Autologous transplant vs. CAR-T therapy in patients with DLBCL treated while in complete remission.

In patients with relapsed DLBCL in complete remission (CR), autologous hematopoietic cell transplantation (auto-HCT) and CAR-T therapy are both effective, but it is unknown which modality provides superior outcomes. We compared the efficacy of auto-HCT vs. CAR-T in patients with DLBCL in a CR. A retrospective observational study comparing auto-HCT (2015-2021) vs. CAR-T (2018-2021) using the Center for International Blood & Marrow Transplant Research registry. Median follow-up was 49.7 months for the auto-HCT and 24.7 months for the CAR-T cohort. Patients ages 18 and 75 with a diagnosis of DLBCL were included if they received auto-HCT (n = 281) or commercial CAR-T (n = 79) while in a CR. Patients undergoing auto-HCT with only one prior therapy line and CAR-T patients with a previous history of auto-HCT treatment were excluded. Endpoints included Progression-free survival (PFS), relapse rate, non-relapse mortality (NRM) and overall survival (OS). In univariate analysis, treatment with auto-HCT was associated with a higher rate of 2-year PFS (66.2% vs. 47.8%; p < 0.001), a lower 2-year cumulative incidence of relapse (27.8% vs. 48% ; p < 0.001), and a superior 2-year OS (78.9% vs. 65.6%; p = 0.037). In patients with early (within 12 months) treatment failure, auto-HCT was associated with a superior 2-year PFS (70.9% vs. 48.3% ; p < 0.001), lower 2-year cumulative incidence of relapse (22.8% vs. 45.9% ; p < 0.001) and trend for higher 2-year OS (82.4% vs. 66.1% ; p = 0.076). In the multivariable analysis, treatment with auto-HCT was associated with a superior PFS (hazard ratio 1.83; p = 0.0011) and lower incidence of relapse (hazard ratio 2.18; p < 0.0001) compared to CAR-T. In patients with relapsed LBCL who achieve a CR, treatment with auto-HCT is associated with improved clinical outcomes compared to CAR-T. These data support the consideration of auto-HCT in select patients with LBCL achieving a CR in the relapsed setting.

Chimeric antigen receptor T-cell infusion for large B-cell lymphoma in complete remission: a center for international blood and marrow transplant research analysis.

CD19 CAR T-cell (CAR-T) therapy is commonly administered to patients with relapsed or refractory large B-cell lymphomas (LBCL), but salvage or bridging therapy can sometimes lead to a complete response (CR) prior to infusion. Limited studies have assessed the outcomes of patients infused in CR. A total of 134 patients with LBCL in CR prior to CAR-T infusion were identified from the CIBMTR registry, with median prior lines of therapy of 3 (range 2-9). At two years post-infusion, the probability of progression-free survival was 43.5% (95% CI 34.4-52.8) and the probability of overall survival was 63.8% (95% CI 54.4-72.6). The cumulative incidence rates of non-relapse mortality and relapse/progression at two years were 9.2% (95% CI 4.5-15.4) and 47.3% (95% CI 38.2-56.6), respectively. The rate of grade 3 or higher cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were 2.2% and 8.2%, respectively. In summary, CAR-T in heavily pretreated patients with LBCL who are in CR following two or more lines of prior therapy demonstrate that a subset of patients may remain free of progression at two years. Additionally, the toxicity profile was impressive with very low rates of grade 3 CRS and ICANS.

Unsupervised Online Paired Associates Learning Task from the Cambridge Neuropsychological Test Automated Battery (CANTAB®) in the Brain Health Registry.

BACKGROUND: Unsupervised online cognitive assessments have demonstrated promise as an efficient and scalable approach for evaluating cognition in aging, and Alzheimer's disease and related dementias. OBJECTIVES: The aim of this study was to evaluate the feasibility, usability, and construct validity of the Paired Associates Learning task from the Cambridge Neuropsychological Test Automated Battery® in adults enrolled in the Brain Health Registry. DESIGN, SETTING, PARTICIPANTS, MEASUREMENTS: The Paired Associates Learning task was administered to Brain Health Registry participants in a remote, unsupervised, online setting. In this cross-sectional analysis, we 1) evaluated construct validity by analyzing associations between Paired Associates Learning performance and additional participant registry data, including demographics, self- and study partner-reported subjective cognitive change (Everyday Cognition scale), self-reported memory concern, and depressive symptom severity (Patient Health Questionnaire-9) using multivariable linear regression models; 2) determined the predictive value of Paired Associates Learning and other registry variables for identifying participants who self-report Mild Cognitive Impairment by employing multivariable binomial logistic regressions and calculating the area under the receiver operator curve; 3) investigated feasibility by looking at task completion rates and statistically comparing characteristics of task completers and non-completers; and 4) evaluated usability in terms of participant requests for support from BHR related to the assessment. RESULTS: In terms of construct validity, in participants who took the Paired Associates Learning for the first time (N=14,528), worse performance was associated with being older, being male, lower educational attainment, higher levels of self- and study partner-reported decline, more self-reported memory concerns, greater depressive symptom severity, and self-report of Mild Cognitive Impairment. Paired Associates Learning performance and Brain Health Registry variables together identified those with self-reported Mild Cognitive Impairment with moderate accuracy (areas under the curve: 0.66-0.68). In terms of feasibility, in a sub-sample of 29,176 participants who had the opportunity to complete Paired Associates Learning for the first time in the registry, 14,417 started the task. 11,647 (80.9% of those who started) completed the task. Compared to those who did not complete the task at their first opportunity, those who completed were older, had more years of education, more likely to self-identify as White, less likely to self-identify as Latino, less likely to have a subjective memory concern, and more likely to report a family history of Alzheimer's disease. In terms of usability, out of 8,395 received requests for support from BHR staff via email, 4.4% (n=374) were related to PAL. Of those, 82% were related to technical difficulties. CONCLUSIONS: Our findings support moderate feasibility, good usability, and construct validity of cross-sectional Paired Associates Learning in an unsupervised online registry, but also highlight the need to make the assessment more inclusive and accessible to individuals from ethnoculturally and socioeconomically diverse communities. A future, improved version could be a scalable, efficient method to assess cognition in many different settings, including clinical trials, observational studies, healthcare, and public health.

Pysanky to Microfluidics: An Innovative Wax-Based Approach to Low Cost, Rapid Prototyping of Microfluidic Devices.

A wax-based contact printing method to create microfluidic devices is demonstrated. This printing technology demonstrates a new pathway to rapid, cost-effective device prototyping, eliminating the use of expensive micromachining equipment and chemicals. Derived from the traditional Ukrainian Easter egg painting technique called "pysanky" a series of microfluidic devices were created. Pysanky is the use of a heated wax stylus, known as a "kistka", to create micro-sized, intricate designs on the surface of an egg. The proposed technique involves the modification of an x-y-z actuation translation system with a wax extruder tip in junction with Polydimethysiloxane (PDMS) device fabrication techniques. Initial system optimization was performed considering design parameters such as extruder tip size, contact angle, write speed, substrate temperature, and wax temperature. Channels created ranged from 160 to 900 µm wide and 10 to 150 µm high based upon system operating parameters set by the user. To prove the capabilities of this technology, a series of microfluidic mixers were created via the wax technique as well as through traditional photolithography: a spiral mixer, a rainbow mixer, and a linear serial dilutor. A thermo-fluidic computational fluid dynamic (CFD) model was generated as a means of enabling rational tuning, critical to the optimization of systems in both normal and extreme conditions. A comparison between the computational and experimental models yielded a wax height of 57.98 µm and 57.30 µm, respectively, and cross-sectional areas of 11,568 µm2 and 12,951 µm2, respectively, resulting in an error of 1.18% between the heights and 10.76% between the cross-sectional areas. The device's performance was then compared using both qualitative and quantitative measures, considering factors such as device performance, channel uniformity, repeatability, and resolution.

Review of imaging test phantoms.

Significance: Photoacoustic tomography has emerged as a prominent medical imaging technique that leverages its hybrid nature to provide deep penetration, high resolution, and exceptional optical contrast with notable applications in early cancer detection, functional brain imaging, drug delivery monitoring, and guiding interventional procedures. Test phantoms are pivotal in accelerating technology development and commercialization, specifically in photoacoustic (PA) imaging, and can be optimized to achieve significant advancements in PA imaging capabilities. Aim: The analysis of material properties, structural characteristics, and manufacturing methodologies of test phantoms from existing imaging technologies provides valuable insights into their applicability to PA imaging. This investigation enables a deeper understanding of how phantoms can be effectively employed in the context of PA imaging. Approach: Three primary categories of test phantoms (simple, intermediate, and advanced) have been developed to differentiate complexity and manufacturing requirements. In addition, four sub-categories (tube/channel, block, test target, and naturally occurring phantoms) have been identified to encompass the structural variations within these categories, resulting in a comprehensive classification system for test phantoms. Results: Based on a thorough examination of literature and studies on phantoms in various imaging modalities, proposals have been put forth for the development of multiple PA-capable phantoms, encompassing considerations related to the material composition, structural design, and specific applications within each sub-category. Conclusions: The advancement of novel and sophisticated test phantoms within each sub-category is poised to foster substantial progress in both the commercialization and development of PA imaging. Moreover, the continued refinement of test phantoms will enable the exploration of new applications and use cases for PA imaging.

Impact of thiotepa dose-intensity in primary diffuse large B-cell lymphoma of the central nervous system undergoing autologous hematopoietic cell transplant with thiotepa/carmustine conditioning.

Thiotepa/carmustine (TT-BCNU) is a commonly used autologous transplant (ASCT) conditioning regimen for primary DLBCL of the CNS (PCNSL). The total thiotepa dose varies among TT-BCNU recipients, with some centers administering a total dose of 20 mg/kg, while others using 10 mg/kg. We retrospectively assessed the impact of thiotepa dose intensity on ASCT outcomes in 218 adult PCNSL patients who underwent a first ASCT with TT-BCNU conditioning and received either a total thiotepa dose of 10 mg/kg (TT-10 group; N = 90), or 20 mg/kg (TT-20 group; N = 128). The median follow-up of survivors was 22 months. The cumulative incidence of 1-year non-relapse mortality (NRM) for TT-10 and TT-20 cohorts were 6% (95%CI = 2-12%) vs. 4% (95%CI = 1-8%), respectively (p = 0.66). The 3-year cumulative incidence of relapse (15% vs. 13%; p = 0.67), progression-free survival (PFS) (71% vs. 80%; p = 0.25) and overall survival (OS) (79% vs. 83%; p = 0.56) were similar in the TT-10 and TT-20 groups, respectively. On multivariate analysis compared to TT-10, the TT-20 cohort was not associated with significantly different risk of NRM (Hazard ration [HR] = 0.77; p = 0.64), relapse/progression (HR = 0.87; p = 0.74), PFS (HR = 0.80; p = 0.48) or OS (HR = 1.10; p = 0.80). In conclusion thiotepa dose-intensity in TT-BCNU conditioning does not impact ASCT outcomes of PCNSL patients.

Allogeneic haematopoietic cell transplant in patients with relapsed/refractory anaplastic large cell lymphoma.

The prognosis of relapsed/refractory (R/R) anaplastic large cell lymphoma (ALCL) is poor. Large studies evaluating outcomes of allogeneic haematopoietic cell transplantation (allo-HCT) in systemic R/R ALCL are not available. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we evaluated outcomes of 182 adults (aged ≥18 years) with R/R ALCL undergoing allo-HCT between 2008 and 2019. Non-relapse mortality (NRM), disease relapse/progression (REL), progression-free survival (PFS), and overall survival (OS) were modelled using Cox proportional hazards models. The median (range) follow-up of survivors was 62 (3-148) months. The 1-year NRM was 18%. The 5-year REL, PFS and OS were 32%, 41% and 56% respectively. On multivariable regression analysis African American race (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.6-4.8; p < 0.001) and refractory disease at allo-HCT (HR 3.2, 95% CI 1.6-6.2; p < 0.001) were predictive of inferior OS. Similarly, African-American race (HR 2.1, 95% CI 1.3-3.4; p = 0.003), other minority race (HR 2.5, 95% CI 1.2-5.3; p = 0.02) and refractory disease (HR 2.2, 95% CI 1.2-4.3; p = 0.01) were predictive of inferior PFS. These data, demonstrate that allo-HCT can result in durable disease control in a sizable proportion of patients with R/R ALCL. Refractory disease and racial minority status predicted inferior allo-HCT outcomes. Whether the inferior outcomes of racial minorities with R/R ALCL after allo-HCT are driven by differences in disease biology or disparities in post allo-HCT care, or both, requires further investigation.

KIR-favorable TCR-αß/CD19-depleted haploidentical HCT in children with ALL/AML/MDS: primary analysis of the PTCTC ONC1401 trial.

We performed a prospective multicenter study of T-cell receptor αß (TCR-αß)/CD19-depleted haploidentical hematopoietic cell transplantation (HCT) in children with acute leukemia and myelodysplastic syndrome (MDS), to determine 1-year disease-free survival (DFS) and compare 2-year outcomes with recipients of other donor cell sources. Fifty-one patients aged 0.7 to 21 years were enrolled; donors were killer immunoglobulin-like receptor (KIR) favorable based on ligand mismatch and/or high B content. The 1-year DFS was 78%. Superior 2-year DFS and overall survival (OS) were noted in patients <10 years of age, those treated with reduced toxicity conditioning (RTC) rather than myeloablative conditioning, and children with minimal residual disease <0.01% before HCT. Multivariate analysis comparing the KIR-favorable haploidentical cohort with controls showed similar DFS and OS compared with other donor cell sources. Multivariate analysis also showed a marked decrease in the risk of grades 2 to 4 and 3 to 4 acute graft versus host disease (aGVHD), chronic GVHD, and transplant-related mortality vs other donor cell sources. Ethnic and racial minorities accounted for 53% of enrolled patients, and data from a large cohort of recipients/donors screened for KIR showed that >80% of recipients had a KIR-favorable donor by our definition, demonstrating that this approach is broadly applicable to groups often unable to find donors. This prospective, multicenter study showed improved outcomes using TCR-αß/CD19-depleted haploidentical donors using RTC for children with acute leukemia and MDS. Randomized trials comparing this approach with matched unrelated donors are warranted. This trial was registered at https://clinicaltrials.gov as #NCT02646839.

Outcomes of Autologous Hematopoietic Cell Transplantation in Older Patients with Diffuse Large B-Cell Lymphoma.

Data for outcomes after autologous hematopoietic cell transplantation (auto-HCT) in diffuse large B-cell lymphoma (DLBCL) patients ≥70 years are limited. Auto-HCT is feasible in older DLBCL patients. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes of auto-HCT in DLBCL patients aged 60 to 69 years (n = 363) versus ≥70 years (n = 103) between 2008 and 2019. Non-relapse mortality (NRM), relapse/progression (REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models. All patients received BEAM conditioning (carmustine, etoposide, cytosine arabinoside and melphalan). On univariate analysis, in the 60 to 69 years versus ≥70 years cohorts, 100-day NRM was 3% versus 4%, 5-year REL was 47% versus 45%, 5-year PFS 40% versus 38% and 5-year OS 55% versus 41%, respectively. On multivariate analysis, patients ≥70 had no significant difference in NRM (hazard ratio [HR] 1.43, 95% confidence interval [CI] 0.85-2.39), REL (HR 1.11, 95% CI 0.79-1.56), PFS (HR 1.23, 95% CI 0.92-1.63) compared to patients 60 to 69 years. Patients ≥70 years had a higher mortality (HR 1.39, 95% CI 1.05-1.85, p=0.02), likely because of inferior post-relapse OS in this cohort (HR 1.82, 95% CI 1.27-2.61, P = .001). DLBCL was the major cause of death in both cohorts (62% versus 59%). Older patients should not be denied auto-HCT solely on the basis of chronological age.

Impact of conditioning regimen intensity on the outcomes of peripheral T-cell lymphoma, anaplastic large cell lymphoma and angioimmunoblastic T-cell lymphoma patients undergoing allogeneic transplant.

There have been no large studies comparing reduced-intensity/non-myeloablative conditioning (RIC/NMA) to myeloablative conditioning (MAC) regimens in T-cell non-Hodgkin lymphoma (T-NHL) patients undergoing allogeneic transplant (allo-HCT). A total of 803 adults with peripheral T-cell lymphoma, anaplastic large cell lymphoma and angioimmunoblastic T-cell lymphoma (age 18-65 years), undergoing allo-HCT between 2008-2019 and reported to the Center for International Blood and Marrow Transplant Research with either MAC (n = 258) or RIC/NMA regimens (n = 545) were evaluated. There were no significant differences between the two cohorts in terms of patient sex, race and performance scores. Significantly more patients in the RIC/NMA cohort had peripheral blood grafts, haematopoietic cell transplantation-specific comorbidity index (HCT-CI) of ≥3 and chemosensitive disease compared to the MAC cohort. On multivariate analysis, overall survival (OS) was not significantly different in the RIC/NMA cohort compared to the MAC cohort (hazard ratio (HR) = 1.01, 95% confidence interval (CI) = 0.79-1.29; p = 0.95). Similarly, non-relapse mortality (NRM) (HR = 0.85, 95% CI = 0.61-1.19; p = 0.34), risk of progression/relapse (HR = 1.29; 95% CI = 0.98-1.70; p = 0.07) and therapy failure (HR = 1.14; 95% CI = 0.92-1.41, p = 0.23) were not significantly different between the two cohorts. Relative to MAC, RIC/NMA was associated with a significantly lower risk of grade 3-4 acute graft-versus-host disease (HR = 0.67; 95% CI = 0.46-0.99, p = 0.04). Among chemorefractory patients, there was no difference in OS, therapy failure, relapse, or NRM between RIC/NMA and MAC regimens. In conclusion, we found no association between conditioning intensity and outcomes after allo-HCT for T-cell NHL.

Effect of time to relapse on overall survival in patients with mantle cell lymphoma following autologous haematopoietic cell transplantation.

In young and fit patients with mantle cell lymphoma (MCL), intensive induction therapy followed by a consolidative autologous haematopoietic cell transplant (autoHCT) is the standard of care in the front-line setting. Recently, time-to-event analysis has emerged as an important risk assessment tool in lymphoma, though its impact in MCL is not well defined. We utilized the Center for International Blood and Marrow Transplant Research database to evaluate the effect of post-autoHCT time to relapse on overall survival (OS) over time in 461 patients who underwent autoHCT within 12 months of MCL diagnosis. On multivariate analysis, the impact of relapse on OS was greatest at the six-month [hazard ratio (HR) = 7·68], 12-month (HR = 6·68), and 18-month (HR = 5·81) landmark timepoints. Using a dynamic landmark model we demonstrate that adjusted OS at five years following each landmark timepoint improved with time for relapsing and non-relapsing patients. Furthermore, early relapse (<18 months) following autoHCT defines a high-risk group with inferior post-relapse OS. This retrospective analysis highlights the impact of time to relapse on OS in MCL patients undergoing up-front autoHCT and emphasizes the need to consider novel therapeutic approaches for patients suffering early relapse.

Outcomes and Utilization Trends of Front-Line Autologous Hematopoietic Cell Transplantation for Mantle Cell Lymphoma.

Although autologous hematopoietic cell transplantation (auto-HCT) has become a common practice for eligible patients in the front-line setting with mantle cell lymphoma (MCL), there are limited data regarding trends in auto-HCT utilization and associated outcomes. This study used the Center for International Blood and Marrow Transplant Research (CIBMTR) database to evaluate survival outcomes and auto-HCT utilization in adults age ≥18 years who underwent auto-HCT within 12 months of diagnosis of MCL between January 2000 and December 2018. The 19-year period from 2000 to 2018 was divided into 4 separate intervals-2000 to 2004, 2005 to 2009, 2010 to 2014, and 2015 to 2018-and encompassed 5082 patients. To evaluate transplantation utilization patterns, we combined MCL incidence derived from the SEER 21 database with CIBMTR- reported auto-HCT activity within 12 months of diagnosis of MCL. Primary outcomes included overall survival (OS) along with the auto-HCT utilization rate. The cumulative incidence of nonrelapse mortality at 1 year decreased from 7% in the earliest cohort (2000 to 2004) to 2% in the latest cohort (2015 to 2018). Mirroring this trend, OS outcomes improved continually with time, with a 3-year OS of 72% in the earliest cohort improving to 86% in the latest cohort. In addition, we noted an increase in auto-HCT utilization from 2001 to 2018, particularly in patients age ≤65 years. This large retrospective analysis highlights trends in auto-HCT utilization and outcomes in patients with MCL and emphasizes the need to optimize pretransplantation and post-transplantation treatment strategies to enhance survival outcomes.

Outcomes Associated With Thiotepa-Based Conditioning in Patients With Primary Central Nervous System Lymphoma After Autologous Hematopoietic Cell Transplant.

IMPORTANCE: Primary central nervous system lymphoma (PCNSL) requires induction and consolidation to achieve potential cure. High-dose therapy and autologous hematopoietic cell transplant (AHCT) is an accepted and effective consolidation strategy for PCNSL, but no consensus exists on the optimal conditioning regimens. OBJECTIVE: To assess the outcomes in patients with PCNSL undergoing AHCT with the 3 most commonly used conditioning regimens: thiotepa/busulfan/cyclophosphamide (TBC), thiotepa/carmustine (TT-BCNU), and carmustine/etoposide/cytarabine/melphalan (BEAM). DESIGN, SETTING, AND PARTICIPANTS: This observational cohort study used registry data from the Center for International Blood and Marrow Transplant Research registry. The Center is a working group of more than 380 transplantation centers worldwide that contributed detailed data on HCT to a statistical center at the Medical College of Wisconsin, Milwaukee. The participant data were from 603 adult patients with PCNSL who underwent AHCT as initial, or subsequent, consolidation between January 2010 and December 2018. Patients were excluded if they had a non-Hodgkin lymphoma subtype other than diffuse large B-cell lymphoma, systemic non-Hodgkin lymphoma, or HIV; received an uncommon conditioning regimen; or were not in partial remission or complete remission prior to AHCT. Statistical analysis was performed from July 5, 2020, to March 1, 2021. INTERVENTIONS: Patients received 1 of 3 conditioning regimens: TBC (n = 263), TT-BCNU (n = 275), and BEAM (n = 65). MAIN OUTCOMES AND MEASURES: The primary outcome was progression-free survival. Secondary outcomes included hematopoietic recovery, incidence of relapse, nonrelapse mortality, and overall survival. RESULTS: Of 603 patients, the mean age was 57 (range, 19-77) years and 318 (53%) were male. The 3-year adjusted progression-free survival rates were higher in the TBC cohort (75%) and TT-BCNU cohort (76%) compared with the BEAM cohort (58%) (P = .03) owing to a higher relapse risk in the BEAM cohort (hazard ratio [HR], 4.34; 95% CI, 2.45-7.70; P < .001). In a multivariable regression analysis, compared with the TBC cohort, patients who received TT-BCNU had a higher relapse risk (HR, 1.79; 95% CI, 1.07-2.98; P = .03), lower risk of nonrelapse mortality (NRM) (HR, 0.50; 95% CI, 0.29-0.87; P = .01), and similar risk of all-cause mortality more than 6 months after HCT (HR, 1.54; 95% CI, 0.93-2.55; P = .10). Age of 60 years or older, Karnofsky performance status less than 90, and an HCT-comorbidity index greater than or equal to 3 were associated with lower rates of survival across all 3 cohorts. Subgroup analyses demonstrated that patients aged 60 years and older had considerably higher NRM with TBC. CONCLUSIONS AND RELEVANCE: In this cohort study, thiotepa-based conditioning regimen was associated with higher rates of survival compared with BEAM, despite higher rates of early toxic effects and NRM; these findings may assist clinicians in choosing between TBC or TT-BCNU based on patient and disease characteristics.

An Integrated Centrifugal Degassed PDMS-Based Microfluidic Device for Serial Dilution.

We propose an integrated serial dilution generator utilizing centrifugal force with a degassed polydimethylsiloxane (PDMS) microfluidic device. Using gas-soluble PDMS as a centrifugal microfluidic device material, the sample can be dragged in any arbitrary direction using vacuum-driven force, as opposed to in a single direction, without adding further actuation components. The vacuum-driven force allows the device to avoid the formation of air bubbles and exhibit high tolerance in the surface condition. The device was then used for sample metering and sample transferring. In addition, centrifugal force was used for sample loading and sample mixing. In this study, a series of ten-fold serial dilutions ranging from 100 to 10-4 with about 8 µL in each chamber was achieved, while the serial dilution ratio and chamber volume could easily be altered by changing the geometrical designs of the device. As a proof of concept of our hybrid approach with the centrifugal and vacuum-driven forces, ten-fold serial dilutions of a cDNA (complementary DNA) sample were prepared using the device. Then, the diluted samples were collected by fine needles and subject to a quantitative polymerase chain reaction (qPCR), and the results were found to be in good agreement with those for samples prepared by manual pipetting.

Impact of Reduced-Intensity Conditioning Regimens on Outcomes in Diffuse Large B Cell Lymphoma Undergoing Allogeneic Transplantation.

Reduced-intensity conditioning (RIC) regimens are frequently used for allogeneic hematopoietic cell transplantation (allo-HCT) in patients with diffuse large B cell lymphoma (DLBCL). However, the RIC regimen with the best risk/benefit profile for allo-HCT in DLBCL is not known. This is particularly important because patients with DLBCL undergoing allo-HCT in the future would be enriched for those whose lymphoma has failed chimeric antigen receptor T cell (CAR-T) therapy or other novel immunotherapies, with potentially more advanced disease and suboptimal performance scores. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we report the outcomes of the 3 most commonly used allo-HCT RIC regimens in patients with DLBCL. Our analysis included a total of 562 adult DLBCL patients in the CIBMTR registry undergoing allo-HCT using matched related or unrelated donors, between 2008 and 2016. Patients received 1 of 3 RIC regimens: fludarabine/i.v. busulfan ~6.4 mg/kg (Flu/Bu), fludarabine/melphalan 140 mg/m2 (Flu/Mel140), or BCNU/etoposide/cytarabine/melphalan (BEAM). Accordingly, the study group was divided into 3 groups: Flu/Bu (n = 151), Flu/Mel140 (n = 296), and BEAM (n = 115). Relative to Flu/Bu, the Flu/Mel140 (hazard ratio [HR], 2.33; 95% confidence interval [CI], 1.42 to 3.82; P = .001) and BEAM (HR, 2.54; 95% CI, 1.34 to 4.80; P = .004) regimens were associated with a risk of higher nonrelapse mortality (NRM). Although the risk of relapse with Flu/Mel140 was lower than that with Flu/Bu (HR, .70; 95% CI, .52 to .95; P = .02), this did not translate to improved progression-free survival (HR, 1.04) or overall survival (HR, 1.30). There was a significantly higher risk of grade III-IV acute graft-versus-host disease with BEAM compared with Flu/Bu (HR, 2.19; 95% CI, 1.10 to 4.35; P = .03). In the chemosensitive subset, multivariate analysis showed a significantly higher mortality risk with Flu/Mel140 (HR, 1.48; 95% CI, 1.07 to 2.04; P = .02) relative to Flu/Bu conditioning. In the largest analysis comparing the impact of various RIC regimens on the survival of DLBCL patients undergoing allo-HCT, our results suggest that Flu/Bu is a better RIC choice in less fit or heavily pretreated patients due to lowest NRM risk.

Is autologous transplant in relapsed DLBCL patients achieving only a PET+ PR appropriate in the CAR T-cell era?

For relapsed chemosensitive diffuse large B-cell lymphoma (DLBCL), consolidation with autologous hematopoietic cell transplantation (auto-HCT) is a standard option. With the approval of anti-CD19 chimeric antigen receptor T cells in 2017, the Center for International Blood and Marrow Transplant Research (CIBMTR) reported a 45% decrease in the number of auto-HCTs for DLBCL in the United States. Using the CIBMTR database, we identified 249 relapsed DLBCL patients undergoing auto-HCT from 2003 to 2013 with a positive positron emission tomography/computed tomography (PET/CT)+ partial response prior to transplant were identified. The study cohort was divided into 2 groups: early chemoimmunotherapy failure (ECF), defined as patients with primary refractory disease (PRefD) or relapse within 12 months of diagnosis and late chemoimmunotherapy failure, defined as patients relapsing after ≥12 months. Primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS) and relapse. A total of 182 patients had ECF, whereas 67 did not. Among ECF cohort, 79% had PRefD. The adjusted 5-year probabilities for PFS and OS (ECF vs no ECF) were not different: 41% vs 41% (P = .93) and 51% vs 63% (P = .09), respectively. On multivariate analysis, ECF patients had an increased risk for death (hazard ratio, 1.61; 95% confidence interval, 1.05-2.46; P = .03) but not for PFS or relapse. In conclusion, for relapsed chemosensitive DLBCL patients with residual PET/CT+ disease prior to auto-HCT, the adjusted 5-year PFS (41%) was comparable, irrespective of time to relapse. These data support ongoing application of auto-HCT in chemosensitive DLBCL.

Passive micropumping in microfluidics for point-of-care testing.

Suitable micropumping methods for flow control represent a major technical hurdle in the development of microfluidic systems for point-of-care testing (POCT). Passive micropumping for point-of-care microfluidic systems provides a promising solution to such challenges, in particular, passive micropumping based on capillary force and air transfer based on the air solubility and air permeability of specific materials. There have been numerous developments and applications of micropumping techniques that are relevant to the use in POCT. Compared with active pumping methods such as syringe pumps or pressure pumps, where the flow rate can be well-tuned independent of the design of the microfluidic devices or the property of the liquids, most passive micropumping methods still suffer flow-control problems. For example, the flow rate may be set once the device has been made, and the properties of liquids may affect the flow rate. However, the advantages of passive micropumping, which include simplicity, ease of use, and low cost, make it the best choice for POCT. Here, we present a systematic review of different types of passive micropumping that are suitable for POCT, alongside existing applications based on passive micropumping. Future trends in passive micropumping are also discussed.

Impact of type of reduced-intensity conditioning regimen on the outcomes of allogeneic haematopoietic cell transplantation in classical Hodgkin lymphoma.

Reduced-intensity conditioning (RIC) allogeneic haematopoietic cell transplantation (allo-HCT) is a curative option for select relapsed/refractory Hodgkin lymphoma (HL) patients; however, there are sparse data to support superiority of any particular conditioning regimen. We analyzed 492 adult patients undergoing human leucocyte antigen (HLA)-matched sibling or unrelated donor allo-HCT for HL between 2008 and 2016, utilizing RIC with either fludarabine/busulfan (Flu/Bu), fludarabine/melphalan (Flu/Mel140) or fludarabine/cyclophosphamide (Flu/Cy). Multivariable regression analysis was performed using a significance level of <0·01. There were no significant differences between regimens in risk for non-relapse mortality (NRM) (P = 0·54), relapse/progression (P = 0·02) or progression-free survival (PFS) (P = 0·14). Flu/Cy conditioning was associated with decreased risk of mortality in the first 11 months after allo-HCT (HR = 0·28; 95% CI = 0·10-0·73; P = 0·009), but beyond 11 months post allo-HCT it was associated with a significantly higher risk of mortality, (HR = 2·46; 95% CI = 0·1.32-4·61; P = 0·005). Four-year adjusted overall survival (OS) was similar across regimens at 62% for Flu/Bu, 59% for Flu/Mel140 and 55% for Flu/Cy (P = 0·64), respectively. These data confirm the choice of RIC for allo-HCT in HL does not influence risk of relapse, NRM or PFS. Although no OS benefit was seen between Flu/Bu and Flu/Mel 140; Flu/Cy was associated with a significantly higher risk of mortality beyond 11 months from allo-HCT (possibly due to late NRM events).