Abstract Background Contemporary outcomes and relapse patterns in primary CNS lymphoma (PCNSL) are lacking. We analyzed factors associated with relapse in a large cohort with extensive follow-up. ...Methods T1-post-contrast-enhancing disease was characterized in immunocompetent PCNSL (diffuse large B-cell) patients from 1983 to 2020. Patients were stratified by response to induction and consolidation (complete/unconfirmed CR/CRu, partial, stable, progression POD). Refractory was POD during (or relapse ≤3 months of) induction. Initial relapse site was categorized as local (involving/adjacent to baseline), distant intraparenchymal, leptomeningeal, or other. Progression-free (PFS) and overall survival (OS) were assessed with proportional hazards. Cumulative incidence with competing risks was used to assess local relapse. Results Median follow-up was 7.4 years (N = 559). Most (321, 57%) were recursive partitioning analysis class 2 (age ≥50, Karnosfky Performance Status KPS ≥70). Most had supratentorial (420, 81%), multifocal (274, 53%), bilateral (224, 43%), and deep structure involvement (314, 56%). Nearly all received methotrexate-based induction (532, 95%). There was no difference in PFS or OS from consolidation based on initial response to induction (CR/CRu vs PR) in patients who ultimately achieved a CR/CRu to consolidation. PFS at 1-, 5 years for 351 patients with CR/CRu to consolidation was 80% (95% confidence interval 95% CI: 76%–84%) and 46% (95% CI: 41%–53%), respectively; 1-year cumulative incidence of local versus nonlocal relapse was 1.8% versus 15%, respectively. For 97 refractory patients, 1-year cumulative incidence of local versus nonlocal relapse was 57% versus 42%, respectively. Deep structure involvement (HR 1.89, 95% CI: 1.10%–3.27%) was associated with local relapse in refractory patients. Conclusions We report the first comprehensive relapse patterns in a large PCNSL cohort. While relapses post-CR to consolidation are typically distant and unpredictable, refractory patients had a relatively high incidence of local relapse. These findings can help optimize multimodality therapy for this highest-risk population.
Introduction: For patients with relapsed or primary refractory (rel/ref) diffuse large B-cell lymphoma (DLBCL) who respond to salvage chemotherapy, high-dose chemotherapy and autologous hematopoietic ...cell transplantation (HDT-AHCT) is considered standard of care. Patients with refractory disease to salvage chemotherapy, defined as stable disease (SD) or progressive disease (PD), by functional imaging are ineligible for HDT-AHCT, and have a poor prognosis. In practice, we have attempted to salvage these patients with radiation therapy (RT) to residual sites of active disease prior to consolidative HDT-AHCT. The outcome of this unique combined modality salvage paradigm has not been previously reported.
Methods: We retrospectively reviewed all patients with rel/ref DLBCL who received salvage chemotherapy followed by salvage RT and HDT-AHCT between the years of 2000 and 2017 at a single center. Only patients with SD or PD as defined on the 5-point Deauville scale after salvage chemotherapy and who had at least 1 year of follow-up were included in this analysis. The second-line age-adjusted International Prognostic Index (sAAIPI) was determined at the time of initiation of salvage chemotherapy.Survival functions were estimated by the Kaplan-Meier method and compared using a log-rank test.
Results: Thirty-six patients, 12 with relapsed and 24 with primary refractory disease, with a median age of 44 years (range: 19-68 years) were analyzed. Twenty-three patients had DLBCL while 13 had primary mediastinal B-cell lymphoma (PMBCL). The majority of patients had KPS 80-100 (n=32, 89%), 0-1 extranodal sites (n=30, 83%), and normal LDH (n=21, 58%). The sAAIPI scores for this cohort were as follows: 0 (n=10), 1 (n=21), 2 (n=4), and 3 (n=1). All patients received salvage chemotherapy with subsequent functional imaging showing SD (n=32) and PD (n=4) and then went on to receive salvage RT to the sites of active disease. Median RT dose was 39.6Gy (range: 30-54Gy). Six patients also received TBI as part of their conditioning regimen prior to HDT-AHCT.
With median follow up of 4.0 years (range: 1.0-12.3 years) for survivors, 4-year relapse-free survival (RFS) was 75.6% and 4-year overall survival (OS) was 80.3% (Figure 1a). There was no significant difference in 4-year RFS for patients with relapsed versus primary refractory disease (80.2% vs 74.8%, p=0.59). PMBCL patients had better RFS than DLBCL patients (92.3% vs 67.8%, p=0.12).
Using the composite sAAIPI score was highly prognostic with worse outcomes for patients with higher risk sAAIPI scores. By sAAIPI score, 4-year RFS was 80.0% for a score of 0, 90.2% for a score of 1, and 0% for scores of 2 and 3. Patients with low- and low-intermediate risk sAAIPI scores of 0 and 1 had improved RFS as compared to patients with sAAIPI scores of 2 and 3 (87.0% vs 0%, p<0.0001 (Figure 1b).
Conclusions: Patients with chemorefractory rel/ref DLBCL who have had minimal or no response to systemic salvage therapy may benefit from salvage RT to the residual PET-avid disease followed by HDT-AHCT, particularly if their sAAIPI score is ≤ 1. The outcome of this retrospective cohort is markedly superior to outcomes described in the literature for this high-risk population and represents a promising treatment paradigm to be further explored. Emerging data suggest similar patients may benefit from CAR T-cell therapy. Given the limited availability and high cost of CAR T-cell therapy, we suggest there may be a role for sequencing this combined-modality salvage paradigm prior to CAR T-cell therapy in order to provide these poor-risk patients with an additional line of therapy.
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Scordo:Angiocrine Bioscience, Inc.: Consultancy; McKinsey & Company: Consultancy. Sauter:Sanofi-Genzyme: Consultancy, Research Funding; GSK: Consultancy; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Genmab: Consultancy; Precision Biosciences: Consultancy; Kite/Gilead: Consultancy; Celgene: Consultancy; Juno Therapeutics: Consultancy, Research Funding.
•Day 100 grade 2 to 3 acute kidney injury (AKI) incidence is high after adult cord blood transplantation.•Grade 1 to 2 AKI can be present with a normal creatinine.•A higher pretransplant serum ...albumin protects against AKI.•Critical illness and nephrotoxic drugs increase AKI risk.•Early post-transplant AKI increases 2-year chronic kidney disease risk.
Although cord blood transplantation (CBT) extends allograft access, patient comorbidities, chemoradiation, and nephrotoxic medications all contribute to acute kidney injury (AKI) risk. We analyzed AKI in adult myeloablative CBT recipients who underwent transplantation from 2006 to 2017 for hematologic malignancies using cyclosporine A (CSA)/mycophenolate mofetil immunosuppression. Maximum grades of AKI were calculated using Kidney Disease: Improving Global Outcomes (grade 1, 1.5 to <2-fold; grade 2, 2 to <3-fold; or grade 3, ≥3-fold over baseline) definitions. In total, 153 patients (median 51 years range, 23-65, 114/153 75% acute leukemia, 27/153 18% African, 88/153 58% cytomegalovirus seropositive, median age-adjusted hematopoietic cell comorbidity index 3 range, 0-9, median pretransplant albumin 4.0 g/dL range, 2.6-5.2) underwent transplantation. The day 100 cumulative incidence of grade 1-3 AKI was 83% (95% confidence interval CI, 77%-89%) (predominantly grade 2, median onset 40 days, range 0 to 96), and grade 2-3 AKI incidence was 54% (95% CI, 46%-62%) (median onset 43 days, range 0 to 96). Mean CSA level preceding AKI onset was high (360 ng/mL, target range 300-350). In multivariate analysis, African ancestry, addition of haploidentical CD34+ cells, low day –7 albumin, critical illness/intensive care admission, and nephrotoxic drug exposure (predominantly CSA and/or foscarnet) were associated with AKI. In a day 100 landmark analysis, 6% of patients with no prior AKI had chronic kidney disease (CKD) at 2 years versus 43% with prior grade 1 and 38% with prior grade 2-3 AKI (overall P= .02). Adult CBT recipients are at significant AKI risk, and AKI is associated with increased risk of CKD. Prevention strategies, early recognition, and prompt intervention are critical to mitigate kidney injury.
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