Long-term remissions in patients with early relapse of diffuse large B-cell lymphoma following high-dose chemotherapy, autologous stem cell transplantation, and radiotherapy of residual disease.

PURPOSE: The prognosis of an early relapse of diffuse large B-cell lymphoma (DLBCL) appears to be poor following autologous stem cell transplantation (ASCT). The aim of this study is to contribute data to the open question on whether additional radiotherapy can improve the outcome. PATIENTS AND METHODS: Forty-eight patients with an early relapse (median 4 months after the end of initial immunochemotherapy, range 1-11) of DLBCL have been treated in our institution with high-dose therapy (usually the BEAM protocol) and ASCT since 2008 (median age 61 years, range 28-73). Twenty-three patients received ASCT in a second treatment line, 25 in a third line (19 refractory to second-line salvage therapy, 5 after second relapse). Fifteen of these 48 patients received radiotherapy (36-50 Gy, median 40) of residual masses after ASCT. RESULTS: Three-year overall survival (OS) and progression-free survival (PFS) after second-line ASCT were 61 and 57%, after third-line ASCT 47 and 44%, respectively, without significant differences. A prognostic factor was the International Prognostic Index (IPI) at the start of salvage therapy. Three-year OS and PFS in low-risk patients were 69 and 69%, in low-intermediate-risk 63 and 53%, and in high-intermediate-risk 23 and 23%, respectively (p = 0.033). Twenty-three patients achieved a sustained complete remission (13-146 months, median 62). CONCLUSION: Sustained long-term remissions can be achieved in patients with early relapse of DLBCL following ASCT in a second or third treatment line, particularly in patients with low- and low-intermediate-risk IPI, following radiotherapy of residual disease after ASCT. Further investigations are required to clarify which patients need an alternative therapy (potentially CAR T­cells or allogeneic transplantation).

Evaluation of Prognostic Factors and Role of Participation in a Randomized Trial or a Prospective Registry in Pediatric and Adolescent Nonmetastatic Medulloblastoma - A Report From the HIT 2000 Trial.

PURPOSE: We aimed to compare treatment results in and outside of a randomized trial and to confirm factors influencing outcome in a large retrospective cohort of nonmetastatic medulloblastoma treated in Austria, Switzerland and Germany. METHODS AND MATERIALS: Patients with nonmetastatic medulloblastoma (n = 382) aged 4 to 21 years and primary neurosurgical resection between 2001 and 2011 were assessed. Between 2001 and 2006, 176 of these patients (46.1%) were included in the randomized HIT SIOP PNET 4 trial. From 2001 to 2011 an additional 206 patients were registered to the HIT 2000 study center and underwent the identical central review program. Three different radiation therapy protocols were applied. Genetically defined tumor entity (former molecular subgroup) was available for 157 patients. RESULTS: Median follow-up time was 7.3 (range, 0.09-13.86) years. There was no difference between HIT SIOP PNET 4 trial patients and observational patients outside the randomized trial, with 7 years progression-free survival rates (PFS) of 79.5% ± 3.1% versus 78.7% ± 3.1% (P = .62). On univariate analysis, the time interval between surgery and irradiation (≤ 48 days vs ≥ 49 days) showed a strong trend to affect PFS (80.4% ± 2.2% vs 64.6% ± 9.1%; P = .052). Furthermore, histologically and genetically defined tumor entities and the extent of postoperative residual tumor influenced PFS. On multivariate analyses, a genetically defined tumor entity wingless-related integration site-activated vs non-wingless-related integration site/non-SHH, group 3 hazard ratio, 5.49; P = .014) and time interval between surgery and irradiation (hazard ratio, 2.2; P = .018) were confirmed as independent risk factors. CONCLUSIONS: Using a centralized review program and risk-stratified therapy for all patients registered to the study center, outcome was identical for patients with nonmetastatic medulloblastoma treated on and off the randomized HIT SIOP PNET 4 trial. The prognostic values of prolonged time to RT and genetically defined tumor entity were confirmed.