Serum Thymus and Activation-Regulated Chemokine Level Monitoring May Predict Disease Relapse Detected by PET Scan after Reduced-Intensity Allogeneic Stem Cell Transplantation in Patients with Hodgkin Lymphoma

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Differential Effects of Brain Disorders on Structural and Functional Connectivity

Different measures of brain connectivity can be defined based on neuroimaging read-outs, including structural and functional connectivity. Neurological and psychiatric conditions are often associated with abnormal connectivity, but comparing the effects of the disease on different types of connectivity remains a challenge. In this paper, we address the problem of quantifying the relative effects of brain disease on structural and functional connectivity at a group level. Within the framework of a graph representation of connectivity, we introduce a kernel two-sample test as an effective method to assess the difference between the patients and control group. Moreover, we propose a common representation space for structural and functional connectivity networks, and a novel test statistics to quantitatively assess differential effects of the disease on different types of connectivity. We apply this approach to a dataset from BTBR mice, a murine model of Agenesis of the Corpus Callosum (ACC), a congenital disorder characterized by the absence of the main bundle of fibers connecting the two hemispheres. We used normo-callosal mice (B6) as a comparator. The application of the proposed methods to this data-set shows that the two types of connectivity can be successfully used to discriminate between BTBR and B6, meaning that both types of connectivity are affected by ACC. However, our novel test statistics shows that structural connectivity is significantly more affected than functional connectivity, consistent with the idea that functional connectivity has a robust topology that can tolerate substantial alterations in its structural connectivity substrate

A phase II study on the role of gemcitabine plus romidepsin (GEMRO regimen) in the treatment of relapsed/refractory peripheral T-cell lymphoma patients

Background: There is no consensus regarding optimal treatment for peripheral T-cell lymphomas (PTCL), especially in relapsed or refractory cases, which have very poor prognosis and a dismal outcome, with 5-year overall survival of 30 %. Methods: A multicenter prospective phase II trial was conducted to investigate the role of the combination of gemcitabine plus romidepsin (GEMRO regimen) in relapsed/refractory PTCL, looking for a potential synergistic effect of the two drugs. GEMRO regimen contemplates an induction with romidepsin plus gemcitabine for six 28-day cycles followed by maintenance with romidepsin for patients in at least partial remission. The primary endpoint was the overall response rate (ORR); secondary endpoints were survival, duration of response, and safety of the regimen. Results: The ORR was 30 % (6/20) with 15 % (3) complete response (CR) rate. Two-year overall survival was 50 % and progression-free survival 11.2 %. Grade >= 3 adverse events were represented by thrombocytopenia (60 %), neutropenia (50 %), and anemia (20 %). Two patients are still in CR with median response duration of 18 months. The majority of non-hematological toxicities were mild and transient. No treatment-related death occurred and no toxicity led to treatment interruption. Conclusions: GEMRO combination regimen shows efficacy data similar to those of single-agent romidepsin with additional hematologic toxicities. Synergy observed in preclinical phase did not turn into ability to improve clinical outcomes

Bortezomib Plus Dexamethasone Followed by Escalating Donor Lymphocyte Infusions for Patients with Multiple Myeloma Relapsing or Progressing after Allogeneic Stem Cell Transplantation

Abstract Multiple myeloma relapsing after allogeneic stem cell transplantation (alloSCT) has a poor outcome. To assess the safety and efficacy of bortezomib and dexamethasone (VD) combination followed by donor lymphocyte infusions (DLIs) in myeloma patients relapsing or progressing after alloSCT, a prospective phase II study was designed. The treatment plan consisted of three VD courses followed by escalated doses of DLIs in case of response or at least stable disease. Nineteen patients were enrolled with a median age of 57 years (range, 33 to 67); 14 patients were allografted from human leukocyte antigen–identical siblings and 5 from alternative donors. Sixteen of 19 patients received the planned treatment, but 3 patients did not: 2 patients because of disease progression and 1 refused. After the VD phase the response rate was 62%, with 1 complete remission, 6 very good partial remissions, 5 partial remissions, 2 patients with stable disease, and 5 with progressive disease. After the DLI phase, the response rate was 68%, but a significant upgrade of response was observed: 3 stringent complete remissions, 2 complete remissions, 5 very good partial remissions, 1 partial remission, 4 with stable disease, and 1 with progressive disease. With a median follow-up of 40 months (range, 29 to 68), the 3-year progression-free survival and overall survival rates were 31% and 73%, respectively. Neither unexpected organ toxicities, in particular severe neuropathy, nor severe acute graft-versus-host disease flares were observed. VD-DLIs is a safe treatment for multiple myeloma patients relapsing or progressing after alloSCT and may be effective

Impact of Cytomegalovirus Replication and Cytomegalovirus Serostatus on the Outcome of Patients with B Cell Lymphoma after Allogeneic Stem Cell Transplantation

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Allogeneic Stem Cell Transplantation for Relapsed/Refractory B Cell Lymphomas: Results of a Multicenter Phase II Prospective Trial including Rituximab in the Reduced-Intensity Conditioning Regimen.

The treatment of patients with refractory/relapsed B cell non-Hodgkin lymphoma (NHL) is evolving because of the availability of novel drugs. Allogeneic stem cell transplantation (alloSCT) can be curative, but its morbidity and mortality remain a matter of concern. We conducted a multicenter prospective phase II trial to evaluate the benefit of including only 1 dose of rituximab in the conditioning regimen before alloSCT. The primary endpoint was progression-free survival. The study enrolled 121 patients with relapsed/refractory B cell lymphomas. The conditioning regimen consisted of thiotepa, cyclophosphamide, fludarabine, and rituximab (500\u2009mg/m2). Rabbit antithymocyte globulin was administered only in case of unrelated donors. Sixty-seven (55%) and 54 (45%) patients received grafts from related and unrelated donors, respectively. The crude cumulative incidence (CCI) of nonrelapse mortality (NRM) was 21% at 3 years. The CCIs of chronic graft-verus-host disease (GVHD) at 3 years were 54% and 31% in recipients of matched sibling and unrelated grafts, respectively. At a median follow-up of 41 months, the estimated 3-year progression-free and overall survival were 50% and 61%, respectively. Long-term outcome was also evaluated with the composite endpoint of GVHD-free and relapse-free survival (GRFS). This is the first work evaluating the GRFS in a prospective trial of lymphoma patients: the 1-year and 3-year GRFS were 40% and 34%, respectively. AlloSCT can cure a fraction of patients with rather low NRM and an encouraging PFS and GRFS

Qualitative and quantitative polymerase chain reaction monitoring of minimal residual disease in relapsed chronic lymphocytic leukemia: early assessment can predict long-term outcome after reduced intensity allogeneic transplantation

Allogeneic stem cell transplantation is being considered as a potentially curative treatment for patients with chronic lymphocytic leukemia. The findings of this study suggest that relapsed patients can achieve molecular remission after reduced intensity conditioning and allogeneic stem cell transplantation