Confirmatory Typing Research Articles

Enhancing mathematics learning with 3D augmented reality escape room

Learning mathematics is a challenge for many students, especially because of the traditionalist method with which its contents are taught. To a large extent, mathematics classes generate little motivation in students, so in this research, a novel technological method based on augmented reality is applied to improve the mathematics learning process, particularly the techniques of solving systems of linear equations. The research design used was a two-phase mixed sequential confirmatory type. The research worked with a sample of 65 students (Mage=17.72, SD=0.65; 58.5% female and 41.5% male). In the first phase, a quasi-experimental study was designed with an experimental group (M=32) and a control group (M=33). The experimental group received a mathematics teaching and learning intervention based on augmented reality vs. the control group, which received a traditional educational process. The experimental group showed improvements in acquired knowledge and motivation compared to the control group students. In the qualitative phase, two focus groups were conducted with students from their respective groups. In the experimental group, the following categories were identified: interesting, fun, innovative, and entertaining. The control group identified the following categories: little attention, low interest in learning, tired knowledge, and lack of motivation. The results are discussed in relation to the need to generate educational processes that benefit mathematics learning.

Challenges and solutions in current human leukocyte antigen confirmatory typing of hematopoietic stem cell transplantation

The impact of human leukocyte antigen (HLA) on hematopoietic stem cell transplantation (HSCT) necessitates high precision in HLA genotyping. Confirmatory typing for patients and their related or unrelated donors before HSCT is critical. This study seeks to standardize HLA confirmatory typing in laboratories by examining the current state of HLA genotyping in the country, building upon the National Standards and Industrial Standards for HLA, and highlighting the significance of confirmatory typing for patients and potential donors prior to HSCT. A retrospective analysis over a decade reveals initial typing errors, indicating potential issues and critical considerations in pre-analytical, analytical, and post-analytical stages. Problems are attributed to three main causes: (1) random human errors, including technical mistakes, sample mix-up, and transcription inaccuracies; (2) limitations of technical methods, such as the varied sequence ranges between confirmatory and initial typing; (3) patient factors, involving high tumor burden, the influence of certain drugs on HLA genotyping results, and the second transplantation. Solutions are proposed for these problems, along with recommendations to standardize HLA confirmatory typing.

Adjustment Estimation and Validation of the Addiction to Social Networks Scale Using the SEM Methodology

Currently, social networks serve as communication tools, but the problem of excessive usage leading to addiction is on the rise. Therefore, the purpose of this study is to validate the Social Network addiction (SNA) scale in university students. The study is developed from a quantitative approach, of an exploratory and confirmatory type. The type of sampling is non-probabilistic by self-determination, and the participation of 200 students was achieved, to whom the reason for the survey was explained, who agreed to participate voluntarily. For data analysis, the instrument was validated according to Cronbach's alpha criteria and after, for the analysis, the SEM methodology was used. The most important findings show only the conformation of a two-factor model, which includes the seven most representative items, and which are feasible to analyze in this study group. The goodness-of-fit index (GFI) value is acceptable since it exceeds the theoretical threshold greater than 0.9 and the root mean square error of approximation (RMSEA) is less than 0.05. The Tucker-Lewis index (TLI) and the norm adjustment index (NFI) are greater than 0.9. Based on the results, it can be concluded that students exhibit a strong desire for connectivity. Furthermore, they invest a significant amount of time in their online networks and experience uncertainty about how to occupy their when they are not connected.

Analysis of 3,843 Unrelated Donors (URD) for 455 Allograft Candidates Reveals Low URD Availability with Marked Racial/ Ethnic Disparities: Major Implications for Transplant Center & Registry Operations

Introduction: Although hematologic malignancies patients (pts) often require urgent transplants, the degree to which unrelated donor (URD) availability is a barrier to prompt allografting is not established. Methods: We evaluated availability of requested URDs 1/2020-12/2022, overall & by pt ancestry, in 455 consecutive adults with acute leukemia, MDS or MPN who had a formal URD search & for whom ≥ 1 URDs were pursued for confirmatory typing (CT). We also examined donor location & Donor Readiness Score (DRS; the prediction of a donor's likelihood of availability for CT) by pt ancestry. We hypothesized that URD availability is a major barrier to transplant for underserved racial/ ethnic groups & this has not improved in the post-pandemic era. Results: Of 455 pts [median age 63 yrs, range 21-81; 250/455 (55%) with acute leukemia], 74% (335/455) had European (EURO) & 26% (120/455) non-European (non-EURO) ancestry. For these 455 pts, 3,843 URDs (median age 27 yrs, range 17-61; 1,951/3,843 [51%] male) were requested for CT or simultaneous CT-workup; 71% (2,730/3,843) of URDs were for EURO & 29% (1,113/3,843) for non-EURO pts; & 56% (2,140/3,843) were from domestic & 44% (1,703/3,843) international registries. Of 2,775 URDs with an assigned DRS, the median score was 63% (range 16-94%). URDs requested for non-EURO pts were more likely to be domestic [EUROs: 1,411/2,730 (52%) vs non-EUROs: 729/1,113 (65%), p < .001]. Also, URDs for non-EUROs had markedly lower median DRS (EUROs: 71% vs non-EUROs: 52%) with over 15x the proportion with DRS ≤ 30% [EUROs: 30/2,073 (1.5%) vs non-EUROs: 160/702 (23%), p < .001]. Table 1A-C outlines URD availability at CT & workup, overall & by pt ancestry. In summary: At CT, per pt: More non-EURO pts had greater than 10 URDs requested (p = .045), less than 5 URDs that agreed to CT (p < .001), & at least 5 URDs unavailable (p < .001), compared with EUROs.At workup, per pt: For over one-quarter (134/455, 29%), 3-5 URDs were requested. More non-EURO pts had less than 2 URDs that agreed to workup (p = .007) & at least 2 URDs unavailable (p = .017), compared with EUROs.At CT: Only half (2,036/3,843, 53%) of requested URDs were available for CT or CT-workup. URDs were less likely to agree to CT if requested for non-EURO pts ( vs EUROs), if domestic ( vs international), or if lower DRS (p < .001 for each).At workup: Of URDs requested for workup after CT, while 461/598 (77%) agreed, URDs requested for non-EURO pts were less likely to agree (p < .001).Overall: Availability of the 3,843 URDs requested for the 455 pts was low, with less than half available (Fig. 1A). Notably, URDs requested for non-EURO pts had lower availability (p < .001).By ancestry sub-type: African & non-Black Hispanic pts had the lowest URD availability.Over time: When examining 2020-2022, the worse URD availability for non-EURO pts is not improving in the post-pandemic era (Fig. 1B).URD provision: Of pts with ≥ 1 URD who agreed to workup, 12% did not have an URD available within 14 days of the 1st proposed collection date, & of 263 5-8/8 URD recipients for whom a primary URD was selected, over one third (103/263, 39%) were not transplanted with that donor. Of transplanted pts, as expected, non-EURO pts were less likely to receive 8/8 URDs (p < .001) &, for those who did, their URDs were older (p = .018), & 5-7/8 URDs requested for non-EUROs were more HLA-mismatched (p < .001). Conclusions: We demonstrate significant ongoing disparities in URD access that have major implications for transplant center & registry operations. Incorporating careful assessment of pt ancestry, transplant centers should pursue, & registries should permit, simultaneous pursuit of multiple URDs, especially for non-EURO pts, deciding at the outset what degree of HLA-mismatch will be accepted if an URD is desired but an 8/8 URD is unlikely (Davis et al, TCT 2023). Moreover, centers are ethically obliged to inform pts if timely URD procurement is unlikely, especially as these pts are commonly from underserved racial/ ethnic groups. Registries need to address high URD attrition, & prospective investigation of efforts to speed donor identification are needed. Finally, utilization of all alternative donors (5-7/8 URD, haploidentical & cord blood) is needed to facilitate donors for all in the time required for optimized transplantation.

5 years DKMS Chile: approach, results and impact of the first unrelated stem cell donor center in Chile.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is performed worldwide to treat blood cancer and other life-threatening blood disorders. As successful transplantation requires an HLA-compatible donor, unrelated donor centers and registries have been established worldwide to identify donors for patients without a family match. Ethnic minorities are underrepresented in large donor registries. Matching probabilities are higher when donors and patients share the same ethnic background, making it desirable to increase the diversity of the global donor pool by recruiting donors in new regions. Here, we report the establishment and the first 5 years of operation of the first unrelated stem cell donor center in Chile, a high-income country in South America with a population of over 19 million. We used online and in-person donor recruitment practices through patient appeals and donor drives in companies, universities, the armed forces, and public services. After confirmatory typing donors were subjected to medical work-up and cleared for donation. We recruited almost 170,000 donors in 5 years. There were 1,488 requests received for confirmatory typing and donor availability checks, of which 333 resulted in medical work-up, leading to 194 stem cell collections. Products were shipped to Chile (48.5%) and abroad. Even when the COVID-19 pandemic challenged our activities, the number of donors recruited and shipped stem cell products remained steady. In Chile there was an almost 8-fold increase in unrelated donor transplantation activity from 16 procedures in 2016-2018 to 124 procedures in 2019-2021, mainly for pediatric patients following the center's establishment. We estimate that 49.6% of Chilean patients would find at least one matched unrelated donor in the global DKMS donor pool. Establishing a DKMS donor center in Chile has significantly increased donor availability for Chilean patients and contributed to an increase of unrelated donor stem cell transplant activity.

Systemic AL amyloidosis: current approach and future direction

Systemic Light chain (AL) amyloidosis is a monoclonal plasma cell proliferative disorder characterized by deposition of amyloidogenic monoclonal light chain fragments causing organ dysfunction. It is a fatal disease and if not diagnosed and treated early can lead to organ failure and potentially death. The renal system along with the cardiovascular system are the most common organs involved but other organs such as gut and liver can be involved as well. The initial evaluation of patients requires confirming the diagnosis with tissue biopsy and staining with Congo red followed by confirmatory typing with mass spectrometry of the Congo red positive tissue. Then establishing the extent of the organs involvement by various staging and biomarkers testing. The treatment options and the tolerability of therapy depend on the disease staging, frailty, and co-morbidities. The autologous hematopoietic cell transplantation (HCT) after high dose melphalan therapy is an effective strategy which is usually done after initial bortezomib induction therapy. Unfortunately, most systemic AL amyloidosis patients are not candidate for HCT due to frailty, old age, multi-organ involvement, renal and heart failure at the time of diagnosis. While it is widely accepted that the patients need to be treated until they achieve complete hematologic response, the maintenance therapy after HCT is not well established in AL amyloidosis. In this review, we report the literature on the latest treatment updates of AL amyloidosis and the ongoing clinical trials highlighting the future treatments.

Development of Poland's Central Bone Marrow Donor Registry Affects Donor Searches for Patients With Hematological Diseases

In the last 10 years, numbers of donors in the case of Polish potential unrelated hematopoietic stem cells (HSC) have increased dynamically, reaching 1,900,000 in 2020 (including donors presented in World Marrow Donor Association as PL6). On the world scale, the share of Polish donors in the global registry increased from 1% in 2010 to about 5% in 2020. The level and range of typing of potential donors has also been improving steadily toward the international "gold standard." At the end of 2020, 92% of Polish resources were at least HLA-A, B, C, DR, DQ high- or intermediate-resolution typed, mostly by way of genomic typing techniques, mostly by way of genomic typing techniques. The Central Bone Marrow Donor Registry (CBMDR) also stands out in terms of the young ages of potential donors. As of 2020, 27.2% of those registered were younger than 30 years of age, and 36.3% were aged between 30 and 40 years. Sixty percent of registered donors were female. The data in question were presented at the World Marrow Donor Association Search & Match Service, ensuring their visibility and accessibility to Polish and international search units and registries. In 2020, donors in Poland were the subject of almost 18,000 search requests from 40 countries, with 271 extended typing requests and more than 7600 confirmatory typing requests. The total number of donations from Polish donors also increased. In 2020, HSC of bone marrow, peripheral blood, or lymphocytes were collected from 1391 donors, as opposed to 94 donors in 2010. The growing number of donors available in the CBMDR means a better chance of a donor being found among Polish resources, without any need to resort to international registers. Although in 2010, just 24% of Polish recipients received HSC from Polish donors, by 2019 the figure was as high as 67%, and reached 63% in 2020. The CBMDR is an example of proper strategy on registry development being implemented in Poland.

Turn around time in matched unrelated donor search workup national versus international registries: Retrospective study

Background: Timeline is a key factor for hematopoietic stem cell transplant (HSCT) recipient. HSCT by matched unrelated donor (MUD) is a standard definitive therapeutic approach for many hematological disorders which are not amenable to chemotherapy and other conventional treatment. Aims and Objectives: The aim of the present study was to compare the turnaround time (TAT) involved in completion of MUD HSCT workup from an Indian registry (Genebandhu) with international registries. Materials and Methods: On receipt of pre-transplant matching request through a transplant physician, patient's human leukocyte antigen (HLA) type was entered in both Genebandhu and World Marrow Donor Association search tool for initiating a “search.” The software gave the descending order of the best possible matches by performing computational analysis. The search result was considered a “match” when potential 10/10 HLA match was found. The average TAT was calculated in the middle of search request and HLA confirmatory typing (CT) and infectious disease marker (IDM). Further, TAT was also determined between the infusion of harvested stem cell product and CT and IDM. At last, the total time engaged in completion of each MUD HSCT workup was determined and compared in national versus international registries. Results: The average TAT involved in between search request and CT and IDM was 71 days in case of global registry and 67 days in case of Genebandhu. Similarly, the average TAT involved between infusion of harvested cell product and CT and IDM testing in case of donor identified in global stem cell registry was 65 days whereas 45 days in case of Genebandhu. At last, the average time associated with the finishing of a MUD workup was 136 days in case of global registry, whereas 112 days in the case of Genebandhu at P ≤ 0.05 with a 95% confidence interval. Conclusion: To conclude, the average TAT obtained through this study clearly demonstrates the advantages in terms of donor availability for MUD HSCT through the national registry.

Determinant Factors in Influencing Purchase Intention and Word of Mouth in Social Commerce: An Indonesia Case Study

Social media becomes the new reality perceived in the present generation. Further, the role of social network has extended to which the people can do business transactions in its platform. The present research explores the role of purchase intention and word of mouth to understand better how consumers behave. A total of 9 factors are used in this research model. A total of 8 hypotheses are investigated. The present study uses factor analysis with the confirmatory type to see the correlational factors. The Structural Equation Model (SEM) is used to see the path and hypotheses validation. A total of 231 respondents have participated in this research. The result shows that 5 out of 8 hypotheses are accepted. The present model exposes a total of 70 and 51 percent R2 for both PI and WOM, which indicates the overall model can capture the excellent representation of consumer behavior assessment. Practical and implication insights are further discussed in this paper.

Adoptive Immunotherapy with Cord Blood (CB) Grafts Targeting Shared Inherited Paternal Antigens (IPA) and/or Non-Inherited Maternal Antigens (NIMA) during Induction Treatment for High Risk Myeloid Malignancies: Safety and Preliminary Results

BackgroundSeveral groups have reported use of haploidentical peripheral blood donor cells as adjunct to chemotherapy in remission induction of myeloid leukemia (Colvin et al, BBMT 2009, Gue et al, Blood 2011). Moreover, CB grafts have been associated with greater disease control and enhanced graft-versus-leukemia responses, as a consequence of the fetal-maternal interactions during pregnancy (van Rood et al, PNAS 2009 and PNAS 2012).We evaluated prospectively the feasibility and tolerability of infusing partially HLA matched cord blood units (CBUs) with specific alloreactive properties after salvage chemotherapy to patients (pts) with refractory myeloid leukemia.Patients and MethodsPts with confirmed diagnosis of AML or MDS, according to WHO classification (excluding acute promyelocytic leukemia) who had received two or more previous induction/re-induction regimens were eligible. All pts were treated at NYPH and all CBUs were obtained from the NCBP. The study was performed under FDA IND and was approved by the IRBs of both institutions. Pts received induction chemotherapy followed by CBU infusion (1-3 days later) without any immunosuppression.CBUs eligible for the study contained a pre-cryopreservation Total Nucleated Cell (TNC) dose of 0.5-2.5x107/kg. They were HLA matched at 4-6/6, HLA-A, -B intermediate resolution, -DRB1 high resolution. CBUs had undergone HLA typing of the mother, thus allowing determination of the paternal and maternal antigens. CBUs with shared IPA targets and/or NIMA match were selected for cell therapy.ResultsA total of 34 patients underwent CBU search. Mean CBU number per search was 134 (range: 7-250) with 58% potentially eligible CBUs per pt (range: 5-159). A total of 143 CBUs underwent testing including HLA confirmatory typing. At least one eligible CBU was identified for each pt. Higher HLA allele level match was preferred in the final selection.Of the 34 pts, 23 did not receive treatment because of progressive disease and death (n=8); other clinical trials/treatments (n=6); hematopoietic stem cell transplants (HSCT) (n=9); while one is currently undergoing evaluation. Ten pts have been treated (Table); 8 had AML, 7 with primary induction failure (PIF); one had myeloid blast phase CML and one with high risk MDS. Nine pts had poor risk karyotype and 4 had prior allografts. Median age was 52 years (range: 34-67); median number of prior treatments was 11 (2-15) and median HSCT-CI was 3 (0-7).Of the CBUs infused, six were 5/6 and four were 4/6 HLA matched. The allele level compatibility and presence of shared IPA targets and/or NIMA matches are shown in the Table. CBU median TNC was 90x107 (range: 63-151) and they tended to be “older” with a median cryopreservation time of 10 years. CBUs provided a mean cell dose of 1.66 x 107 TNC/kg (range: 1.1-2.4). Mean post-thaw CD34+ and CD3+ cell doses were 52x103/kg (range: 20-90) and 0.34x107/kg (range: 0.24-0.52; SD: 0.08), respectively, with excellent post-thaw CD34+ viability (93.5%-98.3%).No CBU infusion reactions or cytokine release syndrome were observed. One pt, recipient of a prior allograft with no history of GVHD, experienced skin rash 1 week after CBU infusion. The skin biopsy was consistent with GVHD. No GVHD was observed in the other 9 pts. One pt died of disseminated adenovirus infection early after treatment; viremia was present at the initiation of chemotherapy.Transient CBU chimerism was detected in 5 of the 10 pts as early as one week and as late as 6 months after CBU infusion. Four pts with median pre-treatment BM blast counts of 56% (range 13-94) had objective hematologic responses (Cheson B JCO 2003) with median post-treatment blast counts of 0% (range 0-12), 3 with morphologic leukemia free state and one with a partial response. One patient had aplastic marrow but with flow cytometry evidence of persistent leukemia; while 4 pts recovered with morphologic persistent leukemia. Six pts went on to receive HSCT. Two subsequently relapsed and one died of disseminated adenovirus, while 3 pts remain in remission.ConclusionUse of CBUs as adoptive immunotherapy for pts with refractory myeloid leukemia represents a safe, well tolerated treatment, in which the potential for alloreactivity can be enhanced through the selection of CBUs by targeting shared IPA and NIMA present in the patients. Further, smaller CBUs, unlikely to be adequate grafts for adult transplantation, can be utilized for cell therapy. [Display omitted] DisclosuresRoboz:Cellectis: Research Funding; AbbVie, Agios, Amgen, Amphivena, Array Biopharma Inc., Astex, AstraZeneca, Celator, Celgene, Clovis Oncology, CTI BioPharma, Genoptix, Immune Pharmaceuticals, Janssen Pharmaceuticals, Juno, MedImmune, MEI Pharma, Novartis, Onconova, Pfizer, Roche Pharmace: Consultancy. Ritchie:Celgene: Consultancy, Other: Travel, Speakers Bureau; Pfizer: Consultancy, Other: Research funding to my institution; Incyte: Consultancy, Speakers Bureau; Astellas Pharma: Other: Research funding to my institution; NS Pharma: Other: Research funding to my institution; Bristol-Myers Squibb: Other: Research funding to my institution; Novartis: Consultancy, Other: Research funding to my institution, and travel, Speakers Bureau. Lee:Amgen: Consultancy; Baxalta: Consultancy; Clinipace: Consultancy; Alexion Pharmaceuticals: Consultancy.

Stem cell donor registry activities during the COVID-19 pandemic: a field report by DKMS

The COVID-19 pandemic has serious implications also for patients with other diseases. Here, we describe the effects of the pandemic on unrelated hematopoietic stem cell donation and transplantation from the perspective of DKMS, a large international donor registry. Especially, we cover the development of PBSC and bone marrow collection figures, donor management including Health and Availability Check (HAC), transport and cryopreservation of stem cell products, donor recruitment and business continuity measures. The total number of stem cell products provided declined by around 15% during the crisis with a particularly strong decrease in bone marrow products. We modified donor management processes to ensure donor and product safety. HAC instead of confirmatory typing was helpful especially in countries with strict lockdowns. New transport modes were developed so that stem cell products could be safely delivered despite COVID-19-related travel restrictions. Cryopreservation of stem cell products became the new temporary standard during the pandemic to minimize risks related to transport logistics and donor availability. However, many products from unrelated donors will never be transfused. DKMS discontinued public offline donor recruitment, leading to a 40% decline in new donors during the crisis. Most DKMS employees worked from home to ensure business continuity during the crisis.

Substituting imputation of HLA antigens for high-resolution HLA typing: Evaluation of a multiethnic population and implications for clinical decision making in transplantation.

Molecular mismatch analysis for assessment of histocompatibility in transplantation requires high-resolution HLA typing. Algorithms to "guesstimate" high-resolution from low-resolution typing exist, but their accuracy remains unknown. We converted high-resolution, sequence-based, HLA typing of 310 subjects from an ethnically heterogeneous population to low-resolution equivalents and tested the ability of the NMDP HaploStats and HLA Matchmaker programs to impute/reproduce the measured high-resolution HLA type, using the more common "winner-takes-all" approach. Only 35.6% of the HaploStats imputed HLA-A, -B, -C, -DRB1, and -DQB1 haplotypes had no mistakes, and the accuracy was significantly lower for non-Caucasians (29.1%) compared to Caucasians (45.2%) (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.3-0.8; P=.004). HLA Matchmaker was not able to provide high-resolution haplotypes for 45.2% of Caucasian subjects and 63.5% of non-Caucasian subjects (P=.002). Of those with an imputed result, only 10.3% of Caucasians and 4.8% of non-Caucasians had accurate 10-allele high-resolution output. Eplet analysis revealed additional, inaccurate eplets in 37% of individuals, with 22.5% showing at least 2 additional, inaccurate eplets; incorrect eplets were more common among non-Caucasians (OR, 1.8; 95% CI, 1.1-2.9; P=.018). Given this high error rate, caution should be taken before using imputation tools for clinical or research purposes, especially for non-Caucasian individuals.

Cord Blood Unit (CBU) search and distribution to Transplant Centers (TC): real-life experience from the National Cord Blood Program (NCBP)

Background & Aim One of the most important attributes of cord blood is the prompt availability of high quality cell therapy products for clinical use. To achieve this, the NCBP has implemented a strong infrastructure supporting CBU search, selection, review and release. The key components include: - Fully integrated IT system for running searches in real-time, generating reports, receiving/sharing results and documents - Streamlined procedures for management of search requests - Expert review and search flexibility - Verification of product quality - Timely CBU release to TC - Expertise in regulatory requirements and shipment logistics Methods, Results & Conclusion We describe our recent clinical activity (period: 04/2016-12/2019) following this strategy. Our dedicated website, WebSearch, is used for CBU reservations directly by TC or requests received via registries (National Marrow Donor Program [NMDP] or International Registries). During the study period, 3943 CBU were reserved for 2831 patients from 153 TC. All reservations trigger full review of CBU information as well as confirmatory HLA typing (CT), effectively preparing the reserved CBU for shipment. Each patient's search is reviewed by a medical and an HLA expert within 48 hours to identify the best CBU and share recommendations with the TC. Further, the system is flexible, allowing “customized” searches that include TC's own selection criteria such as high CD34 counts, HLA requirements (allele level matching, patient's anti-HLA antibodies, maternal HLA), eligibility, CBU storage time, and various clinical study specifications. High resolution CT results are obtained routinely within 6 business days. All units with available segments are evaluated for potency (CD34/CD45 counts and viability and CFU) at reservation and/or shipment. During this period, 514 CBU were shipped for 501 patients to 91 TC; 53% were facilitated by the NMDP and the remaining were direct shipments. 170 CBU went to 23 International TC in 20 countries. Average time between shipment request and shipment was 5 business days (Figure 1). TC's shipment schedule requirements were met in all cases. With over 60,000 CBU available, the NCBP Inventory holds almost 8% of the world's unrelated CBU, including 11,100 FDA licensed products (HEMACORD®). The flexibility and efficiency of the search and review procedures, as well as the fact that 10% of the CBU have CT already performed and are “ready to ship”, enable us to process routine or emergency shipment requests expeditiously.

The role of prospection in altruistic bone marrow donation decisions.

The decision to become an unrelated allogeneic bone marrow or hematopoietic stem cell (HSC) donor is a consequential and complex one. Although new registry members pledge to donate if asked in the future, significant proportions ultimately reconsider when they are notified as a potential match for a patient and are asked to undergo confirmatory typing (CT), resulting in many patients failing to receive transplants. We consider the roles of prospection, or thinking about the future, and ambivalence, or having mixed emotions about an event, in this phenomenon. Prospection theory dictates that distant and improbable events are construed more abstractly than near-term and probable events. We hypothesized that construals about donation in new registry members versus those asked to undergo CT would differ in accordance with these patterns, and that variation in construals would be associated with decisions about whether to proceed toward donation. In collaboration with the National Marrow Donor Program, we measured donation intentions and CT decisions in 516 new registry members and 213 members asked to undergo CT, respectively. Participants were asked to describe what they imagined would happen in the donation process. We found that the valence and heterogeneity with which registry members construed donation were significant predictors of donation-related decisions. Assuming the temporal ordering of cognitive processes, ambivalence about donation was a mediator of these relationships. Findings suggest that encouraging a focus on positive central features of marrow and HSC donation may reduce ambivalence and decrease attrition from the registry. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Ciprofloxacin Resistant Salmonella Typhi Isolated at National Microbiology Reference Laboratory in Harare, Zimbabwe (January to April 2016)

Background: Typhoid is a life-threatening infectious disease requiring the administration of antibiotics for treatment. Ciprofloxacin is the antibiotic of choice for diarrheal cases in Zimbabwe, adopted by the Ministry of Health and Child Care, from current World Health Organisation (WHO) guidelines. However, there has been an increase in the emergence and spread of multidrug resistance against ciprofloxacin and conventional drugs antibiotics for the treatment of typhoid. Objective: This cross-sectional study aimed to determine the prevalence of ciprofloxacin-resistant Salmonella Typhi (S. Typhi) isolated in Harare for the first quarter of 2016. Methods: This study was carried out at the National Microbiology Reference Laboratory (NMRL), located at Harare Central Hospital, in Zimbabwe. The NMRL carries out confirmatory tests and molecular typing of pathogens isolated at different national laboratories. The current study retrieved demographics, clinical data, and isolates for confirmed typhoid cases out of 402 suspected specimens. The isolates from Harare, confirmed as S. Typhi, between January and April 2016, were evaluated for ciprofloxacin resistance. Results: A total of 35 S. Typhi isolates were recovered for the period from January to April 2016. When the 35 isolates were characterised, nine (25.7%) were resistant to ciprofloxacin. The area with the highest recorded cases of typhoid fever was Budiriro High-Density Suburb in Harare. This area has been hit by other diarrheal outbreaks in the past, most likely due to the intermittent supply of safe water. Conclusion: Most high-density areas, where S. Typhi positive specimens originated, are overpopulated and have regular water cuts, resulting in a decrease in hygiene. More than a quarter of isolates are resistant to ciprofloxacin, agreeing with other reports from Zimbabwe. The misuse of antibiotics could be associated with resistance, necessitating education on the correct use of antibiotics in the community and other preventive measures. Additionally, molecular research on geographic and phylogenetic relatedness of isolates and other holistic approaches for studying the development of antimicrobial resistance mutations, using whole-genome sequencing, in this setting, are warranted.

Identification and Utilization of Pre-Search Killer Cell Immunoglobulin-Type Receptor (KIR) B(x) Unrelated Donors Improves the Selection of KIR Favorable Donors, the Transplant Coordinator Perspective

Background KIR B(x) haplotype donors have been reported to improve outcomes in patients (pts) receiving unrelated donors (URD) for myeloid malignancies, non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). Donors are categorized as KIR “Best” or “Better”. Our center performs donor KIR genotyping and haplotype assignment routinely as part of our URD evaluation for pts undergoing transplantation for myeloid disorders, NHL and MM. When presented with multiple equivalently HLA matched URDs, our physicians will prioritize KIR B(X) donors over KIR A/A donors. Weisdorf et. al. (BBMT 2018) suggested that pre-search donor KIR genotyping would accelerate/optimize donor selection. Since 2015, donor KIR genotyping data for > 3 million donors from the DKMS registry is available. We investigated our ability to enhance KIR-favorable donor selections using the DKMS pre-search KIR. Methods In 2018 we requested access to individual KIR donor typing through the National Marrow Donor Program (NMDP) Scientific Services for donors registered by DKMS Germany, DKMS Poland and obtained access to the DKMS Donor Navigator website. Pts with multiple suitable donors were sorted for KIR, if registered by DKMS. Up to 6 donors per patient were selected from the pre-search KIR B(x) donors who ranked KIR “Best”, “Better” and “Neutral”. For pts whose pre-search screen did not identify an adequate number of KIR B(x) informative donors we selected additional donors (KIR unknown) for confirmatory typing. Results Thirty-five pts had informative KIR B(x) pre-search donors identified. There were 1-27 KIR B(x) available donors per pt. The online KIR B Content Calculator ranked these donors as KIR “Best”, “Better”, or “Neutral”. Donors were selected by the physicians, who were unaware of the pre-search ranking. As of Oct 2019, 23 pts were transplanted, 4 are pending. Of these 27 donors selected, 18 were identified in the pre-search group. Six donors (33%) were ranked KIR B “Best”, 10 (55%) “Better”, and 2 (11%) “Neutral”. Nine pts used donors without a pre-search. Five pts did not proceed to an URD transplant, and 3 pts have ongoing searches. Using the pre-search information, 66% of pts received a KIR B(x) donor and we were able to enrich KIR B(x) “Best” and “Better” donor options. Based on registry data, approximately 11%, 20% and 69% of donors randomly selected from a donor registry will be ranked KIR “Best”, “Better” and “Neutral “respectively. For our pt population, we were able to more than double the selection of KIR “Best” and “Better” donors for transplantation. Conclusion The inclusion of KIR donor genotyping on donor registries enriches the number of preferred KIR B (x) donors available and allows a more efficient selection of KIR “Best” and “Better” donors.

P034 Next generation sequencing - the ultimate tool for confirmatory HLA typing in cadaveric donors? A case report

P034 Next generation sequencing - the ultimate tool for confirmatory HLA typing in cadaveric donors? A case report

A Pilot Study: Identification and Reduction of Barriers for Unrelated Allogeneic Hematopoietic Stem Cell Transplantation in Patients with High-Risk Hematologic Malignancies

The timeliness to Hematopoietic Stem Cell Transplant (HSCT) as a potential curative treatment for patients with high-risk hematologic malignancies such as acute leukemias, refractory disease, progressive disease, or other poor prognostic disease specific indications has been well established [3]. Timing is crucial from date of diagnosis, initiation of induction therapy, donor identification and transplantation. Any delay can provoke unfavorable patient outcomes and reinforces the critical need to reduce barriers for timeline to transplant [1]. Unrelated allogeneic HSCT pose greater risks due to the complexity of donor barriers versus match/mismatched related donor transplants [1]. Key factors resulting in delayed unrelated donor transplantation include; poor donor match probabilities – lack of ethnic minority populations or patients with rare allelic haplotype associations, low resolution Human Leukocyte Antigen (HLA) typing in donor registry, limited donor availability, lack of donor health history information, unknown infectious disease markers results, etc. [4]. Other potential areas for significant delay include time requirements for allele level HLA resolution, final donor selection and donor workup process. Given the high-risk patient population, identified existing donor barriers and finite window of opportunity for favorable HSCT outcomes; our center proposed a pilot study in conjunction with the National Marrow Donor Program (NMDP) to reduce barriers for rapid donor identification, selection and workup. The main objective of the proposed study was to identify and select a workup ready unrelated donor within 14 days of search initiation. Selected high-risk patients were enrolled in the pilot program from September 2016 through March 2018 (N = 25). Throughout the pilot study our center was able to identify areas of process improvement within our collective transplant program. Process improvements were also established in collaboration with the NMDP and their respective donor centers and collection centers. Following the completion of the study, we retrospectively analyzed our center's transplant data from 2017 and compared the time to transplant for pilot study patients (n = 15) versus all primary unrelated donor transplants (n = 100) performed, with the exclusion of cord blood unit transplants. We were able to obtain donor confirmatory typing appointments with a median of 7 days from formal search initiation. We were also able to reduce the median days for formal search to workup for the pilot study donors to 28 days versus 56 days, and the median days for formal search to donor collection to 35 days versus 97 days. Although we did not meet our proposed primary objective of 14 days, our center was able to successfully reduce the time needed to identify, select, and collect an unrelated donor for transplantation using the expedited process.

P014 Next generation sequencing is capable of detecting contaminating alleles from malignancy for a bone marrow transplant recipient

HLA typing using Next Generation Sequencing (NGS) for bone marrow transplant (BMT) patients has been recognized to outperform traditional molecular typing methodologies in detecting contaminating alleles from malignancy. Here we report a case with ambiguous HLA typing that was clearly resolved by NGS. A 61 year old female with atypical chronic myeloid leukemia was evaluated for allogeneic BMT. Initial HLA typing by NGS on peripheral blood (PB) of the patient and her 2 siblings showed that one sibling was most likely HLA identical, and the other was haplo-identical to the patient, except an extra HLA-DRB1* allele was detected in the patient. NGS presented a mixture of DRB1*03:01 and 03:16 for the patient and DRB1*03:01 only for both siblings (Table 1a). The difference between DRB1*03:01 and 03:16 is located in Exon 2 at NT 229 as C and T, respectively. The number of NGS reads (R#345) from the patients’ PB at this position showed 10 reads mapping to DRB1*03:01 and 335 to DRB1*03:16, indicating 2.9% DRB1*03:01 and 97.1% DRB1*03:16. To investigate the possible involvement of malignant cells, DNA from the patients’ buccal swab (BS) was typed by NGS and also revealed a mixture of DRB1*03:01 and 03:16. The number of NGS reads (R#543) showed 420 and 123 reads (77.3% and 22.7%) mapped to the DRB1*03:01 and 03:16, respectively (Table 1b). Confirmatory typing of the patients’ PB and BS verified the initial typing result, thus concluding the DRB1*03:16 allele originated in the malignancy of the patient. BMT was performed with the HLA identical sibling. Parallel testing by NGS typing and engraftment monitoring by short tandem repeat (STR) was performed with post-BMT PB. Interestingly, NGS analysis indicated 63.1% of DRB1*03:01 and 36.9% of DRB1*03:16, which presented a close correlation with 61% and 39% donor and recipient chimerism, respectively, as detected by STR (Table 1c). This case study highlights the great potential of NGS in detecting minor component alleles from malignancy in a semi-quantitative manner.

The challenge of discriminating between HIV-1, HIV-2 and HIV-1/2 dual infections.

Discrimination between HIV-1 and HIV-2 is important to ensure appropriate antiretroviral treatment (ART) and epidemiological surveillance. However, serological tests have shown frequent mistyping when applied in the field. We evaluated two confirmatory tests, INNO-LIA HIV I/II Score and ImmunoComb HIV 1/2 BiSpot, for HIV type discriminatory capacity. Samples from 239 ART-naïve HIV-infected patients from the Bissau HIV Cohort in Guinea-Bissau were selected retrospectively based on the initial HIV typing performed in Bissau, ensuring a broad representation of HIV types. INNO-LIA results were interpreted by the newest software algorithm, and three independent observers read the ImmunoComb results. HIV-1/HIV-2 RNA and DNA were measured for confirmation. INNO-LIA results showed 123 HIV-1 positive samples, 69 HIV-2 positive and 47 HIV-1/2 dually reactive. There was agreement between INNO-LIA and HIV-1/HIV-2 RNA and DNA detection, although not all HIV-1/2 dually reactive samples could be confirmed by the nucleic acid results. Overall, the observers found that the ImmunoComb results differed from the INNO-LIA results, with agreements of 90.4, 91.2 and 92.5%, respectively, for HIV-1, HIV-2 and HIV-1/2. The combined kappa-score for agreement between the three observers was 0.955 (z-score 35.1; P < 0.01). Of the HIV-2 mono-reactive samples (INNO-LIA), the three observers interpreted 24.6-31.9% as HIV-1/2 dually infected by ImmunoComb. None of these samples had detectable HIV-1 RNA or DNA. There was accordance between INNO-LIA calls and nucleic acid results, whereas ImmunoComb overestimated the number of HIV-1/2 dually infected patients. Confirmatory typing is needed for patients diagnosed with HIV-1/2 dual infection by ImmunoComb.