Cyclophosphamide-bortezomib-dexamethasone compared with bortezomib-dexamethasone in transplantation-eligible patients with newly diagnosed multiple myeloma.

Introduction: Cyclophosphamide-bortezomib-dexamethasone (CyBorD) is considered a standard induction regimen for transplant-eligible patients with newly diagnosed multiple myeloma (mm). It has not been prospectively compared with bortezomib-dexamethasone (Bor-Dex). We aimed to compare the efficacy of CyBorD and Bor-Dex induction in transplant-eligible patients. Methods: In a retrospective observational study at a single tertiary centre, all patients with transplant-eligible mm who received induction with CyBorD or Bor-Dex between March 2008 and April 2016 were enrolled. Progression-free survival (pfs), response, and stem-cell collection for a first autologous stem-cell transplantation (ahsct) were compared. Results: Of 155 patients enrolled, 78 (50.3%) had received CyBorD, and 77 (49.7%), Bor-Dex. The patients in the Bor-Dex cohort were younger than those in the CyBorD cohort (median: 57 years vs. 62 years; p = 0.0002) and more likely to have had treatment held, reduced, or discontinued (26% vs. 14.5%, p = 0.11). The stem-cell mobilization regimen for both cohorts was predominantly cyclophosphamide and granulocyte colony-stimulating factor (gcsf). Plerixafor was used more often for the CyBorD cohort (p = 0.009), and more collection failures occurred in the CyBorD cohort (p = 0.08). In patients receiving Bor-Dex, more cells were collected (9.9×106 cells/kg vs. 7.7×106cells/kg, p = 0.007). At day +100, a very good partial response or better was achieved in 75% of the CyBorD cohort and in 73% of the Bor-Dex cohort (p = 0.77). Median pfs was 3.2 years in the Bor-Dex cohort and 3.7 years in the CyBorD cohort (p = 0.56). Conclusions: Overall efficacy was similar in our patients receiving CyBorD and Bor-Dex. After ahsct, no difference in depth of response or pfs was observed. Cyclophosphamide-gcsf seems to increase collection failures and hospitalizations in patients receiving CyBorD. Prospective studies are required to examine that relationship.

Non-myeloablative allogeneic hematopoietic transplantation for patients with hematologic malignancies: 9-year single-centre experience.

Matched related and unrelated allogeneic nonmyeloablative hematopoietic transplantation (nmt) is increasingly being used in patients with hematologic malignancies. Conditioning regimens and indications for nmt vary considerably from centre to centre. Our institution uses intravenous fludarabine and cyclophosphamide, plus graft-versus-host disease (gvhd) prophylaxis with tacrolimus and mycophenolate mofetil. We retrospectively analyzed 89 consecutive patients who underwent nmt (65 related, 24 unrelated) at our institution from October 2002 to September 2011. The most frequent indications for nmt were acute myelocytic leukemia (high-risk in first complete or subsequent remission: n = 20, 22.5%) and relapsed follicular lymphoma (n = 18, 20.2%). The cumulative incidence of acute gvhd (grades 2-4) was 28.1% (n = 25), and rates were similar for related (n = 18, 28%) and unrelated (n = 7, 29%) nmt. At a median follow-up of 22.6 months, the cumulative incidence of chronic gvhd (limited and extensive) was 68% (n = 61): 68.5% (n = 44) for related and 71% (n = 17) for unrelated nmt. The 100-day transplant-related mortality rate was 2.2%: 1.5% for related and 4.2% for unrelated nmt. Of the 89 patients, 30 (33.7%) have relapsed: 41.5% after related and 12.5% after unrelated nmt. Relapse rates were similar in patients with myeloid and lymphoid malignancies (36.4% vs. 33.3%). The 3-year overall and progression-free survival rates were 50.0% and 43.4% respectively, with multivariate analysis showing that neither rate was affected by age, disease group, status at transplantation, or related compared with unrelated nmt. Our findings indicate that, despite its limitations, including the incidence of chronic gvhd, nmt is an important treatment modality for a selected subgroup of patients with hematologic malignancies.

Characterization of attenuated Renibacterium salmoninarum strains and their use as live vaccines.

Two nutritionally mutant strains of Renibacterium salmoninarum (Rs) were isolated that grew on tryticase soy agar (Rs TSA1) or brain heart infusion agar (Rs BHI1). These 2 strains could be continuously cultured on these media, whereas typical R. salmoninarum would only grow on KDM-2 agar. We determined no other phenotypic difference that could be used to distinguish them from wild-type R. salmoninarum. Both strains were found to be avirulent when 5 x 10(6) bacteria were intraperitoneally (i.p.) injected into Atlantic salmon. Rs TSA1, Rs BHI1, and Rs MT-239 (a R. salmoninarum strain previously shown to be attenuated) were tested as live vaccines in 2 separate trials. The best protection was seen with Rs TSA1. Vaccinated Atlantic salmon had relative percent survival (RPS) of 50 at 74 d post-challenge in Trial 1 and 76 at 60 d post-challenge in Trial 2. In both trials, 100% of the control salmon died from bacterial kidney disease (BKD) (within 40 d for Trial 1 and 50 d for Trial 2) after i.p. challenge with 5 x 10(6) live cells of the virulent isolate Rs Margaree.

The cell surface of Aeromonas salmonicida determines in vitro survival in cultured brook trout (Salvelinus fontinalis) peritoneal macrophages.

Aeromonas salmonicida strains phenotypically differing in their A-layer, lipopolysaccharide, and macrophage cytotoxicity were tested in vitro for survivability in brook trout (Salvelinus fontinalis) serum with or without antibodies, and in vivo following intraperitoneal injection. The ability of brook trout peritoneal macrophages to phagocytize and kill the different phenotypes was investigated in an in vitro assay. The virulent strain, A. salmonicida 80204, which has the full complement of known virulence factors, as well as the recently described macrophage cytotoxin, was resistant in vitro to both the bactericidal activity of normal and immune serum, and to brook trout peritoneal macrophages. A. salmonicida SS-70.1, which possesses the A-layer but lacks the cytotoxin, was resistant to the bactericidal activity of normal and immune serum but was avirulent and killed by macrophages. Phenotypes lacking the A-layer, regardless of whether or not they possessed the macrophage cytotoxin were avirulent, susceptible to normal and immune serum and the bactericidal activity of peritoneal macrophages. A. salmonicida virulence expression requires both the A-layer and the macrophage cytotoxin.