Transplantation Techniques Research Articles

Allogeneic stem cell Transplant in Hematological Disorders: A Decade of Experience

Background: Allogeneic hematopoietic cell transplantation (allo-HCT) is a complex procedure with the potential to provide curative treatment for various hematological disorders. This study aims to evaluate the outcomes of allo-HCT in hematological diseases and identify significant complications in a single-center setting. Materials and Methods: We conducted a retrospective analysis of 180 patients with hematological diseases who underwent allo-HCT between January 2011 and December 2021. Key outcomes, including indications for transplantation, overall survival, engraftment time, relapse rates, graft-versus-host disease (GVHD), and transplant-related mortality (TRM) were assessed. Results: The most common indications for allo-HCT were benign hematological diseases, particularly aplastic anemia, and thalassemia major. Despite the majority of patients receiving fully matched transplants, Acute GVHD was observed in 30% of the cohort. Graft failure occurred in 13 patients, with primary and secondary graft failure rates of 1.6% and 5.5%, respectively. Sepsis emerged as the primary cause of non-relapsed mortality at day 100 and beyond. The overall survival rate in this study was 62%, with 79% of patients disease-free on their last visit. Conclusion: This study provides valuable insights into the treatment strategies and patient care of allo-HCT for hematological disorders by offering a comprehensive overview of multiple relevant outcomes. The findings underscore the significance of addressing complications and risk factors associated with allogeneic transplantation, including GVHD and infections. Future research should focus on further optimizing transplantation techniques to minimize complications and enhance patient survival.

Identification and Manipulation of Spermatogonial Stem Cells with the Aim of Inducing Spermatogenesis in Vitro.

Assisted reproduction techniques for infertile men with non-obstructive azoospermia require a sufficient number of functional germ cells produced in vitro. Understanding the mechanisms that allow the resumption of spermatogenesis outside the testicular environment is crucial for fertility preservation in these patients. A review of the literature was conducted using databases such as PubMed, Scopus and Web of Science, with keywords including "spermatogonial stem cell," "germ cells," "male factor infertility," and "enrichment and propagation of SSCs in vitro." Currently, two models-"in vivo" and "in vitro"-have been developed for producing haploid germ cells. The "in vivo" models include spermatogonial stem cell transplantation and testicular xenograft techniques. In contrast, the "in vitro" models consist of conventional culture systems, organ culture, and three-dimensional culture systems, all designed to induce spermatogenesis in vitro. These culture systems enable the simulation of the seminiferous epithelium in vitro, which facilitates better regulation of cell-signaling pathways that control the self-renewal and differentiation of SSCs. This review provides up-to-date information on the organization of SSCs, focusing on the identification, proliferation, and differentiation of spermatogonia in vitro.

Cervical heterotopic heart transplantation in mice using a novel suture technique

BackgroundVascularized transplantation models in mice are critical to understand mechanisms that mediate rejection and to develop new therapeutics. Standard abdominal heterotopic heart transplantation techniques employ an end-to-side suture technique and are the workhouse of transplant immunology research laboratories. Recently, cervical heterotopic heart transplantation in mice has emerged as an alternative due to several advantages but is conventionally performed by suture or cuff techniques in an end-to-end fashion. Therefore, we introduce an end-to-side anastomosis technique. MethodsThe donor pulmonary artery is end-to-side anastomosed to the recipient right external jugular vein, using a continuous 10-0 nylon suture. Vascular suturing is accomplished inside the vessel on the posterior wall, and then outside the vessel on the anterior wall. Finally, the donor ascending aorta is end-to-side anastomosed to the recipient common carotid artery with an identical suture technique. ResultsThe median times for the donor heart harvest, recipient preparation, anastomoses of the pulmonary artery to the external jugular vein, and the ascending aorta to the common carotid artery were 12, 10, 12 and 11 min, respectively. The survival rate was 100% (n=20). ConclusionsWe provide a detailed description of how to perform end-to-side anastomoses using a suture technique in the mouse cervical heart transplantation model. This procedure reconstitutes coronary blood flow in the heart graft with minimal interruption to recipient anatomy and provides an experimental platform to study transplant immunology.

Current Scenario and Future Perspectives of Porcine Corneal Xenotransplantation.

Corneal diseases represent a significant cause of blindness worldwide, with corneal transplantation being an effective treatment to prevent vision loss. Despite substantial advances in transplantation techniques, the demand for donor corneas exceeds the available supply, particularly in developing countries. Cornea xenotransplantation has emerged as a promising strategy to address the worldwide scarcity, notably using porcine corneas. In addition to the inherent immune privilege of the cornea, the low cost of porcine breeding and the anatomical and physiological similarities between humans and pigs have made porcine corneas a viable alternative. Nonetheless, ethical concerns, specifically the risk of xenozoonotic transmission and the necessity for stringent biosafety measures, remain significant obstacles. Moreover, the success of xenotransplantation is compromised by innate and adaptive immune responses, which requires meticulous consideration and further studies. Despite these challenges, recent breakthroughs have further contributed to reducing immunogenicity while preserving the corneal architecture. Advances in genetic engineering, such as the use of CRISPR-Cas9 to eliminate critical porcine antigens, have shown promise for mitigating immune reactions. Additionally, new immunosuppressive protocols, such as have techniques like decellularization and the use of porcine-derived acellular matrices, have greatly increased graft survival in preclinical models. Future research must focus on refining immunomodulatory strategies and improving graft preparation techniques to ensure the long-term survival and safety of porcine corneal xenotransplantation in clinical trials in humans.

Analysis of two reperfusion techniques in uterine transplantation in an experimental model.

Uterine transplantation was developed for the treatment of absolute uterine factor infertility. As it is a new modality of transplantation, there is still room for technical improvement. A factor that impacts graft survival in organ transplantation is the warm ischemia time. In uterine transplantation specifically, at least two vascular anastomoses are performed on each side of the uterus, and the graft revascularization takes place when the vascular clamps of the arteries and veins are released on both sides simultaneously. For this reason, the warm ischemia time in uterine transplant is expected to be considerably long. The purpose of this study was to compare the sequential technique of uterine graft revascularization, which aims to reduce the warm ischemia time of the procedure, with the simultaneous revascularization technique. For the procedure, the uterine auto-transplantation technique was performed using 10 non-pregnant adult ewes weighing about 45 kg, divided into two groups: simultaneous revascularization group (5 animals) and sequential revascularization group (5 animals). To evaluate the groups, we analyzed the procedure and warm ischemia times, graft macroscopy, hemodynamic, laboratory, and histological parameters of the uterus. The sequential revascularization technique group had similar surgical procedure times, and the warm ischemia time was significantly shorter with medians of 32 min in the sequential group versus 72 min in the simultaneous group (p < 0.008). The graft macroscopy and hemodynamic, laboratory, and histological parameters evaluated were similar between the groups. The sequential revascularization technique proved to reduce the warm ischemia time in the sheep uterine auto-transplantation model without compromising graft viability.

A novel technique for pancreatic juice drainage to the remaining graft duodenum after blood reperfusion in pancreas transplantation

TechniqueIn pancreatic transplantation, during bench surgery, the oral and anal sides of a graft duodenum are cut with linear staplers to be as short as possible in order to ascertain blood flow to the graft duodenum stumps. However, this can lead to a distended graft duodenum owing to the large amount of pancreatic juice produced after blood reperfusion during the recipient operation. Controlling bleeding after blood reperfusion and ensuring complete hemostasis are difficult due to obstructed vision caused by the distended graft duodenum. Additionally, the edematous mucosa due to the distended graft duodenum makes it difficult to anastomose the graft duodenum to the recipient's small intestine. Herein, we developed a novel technique during bench surgery to overcome these disadvantages of a distended graft duodenum, by initially leaving the anal side of the graft duodenum uncut to drain the produced pancreatic juice following blood reperfusion. After confirming the hemostasis and anastomosing the graft duodenum to the small intestine, the anal side of the graft duodenum is cut with a linear stapler at the point where sufficient blood flow is confirmed based on duodenal color. ResultsThis technique enables us to concentrate on the hemostasis and anastomosis without attending to the distended graft duodenum. Furthermore, stump issues due to insufficient blood flow can be avoided. ConclusionThis pancreatic juice drainage technique in pancreas transplantation can be useful to reduce postoperative complications.

Endovascular Management of Thrombosed Cavoportal Anastomosis After Liver Transplantation Using Catheter Directed Thrombolysis and Stent Placement: A Case Report

Cavoportal hemitransposition (CPHT) is a rarely performed treatment technique in liver transplantation in cases of extensive splanchnic thrombosis, in which the inferior vena cava of the recipient is used to perfuse the portal vein of the allograft. A case of a 65-year-old liver transplantation patient with an acutely thrombosed cavoportal anastomosis is presented. After unsuccessful medical treatment, recanalization was obtained with transfemoral catheter directed thrombolysis, angioplasty and stent placement. Although this type of treatment has been extensively documented for the management of portal anastomotic problems after orthotopic liver transplantation, data on its application in modified transplantation techniques including CPHT are rare. This technique provides a minimally invasive treatment option in CPHT patients with cavoportal anastomotic problems, who might otherwise require complex surgical repair or retransplantation.

Evolving indications and surgical techniques for corneal transplantation at a tertiary eye care center in southern China

BackgroundThis retrospective study aimed to analyze the evolution of primary indications and surgical techniques for corneal transplantation in Southern China from 2012 to 2021.MethodsThe medical charts of all patients who underwent keratoplasty between January 2012 and December 2021 at Zhongshan Ophthalmic Centre, Sun Yat-Sen University, Guangzhou, Southern China were reviewed. We collected and analyzed the primary indications for corneal transplantation and the surgical methods used in each keratoplasty.ResultsThe total number of corneal transplantations was 7,286 during this decade, increasing from 210 cases in 2012 to 1054 cases in 2021. The primary indications for keratoplasty included acquired nontraumatic corneal diseases (56.2%), congenital corneal abnormalities (16.4%), acquired traumatic corneal diseases (14.0%), and regraft (13.4%). Infectious keratitis was the leading indication among all keratoplasties (18.5%), followed by regraft (13.4%). Over the decade, the proportion of infectious keratitis gradually decreased (P = 0.013), while the proportion of regraft increased (P = 0.019). The predominant surgical technique was penetrating keratoplasty (PKP), accounting for 56.7%. However, the number of deep anterior lamellar keratoplasty (DALK) and endothelial keratoplasty (EK) significantly increased from 2012 to 2021 (P = 0.007 and P = 0.002).ConclusionsThe annual number of corneal transplants significantly increased from 2012 to 2021. In the past decade, infectious keratitis and regraft have become the leading primary indications for corneal transplantation. Although the use of customized lamellar techniques has dramatically increased, PKP remains the predominant surgical technique for keratoplasty.

Lantidra: Cell Therapy for Treatment of Type 1 Diabetes Mellitus

The more recent cell treatment for type 1 Diabetes is called lantidra. Lantidra has recently received approval to treat type 1 Diabetes mellitus. The first allogeneic (deceased donor) pancreatic islet cell therapy, lantidra (donislecel), was approved by the FDA Centre for Biologics Evaluation and Research (CBER) on June 28, 2023. It is intended to treat adults with type 1 diabetes who, despite current management, do not achieve target glycosylated hemoglobin levels due to recurrent episodes of severe hypoglycemia. The editorial’s goal is to draw attention to the growing impact of type 1 diabetes on the world’s health, discuss earlier attempts at pancreatic transplant techniques, and announces the first regulatory approval of a revolutionary transplant strategy called allogeneic pancreatic islet beta cell infusion.

Research progress of stem cell therapy for neurological diseases

Neurological diseases are considered one of the leading causes of death and disability worldwide; not only do patients suffer, but they also place a significant economic burden on families and society. Traditional medications now show limited efficacy, and surgical interventions can be dangerous. The need to develop new medicines is critical as more people become aware of the immense burden this disease imposes on society and the limited number of viable therapeutic options that currently exist. Modern research is increasingly focusing on novel and potent approaches to treat neurological illnesses to address these challenges. One promising method is the stem cell-based therapy. The development of stem cell transplantation techniques and cellular therapies in recent years has provided new hope for the treatment of neurological disorders. Stem cell therapies have demonstrated therapeutic potential in animal models, and different types of stem cells have been used in clinical trials. In this study, we explored the applications of mesenchymal stem cells, dental pulp stem cells, and induced pluripotent stem cells in neurological diseases. In recent years, we have examined the current status and progress of stem cell applications in treating neurological diseases, both domestically and internationally, and reviewed some of the key challenges encountered.

Cryoablation Does Not Significantly Contribute to Systemic Effector Immune Responses in a Poorly Immunogenic B16F10 Melanoma Model.

Cryoablation is a minimally invasive procedure implemented to destroy solid tumors. It also results in the release of tumor antigens into the systemic circulation. Preclinical studies using immunogenic tumor models have shown that cryoablation evokes antitumor immune responses. The mechanisms by which cryoablation impacts immune responses in poorly immunogenic tumors have not been sufficiently explored. We used a bilateral B16F10 melanoma model devoid of strong immunogenic antigens. Cryoablation-induced effector immune responses were investigated, also in combination with a peritumoral STING agonist and systemic anti-PD-1. Selective immune cell depletion, T-cell migration arrest, in vivo T-cell transplantation, and cryoablation versus surgical removal techniques were used to determine the contribution of cryoablation and immunotherapies to systemic antitumor effector immune responses. Treatment of a tumor with cryoablation + STING agonist + anti-PD-1 resulted in the rejection of unablated, contralateral tumors. Depletion studies demonstrated that tumor rejection is essentially dependent on CD8+ T cells. T-cell arrest in the lymph nodes had no effect on the rejection process. Splenic CD8+ T cells isolated from cryoablation-treated mice with B16F10 melanoma, upon transplantation into melanoma-bearing recipients, did not impact the recipient's tumor growth. Finally, comparison of cryoablation + STING agonist + anti-PD-1 versus surgery + STING agonist + anti-PD-1 in the bilateral tumor model showed no difference in the rejection of contralateral tumors. Cryoablation does not significantly contribute to systemic antitumor effector immune responses in a B16F10 melanoma model. Cryoablation primarily performs tumor debulking, and immunotherapy functions independently of cryoablation in eliciting antitumor effector immune responses.

Clinical practice guideline for autologous bone grafting in China (2024 edition)

Autogenous bone has always been the gold-standard bone graft material. As such, it is the primary choice for bony grafts. Autogenous bone grafting has been performed for hundreds of years, and more than 2 million cases of autogenous bone transplantation are performed each year worldwide. It has become the most commonly used surgical method in orthopedics. Numerous studies have suggested methods to select the appropriate donor area, standardize the surgical procedure, and reduce donor site complications, but clinical standards and guidelines remain to be established. To better guide the clinical practice of physicians in China, the Trauma Orthopedic Branch of the Chinese Orthopedic Association, the External Fixation and Limb Reconstruction Branch of the Chinese Orthopedic Association, and the Microsurgery Branch of the Beijing Orthopedic Association developed the "Clinical practice guideline for autogenous bone grafting in China (2024 edition)" based on current medical evidence. This guideline systematically evaluates recent domestically and internationally published literature and medical research evidence in the field of autologous bone grafting in the Chinese population. The guideline was produced with the aim of standardizing the indications and techniques for autogenous bone transplantation, as well as preventing complications at the harvesting site of autologous bone, in the Chinese population.

The First Case of Intra-portal Islet Implantation During Liver Machine Perfusion Allowing Simultaneous Islet-liver Transplantation in A Human: A New and Safe Treatment for End-stage Liver Disease Combined With Diabetes Mellitus.

Evaluating the safety and efficacy of implanting a liver with islet grafts into patients with end-stage liver disease and diabetes mellitus (DM). DM and end-stage liver diseases are significant health concern worldwide, often coexisting and mutually influencing each other. Addressing both diseases simultaneously is paramount. We utilized the islet transplantation combined ischemia-free liver transplantation (ITIFLT) technique to treat a patient with hepatocellular carcinoma (HCC) and type 2 diabetes mellitus (T2DM). The liver was procured and preserved using the ischemia-free liver transplantation (IFLT) technique, and during normothermic machine perfusion (NMP), isolated and purified islet grafts were transplanted into the liver through the portal vein. Finally, the liver, incorporating with the transplant islet grafts, was implanted into the recipient without interruption of blood supply. The patient received both liver and islet graft from the same donor. The patient achieved insulin-independence by post-transplant day (PTD) 9, and both liver and islet function remained robust. The patient was discharged on PTD 18 and experienced no surgical or transplantation-related complications during the follow-up period. Furthermore, islet grafts presence was observed in liver biopsies after islet transplantation. This landmark case marks the inaugural application of ITIFLT in humans, signifying its potential as a promising treatment modality for end-stage liver disease with DM.

P.185: Urological complications following the use of a modified ureteral reimplantation technique in kidney transplantation.

P.185: Urological complications following the use of a modified ureteral reimplantation technique in kidney transplantation.

Utilizing Multifaceted Approaches to Target Drug Delivery in the Brain: From Nanoparticles to Biological Therapies.

The blood-brain barrier (BBB) poses an important obstacle to treating neurological disorders because it limits the entry of therapeutic agents into the central nervous system (CNS). Surmounting this barrier is crucial for delivering drugs effectively and targeting precise areas of the brain affected by conditions like Parkinson's disease, Alzheimer's disease, and brain tumors. This review examines the diverse strategies employed to enhance brain targeting, including nanotechnology, viral vectors, and biological therapies. Nanoparticles, liposomes, and dendrimers offer promising approaches for encapsulating drugs and facilitating their transport across the BBB. Viral vectors, such as adeno-associated viruses, demonstrate high transfection efficiency for gene therapy applications in CNS diseases. Biological therapies, including stem cell transplantation and neuromodulation techniques, can potentially restore normal cellular function and treat genetic disorders. Challenges such as BBB permeability, safety concerns, and regulatory considerations are discussed, along with future perspectives on precision medicine, noninvasive delivery methods, and biomarker discovery. By addressing these challenges and embracing innovative approaches, the field of brain drug targeting aims to transfer the way that neurological illness is treated and improve patient outcomes.

200.1: Surgical modifications to the conventional kidney transplant technique - The Miami transplant institute approach.

200.1: Surgical modifications to the conventional kidney transplant technique - The Miami transplant institute approach.

Femtosecond Laser-Assisted Autologous Glueless Simple Limbal Epithelial Transplantation in Unilateral Limbal Stem Cell Deficiency: 12-Month Outcome of the First Clinical Cases.

Surgical treatment of unilateral limbal stem cell deficiency (LSCD) is based on limbal stem cell transplantation. Glueless simple limbal epithelial transplantation (G-SLET) technique implements several limbal micrografts harvested from the healthy eye of the same patient into the peripheral corneal tunnels without the use of fibrin glue and human amniotic membrane. A novel customized algorithm and software for a low-energy femtosecond laser (FSL) were developed and tested using 5 pairs of isolated porcine eyes. FSL-assisted G-SLET modification was assessed in 3 clinical cases of unilateral LSCD caused by chemical burns. Corneal epithelization efficacy, best-corrected visual acuity, corneal epithelial mapping, central corneal thickness, and impression cytology with immunohistochemical examination were evaluated. All patients were followed up for 12 months postoperatively. The FSL set for 100% energy and the pattern of 8 nonpenetrating vertical cuts with oblique tunnel portions having variable incision depths and diameter of 8.5 mm and higher were selected for further clinical evaluation. Clinically, stable corneal epithelialization was achieved 2 to 3 weeks after intervention. At the 6-month follow-up, all patients had a healthy corneal epithelium with limbal micrografts visible inside the corneal tunnels. Best-corrected visual acuity markedly improved in 2 cases, but not in the third case with severe corneal stromal scarring. In addition, all patients noted a full-scale reduction in subjective complaints and substantial improvement in their quality of life. The FSL-assisted G-SLET is a new technique for autologous limbal stem cell transplantation in patients with unilateral LSCD. It allows the standardization of corneal tunnel localization and dimensions, thereby increasing the safety of the surgical procedure.

Assessment of Generative Artificial Intelligence (AI) Models in Creating Medical Illustrations for Various Corneal Transplant Procedures.

This study aimed to task and assess generative artificial intelligence (AI) models in creating medical illustrations for corneal transplant procedures such as Descemet's stripping automated endothelial keratoplasty (DSAEK), Descemet's membrane endothelial keratoplasty (DMEK), deep anterior lamellar keratoplasty (DALK), and penetrating keratoplasty (PKP). Methods: Six engineered prompts were provided to Decoder-Only Autoregressive Language and Image Synthesis 3 (DALL-E 3) and Medical Illustration Manager (MIM) to guide these generative AI models in creating a final medical illustration for each of the four corneal transplant procedures. Control illustrations were created by the authors for each transplant technique for comparison. A grading system with five categories with a maximum score of 3 points each (15 points total) was designed to objectively assess AI's performance. Four independent reviewers analyzed and scored the final images produced by DALL-E 3 and MIM as well as the control illustrations. All AI-generated images and control illustrations were then provided to Chat Generative Pre-Trained Transformer-4o (ChatGPT-4o), which was tasked with grading each image with the grading system described above. All results were then tabulated and graphically depicted. The control illustration images received significantly higher scores than produced images from DALL-E 3 and MIM in legibility, anatomical realism and accuracy, procedural step accuracy, and lack of fictitious anatomy (p<0.001). For detail and clarity, the control illustrations and images produced by DALL-E 3 and MIM received statistically similar scores of 2.75±0.29, 2.19±0.24, and 2.50±0.29, respectively (p=0.0504). With regard to mean cumulative scores for each transplant procedure image, the control illustrations received a significantly higher score than DALL-E 3 and MIM (p<0.001). Additionally, the overall mean cumulative score for the control illustrations was significantly higher than DALL-E 3 and MIM (14.56±0.51 (97.1%), 4.38±1.2 (29.2%), and 5.63±1.82 (37.5%), respectively (p<0.001)). When assessing AI's grading performance, ChatGPT-4o scored the images produced by DALL-E 3 and MIM significantly higher than the average scores of the independent reviewers (DALL-E 3: 10.0±0.0 (66.6%) vs. 4.38±1.20 (29.2%),p<0.001; MIM: 10.0±0.0 (66.6%) vs. 5.63±1.82 (37.5%), p<0.001). However, mean scores for the control illustrations between ChatGPT-4o and the independent reviewers were comparable (15.0±0.0 (100%) vs. 14.56±0.13 (97.1%); p>0.05). AI is an extremely powerful and efficient tool for many tasks, but it is currently limited in producing accurate medical illustrations for corneal transplant procedures. Further development is required for generative AI models to create medically sound and accurate illustrations for use in ophthalmology.

SARS-CoV2 infection in whole lung primarily targets macrophages that display subset-specific responses

Deciphering the initial steps of SARS-CoV-2 infection, that influence COVID-19 outcomes, is challenging because animal models do not always reproduce human biological processes and in vitro systems do not recapitulate the histoarchitecture and cellular composition of respiratory tissues. To address this, we developed an innovative ex vivo model of whole human lung infection with SARS-CoV-2, leveraging a lung transplantation technique. Through single-cell RNA-seq, we identified that alveolar and monocyte-derived macrophages (AMs and MoMacs) were initial targets of the virus. Exposure of isolated lung AMs, MoMacs, classical monocytes and non-classical monocytes (ncMos) to SARS-CoV-2 variants revealed that while all subsets responded, MoMacs produced higher levels of inflammatory cytokines than AMs, and ncMos contributed the least. A Wuhan lineage appeared to be more potent than a D614G virus, in a dose-dependent manner. Amidst the ambiguity in the literature regarding the initial SARS-CoV-2 cell target, our study reveals that AMs and MoMacs are dominant primary entry points for the virus, and suggests that their responses may conduct subsequent injury, depending on their abundance, the viral strain and dose. Interfering on virus interaction with lung macrophages should be considered in prophylactic strategies.

Influence of comorbidities on outcome in 1102 patients with an allogeneic hematopoietic stem cell transplantation.

The hematopoietic comorbidity risk index (HCT-CI) is a pre-transplant risk assessment tool used to qualify comorbidities to predict non-relapse mortality (NRM) of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). HSCT procedures continue to improve. Therefore, the predictive value of HCT-CI needs to be re-evaluated. Our study is a retrospective analysis of pre-existing comorbidities assessing the relevance of the HCT-CI on the outcome of consecutive patients (n = 1102) undergoing allo-HSCT from 2006-2021. HCT-CI was classified as low (HCT-CI 0), intermediate (HCT-CI 1-2) and high-risk (HCT-CI ≥ 3). At 10 years, NRM for low, intermediate, and high-risk HCT-CI group was 21.0%, 26.0%, and 25.8% (p = 0.04). NRM difference was significant between low to intermediate (p < 0.001), but not between intermediate to high-risk HCT-CI (p = 0.22). Overall survival (OS) at 10 years differed significantly with 49.9%, 39.8%, and 31.1%, respectively (p < 0.001). In multivariate analysis of HCT-CI organ subgroups, cardiac disease was most strongly associated with NRM (HR = 1.73, p = 0.02) and OS (HR = 1.77, p < 0.001). All other individual organ comorbidities influenced NRM to a lesser extent. Further, donor (HR = 2.20, p < 0.001 for unrelated and HR = 2.17, p = 0.004 for mismatched related donor), disease status (HR = 1.41, p = 0.03 for advanced disease) and previous HSCT (HR = 1.55, p = 0.009) were associated with NRM. Improvement in transplant techniques and supportive care may have improved outcome with respect to comorbidities.