Donor Selection Research Articles

Donor selection in allogeneic stem cell transplantation.

Recent progress in human leukocyte antigen (HLA) characterization, increased accrual of unrelated donors and cord blood units, and a new platform for haploidentical transplantation have resulted in the widespread availability of donors for allogeneic hematopoietic stem cell transplantation. Advances in HLA typing have identified an increasing number of loci and alleles that are crucial for successful transplantation. Newer HLA A, B, C, DRB1, and DQB1 alleles, DPB1 mismatches, and HLA B leader sequence matching are incorporated into donor selection algorithms. Donor selection is highly relevant because of recently published conflicting studies using different donor types. These studies are largely retrospective and compare patients with different diseases and stages, conditioning regimens, graft versus host disease (GVHD) prophylaxis, and time periods. A broad consensus indicates that the best donor is an available matched sibling, followed by a matched unrelated donor, and then alternative donors such as haploidentical, mismatched unrelated, and cord blood units. This consensus is being challenged by other factors, such as donor age, patient condition, urgency of transplantation, and costs involved. In this review, we will analyze the unique characteristics of each donor type, the HLA and non HLA factors that affect donor choices, and the outstanding comparative outcome studies of different donor usage in hematologic malignancies.

Germ line ERG haploinsufficiency defines a new syndrome with cytopenia and hematological malignancy predisposition

AbstractThe genomics era has facilitated the discovery of new genes that predispose individuals to bone marrow failure (BMF) and hematological malignancy (HM). We report the discovery of ETS-related gene (ERG), a novel, autosomal dominant BMF/HM predisposition gene. ERG is a highly constrained transcription factor that is critical for definitive hematopoiesis, stem cell function, and platelet maintenance. ERG colocalizes with other transcription factors, including RUNX family transcription factor 1 (RUNX1) and GATA binding protein 2 (GATA2), on promoters or enhancers of genes that orchestrate hematopoiesis. We identified a rare heterozygous ERG missense variant in 3 individuals with thrombocytopenia from 1 family and 14 additional ERG variants in unrelated individuals with BMF/HM, including 2 de novo cases and 3 truncating variants. Phenotypes associated with pathogenic germ line ERG variants included cytopenias (thrombocytopenia, neutropenia, and pancytopenia) and HMs (acute myeloid leukemia, myelodysplastic syndrome, and acute lymphoblastic leukemia) with onset before 40 years. Twenty ERG variants (19 missense and 1 truncating), including 3 missense population variants, were functionally characterized. Thirteen potentially pathogenic erythroblast transformation specific (ETS) domain missense variants displayed loss-of-function (LOF) characteristics, thereby disrupting transcriptional transactivation, DNA binding, and/or nuclear localization. Selected variants overexpressed in mouse fetal liver cells failed to drive myeloid differentiation and cytokine-independent growth in culture and to promote acute erythroleukemia when transplanted into mice, concordant with these being LOF variants. Four individuals displayed somatic genetic rescue by copy neutral loss of heterozygosity. Identification of predisposing germ line ERG variants has clinical implications for patient and family diagnoses, counseling, surveillance, and treatment strategies, including selection of bone marrow donors and cell or gene therapy.

Advances in second hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) is a widely used treatment for malignant hematological diseases; however, some patients inevitably experience relapse. Therefore, for patients who relapse after the first HSCT (HSCT1), a standard treatment regimen must be developed. A second hematopoietic stem cell transplantation (HSCT2) is a possible treatment option. Several studies have analyzed the feasibility of HSCT2. Previous studies have shown that various factors may affect the efficacy of HSCT2, including the hematopoietic cell transplantation comorbidity index, duration of remission after HSCT1, occurrence of chronic graft-versus-host disease, and disease status before HSCT2. However, the selection of donors for HSCT2 does not affect the transplantation efficacy. HSCT2 also presents a risk of relapse, and the prognosis of patients after relapse is poor. Further research on the treatment of patients after relapse is warranted.

Blood safety markers in Dutch donors after relaxation of deferral for men who have sex with men: re-emergence of syphilis and HIV pre-exposure prophylaxis use.

Less discriminatory donor selection policies for men who have sex with men (MSM) may impact transfusion safety in terms of higher residual risks for known transfusion-transmitted infections (TTIs), increased vulnerability toward new TTIs that are also transmitted via sex, and HIV infections masked by pre-exposure prophylaxis (PrEP). TTI trends in Dutch donors were studied over a 13-year period (2011-2023), characterized by successive relaxations of MSM deferral criteria. Structured posttest counseling was performed to determine risk factors in TTI-positive donors. PrEP drug levels were measured in 9977 donations from male donors living in urban areas and in 67 donors with active or resolved syphilis. HIV incidence (from 5.8 to 1.5 per 1,000,000 donor years (DY)) and HBV incidence (from 12.4 to 4.5 per 1,000,000 DY) in Dutch donors decreased with less stringent MSM deferral criteria, while syphilis prevalence (from 26.4 to 44.1 per 100,000 new donors) and syphilis incidence (from 18.3 to 46.3 per 1,000,000 DY) increased over time. The proportion of MSM-related syphilis rose from 2% to 32% in new donors and from 12% to 27% in repeat donors. PrEP was detected in 2 of 9977 (0.02%) donations from male donors living in urban areas, and in 1 of 39 (2.6%) male donors with syphilis. To date, phasing out donor deferral for MSM had no significant impact on transfusion safety in the Netherlands. However, rising syphilis rates and (recent) PrEP use in the blood donor population, albeit rare, suggest an influx of donors with higher sexual risk profiles and requires intensified TTI surveillance in donors.

The Efficiency of Volumetry in Graft Weight Assessment in Living Donor Liver Transplant

Abstract Background Liver transplantation is the treatment of choice for end-stage hepatic diseases. The most important factor responsible for the success of the transplant is the size of the graft and the remnant liver volume in the donor. A small graft may not meet the metabolic demands of the recipient resulting in impaired liver functions such as hyperbilirubinemia, prolonged prothrombin time (PT), ascites and portal hypertension. Patient and Methods This comparative study was conducted on manual contrast enhanced hepatic CT scans of 40 potential living liver donors (29) male and (11) female Age range from (18 to 50 ) in Ain shams specialized hospital and some private centers during the period from May 2021 till July 2022. The potential donors were investigated using 16 channel multi-detector row CT scanner (Alexion; Toshiba medical systems). All potential donors underwent 1st step laboratory investigations to enter the 2nd step investigations for living donor liver transplantation operations. All potential donors were of average weight and physically fit for operation with no history of any medical diseases. Results We correlated the results of CT volumetry of right lobe graft weight with the intra-operative weight of liver graft in patients undergoing Living Donor Liver Transplantation(LDLT). CT Volumetry is an efficient and a reliable tool for assessing potential donors undergoing liver transplant, and this information is essential for donor selection and pre operative surgical planning as well as it ensure that the liver remnant volume is at least 30 % which guarantee the safety of the donor. Conclusion The size of the right lobe graft for LDLT can be precisely calculated from pre-operative CT Volumetry with confidence and accuracy up to 95%.

P-497 Increasing use of pan-ethnic carrier screening for donor gametes creates new challenges for clinics and recipient counselling

Abstract Study question How can clinics support recipients to understand a positive or negative carrier status following pan-ethnic carrier screening. Summary answer A combination of recipient testing and genetic counselling enables the use of donor sperm irrespective of pan-ethnic screening results. What is known already Data reported by the HFEA, UK reveals that in 2020, more than half of new donor registrations were from donor imports - 48% were American or Danish in origin, where the level of genetic screening for recessive conditions can vary from 3 to 502 genes. Donor banks generally state that donors are screened to professional guidelines for the countries they supply. Variations in the practice for carrier screening of gamete donors and how this information is shared and charged can be opaque to clinics and complex for recipients to navigate without specialist support to understand relevance and reproductive risk. Study design, size, duration This study reports on the number of genetic counselling requests from several IVF clinic referrals in the UK for the period Jan 2020 - Dec 2023. A total of 412 recipients interested in purchasing samples from donors identified as a positive carrier of one or more recessive condition(s) after undergoing extended carrier screening. Referrals for ECS negative donors were not received. Participants/materials, setting, methods Recipients were provided with the opportunity of genetic counselling to include the meaning of the carrier status, risk estimates, and options. Recipients were then given the opportunity to review the consultation report and were supported through their subsequent decision-making. The recipient’s choice to accept the risk for using the donor or proceed to counter-screening was evaluated to give insight into the recipient decision-making for accepting risk or wishing to undertake carrier screening. Main results and the role of chance UK screening recommendations cumulatively account for only 9.3% of identified mutations within a sperm donor applicant population at a single commercial US sperm bank screened using ECS, highlighting international inconsistencies in donor recruitment and acceptance criteria. 15.3 % (n = 63) of recipients elected to be screened for the conditions their donor was a carrier for, with most opting to be screened on a matched gene panel to provide information for a child and allow future matching with an alternative donor. 84.7% (n = 359) proceeded with treatment without counter screening appreciating their relatively low reproductive risk. Patients who undertake consultation with a genetic professional can understand their reproductive risk for autonomous decision-making, indicating ECS positive results are not a barrier to donor gamete selection for treatment. Limitations, reasons for caution ECS panels are variable by commercial provider, donor banks may vary their carrier screening policy or commercial ECS options over time, limiting the findings to the time frame in which the abstract was written Wider implications of the findings Review and implementation of carrier screening guidelines are required to ensure consistency and transparency with access to suitably qualified genetics professionals to provide information counselling and genetic testing options. This allows recipients to maintain a level of autonomy for donor selection and may ultimately widen the available donor pool. Trial registration number not applicable

The Centennial Allograft: Cumulative Kidney and Liver Function for More Than 100 Years

The maximum cumulative life span of kidneys and livers first in donors and then in transplant recipients has not been established. The purpose of this study was to determine if cumulative organ function for more than 90 years is possible for transplanted kidneys and livers. This study included kidney and liver transplants from living or deceased donors ≥55 years. Cumulative organ function (COF) = Organ Age at Donation [Years] + Tx Allograft Function [Years]. Univariate and multivariable methods were used to describe characteristics and outcomes. Between 1987 and 2022, a total of 81,807 kidney and 37,099 liver transplants were included in this study. Of all kidney grafts 2.7% but 16.6% of all liver grafts reached the 90-year COF mark. There were only 2 living donor kidneys that surpassed the 100-year mark versus 29 deceased liver grafts. The longest kidney function was 104 years and longest liver function 108 years. Multivariate analysis showed that optimal donor and recipient selection and management are predictors for allograft longevity. COF in organs exceeding 100 physiologic years is possible. Extended organ longevity was 5 times more common for livers than kidneys. These analyses support that age alone should not exclude older kidney and liver donors from consideration for transplantation.

Impact of Age of Heart Transplant Program on Patient Survival and Post-Transplant Outcomes.

The relationship between age of a heart transplant (HT) program and outcomes has not been explored. We performed a retrospective cohort analysis of the United Network for Organ Sharing database of all adult HTs between 2009 and 2019. For each patient, we created a variable that corresponded to program age: new (<5), developing (≥5 but <10) and established (≥10) years. Of 20 997 HTs, 822 were at new, 908 at developing, and 19 267 at established programs. Patients at new programs were significantly more likely to have history of cigarette smoking, ischemic cardiomyopathy, and prior sternotomy. These programs were less likely to accept organs from older donors and those with a history of hypertension or cigarette use. As compared to patients at new programs, transplant patients at established programs had less frequent rates of treated rejection during the index hospitalization (HR 0.43 [95% CI, 0.36-0.53] p<0.001) and at 1 year (HR 0.58 [95% CI, 0.49-0.70], p<0.001), less frequently required pacemaker implantations (HR 0.50 [95% CI, 0.36-0.69], p<0.001), and less frequently required dialysis (HR 0.66 [95% CI, 0.53-0.82], p<0.001). However, there were no significant differences in short- or long-term survival between the groups (log-rank p = 0.24). Patient and donor selection differed between new, developing, and established HT programs but had equivalent survival. New programs had increased likelihood of treated rejection, pacemaker implantation, and need for dialysis. Standardized post-transplant practices may help to minimize this variation and ensure optimal outcomes for all patients.

BLOOD DONATION BAN POLICIES AND FUNDAMENTAL RIGHTS OF LGBTQI COMMUNITY: DOES IT NEED A POTENTIAL SOCIO-LEGAL REFORMS FOR INCLUSIVITY?

The current debate on the subject has drawn ample attention of the civil society towards a case pending before the Hon’ble Apex Court comprising of a bench headed by Chief Justice of India D. Y. Chandrachud who has also sought responses from the National AIDS Control Organisation (NACO) and the National Blood Transfusion Council (NBTC). In his petition, Sharif D. Rangnekar, represented by attorneys Rohit Bhatt and Ibad Mushtaq, contested the legality of Clause 12 of the "Guidelines for Blood Donor Selection &amp; Blood Donor Referral, 2017" that were published on October 11, 2017, by the National Aids Control Organization and the National Blood Transfusion Council (NBTC). Thus, Rangnekar requested that the SC order the Centre to create rules permitting homosexual and LGBTQI (lesbian, gay, bisexual, transgender, queer, intersex) individuals to donate blood, subject to appropriate limitations based on "screen and defer" or "assess and test" regulations. The petitioner challenge the ban stating that “It is presumed that a particular group of persons may be suffering from sexually transmitted diseases. Medical technology and education, especially in the field of haematology, has progressed tremendously. The screening of donors is conducted for every donation before a transfusion,” further, it was also claimed by the petitioner that “Today, a blanket prohibition does not stand to reason.

Characteristics of first-time blood donors with unsatisfactory hemoglobin level and positive hepatitis B test in Binh Dinh Province

Blood transfusion is essential in the treatment of a various diseases. In order to guarantee a safe and sufficient volume of blood supply, it is crucial to select appropriate donors based on stringent eligibility criteria. The objective of this study was to furnish robust epidemiological information and identify the risk factors linked to hepatitis B virus (HBV) infection and low hemoglobin levels in first-time blood donors in Binh Dinh. Understanding the causes for donor deferrals can assist better plan and establish an efficient recruiting strategies as well as evaluate donor selection criteria. A cross-sectional study was undertaken in Binh Dinh Provincial General Hospital from November 2022 to February 2023 to examine individuals in their first-time blood donation. Data were sourced directly from voluntary blood donation registration forms. HBsAg results were assessed using rapid immunochromatographic tests and chemiluminescent immunoassays. The rate of unsatisfactory hemoglobin levels was 2.56% tested on 1,638 participants. This rate was significantly associated with female sex (18 times greater odds than males), and lower weight. The results revealed that the rate of HBV infection was 3.13% when detected by the rapid test, but increased by 0.58% when measured by chemiluminescent microparticle immunoassay. The positive hepatitis B deferral correlated with sex (p&lt;0.05), age group (p&lt;0.05) and occupation (p&lt;0.05). HBV was found the leading cause of deferral in the study area and associated with males, age groups (25–35 and 36–44), officer, worker-farmer, and self-employed people. The prevalence of low hemoglobin donor deferral obtained was 2.56%. Low hemoglobin deferral is associated with female gender, lower body weight, worker-farmer, and self-employed - others. This finding underscores a significant public health concerns, highlighting the need for strategies to lower the infection rates. Understanding the factors leading to defered donation can contribute to development of proactive strategies for recruiting and retaining donors.

Recent trends and new developments in liver transplantation.

Liver transplantation (LT) has been an established treatment for end-staged liver disease for acute, chronic, metabolic diseases and liver cancer. Advanced surgical techniques, refined indications and contraindications for LT, improvements of donor selection, prognostic scorings system and immunosuppressive regimens have contributed to the improved outcomes of liver transplantation. The etiologies of cirrhosis have been shifting from viral hepatitis to metabolic associated fatty liver disease. New indications include peripheral or mass forming bile duct cancer, metastases from bowel cancers or neuroendocrine tumors. Resection and partial liver segments 2-3 transplantation with delayed total hepatectomy has been performed to the limited cases, which was the explored technique of auxiliary partial orthotopic LT. Minimally invasive donor hepatectomy (laparoscopic or robotic) has been increasingly done. In this review are described the recent pressing topics in LT.

Impact of Western Diet on Enterohemorrhagic Escherichia coli Colonization in the Human In Vitro Mucosal Artificial Colon as Mediated by Gut Microbiota.

Enterohemorrhagic Escherichia coli (EHEC) is a major food-borne pathogen that causes human disease ranging from diarrhea to life-threatening complications. Accumulating evidence demonstrates that the Western diet enhances the susceptibility to enteric infection in mice, but the effect of diet on EHEC colonization and the role of human gut microbiota remains unknown. Our research aimed to investigate the effects of a Standard versus a Western diet on EHEC colonization in the human in vitro Mucosal ARtificial COLon (M-ARCOL) and the associated changes in the gut microbiota composition and activities. After donor selection using simplified fecal batch experiments, two M-ARCOL bioreactors were inoculated with a human fecal sample (n = 4) and were run in parallel, one receiving a Standard diet, the other a Western diet and infected with EHEC O157:H7 strain EDL933. EHEC colonization was dependent on the donor and diet in the luminal samples, but was maintained in the mucosal compartment without elimination, suggesting a favorable niche for the pathogen, and may act as a reservoir. The Western diet also impacted the bacterial short-chain fatty acid and bile acid profiles, with a possible link between high butyrate concentrations and prolonged EHEC colonization. The work demonstrates the application of a complex in vitro model to provide insights into diet, microbiota, and pathogen interactions in the human gut.

A survey study evaluating donor gamete utilization rates, patient satisfaction, and fertility treatment outcomes according to desired race and ethnicity

To evaluate donor gamete utilization, patient satisfaction, and fertility treatment outcomes of patients pursuing treatment with donor gametes stratified by the desired race as well as ethnicity of the gamete donor. Survey study. Clinic. Patients planning to undergo treatment using donor sperm and/or donor oocytes at a single academic fertility clinic in the Southeastern United States between 2015 and2020. None. Utilization rates of donor gametes, satisfaction with donor gamete selection, and fertility treatment outcomes stratified by race and ethnicity of patient, as well as that of their gamete donor. Four hundred fifty patients were eligible for inclusion and 170 (38%) responded to the survey. Among the respondents, 59% desired a non-Hispanic White gamete donor and 20% desired a non-Hispanic Black gamete donor. Patients seeking a non-Hispanic Black gamete donor had lower odds of using donor gametes (Odds ratio [OR], 0.13; 95% confidence interval [CI], 0.04-0.40) compared with individuals seeking a non-Hispanic White gamete donor. When evaluating satisfaction with donor gamete selection, patients seeking a non-Hispanic Black gamete donor reported lower satisfaction compared with individuals seeking a non-Hispanic White gamete donor (OR, 0.19; 95% CI, 0.09-0.43). When evaluating fertility outcomes, Non-Hispanic Black patients and those using non-Hispaninc Black gamete donors were found to have lower odds of successful conception compared with non-Hispanic White patients (OR, 0.18; 95% CI, 0.07-0.46) and individuals seeking non-Hispanic White gamete donors (OR, 0.26; 95% CI, 0.09-0.75), respectively. Patients seeking non-Hispanic Black donor gametes have lower utilization rates, less satisfaction with gamete donor selection, and lower odds of conception when compared with those seeking non-Hispanic White gamete donors. These findings highlight the need for more racial diversity within donor gamete banks, as well as within the donor pools available through agencies and fertility clinics.

ProtoSpaceJAM: an open-source, customizable and web-accessible design platform for CRISPR/Cas insertional knock-in.

CRISPR/Cas-mediated knock-in of DNA sequences enables precise genome engineering for research and therapeutic applications. However, designing effective guide RNAs (gRNAs) and homology-directed repair (HDR) donors remains a bottleneck. Here, we present protoSpaceJAM, an open-source algorithm to automate and optimize gRNA and HDR donor design for CRISPR/Cas insertional knock-in experiments, currently supporting SpCas9, SpCas9-VQRand enAsCas12a Cas enzymes. protoSpaceJAM utilizes biological rules to rank gRNAs based on specificity, distance to insertion site, and position relative to regulatory regions. protoSpaceJAM can introduce 'recoding' mutations (silent mutations and mutations in non-coding sequences) in HDR donors to prevent re-cutting and increase knock-in efficiency. Users can customize parameters and design double-stranded or single-stranded donors. We validated protoSpaceJAM's design rules by demonstrating increased knock-in efficiency with recoding mutations and optimal strand selection for single-stranded donors. An additional module enables the design of genotyping primers for deep sequencing of edited alleles. Overall, protoSpaceJAM streamlines and optimizes CRISPR knock-in experimental design in a flexible and modular manner to benefit diverse research and therapeutic applications. protoSpaceJAM is available open-source as an interactive web tool at protospacejam.czbiohub.org or as a standalone Python package at github.com/czbiohub-sf/protoSpaceJAM.

From dysbiosis to defense: harnessing the gut microbiome in HIV/SIV therapy

BackgroundAlthough the microbiota has been extensively associated with HIV pathogenesis, the majority of studies, particularly those using omics techniques, are largely correlative and serve primarily as a basis for hypothesis generation. Furthermore, most have focused on characterizing the taxonomic composition of the bacterial component, often overlooking other levels of the microbiome. The intricate mechanisms by which the microbiota influences immune responses to HIV are still poorly understood. Interventional studies on gut microbiota provide a powerful tool to test the hypothesis of whether we can harness the microbiota to improve health outcomes in people with HIV.ResultsHere, we review the multifaceted role of the gut microbiome in HIV/SIV disease progression and its potential as a therapeutic target. We explore the complex interplay between gut microbial dysbiosis and systemic inflammation, highlighting the potential for microbiome-based therapeutics to open new avenues in HIV management. These include exploring the efficacy of probiotics, prebiotics, fecal microbiota transplantation, and targeted dietary modifications. We also address the challenges inherent in this research area, such as the difficulty in inducing long-lasting microbiome alterations and the complexities of study designs, including variations in probiotic strains, donor selection for FMT, antibiotic conditioning regimens, and the hurdles in translating findings into clinical practice. Finally, we speculate on future directions for this rapidly evolving field, emphasizing the need for a more granular understanding of microbiome-immune interactions, the development of personalized microbiome-based therapies, and the application of novel technologies to identify potential therapeutic agents.ConclusionsOur review underscores the importance of the gut microbiome in HIV/SIV disease and its potential as a target for innovative therapeutic strategies.

The Impact of Fecal Microbiota Transplantation on the Intestinal Microecology of Patients with Colorectal Cancer

This study investigated the impact of fecal microbiota transplantation (FMT) on the intestinal microecology of patients with colorectal cancer. The intestinal microbiota structure of patients with colorectal cancer often undergoes significant changes, which are closely related to the occurrence and development of the disease. As a novel therapeutic approach, FMT aims to rebuild intestinal microecological balance and thereby improve clinical symptoms and prognosis of patients with colorectal cancer. This study found that FMT can effectively alter the intestinal microbiota structure of patients with colorectal cancer, increase microbial diversity, reduce intestinal inflammation, and potentially enhance the patient s immune function. However, FMT still faces challenges in clinical application, such as donor selection, ethical issues, and the stability of transplantation effects. Future research needs to further explore optimization strategies for FMT to fully realize its potential in the treatment of colorectal cancer.

Elecsys® AMH assay: Determination of Anti-Müllerian hormone levels and evaluation of the relationship between superovulation response in Holstein dairy cows.

Anti-Müllerian Hormone (AMH) serves as a crucial parameter in assessing the reproductive herd life and ovarian reserve in cattle. Consequently, extensive research is conducted on AMH levels. Various measurement methods can be employed to determine AMH levels. However, to our knowledge, no study has been conducted on Holstein donors using the Elecsys® AMH kit. This study was designed to determine AMH levels in donors utilising the Elecsys® AMH kit and to evaluate the relationship between superovulation response parameters and AMH levels. In this study, we measured the serum AMH levels of 36 cows using the Elecsys® AMH automated assay before the superovulation protocol (1st sample) and FSH injections (2nd sample). The cows were categorised into three groups based on their AMH levels: low, medium, and high AMH. Positive correlations were identified between AMH and parameters associated with superovulation response. The high AMH level group exhibited significantly greater numbers of corpus luteum, total embryos, transferable embryos, and grade 1 embryos compared to the medium and low AMH groups (p < 0.05) There was no significant difference between AMH levels before the superovulation protocol and FSH injections(p > 0.05). Body condition score and parity did not significantly affect AMH levels in cows (p > 0.05). Also, AMH cut-off values for the number of corpus luteum, total embryo, and transferable embryoswere detectedas 234, 227, and 210 pg/mL, respectively. These findings demonstrate that a high serum AMH level has a positive influence on the superovulation response. AMH can be used as a reliable marker for the selection of donors in Holstein cows.

Evaluation of Renal Function in Living Kidney Donors by Isotopic Measurement of Glomerular Filtration Rate with 99mTc-DTPA

Introduction. Accurate assessment of kidney function in living kidney donors is essential prior to surgery. The aim of this study is to demonstrate the value of 99mTc DTPA isotope Glomerular Filtration Rate measurements (GFRmDTPA) in kidney donors compared to the estimated technique (GFReMDRD). Methods. 203 kidney donor’s candidates (119 women and 84 men) had a GFRmDTPA after intravenous injection of 37 MBq 99mTc-DTPA, followed by two blood samples at 2h and 4h post-injection. DFGmDTPA was compared to GFReMDRD and patients were classified according to KDIGO 2012 stages. Patients selected for transplantation were those with a GFR ≥ 80ml/min/1.73m2. Results. Mean GFRmDTPA was 93 ml/min/1.73m2 versus 95 ml/min/1.73m2 for GFReMDRD. 124 patients (61.1%) were at stage 1 with GFRmDTPA vs 113 by GFReMDRD (55.7%). 73 patients (36%) at stage 2 by GFRmDTPA vs 87 by GFReMDRD (42.9%). 6 patients (3%) were at stage 3 by GFRmDTPA and 3 by GFReMDRD (1.5%). A total of 151 patients achieved a GFRmDTPA ≥ 80ml/min/1.73m2 and selected into the transplant protocol, compared to 146 by GFReMDRD. 52 patients with GFRmDTPA less than 80ml/min/1.73m2 compared to 57 by estimated technique were rejected from the transplant protocol based on GFRmDTPA results. Conclusion. GFRmDTPA is a referent method in the evaluation and selection of potential kidney donors’ candidates with an impact on the transplant decision, but requires indications adapted to this population.

Reexploring cytomegalovirus serology in allogeneic hematopoietic cell transplantation.

Discuss the recent evidence on cytomegalovirus (CMV) serology in allogeneic hematopoeic cell transplant (HCT) recipients. Whereas the role CMV-specific cellular mediated immunity has recently emerged as an important factor of CMV DNAemia posttransplant, the value of CMV serology has remained unchanged through decades, associated with donor selection and posttransplant prophylactic and monitoring strategies. In this review, we describe and discuss the emerging reports on the association between the magnitude of pretransplant CMV immunoglobulin G (IgG) titer and the posttransplant incidence of CMV DNAemia, as CMV IgG titer could become an additional tool in CMV risk assessment in the future. Pretransplant recipient CMV serology may have significant implications in posttransplant CMV reactivation in allogeneic HCT recipients.

Haploidentical HSCT in the Treatment of Pediatric Hematological Disorders.

Allogeneic hematopoietic stem cell transplantation has become a treatment option for otherwise non-curative conditions, both malignant and benign, affecting children and adults. Nevertheless, the latest research has been focusing extensively on transplantation from related and unrelated haploidentical donors, suitable for patients requiring emergent hematopoietic stem cell transplantation (HSCT) in the absence of an HLA-matched donor. Haploidentical HSCT (haplo-HSCT) can be an effective treatment for non-malignant pediatric disorders, such as primary immunodeficiencies or hemoglobinopathies, by enabling a much quicker selection of the appropriate donor for virtually all patients, low incidence of graft-versus-host disease (GVHD), and transplant-related mortality (TRM). Moreover, the outcomes of haplo-HSCT among children with hematological malignancies have improved radically. The most demanding tasks for clinicians are minimizing T-cell-mediated alloreactivity as well as early GVHD prevention. As a result, several T-cell depletion approaches, such as ex vivo T-cell depletion (TCD), and T-cell replete approaches, such as a combination of anti-thymocyte globulin (ATG), post-transplantation cyclophosphamide (PTCy), cyclosporine/tacrolimus, mycophenolate mofetil, or methotrexate, have been taken up. As more research is needed to establish the most beneficial form of therapy, haplo-HSCT is currently considered an alternative donor strategy for pediatric and adult patients with complications like viral and bacterial infections, invasive fungal disease, and GVHD.