Treatment of Antibody-Mediated Renal Allograft Rejection: Improving Step by Step

Throughout the past years we stepwise modified our immunosuppressive treatment regimen for patients with antibody-mediated rejection (ABMR). Here, we describe three consecutive groups treated with different regimens. From 2005 until 2008, we treated all patients with biopsy-proven ABMR with rituximab (500 mg), low-dose (30 g) intravenous immunoglobulins (IVIG), and plasmapheresis (PPH, 6x) (group RLP, n=12). Between 2009 and June 2010, patients received bortezomib (1.3 mg/m2, 4x) together with low-dose IVIG and PPH (group BLP, n=11). In July 2010, we increased the IVIG dose and treated all subsequent patients with bortezomib, high-dose IVIG (1.5 g/kg), and PPH (group BHP, n=11). Graft survival at three years after treatment was 73% in group BHP as compared to 45% in group BLP and 25% in group RLP. At six months after treatment median serum creatinine was 2.1 mg/dL, 2.9 mg/dL, and 4.2 mg/dL in groups BHP, BLP, and RLP, respectively (p=0.02). Following treatment, a significant decrease of donor-specific HLA antibody (DSA) mean fluorescence intensity from 8467±6876 to 5221±4711 (p=0.01) was observed in group BHP, but not in the other groups. Our results indicate that graft survival, graft function, and DSA levels could be improved along with stepwise modifications to our treatment regimen, that is, the introduction of bortezomib and high-dose IVIG treatment

Allogeneic partially HLA-matched dendritic cells pulsed with autologous tumor cell lysate as a vaccine in metastatic renal cell cancer

Multi-kinase inhibitors have been established for the treatment of advanced renal cell cancer, but long-term results are still disappointing and immunotherapeutic approaches remain an interesting experimental option particularly in patients with a low tumor burden. DC are crucial for antigen-specific MHC-restricted T cell immunity. Furthermore, allogeneic HLA-molecules pose a strong immunogenic signal and may help to induce tumor-specific T cell responses. In this phase I/II trial, 7 patients with histologically confirmed progressive metastatic RCC were immunized repetitively with 1 × 10(7) allogeneic partially HLA-matched DC pulsed with autologous tumor lysate following a schedule of 8 vaccinations over 20 weeks. Patients also received 3 Mio IE IL-2 s.c. once daily starting in week 4. Primary endpoints of the study were feasibility and safety. Secondary endpoints were immunological and clinical responses. Vaccination was feasible and safe with no severe toxicity being observed. No objective response could be documented. However, while all patients had documented progress at study entry, 29% of the patients showed SD throughout the study with a mean TTP of 24.6 weeks (range 5 to 96 weeks). In 3/7 patients, TH1-polarized immune responses against RCC-associated antigens were observed. In one patient showing a minimal clinical response and a TTP of 96 weeks, clonally proliferated T cells against yet undefined antigens were induced by the vaccine. Vaccination with tumor antigen loaded DC remains an interesting experimental approach, but should rather be applied in the situation of minimal residual disease after systemic therapy. Additional depletion of regulatory cells might be a promising strategy

Spenderauswahl, allogene Stammzelltransplantation

Die allogene Stammzelltransplantation besitzt für viele schwere, maligne und nicht-malígne hämatologische Erkrankungen ein hohes kuratives Potenzial. Ein kritisches Element der Stammzelltransplantation ist die Auswahl geeigneter Spender. Ziel dieser Leitlinie ist es, den klinisch tätigen Hämatologen/Internistischen Onkologen einen hierarchischen Algorithmus für die Spenderauswahl an die Hand zu geben. Zusätzlich wird die Wertigkeit von alternativen Transplantatquellen (Nabelschnurblut, haploidente Spender) dargestellt. Dabei werden Spenderverfügbarkeit und individuelles Erkrankungsrisiko in Beziehung gesetzt. Die vorliegende Leitlinie stellt eine Zusammenfassung des aktuellen Konsensus der Deutschen Gesellschaft für Immungenetik (DGI) und der Deutschen Arbeitsgemeinschaft für Knochenmark- und Blutstammzelltransplantation (DAG-KBT) als Fachgremium der DGHO dar

Spenderauswahl, allogene Stammzelltransplantation

Die allogene Stammzelltransplantation besitzt für viele schwere, maligne und nicht-malígne hämatologische Erkrankungen ein hohes kuratives Potenzial. Ein kritisches Element der Stammzelltransplantation ist die Auswahl geeigneter Spender. Ziel dieser Leitlinie ist es, den klinisch tätigen Hämatologen/Internistischen Onkologen einen hierarchischen Algorithmus für die Spenderauswahl an die Hand zu geben. Zusätzlich wird die Wertigkeit von alternativen Transplantatquellen (Nabelschnurblut, haploidente Spender) dargestellt. Dabei werden Spenderverfügbarkeit und individuelles Erkrankungsrisiko in Beziehung gesetzt. Die vorliegende Leitlinie stellt eine Zusammenfassung des aktuellen Konsensus der Deutschen Gesellschaft für Immungenetik (DGI) und der Deutschen Arbeitsgemeinschaft für Knochenmark- und Blutstammzelltransplantation (DAG-KBT) als Fachgremium der DGHO dar