), B‐symptoms ( P < 0·001), male sex ( P < 0·05) and increased spontaneous and decreased Concanavalin A induced blood lymphocyte DNA‐synthesis ( P < 0·05). Actuarial survival of patients with high sCD8 levels was significantly worse than that of the remainder ( P < 0·05). However, the sCD8 level did not add prognostic information to that achieved by age, sex, lactate dehydrogenase (LDH) or clinical stage. A significant correlation between the sCD8 and LDH levels ( r = 0·33; P < 0·001) and inverse correlations between sCD8 levels and total blood CD4 + ( r = −0·52; P < 0·001) and CD3 + ( r = −0·39; P < 0·01) cell counts were found. Ten patients were also studied in complete remission, showing a significantly reduced sCD8 level in comparison to the pretreatment value ( P < 0·05). Increased sCD8 in HD may indicate enhanced suppressor T cell activity possibly compromising the host disease balance which could explain the association with prognosis.
Multiple myeloma (MM) is a B‐lineage malignancy with unknown aetiology. It has been considered that predisposing genetic factors might be implicated in the disease. In this study, the microsatellite polymorphism in the exon 3 of the cytotoxic T‐lymphocyte antigen‐4 (CTLA‐4) gene was analysed in patients with MM and monoclonal gammopathy of undetermined significance (MGUS), together with ethnically matched healthy controls. The results showed that frequencies of the genotype 86/86 and of the allele 86 were significantly decreased in MM and MGUS compared with matched healthy controls, indicating that the CTLA‐4 microsatellite polymorphism might represent a susceptibility locus for MM and MGUS.
20 patients with benign monoclonal gammopathy (BMG) have been studied for blood lymphocyte and subpopulations. 4 patients had slightly decreased T‐lymphocyte values. Total B‐lymphocytes were within the normal range. In 3 BMG patients an abnormal ratio between χ‐ and Λ‐bearing lymphocytes was detected indicating circulating monoclonal cells. 41 patients with untreated multiple myeloma have also been analysed for blood monoclonal lymphoid cells using the χ:Λ‐ratio. 54% of the patients had monoclonal blood cells at diagnosis. The incidence and numbers of such cells increased with advanced clinical stage. Thus, it seems as if tumor volume is the main factor responsible for the appearance of monoclonal blood cells in multiple myeloma.
Background: Circulating tumor DNA (ctDNA) quantification has been shown to predict therapeutic benefit in patients (pts) with DLBCL. We recently investigated the prognostic impact of total metabolic tumor volume (TMTV) in DLBCL pts responder to R-CHOP in the REMARC study. In the present ancillary study, we wish to analyze the potential correlation of ctDNA with the outcome and relate these results to functional imaging by PET/CT (TMTV). We also aim to correlate the circulating tumor DNA load with the new score TMTV plus ECOG PS. Patients and Methods: 794 pts were included in the study either at diagnosis (n = 446) or at the end of R-CHOP (n = 347). At the end of R-CHOP, 650 pts achieved a complete response and were randomized to receive 2 years of lenalidomide or placebo. Tumoral cfDNA measurements were performed using a dedicated 36 genes panel with the QiaSeq® technology. CtDNA concentrations were expressed in haploid genome equivalents per mL of plasma (hGE/mL) and calculated by multiplying the mean variant allele frequency (VAF) by the concentration of total cfDNA (Bohers et al. Blood Cancer J 2018).The optimal ctDNA cut-offs for PFS and OS were determined by X-tile analyses and confirmed by a training validation method. Results: A total of 240 pts were analyzed, including 62 non-responder and non-randomized pts (NR-NRP) and 173 responder and randomized pts (REMARC pts). 5 pts had no interpretable ctDNA analysis and were excluded. Among the 235 NR-NRP/REMARC cohort, a ctDNA > 3.74 was present in 14% of pts and was predictive for PFS (HR = 1.68, 95%CI 1.02–2.76, p = 0.0397) and OS (HR = 2.15, 95%CI 1.28-3.61, p = 0.0031). The 3y-PFS for pts with a ctDNA > 3.74 was 47.3% (95%CI: 30%-63%) vs 71.5% (95% CI: 65%-77%) for pts with a ctDNA ≤ 3.74. The 3y-OS for pts with a ctDNA > 3.74 was 56.4% (95%CI: 38%-71%) vs 81.8% (95% CI: 76%-87%) for pts with a ctDNA ≤ 3.74. Among the 173 R-CHOP responder patients (REMARC cohort), the 12 months-relapse free survival since last cycle of R-CHOP for pts with a ctDNA > 3.74 at diagnosis was 61.1% (95%CI: 35%-79%) vs 88.7% (95%CI: 82%-93%) for pts with a ctDNA ≤ 3.74 (p = 0.009). However, a ctDNA > 3.74 was not predictive either for PFS (HR = 1.64, 95%CI: 0.84-3.21, p = 0.14) nor for OS (HR = 1.91 95%CI: 0.93-3.89, p = 0.07). Among the 100 pts with ctDNA and TMTV available, median log ctDNA was found significantly higher in TMTV > 220 (n = 58) vs TMTV < 220 (p = 0.002). However, no significant impact of ctDNA (threshold 3.4) and TMTV(threshold 220) was observed on PFS and OS. Conclusion: Using a routinely targeted sequencing panel for ctDNA measurement, we confirmed the prognostic value of ctDNA concentration to predict outcome in DLBCL patients. For patients responding to R-CHOP, high ctDNA level was significantly associated with high TMTV and early relapse. The research was funded by: BMS Keywords: Diagnostic and Prognostic Biomarkers, Aggressive B-cell non-Hodgkin lymphoma No conflicts of interest pertinent to the abstract.
