Lenalidomide, bendamustine and prednisolone exhibits a favourable safety and efficacy profile in relapsed or refractory multiple myeloma: final results of a phase 1 clinical trial OSHO - #077.

This phase 1 dose finding study tested a combination of lenalidomide, bendamustine and prednisolone (RBP) in 21 patients in five cohorts with advanced multiple relasped/refractory myeloma (MM) to determine the maximum tolerable dose (MTD) of the combination. The first cohort received a starting dose of lenalidomide 10 mg/d, days 1-21, bendamustine 60 mg/m(2) /d, days 1-2, and prednisolone 100 mg/d, days 1-4. Dose escalation was done in cohorts of three to six patients with lenalidomide dose increasing to 15, 20 and 25 mg, and after reaching 25 mg/d, bendamustine was increased to 75 mg/m(2) . A total of 21 patients were enrolled and all completed at least two cycles. Two patients developed dose-limiting haemotoxicity: one patient on lenalidomide 25 mg/d and bendamustine 60 mg/m(2) and another patient at the highest dose level (lenalidomide 25 mg/d and bendamustine 75 mg/m(2) ). The MTD was not reached. Sixteen patients (76%) responded after at least two cycles of RBP with one stringent complete response (CR), one near CR, five very good partial response and nine partial response. After a median observation time of 16 months, progression-free survival at 18 months was 48% and overall survival was 64%. In conclusion, RBP with lenalidomide 25 mg/d, days 1-21 and bendamustine 75 mg/m(2) days 1-2 is well tolerated in patients with relapsed/refractory MM.

Long-term outcome of pediatric renal transplantation in boys with posterior urethral valves.

PURPOSE: To determine whether there is a difference in the outcome of renal transplantation (RT) in patients with posterior urethral valves (PUV) and children with non-uropathy related end stage renal disease. METHODS: Data were acquired retrospectively. We analyzed possible factors that influence the function of renal allografts and graft survival. Between 1995 and 2016 there were 149 RT. Out of them, there were 27 boys with PUV, who received 29 kidneys. Thirty patients, who received a total of 31 renal grafts due to a non-uropathic (NU) diagnosis, served as control group. Mean follow-up was 7.4 to 10.2 years. RESULTS: There was no difference in estimated graft survival between patients with PUV and NU patients. Graft failure occurred in 23.1% of PUV patients and 34.5% patients of the NU group. There was no statistically significant disparity in graft function between the two groups. Age at transplantation and donor age were the only factors that had a significant impact on renal function. There was a higher incidence of UTI in the PUV group (96%) than in the NU group (67%). Vesicostomy was the favourable intervention in regards of graft function. CONCLUSIONS: RT in PUV patients is successful with the same outcome as in NU patients. Bladder dysfunction may not have a major impact on graft function and graft survival. It seems that the type of pre-transplant surgical procedures may influence outcome. Therefore, these interventions -if necessary- should be limited to a minimum. TYPE OF STUDY: Retrospective Comparative Study LEVEL OF EVIDENCE: Level III.

Low tumor burden is associated with early B-cell reconstitution and is a predictor of favorable outcome after non-myeloablative stem cell transplant for chronic lymphocytic leukemia.

Abstract Reconstitution, engraftment kinetics and tumor cell clearance were analyzed after reduced intensity conditioning hematopoietic cell transplant (RIC-HCT) in patients with chronic lymphocytic leukemia (CLL). Patients were transplanted from unrelated (n = 40) or related (n = 10) donors after fludarabine and 2 Gy total body irradiation followed by cyclosporine and mycophenolate mofetil. The vast majority of patients (96%) engrafted with absolute neutrophil count (ANC) > 0.5 × 10(9)/L at day + 22. CLL cells decreased (median 2%, range 0-69%) within 28 days, but disappeared by day + 180 after HCT. Donor T-cell chimerism increased to > 95% at day 56 and donor B-cell chimerism to 94% at day + 360. Overall survival was 51 ± 8%, incidence of progression 37 ± 7% and non-relapse related mortality (NRM) 30 ± 7% at 4 years. The most common causes of NRM were graft-versus-host disease (GvHD) (14%) and sepsis (6%). Disease status at HCT was significantly associated with early B-cell reconstitution (p = 0.04) and with increased risk of relapse/progression in univariate and multivariate analysis (p = 0.022). Tumor cells were undetectable by day + 180, although B-cell reconstitution did not occur until 1.5 years after RIC-HCT. The best predictors for progression-free survival (PFS) and overall survival (OS) were complete response (CR) or first partial response (PR1) and the absence of bulky disease at transplant, respectively.