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Transformed lymphoma (TL) is historically associated with a poor prognosis, though autologous stem cell transplantation (ASCT) has been applied successfully. Better patient selection is needed for this intensive therapy. We analyzed the outcomes between de novo and transformed large B-cell lymphoma in patients undergoing ASCT, with regard to the immunohistochemical (IHC) features of potential prognostic utility including CD10, BCL6, MUM-1, Ki67, and BCL2. Of all patients undergoing ASCT for large B-cell lymphoma at the Cleveland Clinic Taussig Cancer Institute between 2003 and 2008, 56 patients (31 de novo and 25 TL) had undergone detailed IHC analysis. Three-year relapse-free-survival (RFS) and overall survival (OS) for TL vs. patients with de novo large B-cell lymphoma were 64%vs. 59% and 63%vs. 59%, respectively. More patients with TL were characterized as germinal-center B cell-of-origin (92%) than patients with de novo large B-cell lymphoma (71%). Immunohistochemistry did not predict relapse-free or overall survival, and ASCT afforded a high rate of PFS in patients with TL. [ABSTRACT FROM AUTHOR]

Pre-transplant PET/CT may be prognostic in diffuse large B-cell lymphoma (DLBCL) patients undergoing autologous stem cell transplantation (ASCT). We reviewed relapsed and pre-transplant PET/CT scans of 32 patients with DLBCL treated with ASCT to determine the Deauville score and the maximum standardized uptake value (SUVmax). Patients with a Deauville score of 4 had a significantly inferior prognosis. The 3-year progression-free survival (PFS) for patients with Deauville 1-3 score was 64%, compared to 0% for Deauville 4, while the 3-year overall survival (OS) was 84% and 25%, respectively (p < .001, p = .002). The change in the SUVmax (>66 versus ≤66%) was not predictive of PFS or OS, but a high pre-transplant SUVmax (>6) demonstrated a trend towards an inferior PFS. Pre-transplant PET/CT is a tool for identifying DLBCL patients at high risk for treatment failure with ASCT and could be used to risk-stratify patients in prospective clinical trials of novel transplant strategies. [ABSTRACT FROM AUTHOR]

B-cell non-Hodgkin lymphomas (NHL) display dysregulation of pathways controlling cell proliferation and apoptosis. Combined proteasome and mTOR inhibition, demonstrated with bortezomib and everolimus in a preclinical model, thus warrants evaluation in humans. We conducted a phase I study to identify the maximum tolerated dose (MTD) and safety of this combination in relapsed/refractory (r/r) NHL. Twenty-nine patients were enrolled from July 2008 to March, 2015. Toxicities were primarily hematologic, and dose-limiting thrombocytopenia defined the MTD as 5mg everolimus daily with 1.3 mg/m² bortezomib d1, 4, 8, and 11 every 21 days. Of 25 response-evaluable patients there was one complete response in a patient with MCL and three partial responses (two MCL, one FL) for an overall response rate of 16%. In conclusion, the combination of everolimus and bortezomib results in dose limiting thrombocytopenia, but is tolerable. This combination has limited clinical activity in heavily pretreated NHL. [ABSTRACT FROM AUTHOR]

Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone combined with cytarabine and methotrexate) is an intense chemotherapy regimen frequently used for hematologic malignancies including mantle cell lymphoma. To address whether treatment with hyper-CVAD impairs mobilization of peripheral blood stem cells, we retrospectively analyzed mobilization data from 77 consecutive adult patients with mantle cell lymphoma who underwent peripheral blood stem cell (PBSC) mobilization for planned autologous stem cell transplant (ASCT). Compared to patients treated with alternative regimens, patients treated with hyper-CVAD collected fewer CD34++ cells, required more total days of pheresis, and more frequently required a second mobilization attempt, despite being more likely to have undergone mobilization with a VP16-containing regimen. In multivariable linear regression analysis, treatment with hyper-CVAD was associated with a significant reduction in total CD34++ cells mobilized ( p < 0.001). These findings suggest that alternative mobilizing strategies prior to ASCT are needed for patients with mantle cell lymphoma who have received hyper-CVAD. [ABSTRACT FROM AUTHOR]

Data from 131 consecutive adult patients who underwent allogeneic bone marrow transplantation (BMT) at a tertiary care center from 1997 to 1999 suggest that the presence of an in-hospital lay care-partner during the patients' hospital stay is a powerful prognostic variable of survival. One year after the transplant, 75% of the patients with a lay care-partner were alive versus 26% of those without a care-partner. A multivariable survival analysis revealed not having an in-hospital lay care-partner as a significant independent risk factor for death (p <.001). This relationship held when adjusting for other such risk factors: i.e., primary diagnosis, disease status, and source of donor marrow. The idiosyncratic nature and importance of partnered relationships for survival in allogeneic BMT and the need to intervene and improve outcomes for patients are discussed with regard to future research and clinical programs. [ABSTRACT FROM AUTHOR]

A continuous flow, magnetic separation method has been proposed to isolate large numbers of cells for clinical and biotechnological applications. The separation system, based on the quadrupole magnet flow sorter, has been tested on magnetically labeled, human blood progenitor cells using monoclonal antibody against the cluster of differentiation 34 (CD34) molecule and a magnetic colloid. A small volume of the cell suspension was injected into the sorter at variable volumetric flow rates, and the resulting cell elution profiles were analyzed for cell recovery in the magnetically enriched and depleted cell fractions. Independently, the cell motion in the magnetic field has been analyzed using a novel technique of cell tracking velocimetry, which allowed the determination of cell magnetophoretic mobility. A mathematical model of the cell motion inside the quadrupole flow sorter was used to calculate the recovery of the sorted fractions based on the cell magnetophoretic mobility distribution. A comparison of experimental and theoretical data allowed the verification of assumptions underlying the magnetic cell separation process, and provided guidelines for engineering design of the magnetic flow sorter. [ABSTRACT FROM AUTHOR]