Outcomes of Human Leukocyte Antigen-Matched Related Donor and Haploidentical Allogeneic Hematopoietic Cell Transplantation Recipients by Immune Profiles of Recipients and Donors.

Haploidentical (Haplo) allogeneic HCTs (alloHCT) have been used more frequently over the last decade as survival is similar to HLA-matched related donor (MRD) alloHCTs. We aimed to identify donor and recipient immune signatures before alloHCT that are associated with clinically meaningful outcomes in MRD vs Haplo alloHCT recipients. This retrospective cohort study of 165 MRD (n = 132) and Haplo (n = 33) alloHCT recipients and their related donors between 2007-2019 with paired peripheral blood samples immunophenotyped for T-cell, B-cell, NK cell and dendritic cell (DC) subsets. Immune cells were quantified before alloHCT in donors and recipients; calculations of immune cell ratios were classified as high, intermediate, and low and analyzed with alloHCT outcomes. Haplo donors were younger than MRD donors (median: 35 vs 51 years), whereas Haplo recipients were older than MRD recipients (median: 68 vs 54 years), were more likely to have a Karnofsky Performance Score ≤ 70 (76% vs 57%), 3+ comorbidities (54% vs 47%), and were in complete remission prior to alloHCT (58% vs 42%). In MRD alloHCT, a lower ratio of CD4+ to CD8+ effector memory cells in the donor was associated with lower 4-yr overall survival (OS; 25% vs 61%; P = .009), lower 4-yr progression free survival (PFS; 25% vs 58%; P = .014) and higher incidence of 1-yr transplant-related mortality (TRM; 39% vs 7%; P = .009) in recipients. A higher ratio of CD8+ effector memory to total NK cells measured in MRD recipients was associated with a higher incidence of grade II-IV aGvHD (63% vs 37%; P = .004) but was not statistically significant for III-IV aGvHD (23% vs 12%). In Haplo alloHCT, a lower ratio of total T-regulatory to CD4+ central memory cells in the donor was associated with lower 4-yr PFS (22% vs 60%; P = .0091). A higher ratio of CD4+ effector memory to CD8+ effector memory cells measured in Haplo recipients pre-alloHCT was associated with lower 4-yr OS (25% vs 88%; P = .0039). In both MRD and Haplo recipients, a higher ratio of CD4+ naïve to CD4+ central memory cells was associated with a higher incidence of grade II-IV aGvHD (64% vs 38%; P = .04). Evaluation of pre-alloHCT immune signatures of the donor and recipient may influence clinically meaningful patient outcomes in both MRD and Haplo transplants.

An automated parametric ear model to improve frugal 3D scanning methods for the advanced manufacturing of high-quality prosthetic ears.

Ear prostheses are commonly used for restoring aesthetics to those suffering missing or malformed external ears. Traditional fabrication of these prostheses is labour intensive and requires expert skill from a prosthetist. Advanced manufacturing including 3D scanning, modelling and 3D printing has the potential to improve this process, although more work is required before it is ready for routine clinical use. In this paper, we introduce a parametric modelling technique capable of producing high quality 3D models of the human ear from low-fidelity, frugal, patient scans; significantly reducing time, complexity and cost. Our ear model can be tuned to fit the frugal low-fidelity 3D scan through; (a) manual tuning, or (b) our automated particle filter approach. This potentially enables low-cost smartphone photogrammetry-based 3D scanning for high quality personalised 3D printed ear prosthesis. In comparison to standard photogrammetry, our parametric model improves completeness, from (81 ± 5)% to (87 ± 4)%, with only a modest reduction in accuracy, with root mean square error (RMSE) increasing from (1.0 ± 0.2) mm to (1.5 ± 0.2) mm (relative to metrology rated reference 3D scans, n = 14). Despite this reduction in the RMS accuracy, our parametric model improves the overall quality, realism, and smoothness. Our automated particle filter method differs only modestly compared to manual adjustments. Overall, our parametric ear model can significantly improve quality, smoothness and completeness of 3D models produced from 30-photograph photogrammetry. This enables frugal high-quality 3D ear models to be produced for use in the advanced manufacturing of ear prostheses.

Short-Term Storage of Mobilized Peripheral Blood Stem Cells in a Closed System Changes the Microenvironment and May Affect the Quantity of CD34+ and CD34+CD38-CD45RA-CD90+ Cells.

Hypoxic conditions preserve the multipotency and self-renewing capacity of murine bone marrow and human cord blood stem cells. Blood samples stored in sealed blood gas tubes become hypoxic as leukocytes metabolize and consume oxygen. Taken together, these observations suggest that peripheral blood stem cell (PBSC) samples stored under airtight conditions become hypoxic, and that the stem cells contained may undergo qualitative or quantitative changes. This study aimed to determine the effect of storage for 8 hours in a sealed system on PBSC samples. Granulocyte colony-stimulating factor-mobilized PBSC samples were collected prospectively from 9 patients with myeloma or amyloidosis prior to apheresis, followed by measurement of CO2, O2, hydrogen ion (pH), lactate, and glucose concentrations in the blood and immunophenotyping of stem cell and multipotent progenitor cell populations before and after 8 hours of storage in sealed blood collection tubes. Blood concentrations of O2 and glucose and pH measurements were significantly decreased, whereas concentrations of CO2 and lactate were significantly increased after storage. Significantly higher concentrations of CD34+ cells (552 ± 84 cells/106 total nucleated cells [TNCs] versus 985 ± 143 cells/106 TNCs; P = .03), CD34+CD38- cells (98 ± 32 cells/106 TNCs versus 158 ± 52 cells/106 TNCs; P = .03), CD34+CD38+ cells (444 ± 92 cells/106 TNCs versus 789 ± 153 cells/106 TNCs; P = .03), and CD34+CD38-CD45RA-CD90+ cells (55 ± 17 cells/106 TNCs versus 89 ± 25 cells/106 TNCs; P = .02) were detected after 8 hours of storage. The changes in concentrations of CD34+CD38+ cells and CD34+ cells were inversely associated with the change in glucose concentration (P = .003 and P < .001, respectively) and positively associated with the change in lactate concentration (P = .01 and P <.001, respectively) after 8 hours of airtight storage. Storage of PBSC samples in a sealed, airtight environment is associated with microenvironmental changes consistent with hypoxia and increased concentrations of immunophenotypically defined stem cells. These results may have clinical implications with regard to the collection and processing of stem cell products and warrant confirmation with functional and mechanistic studies.

Ultrasound Imaging Offers Promising Alternative to Create 3-D Models for Personalised Auricular Implants.

Three-dimensional imaging and advanced manufacturing are being applied in health care research to create novel diagnostic and surgical planning methods, as well as personalised treatments and implants. For ear reconstruction, where a cartilage-shaped implant is embedded underneath the skin to re-create shape and form, volumetric imaging and segmentation processing to capture patient anatomy are particularly challenging. Here, we introduce 3-D ultrasound (US) as an available option for imaging the external ear and underlying auricular cartilage structure, and compare it with computed tomography (CT) and magnetic resonance imaging (MRI) against micro-CT (µCT) as a high-resolution reference (gold standard). US images were segmented to create 3-D models of the auricular cartilage and compared against models generated from µCT to assess accuracy. We found that CT was significantly less accurate than the other methods (root mean square [RMS]: 1.30 ± 0.5 mm) and had the least contrast between tissues. There was no significant difference between MRI (RMS: 0.69 ± 0.2 mm) and US (0.55 ± 0.1 mm). US was also the least expensive imaging method at half the cost of MRI. These results unveil a novel use of ultrasound imaging that has not been presented before, as well as support its more widespread use in biofabrication as a low-cost imaging technique to create patient-specific 3D models and implants.

Replicated Risk Index of Patient Functional Status Prior to Allogeneic Hematopoietic Cell Transplantation Predicts Healthcare Utilization and Survival.

Poor physical functioning is associated with adverse outcomes after allogeneic hematopoietic cell transplantation (alloHCT). Analytic tools to predict mortality in alloHCT recipients include the HCT Comorbidity Index (HCT-CI) based on comorbidities and the Disease Risk Index (DRI) based on disease and disease status. We developed and replicated a risk model for overall survival (OS), early mortality (ie, death from any cause at or before day +100), initial hospital length of stay (LOS), and percentage of inpatient days within the first year post-alloHCT. In this study, we incorporated a physical therapy (PT) assessment with the HCT-CI and DRI to improve outcome predictions. The well-defined and feasible measure of functional status for assessing risk includes (1) the number of sit-to-stands performed in 30 seconds, (2) performance of 25 step-ups on the right/left side with (3) oxygen saturation recovery and (4) heart rate recovery, (5) weight-bearing ability, (6) assistance with ambulation, (7) motor and grip strength, (8) sensory and coordination impairment (eg, self-reported peripheral neuropathy, imbalance), (9) self-reported pain, and (10) limited endurance (ie, inability to complete step-ups and/or sit-to-stands). Our training cohort (TC) included 349 consecutive alloHCT recipients at Roswell Park treated between 2010 and 2016 and a subsequent replication cohort (RC; n = 163) treated between 2016 and 2019. Four of the 10 metrics-self-reported pain, limited endurance, self-reported neuropathy, and <10 sit-to-stands in 30 seconds-were identified as significant predictors and were included in the multivariable models with the HCT-CI and DRI to create a new risk index (HCT-PCDRI: HCT-physical, comorbidity, and DRI) for outcomes. Models were tested in the RC. Shorter OS was associated with self-reported pain, limited endurance, higher HCT-CI, and higher DRI. At a median follow-up of 34 months, the 3-year OS based on the HCT-PCDRI was 30% for the very-high-risk group, 54% for the high-risk group, 49% for the intermediate-risk group, and 80% for the low-risk group. The number of patients identified as very high risk increased from 55 using HCT-CI alone to 120 with the new HCT-PCDRI, whereas the number in the low-risk group decreased from 91 to 45. Early mortality and a higher percentage of inpatient days within the first year post-alloHCT (a proxy for poor quality of life and high healthcare utilization) were associated with self-reported pain, higher HCT-CI, and higher DRI. A shorter initial LOS (ie, initial low healthcare utilization) was associated with performance of >10 sit-to-stands in 30 seconds, no self-reported neuropathy, and lower HCT-CI. These PT metrics combined with the HCT-CI and DRI created the HCT-PCDRI, which resulted in more patients being categorized accurately as high risk versus low risk. The HCT-PCDRI results were replicated in an independent cohort. Pre-alloHCT PT metrics with self-reported symptoms (pain and neuropathy) were associated with survival post-alloHCT and prolonged hospital LOS. The HCT-PCDRI scoring system for risk stratification of alloHCT recipients more accurately identifies patients at potential risk of poor outcomes. The HCT-PCDRI can be tested in <15 minutes to identify patients for intervention before or during treatment to potentially improve outcomes.

Frugal 3D scanning using smartphones provides an accessible framework for capturing the external ear.

Three-dimensional (3D) scanning technologies, such as medical imaging and surface scanning, have important applications for capturing patient anatomy to create personalised prosthetics. Digital approaches for capturing anatomical detail as opposed to traditional, invasive impression techniques significantly reduces turnaround times and lower production costs while still maintaining the high aesthetic quality of the end product. While previous case studies utilise expensive 3D scanning and modelling frameworks, their clinical translation is limited due to high equipment costs. In this study, we develop and validate a low-cost framework for clinical 3D scanning of the external ear using photogrammetry and a smartphone camera. We recruited five novice operators who watched an instructional video before scanning 20 healthy adult participant ears who did not have microtia. Our results show that the smartphone-based photogrammetry methodology produces 3D scans of the external ear that were accurate to (1.5 ± 0.4) mm and were (71 ± 14) % complete compared with those from a gold standard reference scanner, with no significant difference observed between operators. A moderate to strong interrater reliability was determined for all novice operators, suggesting that all novice operators were able to capture repeatable scans. The development of this smartphone photogrammetry approach has the potential to provide a non-invasive, inexpensive and accessible means to capture patient morphology for use in clinical assessment and personalised device manufacture, specifically for ear prostheses. We also demonstrate that inexperienced operators can rapidly learn and apply smartphone photogrammetry for accurate and reliable scans of the external ear with important applications for future clinical translation.

Optical Coherence Tomography for Quantifying Human Cutaneous Chronic Graft-versus-Host Disease.

Chronic graft-versus-host disease (cGVHD) is the most common cause of nonrelapse mortality after allogeneic hematopoietic cell transplantation (alloHCT). Cutaneous cGVHD is characterized by thickening of the skin and connective tissues, causing discomfort and limited mobility. Current assessment of these skin lesions is based on physical examination of their thickening, pinchability, and movability. Optical coherence tomography (OCT) is a noninvasive, high-resolution technique using near-infrared light to interrogate tissues and image the microstructure without the use of contrast agents. We determined the applicability of OCT to human cutaneous cGVHD. Seven patients with varying degrees of cutaneous cGVHD, including 3 controls who underwent autologous HCT were prospectively examined using the cGVHD Skin (Vienna) Scale and imaged with OCT. Analysis of OCT images and clinical exams revealed that stratum corneum thickness, epidermal thickness, and depth of light transmission were correlated with cutaneous cGVHD severity in the hands, forearms, upper arms, legs, thighs, and upper back (P ≤ .03). Longitudinal OCT changes during cGVHD treatment paralleled clinical changes in the arm and upper back. OCT changes were observed in the absence of clinical changes. OCT imaging reflects the severity of cutaneous cGVHD and can be used to follow these lesions. OCT may facilitate the design of therapeutic trials in cGVHD by providing a quantitative measurement of cGVHD severity. Additional studies are needed.

A Method for Economical Smartphone-Based Clinical 3D Facial Scanning.

PURPOSE: Three-dimensional (3D) facial scanning is an emerging clinical tool to capture external anatomical features for quantitative assessment and treatment in a wide range of clinical settings. MATERIALS AND METHODS: In this study, an economical approach for rapid scanning of faces in the clinic was developed and validated to record valuable 3D patient data using smartphone cameras and photogrammetry software. Five novice operators were recruited to watch an instructional video developed on the technique before scanning 20 healthy adult participants. RESULTS: The smartphone-based photogrammetry approach produced scans with 1.3 mm (±0.3 mm) accuracy in comparison to a metrology-rated gold standard device and were 88% (±14%) complete, with no significant difference observed between operators. A moderate to strong intrarater reliability was determined for all novice operators, suggesting that first-use operators can capture consistent scans based on watching an instructional video. CONCLUSION: Smartphone photogrammetry could provide a rapid, noninvasive and economical method to capture patient morphological data for clinical assessment and personalized device manufacture. Inexperienced operators can quickly learn and utilize smartphone photogrammetry to provide accurate and reliable facial scans, essential for future clinical translation.

Past, Present, and Future of Soft-Tissue Prosthetics: Advanced Polymers and Advanced Manufacturing.

Millions of people worldwide experience disfigurement due to cancers, congenital defects, or trauma, leading to significant psychological, social, and economic disadvantage. Prosthetics aim to reduce their suffering by restoring aesthetics and function using synthetic materials that mimic the characteristics of native tissue. In the 1900s, natural materials used for thousands of years in prosthetics were replaced by synthetic polymers bringing about significant improvements in fabrication and greater realism and utility. These traditional methods have now been disrupted by the advanced manufacturing revolution, radically changing the materials, methods, and nature of prosthetics. In this report, traditional synthetic polymers and advanced prosthetic materials and manufacturing techniques are discussed, including a focus on prosthetic material degradation. New manufacturing approaches and future technological developments are also discussed in the context of specific tissues requiring aesthetic restoration, such as ear, nose, face, eye, breast, and hand. As advanced manufacturing moves from research into clinical practice, prosthetics can begin new age to significantly improve the quality of life for those suffering tissue loss or disfigurement.

Identification of Neurotoxicity after Chimeric Antigen Receptor (CAR) T Cell Infusion without Deterioration in the Immune Effector Cell Encephalopathy (ICE) Score.

A consensus grading schema for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) resulting from chimeric antigen receptor (CAR) T cell therapy was published in 2019. Although this consensus grading schema has been imperative in identifying and monitoring CRS and ICANS in our CAR T cell population, we observed patients exhibiting subtle neurotoxicity symptoms prior to a decrease in their immune effector cell (ICE) score, which is one component of ICANS. Because we treat grade 1 ICANS at our institution, identification of early neurotoxicity symptoms is important. Additionally, we found changes in personality, occupational confusion, or inability to answer dichotomous questions were early signs of neurotoxicity. Therefore, we developed a 3-step command tool to supplement the ICE evaluation. We present 2 examples of patients who exhibited early neurotoxicity symptoms and led us to develop this tool and 1 in whom it was effective. We propose that CAR T cell patients are consistently followed by a clinical care provider who is familiar with the patient to recognize early changes in personality, behavior, and cognition. Additionally, we propose that the multistep command tool be used in conjunction with the ICE score to detect early symptoms of ICANS. Early intervention has the potential to prevent irreversible neurotoxicity.

Low-Level Cytomegalovirus Antigenemia Promotes Protective Cytomegalovirus Antigen-Specific T Cells after Allogeneic Hematopoietic Cell Transplantation.

Previous studies have reported a beneficial effect from cytomegalovirus (CMV) reactivation after allogeneic hematopoietic stem cell transplantation (alloHCT) on immune reconstitution. We determined the CMV antigenemia level associated with increased CMV antigen-specific T cells (CASTs) at day +100 and decreased CMV reactivation after day +100. CMV reactivation and CASTs were measured with CMV antigenemia and CMV-specific major histocompatibility complex multimers. The analysis consisted of 775 CAST measurements obtained before and 30, 100, and 365 days post-alloHCT from 327 consecutive patients treated between 2008 and 2016. Detectable CASTs correlated with recipient (P < .0001) and donor (P < .0001) CMV seropositivity pre-alloHCT. CMV reactivation before day +100 was associated with a higher proportion of patients who achieved ≥3 CASTs/µL by day +100 (61% with versus 39% without reactivation, P < .001). In alloHCT recipients at high risk for CMV reactivation (R+D±) with a maximum of grade II acute graft-versus-host-disease, reactivating CMV before day +100 and achieving ≥3 versus <3 CASTs/µL at day +100 was associated with reduced CMV reactivation from day +100 to +365 (27% versus 62%, P = .04). This protective effect was observed with low-level but not high-level CMV reactivation (<5 versus ≥5/50,000 polymorphonuclear leukocytes + pp65, respectively). These findings suggest low-level CMV reactivation may be beneficial and that treatment may be delayed until progression. These findings will need validation in prospective clinical trials using CMV PCR and antigenemia assays.

An advanced prosthetic manufacturing framework for economic personalised ear prostheses.

Craniofacial prostheses are commonly used to restore aesthetics for those suffering from malformed, damaged, or missing tissue. Traditional fabrication is costly, uncomfortable for the patient, and laborious; involving several hours of hand-crafting by a prosthetist, with the results highly dependent on their skill level. In this paper, we present an advanced manufacturing framework employing three-dimensional scanning, computer-aided design, and computer-aided manufacturing to efficiently fabricate patient-specific ear prostheses. Three-dimensional scans were taken of ears of six participants using a structured light scanner. These were processed using software to model the prostheses and 3-part negative moulds, which were fabricated on a low-cost desktop 3D printer, and cast with silicone to produce ear prostheses. The average cost was approximately $3 for consumables and $116 for 2 h of labour. An injection method with smoothed 3D printed ABS moulds was also developed at a cost of approximately $155 for consumables and labour. This contrasts with traditional hand-crafted prostheses which range from $2,000 to $7,000 and take around 14 to 15 h of labour. This advanced manufacturing framework provides potential for non-invasive, low cost, and high-accuracy alternative to current techniques, is easily translatable to other prostheses, and has potential for further cost reduction.

Advancements in Soft-Tissue Prosthetics Part B: The Chemistry of Imitating Life.

Each year, congenital defects, trauma or cancer often results in considerable physical disfigurement for many people worldwide. This adversely impacts their psychological, social and economic outlook, leading to poor life experiences and negative health outcomes. In many cases of soft tissue disfigurement, highly personalized prostheses are available to restore both aesthetics and function. As discussed in part A of this review, key to the success of any soft tissue prosthetic is the fundamental properties of the materials. This determines the maximum attainable level of aesthetics, attachment mechanisms, fabrication complexity, cost, and robustness. Since the early-mid 20th century, polymers have completely replaced natural materials in prosthetics, with advances in both material properties and fabrication techniques leading to significantly improved capabilities. In part A, we discussed the history of polymers in prosthetics, their ideal properties, and the application of polymers in prostheses for the ear, nose, eye, breast and finger. We also reviewed the latest developments in advanced manufacturing and 3D printing, including different fabrication technologies and new and upcoming materials. In this review, Part B, we detail the chemistry of the most commonly used synthetic polymers in soft tissue prosthetics; silicone, acrylic resin, vinyl polymer, and polyurethane elastomer. For each polymer, we briefly discuss their history before detailing their chemistry and fabrication processes. We also discuss degradation of the polymer in the context of their application in prosthetics, including time and weathering, the impact of skin secretions, microbial growth and cleaning and disinfecting. Although advanced manufacturing promises new fabrication capabilities using exotic synthetic polymers with programmable material properties, silicones and acrylics remain the most commonly used materials in prosthetics today. As research in this field progresses, development of new variations and fabrication techniques based on these synthetic polymers will lead to even better and more robust soft tissue prosthetics, with improved life-like aesthetics and lower cost manufacturing.

Advancements in Soft-Tissue Prosthetics Part A: The Art of Imitating Life.

Physical disfigurement due to congenital defects, trauma, or cancer causes considerable distress and physical impairment for millions of people worldwide; impacting their economic, psychological and social wellbeing. Since 3000 B.C., prosthetic devices have been used to address these issues by restoring both aesthetics and utility to those with disfigurement. Internationally, academic and industry researchers are constantly developing new materials and manufacturing techniques to provide higher quality and lower cost prostheses to those people who need them. New advanced technologies including 3D imaging, modeling, and printing are revolutionizing the way prostheses are now made. These new approaches are disrupting the traditional and manual art form of prosthetic production which are laborious and costly and are being replaced by more precise and quantitative processes which enable the rapid, low cost production of patient-specific prostheses. In this two part review, we provide a comprehensive report of past, present and emerging soft-tissue prosthetic materials and manufacturing techniques. In this review, part A, we examine, historically, the ideal properts of a polymeric material when applied in soft-tissue prosthetics. We also detail new research approaches to target specific tissues which commonly require aesthetic restoration (e.g. ear, nose and eyes) and discuss both traditional and advanced fabrication methods, from hand-crafted impression based approaches to advanced manufactured prosthetics. We discuss the chemistry and related details of most significant synthetic polymers used in soft-tissue prosthetics in Part B. As advanced manufacturing transitions from research into practice, the five millennia history of prosthetics enters a new age of economic, personalized, advanced soft tissue prosthetics and with this comes significantly improved quality of life for the people affected by tissue loss.

Design tools for patient specific and highly controlled melt electrowritten scaffolds.

Melt electrowriting (MEW) has grown in popularity in biofabrication research due to its ability to fabricate complex, high-precision networks of fibres. These fibres can mimic the morphology of a natural extracellular matrix, enabling tissue analogues for transplantation or personalised drug screening. To date, MEW has employed two different collector-plate modalities for the fabrication of constructs. Flat collector plates, typical of traditional 3D printing methods, allow for the layer-by-layer fabrication of 2D structures into complex 3D structures. Alternatively, rotating mandrels can be used for the creation of tubular scaffolds. However, unlike other additive manufacturing techniques that can immediately start and stop the extrusion of material during printing, MEW instead requires a continuous flow of polymer. Consequently, conventional g-code control software packages are unsuitable. To overcome this challenge, a suite of customised pattern generation software tools have been developed to enable the design of MEW scaffolds with highly-controlled geometry, including crosshatch, gradient porosity, tubular, and patient-specific configurations. The high level of design control using this approach enables the production of scaffolds with highly adaptable mechanical properties, as well as the potential to influence biological properties for cell attachment and proliferation.

KIR B donors improve the outcome for AML patients given reduced intensity conditioning and unrelated donor transplantation.

Natural killer (NK) cell recognition and killing of target cells are enhanced when inhibitory killer immunoglobulin-like receptors (KIR) are unable to engage their cognate HLA class I ligands. The genes of the KIR locus are organized into either KIR B haplotypes, containing 1 or more activating KIR genes or KIR A haplotypes, which lack those genes. Analysis of unrelated donor (URD) hematopoietic cell transplants (HCT), given to acute myeloid leukemia (AML) patients between 1988 and 2009, showed that KIR B haplotype donors were associated with better outcomes, primarily from relapse protection. Most of these transplants involved marrow grafts, fully myeloablative (MAC) preparative regimens, and significant HLA mismatch. Because the practice of HCT continues to evolve, with increasing use of reduced intensity conditioning (RIC), peripheral blood stem cell grafts, and better HLA match, we evaluated the impact of URD KIR genotype on HCT outcome for AML in the modern era (2010-2016). This analysis combined data from a prospective trial testing URD selection based on KIR genotypes (n = 243) with that from a larger contemporaneous cohort of transplants (n = 2419). We found that KIR B haplotype donors conferred a significantly reduced risk of leukemia relapse and improved disease-free survival after RIC, but not MAC HCT. All genes defining KIR B haplotypes were associated with relapse protection, which was significant only in transplant recipients expressing the C1 epitope of HLA-C. In the context of current HCT practice using RIC, selection of KIR B donors could reduce relapse and improve overall outcome for AML patients receiving an allogeneic HCT.

Correction: Immune profiling in diffuse large B-cell lymphoma and mantle cell lymphoma patients treated with autologous hematopoietic cell transplant.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Immune profiling in diffuse large B-cell lymphoma and mantle cell lymphoma patients treated with autologous hematopoietic cell transplant.

This is the first longitudinal study of immune profiles and autologous hematopoietic cell transplant (AHCT) survival in B-cell non-Hodgkin lymphoma (B-NHL) patients and the effect of plerixafor mobilization on immune reconstitution in this population. A comprehensive immunophenotyping panel was performed in 104 consecutive adult B-NHL patients (58% diffuse large B cell and 42% mantle cell) who received AHCT (1/2008-11/2014), at a median of 28 days pre-AHCT (N = 104) and Day +100 (N = 83) post-AHCT. Median follow-up post-AHCT was 61 months (range: 8-120 months). Compared to patients mobilized with filgrastim and plerixafor, patients mobilized with filgrastim alone had a higher proportion of CD4+ naïve (p = 0.006) and CD8+ central memory T-cells (p = 0.006) pre-AHCT. For patients transplanted in complete remission (CR), a higher proportion of CD8+ effector memory T-cells pre-AHCT was associated with worse progression-free survival (PFS; p < 0.01) and overall survival (OS; p < 0.01). A higher ratio of CD8:CD4+ central memory T-cells pre-AHCT was associated with worse PFS (p < 0.0001) and OS (p = 0.0034). This same ratio measured post-AHCT among patients in CR on Day +100 was associated with worse and OS (p = 0.008) but not PFS (p = not significant). These immune subsets are complementary biomarkers which identify patients transplanted in CR who have poor survival prognoses and may warrant further clinical interventions.