[The prognostic value of colonoscopy grading for acute graft-versus-host disease in patients with malignant hematological disorders after unrelated cord blood transplantation].

Objective: To investigate the prognostic value of enteroscopic grading for the prognostic assessment of patients with malignant hematological diseases who developed intestinal acute graft-versus-host disease (IT-aGVHD) after unrelated cord blood transplantation (UCBT) . Methods: Fifty patients with IT-aGVHD who developed hormone resistance after UCBT from June 2016 to June 2023 at Anhui Provincial Hospital were collected to compare the effective and survival rates of IT-aGVHD treatment in the group with milder enteroscopic mucosal injury (27 cases, enteroscopic grading of Ⅰ and Ⅱ) and the group with more severe injury (23 cases, enteroscopic grading of Ⅲ and Ⅳ) and to retrospectively analyze the factors affecting patients' prognosis. Results: Patients in the mild and severe groups had an effective rate of 92.6% and 47.8% at 28 days after colonoscopy (P<0.001), 81.5% and 39.1% at 56 days after colonoscopy (P=0.002), with optimal effective rate of 92.6% and 65.2% (P=0.040), respectively, and the differences were statistically significant. The multifactorial analysis found that enteroscopic grading was an independent risk factor affecting the effective rate of IT-aGVHD treatment. The overall survival rate at 2 years after colonoscopy was 70.4% (95% CI 52.0% -88.8% ) and 34.8% (95% CI 14.8% -54.8% ) for patients in the mild and severe groups, respectively, and the difference was statistically significant (P=0.003). Multifactorial analysis revealed that enteroscopic grading, cytomegalovirus infection status, second-line treatment regimen, and patients' age were independent risk factors for survival. Conclusion: The treatment efficacy and prognosis of patients in the group with less severe enteroscopic injury (grades Ⅰ and Ⅱ) were better than those in the group with more severe injury (grades Ⅲ and Ⅳ) .

invariant Natural Killer T cell therapy as a novel therapeutic approach in hematological malignancies.

Invariant Natural Killer T cell therapy is an emerging platform of immunotherapy for cancer treatment. This unique cell population is a promising candidate for cell therapy for cancer treatment because of its inherent cytotoxicity against CD1d positive cancers as well as its ability to induce host CD8 T cell cross priming. Substantial evidence supports that iNKT cells can modulate myelomonocytic populations in the tumor microenvironment to ameliorate immune dysregulation to antagonize tumor progression. iNKT cells can also protect from graft-versus-host disease (GVHD) through several mechanisms, including the expansion of regulatory T cells (Treg). Ultimately, iNKT cell-based therapy can retain antitumor activity while providing protection against GVHD simultaneously. Therefore, these biological properties render iNKT cells as a promising "off-the-shelf" therapy for diverse hematological malignancies and possible solid tumors. Further the introduction of a chimeric antigen recetor (CAR) can further target iNKT cells and enhance function. We foresee that improved vector design and other strategies such as combinatorial treatments with small molecules or immune checkpoint inhibitors could improve CAR iNKT in vivo persistence, functionality and leverage anti-tumor activity along with the abatement of iNKT cell dysfunction or exhaustion.

Sex differences in donor T cell targeting of host splenocyte subpopulations in acute and chronic murine graft-vs.-host disease: implications for lupus-like autoimmunity.

This study sought to compare in vivo sex differences in either a Th1-dominant CTL response or a Tfh-mediated lupus-like antibody response using the parent-into F1 murine model of acute or chronic GVHD respectively. In acute GVHD we observed no significant sex differences in the hierarchy of donor CD8 CTL elimination of splenocyte subsets. B cells were the most sensitive to elimination in both sexes; however, the male response was significantly stronger. Sex differences in chronic GVHD were more widespread; females exhibited significantly greater numbers of total splenocytes and host CD4 Tfh cells, B cells and CD8 T cells consistent with reports of greater female autoantibody production in this model. The more potent male CTL response in acute GVHD conflicts with reports of greater female CTL responses following infections or vaccines and may reflect the absence of exogenous innate immune stimuli in this model.

The rationale behind grafting haploidentical hematopoietic stem cells.

The ability to perform hematopoietic cell transplant across major histocompatibility complex barriers can dramatically increase the availability of donors and allow more patients across the world to pursue curative transplant procedures for underlying hematologic disorders. Early attempts at haploidentical transplantation using broadly reactive T-cell depletion approaches were compromised by graft rejection, graft-versus-host disease and prolonged immune deficiency. The evolution of haploidentical transplantation focused on expanding transplanted hematopoietic progenitors as well as using less broadly reactive T-cell depletion. Significant outcome improvements were identified with technology advances allowing selective depletion of donor allospecific T cells, initially ex-vivo with evolution to its current in-vivo approach with the infusion of the highly immunosuppressive chemotherapy agent, cyclophosphamide after transplantation procedure. Current approaches are facile and portable, allowing expansion of allogeneic hematopoietic cell transplantation for patients across the world, including previously underserved populations.

Mesenchymal stromal cells in the treatment of pediatric hematopoietic cell transplantation-related complications (graft vs. host disease, hemorrhagic cystitis, graft failure and poor graft function): a single center experience.

Objectives: To describe mesenchymal stromal cells (MSCs) in the treatment of hematopoietic stem cell transplantation (HSCT) complications and to assess its safety and efficacy. Methods: Single-center retrospective study (2016-2023). Patients under 20 years who received MSCs for the treatment of HSCT-related complications were included. Results: Thirty patients (53.7% boys), median age at transplant 11 years (range 2-19) were included. MSCs indications were: graft-vs.-host disease (GVHD) in 18 patients (60%), of them 13 had acute GVHD (43.3%) and 5 chronic GVHD (16.7%); Grade 3-4 hemorrhagic cystitis (HC) in 4 (13.3%); poor graft function (PGF) in 6 (20%), 5 of them receiving MSCs with a CD34 stem cell-boost coinfusion; graft failure (GF) in 2 (6.7%), to enhance engraftment after a subsequent HSCT. Infusion-related-adverse-events were not reported. Overall response (OR) was 83% (25/30); 44% of responders (11/25) showed complete response (CR). OR for GVHD, HC, PGF and GF was 83.3%, 100%, 66.7% and 100% respectively. Response rate was 40% (95% CI: 20-55) and 79% (95% CI: 57-89) at 15 and 30 days. With a median follow-up of 21 months (IQR11-52.5), overall survival (OS) was 86% (95% CI: 74-100) and 79% (95% CI: 65-95) at 6 and 12 months post-MSCs infusion. Conclusion: In our study, the most frequent indication of MSCs was refractory aGVHD (43.3%). Response rates were high (OR 83%) and safety profile was good.

The ABO blood group antigens in patients with oral lichenoid reaction.

Evaluating the association of ABO blood group with different delayed hypersensitivity reactions, such as oral lichenoid reaction (OLR), can provide a new perspective for clinical practice. Therefore, this study designed to investigate ABO blood group antigens in OLR patients. In this case-control study, the ABO blood group of 112 OLR patients and 117 individuals without oral lesions were included. Gender, age, characteristics of the lesions, medications and restorative materials recorded. Chi-square test used to compare the frequency of ABO blood groups in OLR patients with controls. The O blood group was significantly higher in OLR patients and all its subtypes. Also, there were significant relation between O blood group, and severity of lesions. The frequency of dysplasia was non-statistically significant higher in OLR patients with O blood group than other blood group. Based on the results of the present study, O blood group was significantly more in patients with lichenoid reaction than control group, and AB blood group was the lowest. Also, O blood group showed a positive association with the more severe form of OLR lesions and frequency of dysplasia.

Immediate pain alleviation in oral mucositis and other oral ulcerative diseases through photobiomodulation therapy: the preemptive treatment concept.

OBJECTIVE: Photobiomodulation therapy is recommended by multiple international societies for managing oral mucositis. These recommendations are based on extensive evidence. However, the search for an optimal photobiomodulation protocol continues. This mapping review focuses on a novel aspect of photobiomodulation therapy which is the immediate effect on pain levels associated with oral ulcerative conditions. DATA SOURCES: This literature review systematically compiles and evaluates the evidence about oral mucositis, alongside other oral ulcerative conditions, as the protocols that achieved pain relief for these oral conditions may have potential applicability to oral mucositis management. The scientific database used was PubMed. CONCLUSION: Whereas most of the randomized controlled trials about photobiomodulation therapy for oral mucositis and other ulcerative oral diseases reported delayed pain relief, certain photobiomodulation therapy protocols reported immediate pain relief. The results of this review highlight the concept of preemptive photobiomodulation therapy, in which photobiomodulation therapy is delivered early in the development of oral mucositis throughout the oncotherapy and may achieve immediate pain relief consistently in most of the patients and close to a negligible pain level. Photobiomodulation therapy, as a powerful nonpharmacologic tool for immediate pain relief, has a great beneficial value in patients suffering from oral mucositis and other painful oral ulcerative diseases such as recurrent aphthous stomatitis and chronic graft-versus-host disease.

Exploring strategies to optimise outcomes in hepatitis-associated aplastic anaemia patients following haematopoietic stem cell transplantation.

This study aimed to assess haematopoietic stem cell transplantation (HSCT) safety and efficacy while exploring strategies for optimising outcomes in patients with hepatitis-associated aplastic anaemia (HAAA). We retrospectively reviewed 35 HAAA patients who underwent HSCT at a large Chinese blood disease hospital between 2008 and 2022. HAAA patients receiving HSCT typically presented with severe (28.6%) and very severe (65.7%) AA. Male patients predominated (68.6%), with a median onset age of 23 years (range, 9-44). Haploidentical donor-HSCT and matched sibling donor-HSCT were in comparable proportions. The 5-year overall survival (OS) rate was 74.0%, with cumulative incidences of grade II-IV acute and chronic graft-versus-host disease (GVHD) at 37.1% and 22.4%, respectively. A diagnosis-to-HSCT interval ≥ 75 days, acute GVHD, and post-HSCT liver events (e.g., hepatic GVHD and a three-fold increase in aminotransferase or bilirubin) significantly worsened 5-year OS. In the multivariate models, recipients with sex-matched grafts had better OS, and those with younger male donors had a lower incidence of II-IV aGVHD. Higher HLA matching degree (HLA > = 7/10) was an independent prognostic factor associated with better OS and GFFS. A diagnosis-to-HSCT interval ≥ 75 days was predictive of post-transplant liver events in HAAA patients. In conclusion, HSCT was a safe and effective treatment for HAAA. Early transplantation, careful donor selection and improving post-transplant liver events were crucial to optimise outcomes.

Severe Liver Dysfunction after Donor Lymphocyte Infusion for Relapsed Multiple Myeloma.

Donor lymphocyte infusion (DLI) is performed to augment an anti-tumor immune response or ensure donor stem cells remain engrafted following allogeneic stem cell transplantation but may induce graft-versus-host disease (GVHD) involving skin, intestine, and liver. Although hepatic involvement of GVHD can manifest as mild to severe hepatitis, few reports have mentioned acute severe liver dysfunction with encephalopathy. We experienced a case of acute severe liver dysfunction with semicoma after DLI in a patient with relapsed multiple myeloma following allogeneic stem cell transplantation, in whom chronic viral hepatitis B had been suppressed by antiviral treatment. The patient recovered after high-dose glucocorticoid administration based on an assessment of hepatic GVHD. Clinicians should be aware of the possibility of this catastrophic hepatic complication after DLI in hematologic disorders.

Cellular senescence promotes meibomian gland dysfunction in a chronic graft-versus-host disease mouse model.

PURPOSE: Aging is a well-established risk factor for meibomian gland dysfunction (MGD). We previously reported an accelerated cellular senescence phenomenon in the lacrimal glands of a murine model of chronic graft-versus-host disease (cGVHD). Herein, we aimed to elucidate the relationship between cellular senescence and MGD in cGVHD mice, utilizing the senolytic agent ABT-263. METHODS: A cGVHD mouse model was established through allogeneic bone marrow transplantation (BMT) from B10.D2 to BALB/c mice. Subsequently, cGVHD mice were treated with either ABT-263 or vehicle. The eyelids of recipients were analyzed at 4-week intervals post-BMT in both groups. RESULTS: Meibomian gland (MG) area was significantly smaller in cGVHD mice than in syngeneic control mice. ABT-263-treated mice retained a significantly larger MG area than their vehicle-treated counterparts. Pathological and immunohistochemical examinations revealed significant reductions in eyelid tissue inflammation and pathological fibrosis in the ABT-263 group compared to that in the vehicle-treated group. Additionally, expression of DNA damage markers, senescent cell markers, and senescence-associated secretory phenotype (SASP) factors was elevated in the eyelids of cGVHD mice compared with that in syngeneic mice. The expression of these cellular senescence-associated molecules was considerably suppressed in ABT-263-treated eyelids compared to that in vehicle-treated ones. CONCLUSIONS: Cellular senescence, along with expression of SASP factors, exhibited increased activity in the eyelids, particularly in the MGs of cGVHD mice. ABT-263 mitigated the severity of MGD. These findings highlight the potential of targeting cellular senescence as an effective approach for MGD treatment in cGVHD.

Long-Term Clinical Outcomes and B Cell Immune Reconstitution Following Allo-HCT With Prophylactic, Post-Transplant Rituximab.

Chronic graft-versus-host disease (cGVHD) remains a significant source of morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Post-transplant, prophylactic rituximab has successfully decreased cGHVD rates in clinical trials, but the durability of this strategy is uncertain. The long-terms effect of post-HCT B cell depletion on immune reconstitution, B cell function, and infectious complications are also unknown. In this study, we provide 10 yr follow-up and correlative analyses on patients given post-HCT, prophylactic rituximab. The objective of the study is to examine the durability of cGVHD protection as well as the long-term effect of rituximab prophylaxis on protective immune reconstitution, B cell function, and alloantibody formation. We analyzed 35 patients given prophylactic rituximab on phase II clinical trial. Clinical outcomes included cGVHD development, relapse and survival outcomes, and infectious outcomes. Correlative analyses included B cell subset analysis, development of antibodies to infectious antigens, and, for male patients receiving female donor grafts, development of antibodies to HY antigens. To further investigate the effect of rituximab on immune reconstitution and function, we also analyzed 43 similarly transplanted patients who did not receive post- or peri-HCT rituximab as a comparator group. For patients who received rituximab, the 8-yr cumulative incidence of cGHVD and freedom from immunosuppression were 20.0% and 76.2%, respectively. Importantly, no late incidences of cGVHD developed beyond 14 mo post-HCT. Relative to patients who did not receive rituximab, post-HCT rituximab was associated with increased B cell aplasia at 1 yr post-HCT (42.9% versus 11% of patients, P = .037); by 3 yr post-HCT, this aplasia resolved. Patients who received rituximab also had a significantly lower proportion of IgD+/CD38+ transitional B cells at 3 yr post-HCT (78.8% versus 89.9%, P = .039); at 10 yr post-HCT, this percentage remained markedly decreased at 50.7%. Rituximab prophylaxis altered B cell function. In male patients receiving female donor grafts, fewer patients developed HY antibodies at 3 yr post-HCT (20% versus 78%, P = .04). At 10 yr post-HCT, HY antibody production remained decreased at 33%. Rituximab prophylaxis was also associated with significantly lower antibody response to tetanus and EBV infectious antigens as well as lower IgG levels. Despite these changes, post-HCT was not associated with increased infections, although patients who received rituximab required intravenous immunoglobulin (IVIG) supplementation more frequently than those who did not (62.9% versus 32.6% of patients, P = .01). Prior data on the efficacy and feasibility of rituximab prophylaxis are durable, with persistent reduction in cGVHD. Rituximab prophylaxis also results in lasting B cell immunologic changes, with altered B cell subset composition and decreased alloantibody formation. Associated infectious risks were not increased, perhaps mitigated by high IVIG use.

Autologous Gastrointestinal Graft-vs-Host Disease in a Patient With Multiple Myeloma and Hematopoietic Stem Cell Transplantation.

Graft-vs-host disease (GVHD) of the gastrointestinal (GI) tract is notably a serious complication of allogeneic hematopoietic stem cell transplant (HSCT). However, GI GVHD has rarely been reported in autologous HSCT, and the pathophysiology remains unclear. Diagnosing GVHD after autologous HSCT requires a high level of clinical suspicion, given its nonspecific clinical presentation and endoscopic findings necessitating a histological diagnosis for confirmation. We present a case of autologous GVHD involving the GI tract in a patient with multiple myeloma who responded well to corticosteroids, highlighting the importance of early identification of this rare entity to initiate therapy and improve outcomes.

Cost-Effectiveness of Extracorporeal Photopheresis in Patients With Chronic Graft-vs-Host Disease.

Background: The mainstay first-line therapy for chronic graft-vs-host disease (cGVHD) is corticosteroids; however, for steroid-refractory patients, there is a distinct lack of cost-effective or efficacious treatment. The aim of this study was to assess the cost-effectiveness of extracorporeal photopheresis (ECP) compared with standard-of-care therapies for the treatment of cGVHD in Australia. The study formed part of an application to the Australian Government to reimburse ECP for these patients. Methods: A cost-utility analysis was conducted comparing ECP to standard of care, which modeled the response to treatment and disease progression of cGVHD patients in Australia. Mycophenolate, tacrolimus, and cyclosporin comprised second-line standard of care based on a survey of Australian clinicians. Health states in the model included treatment response, disease progression, and death. Transition probabilities were obtained from Australian-specific registry data and randomized controlled evidence. Quality-of-life values were applied based on treatment response. The analysis considered costs of second-line treatment and disease management including immunosuppressants, hospitalizations and subsequent therapy. Disease-specific mortality was calculated for treatment response and progression. Results: Over a 10-year time horizon, ECP resulted in an average cost reduction of $23 999 and an incremental improvement of 1.10 quality-adjusted life-years per patient compared with standard of care. The sensitivity analysis demonstrated robustness over a range of plausible scenarios. Conclusion: This analysis demonstrates that ECP improves quality of life, minimizes the harms associated with immunosuppressant therapy, and is a highly cost-effective option for steroid-refractory cGVHD patients in Australia. Based in part on this analysis, ECP was listed on the Medicare Benefits Schedule for public reimbursement.

Group Coping Intervention in Patients With Chronic Graft-Versus-Host Disease: A Pilot Randomized Clinical Trial.

BACKGROUND: More than half the long-term survivors of allogeneic hematopoietic cell transplantation develop chronic graft-versus-host disease (GVHD), a debilitating inflammatory syndrome. Supportive interventions to assist survivors in coping with chronic GVHD are critically needed. PATIENTS AND METHODS: We conducted a pilot randomized clinical trial of a multidisciplinary group intervention (Horizons Program; n=39) versus minimally enhanced usual care (n=41) for patients with moderate or severe chronic GVHD. Horizons participants received 8 weekly sessions about GVHD and coping co-led by a transplant clinician and a behavioral health expert via a secure videoconferencing platform. Participants completed the following surveys before randomization, at 10 weeks, and at 18 weeks: Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT) for quality of life (QoL), Lee Symptom Scale for symptom burden, and Hospital Anxiety and Depression Scale-Depression Symptoms (HADS) for mood. The primary endpoint was feasibility (≥50% enrollment, ≥80% attendance in half the sessions for the Horizons arm only, and ≥80% retention). We also explored preliminary efficacy of the Horizons intervention on changes in patient-reported outcomes with linear mixed effects models and estimates of effect size at 10 weeks. RESULTS: We enrolled and registered 80 (67.2%) of 119 eligible patients (mean age, 62 years; 48.8% female). Of the participants in the Horizons Program, 84.6% attended at least half the sessions. Of registered participants, 91.3% completed assessment follow-ups (Horizons, 35/39 [89.7%]; minimally enhanced usual care, 38/41 [92.7%]). Horizons participants reported improvements in QoL (b = 2.24; d=0.53), anxiety symptoms (b = -0.10; d=0.34), and depression symptoms (b = -0.71; d=0.44) compared with participants who received minimally enhanced usual care. CONCLUSIONS: Participation in a multidisciplinary group intervention study was feasible for patients with chronic GVHD, with promising signals for improving QoL and mood. A full-scale efficacy trial is needed to confirm effects on patient-reported outcomes.

Vitiligo and Alopecia Areata After Donor Lymphocyte Infusions in a Child With Relapsed Acute Myeloid Leukemia.

Rarely do patients with chronic graft-versus-host disease (cGVHD) experience vitiligo and alopecia areata. Nevertheless, the exact cause of vitiligo and alopecia areata is still not fully understood. The patient experienced a relapse of acute myeloid leukemia (AML) following a second complete remission after undergoing HLA-6/8 mismatched unrelated donor hematopoietic cell transplantation (HCT). Achieving full donor chimerism was successful during the initial stages of the transplant. Nevertheless, the molecular evidence of measurable residual disease remained, prompting the administration of donor lymphocyte infusions (DLI) following a dose-escalation protocol. After three cycles of DLI given at two-month intervals, the circulating blasts eventually vanished. After the third DLI dose, vitiligo developed despite achieving molecular remission. The dermatologist confirmed the presence of vitiligo and alopecia areata, along with cutaneous cGVHD. The outcome was the complete elimination of the molecular presence, and the patient experienced both clinical and molecular remission for a period of five years following DLI. Based on our observations, it was found that DLI could effectively eradicate molecular leukemia in cases of AML relapse after HCT. The development of vitiligo and alopecia areata was influenced by the destruction of melanocytes due to autoimmune reactions caused by cGVHD.

Comparison of tacrolimus vs. cyclosporine in pediatric hematopoietic stem cell transplantation for thalassemia.

OBJECTIVES: Graft-versus-host disease (GvHD) is one of the leading causes of morbidity and mortality in patients undergoing allogeneic HSCT, and effective prevention of GvHD is critical for the success of the HSCT procedure. Calcineurin inhibitors (CNI) have been used for decades as the backbone of GvHD prophylaxis. In this study, the efficacy and safety of Cyclosporine A (CsA) and tacrolimus (TCR) were compared in pediatric HSCT for thalassemia. MATERIALS AND METHODS: This is a retrospective analysis of 129 pediatric patients who underwent HSCT with the diagnosis of thalassemia at Medicalpark Göztepe and Antalya Hospitals between January 2017 and December 2020. RESULTS: Despite the GvHD prophylaxis, grade II-IV acute GvHD developed in 29 patients. Of these patients, 12 had only gut, 10 had only skin, 6 had combined gut and skin, and one had only liver GvHD. Fifteen of these 29 patients were in the CsA group, and 14 of them were in the TCR group. There was no significant difference between the groups in terms of acute GvHD occurrence, GvHD stage, or involvement sites. In terms of CNI-related toxicity, neurotoxicity in 15 (CsA n = 9, TCR n = 6) and nephrotoxicity in 18 (CsA n = 4, TCR n = 14) patients were observed. While there was no difference between the two groups in terms of neurotoxicity, more nephrotoxicity developed in patients using TCR (p = .013). There was no significant difference between the groups in terms of engraftment syndrome, veno-occlusive disease, CMV reactivation, PRES, or graft rejection. CONCLUSION: Regarding GvHD, there was no difference in efficacy between TCR and CsA usage. Patients taking TCR experienced noticeably higher nephrotoxicity in terms of adverse effects. This difference should be considered according to the patient's clinical situation while choosing a CNI.

Oral squamous cell carcinoma arising from areas of Graft-versus-host disease: A systematic review / Carcinoma oral de células escamosas que surge de áreas de enfermedad de injerto contra huésped: una revisión sistemática

Background: Graft-versus-host disease (GVHD) is an immune system reaction that occurs in patients with ahistory of hematopoietic stem cell transplantation (HSCT), in which the grafted donor's cells attack those of thehost. The objective of this systematic review was to present a study on oral squamous cell carcinoma (OSSC) thatdeveloped from GVHD areas in patients undergoing HSCT.Material and Methods: An electronic search was conducted in the databases PUBMED, WEB OF SCIENCE,SCOPUS, MEDLINE and SCIENCE DIRECT, according to PRISMA guidelines. Results: Of the 1582 results, 23 articles were included, resulting in 81 cases. The most common underlying diseasefor performing the transplant was Myeloid Leukemia (55.6%). The mean age was 39 years, with a predilection formales (64.2%). The tongue was the site of GVHD that most frequently underwent transformation to SCC (59.3%).The average time between transplantation and the development of GVHD was of approximately of 8 months, whilethe average period of development between transplantation and the development of OSCC was of approximately of111 months. The most common treatment to GVHD was cyclosporine associated with corticosteroids.Conclusions: OSCCs arising from areas of GVHD present a different evolution from conventional oral carcinomas,since they affect younger patients, smoking and alcohol are not important etiological factors and finally because theypresent good prognosis, but further studies with larger number cases followed are needed to confirm our findings.(AU)

TNF-α Pretreated Hematopoietic Stem Cells Inhibit the Migration and Inflammatory Response of HUVECs and Attenuate GVHD.

BACKGROUND: Hematologic diseases have seriously threatened human health. Although hematopoietic stem cell transplantation (HSCT) is an effective curative option, the complications, especially graft-versus-host disease (GVHD), are a big problem. METHODS: TNF-α pretreatment of hematopoietic stem cells. Apoptosis was detected by flow cytometry, Transwell, and wound healing assays were used to assess cell migration and invasion, E-selectin expression was observed by fluorescence imaging, the levels of NO were measured by a kit, the expression of Ecadherin, MMP2, and MMP9 was detected in cells by qRT-PCR, and western blot was used to analyze the expression of E-cadherin, CXCL12, MCP-1, MCP-3, MMP2, and MMP9. RESULTS: TNF-α induces a high apoptosis rate of CD3, CD19, and CD133 and a low apoptosis rate of CD34. The level of Fas and TNF-R1 was significantly high than that of TNF-R2. HSCs treated with TNF- α declined the invasion and migration of HUVECs. E-selectin, MMP2 and MMP9 mRNA levels of HUVECs and MMP2, CXCL12, MCP-1, and MCP-3 were decreased after HSCs-TNF-α treatment, while the E-cadherin mRNA and protein level of HUVECs was enhanced with HSCs-TNF-α treatment. CONCLUSION: TNF-α pretreated HSCs can lead to reduced levels of migration, adhesion, and chemokines of HUVECs, thereby declining the inflammatory response and GVHD.

Adolescent and Young Adult Patients with Vaginal Graft-vs-Host Disease and Hematocolpos Managed with Vaginal Stents: A Case Series.

STUDY OBJECTIVE: Vaginal stenosis can be acquired as a result of vaginal graft-vs-host disease (GVHD) in patients who have undergone hematopoietic stem cell transplant (HSCT). Little data exist to guide the management of vaginal GVHD, particularly in adolescent and young adult patients. The objective of this study was to detail the management of vaginal stenosis with lysis of adhesions and vaginal stent placement in 3 young patients with vaginal GVHD. METHODS: A retrospective chart review was done for 3 patients with vaginal GVHD causing vaginal stenosis with hematometrocolpos. All 3 were treated using vaginal stent placement. Additionally, a literature review was conducted through PubMed and Google Scholar to identify 21 case reports (with a total of 35 patients) of menstrual obstruction due to GVHD. RESULTS: Obstructive vaginal stenosis secondary to vaginal GVHD occurred in our patients at ages 15, 16, and 24 years. Resolution of hematocolpos was obtained with lysis of vaginal adhesions with vaginal stent placement in all patients, with varying regimens of systemic and topical hormones, topical corticosteroids, and dilator therapy. DISCUSSION: Vaginal stenosis secondary to vaginal GVHD should be considered in patients with a history of allogeneic HSCT presenting with amenorrhea, especially those with a diagnosis of primary ovarian insufficiency. The use of vaginal stents, along with postoperative medical and dilator management as appropriate, may prevent re-stenosis, although more information is needed regarding the efficacy of treatments.