Unavailability Of Donors Research Articles

Bioactive Hydrogels Inspired by Laminin: An Emerging Biomaterial for Tissue Engineering Applications.

Tissue or organ damage due to severe injuries or chronic diseases can adversely affect the quality of life. Current treatments rely on organ or tissue transplantation which has limitations including unavailability of donors, ethical issues, or immune rejection after transplantations. These limitations can be addressed by tissue regeneration which involves the development of bioactive scaffolds closely mimicking the extracellular matrix (ECM). One of the major components of ECM is the laminin protein which supports several tissues associated with important organs. In this direction, peptide-based hydrogels can effectively mimic the essential characteristics of laminin. While several reports have discussed the structure of laminin, the potential of laminin-derived peptide hydrogels as effective biomaterial for tissue engineering applications is yet to be discussed. In this context, the current review focuses on the structure of laminin and its role as an essential ECM protein. Further, the potential of short peptide hydrogels in mimicking the crucial properties of laminin is proposed. The review further highlights the significance of bioactive hydrogels inspired by laminin - in addressing numerous tissue engineering applications including angiogenesis, neural, skeletal muscle, liver, and adipose tissue regeneration along with a brief outlook on the future applications of these laminin-based hydrogels.

Evaluation of Three-Dimensional Reconstruction Technology in Precision Hepatectomy for Primary Liver Cancer

Abstract Background Primary Liver Cancer has become a potent threat to the world due to its high morbidity and mortality rate. Up till now, Liver transplantation is the most suggested treatment but it is not feasible owing to the unavailability of donors and high cost. Hepatectomy provides an alternative treatment to this deadliest disease. Precision hepatectomy is performed with the aid of traditional 2 dimensional technology and image processing such as CT scan and Magnetic Resonance Imaging. However, it requires extensive expertise and pose challenges to the young doctors in decision making. Modern imaging and computer technology has opened the new avenues in medical field with the advent of 3 dimensional Reconstruction and visualization methods. Material and Methods We conducted a cohort retrospective study. In this study, we tried to evaluate the efficacy an impacts of 3 dimensional reconstruction on the preoperative planning of hepatectomy, intraoperative conditions and postoperative complications. We took 95 patients and divided them in two groups A and B. Group A has 67 patients who underwent hepatectomy before the application of 3 dimensional reconstruction and 28 patients on whom hepatectomy was performed according to the planning and methods of 3dimensional reconstruction and results were evaluated. Results Our study found that 3 dimensional reconstruction can help in better diagnosis, resection planning and reduce the postoperative complication. Results were not significant difference p > 0.05 on the incidence of postoperative complication between group A and B. Results were significant p < 0.05 for the intraoperative blood loss, optimal surgery time and postoperative hospitalization. Conclusion Hence, 3 dimensional reconstruction is a landmark discovery in medical sciences for the accurate evaluation and resection of complex liver cancers.

Tyrosine Kinase Inhibitor (TKI) Discontinuation in Non-Allografted Ph+ Acute Lymphoblastic Leukemia Patients, a Campus ALL Real-Life Study

Introduction. Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) patients are commonly treated with tyrosine kinase inhibitors (TKI) in combination with either steroids, chemotherapy and more recently also immunotherapy. In the past, allogeneic transplant (SCT) was considered the only curative option; however, with the introduction of more potent TKIs as well as immunotherapy this milestone is nowadays debated, mostly for patients who achieve a molecular response. Moreover, as in chronic myeloid leukemia (CML), it is becoming relevant to understand if patients may over time discontinue TKI treatment. For this purpose, it is pivotal to report the outcome of Ph+ ALL patients who, for any reason, stopped TKI treatment. Patients and Methods. Forty-seven adult Ph+ ALL patients treated since 1 January 2000, and who did not undergo a SCT, were retrospectively collected from 12 Italian centers participating to the Campus ALL network. Their treatment plan included a TKI +/- chemotherapy according to the center current practice and/or according to the ongoing national trial they were enrolled in. The median age was 63 years (20-84), 20 patients (43%) were males, 30 patients harbored a p190 transcript, 15 a p210 transcript and 2 had both transcripts. Twenty-six patients were treated within a trial, while 21 were off-protocol. For 32 patients, induction was based only on a TKI plus steroids, whereas the remaining 15 received a combination of a TKI plus chemotherapy (in 3 cases high intensity protocols such as the NILG (Northern Italian Leukemia Group) and HCVAD regimens, in 12 low dose chemotherapy). The reasons not to transplant patients were: donor unavailability (5), clinical decision, mainly due to age/unfitness (30), patient's refusal (4), and achievement of a molecular response (i.e. at least BCR-ABL/ABL ≤0.01%) (8). The median follow-up was 60 months, with a median overall survival (OS) not reached at the last follow-up and a median disease-free survival (DFS) of 12 years. At the last follow-up, 12/47 patients had experienced a relapse. At the end of the induction (i.e. after 3 months, at a median of +82 days, from treatment initiation), 27 patients had achieved a molecular response. Overall. a molecular response was obtained in 40/46 pts (data not available for 1 case) after a median of 5 month, and was associated with a significantly lower hazard of disease recurrence (HR=0.057, 95% CI: 0.006-0.51, p=0.011) after adjusting for gender, fusion protein, association with chemotherapy, CMR at 3 months. Results. TKI treatment was discontinued in 14 of the 47 patients evaluated. The reasons for discontinuation were either toxicity (6) or clinical/patient decision (8). Eight patients harbored a p190 transcript, 5 a p210 transcript and 1 carried both. At the time of discontinuation, the median age was 75 years (23-87) and patients had been on a TKI for a median of 57.5 months (8-160) prior to stopping treatment. For these cases, the median WBC at diagnosis were 8.6 x 10 9/l (2.1-306 x 10 9/l). In 7 patients the first TKI used was imatinib, in 3 dasatinib, in 3 ponatinib and in 1 nilotinib. All patients but 1 had achieved a molecular response before stopping treatment; the only patient who never achieved a molecular response prior to discontinuing the TKI had a rapid relapse (1 month). At the last follow-up, 9 cases were still in treatment-free remission (TFR), whereas 5 eventually relapsed after 1, 1, 4, 14 and 30 months, respectively. Re-challenge with a TKI led to a hematological and molecular response in 3 of the 5 patients. The remaining 2 patients, who had been previously heavily treated and whose TFR was of only 1 month, received salvage standard chemotherapy but eventually died from ALL progression. The median time of TFR for the entire cohort of 14 patients was 20.5 months (1-82). When considering only the 9 patients who remain off treatment, the median time of TFR was 29.5 months (7-82) (Table 1, Figure 1). Conclusions. We report the outcome of 14 Ph+ ALL patients who discontinued TKI treatment due to various reasons. Nine of them are still on TFR after more than 2 years at the last follow-up, reinforcing the concept that a TFR is feasible in selected adult Ph+ ALL patients. Of further relevance, TKI re-challenge was successful in 3/5 patients who relapsed, similarly to what observed in CML.

Preemptive living donor kidney transplantation: Access, fate, and review of the status in Egypt.

Preemptive living donor kidney transplantation (PLDKT) is recommended as the optimal treatment for end-stage renal disease. To assess the rate of PLDKT among patients who accessed KT in our center and review the status of PLDKT in Egypt. We performed a retrospective review of the patients who accessed KT in our center from November 2015 to November 2022. In addition, the PLDKT status in Egypt was reviewed relative to the literature. Of the 304 patients who accessed KT, 32 patients (10.5%) had preemptive access to KT (PAKT). The means of age and estimated glomerular filtration rate were 31.7 ± 13 years and 12.8 ± 3.5 mL/min/1.73 m2, respectively. Fifty-nine patients had KT, including 3 PLDKTs only (5.1% of total KTs and 9.4% of PAKT). Twenty-nine patients (90.6%) failed to receive PLDKT due to donor unavailability (25%), exclusion (28.6%), regression from donation (3.6%), and patient regression on starting dialysis (39.3%). In multivariate analysis, known primary kidney disease (P = 0.002), patient age (P = 0.031) and sex (P = 0.001) were independent predictors of achievement of KT in our center. However, PAKT was not significantly (P = 0.065) associated with the achievement of KT. Review of the literature revealed lower rates of PLDKT in Egypt than those in the literature. Patient age, sex, and primary kidney disease are independent predictors of achieving living donor KT. Despite its non-significant effect, PAKT may enhance the low rates of PLDKT. The main causes of non-achievement of PLDKT were patient regression on starting regular dialysis and donor unavailability or exclusion.

Smart monitoring, management and control of Blood bank Management System using IoT

An emergency system that directs the quick accessibility and availability of blood and delivery is entitled in a blood donation center. There exists a high demand for blood as a life saver in case of emergencies and the primary purpose of these blood donation centers meant to supply blood to the needy people. The unavailability of donor at the correct time is the foremost issue met by several people in case of emergencies. In our work, a group of people with data about their blood group and other details are made as a software for easy access. An application software has been developed where the Blood donation centers can inform about the Blood Stock and supply to people at urgent times. Since there are several steps involved in donating blood manually, the reliability and precision will be less. The proposed automatic blood bank system has been planned and developed into sector which involves sensors like temperature sensor, IR sensor, GSM module interfaced with Arduino Mega. Subsequent sector comprises of Wi-Fi module for files transference to administrator and third sector has been designed to monitor the position of existing blood stock. Entirely the web page designed narrates the obtainable blood stock in the blood bank which will be displayed on web page, so that the needy person can acquire required blood group from neighboring blood donation center.

Numerical assessment of hemodynamic perspectives of a left ventricular assist device and subsequent proposal for improvisation

Due to the unavailability of donors, the use of left ventricular assist devices has emerged to be a reliable line of alternative treatment for heart failure. However, ventricular assist devices (VAD) have been associated with several postoperative complications such as thrombosis, hemolysis, etc. Despite considerable improvements in technology, blood trauma due to high shear stress generation has been a major concern that is largely related to the geometrical feature of the VAD. This study aims to establish the design process of a centrifugal pump by considering several variations in the geometrical feature of a base design using the commercial solver ANSYS-CFX. To capture the uncertain behavior of blood as fluid, Newtonian, as well as non-Newtonian (Bird-Carreau model), models are used for flow field prediction. To assess the possibility of blood damage maximum wall shear stress and hemolysis index have been estimated for each operating point. The results of the simulations yield an optimized design of the pump based on parameters like pressure head generation, maximum shear stress, hydraulic efficiency, and hemolysis index. Further, the design methodology and the steps of development discussed in the paper can serve as a guideline for developing small centrifugal pumps handling blood.

Platelet storage: Progress so far.

There is a crucial need for platelet transfusion during an emergency-surgery and treatment of platelet disorders. The unavailability of donors has furthermore increased the demand for platelet storage. Platelets have limited shelf life due to bacterial contamination and storage lesions. Temperature, materials, oxygen availability, media, platelet processing and manufacturing methods influence the platelet quality and viability during storage. The conception of various platelet additive solutions along with the advent of plastic storage during the 1980s led to enormous developments in platelet storage strategies. Cold storage of platelets gained attention despite its inability to contribute to platelet survival post-transfusion as it offers faster haemostasis. Several developments in platelet storage strategies over the years have improved the quality and shelf-life of stored platelets. Despite the progress, the efficacy of platelets during storage beyond a week has not been achieved. Antioxidants as additives have been explored in platelet storage and have proven to enhance the efficacy of platelets during prolonged storage. However, the molecular interactions of antioxidants in platelets can provide a better understanding of their mechanism of action. Optimization of dosage concentrations of antioxidants is also a critical parameter to be considered as they tend to exhibit toxicity at certain levels. This review provides comprehensive insights into the critical factors affecting platelet storage and the evolution of platelet storage. It also emphasizes the role of antioxidants as additives in platelet storage solutions and their future prospects towards better platelet banking.

A facile 3D bio-fabrication of customized tubular scaffolds using solvent-based extrusion printing for tissue-engineered tracheal grafts.

Tracheal implantation remains a major therapeutic challenge due to the unavailability of donors and the lack of biomimetic tubular grafts. Fabrication of biomimetic tracheal scaffolds of suitable materials with matched rigidity, enhanced flexibility and biocompatibility has been a major challenge in the field of tracheal reconstruction. In this study, customized tubular grafts made up of FDA-approved polycaprolactone ( ) and polyurethane ( ) were fabricated using a novel solvent-based extrusion 3D printing. The printed scaffolds were investigated by various physical, thermal, and mechanical characterizations such as contact angle measurement, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), radial compression, longitudinal compression, and cyclic radial compression. In this study, the native goat trachea was used as a reference for the fabrication of different types of scaffolds (cylindrical, bellow-shaped, and spiral-shaped). The mechanical properties of the goat trachea were also compared to find suitable formulations of . Spiral-shaped scaffolds were found to be an ideal shape based on longitudinal compression and torsion load maintaining clear patency. To check the long-term implantation, in vitro degradation test was performed for all the 3D printed scaffolds and it was found that blending of with reduced the degradation behavior. The printed scaffolds were further evaluated for biocompatibility assay, live/dead assay, and cell adhesion assay using bone marrow-derived human mesenchymal stem cells (hMSCs). From biomechanical and biological assessments, of spiral-shaped scaffolds could be a suitable candidate for the development of tracheal regenerative applications.

A Review of Corneal Blindness: Causes and Management.

Corneal blindness refers to a group of eye disorders that change thecorneal transparency, causing corneal scarring and blindness. The leading causes of corneal blindness include infectious causes, i.e., due to bacteria, viruses, fungi, and protozoa. The most common predisposing factors are trauma, contact lens usage, or the use of steroid medications. The various other diseases included are trachoma, dry eye disease, keratoconus, ophthalmia neonatorum, and non-infectious uveitis. Various clinical modalities are used for treating corneal blindness, including organ transplantation. Organ donation is cumbersome as various ethical and other factors are involved. Hence the concept of eye banking was introduced to meet the increasing demand for donors of the cornea. The eye bank's role is harvesting, processing, and keeping a record of the cornea being transplanted and donated. Furthermore, various recent advancements have been made for lamellar keratoplasty surgeries, including bioengineered corneas to fulfil the need for the unavailability of donors for the cornea. Various specific health interventions have been implemented to reduce the prevalence of corneal blindness globally. For proper management of corneal blindness, we have three components that are needed to be taken care of: prevention of corneal blindness, appropriate treatment modalities, and providing adequate rehabilitation services to the patients. This review encompasses the main reasons for corneal blindness and the management and treatment modalities available for the patients. The terms cornea, corneal blindness, treatment, management, causes, and complications were used for the review article on PubMed.

Allogeneic Stem Cell Transplantation for the Treatment of Lymphoproliferative Disorders in Patients Affected By Primary Immunodeficiencies: The UK Experience

▪Malignancies represent a significant morbidity for patients (pts) affected by primary immunodeficiency (PID). 4-25% of pts with PID will develop a malignancy during the course of their life, lymphoproliferative disorders being the most common. Dysfunctional T-cell surveillance, particularly against EBV, and impaired DNA repair mechanisms lie at the basis of this susceptibility. Malignancies in PID pts are difficult to treat as these pts often harbor co-morbidities that increase the risk of treatment-related toxicity. Allogeneic stem cell transplantation (SCT) offers a treatment for both PID and LPD. Data on the outcome of pts referred to SCT for LPD in PID are scant, as PID are rare and sometimes under diagnosed.We retrospectively collected data on pts 0-18 years referred to SCT for LPD in PID in the 12 pediatric SCT centres in the UK from 2000 to 2015. Centralized review for histopathology specimens and radiological imaging was performed to confirm the LPD diagnosis and the disease staging/remission status at SCT. Ethical approval was obtained.40 patients affected by 13 different PIDs were identified, X-linked lymphoproliferative disease being the most common (15% of the pts).Median age at LPD diagnosis was 6.1 years (range 0.2-17.2). Pts were diagnosed with a B-cell lymphoma (60%), Hodgkin lymphoma (15%), polymorphic LPD (10%), plasmacytic hyperplasia (7%), T-cell lymphoma (5%) or atypical lymphoid proliferation (3%). 83% of the pts presented with stage III/IV disease, 4% had CNS involvement. LPD proved EBER positive in 66% of the tested samples. Pts received a median of 2 lines of chemo/immunotherapy to treat LPD, which proved resistant to front line treatment in 64% of the pts. 7 pts were referred for SCT but did not receive one due to disease progression (3), donor unavailability (1) or medical decision (3). Among the non-transplanted pts, 1 died from sepsis during chemotherapy, 4 died from disease progression; the OS of this group is 28% at a median follow up of 10 months from LPD diagnosis. For the 33 pts who underwent SCT, median age at SCT was 8.4 yrs (range 0.6-17.7). 58% of the pts had 1 or more comorbidities at SCT (chronic lung disease being most common). Of these, 67% of the pts receiving SCT were in complete remission (CR), 24% in partial remission, and 10% had active disease when starting their conditioning regimen.7 different types of conditioning regime were used, as per participating center local policies. In 94% of the cases a reduced intensity conditioning (RIC) was used. 74% of treated pts received in vivo T cell depletion with Alemtuzumab (71%) or Anti-Thymocyte Globulin (3%). 27% of the pts received the graft from a matched related, 39% matched unrelated and 33% mismatched donor. Bone marrow and peripheral blood were the most common sources of stem cells (46% and 42% of the cases, respectively).All pts achieved neutrophil engraftment and secondary graft loss was experienced by 2 pts (6%). 4 pts (12%) died from SCT related toxicity (3 infections, 1 pulmonary VOD/hemorrhage). Acute GVHD grade I-IV developed in 42% of the pts. LPD recurred in 2 cases (1 after secondary graft loss) and was successfully treated with surgery/chemotherapy. With a median follow up of 48 months, 88.0% patients are alive, in CR post SCT. 76% of the evaluable patients exhibited a full donor engraftment at the latest follow up.Disease stage, histology, underlying PID and remission status at SCT did not impact on the patients´ outcomes. Overall survival was significantly higher in SCT recipients as compared to patients who did not receive SCT (88 vs 28%, p= 0.03). Even among the 3 pts who underwent SCT without achieving LPD remission, OS was 67%, thus underlying that restoring competent immunity might play a role in this context, allowing for LPD control post SCT via the newly grafted T-cells.This cohort of pts is the largest described of its kind. We conclude that SCT with RIC is safe and efficacious for pts affected by LPD in PID. While larger cohorts of pts are required to confirm these data, our study suggests that remission status at SCT plays a partial role in LPD control. As a consequence, limited pre-SCT chemotherapy might be required and SCT indication might be plausible for pts not achieving CR. DisclosuresLucchini:Alexion: Membership on an entity's Board of Directors or advisory committees.

Autologous Hematopoietic Stem Cell Transplant: A Potential Option for Relapsed Pediatric Acute Myeloid Leukemia With Lack of Matched Sibling Donor and Resource Challenge

Though allogeneic hematopoietic stem cell transplant (HSCT) is standard for relapsed pediatric acute myeloid leukemia, often it may not be accessible due to donor unavailability and resource limitations. We retrospectively analyzed outcomes of 26 children (mean age: 10.9±4.5 y) who underwent autologous HSCT in complete remission 2. Three-year event-free survival and overall survival were 50.1±10.7% and 63.3±9%, respectively; with 1 treatment-related death and 46% relapse rate. Notwithstanding the retrospective study design and somewhat favorable patient characteristics, the outcomes are comparable with those of other series and our own allogeneic HSCT data. Autologous HSCT is a potential alternative to allogeneic HSCT, especially in countries with poorly maintained donor registries.

Repetitively Administered Low-Dose Donor Lymphocyte Infusion for Prevention of Relapse after Allogeneic Stem Cell Transplantation in Patients with High-Risk Acute Leukemia.

Simple SummaryPatients with high-risk acute leukemia (AL) have a high risk of relapse after allogeneic stem cell transplantation (allo-SCT). Prophylactic donor lymphocyte infusion (pro-DLI) has shown significant efficacy in reducing relapse rate but its widespread application has been limited due to concerns of graft versus host disease (GVHD) development. In the present study, we tested the safety and efficacy of a novel method of pro-DLI based on repetitive administration of low lymphocyte doses. Low-dose pro-DLI was administered every two months for at least 3-years. Forty-four high-risk AL patients with a median age of 53-years who underwent allo-SCT from a matched-sibling (38pts) or a matched-unrelated donor (6pts) received pro-DLI. Acute and chronic-GVHD developed in 14% and 12% of patients. With a median follow-up of 44-months, the cumulative incidence of relapse and non-relapse mortality was 12% and 13%, while the overall survival was 78%. Prolonged up to 3-years low-dose pro-DLI administered every two months is safe and effective in reducing relapse rate in patients with high-risk AL. The low-dose repetitive administration DLI strategy reduced the risk of DLI-mediated GVHD, while the prolonged repeated administration helped in preventing relapse, possibly by inducing a sustained and prolonged immunological pressure on residual leukemic cells. Background: Patients with high-risk acute leukemia have a high risk of relapse after allogeneic stem cell transplantation (allo-SCT). In an effort to reduce the relapse rate, various therapeutic methods have been implemented into clinical practice. Among them, prophylactic donor lymphocyte infusion (pro-DLI) has shown significant efficacy. However, the widespread application of pro-DLI has been restricted mostly due to concerns regarding the development of graft versus host disease (GVHD). In the present study, we tested the safety and efficacy of a novel method of prophylactic-DLI based by repetitive administration of low lymphocyte doses. Methods: DLI was administered to patients with high-risk acute leukemia at a dose of 2 × 106/kg CD3-positive cells. DLI at the same dose was repeated every two months for at least 36 months post-allo-SCT, or until relapse or any clinical or laboratory feature suggested GVHD, whichever occurred first. Forty-four patients with a median age of 53 years (range 20–67) who underwent allo-SCT between 2011 and 2020 were included in our study. Thirty-three patients with high-risk acute myeloid leukemia (AML) and 11 with high-risk acute lymphoblastic leukemia (ALL) after allo-SCT from a matched sibling (MSD, no = 38 pts) or a matched-unrelated donor (MUD, no = 6 pts) received pro-DLI. Twenty-three patients were in CR1, all with unfavorable genetic features; 12 patients were in CR2 or beyond; and 9 patients had refractory disease at the time of transplant. Ten out of 23 patients in CR1 had detectable minimal residual disease (MRD) at the time of allo-SCT. Disease risk index (DRI) was high and intermediate in 21 and 23 patients, respectively. Conditioning was myeloablative (MAC) in 36 and reduced intensity (RIC) in 8 patients, while GVHD prophylaxis consisted of cyclosporine-A in combination with low-dose alemtuzumab in 39 patients or with low-dose MTX in 5 patients, respectively. Results: Thirty-five patients completed the scheduled treatment and received a median of 8 DLI doses (range 1–35). Fifteen out of 35 patients received all planned doses, while DLI was discontinued in 20 patients. Reasons for discontinuation included GVHD development in nine, donor unavailability in seven, disease relapse in three, and secondary malignancy in one patient, respectively. Nine patients were still on treatment with DLI, and they received a median of four (range 2–12) doses. Fourteen percent of patients developed transient grade-II acute GVHD while 12% developed chronic GVHD post-DLI administration. Acute GVHD was managed successfully with short course steroids, and four out of five patients with cGVHD were disease-free and off immunosuppression. With a median follow-up of 44 months (range 8–120), relapse-free (RFS) and overall survival (OS) were 74%, (95% CI, 54–87%) and 78%, (95% CI, 58–89%) respectively, while the cumulative incidence of non-relapse mortality (NRM) was 13% (95% CI, 4–28%). The cumulative incidence of relapse in patients with intermediate and high DRI is 7% and 15%, respectively. Conclusion: Prolonged—up to three years—low-dose pro-DLI administered every two months is safe and effective in reducing relapse rate in patients with high-risk acute leukemia. The low-dose repetitive administration DLI strategy reduced the risk of DLI-mediated GVHD, while the prolonged repeated administration helped in preventing relapse, possibly by inducing a sustained and prolonged immunological pressure on residual leukemic cells. This novel strategy deserves testing in larger cohort of patients with high-risk acute leukemia.

Kidney failure after lung transplantation in systemic scleroderma: a case report with literature review

BackgroundSystemic scleroderma (SSc) involves multiple organs including the skin, the lung, the kidney, and the esophagus. Nowadays, patient life prognosis has substantially improved due to more appropriate management of lung complications, including lung transplantation. However, the extension of their survival may increase SSc patients with chronic kidney diseases and requiring renal replacement therapy (RRT).Case presentationA 51-year-old female with SSc who underwent unilateral deceased-donor lung transplantation was referred because of progressive renal dysfunction. Despite no episodes of scleroderma renal crisis, her renal function gradually deteriorated for 2 years with her serum creatinine level increasing from 0.5 mg/dL at transplantation to 4.3 mg/dL. Although we reinforced antihypertensive treatment and reduced calcineurin inhibitor dose, she thereafter developed symptomatic uremia. Due to impaired manual dexterity with contracture of the interphalangeal joints, no caregivers at home, and kidney transplantation donor unavailability, maintenance hemodialysis was chosen as RRT modality. Further, due to the narrowing of superficial vessels in the sclerotic forearm skin and post-transplant immunocompromised status, the native left brachiocephalic arteriovenous fistula was created. Post-operative course was uneventful while any sign of cutaneous infection and pulmonary hypertension was closely monitored. Our literature review also indicates several difficulties with initiating and maintaining RRT in patients with SSc although case reports of kidney failure after lung transplanation in SSc were not accumulated.ConclusionsWith respect to initiating RRT for post-lung transplant patients with SSc, the clinical course of our case exemplifies recent complex trends of renal management. The optimal modality with secured initiation of RRT should be carefully determined based on the severity and risk for the cardiopulmonary, peripheral vascular, cutaneous, and systemic or local infectious complications.

The impact of allogeneic hematopoietic cell transplantation on the mortality of poor-risk non-Hodgkin lymphoma: an intent-to-transplant analysis.

Purpose of this single-centre retrospective study was to assess the outcome of allogeneic hematopoietic cell transplantation (alloHCT) for relapsed/refractory (r/r) non-Hodgkin lymphoma (NHL) by intent-to-transplant (ITT). Included were all consecutive patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and peripheral T-cell lymphoma (PTCL) for whom a donor search was performed between 2004 and 2018. Primary endpoint was overall survival (OS) measured from search initiation. A donor search was initiated for 189 patients (DLBCL 61, FL 32, MCL 43, and PTCL 53), with 76% of the patients having active disease. OS at 5 years after search initiation for DLBCL, FL, MCL, and PTCL was 26%, 44%, 52%, and 50%, respectively. AlloHCT was performed in 137 patients (72%; DLBCL 64%). Main reason for not undergoing alloHCT was disease progression, whereas donor unavailability accounted for only 4% of pretransplantation failures. These results suggest that survival of patients with r/r NHL entering the alloHCT route may be overestimated by a factor of 1.2-1.4 if based on actually transplanted patients only. This effect should be taken into account when using alloHCT as benchmark for new therapeutic approaches for the treatment of poor-risk NHL.

Mesenchymal stem cells transplantation reduces diabetic nephropathy

Diabetes mellitus is a metabolic disease in which the pancreas is unable to produce enough insulin due to the destruction of b -cells or the body does not utilize insulin properly. Continuous fluctuation of blood glucose levels is responsible for prolonged complications such as diabetic nephropathy (DN), diabetic retinopathy, or diabetic cardiomyopathy. Approximately, 20-30% of all diabetic patients face DN, which causes the formation of diabetic glomerular lesions and reduced glomerular filtration rate. In the case of renal failure, kidney transplantation is the only available therapy, however, it is expensive and almost unattainable due to unavailability of donors and host immune rejection. Stem cells are an alternative and attractive source of therapy because of their proliferative nature and the ability to produce distinct specialized cells. Mesenchymal stem cells (MSCs), which are derived from bone marrow, possess an anti-inflammatory property and the ability of selfrenewal and differentiation into a variety of specialized cells. MSCs are widely used to treat different diseases including DN and they have shown encouraging outcomes. This review provides details about the regenerative efficiency of using MSCs in treating diabetic nephropathy.

Human umbilical cord mononuclear cells could ameliorate schistosomal hepatic fibrosis. An experimental study

Hepatic fibrosis is considered a worldwide public health problem. Liver transplantation is the treatment of choice. Rejection, post-operative complications and unavailability of donors are major obstacles. Recent treatment modalities include cell therapy but more researches are still needed. Human umbilical cord blood is a rich source for mononuclear cells which recently have shown promising anti-fibrotic results. The present study aimed to evaluate the potential effect of human umbilical cord blood mononuclear cells infusion on an experimental model of hepatic fibrosis caused by Schistosoma mansoni. Assessment of liver fibrosis was done by haematoxylin, eosin and Masson's trichrome staining. Homing to injured liver was assessed by staining of human specific nuclear antigen. Liver functions, collagen and hepatic stellate cells staining were done. Our results revealed marked improvement of liver fibrosis raising the possibility for the mononuclear cells clinical use in patients with hepatic fibrosis.

Phase II Study of Prophylactic Non-Irradiated Granulocyte Transfusions in AML Patients Receiving Induction Chemotherapy

Background: Patients with Acute Myeloid Leukemia (AML) experience profound neutropenia; infections remain the leading cause of morbidity and mortality. Transfusion of functional non-irradiated allogeneic granulocytes may treat or prevent infections in AML patients, and may also have anti-leukemic benefits. Study Design: Patients free of infection, with a diagnosis of AML or high-risk myelodysplastic syndrome undergoing induction or first-salvage therapy were eligible. Allogeneic Granulocyte Transfusions (GTs) were administered to neutropenic (<0.5 × 109/L) patients every 3-4 days until sustained ANC recovery, initiation of new therapy, or completion of 6 weeks on study. Results: 45 patients enrolled with a median age of 67 years (range 23-83); 27 (60%) were male. Five patients (11%) never received a GT, due to donor screening failure and/or donor unavailability. 119 donors donated 156 granulocyte concentrates to the remaining 40 patients. The median number of GTs transfused per patient was 3 (range 1-9). All patients experienced >1 neutropenic fever, with an average of one infectious episode per patient. Other adverse reactions were urticaria/pruritis (n=1), rash (n=1), and hypotension (n=1). Response to leukemiadirected therapy included complete remission in 50%, overall response rate of 70%, and 8-week mortality of 8%. Median overall survival was 15 months, with 51% 1-year survival. Conclusion: Administration of non-irradiated functional allogeneic GTs to neutropenic MDS/AML patients is safe and feasible. No transfusion-associated graft-versus-host-disease (TA-GVHD) was reported and no increased toxicity was described, including among the 10% receiving subsequent allogeneic stem cell transplant. The favorable patient outcomes within this diverse group of primarily elderly AML are notable.

Influence of Matched Sibling Donor's Availability and Stem Cell Transplantation on Treatment Outcome for Acute Lymphoblastic Leukemia; Study on 294 Patients

IntroductionPredicting treatment outcome of acute leukemia has been an important issue. Many factors have been elucidated. We evaluated the impact of donor's availability on treatment outcome including mortality in patients with acute lymphoblastic leukemia (ALL).MethodsA total of 294 patients with ALL were evaluated after receiving chemotherapy between year 2001 and July 2014 at our center. Patients were assessed for the need of hematopoietic stem cell transplants (HSCT), availability of HLA sibling match donor and the impact on overall outcome. Indications for transplantation were defined as (1) WBC->100,000 for T-ALL, >30 for B-ALL with, (2) cytogenetic abnormalities of t(9:22), (4:11) or (1:19), (3) relapse or primary refractory disease or (4) MRD positivity. Patients were divided into 3 categories, group A with an indication for HSCT and available donor (HSCT+/D+), group B with HSCT indication but no available donor (HSCT+/D-) and group C with no indication for HSCT regardless of donor status (HSCT-).ResultsThe median age was 20 (14-63 years). 95 (32%) were female while 198 (68%) were male. 276 (86%) patients were newly diagnosed while 18 (14%) were relapsed. Immuno-phenotype was B for 191 (65%), T for 91 (31%) versus mixed lineage for 12 (4%). 33 (11%) patients were positive for Philadelphia chromosome. Median WBC at diagnosis was 23.2X109/L CNS involvement was positive in 26 (8%) patients.With a median follow-up of 60 months for survivors (range 2 to 116.5 months), 148 (50%) patients showed HSCT+/D+, HSCT+/D- in 79 (27%) and HSCT- in 67 (23%) patients.the 5-year OS for HSCT+/D-, HSCT+/D+ and HSCT- were 29%, 57% and 55% (p value <0.001), (figure A) while DFS was 25%, 44% and 44% (p value =0.004), respectively. No statistical significance difference was noted on NRM between the groups. On multivariate analysis for OS, donor unavailability was confirmed as an independent risk factor (p<0.001, HR 2.21).ConclusionOur study suggested that unavailability of donor is an independent risk factor on OS. The use of alternative donor and building national /regional unrelated donor registry is highly warranted even in countries with high probability of finding matched sibling donor. [Display omitted] DisclosuresKim:Bristol-Myers Squibb: Consultancy, Research Funding; Novartis Pharmaceuticals: Consultancy, Research Funding.

Managing Hodgkin lymphoma relapsing after autologous hematopoietic cell transplantation: a not-so-good cancer after all!

Hodgkin lymphoma (HL) relapsing after an autologous hematopoietic cell transplant (HCT) poses a therapeutic challenge. In this setting, salvage chemotherapy (for example, gemcitabine-based, ifosfamide-containing and others) or immunotherapy (for example, brentuximab vedotin) is essential as a bridging-cytoreduction strategy to an allogeneic HCT. Myeloablative allogeneic hematopoietic cell transplantation in relapsed HL is associated with high rates of non-relapse mortality. In carefully selected patients with chemosensitive disease, allografting following lower-intensity conditioning regimens can provide durable disease control rates of about 25-35%. Promising early results with haploidentical and umbilical cord transplantation are noteworthy and are expanding this procedure to patients for whom HLA-matched related or unrelated donors are not available. Unfortunately, a significant number of HL patients relapsing after an autologous HCT are not candidates for allografting because of the presence of resistant disease, donor unavailability or comorbidities. Brentuximab vedotin is approved for HL relapsing after a prior autograft. Rituximab and bendamustine are also active in this setting, albeit with short durations of remission. Histone deacetylase inhibitors (for example, panobinostat, mocetinostat), mTOR inhibitors (for example, everolimus) and immunomodulatory agents (lenalidomide) have shown activity in phase II trials, but currently are not approved for this indication. Second autologous HCT are rarely performed but this approach should not be considered standard practice at this time. The need for effective agents for post autograft failures of HL largely remains unmet. Continuous efforts to ensure early referral of such patients for allogeneic HCT or investigational therapies are the key to improving outcomes of this not-so-good lymphoma.

The optimal immunosuppressive therapy for aplastic anemia

Immunosuppressive treatment (IST) has been the most effective therapeutic modality for patients with aplastic anemia (AA) who are not eligible for allogeneic stem cell transplantation from HLA-matched siblings because of donor unavailability, old age, or comorbidities. The combination of horse anti-thymocyte globulin (ATG) with cyclosporine A (CsA) has shown satisfactory results for these patients, and so it has been regarded as the standard IST regimen. However, treatment failure including unresponsiveness, relapse, and occurrence of clonal evolution remains a major problem, although the results of IST have been improved in the past two decades. Many studies have been conducted to overcome these problems; however, they have yet to show any satisfactory results. This review will discuss immune-mediated pathophysiology of AA, which is associated with therapeutic targets of immunosuppressive agents and clinical outcomes of most commonly used IST regimens. Several trials to improve IST including the addition of other immunosuppressive agents or growth factors to standard IST regimen, comparison between horse ATG/CsA and rabbit ATG/CsA as first-line treatment, and promising alternative agents including alemtuzumab and eltrombopag will also be discussed, focusing on recently published literatures.