SUMMARY BackgroundThe diagnostic accuracy of two indirect tests of lactose digestion, lactose breath hydrogen and lactose tolerance tests, have not been systematically reviewed for comparison with available publications on genotype.
Background Passenger Lymphocyte Syndrome (PLS) is a rare complication of solid organ transplantation (SOT) and is marked by production of donor-derived antibodies towards host red blood cell (RBC) antigens. At Canada's largest SOT program, >400 transplants are conducted annually. The affiliated Transfusion Laboratory detects possible cases of PLS when previously seronegative hosts develop (delayed, non-transfusion-attributable) post-transplant antibodies (Ab) bearing unexpected, autoreactive (rather than alloreactive) RBC specificities. Donor attributability is established by discovery of the same specificity (on serologic lookback) and/or by the antithetical (seroconversion risk) phenotype. The incidence, duration, and severity of PLS remain unknown due to the infrequency of reported cases and the general absence of active surveillance. Method Between 1/10/2006 – 30/06/2013, PLS cases were discovered by the Blood Bank through pre-transfusion specimens. The specificities, phase (direct or indirect), correlative markers of hemolysis, and temporal profile of the Ab were subsequently followed according to patient and clinician interest. The severity of hemolysis (grade 0 to 5) at the time of nadir hemoglobin was judged according to the tiers defined by the Canadian Blood Services/IVIG Hemolysis Pharmacovigilance Group (CL#2011-34). Implicated organ and donor review (for relevant serology, and outcomes in any parallel organ distributions) were also attempted. Results Over 88 months, 2772 transplants occurred (992 kidney, 187 pancreas [with/after kidney in 113/74 respectively], 909 liver, 529 lung [437 double, 83 single, 9 +heart], 151 heart, 4 bowel). PLS was found in 14 or 0.5% (sex: 5F: 9M; mean age 56 years), with the implicated organ being lung or liver (9 [2%] and 5 [0.6%] respectively). All had a negative pre-transplant DAT with a pre-sensitized donor. PLS Ab specificities included ABO (8: 5A, 3B), RH (5 with ≥1 target [C:3, D:5, E:2, V:1]), and others (KIDD: Jka in 2; MNS: N in 1; unidentified in 1). Multiple Ab occurred in 5 (36%), usually within the same system (3 RH cases: C,D,E in 2; C,D,V in 1), but otherwise towards ABO + ≥1 target (B,Jka,N; B, unidentified). The time to the first detectable expression of an Ab (as signaled by a +DAT and/or screen) was 4-120 days (mean 24, median 15, n=14). Clinically significant hemolysis occurred in 11 (79%), with six grade 3 and five grade 4; the duration of hemolysis was 0-776 days (mean 148, median 38, n=11). The duration of Ab detectability (or the point of “last positivity”) was 12-851 days (mean 196, median 78, n=10), while the point of disappearance (“subsequent sustained negativity”) occurred between day 12-1288 (mean 298, median 45, n=10). Lookbacks were feasible with 5 implicated donors, and in only 1 case (of a contralateral lung's transplantation) was PLS detected in another recipient. PLS did not account directly for any deaths in the cohort, although hemolytic morbidity required treatment in 2 cases. Transfusion support with antigen-negative blood was provided to 11 patients for anemia that may have been due to hemolysis and/or other causes while the Ab was still evident. In one case, severe hemolysis provoked rate-uncontrolled atrial fibrillation with a supply and demand ischemia which culminated in irreversible congestive heart failure and cardiac death 2 months after PLS resolution. Discussion/Conclusions This is the largest series of PLS reported to date. Clinician-driven submissions of blood for transfusion compatibility testing, and the discovery of discrepant serologies, represented an unforced but prospective means by which to identify PLS in roughly 1 in 200 transplants. Several cases transcended the limits of previously described temporal profiles (with the most delayed onset at 120 days, and the most prolonged duration at 2.3 years). The duration of hemolysis was consistently shorter than the duration of seropositivity, and was rarely life-threatening, while the most severe grades associated with RH rather than ABO or other targets. The surveillance achieved in this cohort revealed a longer-than-previously-appreciated duration of Ab productivity, and raised the question of whether or not such prolongation is a function of observation bias or the current-day armamentarium of anti-rejection therapeutics, which may be more permissive to donor-derived chimerism. Disclosures: No relevant conflicts of interest to declare.
e19520 Background: Research into novel therapies for relapsed/refractory DLBCL may be hindered by the perception these patients are difficult to capture in clinical trials. We performed a retrospective analysis of all DLBCL at our institution from 01/2006 to 03/2012 to identify hurdles to trial enrolment. Methods: All DLBCL cases were identified through the hospital tumor registry. Patients were included in the analysis if they had any diagnosis of DLBCL relapsed or refractory to standard therapy. Baseline demographic and clinical characteristics, details of treatment, responses, relapse, evaluation for clinical trials and participation in clinical trials were determined by review of hospital charts. Results: Of a total of 284 patients, 76 had relapsed/refractory disease, 10 of 20 had a successful ASCT, and there is insufficient data on 1 patient. Of the remaining 65, 11 (17%) made it to trial. The median age was 65, 34 were male, median number of prior therapies was 2, 74% had at least one comorbidity and 46% had at least 2, 62% of patients had de novo DLBCL, 18% transformed and 20% composite. 81% of cases were discussed at tumor board. Reasons for failing to enroll on trial included prohibitive comorbidity (21%), rapid progression (15%), decision for palliation (15%), prior second malignancy (9%), thrombocytopenia (13%), CNS disease (9%), proximity to ASCT (2%), no protocol for DLBCL (6%), palliative radiation (6%). Conclusions: We demonstrate that 17% of patients with DLBCL not responding to standard therapy make it to trial, the remainder does not mainly beacause of comorbidity and rapid progression. Similar barriers were found for solid tumor patients (Lara, JCO 2001) and a similar accrual rate was seen in relapsed non-small cell lung cancer (Baggstrom,J Thor Oncol 2011) . Relapsed DLBCL is a population for whom clinical trial research is challenging but possible.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.