Complication Of Bone Marrow Transplantation Research Articles

Pulmonary complications of bone marrow transplantation.

Bone marrow transplantation, now often known as haematopoietic stem cell transplantation (HSCT), is a complex choreographed procedure used to treat both acquired and inherited disorders of the bone marrow. It has proven invaluable as therapy for haematological and immunological disorders, and more recently in the treatment of metabolic and enzyme disorders. As the number of performed transplants grows annually, and with patients enjoying improved survival, a knowledge of both early and late complications of HSCT is essential for respiratory trainees and physicians in practice. This article highlights the spectrum of respiratory complications, both infectious and non-infectious, the timeline of their likely occurrence, and the approaches used for diagnosis and treatment, keeping in mind that more than one entity may occur simultaneously. As respiratory issues are often a leading cause of short- and long-term morbidity, consideration of a combined haematology/respiratory clinic may prove useful in this patient population.

Noncongenital Vaginal Obliteration: Surgical Restoration of Vaginal Patency for GVHD

SettingGenital graft-versus-host disease (GVHD) is a known possible complication of bone marrow transplant (BMT). This condition can lead to vaginal obliteration, affecting sexual performance and quality of life. ObjectivesTo provide a brief overview of non-congenital causes of vaginal obliteration and stenosis, discuss a unique case of vaginal agglutination in a patient who developed genital GVHD after receiving a BMT, and present the steps of a laparoscopic total hysterectomy and lysis of vaginal adhesions that successfully restored vaginal patency without the need for grafting. Design and InterventionsThis video gives an overview of non-congenital causes of vaginal obliteration with a focus on genital GVHD. We discuss the clinical course of a 54-year-old female with history of acute monocytic leukemia treated with chemotherapy and a BMT. She subsequently developed genital GVHD with complete vaginal obliteration, precluding penetrative intercourse and causing pain, discomfort, and decreased quality of life. We present a combined laparoscopic and vaginal surgical procedure that allowed for the creation of a neovagina with a normal length and caliber. While grafting is sometimes necessary due to inflammation and scarring, we were able to avoid a graft by using a combined laparoscopic and vaginal approach, followed by restoration of continuity between the unaffected upper and lower vaginal tissues. ConclusionGVHD can be quite debilitating for patients. A combined surgical approach is a feasible option for patients with complex pathology not amenable to simple transvaginal adhesiolysis. Surgical restoration of the vagina does not necessarily require the use of a graft if the anatomy is reestablished successfully.

Non infectious ocular surface inflammation: Paediatric GVHD

Although ocular findings and treatment for GVHD are described in adult patients, the literature describing this condition in paediatric patients is relatively few. In children, detection of symptoms and diagnosis of ophthalmic findings are more difficult than in adults, as history taking, clinical examination and diagnostic tests such as fluorescein staining or Schirmer tests are difficult to perform due to limited cooperation. Also patients cannot specify their complaints and symptoms especially in younger age group. Follow‐up and frequent ophthalmic evaluation are important in diagnosis and management of children who had bone marrow transplantation. Even though ophthalmic findings are common in children, usually milder than adults but timely diagnosis and management are very important to decrease secondary eye complications such as corneal ulcers and vision loss and also to improve quality of life.Graft‐versus‐host disease (GVHD) is a major complication of bone marrow transplantation that is performed for haematological malignancies and diseases and seen in 50–70% of cases. It is a complex clinical disease with many organ and system involvement. Acute form is seen in the first 3 months after transplantation, systemic manifestation mainly include hepatitis and skin involvement and chronic form is mostly seen after acute GVHD. Ocular manifestations can be classified as acute and chronic and also as anterior and posterior. Most common ocular finding is dry eye with corneal involvement and seen in 40–90% of patients with chronic GVHD. Corneal vascularization, keratitis and even perforation can be seen. Conservative treatment with topical steroids, autologous serum, lubricant eye drops and ointments should be integrated with topical cyclosporine‐A that might be an effective and safe treatment option in dry eye related to chronic GVHD.

Kaposi's Sarcoma in Children After Hematopoietic Stem Cell Transplantation: Two Cases of Rare Primary Tumor Localizations in the Lungs and Lymph Node.

Kaposi's sarcoma (KS) is a vascular / mesenchymal tumor with an indefinite degree of malignancy, caused by complex etiopathogenetic factors including Human Herpes Virus-8 infection of immunocompromised patients. For example, KS is more common in adult men with HIV. We describe 2 very rare cases of iatrogenic KS in children after hematopoietic stem cell transplant with isolated organ damage (case 1: lung; case 2: inguinal lymph node). KS is a potential complication of bone marrow transplant in pediatric patients and can occur in different age groups and at atypical sites.

Anandamide reduces the migration of lymphocytes to the intestine by CB2 activation and reduces TNF-α in the target organs, protecting mice from graft-versus-host disease

Graft-versus-host disease (GVHD) is a serious inflammatory illness that often occurs as a secondary complication of bone marrow transplantation. Current therapies have limited effectiveness and fail to achieve a balance between inflammation and the graft-versus-tumor effect. In this study, we investigate the effects of the endocannabinoid anandamide on the complex pathology of GVHD. We assess the effects of an irreversible inhibitor of fatty acid amine hydrolase or exogenous anandamide and find that they increase survival and reduce clinical signs in GVHD mice. In the intestine of GVHD mice, treatment with exogenous anandamide also leads to a reduction in the number of CD3+, CD3+CD4+, and CD3+CD8+ cells, which reduces the activation of CD3+CD4+ and CD3+CD8+ cells, as assessed by enhanced CD28 expression, a T cell co-stimulatory molecule. Exogenous AEA was also able to reduce TNF-α and increase IL-10 in the intestine of GVHD mice. In the liver, exogenous AEA reduces injury, TNF-α levels, and the number of CD3+CD8+ cells. Interestingly, anandamide reduces Mac-1α, which lowers the adhesion of transplanted cells in mesenteric veins. These effects are mimicked by JWH133—a CB2 selective agonist—and abolished by treatment with a CB2 antagonist. Furthermore, the effects caused by anandamide treatment on survival were related to the CB2 receptor, as the CB2 antagonist abolished it. This study shows the critical role of the CB2 receptor in the modulation of the inflammatory response of GVHD by treatment with anandamide, the most prominent endocannabinoid.

The significance of M1‐polarized CD163+ macrophages in acute graft‐versus‐host disease (GVHD): Possible mechanisms of GVHD in the development of skin lesions

AbstractObjectivesGraft‐versus‐host disease (GVHD) is an important complication of bone marrow transplantation. Recent reports suggest the significance of T‐cell subsets (Th1, Th17, and cytotoxic CD8+ T cells) as well as CD163+ macrophages in the development of cutaneous GVHD. CD163+ macrophages produce various chemokines to establish the immunological microenvironment following stimulation by stromal factors in lesional skin. Thus, the purpose of this study is to determine the main source of IFN‐inducible chemokines in the lesional skin of GVHD.MethodsWe employed immunohistochemical (IHC) staining for CD163 as well as interferon (IFN)‐inducible chemokines (CXCL9, CXCL10, CXCL11) to determine if the main source of IFN‐inducible chemokines in the lesional skin of GVHD was CD163+ macrophages. Moreover, we investigated the possible cytokine profiles of lesional skin in GVHD by evaluating phospho‐signal transducer and activator of transcription (pSTAT) expression in epidermal keratinocytes.ResultsImmunohistochemical staining of serial sections for CD163 revealed that CXCL9‐expressing cells, CXCL10‐expressing cells, and CXCL11‐expressing cells were detected in adjacent to CD163+ TAMs in the dermis. In contrast, there were no CCL17‐expressing cells or CCL22‐expressing cells in the dermis. The nuclei of epidermal keratinocytes in GVHD expressed pSTAT1, pSTAT3, and pSTAT5B.ConclusionsThe chemokine expression patterns on CD163+ macrophages matched the expected phosphorylation pattern of epidermal STATs. Our present study suggested that CD163 + macrophages may be a therapeutic target in GVHD.

Acute Myocardial Infarction in a 13-Year-Old Boy after Bone Marrow Transplantation

BackgroundAdvances in bone marrow transplantation (BMT) present a unique opportunity for treating leukemia in children. It has also increased the risk of long-term complications in the lungs, genitourinary tract, and nervous system. Coronary artery disease is the most common type of heart disease in older adults, but is not generally acknowledged as a complication of BMT, especially in young patients. Case ReportWe report the occurrence of acute myocardial infarction in a 13-year-old boy, approximately 5 years after he received a half-matched related bone marrow transplant from his father for T-cell lymphoblastic leukemia. Acute myocarditis was suspected early in the clinical course on the basis of his age and clinical presentations, such as atypical chest pain and dyspnea. Follow-up coronary angiography revealed a total occlusion of the right coronary artery, as well as diffused lesions of the left main, anterior descending, and circumflex branch. Fortunately, he was discharged from the hospital in satisfactory general condition after complex treatment.Why Should An Emergency Physician Be Aware of This? In this case, its rarity and poor clinical recognition were the main reasons for delayed diagnosis, which led to a delay to coronary angiography. Given the high mortality in cardiovascular complications among BMT recipients, the correct diagnostic assessment in such cases becomes particularly relevant.

Mature Naive B Cells Regulate the Outcome of Murine Acute Graft-versus-Host Disease in an IL-10-Independent Manner

Graft-versus-host disease (GVHD) is the main complication of bone marrow transplantation (BMT). CD4+ T lymphocytes are the main effector cells for disease development, but other cell types can determine disease outcome through cytokine production and antigen presentation. B cells are abundant in BMT products and are involved in chronic GVHD immunopathogenesis. However, their role in acute GVHD is still unclear. Here we studied the role of donor resting B cells in a model of acute GVHD. Animals receiving transplants depleted of B cells developed more severe disease, indicating a protective role for B cells. Mice undergoing transplantation with IL-10 knockout B cells developed GVHD as severe as those receiving wild-type B cells. Moreover, mice that received MHC II-deficient B cells, and thus were unable to present antigen to CD4+ T cells, developed as severe GVHD as animals receiving transplants without B cells. This result suggests that the protection provided by mature naive B cells depends on antigen presentation and not on IL-10 production by B cells. Mice who underwent transplantation in the absence of donor B cells exhibited disorganized lymphoid splenic tissue. In addition, donor B cell depletion diminished the follicular T (Tfh)/effector T (Teff) cell ratio, suggesting that protection was correlated with a shift to Tfh differentiation, reducing the number of Teff cells. Importantly, the Tfh/Teff shift impacts disease outcome, with observed proinflammatory cytokine levels and tissue damage in target organs consistent with disease protection. The role of transplanted B cells in the outcome of BMT and the development of acute GVHD merits careful study, given that these cells are abundant in BMT products and are potent modulator and effector cells in the allogeneic response.

Graves’ Disease, a Late Complication of Chronic Graft vs Host Disease

Introduction: Graft-versus-host disease (GVHD), a complication of bone marrow transplant (BMT), occurs when the donor white blood cells attack the recipient’s host cells and can occur acutely or chronically several years post-transplant. It is very rare for chronic GVHD to cause hyperthyroidism due to Grave’s disease and thyrotoxicosis years after BMT. Hyperthyroidism after BMT is thought to occur by GVHD or by donor’s auto-reactive lymphocytes transferred to recipient, with majority of cases occurring with donors that have an underlying autoimmune thyroid condition. Case Report: We report a 62 year old male who presented with palpitations, tremors, sweating, weight loss, and anxiety for 3 weeks. Past medical history was significant for allogenic BMT due to AML 14 years ago, which was further complicated by GVHD of eye, liver and skin. Physical exam was negative for thyromegaly or thyroid tenderness. Initial work up showed TSH 0.03 (normal 0.4-5.0 MUI/l), free T4 3.32 (normal 0.6-1.2 ng/dl), TSI 194 % (normal <140 %). Ultrasound revealed a diffuse hypervascular thyroid gland with numerous avascular cystic areas in both lobes and increased homogenous, symmetrical uptake consistent with Graves’ disease was noted on radioactive iodine uptake scan. With clinical suspicion of GVHD leading to Graves’ disease with subsequent thyrotoxicosis, he was started on methimazole. However, due to persistent increase in transaminases, concern for agranulocytosis with methimazole, and risk of developing worsening GVHD of the skin or eye with radioactive iodine therapy, he underwent total thyroidectomy. His pathology showed bilateral lymphoepithelial lesions with florid follicular hyperplasia, marked monocytoid hyperplasia, and Germinal B cells positive for CD10 and negative for BCL2. Lymphoepithelial lesions can be seen in chronic lymphocytic thyroiditis due to persistent inflammation. Conclusion: This case raises the question on the etiology of thyroid nodules and Graves’ disease occurring after BMT. We believe that his pathology findings may be due to chronic GVHD. Hyperthyroidism after BMT is extremely rare, with only a few case reports documenting this phenomenon. We believe that our patient developed hyperthyroidism 14 years after BMT most likely as a sequela of chronic GVHD with underlying immune dysregulation leading to formation of TSI and thyroiditis due to cellular invasion. This suggest a multifactorial etiology of hyperthyroidism in patients with GVHD. However, more prospective studies are required to the explain etiology of hyperthyroidism in GVHD. Moreover, such patients should be closely monitored for development of thyroid dysfunction or thyroid nodules.

Allojenik Kök Hücre Nakli Yapılan Bir Hastada BK Virüsüne Bağlı Gelişen Hemorajik Sistitte Kullanılan Cidofovire Bağlı Olarak Ortaya Çıkan Akut Proksimal Tübüler Nekroz

Hemorrhagic cystitis (HS) is a frequently seen complication of bone marrow transplantation. This condition occurs depending on the preparatory regimen of bone marrow transplantation. The BK virus (BKV), a human polyomavirus, is a small double helix DNA virüs belonging to the Papovaviridae family. It is commonly found in societies as an occult infection. Whereas, cidofovir (CDV), an acyclic nucleoside phosphonate, is used as a proven antiviral agent against polyomaviruses. In this case report, acute proximal tubular necrosis due to cidofovir used in hemorrhagic cystitis caused by BK virus, and its treatment in a patient diagnosed with T-lymphoblastic lymphoma in remission, and underwent allogeneic stem cell transplantation, was presented.

10-Year Mortality in Patients with Sickle Cell Disease from a Large Population-Based Cohort

Background Mortality rates and causes of death in children with sickle cell disease (SCD) have changed significantly over the past several decades. With ongoing improvements in standards of care, modern mortality estimates must be updated. Children's Healthcare of Atlanta (CHOA) houses one of the largest pediatric SCD programs in the country. This analysis reviews mortality in children with SCD who were treated at CHOA between June 2010-June 2020. Methods We reviewed the CHOA's Sickle Cell Clinical Database (SCCD) for deceased patients. Demographics, SCD genotype, date and age at death, healthcare utilization, hydroxyurea (HU) use, chronic transfusion therapy (CTT), and bone marrow transplant (BMT) were obtained from the SCCD. Cause of death and history of significant comorbidities were abstracted from the medical record. Mortality rates were calculated using person-time for all CHOA SCD patients and population-based mortality was obtained from CDC WONDER Online Database. Results A total of 3,698 patients with SCD were seen at CHOA from June 2010-June 2020 and accounted for 19,998 person-years. Of the 46 patients who died during that time, all but 1 patient had been seen in the CHOA Sickle Cell Outpatient Clinic at least once. That patient received SCD care at a different institution, died from complications of a non-SCD related disease following transfer to CHOA, and was excluded from analysis. Of the 45 remaining patients (178 person-years), the majority were sickle cell anemia genotypes (n=37, 82%; Hb SS or Hb S β0 thalassemia), followed by Hb SC (n=5, 11.1%) and Hb S β+ thalassemia (n=3, 6.7%); 53% (n=24) were female. The average age at death was 12.8 years (1.0-22.8 years). Twenty-one (46.7%) patients had ever been treated with HU and 11 (24.4%) were currently on HU at the time of last contact (either death or last CHOA encounter). Eleven (24.4%) patients had ever been treated with CTT, and 3 (8.9%) were being treated with CTT at time of last contact. In comparison, during the same time period an average of 58% and 12% of the overall CHOA SCD population were being treated with HU and CTT, respectively. Forty-one patients had at least 1 SCD-related encounter at CHOA within 12 months prior to death. For the 4 patients who had not been seen at CHOA within 12 months, the average time since last contact was 1.72 years (1.03 - 2.7 years). Eighty percent (n=8) of the 10 patients who died at age &amp;gt;19 had either recently transitioned to adult care or had documentation of a transition plan. During this 10-year period, the crude death rate was 2.3 per 1,000 person-years. The majority of deaths (62%, n=28) were attributable SCD-related causes and corresponded to a cause-specific mortality rate of 1.40 per 1,000 person-years. The remaining 38% (n=17) of deaths were caused by complex non-SCD comorbidities or accidental trauma and corresponded to a non-SCD related mortality rate of 0.85 per 1,000 person-years. In comparison, the mortality rate for African American persons age &amp;lt;22 in Georgia from 2009-2018 was 0.9 per 1,000 person-years. Of the 28 patients who died due to an SCD-related cause: 12 (27%) experienced an acute illness related to SCD, 4 (9%) succumbed to acute bacterial infections, 3 (7%) died from complications of SCD treatment (1 procedure-related, 2 drug-induced hemolytic anemia), and 1 (2%) died from complications of BMT. Nine (20%) had either recently transitioned to adult care or were lost to follow-up and had no significant non-SCD comorbidities, therefore cause of death was unknown. Of the 17 non-SCD related deaths, 16 (36%) were due to complex non-SCD comorbidities (including cancers, autoimmune disorders, and congenital heart disease) and 1 (2%) from an accidental trauma. Conclusions To our knowledge, this is the largest and most recent study of mortality in patients with SCD from a single institution. Overall, the demographics of deceased patients were similar to those of the CHOA SCD population as a whole. This cohort indicates that trends in mortality of children with SCD have largely shifted away from bacterial infections to other complications of SCD, subsequent treatments, or comorbidities. Our data confirm that patients nearing transition to adult care are at high risk of mortality. This study is limited to deaths that are known to the CHOA system, so future analyses will expand this cohort to include data from death certificates and CDC's National Death Index. Disclosures Lane: FORMA Therapeutics: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Evaluation of platelets transfusion in patients undergoing high dose chemotherapy for bone marrow transplantation

Introduction: Microvascular endothelial damage is a well-recognized complication of bone marrow transplantation (BMT) and the mechanisms of this disorder are still poorly under­stood. The objective of this scenario is to evaluate the relationship between inflammatory markers and other factors that influence platelet consumption and platelet transfusion yield, as well as the presence of embolic and / or vascular thrombotic events in patients submitted to high-dose chemotherapy conditioning for Bone marrow transplant.&#x0D; Material and Methods: Prospective analysis of patients, including 25 patients who under­went autologous and allogenic BMT. The patients were evaluated in relation to previous radiotherapy, CD34 + cell count, period of neutropenia, body mass index (BMI), ferritin, re­active C protein (RCP), relating these factors to the number of platelet transfusions, plate­let refractoriness and vascular events such as sinusoidal obstruction syndrome (SOS) and bone marrow grafting syndrome.&#x0D; Results: Only BMI&gt; 25 Kg / m2 of the studied variables presented a statistically significant value (p = 0.003) in relation to the lower need for transfusion of platelet concentrate. For platelet refractoriness and / or vascular events none of the variables was statistically sig­nificant. The conditions found in the 3 cases of platelet refractoriness and in the 2 cases of vascular events have characteristics like those described in the literature.&#x0D; Conclusion: Although the cause is unclear, we agree with data reported in the literature that patients with high BMI have a lower need for transfusion of platelets. Small sampling limits our comparisons and significant statistical inference; however, we cannot rule out the relevance of a descriptive analysis of the results, especially if we consider that each patient should be evaluated in an individualized way in clinical practice.

Bone Marrow Transplantation Platform to Investigate the Role of Dendritic Cells in Graft-versus-Host Disease.

Allogeneic bone marrow transplantation (BMT) is an effective therapy for hematological malignancies due to the graft-versus-leukemia (GVL) effect to eradicate tumors. However, its application is limited by the development of graft-versus-host disease (GVHD), a major complication of BMT. GVHD is evoked when T-cells in the donor grafts recognizealloantigen expressed by recipient cells and mount unwanted immunological attacks against recipient healthy tissues. Thus, traditional therapies are designed to suppress donor T-cell alloreactivity. However, these approaches substantially impair the GVL effect so that the recipient's survival is not improved. Understanding the effects of therapeutic approaches on BMT, GVL, and GVHD, is thus essential. Due to the antigen-presenting and cytokine-secreting capacities to stimulate donor T-cells, recipient dendritic cells (DCs) play a significant role in the induction of GVHD. Therefore, targeting recipient DCs becomes a potential approach for controlling GVHD. This work provides a description of a novel BMT platform to investigate how host DCs regulate GVH and GVL responses after transplantation. Also presented is an effective BMT model to study the biology of GVHD and GVL after transplantation.

A strategy to purify, expand and gene-mark regulatory T cells (tregs) for use in the treatment of chronic Graft-Versus-Host Disease (GVHD)

Background & Aim Chronic Graft-Versus-Host Disease (GVHD) is a major complication of bone marrow transplantation. Regulatory T cells (Tregs) have been shown to ameliorate GVHD in pre-clinical studies and early phase clinical trials. However, Treg adoptive transfer is currently limited by cell dose and purity; and strategies to combine this with in vivo expansion are being actively pursued. In this project, we optimized a clinically applicable method to purify Tregs by Fluorescent-Activated Cell Sorting (FACS). We also developed a method to gene-mark Tregs to enable clinical fate-tracking. Methods, Results & Conclusion We could enrich Tregs to high purity: from 6.6% (±1.4%) in buffy coat samples to 54.1% (±20.9%) after CD25-immunomagnetic selection on a CliniMACS Plus device (Miltenyi Biotec), and to 95.3% (± 1.8%) purity after multiparametric FACS-sorting for CD4+CD25+CD127low Tregs (MacsQuant Tyto, Miltenyi Biotec). The purified Tregs could be expanded with CD3/CD28 activation in medium supplemented with interleukin-2 and rapamycin. We showed that Tregs could be successfully gene-marked with a clinically approved retroviral vector, SFG.iCasp9.2A.ΔCD19. The expanded gene-marked Tregs maintained a high level of FOXP3 expression (92% ± 0.7%) and FOXP3 promoter demethylation, which is a hallmark of bona fide Tregs. Importantly, gene-marking did not alter FOXP3 expression or Treg suppressor function. We will now scale up this process using leukapheresis samples from healthy volunteers in preparation for a phase I clinical study in patients with chronic GVHD using Treg transfer in combination with low-dose interleukin-2 for in vivo expansion. Gene-marking will enable analysis of the contribution of adoptive transfer (gene-marked) versus in vivoexpansion (non-gene marked) Tregs, thus informing rational Treg-directed combination therapy.

KIDNEY INJURY IN CANCER THERAPY

Кidney injury is a frequent and significant complication of cancer and cancer therapy. The kidneys are susceptible to injury from malignant infiltration, damage by metabolites of malignant cells, glomerular injury, nephrotoxic drugs including chemotherapeutic agents. Also bone marrow transplantation complications, infections with immune suppression (including septicemia), tumor lysis syndrome should be taken into account. Chemotherapeutic agents are a common cause of acute kidney injury but can potentially lead to chronic kidney disease development in cancer patients. This article summarizes risk factors of acute kidney injury in cancer patients. Risk factors are divided into two groups. The systemic are decrease of total circulating blood volume, infiltration of kidney tissue by tumor cells, dysproteinemia, electrolyte disturbances. The local (renal) risk factors are microcirculation disturbances, drugs biotransformation with formation of reactive oxygen intermediates, high concentration of nephrotoxic agents in proximal tubules and its sensitivity to ischemia. Drug-related risk factors include: drugs combination with cytotoxic effect high doses long term use necessity, direct cytotoxic effect of not only chemotherapeutic agents but also its metabolites, mean solubility forming intratubular precipitates. Early diagnosis, timely prevention and treatment of these complications provide significantly improve nononcologic results of treatment.

PMD150 - EXPENSIVE COMBINED THERAPIES FOR RARE DISEASES ARE NOT ALWAYS WHAT THEY SEEM: AN ECONOMIC FEASIBILITY AUDIT

Acute graft versus host disease is a complication of bone marrow transplants in which T cells from the donor graft attack the hosts tissues. Treatment cost is often used as a determinant of treatment choice, but little economic data exists to inform decisions. Non-responders to treatment are less likely to survive but less likely to incur expensive treatment costs, making it challenging to identify appropriate economic endpoints. At a single institution, we tested the feasibility of an economic approach to measure the value of photopheresis as a combined agent, when compared to immunosuppression alone. The measures of value included net hospital costs and productivity. We examined the records of all patients with severe aGvHD who met published eligibility criteria for photopheresis in the year before the service commenced and during the year after. Resource utilisation was based on number of days in hospital and administration of high cost drugs for GvHD and related complications. Relevance was determined by expert review. Costs were identified using the local pharmacy database and the unit reference costs database. This audit included 9 patients in the study arm and 7 patients in the comparison arm. The mean reduction in hospitalisation days per patient was 21.3% (74.7-58.7) and spend on high cost drugs per patient was reduced by 48.3% (£28,420-£14,688). The mean net reduction in costs per patient, adjusted for photopheresis treatment costs, was £28,040. Furthermore, all patients died in the comparator arm during the audit period, compared to 10% in the study group. The additional costs of treating non responders and treatment complications should be considered alongside direct therapy costs. The results of this audit may support the feasibility of economic studies to evaluate the cost effectiveness of treatments for rare life threatening diseases.

Rare retinal complications of bone marrow transplantation (BMT): a case report

BackgroundBone marrow transplantation retinopathy is a rare condition affecting the posterior pole. The purpose of this case report is to highlight the possible risk factors and clinical features.Case presentationA 19y old male with relapsed and refractory acute lymphoblastic leukaemia was admitted under haematology with pyrexia of unknown origin. At the time of his admission, he reported bilateral and sequential visual impairment for 2 days. On examination, there was bilateral profound retinopathy across the posterior poles. This was symmetrical and with associated macular oedema. Infective aetiology was excluded and cyclosporine was stopped. Although no definitive treatment was initiated the visual acuity improved whilst macular oedema fluctuated.ConclusionBMT and chemotherapy can cause ocular complications but these are usually confined to the anterior segment. Posterior segment complications in the form of retinopathy is very rare. We report this case to highlight some of the clinical features and course of disease.

Caso clínico: Enfermedad Veno-Oclusiva Hepática secundaria a Quimioterapia en un paciente con Sarcoma de Ewing.

Introducción: A pesar del difícil acceso anatómico para los tumores de mediastino, la resección quirúrgica sigue siendo el mejor enfoque diagnóstico y terapéutico. El objetivo de la presente serie de casos presentamos la experiencia de un centro oncológico en el abordaje de tumores del mediastino y sus resultados. Métodos: En el departamento de Jefatura de Cirugía Oncológica del Instituto Oncológico nacional de Solca-Guayaquil, durante los meses de Enero del 2013 a Enero 2017 se realizó un estudio descriptivo, retrospectivo. Se analizaron todos los casos de pacientes derivados del área de pre admisión con diagnóstico inicial de tumor de mediastino, a los cuales previo a realizarles marcadores tumorales, Tomografía de Tórax, y a quienes se les realizó como método diagnóstico y en algunos casos terapéutico con abordaje quirúrgico. Se excluyeron pacientes con neoplasias de origen secundario, con historias clínicas incompletas que imposibilitaron el análisis. Se estudiaron las variables sexo, edad, Tipo de Técnica quirúrgica, localización del tumor, diagnostico histopatológico y mortalidad perioperatoria. El análisis estadístico realizado fue descriptivo. Resultados: Se evaluaron 22 pacientes con diagnóstico tumor de mediastino, con una edad media de 60 años. Fueron 13 hombres (59 %). Catorce pacientes con lesión maligna, 8 fueron operados con resección tumoral y 6 se sometieron a biopsia. Se reportaron fallecimientos post-operatorios hasta los 30 días postquirúrgicos en 5 casos (22.7%). Las intervenciones quirúrgicas realizadas con más frecuencia fueron toracotomías derechas con toma de biopsia o resección tumoral 7 casos (31.8 %). En relación al resultado anatomopatológico de los tumores de mediastino reportados más de la mitad constituyeron Adenocarcinomas 14 casos (63.6 %). Conclusión: Los pacientes portadores de neoplasia benigna en esta serie tuvieron una evolución posquirúrgica satisfactoria. El adenocarcinoma fue el tumor maligno más frecuente en esta serie.

Enfermedad Veno-oclusiva Hepática/Síndrome de Obstrucción Sinusoidal: actualización de los aspectos fisiopatológicos, criterios diagnósticos y opciones terapéuticas.

La enfermedad veno-oclusiva hepática o síndrome de obstrucción sinusoidal se caracteriza clínicamente por presentar hepatomegalia dolorosa, ictericia, ascitis, edema, aumento de peso y/o trombocitopenia refractaria, que generalmente ocurre como una complicación del trasplante de médula ósea y la quimioterapia en algunos tumores sólidos. La fisiopatología es compleja y se relaciona con daño endotelial en los sinusoides hepáticos que condiciona un estado proinflamatorio, protrombótico e hipofibrinolítico. El tratamiento varía de acuerdo a la severidad de cada caso, cuando son cuadros leves a moderados se presenta una resolución espontánea requiriendo medidas de soporte y tratamiento sintomático; mientras que en los casos severos o muy severos se requiere adicionar tratamiento específico debido a la alta mortalidad que presentan estos pacientes. Considerando la alta mortalidad y las escasas opciones terapéuticas aprobadas actualmente, la identificación de factores de riesgo sigue siendo la principal estrategia para disminuir la incidencia de esta enfermedad, de ahí la importancia de esta revisión.

Necrotizing Fasciitis is a Rare Complication after Bone Marrow Transplantation: A Case Report

Necrotizing fasciitis is an uncommon disease and a soft tissue infection that spreads along fascial planes with associated inflammation and necrosis. Herein, this study reported necrotizing fasciitis as a rare complication after bone marrow transplantation (BMT) in a Iranian patient and the efficacy of early treatment in improvement it. A 28-year-old lady had known case of first relapse of Hodgkin’s lymphoma that admitted for auto-BMT in 2016. Five years ago due to abdominal-pelvic massive lymphadenopathy, she was treated with six courses of ABVD regimen combined with involved filed irradiation. Due to Hodgkin’s relapse, the patient was treated with six courses of ICE regimen and after complete remission was selected for auto-BMT. Necrotizing fasciitis was reported by MRI and the patients was treated with combination of a number of antibiotics after fasciectomy. In conclusion, necrotizing fasciitis is a rare complication of BMT, especially autologous type that drug selection and rapid surgical fasciectomy are important decisions for prevention of mortality and morbidity of this complication.