Related Donor Research Articles

Letter to the editor: Improved outcomes of ABO incompatible living donor liver transplant with biologically related donors.

Letter to the editor: Improved outcomes of ABO incompatible living donor liver transplant with biologically related donors.

Comparison of HLA-haploidentical donors with post-transplant cyclophosphamide versus HLA-matched unrelated donors in peripheral blood stem cell transplantation for acute myeloid leukaemia.

HLA-haploidentical haematopoietic cell transplantation with post-transplant cyclophosphamide (PTCy-haplo) is emerging as an effective alternative due to donor availability and safety. We conducted a nationwide retrospective study comparing the outcomes of PTCy-haplo with both anti-thymocyte globulin (ATG)-free and ATG-administered matched unrelated donors (MUD) transplantation, using peripheral blood stem cells as the first transplantation for acute myeloid leukaemia (AML). Our study showed a lower and slower haematopoietic recovery and a higher incidence of infection-related deaths after PTCy-haplo than after MUD transplantation. In addition, we revealed an increased risk of acute and chronic graft-versus-host disease (GVHD) in ATG-free MUD transplantation in comparison to PTCy-haplo. For grades III-IV acute GVHD, the hazard ratio (HR) was 2.71 (95% CI, 1.46-5.01), and for extensive chronic GVHD, the HR was 3.11 (95% CI, 2.07-4.68). There was no significant difference regarding overall survival amongst the groups. In addition, GVHD-free relapse-free survival (GRFS) was lower in ATG-free MUD transplantation than in PTCy-haplo (HR, 1.46; 95% CI, 1.17-1.82). Notably, ATG-administered MUD transplantation showed no significant difference in GRFS from PTCy-haplo, negating the advantage of PTCy. Our results suggest that PTCy-haplo could be viable for AML patients without an HLA-matched related donor.

Reply: Improved outcomes of ABO incompatible living donor liver transplant with biologically related donor.

Reply: Improved outcomes of ABO incompatible living donor liver transplant with biologically related donor.

Comparative outcomes of various transplantation platforms, highlighting haploidentical transplants with post-transplantation cyclophosphamide for adult T-cell leukaemia/lymphoma.

This study retrospectively compared outcomes of various allogeneic haematopoietic cell transplantation (allo-HCT) platforms in patients with adult T-cell leukaemia/lymphoma. Platforms included human leukocyte antigen (HLA)-haploidentical-related donors using post-transplant cyclophosphamide (PTCY), HLA-matched related donors (MRD), HLA-matched unrelated donors (MUD) and cord blood transplantation (CBT). Patients who underwent their first allo-HCT between 2016 and 2021 were included. Outcomes analysed were overall survival (OS), relapse and non-relapse mortality (NRM). Seven hundred patients were included (PTCY, n = 121; MRD, n = 91; MUD, n = 160; CBT, n = 328). With a median follow-up of 794 days for survivors, 2-year OS was 48.1% (PTCY), 48.8% (MRD), 48.4% (MUD) and 34.6% (CBT); the respective 2-year cumulative incidence of relapse was 37.1%, 47.5%, 33.9% and 45.1% and that of NRM was 24.2%, 19.8%, 24.7% and 27.3%. PTCY was associated with delayed platelet engraftment relative to MRD and MUD. There was no increase in the incidence of severe acute or chronic graft-versus-host disease. In the PTCY group, poor performance status was a significant predictor of inferior OS, and infused CD34+ cell numbers of less than 5 × 106/kg were associated with delayed neutrophil and platelet engraftment. These results suggest that allo-HCT with PTCY is a safe and effective platform for patients with adult T-cell leukaemia/lymphoma.

Human milk oligosaccharide profiles remain unaffected by maternal pre-pregnancy body mass index in an observational study.

Human milk oligosaccharides (HMOs) are important carbohydrates in human milk that infants cannot digest, acting as prebiotics linked to infant health. The risk of childhood obesity increases with maternal obesity, potentially mediated through the gut microbiota affected by the available HMOs. Studies on whether maternal obesity affects HMO abundance, yield conflicting results. This study aimed to investigate the HMO profile and its association with maternal obesity measured by pre-pregnancy body mass index (BMI) and infant anthropometrics. The results were discussed in the context of existing literature. 90 human milk samples were collected at 3 months postpartum from mothers in three BMI-groups: 32 normal weight (BMI: 18.5-24.99 kg/m2), 34 overweight (BMI: 25-30 kg/m2), and 24 obese (BMI > 30 kg/m2). The samples were analyzed using nano liquid chromatography chip quadrupole time-of-flight mass spectrometry yielding 51 HMO structures and isomers. Their peak areas were integrated and normalized to determine relative abundances. Univariate and multivariate analysis showed associations between relative HMO abundance and donors' secretor status and specific infant anthropometric variables, but not with maternal pre-pregnancy BMI. This study does not support the hypothesis that maternal overweight influences the HMO profile and highlights the importance of reporting results despite absence of significant correlations.

Applications of Probabilistic Genotyping Method for Combining Evidence Across Microhaplotype DNA Mixture Profiles.

In cases of serious crimes that involve challenging DNA samples from the perpetrator (e.g., a minor contributor to a mixture), there is justification to combine different mixture profiles. In our previous study, we developed a massively parallel sequencing (MPS)-based assay targeting 140 microhaplotype markers. In this study, we extended the use of the microhaplotype panel to common scenarios, such as determining the presence of a common contributor or relatedness between different mixture profiles when no reference source is available. Data interpretation was performed using the R package KinMix. Our findings revealed that correct assignments of a common contributor and relatedness were made between relatively balanced mixtures. However, when profiles suffered from allele imbalance, inclusive assignments were significantly associated with the suspect's mixture proportion. Additionally, our analysis showed zero false-positive rates in the studied scenarios. These results indicate that microhaplotype data can be reliably interpreted for identifying a common donor or related donors among different mixtures. Further research based on larger sample sizes may yield more reliable results, which could assist in solving issues related to complex scenarios where multiple mixed profiles were involved.

Antibody responses to re-immunization in recipients of allogeneic hematopoietic cell transplantation

Abstract Background Immunologic memory against vaccine-preventable diseases is often lost after an allogeneic hematopoietic cell transplant (allo-HCT), therefore recipients are required to be re-immunized after allo-HCT to regain immunity against these infections. But the response to vaccination after an allo-HCT can be highly variable and is not well understood. We performed a single center retrospective study to examine immunization practices and determine the rate of vaccine protection and seroconversion following vaccination after allo-HCT. Methods Electronic medical records (EMR) from patients ≤18 years of age who underwent allo-HCT at St. Jude Childrens’ Research Hospital between 2005 - 2021 were reviewed. Clinical information and serology results before and after completion of the immunizations series were extracted from the EMR. The vaccines included in this analysis were diphtheria, measles, mumps, rubella (MMR), varicella, and polio. Protection was evaluated only for infections with established immune correlates. Seroconversion was defined as 4-fold increase in titers for vaccines with quantitative antibody assays, or as a change from negative to positive IgG for vaccines with qualitative antibody tests. Results 760 patients were included in this cohort. Demographic and clinical data are summarized in Table 1. The mean age at allo-HCT was 10.4 years, most were male (56.8%) and white (74.6%). Acute leukemia accounted for 66.4% of allo-HCT recipients. Conditioning was myeloablative for 53.45%, and reduced intensity for 37.9%. Most received transplants from mismatched-related donors, (44.9%), followed by matched unrelated donors (35.4%) and matched related donors (19.5%). The number of patients who received the full vaccination series at our institution differed by vaccine and ranged from 41-150, and the respective subsets with available pre-vaccination and post-vaccination titers ranged from 24-93. The median time from transplant to initiation of immunizations was 12 months (range: 6-58) for non-live vaccines, 25 months (range: 23, 63) for MMR vaccine, and 28 months (range: 16, 117)) for varicella vaccine. Protection post immunization varied, with less patients demonstrating protections for mumps (79%) and measles (82%) (Figure 1). Seroconversion also varied among the different vaccine components and types of vaccines. Conclusion Current strategies to re-immunize patients after allo-HCT do not provide protection to all patients. Understanding the factors associated with suboptimal immune responses is critical for advancing our knowledge in this area. Whether time-based approaches combined with immune reconstitution data are required to further optimize protection remains unclear. Additionally, different vaccine schedules (i.e., higher doses) may be required in these patients. Figure 1. Protection and seroconversion rate by vaccine target.

BK virus associated hemorrhagic cystitis in pediatric patients undergoing hematopoietic stem cell transplantation

Abstract Background BK virus (BKV) is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic stem cell transplantation (HSCT). Methods Descriptive and retrospective study that included patients from 0-18 years old undergoing HSCT with a diagnosis of HC, admitted from 1/1/2018 to 11/30/2023 in a tertiary care pediatric hospital. Patients with HC were tested for BKV by quantitative polymerase chain reaction (PCR) in urine samples, if positive, plasma viral load was also requested. BKV-HC grading was defined by the European Conference on Infections in Leukemia (ECIL) consensus document. Asymptomatic patients did not undergo standardized screening for BKV. Results During this period 86 HSCT were performed for either malignant (75,6%) or non-malignant disorders (24,4%). Overall, 16 (18,6%) were autologous and 70 (81.4%) were allogeneic: 40 human leukocyte antigen (HLA) matched unrelated donor, 26 HLA-matched related donor and 4 haploidentical. Six patients (7%) suffered HC, all associated with BKV as the cause. These six patients underwent allogeneic HSCT, and 4 of them had HLA-matched unrelated donors. All patients were over 5 years old. Male sex predominated (n:5). All of the patients had hematologic malignancies as the underlying diagnosis (5 with acute lymphoblastic leukemia - ALL). The stem cell source was bone marrow in 3 patients and peripheral blood in the other 3. All patients received myeloablative conditioning regimen and 4 underwent total body irradiation. Only one patient received post-transplant cyclophosphamide. Symptoms (dysuria, abdominal pain, macroscopic hematuria, clots) began more than 14 days after HSCT in 100% of the cases. Hematuria was categorized as grade III in 5 patients and grade IV (severe) only in one. All patients tested positive for BKV PCR in urine samples. High-level BK viruria (>107 copies/mL) was found in 66,6%. BK viremia was detected in 4 patients. All of the patients had another concomitant viral infection, with cytomegalovirus reactivation being the most frequent (n:4). Two patients also had detectable adenovirus (ADV) PCR in urine samples. Acute graft versus host disease (GVHD) was diagnosed in 5 patients, all with skin involvement. All patients were hospitalized and prolonged the length of stay. Regarding treatment, they all received hyperhydration and Cidofovir (more than 3 doses). Dose of immunosuppressive treatment was reduced in 5 cases. Acute kidney failure (AKF) was found in 3 patients. One patient developed chronic kidney failure. The patient with no GVHD was the one who improved the fastest. The patient with severe hematuria required bladder irrigation, had dialysis indication and presented a related death. Conclusion The development of BKV-HC in HSCT patients results in suffering and pain, prolonged hospitalizations and significant morbidity (AKF). Literature shows that male sex, older age and acute GVHD are important risk factors, and this is what we also found in our case series. BKV-HC is considered a difficult and severe condition to manage, remaining troublesome so we should overcome this deficiency with new approaches, particularly emphasizing in preemptive or prophylaxis measures for the benefit of our patients.

Outcomes of haploidentical transplants with PT-CY vs 10/10 MUD transplants with ATG in Germany

AbstractAllogeneic stem cell transplantation (allo-HSCT) is the best curative treatment modality for many malignant hematologic disorders. In the absence of a matched related donor, matched unrelated donors (MUDs) and haploidentical donors (Haplo-Tx) are the most important sources of stem cells. However, multicenter real-life data that compare 10/10 MUD transplantations with Haplo-Tx are still limited. In this registry-based retrospective study, we compared the outcomes of allo-HSCTs from 10/10 MUDs with antithymocyte globulin (ATG)–based regimens (n = 7050) vs Haplo-Tx using posttransplant cyclophosphamide (PT-CY Haplo; n = 487) in adult patients with hematologic malignancies between 2010 and 2020. Cox proportional hazard models and competing risks regression models were formed to compare the outcomes of the groups. Overall survival (OS), Disease-free survival (DFS), and graft-versus-host disease (GVHD)–free and relapse-free survival (GRFS) were superior for 10/10 MUDs (OS [hazard ratio (HR), 1.27; confidence interval (CI), 1.10-1.47; P = .001]; DFS [HR, 1.17; CI, 1.02-1.34; P = .022]; GRFS [HR, 1.34; CI, 1.19-1.50; P < .001]). The risk of acute GVHD (aGVHD) grade 2 to 4, aGVHD grade 3 to 4, and chronic GVHD (cGVHD) was higher in the PT-CY Haplo group than the 10/10 MUD group (aGVHD grade 2-4 [HR, 1.46; CI, 1.25-1.71; P < .001]; aGVHD grade 3-4 [HR, 1.74; CI, 1.37- 2.20; P < .001]; cGVHD [HR, 1.30; CI, 1.11-1.51; P = .001]). A lower incidence of relapse was observed in the PT-CY Haplo group (relapse: HR, 0.83; CI, 0.69-0.99; P = .038). Unrelated 10/10 matched transplantation with ATG treatment leads to lower GVHD rates and improved survival rates compared with PT-CY Haplo transplantation in Germany.

Sequential Conditioning With FLAMSA Does Not Improve Outcomes of Allogeneic Stem Cell Transplantation in Chronic Myelomonocytic Leukemia Patients

As with myelodysplastic syndromes (MDS), effective treatment options for Chronic myelomonocytic leukemia (CMML) are limited, and the optimal treatment approach remains undefined. Allogeneic stem cell transplantation (allo-SCT) is potentially curative therapy for patients with CMML. Sequential conditioning with FLAMSA was initially developed for refractory acute myeloid leukemia (AML) and has since been applied in the treatment of MDS and CMML. Data on optimal allo-SCT conditioning in CMML Patients is scarce. This retrospective study from the Department of Stem Cell Transplantation at the University Medical Center Hamburg, Germany, compared allo-SCT outcomes in CMML patients across three conditioning regimes: Thiotepa-Busulfan (TB), Sequential FLAMSA-Busulfan Fludarabine (FLAMSA-FB), and Treosulfan-Fludarabine (Treo-Flu). Sixty-nine consecutive patients with CMML who underwent allo-SCT between the years 2006-2022 were included in the study. Twenty-two received TB, 27 received FLAMSA-FB, and 20 received Treo-Flu conditioning. Transplant sources included matched related donors (MRD, 8 patients), mismatched related donors (MMRD, 8 all in the TB group), matched unrelated donors (MUD, 31), and mismatched unrelated donors (MMUD, 22) with significant group variations (p<0.001). Most patients received anti-T lymphocyte Globulin (ATLG) for graft versus host disease (GVHD) prophylaxis (TB 68%, FLAMSA-FB 93%, Treo-Flu 85%, p=0.08). CPSS-Molecular score was comparable between the groups. One TB patient experienced primary graft failure, but engraftment times were comparable across the groups. Although not statistically significant, the TB group showed a trend towards improved 3-year OS rates (80%) compared to FLAMSA-FB (37%) and Treo-Flu (55%) (p=0.05). The TB group also displayed significantly higher 3-year PFS rates (80%) compared to FLAMSA-FB (33%) and Treo-Flu (both 39%), (p=0.02). No significant differences were observed in 3-year non-relapse mortality (NRM) across the TB (20%), FLAMSA-FB (30%), and Treo-Flu (26%) groups (p=0.8). Interestingly, no TB patients relapsed at 3 years, contrasting with the FLAMSA-FB (41%) and Treo-Flu groups (30%, p=0.02). Lastly, cumulative incidences of acute and chronic GVHD were similar across groups. Our analysis suggests FLAMSA-FB does not improve transplant outcomes, however TB represents the preferred conditioning regimen for CMML patients undergoing allo-SCT. It demonstrates notable advantages in relapse prevention and leads to improved OS and PFS compared to FLAMSA-FB and Treo-Flu protocols.

Clinical Analysis of Reversible Posterior Encephalopathy Syndrome after Allogeneic Hematopoietic Stem Cell Transplantation in Children

To summarize the clinical features of reversible posterior encephalopathy syndrome (PRES) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children. The clinical data of six children who developed PRES after undergoing allo-HSCT in the Department of Hematology of Wuhan Children's Hospital from June 2016 to December 2022 were retrospectively analyzed, and their clinical characteristics, imaging examination, laboratory examination, and treatment regression were summarized. Among 281 children underwent allo-HSCT, 6 cases (2.14%) developed PRES, with a median age of 5.1(1.5-9.7) years old. 4 cases underwent related haploidentical donor transplantation, and 2 cases underwent sibling allografting and unrelated donor allografting donor transplantation, respectively. All six children had an acute onset of illness, with clinical manifestations of nausea and vomiting, seizures, psychiatric disorders, visual disturbances. The five cases elevated blood pressure. All children with PRES were treated with oral immunosuppressive drugs during seizures, and 3 cases were combined with different degrees of graft-versus-host disease. Most of the children showed effective improvement in clinical symptoms and imaging after adjusting/discontinuing suspected medications (cyclosporine, etc.) and symptomatic supportive treatments (oral antihypertensive, diazepam for antispasmodic, mannitol to lower cranial blood pressure), and one of them relapsed more than 8 months after the first seizure. PRES is rare after hematopoietic stem cell transplantation in children, and its onset may be related to hypertension, cytotoxic drugs, graft-versus-host disease, etc. Most of them can be recovered after active treatment, but not completely reversible, and the prognosis of those who combined with TMA is poor.

Role of sonography in detection and evaluation of post liver transplant complications.

To evaluate the role of sonography in revealing and characterizing liver transplant complications based on gray scale and color Doppler, describe the normal Doppler findings, and discuss the significance of distinguishing normal transient changes in the spectral waveform from findings that may suggests ominous complications. We carried out a retrospective cross-sectional study at Prince Sultan Military Medical City, Riyadh, Saudi Arabia. The medical records and imaging studies of a total of 122 candidates who underwent transplantation between January 2016 to February 2022 were reviewed. Our results showed that most patients were males with the most frequent age group being those between 54-71 years. Hepatitis B virus and hepatic cellular carcinoma were the most common indications for transplants. A total of 95 patients received a graft from a living related donor. Regarding complications, biliary issues (including leaks and ducts dilation) were the second most frequent complication after collections. Vascular complications represented 7.4% of all complications and was the leading cause of death in 4.8% of cases. Among all vascular issues encountered during liver transplant, portal vein thrombosis was the most predominant. In respect to Doppler findings, portal vein velocities and resistive index of hepatic artery had re-averaged within 7-10 post-operative days in most patients. Ultrasound plays crucial role in the post-operative management of compilations, facilitating early detection, which is substantial for the graft survival.

Impact of donor type on the outcomes of acute graft versus host disease to systemic corticosteroid therapy.

Systemic corticosteroid therapy is a well-established first-line treatment for grades II-IV acute graft-versus-host disease (aGVHD). Recently, several developments have occurred, including the introduction of transplantation from human leukocyte antigen (HLA) haploidentical donors using post-transplant cyclophosphamide (PTCY-Haplo), and improvements in prognosis after cord blood transplantation (CBT) in Japan. This study aimed to analyze the association between donor sources and outcomes in patients with aGVHD. Our study included 2732 patients who developed grades II-IV aGVHD, and were treated with systemic corticosteroids. We compared HLA-matched related donors (MRD), HLA-matched unrelated donors (MUD), PTCY-Haplo, and CBT. We set endpoint as response rate, 1-year cumulative incidence of non-relapse mortality (NRM), and overall survival (OS). The adjusted odds ratios for a complete response (CR) were 0.99 (95% confidence interval [CI]: 0.74-1.31, P = 0.925) for MUD, 2.08 (95% CI: 1.35-3.25, P = 0.001) for PTCY-Haplo, and 1.08 (95% CI: 0.83-1.41, P = 0.550) for CBT compared with MRD. A significant increase in response rates for PTCY were only found in a single-organ involvement. No significant association was observed between the donor source and NRM or OS. In conclusion, PTCY-Haplo is associated with a high response rate in patients with a single-organ aGVHD; however, MUD and CBT were not associated with treatment response.

Specifics and results of liver transplantation in elderly patients

Aim. To determine specific features, frequency, and structure of complications, immediate and long-term results of liver transplantation in elderly patients.Materials and methods. Data on 529 liver transplantations performed consecutively in one medical center from 2010 to 2023 were analyzed. In 386 (73%) cases, the right lobe of the liver of related donors was used for transplantation. At the time of surgery, the patient age ranged from 18 years to 71 years, with 57 (11%) patients being over 60 years old, 215 (40%) patients aged 44–59 years, and 257 (49%) patients aged 18–44 years.Results. Prior to operation, elderly patients were statistically significantly more often diagnosed with arterial hypertension (n = 19; 33%), diabetes mellitus (n = 12; 21%), and on average a reduced glomerular filtration rate (82 ml/min/1.73m2 ). The most frequent indication for transplantation in this group was hepatocellular carcinoma in the setting of cirrhosis (n = 19; 33%). No statistically significant differences in other preoperative characteristics, parameters of donors and operations, peculiarities of the course of the early postoperative period, frequency, structure of complications and lethal outcomes were found. The one-, five-, and ten-year survival rates for recipients over 60 years old were 82%, 72%, and 36%; for recipients aged 44–59 years old – 88%, 79%, and 70%; and for recipients aged 18–44 years old – 86%, 80%, and 74%, respectively.Conclusion. In the studied cohort, older age was not associated with excessive risks of complications and early postoperative mortality. Given the higher prevalence of comorbidities in this group, preoperative examination should be aimed at, among other things, diagnostics of possible (hidden) cardiovascular and oncologic diseases. The development and introduction of new cardio-, nephro-, and oncoprotective regimens of immunosuppressive therapy seems to be an important measure not only for the surgical treatment of elderly patients, but also for recipients living with a transplanted liver for a long time.

Analysis of a global wheat panel reveals a highly diverse introgression landscape and provides evidence for inter-homoeologue chromosomal recombination

Key messageThis study highlights the agronomic potential of rare introgressions, as demonstrated by a major QTL for powdery mildew resistance on chromosome 7D. It further shows evidence for inter-homoeologue recombination in wheat.Agriculturally important genes are often introgressed into crops from closely related donor species or landraces. The gene pool of hexaploid bread wheat (Triticum aestivum) is known to contain numerous such “alien” introgressions. Recently established high-quality reference genome sequences allow prediction of the size, frequency and identity of introgressed chromosome regions. Here, we characterise chromosomal introgressions in bread wheat using exome capture data from the WHEALBI collection. We identified 24,981 putative introgression segments of at least 2 Mb across 434 wheat accessions. Detailed study of the most frequent introgressions identified T. timopheevii or its close relatives as a frequent donor species. Importantly, 118 introgressions of at least 10 Mb were exclusive to single wheat accessions, revealing that large populations need to be studied to assess the total diversity of the wheat pangenome. In one case, a 14 Mb introgression in chromosome 7D, exclusive to cultivar Pamukale, was shown by QTL mapping to harbour a recessive powdery mildew resistance gene. We identified multiple events where distal chromosomal segments of one subgenome were duplicated in the genome and replaced the homoeologous segment in another subgenome. We propose that these examples are the results of inter-homoeologue recombination. Our study produced an extensive catalogue of the wheat introgression landscape, providing a resource for wheat breeding. Of note, the finding that the wheat gene pool contains numerous rare, but potentially important introgressions and chromosomal rearrangements has implications for future breeding.

Outcomes of patients undergoing allogeneic haematopoietic stem cell transplantation for congenital amegakaryocytic thrombocytopenia; a study on behalf of the PDWP of the EBMT.

Congenital amegakaryocytic thrombocytopenia is a rare, inherited bone marrow failure syndrome. Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is currently the only curative treatment. In this retrospective study, we analysed 66 patients with allo-HSCT, reported in the European Society for Blood and Marrow Transplantation (EBMT) registry. Bone marrow (BM) was the most widely used stem cell source (n = 40; 61%) followed by peripheral blood (PB) (n = 18; 27%), and unrelated umbilical cord blood (UCB) (n = 8; 12%). Most frequently was a HLA-matched graft from related (n = 26; 39%) and unrelated (n = 15; 23%) donors after a myeloablative busulfan-based conditioning regimen. GvHD prophylaxis was mostly cyclosporine and methotrexate (53%). The 6-year cumulative incidence of graft-failure and second transplant were 25% and 17%, respectively. The 6-year disease-free survival (DFS) and overall survival (OS) were 66.9% and 85.6%, respectively. The 6-year transplant-related mortality (TRM) was 8.0%. In conclusion, most patients with CAMT benefit from allo-HSCT, but with many graft failures.

Access to Allogeneic Cell Transplantation Based on Donor Search Prognosis: An Interventional Trial.

Patients requiring allogeneic hematopoietic cell transplantation have variable likelihoods of identifying an 8/8 HLA-matched unrelated donor. A Search Prognosis calculator can estimate the likelihood. To determine if using a search algorithm based on donor search prognosis can result in similar incidence of transplant between patients Very Likely (>90%) vs Very Unlikely (<10%) to have a matched unrelated donor. This interventional trial utilized a Search Prognosis-based biologic assignment algorithm to guide donor selection. Trial enrollment from June 13, 2019-May 13, 2022; analysis of data as of September 7, 2023 with median follow-up post-evaluability of 14.5 months. National multi-center Blood and Marrow Transplantation Clinical Trials Network 1702 study of US participating transplant centers. Acute myeloid and lymphoid leukemias, myelodysplastic syndrome, Hodgkin's and non-Hodgkin's lymphomas, severe aplastic anemia, and sickle cell disease patients referred to participating transplant centers were invited to participate. 2225 patients were enrolled and 1751 were declared evaluable for this study. Patients were declared evaluable once it was determined no suitable HLA-matched related donor was available. Patients assigned to the Very Likely arm were to proceed with matched unrelated donor, while Very Unlikely were to utilize alternative donors. A third stratum, Less Likely (∼25%) to find a matched unrelated donor, were observed under standard center practices, but were not part of the primary objective. Cumulative incidence of transplantation by Search Prognosis arm. Evaluable patients included 1751 of which 413 (24%) were from racial/ethnic minorities. Search prognosis was 958 (55%) Very Likely, 517 (30%) Less Likely and 276 (16%) Very Unlikely. 1171 (67%) received HCT, 384 (22%) died without HCT, and 196 (11%) remained alive without HCT. Among the 1,234 patients, the adjusted cumulative incidence (95% CI) of HCT at 6-months was 59.8% (56.7-62.8) in the Very Likely group versus 52.3% (46.1-58.5) in the Very Unlikely (P=0.113). A prospective Search Prognosis-based algorithm can be effectively implemented in a national multicenter clinical trial. This approach resulted in rapid alternative donor identification and comparable rates of HCT in patients Very Likely and Very Unlikely to find a matched unrelated donor. Trial Registration: NCT#03904134.

The impact of pulmonary hypertension on the risk of early graft dysfunction in related kidney transplantation

Introduction. Pulmonary hypertension is a common complication among patients with end-stage renal disease and has a significant impact on the outcome of kidney transplantation, including during kidney transplantation from a living related donor.Objective. To study the prevalence of pulmonary hypertension among patients with end-stage renal disease and to determine its impact on the development of early renal graft dysfunction.Material and methods. The study was based on the analysis of treatment results in 650 patients who underwent kidney transplantation from a living related donor. Depending on the graft function, 2 groups of patients were identified: group I consisting of patients with early renal graft dysfunction (n=82); group II (n=79) that included the patients with a primary graft function who were selected by demographic and clinical laboratory data statistically comparable to patients of group I (p&gt;0.5). This allowed us to equalize the chances of achieving the study endpoint (early graft dysfunction). Transthoracic echocardiography was performed in all patients, with the calculation of the mean pulmonary artery pressure. The relative risk of early renal graft dysfunction was calculated depending on the presence of pulmonary hypertension and its severity.Results. Among group I patients, pulmonary hypertension was detected in 97.56% of cases (mean pulmonary artery pressure 48.26±18.63 mmHg), versus 86.08% in patients with a primary graft function (mean pulmonary artery pressure 31.92±16.11 mmHg) (p&lt;0.001). The presence of mild pulmonary hypertension increased the relative risk of early graft dysfunction by 2.58 times (95% CI [0.698-9.547]; p=0.174), moderate by 3.18 times (95% CI [0.860-11.764]; p=0.064), severe by 5.91 times (95% CI [1.644-21.241]; p&lt;0.001) compared with patients without pulmonary hypertension.Conclusions. When performing kidney transplantation from a living donor, the presence of severe pulmonary hypertension in the recipient is associated with an increased risk of early graft dysfunction. This suggests that pulmonary hypertension may be one of the modifiable risk factors for this complication.

Prognostic analysis of 8 patients with hepatic adenoma undergoing allogeneic hematopoietic stem cell transplantation

Objective: To evaluate the safety of patients with hepatic adenoma undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: A retrospective analysis of the clinical characteristics and prognosis of eight patients with hepatic adenoma who underwent allo-HSCT in the Hematology Department of Peking University People's Hospital from January 2010 to March 2024 was conducted. Results: Of the eight patients who underwent allo-HSCT with hepatic adenoma, one patient was considered MDS-h transfusion-dependent and seven had aplastic anemia. The median age of the patients was 23 years (13-48 years). The median time from the diagnosis of AA or MDS to transplantation was 14 years (6-24 years), whereas the median time from taking androgens to diagnosing hepatic adenoma was 9 years (5-13 years). Six cases underwent haplo-HSCT, one case underwent matched unrelated donor HSCT, and one case underwent matched related donor HSCT. All patients achieved neutrophil engraftment at a median time of 11.5 days (11-20 days) and PLT engraftment within 60 days at a median of 19 days (10-37 days) after haplo-HSCT. Moreover, seven patients developed CMV anemia after transplantation, three patients had hemorrhagic cystitis, and two patients developed acute GVHD. During and after transplantation, eight patients did not show severe liver function damage or rupture of hepatic adenoma. In relation to imaging size, four patients showed varying degrees of reduction in hepatic adenoma size after transplantation, whereas four patients did not show significant changes in hepatic adenoma size after transplantation. The median follow-up time was 540.5 (30-2 989) days. Of the eight patients, six survived and two died. Furthermore, no direct correlation was observed between death and hepatic adenoma. Conclusion: Patients with hepatic adenomas undergoing allo-HSCT are not contraindications for transplantation, which will not increase transplant-related mortality.

Establishing the relationship between an adopted recipient and their HLA-matched related donor

Establishing the relationship between an adopted recipient and their HLA-matched related donor