This cohort, the largest reported to date, increases the spectrum of knowledge on PBL, rarely described. However, specific guidelines to clarify treatment are lacking, and may improve the poor prognosis of this rare disease.

Key Points• Rituximab exposure decreased as metabolic tumor volume increased, and correlated with metabolic response and survival.• Rituximab dose could be individualized according to metabolic tumor volume to achieve optimal exposure and therefore optimal response.High variability in patient outcome after rituximab-based treatment is partly explained by rituximab concentrations, and pharmacokinetic (PK) variability could be influenced by tumor burden. We aimed at quantifying the influence of baseline total metabolic tumor volume (TMTV 0 ) on rituximab PK and of TMTV 0 and rituximab exposure on outcome in patients with diffuse large B-cell lymphoma (DLBCL). TMTV 0 was measured by 18 F-fluorodeoxyglucosepositron emission tomography-computed tomography in 108 previously untreated DLBCL patients who received four 375 mg/m 2 rituximab infusions every 2 weeks in combination with chemotherapy in 2 prospective trials. A 2-compartment population model allowed describing rituximab PK and calculating rituximab exposure (area under the concentration-time curve; AUC). The association of TMTV 0 and AUC with metabolic response after 4 cycles, as well as progression-free survival (PFS) and overall survival (OS), was assessed using logistic regression and Cox models, respectively. Cutoff values for patient outcome were determined using receiver operating characteristic curve analysis. Exposure to rituximab decreased as TMTV 0 increased (R 2 5 0.41, P < .0001). A high AUC in cycle 1 ( ‡9400 mg 3 h per liter) was associated with better response (odds ratio, 5.56; P 5 .0006) and longer PFS (hazard ratio [HR], 0.38; P 5 .011) and OS (HR, 0.17; P 5 .001).A nomogram for rituximab dose needed to obtain optimal AUC according to TMTV 0 was constructed, and the 375 mg/m 2 classical dose would be suitable for patients with TMTV 0 <281 cm 3 . In summary, rituximab exposure is influenced by TMTV 0 and correlates with response and outcome of DLBCL patients. Dose individualization according to TMTV 0 should be evaluated in prospective studies. These studies were registered at www.clinicaltrials.gov as #NCT00498043 and

Renal impairment is a common complication of multiple myeloma (MM), accounting for 20-30% of MM patients at diagnosis and 40-50% of patients during the course of their disease. This feature is associated with poor prognosis and shorter survival as compared to patients with normal renal function (NRF). Therefore, therapeutic management is challenging as autologous stem cell transplantation (ASCT) is often not considered as a valuable strategy, mainly due to concerns of toxicity. In this retrospective and multicenter study, we included 55 MM patients with dialysis-dependent or independent renal failure who underwent high-dose melphalan-based ASCT in order to assess the efficacy outcomes and toxicities of this strategy. Response to ASCT was at least VGPR (very good PR) in 58% of patients and 96% of patients who also received bortezomib-based induction were at least in PR after ASCT. Median OS was 76 months and median PFS was 55 months, similarly to MM patients with NRF. In multivariate analysis, dose of melphalan (140 mg/m) was correlated with better PFS (18 months, P = 0.005). Toxicities included febrile neutropenia (75%) and severe mucositis (34%). Overall, this work confirmed that ASCT conditioned by 140 mg/m melphalan is a beneficial procedure for MM patients with renal failure.

NCT01370772.

Patients with Acute Myelogenous Leukemia have a better outcome if reaching molecular remission. We compared the outcome of 373 patients autografted and 335 patients allografted with a 10/10 compatible unrelated donor in first molecular remission. Patients were stratified using the ELN European Leukemia Net classification. ELN favorable group: (234 auto and 70 unrelated transplants). By univariate analysis, in the auto group, the Non Relapse Mortality (NRM) was lower (3.7% versus 19%; P < 10 ), Relapse Incidence (RI) higher (29% versus 17%, P < 10 ), Leukemia Free Survival (LFS) identical (67% versus 64%) and Overall Survival (OS) better than in the allogeneic group (83% versus 62%; P = .008). By multivariate analysis, autologous transplantation was associated with a lower NRM (HR: 4, P = .01) and a better OS (HR: 2.08, P = .04). ELN intermediate group 1: (87 autologous and 172 unrelated transplants). By univariate analysis, in the auto group, NRM was lower (2.5% versus 11.8%; P = .03), RI higher (59% versus 18%, P < 10 ), LFS lower (39% versus 70%; P < 10 ) and OS lower than in the unrelated donor group (61% versus 74%; P = .005). By multivariate analysis, unrelated donor was superior to autologous transplantation for LFS (HR: 0.36, P < 10 and OS (HR: 0.53, P = .01). ELN intermediate group 2: (52 autologous and 93 unrelated donors). The outcome was identical. We conclude that good risk patients get higher benefit from autologous transplantation. Intermediate risk 2 patients have the same outcome and Intermediate risk 1 patients get higher benefit from unrelated donor transplants.