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Background Autologous stem cell transplantation (ASCT) is a commonly used treatment for multiple myeloma (MM). This retrospective cohort study characterizes the risk factors and outcomes associated with bacteremia following ASCT at a single center. Methods We conducted a retrospective analysis in subjects who underwent ASCT for multiple myeloma and other malignancies from May 2014 to March 2015 at a single center. The control cohort included all subjects undergoing ASCT in the same time period who did not develop bacteremia. Results During the study period, 363 ASCTs were completed in 282 discrete patients. Bacteremia was documented in 13% of all transplants. Enterococcus faecium was the most frequent species overall (14/62, 23%). Vancomycin resistance was present in 93% of E faecium isolates. Bacteremia was associated with a significantly decreased survival in patients who received their transplant after the first year of myeloma treatment. Overall survival (OS) was not significantly different in the two cohorts among patients undergoing ASCT within the first year of myeloma treatment. Survival analysis showed a significantly decreased OS in patients who developed Enterococcus bacteremia as compared to the non-bacteremia cohort. Enterococcal bacteremia was associated with significantly longer duration of neutropenia (mean 14 vs 9.7 days, P = 0.01), hospitalization (mean 61.7 vs 20.4 days, P = 0.0006), and higher mortality (69% vs 25%, P = 0.01) as compared to other bacteremias. Conclusion We found a high incidence of E faecium and a low incidence of MRSA and Pseudomonas bacteremias following ASCT in our patient population. Survival analysis in our cohort suggests that the effect of underlying disease status and cumulative chemotherapy is critically important in determining outcomes related to bacteremia. Enterococcal bacteremias following ASCT were associated with significantly higher morbidity and mortality than non-enterococcal bacteremias.

Interest in natural killer (NK) cell-based immunotherapy has resurged since new protocols for the purification and expansion of large numbers of clinical-grade cells have become available.We have successfully adapted a previously described NK expansion method that uses K562 cells expressing interleukin (IL)-15 and 4-1 BB Ligand (BBL) (K562-mb15-41BBL) to grow NK cells in novel gas-permeable static cell culture flasks (G-Rex).Using this system we produced up to 19 × 10(9) functional NK cells from unseparated apheresis products, starting with 15 × 10(7) CD3(-) CD56 (+) NK cells, within 8-10 days of culture. The G-Rex yielded a higher fold expansion of NK cells than conventional gas-permeable bags and required no cell manipulation or feeding during the culture period. We also showed that K562-mb15-41BBL cells up-regulated surface HLA class I antigen expression upon stimulation with the supernatants from NK cultures and stimulated alloreactive CD8 (+) T cells within the NK cultures. However, these CD3 (+) T cells could be removed successfully using the CliniMACS system. We describe our optimized NK cell cryopreservation method and show that the NK cells are viable and functional even after 12 months of cryopreservation.We have successfully developed a static culture protocol for large-scale expansion of NK cells in the gas permeable G-Rex system under good manufacturing practice (GMP) conditions. This strategy is currently being used to produce NK cells for cancer immunotherapy.

Background Daratumumab is an IgG kappa monoclonal antibody (mAB) against CD38 which is expressed on myeloma cells. It has recently been approved for treatment of patients with relapsed refractory multiple myeloma. Our objective was to identify the potential infectious complications associated with daratumumab use. Methods We conducted a retrospective analysis of myeloma patients who received daratumumab at our institution from October 2015 to December 2016. Patients were divided into four groups based on administration regimen of daratumumab: (1) single agent with dexamethasone; (2) triple therapy with proteasome inhibitor (PI), immune-modulating drug (IMiD), mitogen-activated protein kinase (MEK) inhibitor or mAB; (3) quadruple therapy with IMiD + PI ± mAB or cyclophosphamide; (4) with high-dose chemotherapy. For each group, we evaluated the incidence of infection, neutropenia (defined as ANC

Background: IL-6 is a pleiotropic cytokine, the dysregulation of which plays an etiological role in many diseases. Multicentric Castleman’s disease (CD) is a polyclonal lymphoproliferative disorder in which IL-6, overproduced by enlarged lymph nodes, is responsible for B-cell proliferation, auto-immune phenomena, systemic inflammatory manifestations (eg, fever, fatigue, and weight loss) and abnormal laboratory findings, including anemia, hyper-γ-globulinemia, hypoalbuminemia, thrombocytosis and increases in acute-phase proteins (eg, CRP, ESR and fibrinogen). The inflammatory syndrome can be severe and refractory to steroids, chemotherapy and even autologous stem cell transplantation. CNTO 328 is a chimeric mAb that specifically binds and neutralizes human IL-6 with high affinity. A phase I trial is being conducted to assess the safety and PK of CNTO 328 in subjects with CD and other hematological diseases. Methods: This trial enrolls subjects with non Hodgkin’s B-cell lymphoma, multiple myeloma, or CD in cohorts exploring doses ranging from 3 to 12mg/kg given intravenously repeated either weekly, or every 2, or 3 weeks. Dose limiting toxicity (DLT) is defined as a ≥Grade 3 event (excluding hematologic toxicity), or ≥Grade 2 allergic reaction/hypersensitivity by NCI CTCAE attributed to CNTO 328 after the first administration. Clinical benefit assessment is based on improvements in Hb, fatigue, anorexia, fever/night sweats, weight, and size of target lymph node. Results: Results from the first 7 CD subjects enrolled in Cohorts 1 (n=1, CNTO 328 3mg/kg q 2 weeks), 2 (n=2, CNTO 328 6mg/kg q 2 weeks) and 3 (n=4, CNTO 328 12mg/kg q 3 weeks) are currently available. At present time, subjects have received a median number of 4 (range 3 to 21) doses. CNTO 328 alone was well tolerated and no DLTs were observed. Non-related to CNTO 328 Grade 3 AEs such as anemia, thrombocytosis, fatigue and one possibly-related AE (ie, vomiting, grade 3) were observed. In addition, 3 subjects experienced Grade 3 SAEs that were deemed either unrelated or unlikely related to CNTO 328. Six evaluable subjects with CD showed a response by clinical benefit assessment including improvement in Hb and in severe thrombocytosis, and fatigue, reduction of fever, resolution of rash, improvement in skin tumors, or decrease in lymphadenopathy. PK and PD analysis from these subjects is currently ongoing and data from these analyses will be presented. Conclusions: Treatment with CNTO 328 has been well tolerated in CD subjects at doses up to 12mg/kg q 3 weeks, and no allergic reactions have been observed after repeated dosing. Preliminary results suggest that CNTO 328 can abrogate the effects of IL-6 and induce both clinical and biochemical responses in CD.