The Impact of Alemtuzumab and Basiliximab Induction on Patient Survival and Time to Bronchiolitis Obliterans Syndrome in Double Lung Transplantation Recipients.

We examined the effect of alemtuzumab and basiliximab induction therapy on patient survival and freedom from bronchiolitis obliterans syndrome (BOS) in double lung transplantation. The United Network for Organ Sharing database was reviewed for adult double lung transplant recipients from 2006 to 2013. The primary outcome was risk-adjusted all-cause mortality. Secondary outcomes included time to BOS. There were 6117 patients were identified, of whom 738 received alemtuzumab, 2804 received basiliximab, and 2575 received no induction. Alemtuzumab recipients had higher lung allocation scores compared with basiliximab and no-induction recipients (41.4 versus 37.9 versus 40.7, p < 0.001) and were more likely to require mechanical ventilation before to transplantation (21.7% versus 6.5% versus 6.2%, p < 0.001). Median survival was longer for alemtuzumab and basiliximab recipients compared with patients who received no induction (2321 versus 2352 versus 1967 days, p = 0.001). Alemtuzumab (hazard ratio 0.80, 95% confidence interval 0.67-0.95, p = 0.009) and basiliximab induction (0.88, 0.80-0.98, p = 0.015) were independently associated with survival on multivariate analysis. At 5 years, alemtuzumab recipients had a lower incidence of BOS (22.7% versus 55.4 versus 55.9%), and its use was independently associated with lower risk of developing BOS on multivariate analysis. While both induction therapies were associated with improved survival, patients who received alemtuzumab had greater median freedom from BOS.

Localizing the sentinel node outside of the specialty center: success of a lymphatic mapping course in disseminating new technology.

BACKGROUND: Sentinel node biopsy (SNB) is an evolving technology in the management of breast cancer. The purpose of this study was to determine the success of an SNB course in emphasizing principles for participants to successfully initiate an SNB program at their institution. METHODS: Participants in a university-sponsored course were queried 6 to 18 months after the course regarding their success in initiating SNB in their practice. Univariate analysis was used to determine the likelihood of implementing a SNB program. RESULTS: Ninety-one participants responded. Of these respondents, 56 had initiated an SNB program at their hospital, and 20 had completed a "validation" phase. "Validation" consisted of less than 10 cases for 11 respondents, 11 to 20 cases for 5 respondents, and 20 to 30 cases for 3 respondents and >30 cases for 1 respondent. Twenty-eight percent initiated the learning curve without an Institutional Review Board (IRB) protocol, and a further 20% went on to utilize SNB without axillary dissection in sentinel node-negative patients without IRB approval. Univariate analysis revealed that surgeons practicing in a group whose caseload consisted of more than 25% breast surgery cases were most likely (P < 0.05) to implement SNB in their practice. CONCLUSIONS: Success in applying SNB after a course is high among surgeons in groups with a significant breast caseload, although recommendations for obtaining institutional approval and completing a 30-case validation series are often disregarded.

Dendritic cells improve the generation of Epstein-Barr virus-specific cytotoxic T lymphocytes for the treatment of posttransplantation lymphoma.

BACKGROUND: The use of immunosuppressive therapies after solid organ transplantation has been shown to increase a patient's risk for Epstein-Barr virus (EBV)-associated lymphoma. A potential therapy for this disorder is the adoptive transfer of EBV-specific cytotoxic T lymphocytes (CTLs). We proposed that dendritic cells (DCs) could be loaded with EBV antigens and be used to improve the in vitro generation of EBV-specific CTLs. METHODS: Autologous EBV-transformed B-lymphoblastoid cell lines (BLCLs) were generated from normal donors, and CTLs were initiated by culturing peripheral blood mononuclear cells with DCs alone, disrupted BLCLs alone, intact, irradiated BLCLs alone, and DCs loaded with disrupted BLCLs. Lytic activities were determined with a 4-hour chromium-release assay against autologous BLCLs, and statistical calculations were performed by a Student t test assuming equal variance. RESULTS: The lytic activity of CTLs generated with DCs loaded with disrupted BLCLs reached 78% and was statistically significant (P < .01) at all effector/target ratios compared with CTLs generated with DCs alone, disrupted BLCLs alone, or intact BLCLs alone. Total numbers of CTLs were also greater than those of control groups for DCs loaded with disrupted BLCLs. CONCLUSIONS: DCs improved the in vitro generation of EBV-specific CTLs as evidenced by this group's significantly increased lytic activity over that of the control group. The improved lytic activity of DC-generated EBV-CTLs suggests that adoptive transfer of these cells could lead to a more effective immunotherapeutic response against posttransplantation EBV-associated lymphoma.

Active immunization using dendritic cells mixed with tumor cells inhibits the growth of primary breast cancer.

BACKGROUND: Dendritic cells (DCs) are potent antigen-presenting cells regarded as crucial in the priming of an immune response. The goal of our study was to test whether bone marrow-generated DCs are capable of inducing protective immunity against a murine breast carcinoma (4T1). METHODS: DCs were grown from Balb/c mice by culturing lymphocyte-immunodepleted bone marrow in murine granulocyte-macrophage colony-stimulating factor containing medium for 10 days. Balb/c mice (five to eight per group) were immunized intradermally with 1 x 10(6) DCs mixed with 2 x 10(6) lethally irradiated 4T1 cells on day 0. Mice in control groups were given intradermal inoculations of phosphate-buffered saline solution, 1 x 10(6) DCs, or lethally irradiated 4T1 cells alone. Booster intraperitoneal immunizations of 2 x 10(6) lethally irradiated 4T1 cells were given on days 7 and 14. All mice were challenged with 5 x 10(3) 4T1 cells subcutaneously 7 days after the final immunization. Animals were examined daily, and tumor volume was recorded twice weekly with calipers. RESULTS: At 21 days there was a significant reduction in tumor growth in mice immunized with DCs mixed with irradiated 4T1 cells as compared with the control groups (p = 0.0005, Kruskal-Wallis test). CONCLUSIONS: These results suggest that DCs mixed with tumor cells as a source of undefined tumor antigen can induce an effective antitumor immune response. This finding provides a rationale for the use of cultured DCs in immunotherapy of breast and other cancers.