this is a hypothesis that has yet to be proven, but it remains a viable potential explanation for the immunologic changes we observed.Psomas et al also highlight the different conclusions reached by our trials regarding the effects of maraviroc intensification on changes in T-cell activation and monocyte activation. As discussed in our recent paper, 1 we agree that technical issues and differences in patient populations may have contributed to the reductions in T-cell activation observed in several uncontrolled trials of maraviroc intensification. [2][3][4] Psomas et al discount the possibility that increased adherence to the background antiretroviral therapy regimen could have contributed to the decreased T-cell activation levels or plasma 16S ribosomal DNA levels observed in their study because levels did not significantly change between enrollment and the start of study medication, but adherence typically improves when trial subjects start taking a study medication, particularly when they know that pills are being counted. This appeared to be the case in the placebo arms of our trial and another recent placebo-controlled treatment intensification study. 1,5 This is one of the reasons why double-blind randomized placebo-controlled trials are the gold standard for evidence in clinical research. We agree that further research will be necessary to understand many of the unexpected effects of maraviroc intensification on the immune system in treated HIV infection, but strongly suggest that this work be conducted in the context of adequately powered randomized controlled trials so that observed effects can be clearly attributed to the intervention. To the editor:MYD88 (L265P) mutation is an independent risk factor for progression in patients with IgM monoclonal gammopathy of undetermined significance MYD88 (L265P) is a recurrent somatic mutation in Waldenström macroglobulinemia (WM). 1-4 By means of allele-specific polymerase chain reaction (AS-PCR), the MYD88 mutation is detectable in almost all patients with WM and in roughly half the patients with IgM monoclonal gammopathy of undetermined significance (IgM-MGUS). 2,3,5IgM-MGUS patients have a probability of progression to WM or to other lymphoproliferative disorders (LPD) of ;1.5% per year, and the initial concentration of the serum monoclonal (M) protein is the main predictor of progression. 6In a case-control study of 77 IgM-MGUS patients, we previously demonstrated that the MYD88 mutation was associated with higher disease burden and with a higher risk of progression to WM or to other LPD. 2 We have now analyzed by AS-PCR bone marrow samples, collected at the time of diagnosis, of 136 consecutive IgM-MGUS patients, with the aim to confirm the prognostic role of the MYD88 mutation in a longitudinal study and to evaluate the effect of the MYD88 mutation and of the other potential risk factors in multivariate analysis.Genomic DNA was extracted from bone marrow mononuclear cells (n 5 92) or archival Giemsa-stained slides (n 5 44). AS-PCR was performed as pre...

We characterized immunoglobulin heavy chain (IGH) gene rearrangements and searched for clusters of stereotyped B-cell receptors in 123 patients with Waldenström macroglobulinemia (WM; n = 59) or immunoglobulin M monoclonal gammopathy of undetermined significance (IgM-MGUS) (n = 64). A productive monoclonal IGHV-D-J rearrangement was obtained in 99/123 patients (80%). Immunoglobulin heavy chain variable (IGHV) genes were mutated in 94/99 patients (95%) with a median somatic hypermutation rate of 6.7% (2.1-14.5). Compared with the normal B-cell repertoire, patients with WM/IgM-MGUS showed an over-representation of the IGHV3 subgroup (83% vs. 55%, p < 0.0001) and an under-representation of IGHV1 (7% vs. 14%, p = 0.04) and IGHV4 (7% vs. 23%, p = 0.0001) subgroups. At the gene level, in WM/IgM-MGUS there was an over-representation of IGHV3-23 (24% vs. 12%, p = 0.0003), IGHV3-64 (3% vs. < 1%, p = 0.003), IGHV3-7 (12% vs. 4%, p = 0.0001) and IGHV3-74 (9% vs. 2%, p < 0.0001), while IGHV4-39 was never used (0 vs. 5%, p = 0.03). Intra-WM/IgM-MGUS search for HCDR3 similarity showed no association fulfilling criteria for stereotyped receptors. WM/IgM-MGUS sequences were unrelated to known chronic lymphocytic leukemia (CLL), splenic marginal zone lymphoma (SMZL) or mantle cell lymphoma (MCL) subsets. In conclusion, the IGHV gene usage in WM and IgM-MGUS is remarkably biased as compared to the normal B-cell repertoire. WM and IgM-MGUS-specific HCDR3 clusters do not occur with a frequency detectable with currently available databases, not supporting a B-cell receptor-driven pathogenesis in WM and IgM-MGUS.

There is much evidence demonstrating that psychosocial interventions in caregivers and oncological staff produce an improvement in their patients' quality of life. The aim of this explorative study was to evaluate the effect of a new approach in promoting more functional ways to face stressful situations in the constellation of people around patients: caregivers, physicians and nurses. Thirty-four subjects were divided into three groups: 10 caregivers, 11 physicians, and 13 nurses. A “Balint Group” method modified according to a mindfulness technique was used as the intervention. Three assessment tools were administered to the participants at baseline, during, and after completion of the study: the Response Evaluation Measure (REM-71), the Satisfaction Profile (SAT-P), and the Group Climate Questionnaire (GCQ). Mean values of defense mechanisms determined by the REM-71 were compared with those of the standard population. At baseline, we observed a prevalence of immature defenses in the three groups, with mean values above those in the standard population. After the psychological intervention, a tendency to normalization of the mean values was observed, indicating the development of more adaptive ways of using defense mechanisms and the effectiveness of the intervention. Group climate, assessed through the GCQ, showed an increase in the “Engagement” factor and a decline in the “Conflict” factor in all groups. This study suggests that group treatment focused on changing personal responses to stressful situations can induce more adaptive strategies enabling caregivers, hematologists, and nurses to help patients better and thereby improve their quality of life.