Dry eye disease and risk factors for corneal complications in chronic ocular graft-versus-host disease

Purpose: The current study was carried out to evaluate the clinical features and management outcomes of dry eye disease (DED) in chronic ocular GvHD following allogenic hematopoietic stem cell transplantation (HSCT). Methods: A retrospective review of consecutive patients diagnosed with chronic ocular GvHD between 2011 and 2020 was performed at a tertiary eye care network. Multi?variate regression analysis was carried out for identifying risk factors associated with progressive disease. Results: A total of 34 patients (68 eyes) with a median age of 33 years [inter?quartile range (IQR) 23–40.5] were studied. The most common indication for HSCT was acute lymphocytic leukemia (26%). Ocular GvHD developed at a median of 2 years (IQR 1–5.5 years) after HSCT. Aqueous tear deficiency was present in 71% of the eyes, of which 84% had a Schirmer value of <5 mm. The median visual acuity at presentation and that after a median follow? up of 6.9 months were comparable at 0.1 log minimum angle of resolution (logMAR) (P = 0.97). Topical immunosuppression was required in 88% of cases, and with this, improvement in corneal (53%, P = 0.003) and conjunctival staining scores (45%, P = 0.43) was noted. A progressive disease was present in 32% with persistent epithelial defects being the most common complication. Grade 2 conjunctival hyperemia [odds ratio (OR): 2.6; P = 0.01] and Schirmer’s value <5 mm (OR: 2.7; P = 0.03) were found to be associated with progressive disease. Conclusion: Aqueous deficient DED is the most common ocular manifestation of chronic ocular GvHD, and the risk of the disease progression is greater in eyes with conjunctival hyperemia and severe aqueous deficiency. Awareness among ophthalmologists of this entity is essential for its timely detection and optimal management.

Liver transplantation for acute liver failure in children: 8-year experience in a single center / 器官移植

Objective To evaluate the efficacy of liver transplantation for acute liver failure (ALF) in children. Methods Clinical data of 15 children with ALF who underwent liver transplantation were collected and retrospectively analyzed. The proportion of ALF among children undergoing liver transplantation during the same period was calculated. The characteristics, postoperative complications and clinical prognosis of ALF children receiving liver transplantation were analyzed. Results In the same period, the proportion of ALF was 2.0% (15/743) among pediatric recipients undergoing liver transplantation. All 15 children had acute onset of ALF, and most of them were accompanied by fever, diarrhea and progressive yellowing of skin and sclera. Thirteen children were complicated with hepatic encephalopathy before operation (6 cases of stage Ⅳ hepatic encephalopathy), and two children were complicated with myelosuppression and granulocytopenia before liver transplantation. Ten children underwent living donor liver transplantation with relative donor liver, 4 received liver transplantation from donation after cardiac death (DCD), and 1 underwent Domino donor-auxiliary liver transplantation. Of 15 children, 12 recipients had the same blood type with their donors, 1 recipient had compatible blood type with the donor and 2 cases had different blood type with their donors. Among 15 children, 10 cases developed postoperative complications. Postoperative cerebral edema occurred in 5 cases, of whom 4 cases died of diffuse cerebral edema, and the remaining case was in a persistent vegetative state (eyes-open coma). Postoperative cytomegalovirus (CMV) infection was seen in 5 cases. Two children presented with aplastic anemia and survived after bone marrow transplantation, 1 case died of CMV hepatitis and viral encephalitis, and 2 cases died of diffuse brain edema. One child developed graft-versus-host disease (GVHD) after liver transplantation, and died of septic shock after bone marrow transplantation. Nine children survived and obtained favorable liver function during postoperative follow-up. Conclusions Liver transplantation is an efficacious treatment for ALF in children, which may enhance the survival rate. Brain edema is the main cause of death in ALF children following liver transplantation, and treatment such as lowering intracranial pressure, improving brain metabolism and blood purification should be actively performed. Liver transplantation should be promptly performed prior to the incidence of irreversible neurological damage in ALF children, which might prolong the survival and enhance long-term prognosis.

Advances in extracorporeal photopheresis / 中国输血杂志

Extracorporeal photopheresis(ECP) is a bidirectional cellular immunomodulatory therapy based on leukapheresis, which can mediate not only immunopotentiation but also immunosuppression. Clinically, ECP has been observed to have good efficacy in the treatment of cutaneous T cell lymphoma(CTCL), graft versus-host disease(GVHD) and solid organ transplant rejection, also the US Food and Drug Administration(FDA) has approved ECP for the treatment of CTCL. The treatment guidelines for GVHD in the US and Europe also include ECP, however, there is a lack of relevant guidelines in China. Although the exact mechanism of ECP is not fully explained, recent studies provide a theoretical basis for a further understanding of the bidirectional regulation of ECP.The initial hypothesis was the combination of 8-methoxypsoralen(8-MOP) and ultraviolet A(UVA) to induce apoptosis of immune cells. As the research progressed, this idea was transformed into the differentiation of monocyte to dendritic cell(DC), cytokine alteration and the regulatory T cell(Treg) stimulation.In this article, the current exploration of the immunomodulatory mechanism in ECP and its clinical application were reviewed, also the latest molecular mechanism of ECP mediated immunopotentiation and immunosuppression was comprehensively analyzed, meanwhile the further promotion and clinical application of ECP in China had been prospected.

Diagnostic criteria and its progress on intestinal graft pathology / 器官移植

Intestinal transplantation has become the most ideal treatment for intestinal failure. Modern clinical intestinal transplantation includes three types: isolated intestinal transplantation, combined liver-intestinal transplantation and abdominal multivisceral transplantation. The immunological, anatomical and physiological characteristics of intestinal grafts significantly differ from those of other solid transplant organs. Consequently, intestinal grafts could develop specific and severe complications, such as acute rejection, chronic rejection, graft-versus-host disease (GVHD), infection and posttransplant lymphoproliferative disease (PTLD), among which acute rejection and infection are extremely challenging. Endoscopic examination and intestinal mucosal biopsy of intestinal grafts could be performed to make timely diagnosis and differentiation of these complications, then deliver targeted treatment and guarantee the long-term survival of recipients and intestinal grafts.

Research progress on posttransplant lymphoproliferative disease after lung transplantation / 器官移植

Posttransplant lymphoproliferative disease (PTLD) is a fatal complication after lung transplantation, which is intimately associated with age, immunosuppression level and Epstein-Barr virus (EBV) infection, etc. Reducing immunosuppression level, rituximab therapy and T cell immunotherapy are common treatments for PTLD. With the rapid development of lung transplantation in China, PTLD after lung transplantation has attracted widespread attention. This article reviews the risk factors, pathological types, clinical manifestations, diagnosis, treatment, prognosis and prevention of PTLD after lung transplantation, aiming to provide reference for early monitoring and management of the incidence and progression of PTLD.

Investigation of MHC gamma block C4A and C4B polymorphisms in unrelated hematopoietic stem cell transplantation

ABSTRACT Background: Immunological life-threatening complications frequently occur in post-hematopoietic stem cell transplantation (HSCT), despite matching recipient and donor (R/D) pairs for classical human leukocyte antigens (HLA). Studies have shown that R/D non-HLA disparities within the major histocompatibility complex (MHC) are associated with adverse effects post-HSCT. Methods: We investigated the impact of mismatches of single-nucleotide polymorphisms (SNPs) in C4A/C4B genes, for showing the highest diversity in the MHC gamma block, on 238 patients who underwent HLA 10/10 unrelated donor (URD) HSCT. The endpoints were acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD) and mortality. One hundred and twenty-nine R/D pairs had 23 C4-SNPs typed by PCR-SSP (Gamma-Type™v.1.0), and 109 R/D pairs had these 23 SNPs identified by next-generation sequencing (NGS) using the Illumina platform. Results: The percentage of patients who received HSC from HLA 10/10 donors with 1-7 mismatches was 42.9%. The R/D pairs were considered C4 mismatched when bearing at least one disparity. These mismatches were not found to be risk factors for aGVHD, cGVHD or mortality after unrelated HSCT when SNPs were analyzed together (matched or mm ≥ 1), independently or according to the percentage of incompatibilities (full match for 23 SNPs; 1-3 mm and >3 mm). An exception was the association between 1-3 mismatches at the composite of SNPs C13193/T14952/T19588 with the development of aGVHD (P = 0.012) and with grades III-IV of this disease (P = 0.004). Conclusion: Our data are not consistent with the hypothesis that disparities in C4A/C4B SNPs increase the risks of post-HSCT adverse effects for the endpoints investigated in this study.

Evaluación de formulaciones inmunoterapéuticas experimentales en el modelo hibrido murino de Reaccion del Injerto contra el Hospedador / Evaluation of experimental immunotherapeutic formulations in the hybrid murine model of Graft-versus-Host Reaction

Introducción: La Enfermedad del Injerto Contra el Hospedador es la complicación más frecuente de los Trasplantes de Células Madre Hematopoyéticas y de todos los trasplantes que contengan células inmunocompetentes alogénicas, el 100 por ciento la padecen y cerca del 30 por ciento mueren por su causa; una proporción alta de casos son esteroide-refractarios, asimismo otras medidas inmunosupresoras modernas fracasan. En los campos de la Inmunoterapia y la Vaccinología también existe una escasez preocupante de inmunomoduladores de origen biológico potentes, efectivos, seguros y de amplio espectro. Existe un modelo híbrido murino de gran utilidad metodológica para estudios experimentales. Objetivo: Evaluar dos formulaciones novedosas de origen biotecnológico, una de ellas inmunopotenciadora y otra inmunosupresora, desarrolladas como cocleatos. Material y Métodos: Mediante Microscopia Electrónica y RT-PCR se caracterizaron las formulaciones como nanopartículas y su capacidad de regular la expresión del ARNm de linfoquinas definitorias de sus perfiles, respectivamente. Empleando el modelo de Enfermedad del Injerto Contra el Hospedador en ratón híbrido F1 (CBAxC57BL), se evaluó su carácter inmunomodulador in vivo . Resultados: Partiendo de los proteoliposomas de Neisseria meningitidis, se obtuvieron dos formulaciones en forma de cocleatos, ambas con diámetros de partícula inferior a 100nm. La Formulación 1mostró un perfil proinflamatorio con potente capacidad de aumentar el IFNγ y el TNFα y potenció el Índice de Bazo hasta 2,05 en el modelo EICH con p=0,0002. La Formulación 2 mostró un perfil supresor-regulatorio con potente capacidad de aumentar la IL-10 y el TGFβ y además de suprimir la producción de TNFα. En el modelo usado, esta formulación, suprimió el Índice de Bazo de manera dosis dependiente y con alta significación estadística. Se corroboró el conocido perfil de seguridad y ausencia de reactogenicidad de ambas formulaciones. Conclusiones: Ambas formulaciones tienen potencial aplicación en los campos de la terapia de Enfermedad del Injerto Contra el Hospedador en otras patologías y en Vaccinología. Los resultados obtenidos en el presente trabajo fundamentan la conveniencia de continuar el desarrollo farmacéutico y completar la preclínica de ambas formulaciones(AU)

Introduction: Graft-versus-host disease is the most frequent complication of Hematopoietic Stem Cell Transplants and all transplants containing allogeneic immunocompetent cells; 100 percent of patients suffer from this complication and about 30 percent die for this particular cause. A high proportion of cases are steroid-refractory; likewise, other modern immunosuppressive measures fail. In the fields of Immunotherapy and Vaccinology, there is also a worrying shortage of powerful, effective, safe and broad spectrum immunomodulators of biological origin. There is a hybrid murine model of great methodological utility for experimental studies. Objective: To evaluate two novel formulations of biotechnological origin: an immunopotentiator formulation and an immunosuppressive one, which were developed as cochleates. Material and Methods: The formulations assayed by Electron Microscopy and RT-PCR were characterized as nanoparticles and for their capacity to regulate lymphokine mRNA expression profile, respectively. The immunomodulatory character was evaluated in vivo using Graft-versus-host disease in (CBAxC57BL) F1 hybrid mice. Results: Starting from the proteoliposomes derived from Neisseria meningitides, two cochleate formulations were obtained, both with particle diameters below 100 nm. Formulation 1 showed a proinflammatory profile with potent capacity to increase IFNγ and TNFα, and potentiated the Spleen Index up to 2.05 in the GVDH model with p = 0.0002. Formulation 2 showed a suppressor/regulatory profile with potent capacity to increase IL-10 and TGFβ and suppress the production of TNFα. In the model used, this formulation suppressed the Spleen Index in a dose-dependent manner with high statistical significance. The known safety profile and absence of reactogenicity of both formulations was corroborated. Conclusions: Both formulations have potential application in the fields of GVHD therapy and other pathologies as well as in Vaccinology. The results obtained in the present work suggest the usefulness to continue with the pharmaceutical development and complete the preclinical studies of both formulations(AU)

Application of chimeric antigen receptor-regulatory T cell immunotherapy in organ transplantation / 器官移植

Regulatory T cell (Treg) is a subset of T cells that negatively regulates immunity and has the function of inhibiting rejection. The specific modification of Treg by chimeric antigen receptor (CAR) technology can successfully chime donor-specific antigen onto the surface of Treg, thus regulating the immune function of the body in a real-time manner. It provides a novel and promising therapeutic option for inducing immune tolerance. In this article, research progresses on Treg in immune related diseases, main difficulties in the realization of CAR-Treg technology and its role in inducing transplantation immune tolerance were reviewed, and the opportunities and challenges of CAR-Treg application in the field of organ transplantation are prospected.

Mesenchymal Stem Cells from the Wharton's Jelly of the Human Umbilical Cord: Biological Properties and Therapeutic Potential

Wharton's jelly mesenchymal stem cells (WJ-MSCs) are a class of stem cells with high differentiative potential, an immuno-privileged status and easy access for collection, which raise no legal or ethical issues. WJ-MSCs exhibit several features of embryonic stem cells, both in the phenotypic and genetic aspects, with only a few differences, such as a shorter doubling time and a more extensive ex vivo expansion capacity. WJ-MSCs have immunomodulatory properties, involving both innate and adaptive immune responses. This review focuses on the role of WJ-MSCs in the management of graft-versus-host disease (GvHD), a life-threatening complication of the allogenic transplantation of hematopoietic stem cells. Different studies documented the beneficial effect of the infusion of WJ-MSCs, even when not fully HLA identical, in patients with severe GvHD, refractory to standard treatment. Finally, we summarized current ongoing clinical trials with WJ-MSCs and their potential in regenerative medicine.

Donor characteristics and hematopoietic stem cell transplantation outcome: experience of a single center in Southern Brazil

ABSTRACT Background: Hematopoietic stem cell transplantation is a curative treatment for many patients with hematological disorders. Donor-recipient genetic disparity, especially involving the human leukocyte antigen system is a critical factor for transplant outcome. Objective: To evaluate retrospectively donor characteristics and correlations with the occurrence of acute and chronic graft-versus-host disease, disease-free survival and overall survival in a Brazilian population submitted to allogeneic hematopoietic stem cell transplantation between 1994 and 2012 in a single center. Results: Three hundred and forty-seven consecutive transplantations were included. Related transplants (81.2%) were significantly more common than unrelated transplants (18.7%); donor and recipient median ages were 34 (range: 1-61) and 33 (range: 3-65) years respectively with donor HLAs being matched for 333 (95.9%) patients. Donor gender, cytomegalovirus status and ABO incompatibility did not influence the five-year overall survival. In univariate analyses, overall survival was negatively influenced by the presence of acute graft-versus-host disease (33% vs. 47%, respectively; p-value = 0.04), unrelated transplant (41.5% vs. 50.9%, respectively; p-value = 0.045) and donors aged over 40 years (41% vs. 52%, respectively; p-value = 0.03). Older donors were associated with a higher rate of acute (52% vs. 65.8%; p-value = 0.03) and chronic graft-versus-host disease (60% vs. 43%, respectively; p-value = 0.015). In multivariate analyses, acute graft-versus-host disease [relative risk (RR): 1.8; 95% confidence interval (CI): 1.1-29; p-value = 0.008] and older donors (RR: 1.6; 95% CI 1.11-2.24; p-value = 0.013) were associated with higher transplant-related mortality. Conclusions: In transplant patients, to have a donor older than 40 years of age seems to significantly increase the incidence of acute and chronic graft-versus-host disease and transplant-related mortality with no impact on disease-free survival and overall survival. In spite of the rather small cohort of patients, these findings are similar to what is described in the literature suggesting that a younger donor should be chosen whenever possible.

IMPACT OF CTLA-4 AND NOD2/CARD15 GENE VARIATIONS ON GRAFT- VERSUS-HOST DISEASE AFTER ALLOGENEIC HSCT: A STRUCTURED REVIEW

@#Graft-versus-host Disease (GVHD) is the main cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (alloHSCT). In spite of immune-suppressive prophylaxis, most survivors suffer from acute and chronic GVHD (aGVHD and cGVHD). The outcome of alloHSCT may be affected by the presence of single nucleotide polymorphism (SNP) in non-HLA genes including those involved in innate immune responses. This study aimed to evaluate the impact of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and caspase recruitment domain 15 (NOD2/CARD15) gene polymorphisms on the incidence and severity of aGVHD and cGVHD following alloHSCT. A structured literature review was carried out using various keywords and MESH terms such as stem cell transplantation, allogenic haematopoietic stem cell transplantation, GVHD, and non-HLA gene polymorphism, in PubMed, Google Scholar and Cochrane Database. A total of 8 studies that met inclusion criteria (English publications from 2006 to 2017) were included. Ten SNPs in CTLA-4 gene and three SNPs in NOD2/CARD15 gene were tested in patients with underlying haematological malignancies. Four studies tested the SNPs of CTLA-4 gene and two were found to have an association with CTLA-4 SNPs (rs3087243, rs231775) and increased incidence of aGVHD. The other four studies tested the SNPs of NOD2/CARD15 gene and one found an association between SNP13 and increased incidence of aGVHD. None of these eight studies found any effect on severity of GVHD. In conclusion, two SNPs in CTLA-4 and one SNP in NOD2/CARD15 increased the incidence of aGVHD but not its severity. The higher incidence of aGVHD in studies with larger sample size could support the impact of SNPs in the outcome of alloHSCT. However, due to the heterogeneity of studies in regard to the age of patients and donor, and conditioning regimen, it is difficult to draw a definite conclusion

Pre-sarcopenia and bone mineral density in adults submitted to hematopoietic stem cell transplantation

Abstract Background: The aim of this study was to evaluate the prevalence of pre-sarcopenia and bone mineral density after hematopoietic stem cell transplantation. Methods: The study group consisted of over 18-year-old patients who had been submitted to allogeneic transplantation at least one year previously. Patients and healthy controls were matched by sex, ethnic background, age, and body mass index. Body composition and bone mineral density were measured by dual-energy X-ray absorptiometry. A 24-h food recall and food frequency survey were performed. The biochemical evaluation included calcium, parathormone and vitamin D. Eighty-seven patients (52 men; age: 37.2 ± 12.7 years; body mass index: 25 ± 4.5 kg/m2) were compared to 68 controls [31 men; age 35.4 ± 15.5 years (p = 0.467); body mass index 25.05 ± 3.7 kg/m2 (p = 0.927)]. Results: There was no significant difference in the dietary intake between patients and controls. The mean levels of vitamin D were 23.5 ± 10.3 ng/mL; 29 patients (41.0%) had insufficient and 26 (37.14%) deficient levels. A higher prevalence of reduced bone mineral density was observed in 24 patients (25%) compared to 12 controls (19.1% - p < 0.001). Pre-sarcopenia was diagnosed in 14 (14.4%) patients and none of the controls (p = 0.05). There was a higher prevalence of pre-sarcopenia (66%) in patients with grades III and IV compared to those with grades 0-II graft-versus-host disease (10.9%) (p = 0.004). Conclusion: patients submitted to transplantation had a higher prevalence of pre-sarcopenia and greater changes in bone mineral density compared to controls; the severity of graft-versus-host disease had an impact on the prevalence of pre-sarcopenia.

Gut Microbiota in Graft-versus-Host Disease

Gut microbiota inhabit the host gastrointestinal (GI) tract and play roles in many aspects of metabolic and immunologic homeostasis. Understanding about gut microbiota composition in health and disease is accumulating with the advances in gene sequencing technology. Graft-versus-host disease (GVHD) is a major complication after allogenic bone marrow transplantation (allo-BMT), a gold standard clinical procedure to treat hematologic disorders such as leukemia and lymphomas. Recent studies have shown that a disturbance in the gut microbiota affects GVHD prognosis. Decrease in a compositional diversity is suggested as an independent predictor of GVHD and colonization of noncommensal Enterococcus is shown to be involved in unpleasant treatment outcomes. This article describes current understanding about allo-BMT-induced gut microbiota changes and its involvement in the incidence of GVHD. In addition, several putative therapeutic strategies to decrease GVHD-related mortality after allo-BMT are discussed.

Attenuation of Hepatic Graft-versus-host Disease in Allogeneic Recipients of MyD88-deficient Donor Bone Marrow

Acute graft-versus-host-disease (GVHD) is characterized by selective damage to the liver, the skin, and the gastrointestinal tract. Following allogeneic hematopoietic stem cell transplantation, donor bone marrow (BM) cells repopulate the immune system of the recipient. We previously demonstrated that the acute intestinal GVHD (iGVHD) mortality rate was higher in MyD88-deficient BM recipients than that in the control BM recipients. In the present study, the role of MyD88 (expressed by donor BM) in the pathophysiology of hepatic GVHD (hGVHD) was examined. Unlike iGVHD, transplantation with MyD88-deficient T-cell depleted (TCD) BM attenuated hGVHD severity and was associated with low infiltration of T cells into the liver of the recipients. Moreover, GVHD hosts, transplanted with MyD88-deficient TCD BM, exhibited markedly reduced expansion of CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSC) in the liver. Adoptive injection of the MDSC from wild type mice, but not MyD88-deficient mice, enhanced hepatic T cell infiltration in the MyD88-deficient TCD BM recipients. Pre-treatment of BM donors with LPS increased MDSC levels in the liver of allogeneic wild type BM recipients. In conclusion, hGVHD and iGVHD may occur through various mechanisms based on the presence of MyD88 in the non-T cell compartment of the allograft.

Therapeutic Effects of 0.03% Tacrolimus Eye Drops for Chronic Ocular Graft-Versus-Host Disease

PURPOSE: To evaluate the therapeutic effects of 0.03% tacrolimus eye drops on dry eye associated with chronic ocular graft-versus-host disease (GVHD). METHODS: This study included 24 eyes of 12 patients with refractory dry eye associated with chronic ocular GVHD who were unresponsive to topical steroid and 0.05% topical cyclosporine. The topical steroid and cyclosporine were discontinued for 2 weeks before treatment and 0.03% tacrolimus eye drops were applied twice a day for 1 month. Artificial tears, ointment, and lid cleanser were used in the same manner before initiating tacrolimus treatment. Ocular staining score, tear break-up time, ocular surface disease index (OSDI), and Schirmer I test score were evaluated. RESULTS: Ocular staining score, tear break-up time, and OSDI improved with statistical significance (p < 0.05) after 28 days of treatment. Schirmer I test did not show statistical improvement after treatment. CONCLUSIONS: The use of 0.03% tacrolimus eye drops were effective for refractory dry eye associated with chronic ocular GVHD.

SOCS1 and SOCS3 are expressed in mononuclear cells in human cytomegalovirus viremia after allogeneic hematopoietic stem cell transplantation

BACKGROUND: The expression of the SOCS genes in cytomegalovirus (CMV) viremia after hematopoietic stem cell transplantation (HSCT) remains largely unexplored. METHODS: Using quantitative RT-PCR of mononuclear cells, we conducted pairwise comparison of SOCS1 and SOCS3 expression levels among a healthy donor group (N=55), a pre-HSCT group (N=17), and the recipient subgroup (N=107), which were divided according to the occurrence of CMV viremia and acute graft-versus-host disease (aGVHD). RESULTS: Compared to that in the healthy donor group, SOCS1 expression was higher in the CMV+ subgroup, especially in the CMV+GVHD- group, but decreased in the other subgroups. When compared to the expression in the pre-HSCT group, SOCS1 expression was significantly higher in the CMV+ subgroup, especially in the CMV+GVHD+ subgroup. Meanwhile, compared to that in the healthy donor group, SOCS3 expression was significantly lower in all other groups. The CMV-GVHD- subgroup showed significantly lower SOCS3 expression compared to the CMV+ subgroup, the CMV+GVHD+ subgroup, and the CMV+GVHD- subgroup. CONCLUSION: We report differential expression of SOCS genes according to CMV viremia with acute GVHD occurrence after HSCT, suggesting that regulation of SOCS expression is associated with CMV viremia.

Clinical Manifestations and Risk Factors of Ocular Graft-versus-Host Disease (GVHD) after Hematopoietic Stem Cell Transplantation

PURPOSE: To investigate the incidence, clinical manifestations, and risk factors of ocular graft-versus-host disease (GVHD) as well as the survival of the patients after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: The medical records of 99 patients who visited our clinic and were screened for ocular GVHD after allogeneic HSCT were reviewed retrospectively. Subjects were divided into 2 groups depending on the occurrence of ocular GVHD on slit-lamp biomicroscopy. We compared clinical manifestations and survival between the 2 groups and analyzed the risk factors associated with the development of ocular GVHD. RESULTS: Ocular GVHD was diagnosed in 38 patients (38.38%) at a mean of 315 days after HSCT. Out of the 38 patients who developed ocular GVHD, 22 patients (57.89%) were diagnosed with dry eye only and 16 patients (42.11%) were diagnosed with conjunctival disease. The presence of extraocular GVHD (hazard ratio (HR) 35.76, p < 0.001), the number of extraocular GVHD (HR 3.07, p < 0.001), skin GVHD (HR 2.31, p = 0.029), oral GVHD (HR 8.16, p < 0.001), and gastrointestinal tract GVHD (HR 5.00, p = 0.002) were independent risk factors of ocular GVHD. Comparisons of the survival demonstrated decreased survival of patients with conjunctival disease compared to patients without ocular GVHD and patients with dry eye only, but there was no statistically significant differences (log rank test, p = 0.208). CONCLUSIONS: Ocular GVHD is common after allogeneic HSCT. The majority of ocular GVHD occurs in the chronic stage and is associated with decreased survival. Therefore, more intensive and long-term follow-up with ophthalmic and systemic monitoring is necessary, especially in patients who have extraocular GVHD, for early recognition and proper treatment of ocular GVHD.

HLA Mismatch Allogeneic Blood and Marrow Transplantation / 대한내과학회지

A full haplotype mismatch or mismatched unrelated donor transplantation nowadays are well being focused on, as main alternative donor tools for acute leukemia patients in desperate need of allogeneic blood and marrow transplantation (BMT), the ability to overcome various posttransplant complications by adopting the T-cell replete technique in reality. Increasing numbers of allogeneic BMT in good clinical status are largely because it's the best post-remission therapy especially for many patients with acute leukemias. Due to the problems of unavailable donors at appropriate clinical condition and the process of long duration of donor searching step with relatively much higher cost, some of physicians have indulged in haploidentical BMT rather than mismatched unrelated BMT. Both myeloablative and reduced intensity conditioning regimens for mismatched BMT with T-cell replete or T-cell depletion method have been exploited worldwide. Most of all, Asian countries have experienced lower rates of severe acute and chronic GvHD, graft failure, and impressively low transplant-related mortality with longer follow-up duration. Also, we need many future trials to compare outcomes between these two transplant modalities with cord blood transplant in various diseased patient populations.

Kinetics of IFN-gamma and IL-17 Production by CD4 and CD8 T Cells during Acute Graft-versus-Host Disease

Graft-versus-host disease (GVHD) is a fatal complication that occurs after allogeneic hematopoietic stem cell transplantation. To understand the dynamics of CD4 and CD8 T cell production of IFN-gamma and IL-17 during GVHD progression, we established a GVHD model by transplanting T cell-depleted bone marrow (TCD-BM) and purified T cells from B6 mice into irradiated BALB.B, creating an MHC-matched but minor histocompatibility (H) antigen-mismatched transplantation (B6 --> BALB.B GVHD). Transplantation-induced GVHD was confirmed by the presence of the appropriate compositional changes in the T cell compartments and innate immune cells in the blood and the systemic secretion of inflammatory cytokines. Using this B6 --> BALB.B GVHD model, we showed that the production of IFN-gamma and IL-17 by CD4 T cells preceded that by CD8 T cells in the spleen, mesenteric lymph node, liver, and lung in the BALB.B GVHD host, and Th1 differentiation predated Th17 differentiation in all organs during GVHD progression. Such changes in cytokine production were based on changes in cytokine gene expression by the T cells at different time points during GVHD development. These results demonstrate that both IFN-gamma and IL-17 are produced by CD4 and CD8 T cells but with different kinetics during GVHD progression.

Extensive Fasciitis in Sclerotic-type Chronic Cutaneous Graft-versus-Host Disease / 대한피부과학회지

Fasciitis can occur very rarely with sclerotic-type chronic cutaneous graft-versus-host disease (GVHD). A 54-year-old woman presented with painful skin tightness on upper and lower limb with limited range of movement. She was diagnosed with chronic myelocytic leukemia 5 years ago and underwent allogeneic bone marrow transplantation. Histopathologically, the interlobular septum of subcutis and fascia were remarkably thickened with fibrosis and moderate inflammatory infiltrates accompanying the dilated lymphatic channels with considerable leakage of lymph fluids. Herein, we report a case of extensive fasciitis as a manifestation of chronic GVHD associated with poor prognosis.