Hepatic Resection as the Primary Treatment Method for Hepatocellular Carcinoma After Orthotopic Liver Transplantation.

BACKGROUND: Liver transplantation (LT) is the treatment of choice for end-stage liver disease and certain malignancies such as hepatocellular carcinoma (HCC). Data on the surgical management of de novo or recurrent tumors that develop in the transplanted allograft are limited. This study aimed to investigate the perioperative and long-term outcomes for patients undergoing hepatic resection for de novo or recurrent tumors after liver transplantation. METHODS: The study enrolled adult and pediatric patients from 12 centers across North America who underwent hepatic resection for the treatment of a solid tumor after LT. Perioperative outcomes were assessed as well as recurrence free survival (RFS) and overall survival (OS) for those undergoing resection for HCC. RESULTS: Between 2003 and 2023, 54 patients underwent hepatic resection of solid tumors after LT. For 50 patients (92.6 %), resection of malignant lesions was performed. The most common lesion was HCC (n = 35, 64.8 %), followed by cholangiocarcinoma (n = 6, 11.1 %) and colorectal liver metastases (n = 6, 11.1 %). The majority of the 35 patients underwent resection of HCC did not receive any preoperative therapy (82.9 %) or adjuvant therapy (71.4 %), with resection their only treatment method for HCC. During a median follow-up period of 50.7 months, the median RFS was 21.5 months, and the median OS was 49.6 months. CONCLUSION: Hepatic resection following OLT is safe and associated with morbidity and mortality rates that are comparable to those reported for patients undergoing resection in native livers. Hepatic resection as the primary and often only treatment modality for HCC following LT is associated with acceptable RFS and OS and should be considered in well selected patients.

Self-mentoring: A new deep learning pipeline to train a self-supervised U-net for few-shot learning of bio-artificial capsule segmentation.

BACKGROUND: Accurate segmentation of microscopic structures such as bio-artificial capsules in microscopy imaging is a prerequisite to the computer-aided understanding of important biomechanical phenomenons. State-of-the-art segmentation performances are achieved by deep neural networks and related data-driven approaches. Training these networks from only a few annotated examples is challenging while producing manually annotated images that provide supervision is tedious. METHOD: Recently, self-supervision, i.e. designing a neural pipeline providing synthetic or indirect supervision, has proved to significantly increase generalization performances of models trained on few shots. The objective of this paper is to introduce one such neural pipeline in the context of micro-capsule image segmentation. Our method leverages the rather simple content of these images so that a trainee network can be mentored by a referee network which has been previously trained on synthetically generated pairs of corrupted/correct region masks. RESULTS: Challenging experimental setups are investigated. They involve from only 3 to 10 annotated images along with moderately large amounts of unannotated images. In a bio-artificial capsule dataset, our approach consistently and drastically improves accuracy. We also show that the learnt referee network is transferable to another Glioblastoma cell dataset and that it can be efficiently coupled with data augmentation strategies. CONCLUSIONS: Experimental results show that very significant accuracy increments are obtained by the proposed pipeline, leading to the conclusion that the self-supervision mechanism introduced in this paper has the potential to replace human annotations.

Postoperative Mortality in Patients With Cirrhosis: Reconsidering Expectations.

BACKGROUND: A diagnosis of cirrhosis increases a patient's risk of postoperative mortality. Surgeons are reticent to operate when cirrhosis is known unless no option is available. This study aimed to identify the modern perioperative risk in cirrhotic patients undergoing intervention under general anesthesia for non-transplant operations. METHODS: A retrospective chart review was conducted utilizing the Rush Medical Center electronic medical record. All patients over 18 years of age with a diagnosis of cirrhosis undergoing intervention between 2009 and 2019 were reviewed. 90-day mortality rates in patients grouped by Child's score, Model for End-Stage Liver Disease (MELD), and Model for End-Stage Liver Disease with sodium incorporated (MELDNa) were compared to previously accepted rates. RESULTS: 93 patients (46% women) aged 22-72 years of all Child-Turcot-Pugh (CTP) (40% A, 36% B, and 25% C) classifications and MELD/MELDNa ranging 6-40 were analyzed. 90-day mortality of the entire population was 16%, significantly lower than expected based on CTP score (16% vs. 32%; P = .0005), MELD (16% vs. 41%; P < .0001), and MELDNa (16% vs. 46.8%; P < .0001). This was also true for CTP-B patients (12% vs. 30%; P = .025), CTP-C patients (35% vs. 70%; P = .0002), patients with MELD >14 (27% vs. 70%; P < .001), and patients with MELDNa >14 (23% vs. 70%; P < .0001). CONCLUSION: Data indicate that perioperative mortality is lower than widely accepted. This suggests the need for a national database study using a representative population to determine the risk of mortality for patients with cirrhosis having surgery in recent times. Accurate estimation of this risk allows for meaningful discussion between physicians and patients when deciding to proceed with elective, necessary operations.

Urinary extracellular vesicles: A position paper by the Urine Task Force of the International Society for Extracellular Vesicles.

Urine is commonly used for clinical diagnosis and biomedical research. The discovery of extracellular vesicles (EV) in urine opened a new fast-growing scientific field. In the last decade urinary extracellular vesicles (uEVs) were shown to mirror molecular processes as well as physiological and pathological conditions in kidney, urothelial and prostate tissue. Therefore, several methods to isolate and characterize uEVs have been developed. However, methodological aspects of EV separation and analysis, including normalization of results, need further optimization and standardization to foster scientific advances in uEV research and a subsequent successful translation into clinical practice. This position paper is written by the Urine Task Force of the Rigor and Standardization Subcommittee of ISEV consisting of nephrologists, urologists, cardiologists and biologists with active experience in uEV research. Our aim is to present the state of the art and identify challenges and gaps in current uEV-based analyses for clinical applications. Finally, recommendations for improved rigor, reproducibility and interoperability in uEV research are provided in order to facilitate advances in the field.

Dynamic Interactions Between the Immune System and the Neuroendocrine System in Health and Disease.

The immune system and the neuroendocrine system share many common features. Both consist of diverse components consisting of receptors and networks that are widely distributed throughout the body, and both sense and react to external stimuli which, on the one hand control mechanisms of immunity, and on the other hand control and regulate growth, development, and metabolism. It is thus not surprising, therefore, that the immune system and the neuroendocrine system communicate extensively. This article will focus on bi-directional immune-endocrine interactions with particular emphasis on the hormones of the hypothalamus-pituitary-thyroid (HPT) axis. New findings will be discussed demonstrating the direct process through which the immune system-derived thyroid stimulating hormone (TSH) controls thyroid hormone synthesis and bone metamorphosis, particularly in the context of a novel splice variant of TSHß made by peripheral blood leukocytes (PBL). Also presented are the ways whereby the TSHß splice variant may be a contributing factor in the development and/or perpetuation of autoimmune thyroid disease (AIT), and how systemic infection may elicit immune-endocrine responses. The relationship between non-HPT hormones, in particular adipose hormones, and immunity is discussed.

Improving generalization in MR-to-CT synthesis in radiotherapy by using an augmented cycle generative adversarial network with unpaired data.

PURPOSE: MR-to-CT synthesis is one of the first steps in the establishment of an MRI-only workflow in radiotherapy. Current MR-to-CT synthesis methods in deep learning use unpaired MR and CT training images with a cycle generative adversarial network (CycleGAN) to minimize the effect of misalignment between paired images. However, this approach critically assumes that the underlying interdomain mapping is approximately deterministic and one-to-one. In the current study, we use an Augmented CycleGAN (AugCGAN) model to create a robust model that can be applied to different scanners and sequences using unpaired data. MATERIALS AND METHODS: This study included T2-weighted MR and CT pelvic images of 38 patients in treatment position from five different centers. The AugCGAN was trained on 2D transverse slices of 19 patients from three different sites. The network was then used to generate synthetic CT (sCT) images of 19 patients from the two other sites. Mean absolute errors (MAEs) for each patient were evaluated between real and synthetic CT images. Original treatment plans of nine patients were recalculated using sCT images to assess the dose distribution in terms of voxel-wise dose difference, gamma, and dose-volume histogram analysis. RESULTS: The mean MAEs were 59.8 Hounsfield units ( HU ) and 65.8 HU for the first and second test sites, respectively. The maximum dose difference to the target was 1.2 % with a gamma pass rate using the 3%, 3 mm criteria above 99%. The average time required to generate a complete sCT image for a patient on our GPU was 8.5 s. CONCLUSION: This study suggests that our unpaired approach achieves good performance in generalization with respect to sCT image generation.

Establishing a Case for Anti-complement Therapy in Membranous Nephropathy.

INTRODUCTION: Membranous nephropathy (MN) is a common cause of adult nephrotic syndrome that progresses to end-stage kidney disease in up to 40% of cases. It is an autoimmune disease characterized by glomerular subepithelial deposits containing IgG. In experimental MN, these deposits activate complement and cause kidney damage. The role of complement in human MN is less clearly defined. To address this, the current study focused on the role of complement in 2 independent primary (p) MN cohorts. METHODS: Glomeruli were isolated by laser capture microdissection and analyzed by mass spectrometry, focusing on complement proteins, from kidney biopsy specimens from a pMN cohort (n = 11) and from normal controls (n = 5). Immunohistological staining of kidney biopsy specimens for complement proteins was also done. In a second pMN cohort (n = 13), urine levels of Ba, C5a, and C5b-9 (membrane attack complex [MAC]) were measured. RESULTS: Mass spectrometry identified 8 complement pathway components (C1q, C3, C4, C5, C6, C7, C8, and C9) and 5 complement regulators (complement receptor type 1 [CR1], factor H [FH], FH-related protein 2 [FHR2], vitronectin, and clusterin). All complement levels were significantly higher in the MN groups than in the control group, except the level of CR1, which was lower. All pMN biopsy specimens showed negative or trace staining for C1q, positive staining for C3 and C4, and positive staining for at least 1 component of the lectin pathway. Urine Ba, C5a, and MAC were present in pMN, and their levels correlated (r Ba,C5a = 0.87, r Ba,MAC = 0.89, and r C5a,MAC = 0.97, P = .001 for each correlation). CONCLUSION: Elevated glomerular levels of C3, C4, and components of MAC (C5b-9) and absent or decreased levels of the complement regulator CR1, along with increased levels of complement activation products in the urine, support the involvement of complement in the pathogenesis of MN. These data raise the possibility that anti-complement therapies may be effective in some forms of MN.

Orthostatic Vital Signs Algorithm: Decreasing Falls in Patients Undergoing Blood and Marrow Transplantation or Treatment With Cellular Immunotherapy.

BACKGROUND: Falls experienced by patients undergoing blood and marrow transplantation or treatment with cellular immunotherapy (BMT-CI) may result in injury or death. An algorithm was developed using the patient fall circumstances identified in a chart analysis from 2016. OBJECTIVES: This study aimed to determine if the Moffitt BMT-CI Orthostatic Vital Signs Algorithm could decrease inpatient falls. METHODS: A pre-/post-test program evaluation was conducted for one year pre- and postimplementation of the algorithm on newly admitted inpatients. Adherence rate of nurses using the algorithm was monitored. FINDINGS: Overall falls decreased from 5.38% to 3.44%, with zero falls or injuries related to orthostasis for newly admitted patients. Adherence of nurses using the algorithm increased from 60% to 93%. The fall rate has been sustained less than baseline with 100% adherence, and the algorithm has been adopted as standard of practice.

Thyroid stimulating hormone ß-subunit splice variant is expressed in all fractional subsets of bone marrow hematopoietic cells and peripheral blood leukocytes and is modulated during bacterial infection.

Thyroid stimulating hormone (TSH), a hormone produced in the anterior pituitary, is used to regulate thyroid hormone secretion. It has been known for over three decades that TSH is made by the cells of the immune system; however, the functional role of immune system TSH is unclear. We previously demonstrated that an alternatively-spliced isoform of TSHß, referred to as the TSHß splice variant (TSHßv), is the primary form of TSHß made by hematopoietic cells in mice and humans. Most studies have linked TSHßv expression to myeloid cells of the immune system; however, it has recently been demonstrated that plasma cells in patients with Hashimoto's thyroiditis may be a source of immune system TSHßv. Here, we demonstrate that TSHßv is expressed in bone marrow precursors of lymphoid cells, monocytes, and granulocytes, as well as in mesenteric lymph node (MLN) cells. Plasma cells generated by in vitro culture with bacterial lipopolysaccharide (LPS), and MLN cells from mice infected with L. monocytogenes expressed TSHßv. There was an increase in the intensity of intracellular TSHßv expression in MLN cells following exposure to LPS, and in the proportion of TSHßv+ CD138+ MLN cells following L. monocytogenes infection. The number of TSHßv+ cells increased in MLN cells, particularly among CD138+ cells, following bacterial infection. This was confirmed by an increase in gene expression of BLIMP-1, the transcription factor for CD138, following infection. Levels of circulating thyroxine dropped significantly in mice 24 hrs post-infection. These findings suggest that immune system TSHßv may contribute to the host immune response during bacterial infection.

MR to CT synthesis with multicenter data in the pelvic area using a conditional generative adversarial network.

The establishment of an MRI-only workflow in radiotherapy depends on the ability to generate an accurate synthetic CT (sCT) for dose calculation. Previously proposed methods have used a Generative Adversarial Network (GAN) for fast sCT generation in order to simplify the clinical workflow and reduces uncertainties. In the current paper we use a conditional Generative Adversarial Network (cGAN) framework called pix2pixHD to create a robust model prone to multicenter data. This study included T2-weighted MR and CT images of 19 patients in treatment position from 3 different sites. The cGAN was trained on 2D transverse slices of 11 patients from 2 different sites. Once trained, the network was used to generate sCT images of 8 patients coming from a third site. The Mean Absolute Errors (MAE) for each patient were evaluated between real and synthetic CTs. A radiotherapy plan was optimized on the sCT series and re-calculated on CTs to assess the dose distribution in terms of voxel-wise dose difference and Dose Volume Histograms (DVH) analysis. It takes on average of [Formula: see text] to generate a complete sCT (88 slices) for a patient on our GPU. The average MAE in HU between the sCT and actual patient CT (within the body contour) is 48.5 ± 6 HU with our method. The maximum dose difference to the target is 1.3%. This study demonstrates that an sCT can be generated in a multicentric context, with fewer pre-processing steps while being fast and accurate.

Novel Splicing of Immune System Thyroid Stimulating Hormone ß-Subunit-Genetic Regulation and Biological Importance.

Thyroid stimulating hormone (TSH), a glycoprotein hormone produced by the anterior pituitary, controls the production of thyroxine (T4) and triiodothyronine (T3) in the thyroid. TSH is also known to be produced by the cells of the immune system; however, the physiological importance of that to the organism is unclear. We identified an alternatively-spliced form of TSHß that is present in both humans and mice. The TSHß splice variant (TSHßv), although produced at low levels by the pituitary, is the primary form made by hematopoietic cells in the bone marrow, and by peripheral leukocytes. Recent studies have linked TSHßv functionally to a number of health-related conditions, including enhanced host responses to infection and protection against osteoporosis. However, TSHßv also has been associated with autoimmune thyroiditis in humans. Yet to be identified is the process by which the TSHßv isoform is produced. Here, a set of genetic steps is laid out through which human TSHßv is generated using splicing events that result in a novel transcript in which exon 2 is deleted, exon 3 is retained, and the 3' end of intron 2 codes for a signal peptide of the TSHßv polypeptide.

Heparin Versus Normal Saline: Flushing Effectiveness in Managing Central Venous Catheters in Patients Undergoing Blood and Marrow Transplantation

BACKGROUND: Patients undergoing blood and marrow transplantation (BMT) use a central venous catheter (CVC); heparin is often employed to maintain patency but may increase the risk of complications. Research has not provided conclusive differences in efficacy and safety regarding heparin flushing versus normal saline flushing in CVC maintenance. Minimal research is specific to this patient population. OBJECTIVES: This study aimed to determine if differences exist in CVC patency, tissue plasminogen activator usage, and the incidence of central line-associated bloodstream infections when flushing with normal saline only versus heparin and normal saline among patients undergoing BMT. METHODS: A convenience sample of 30 patients undergoing allogeneic or autologous transplantation with a new non-port/non-peripherally inserted CVC were evaluated. FINDINGS: Elimination of routine heparin use could positively affect outcomes in this patient population.

Management of Bartonella Prosthetic Valve Endocarditis without Cardiac Surgery.

Two cases of Bartonella prosthetic valve endocarditis were cured when treated for 2 weeks with gentamicin and 3 months with doxycycline. Clinical cure correlated with decreased Bartonella antibody titers. This report suggests a strategy to monitor, treat, and cure Bartonella prosthetic valve endocarditis.

Involvement of Ly6C, 4-1BB, and KLRG1 in the activation of lamina propria lymphocytes in the small intestine of sanroque mice.

Roquin is an E3 ligase that regulates mRNA stability. Mice with a mutation in the Rc3h1 gene and Roquin protein, referred to as Roquinsan/san or sanroque mice, develop broad-spectrum chronic inflammatory conditions and autoimmune pathologies. Our laboratory recently reported that sanroque mice also develop extensive inflammation that is localized in the small intestine but is rare in the colon. Here, we demonstrate that small intestinal intraepithelial lymphocytes (IELs) are present in the epithelium of sanroque mice but that cell recoverability is low using standard extraction techniques even though lamina propria lymphocytes (LPLs) can be recovered in normal numbers. In studies aimed at characterizing T cell costimulatory markers and activation molecules on LPLs in sanroque mice, we identified Ly6C and 4-1BB (CD137) as being expressed at elevated levels on sanroque small intestinal LPLs, and we show that both of those subsets, in conjunction with cells expressing the KLRG1 T cell activation molecule, are sources of IL-17A, IFN-γ, and TNFα. TNFα was primarily produced by 4-1BB+, KLRG1-cells, but was also made by some 4-1BB-, KLRG1-cells, and 4-1BB-, KLRG1+ cells. These findings collectively suggest that the small intestinal inflammatory response in sanroque mice is driven, at least in part, by LPL activation through Ly6C and 4-1BB signaling, and they provide further evidence in support of using the sanroque mouse as an animal model of chronic small intestinal inflammation.

Splenic Leukocytes Traffic to the Thyroid and Produce a Novel TSHß Isoform during Acute Listeria monocytogenes Infection in Mice.

The thyroid stimulating hormone beta-subunit (TSHß) with TSHα form a glycoprotein hormone that is produced by the anterior pituitary in the hypothalamus-pituitary-thyroid (HPT) axis. Although TSHß has been known for many years to be made by cells of the immune system, the role of immune system TSH has remained unclear. Recent studies demonstrated that cells of the immune system produce a novel splice variant isoform of TSHß (TSHßv), but little if any native TSHß. Here, we show that within three days of systemic infection of mice with Listeria monocytogenes, splenic leukocytes synthesized elevated levels of TSHßv. This was accompanied by an influx of CD14+, Ly6C+, Ly6G+ cells into the thyroid of infected mice, and increased levels of intrathyroidal TSHßv gene expression. Adoptive transfer of carboxyfluorescein succinimidyl ester (CFSE)-labeled splenic leukocytes from infected mice into non-infected mice migrated into the thyroid as early as forty-eight hours post-cell transfer, whereas CFSE-labeled cells from non-infected mice failed to traffic to the thyroid. These findings demonstrate for the first time that during bacterial infection peripheral leukocytes produce elevated levels of TSHßv, and that spleen cells traffic to the thyroid where they produce TSHßv intrathyroidally.

Comparing Outcomes with Bone Marrow or Peripheral Blood Stem Cells as Graft Source for Matched Sibling Transplants in Severe Aplastic Anemia across Different Economic Regions.

Bone marrow (BM) is the preferred graft source for hematopoietic stem cell transplantation (HSCT) in severe aplastic anemia (SAA) compared with mobilized peripheral blood stem cells (PBSCs). We hypothesized that this recommendation may not apply to those regions where patients present later in their disease course, with heavier transfusion load and with higher graft failure rates. Patients with SAA who received HSCT from an HLA-matched sibling donor from 1995 to 2009 and reported to the Center for International Blood and Marrow Transplant Research or the Japan Society for Hematopoietic Cell Transplantation were analyzed. The study population was categorized by gross national income per capita and region/countries into 4 groups. Groups analyzed were high-income countries (HIC), which were further divided into United States-Canada (n = 486) and other HIC (n = 1264); upper middle income (UMIC) (n = 482); and combined lower-middle, low-income countries (LM-LIC) (n = 142). In multivariate analysis, overall survival (OS) was highest with BM as graft source in HIC compared with PBSCs in all countries or BM in UMIC or LM-LIC (P < .001). There was no significant difference in OS between BM and PBSCs in UMIC (P = .32) or LM-LIC (P = .23). In LM-LIC the 28-day neutrophil engraftment was higher with PBSCs compared with BM (97% versus 77%, P = .002). Chronic graft-versus-host disease was significantly higher with PBSCs in all groups. Whereas BM should definitely be the preferred graft source for HLA-matched sibling HSCT in SAA, PBSCs may be an acceptable alternative in countries with limited resources when treating patients at high risk of graft failure and infective complications.

The Impact of Graft-versus-Host Disease on the Relapse Rate in Patients with Lymphoma Depends on the Histological Subtype and the Intensity of the Conditioning Regimen.

The purpose of this study was to analyze the impact of graft-versus-host disease (GVHD) on the relapse rate of different lymphoma subtypes after allogeneic hematopoietic cell transplantation (allo-HCT). Adult patients with a diagnosis of Hodgkin lymphoma, diffuse large B cell lymphoma, follicular lymphoma (FL), peripheral T cell lymphoma, or mantle cell lymphoma (MCL) undergoing HLA-identical sibling or unrelated donor hematopoietic cell transplantation between 1997 and 2009 were included. Two thousand six hundred eleven cases were included. A reduced-intensity conditioning (RIC) regimen was used in 62.8% of the transplantations. In a multivariate analysis of myeloablative cases (n = 970), neither acute (aGVHD) nor chronic GVHD (cGVHD) were significantly associated with a lower incidence of relapse/progression in any lymphoma subtype. In contrast, the analysis of RIC cases (n = 1641) showed that cGVHD was associated with a lower incidence of relapse/progression in FL (risk ratio [RR], .51; P = .049) and in MCL (RR, .41; P = .019). Patients with FL or MCL developing both aGVHD and cGVHD had the lowest risk of relapse (RR, .14; P = .007; and RR, .15; P = .0019, respectively). Of interest, the effect of GVHD on decreasing relapse was similar in patients with sensitive disease and chemoresistant disease. Unfortunately, both aGVHD and cGVHD had a deleterious effect on treatment-related mortality and overall survival (OS) in FL cases but did not affect treatment-related mortality, OS or PFS in MCL. This study reinforces the use of RIC allo-HCT as a platform for immunotherapy in FL and MCL patients.

MicroRNA signatures differentiate Crohn's disease from ulcerative colitis.

BACKGROUND: Excessive and inappropriate immune responses are the hallmark of several autoimmune disorders, including the inflammatory bowel diseases (IBD): Crohn's disease (CD) and ulcerative colitis (UC). A complex etiology involving both environmental and genetic factors influences IBD pathogenesis. The role of microRNAs (miRNAs), noncoding RNAs involved in regulating numerous biological processes, to IBD pathology, in terms of initiation and progression, remains ill-defined. In the present study, we evaluated the relationship between colon, peripheral blood, and saliva whole miRNome expression in IBD patients and non-inflammatory bowel disease (non-IBD) controls to identify miRNAs that could discriminate CD from UC. Quantitative real-time PCR (qRT-PCR) was used to validate and assess miRNA expression. RESULTS: Microarray analysis demonstrated that upwards of twenty six miRNAs were changed in CD and UC colon biopsies relative to the non-IBD controls. CD was associated with the differential expression of 10 miRNAs while UC was associated with 6 miRNAs in matched colon tissues. CD was associated with altered expression of 6 miRNAs while UC was associated with 9 miRNAs in whole blood. Expression of miR-101 in CD patients and miR-21, miR-31, miR-142-3p, and miR-142-5p in UC patients were altered in saliva. CONCLUSIONS: Our results suggest that there is specific miRNA expression patterns associated with UC versus CD in three separate tissue/body fluids (colon, blood, and saliva). Further, the aberrant miRNA expression profiles indicate that miRNAs may be contributory to IBD pathogenesis, or at least reflect the underlying inflammation. Scrutinizing miRNA expression in saliva and blood samples may be beneficial in monitoring or diagnosing disease in IBD patients. A panel of miRNAs (miR-19a, miR-21, miR-31, miR-101, miR-146a, and miR-375) may be used as markers to identify and discriminate between CD and UC.

Center for International Blood and Marrow Transplant Research chronic graft-versus-host disease risk score predicts mortality in an independent validation cohort.

We previously reported a risk score that predicted mortality in patients with chronic graft-versus-host disease (CGVHD) after hematopoietic stem cell transplantation (HCT) between 1995 and 2004 and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). We sought to validate this risk score in an independent CIBMTR cohort of 1128 patients with CGVHD who underwent transplantation between 2005 and 2007 using the same inclusion criteria and risk score calculations. According to the sum of the overall risk score (range, 1 to 12), patients were assigned to 4 risk groups (RGs): RG1 (0 to 2), RG2 (3 to 6), RG3 (7 to 8), and RG4 (9 to 10). RG3 and RG4 were combined, as RG4 accounted for only 1% of the total cohort. Cumulative incidences of nonrelapse mortality (NRM) and probability of overall survival were significantly different between each RG (all P < .01). NRM and overall survival at 5 years after CGVHD for each RG were 17% and 72% in RG1, 26% and 53% in RG2, and 44% and 25% in RG3, respectively (all P < .01). Our study validates the prognostic value of the CIBMTR CGVHD RGs for overall survival and NRM in a contemporary transplantation population. The CIBMTR CGVHD RGs can be used to predict major outcomes, tailor treatment planning, and enroll patients in clinical trials.