Safety and efficacy of intense pulsed light in the treatment of severe chronic ocular graft-versus-host disease.

OBJECTIVE: To investigate the safety and efficacy of intense pulsed light (IPL) in the treatment of severe chronic ocular graft-versus-host disease (coGVHD). METHODS: A prospective cohort study. Seventeen patients with severe coGVHD were selected for inclusion in this study. All subjects were treated with IPL every fortnight together with conventional treatment, observation time points were pre-treatment (W0), 4 weeks post-treatment (W4), 8 weeks post-treatment (W8) and 12 weeks post-treatment (W12). Dry eye related examinations include Tear meniscus height (TMH), Non-invasive break-up time (NIBUT), Schirmer I test, Tear film lipid layer thickness (LLT), Ocular surface staining (OSS) and assessment of meibomian gland. Corneal epithelial cell morphology and inflammatory cell infiltration were analyzed by corneal confocal microscopy, while goblet cell density and squamous epithelial grade were assessed by conjunctival imprinted cytology. RESULTS: Patients did not experience any adverse reactions during the follow-up period. All subjects showed significant improvement in clinical symptoms and most signs after IPL treatment. The corneal confocal microscopy showed that the number of dendritic cells infiltrates in the corneal stroma was significantly reduced after IPL treatment (p < 0.001). Conjunctival blot cytology suggested an increase in the number of conjunctival goblet cells from 5.12 ± 2.71 cells/mm2 before treatment to 22.00 ± 4.58 cells/mm2 after treatment, with a statistically significant difference (p < 0.001). An improvement in conjunctival epithelial cell morphology and a decrease in squamous epithelial grade was also observed. CONCLUSIONS: IPL treatment can effectively increase tear film stability in patients with severe coGVHD without significant side effects.

Pacritinib Combined with Sirolimus and Low-Dose Tacrolimus for GVHD Prevention after Allogeneic Hematopoietic Cell Transplantation: Preclinical and Phase I Trial Results.

PURPOSE: In this first-in-human, phase I, GVHD prevention trial (NCT02891603), we combine pacritinib (PAC), a JAK2 inhibitor, with sirolimus to concurrently reduce T-cell costimulation via mTOR and IL6 activity. We evaluate the safety of pacritinib when administered with sirolimus plus low-dose tacrolimus (PAC/SIR/TAC) after allogeneic hematopoietic cell transplantation. PATIENTS AND METHODS: The preclinical efficacy and immune modulation of PAC/SIR were investigated in xenogeneic GVHD. Our phase I trial followed a 3+3 dose-escalation design, including dose level 1 (pacritinib 100 mg daily), level 2 (pacritinib 100 mg twice daily), and level 3 (pacritinib 200 mg twice daily). The primary endpoint was to identify the lowest biologically active and safe dose of pacritinib with SIR/TAC (n = 12). Acute GVHD was scored through day +100. Allografts included 8/8 HLA-matched related or unrelated donor peripheral blood stem cells. RESULTS: In mice, we show that dual JAK2/mTOR inhibition significantly reduces xenogeneic GVHD and increases peripheral regulatory T cell (Treg) potency as well as Treg induction from conventional CD4+ T cells. Pacritinib 100 mg twice a day was identified as the minimum biologically active and safe dose for further study. JAK2/mTOR inhibition suppresses pathogenic Th1 and Th17 cells, spares Tregs and antileukemia effector cells, and exhibits preliminary activity in preventing GVHD. PAC/SIR/TAC preserves donor cytomegalovirus (CMV) immunity and permits timely engraftment without cytopenias. CONCLUSIONS: We demonstrate that PAC/SIR/TAC is safe and preliminarily limits acute GVHD, preserves donor CMV immunity, and permits timely engraftment. The efficacy of PAC/SIR/TAC will be tested in our ongoing phase II GVHD prevention trial.

T Helper Cell Lineage-Defining Transcription Factors: Potent Targets for Specific GVHD Therapy?

Allogenic hematopoietic stem cell transplantation (allo-HSCT) represents a potent and potentially curative treatment for many hematopoietic malignancies and hematologic disorders in adults and children. The donor-derived immunity, elicited by the stem cell transplant, can prevent disease relapse but is also responsible for the induction of graft-versus-host disease (GVHD). The pathophysiology of acute GVHD is not completely understood yet. In general, acute GVHD is driven by the inflammatory and cytotoxic effect of alloreactive donor T cells. Since several experimental approaches indicate that CD4 T cells play an important role in initiation and progression of acute GVHD, the contribution of the different CD4 T helper (Th) cell subtypes in the pathomechanism and regulation of the disease is a central point of current research. Th lineages derive from naïve CD4 T cell progenitors and lineage commitment is initiated by the surrounding cytokine milieu and subsequent changes in the transcription factor (TF) profile. Each T cell subtype has its own effector characteristics, immunologic function, and lineage specific cytokine profile, leading to the association with different immune responses and diseases. Acute GVHD is thought to be mainly driven by the Th1/Th17 axis, whereas Treg cells are attributed to attenuate GVHD effects. As the differentiation of each Th subset highly depends on the specific composition of activating and repressing TFs, these present a potent target to alter the Th cell landscape towards a GVHD-ameliorating direction, e.g. by inhibiting Th1 and Th17 differentiation. The finding, that targeting of Th1 and Th17 differentiation appears more effective for GVHD-prevention than a strategy to inhibit Th1 and Th17 cytokines supports this concept. In this review, we shed light on the current advances of potent TF inhibitors to alter Th cell differentiation and consecutively attenuate GVHD. We will focus especially on preclinical studies and outcomes of TF inhibition in murine GVHD models. Finally, we will point out the possible impact of a Th cell subset-specific immune modulation in context of GVHD.

Tyrosine supplement ameliorates murine aGVHD by modulation of gut microbiome and metabolome.

BACKGROUND: Microbial communities and their metabolic components in the gut are of vital importance for immune homeostasis and have an influence on the susceptibility of the host to a number of immune-mediated diseases like acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the functional connections between microbiome and metabolome in aGVHD due to the complexity of the gastrointestinal environment. METHOD: Initially, gut microbiota and fecal metabolic phenotype in aGVHD murine models were unleashed by performing 16S ribosomal DNA gene sequencing and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics. FINDINGS: The group with aGVHD experienced a significant drop in Lachnospiraceae_unclassified but an increase in the relative abundance of Clostridium XI, Clostridium XIVa and Enterococcus. Meanwhile, a lower content of tyrosine was observed in the gut of aGVHD mice. The correlation analysis revealed that tyrosine-related metabolites were inversely correlated with Clostridium XIVa, besides, Blautia and Enterococcus also displayed the negative tendency in aGVHD condition. Apart from exploring the importance and function of tyrosine, different tyrosine diets were offered to mice during transplantation. Additional tyrosine supplements can improve overall survival, ameliorate symptoms at the early stage of aGVHD and change the structure and composition of gut microbiota and fecal metabolic phenotype. In addition, aGVHD mice deprived from tyrosine displayed worse manifestations than the vehicle diet group. INTERPRETATION: The results demonstrated the roles and mechanisms of gut microbiota, indispensable metabolites and tyrosine in the progression of aGVHD, which can be an underlying biomarker for aGVHD diagnosis and treatment. FUNDING: This research was funded by the International Cooperation and Exchange Program (81520108002), the National Key R&D Program of China, Stem Cell and Translation Research (2018YFA0109300), National Natural Science Foundation of China (81670169, 81670148, 81870080 and 91949115) and Natural Science Foundation of Zhejiang Province (LQ19H080006).

Allogeneic bone marrow transplantation with post-transplant cyclophosphamide for patients with HIV and haematological malignancies: a feasibility study.

BACKGROUND: Allogeneic blood or marrow transplantation (alloBMT) is a potentially life-saving treatment for individuals with HIV and haematological malignancies; challenges include identifying donors and maintaining antiretroviral therapy (ART). The objectives of our study were to investigate interventions to expand donor options and to prevent ART interruptions for patients with HIV in need of alloBMT. METHODS: This single-arm, interventional trial took place at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center (Baltimore, MD, USA). Individuals with HIV who were at least 18 years of age and referred for alloBMT for a standard clinical indication were eligible. The only exclusion criterion was a history of documented resistance to enfuvirtide. We used post-transplant cyclophosphamide as graft-versus-host disease (GVHD) prophylaxis to expand donor options and an optimised ART strategy of avoiding pharmacoenhancers and adding subcutaneous enfuvirtide during post-transplant cyclophosphamide and during oral medication intolerance. Our primary outcome was the proportion of participants who maintained ART through day 60 after alloBMT. We measured the HIV latent reservoir using a quantitative viral outgrowth assay. This study is registered on ClinicalTrials.gov, NCT01836068. FINDINGS: Between June 1, 2013, and August 27, 2015, nine patients who were referred for transplant provided consent. Two patients had relapsed malignancy before donor searches were initiated. Seven patients had suitable donors identified (two matched sibling, two matched unrelated, two haploidentical, and one single-antigen mismatched unrelated) and proceeded to alloBMT. All patients maintained ART through day 60 and required ART changes (median 1, range 1-3) in the first 90 days. One patient stopped ART and developed HIV rebound with grade 4 meningoencephalitis at day 146. Among six patients who underwent alloBMT and had longitudinal measurements available, the HIV latent reservoir was not detected post-alloBMT in four patients with more than 95% donor chimerism, consistent with a 2·06-2·54 log10 reduction in the HIV latent reservoir. In the two patients with less than 95% donor chimerism, the HIV latent reservoir remained stable. INTERPRETATION: By using post-transplant cyclophosphamide as GVHD prophylaxis, we successfully expanded alloBMT donor options for patients with HIV. Continuing ART with a regimen that includes enfuvirtide post-alloBMT was safe, but life-threatening viral rebound can occur with ART interruption. FUNDING: amfAR (the Foundation for AIDS Research), Johns Hopkins University Center for AIDS Research, and National Cancer Institute.

Carnitine Profile Changes in Pediatric Hematopoietic Stem Cell Transplant: New Role for Carnitine?

Carnitine is an essential cofactor for mitochondrial import and oxidation of fatty acids. High-dose chemotherapy and radiation, often required for hematopoietic stem cell transplant (HSCT), leads to tissue damage, mitochondrial dysfunction, and alterations in carnitine metabolism. The aim of this pilot cohort study was to describe plasma and urinary carnitine profiles during pediatric HSCT and their relationships with clinical outcomes. Plasma and urinary carnitine samples were collected from 22 pediatric patients before and through day 180 post-HSCT. Associations were observed between graft-versus-host disease and an elevated plasma total carnitine (P=0.019), and also increased plasma acyl:free carnitine ratio with veno-occlusive disease (P=0.016). Mortality was observed in those with their highest urinary total carnitine losses on day 0 (P=0.005), and in those with an abnormal day 28 plasma ratio either above or below the reference range (P=0.007). Changes in carnitine profiles were more reflective of metabolic stress and negative outcomes than of inadequate dietary intake. Associations observed direct larger studies to assess the validity of carnitine profiles as a prognostic indicator and also to assess whether prophylactic carnitine supplementation pre-HSCT could reduce mitochondrial injury and urinary losses and help mitigate inflammatory and metabolic comorbidities of HSCT.

A prospective non-interventional study on the impact of transfusion burden and related iron toxicity on outcome in myelodysplastic syndromes undergoing allogeneic hematopoietic cell transplantation.

Most myelodysplastic syndromes (MDS)-patients receive multiple red blood cell transfusions (RBCT). Transfusions may cause iron-related toxicity and mortality, influencing outcome after allogeneic HSCT. This prospective non-interventional study evaluated 222 MDS and CMML patients undergoing HSCT. Overall survival (OS), relapse-free survival (RFS), non-relapse mortality (NRM), and relapse incidence (RI) at 36 months were 52%, 44%, 25%, and 31%, respectively. Age, percentage of marrow blasts and severe comorbidities impacted OS. RFS was significantly associated with RBCT burden prior to HSCT (HR: 1.7; p = .02). High ferritin levels had a significant negative impact on OS and RI, but no impact on NRM. Administration of iron chelation therapy prior to HSCT did not influence the outcome, but early iron reduction after HSCT (started before 6 months) improved RFS significantly after transplantation (56% in the control group vs. 90% in the treated group, respectively; p = .04). This study illustrates the impact of RBCT and related parameters on HSCT-outcome. Patients with an expected prolonged survival after transplantation may benefit from early iron reduction therapy after transplantation.

Impacts of thymoglobulin in patients with acute leukemia in remission undergoing allogeneic HSCT from different donors.

Antithymocyte globulin (ATG) is widely used to reduce acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD). To clarify the different impacts of ATG for conditioning across different donor types, we retrospectively analyzed patients with acute leukemia (n = 6617) who underwent hematopoietic stem cell transplantation between 2008 and 2015 with ATG (n = 279) or without ATG (n = 6338). Because thymoglobulin is the only ATG drug approved for GVHD prophylaxis in Japan since September 2008, we included thymoglobulin alone in the present analysis. The survivors' median follow-up time was 1081 days. Patients were categorized into 5 groups: cord blood (CB; n = 1915), matched related donor (n = 1772), 1-antigen mismatched related donor (1-MMRD; n = 225), matched unrelated donor (MUD; n = 1742), and 1-allele mismatched unrelated donor (1-MMUD; n = 963). In multivariate analysis, ATG decreased overall survival (hazard ratio [HR], 1.403; P = .054) and GVHD-free/relapse-free survival (GRFS) (HR, 1.458; P = .053) in association with increased nonrelapse mortality (NRM) (HR, 1.608; P =03) with CB, whereas it improved GRFS (HR, 0.515; P < .01) and decreased grades II to IV aGVHD (HR, 0.576; P < .01), extensive cGVHD (HR, 0.460; P = .02), and NRM (HR, 0.545; P = .03) with 1-MMUD. ATG did not impact survival with 1-MMRD and MUD. The use of ATG in conditioning is beneficial due to the reduction in acute/chronic GVHD without increasing NRM or disease relapse only in 1-MMUD transplantation. On the other hand, ATG is not recommended for CB transplantation.

The Gut Microbiota and Hematopoietic Stem Cell Transplantation: Challenges and Potentials.

The human gut microbiota gained tremendous importance in the last decade as next-generation technologies of sequencing and multiomics analyses linked the role of the microbial communities to host physiology and pathophysiology. A growing number of human pathologies and diseases are linked to the gut microbiota. One of the main mechanisms by which the microbiota influences the host is through its interactions with the host immune system. These interactions with both innate and adaptive host intestinal and extraintestinal immunity, although usually commensalistic even mutualistic with the host, in some cases lead to serious health effects. In the case of allogenic hematopoietic stem cell transplantation (allo-HSCT), the disruption of the intestinal microbiota diversity is associated with acute graft-versus-host disease (GvHD). Causing inflammation of the liver, skin, lungs, and the intestine, GvHD occurs in 40-50% of patients undergoing allo-HSCT and results in significant posttransplantation mortality. In this review, we highlight the impact of the gut microbiota on the host immunity in GvHD and the potential of microbiota in alleviation or even prevention of GvHD.

Cutaneous Chronic Graft Versus Host Disease Following Allogeneic Haematopoietic Stem Cell Transplantation in Children: A Retrospective Study.

Chronic graft versus host disease (cGVHD) is a complication of allogeneic haematopoietic stem cell transplantation (HSCT). The aim of this study was to clinically characterize childhood cutaneous cGVHD. A retrospective study of children treated with HSCT at 2 tertiary medical centres in Israel between 2011 and 2014 was performed. A total of 112 children were included. Cutaneous cGVHD developed in 18% of subjects. Risk factors were older age, HSCT from peripheral blood and acute lymphoblastic leukaemia. The eruption was lichenoid in 90% of subjects, of whom one-third progressed to sclerosis. Topical treatments were usually sufficient in localized disease. Widespread eruption necessitated phototherapy, extracorporeal photopheresis and/or systemic immunosuppressants. Patients presenting with palmoplantar keratoderma, developed sclerosis. To the best of our knowledge, this is the first study describing childhood cutaneous cGVHD. Lichenoid eruption is the most common cutaneous pattern of cGVHD in children. Sclerotic changes may be associated with prior keratoderma. cGVHD poses a therapeutic challenge and better treatments should be sought.

Fototerapia UVB banda estrecha en el tratamiento de la enfermedad injerto contra huésped crónica cutánea: reporte de caso / Narrowband UVB phototherapy for the treatment of cutaneous chronic graft versus host disease: case report

Resumen La enfermedad injerto contra huésped crónica (EICHc) es una complicación frecuente en los pacientes que reciben trasplante de progenitores hematopoyéticos (TPH) alogénico, siendo la piel el órgano más frecuentemente afectado. La EICHc cutánea se presenta con lesiones esclerodermiformes y no esclerodermiformes y frecuentemente requiere tratamiento con inmunosupresores sistémicos, fotoféresis extracorpórea o fototerapia. Los inmunosupresores tienen el potencial de producir importantes efectos adversos, por lo que terapias con mejor perfil de seguridad son claramente necesarias. Presentamos el caso de una paciente de 11 años a quien se le realizó un TPH haploidéntico como tratamiento de una leucemia linfocítica aguda. En su evolución desarrolló EICHc cutánea esclerodermiforme. La paciente recibió tratamiento con luz ultravioleta B de banda estrecha (UVBbe), respondiendo satisfactoriamente en los 2 primeros meses. Existen múltiples reportes y series de casos exitosos sobre el tratamiento con fototerapia en distintas modalidades. En relación a la fototerapia con UVBbe, la literatura es escasa, sin embargo, muestran importantes resultados tanto en las formas esclerodermiformes y no esclerodermiformes de la EICHc cutánea y un buen perfil de seguridad. De todas formas, se requieren estudios prospectivos controlados a gran escala para determinar su efectividad como terapia adjuvante o incluso de primera línea y para definir los esquemas terapéuticos y dosis más efectivas.

Summary Chronic graft-vs-host disease (GVHD) is a frequent complication in patients who receive allogeneic hematopoietic cell transplants (HCTs), and the skin is the most common site of involvement. Chronic cutaneous GVHD can present with sclerotic or nonsclerotic changes and often requires treatment with systemic immunosuppressants, extracorporeal photopheresis, or phototherapy. Immunosuppressants carry the potential of causing important side effects, so additional modes of therapy with better security profiles are clearly needed. We report a case of an eleven year old girl, who received allogeneic HCTs to treat acute lymphocytic leukemia. She developed sclerotic chronic GVHD. The patient underwent treatment with narrowband UV-B phototherapy, and a significant improvement was seen over the first 2 months. There are a number of successful series and case reports on different forms of phototherapy. In relation to narrowband UV-B phototherapy, literature is scarce, although shows important results in sclerotic and nonsclerotic forms of chronic cutaneous GVHD and a good safety profile have been seen. Anyway, large-scale controlled prospective trials are needed to evaluate the effectiveness of phototherapy as adjuvant o even first-line therapy, and to establish the most effective therapy schemes and doses.

Post-Transplantation Cyclophosphamide-Based Haploidentical Transplantation as Alternative to Matched Sibling or Unrelated Donor Transplantation for Hodgkin Lymphoma: A Registry Study of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation.

Purpose To compare the outcome of patients with Hodgkin lymphoma who received post-transplantation cyclophosphamide-based haploidentical (HAPLO) allogeneic hematopoietic cell transplantation with the outcome of patients who received conventional HLA-matched sibling donor (SIB) and HLA-matched unrelated donor (MUD). Patients and Methods We retrospectively evaluated 709 adult patients with Hodgkin lymphoma who were registered in the European Society for Blood and Marrow Transplantation database who received HAPLO (n = 98), SIB (n = 338), or MUD (n = 273) transplantation. Results Median follow-up of survivors was 29 months. No differences were observed between groups in the incidence of acute graft-versus-host disease (GVHD). HAPLO was associated with a lower risk of chronic GVHD (26%) compared with MUD (41%; P = .04). Cumulative incidence of nonrelapse mortality at 1 year was 17%, 13%, and 21% in HAPLO, SIB, and MUD, respectively, and corresponding 2-year cumulative incidence of relapse or progression was 39%, 49%, and 32%, respectively. On multivariable analysis, relative to SIB, nonrelapse mortality was similar in HAPLO ( P = .26) and higher in MUD ( P = .003), and risk of relapse was lower in both HAPLO ( P = .047) and MUD ( P < .001). Two-year overall survival and progression-free survival were 67% and 43% for HAPLO, 71% and 38% for SIB, and 62% and 45% for MUD, respectively. There were no significant differences in overall survival or progression-free survival between HAPLO and SIB or MUD. The rate of the composite end point of extensive chronic GVHD and relapse-free survival was significantly better for HAPLO (40%) compared with SIB (28%; P = .049) and similar to MUD (38%; P = .59). Conclusion Post-transplantation cyclophosphamide-based HAPLO transplantation results in similar survival outcomes compared with SIB and MUD, which confirms its suitability when no conventional donor is available. Our results also suggest that HAPLO results in a lower risk of chronic GVHD than MUD transplantation.

Allogeneic Reduced-Intensity Hematopoietic Stem Cell Transplantation for Chronic Granulomatous Disease: a Single-Center Prospective Trial.

PURPOSE: The purpose of this study was to evaluate engraftment and adverse events with a conditioning and prophylactic regimen intended to achieve high rates of engraftment with minimal graft-versus-host disease (GVHD) in allogeneic transplantation for chronic granulomatous disease in a single center. METHODS: Forty patients, 37 male, with chronic granulomatous disease were transplanted. Transplant products were matched sibling peripheral blood stem cells (PBSCs) in four and matched unrelated donor (MUD) bone marrow in three, and one patient received mismatched unrelated PBSCs. Thirty-two patients received MUD PBSCs. All patients received a conditioning regimen of busulfan/alemtuzumab (with low-dose total body irradiation for MUD recipients) with sirolimus graft-versus-host disease prophylaxis. RESULTS: Engraftment occured in 38/40 recipients (95%). Acute or chronic GVHD occurred in 18 (45%) and 5 (12.5%), respectively, with 6 episodes of grades III-IV and/or steroid refractory GVHD. Overall survival was 33/40 (82.5%) and event-free survival was 30/40 (80%). Successful engraftment was associated with myeloid and NK cell, but not CD3+ chimerism. Myeloid engraftment was greater than 70% in 30/32 recipients at mean follow-up of 3.4 years. Evidence of persistent immunodeficiency was not seen in successful transplants. Attempts to rescue failed or poorly functioning grafts were associated with unacceptable morbidity and mortality. CONCLUSIONS: A reduced-intensity allogeneic transplant protocol based on alemtuzumab and busulfan with sirolimus GVHD prophylaxis produced high rates of successful engraftment and minimal regimen-related toxicity. Prolonged clinical follow-up has confirmed its efficacy in ameliorating CGD-related disease. Outcomes were not acceptable with donor cell infusion rescue of cause with poor graft function.

Pediatric Cutaneous Graft Versus Host Disease: A Review.

BACKGROUND: Graft versus host disease (GVHD) is a significant complication following hematopoietic stem cell transplantation in the pediatric population. The most common clinical manifestation of GVHD is in the skin. This article will present a review of key concepts related to pediatric cutaneous GVHD, including pathophysiology, clinical epidemiology, diagnosis, and treatment options. OBJECTIVE: GVHD is an immune-mediated process characterized by an inflammatory immune response in acute GVHD and mixed inflammatory and fibrotic states in chronic GVHD. The clinical presentations of cutaneous GVHD are heterogeneous. METHOD: Acute cutaneous GVHD classically presents as an erythematous morbilliform eruption appearing within a few weeks after transplantation. Chronic cutaneous GVHD may manifest as poikiloderma, lichenoid lesions, or sclerodermatous changes. The sclerodermatous form of cutaneous GVHD is associated with substantial long-term morbidity, including joint contractures, myalgias, and mobility restriction. RESULTS: First-line pharmacologic treatment options typically include corticosteroids and in some cases, calcineurin inhibitors. Biologics and immunotherapies are an active area of investigation for GVHD that is refractory to corticosteroid treatment. Non-pharmacologic treatment options that have shown benefit for cutaneous GVHD include extracorporeal photopheresis and phototherapy. CONCLUSION: Accurate diagnosis and treatment of cutaneous GVHD is essential to preventing and alleviating the long-term sequelae and morbidity associated with this condition.

Photography in Telemedicine: Improving Diagnosis of Chronic Graft-Versus-Host Disease.

BACKGROUND: The long-term follow-up (LTFU) team at the Seattle Cancer Care Alliance uses telemedicine to diagnose and treat post-transplantation complications in hematopoietic cell transplantation (HCT) survivors. Photos are often requested via the telemedicine service to aid in diagnosis, but they are typically of poor quality, making them unusable. OBJECTIVES: This project offered bachelor of science in nursing students, partnered with a comprehensive cancer center, the opportunity to participate in an evidence-based practice project to improve detection and management of chronic graft-versus-host disease (cGVHD) in patients after HCT. METHODS: Students partnered with RNs to develop instructional tools using multiple evidence sources. A brochure and video were developed. FINDINGS: Providing these instructional tools to those in the LTFU program improved patient outcomes for managing cGVHD through telemedicine. This partnership provided an opportunity for mutual learning and improved clinical practice.

Cutaneous manifestations of graft-versus-host disease: role of the dermatologist.

Graft-versus-host disease (GVHD) is the major complication of hematopoietic stem cell transplantation and is associated with high mortality in severe cases. The skin is one of the major organs affected in both acute and chronic GVHD. This review aims to elucidate the basic characteristics of GVHD, and the role and contribution of dermatologists in the care of patients with this condition.

Successful management of Mycobacterium haemophilum lower extremity cutaneous infection in a matched-unrelated donor stem cell transplant recipient.

Nontuberculous mycobacterial infections can often occur in individuals with adequate immune function. Such infections typically have cutaneous involvement and are caused by rapidly growing mycobacterium. Other nontuberculous mycobacteria species, like Mycobacterium haemophilum, almost always present as opportunistic infections occurring in severely immunocompromised hosts. Here, we present a complicated and protracted course of diagnosing M. haemophilum lower extremity cutaneous infection in a matched-unrelated donor stem cell transplant recipient.

Four decades of stem cell transplantation for Fanconi anaemia in the Netherlands.

This article presents the haematopoietic stem cell transplantation (SCT) results of the complete Dutch Fanconi anaemia (FA) patient cohort. Sixty-eight Dutch FA patients have been transplanted since 1972. In total, 63 (93%) patients engrafted, 54 after first SCT and 9 after second SCT. Fludarabine (FLU)-based conditioning was associated with decreased graft failure (odds ratio 0·21, P = 0·01), decreased early mortality (hazard ratio 0·25, P = 0·01) and improved 5-year overall survival (FLU 87·8% [standard error (SE) 5·1%] versus non-FLU 59·3% [SE 9·5%], P = 0·01). Late mortality was mainly caused by squamous cell carcinoma. Twenty-two patients were treated with the current Dutch FA conditioning regimen (FLU 150 mg/m(2) and cyclophosphamide 30 mg/kg ± anti-thymocyte globulin - no irradiation). Stem cell donors were matched related (n = 8) or alternative donors (n = 14). Stable engraftment after first SCT was achieved in 19 (86%) patients. At a median follow-up of 3·9 years 20 (91%) patients are alive. Our study provides a unique overview of a nation-wide SCT cohort illustrating the major improvements in treatment regimen and patient outcome in recent years. It shows that a non-irradiation and busulfan-free conditioning regimen can be used successfully, also in alternative donor SCT. Furthermore, it underlines the importance of late cancer screening and comprehensive care for this complex disorder.

Endoscopic and Histological Findings Are Predicted by Fecal Calprotectin in Acute Intestinal Graft-Versus-Host-Disease.

BACKGROUND: Gastrointestinal graft-versus-host-disease (GI-GVHD) is a major cause of nonrelapse mortality after hematopoietic stem cell transplantation (HSCT) necessitating endoscopic examinations and biopsies for diagnosis. Fecal calprotectin (CPT) has been widely used in gastrointestinal inflammation, but comprehensive data in GI-GVHD are lacking. AIMS: We aimed to identify an association of CPT with endoscopic findings, mucosal damage and symptoms for diagnosing and monitoring acute GI-GVHD. METHODS: Symptoms were prospectively evaluated in 110 consecutive HSCT recipients by standardized questionnaires and Bristol Stool Scale (BSS). CPT was assayed by ELISA. Symptom assessment and CPT were performed weekly and with onset of first symptoms. GVHD was diagnosed according to the Glucksberg criteria and by endoscopic biopsies. Patients with GI-GVHD received standard high-dose corticosteroid therapy and follow-up CPT, and symptom evaluation was performed after 28 days. Patients not responding to steroid treatment were re-evaluated by colonoscopy. RESULTS: GI-GVHD was diagnosed in 40 patients. Twelve patients with GI symptoms and CMV colitis and 24 patients with isolated skin GVHD were included as control subjects. CPT was significantly higher in GI-GVHD compared to skin GVHD and CMV colitis. Endoscopic findings, histological grading, abdominal cramps, diarrhea, urgency and BSS correlated with CPT. At follow-up, CPT correlated with abdominal cramps, diarrhea, urgency and BSS. In steroid refractory patients, CPT level was still significantly associated with severity of mucosal damage. CONCLUSION: CPT predicts endoscopic and histological findings in GI-GVHD and correlates with lower GI symptoms. It enables to discriminate GVHD from CMV colitis and to monitor therapeutic success.

Análisis retrospectivo del papel de la fototerapia en la enfermedad injerto contra huésped crónica cutánea. Revisión de la literatura / The Role of Phototherapy in Cutaneous Chronic Graft-vs-Host Disease: A Retrospective Study and Review of the Literature

INTRODUCCIÓN Y OBJETIVOS: La enfermedad injerto contra huésped (EICH) crónica cutánea es una complicación frecuente tras un trasplante de progenitores hematopoyéticos. La fototerapia es una modalidad terapéutica para pacientes con afectación cutánea o para aquellos que precisan altas dosis de corticoesteroides (CE). El objetivo de este estudio es revisar los casos tratados en nuestro servicio y hacer una revisión de la literatura. MATERIAL Y MÉTODOS: Recogida de datos de manera retrospectiva de todos los casos tratados desde marzo de 2011 a octubre de 2014 en el Servicio de Dermatología del Hospital Universitario y Politécnico la Fe de Valencia. RESULTADOS: Recogimos un total de 16 pacientes, 10 tratados con PUVA y 6 con UVB-BE. Nueve pacientes obtuvieron una respuesta completa y 7 una respuesta parcial, aunque 2 recidivaron tras el tratamiento. Diez pacientes pudieron disminuir la dosis de CE durante el tratamiento y 3 pudieron disminuir el número de otros inmunosupresores. No se presentaron efectos adversos graves. CONCLUSIONES: La fototerapia es una buena opción terapéutica para pacientes con EICH crónica con gran afectación cutánea, para aquellos que no responden al tratamiento tópico o para pacientes corticodependientes. Su mayor beneficio es el de ser un tratamiento dirigido a la piel que permite ahorrar CE y que presenta un buen perfil de seguridad. La pauta de tratamiento se realiza de manera individualizada y, según nuestra experiencia, con dosis iniciales y dosis máximas por sesión menores que para otras enfermedades

INTRODUCTION AND OBJECTIVES: Cutaneous chronic graft-vs-host disease (GVHD) is a common complication of hematopoietic stem cell transplantation. Phototherapy is a therapeutic option for patients with skin involvement and for those who require high doses of corticosteroids. We analyze the cases treated in our department and review the literature. MATERIAL AND METHODS: All patients with GVHD treated with phototherapy in the dermatology department of Hospital Universitario y Politécnico la Fe in Valencia, Spain between March 2011 and October 2014 were identified. Data were gathered retrospectively. RESULTS: There were 16 patients: 10 treated with psoralen-UV-A and 6 with narrowband-UV-B. Complete response was achieved in 9 patients and partial response in 7; 2 patients with partial responses relapsed after treatment. Ten patients were able to decrease their dose of corticosteroids during treatment, and a further 3 decreased the number of other immunosuppressant drugs. No serious adverse effects occurred. CONCLUSIONS: Phototherapy is a good therapeutic option for patients with chronic GVHD with extensive cutaneous involvement, as well as for those who fail to respond to topical treatment or who have become steroid-dependent. The main benefits are that, as the treatment targets the skin, it reduces corticosteroid requirements and has a good safety profile. Treatment must be individualized and, in our experience, both the initial dose and the maximum dose per session can be lower than for other diseases