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Laurent Sutton

Publications and source records attributed to Laurent Sutton.

7 recordsLinked to original sources

Over 20% of patients with chronic lymphocytic leukemia carry stereotyped receptors: Pathogenetic implications and clinical correlations.

The chronic lymphocytic leukemia (CLL) immunoglobulin repertoire is biased and characterized by the existence of subsets of cases with closely homologous ("stereotyped") complementarity-determining region 3 (CDR3) sequences. In the present series, 201 (21.9%) of 916 patients with CLL expressed IGHV genes that belonged to 1 of 48 different subsets of sequences with stereotyped heavy chain (H) CDR3. Twenty-six subsets comprised 3 or more sequences and were considered "confirmed." The remaining subsets comprised pairs of sequences and were considered "potential"; public database CLL sequences were found to be members of 9 of 22 "potential" subsets, thereby allowing us to consider them also "confirmed." The chance of belonging to a subset exceeded 35% for unmutated or selected IGHV genes (eg, IGHV1-69/3-21/4-39). Comparison to non-CLL public database sequences showed that HCDR3 restriction is "CLL-related." CLL cases with selected stereotyped immunoglobulins (IGs) were also found to share unique biologic and clinical features. In particular, cases expressing stereotyped IGHV4-39/IGKV1-39-1D-39 and IGHV4-34/IGKV2-30 were always IgG-switched. In addition, IGHV4-34/IGKV2-30 patients were younger and followed a strikingly indolent disease, contrasting other patients (eg, those expressing IGHV3-21/IGLV3-21) who experienced an aggressive disease, regardless of IGHV mutations. These findings suggest that a particular antigen-binding site can be critical in determining the clinical features and outcome for at least some CLL patients.

ADP-ribosyl Cyclase 1↗

Efficacy of granulocyte and granulocyte-macrophage colony-stimulating factors in the induction treatment of adult acute lymphoblastic leukemia: a multicenter randomized study.

In all, 236 adults with newly diagnosed acute lymphoblastic leukemia (ALL) were randomly assigned to receive either granulocyte colony-stimulating factor (G-CSF), or granulocyte-macrophage CSF (GM-CSF), or no CSF during a 4-week 4-drugs induction chemotherapy. Two successive trials were performed. CSFs were given from the last infusion of anthracycline in Trial 1 or from day 4 of induction therapy in Trial 2 until neutrophil recovery. A total of 95 patients were included in the G-CSF group, 67 in the GM-CSF group, and 74 in the control group. Overall, CSFs showed a trend for a reduced incidence of severe infections and of days with antibiotics. Median time for neutrophil recovery was 17 days with G-CSF, 18 days with GM-CSF, and 21 days without CSF. In Trial 2, duration of hospitalization was significantly lower in the G-CSF group than in the other groups (P < 0.05). Time to neutrophil recovery was also significantly shorter (P < 0.05) and severe infections were lower in the G-CSF group (P = 0.01). CR rate was higher in the GM-CSF group as compared to the control group. This tended to be confirmed for the most aggressive ALL and was statistically significant for Philadelphia-positive ALL after salvage therapy (P = 0.04). There were no significant differences between the three groups in terms of disease-free survival.

Adolescent↗

Chronic graft-versus-host disease after allogeneic blood stem cell transplantation: long-term results of a randomized study.

The use of peripheral blood stem cells (PBSCs) is rapidly growing in the allogeneic transplantation setting as an alternative to bone marrow (BM). We previously reported a higher incidence of chronic graft-versus-host disease (cGVHD) associated with allogeneic PBSC transplantation in a randomized trial. In this follow-up report, we analyzed the evolution of cGVHD in the patients (n = 101) enrolled on this study. At a median follow-up of 45 months (range, 31-57 months), we found that the 3-year cumulative incidence of cGVHD was 65% (95% confidence interval [CI] 51%-78%) in the PBSC group and 36% (95% CI 23%-49%) in the BM group (P =.004). We also found that extensive cGVHD was more frequent in the PBSC group (44% [95% CI 30%-58%] vs 17% [95% CI 7%-27%]; P =.004). The prevalence of cGVHD was always higher in the PBSC arm. Ocular involvement was more frequent in PBSC recipients (P =.02). Cutaneous and liver involvement was similar among BM and PBSC recipients. Chronic GVHD required multiple courses of immunosuppressive therapy in addition to cyclosporine and corticosteroids during longer periods (P =.03). Altogether, this translated into longer periods of hospitalization after transplantation in the PBSC group (P =.04). Finally, we also confirm that cGVHD after PBSC transplantation is associated with an antileukemic effect that is at least as potent as after BM. However, to date, this has not translated into a survival difference, possibly due to the early-stage leukemic status of these patients or to the relatively small size of the study population.

Adult↗

Novel flow-cytometric analysis based on BCD5+ subpopulations for the evaluation of minimal residual disease in chronic lymphocytic leukaemia.

We describe a new flow-cytometric analysis using quadruple labelling with anti-CD19, CD20, CD5, CD79b monoclonal antibodies and sequential gating. We determined a novel criteria defined by BCD5+CD79b-/low/total BCD5+ cells ratio (BCD5+R), and compared it with the previous definition of phenotypic remission, based on CD19+CD5+ coexpression, and with complementarity-determining region 3 polymerase chain reaction (CDR3 PCR) and clonotypic PCR (cPCR). A series of 54 peripheral blood samples from 21 chronic lymphocytic leukaemia (CLL) patients in complete haematological remission and a series of 16 from normal volunteers were analysed. In normal controls, the BCD5+R was always < 0.2. The sensitivity of the BCD5+R was 1 x 10-4vs 5 x 10-2 for CDR3 PCR and 1 x 10-5 for cPCR. Among the 54 CLL samples, 35 had a BCD5+R < 0.2 and showed polyclonal CDR3 PCR, whereas the cPCR was positive in 12 out of 20 tested. In the remaining 19 samples, BCD5+R was > 0.2, CDR3 PCR was monoclonal in 16 out of 19 and cPCR positive in 14 out 14 tested, including one out of three samples with polyclonal CDR3 amplification. Even though cPCR remains the most sensitive method to evaluate MRD, this new, sensitive and specific flow cytometric parameter, the BCD5+R, is more suitable than CDR3 PCR for routine clinical MRD assessment in CLL.

Adult↗