Therapeutic Choices in Patients with Ph-Positive Chronic Myelogenous Leukemia In Mexico in the Era of Tyrosine Kinase Inhibitors: Stem Cell Transplantation or Tyrosine Kinase Inhibitors? Fifteen Years Later

ABSTRACT Background: Chronic myelogenous leukemia is a neoplastic proliferation of the granulocytic series. In Mexico, chronic myelogenous leukemia accounts for approximately 10% of all leukemias. Tyrosine-kinase inhibitors are considered front-line therapy in high-income countries, whereas allogeneic hematopoietic stem cell transplantation is a recognized therapeutic approach, mainly in low- and middle-income countries. Objective: To analyze the overall survival of persons with chronic myelogenous leukemia who have received tyrosine-kinase inhibitors or allogeneic hematopoietic stem cell transplantation in a medical center, since 1994, and briefly discuss the current indications of these treatments in the tyrosine-kinase inhibitors era. Methods: We retrospectively analyzed all patients with a diagnosis of chronic myelogenous leukemia treated in a medical center between 1994 and 2023; subsets of individuals who received an allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors therapy as first-line treatment were analyzed. Results: 60 persons with chronic myelogenous leukemia were treated with allogeneic hematopoietic stem cell transplantation or tyrosine-kinase inhibitors: 35 received an allogeneic hematopoietic stem cell transplantation, whereas 25 were given tyrosine-kinase inhibitors. All patients who underwent an allogeneic hematopoietic stem cell transplantation engrafted successfully, and the procedure was completed on an outpatient basis in most cases (29/35). The median survival in allogeneic hematopoietic stem cell transplantation was 78.3 months (CI 95%: 0-205.6) and in persons given tyrosine-kinase inhibitors the median was not reached. Conclusion: Tyrosine-kinase inhibitors were significantly superior to allogeneic hematopoietic stem cell transplantation in prolonging the overall survival of persons with chronic myelogenous leukemia in our single institution experience. (Rev Invest Clin. 2024;76(2):91-6)

Childhood lichenoid granulomatous stomatitis: a case report and literature review / 口腔疾病防治

Objective@#To investigate the classification, clinical manifestations, diagnosis, differential diagnosis and treatment of oral lichenoid lesions and provide a reference for clinical practice.@*Methods@#Hospital ethical approval and patient informed consent were obtained. We report a case of oral lichenoid lesion in children and review the diagnosis and treatment of oral lichenoid damage in the literature.@*Results@#The patient experienced repeated rupture of the dorsal surface of the tongue with pain for more than 3 years. There was a large area of tongue back surface erosion with an irregular shape, surrounded by pearly-white lines. The left erosive area was accompanied by tissue hyperplasia, which was approximately 1.5 cm × 2.0 cm, with tough texture and broad masses. The pathological diagnosis of the patient was oral lichenoid lesion. After biopsy of the dorsal surface of the tongue, the pathological diagnosis of the patient was granulomatous inflammation. The final diagnosis of lichenoid granulomatous stomatitis was made on the basis of the patient's intraoral damage features, systemic history, medication history and histopathological findings. A review of the literature suggests that oral lichenoid lesions have an unknown etiology and need to be clinically differentiated from oral lichen planus, oral lichenoid drug reactions, oral lichenoid contact damage and chronic ulcerative stomatitis. The clinical treatment of oral lichen planus is based on the topical and/or systemic use of glucocorticoids.@*Conclusion@#There are still no uniform criteria for the classification and diagnosis of oral lichenoid lesions. They rely mainly on history taking, clinical manifestations and histopathological findings, and the treatment is mainly based on the topical and/or systemic use of glucocorticoids.

Clinical analysis of lung transplantation for lung chronic graft-versus-host disease after hematopoietic stem cell transplantation / 器官移植

<b>Objective</b> To evaluate clinical efficacy of lung transplantation for lung chronic graft-versus-host disease (cGVHD) after hematopoietic stem cell transplantation (HSCT). <b>Methods</b> Clinical data of 12 patients undergoing lung transplantation for lung cGVHD were retrospectively analyzed. Preoperative clinical manifestations and involved organs of patients were analyzed. The lung function before and after lung transplantation was compared, and the survival of patients after lung transplantation was analyzed. <b>Results</b> Eleven patients underwent HSCT due to primary hematological malignancies, including 9 cases of leukemia, 1 case of myelodysplastic syndrome, 1 case of lymphoma. And 1 case underwent HSCT for systemic lupus erythematosus. Among 12 cGVHD patients, skin involvement was found in 8 cases, oral cavity involvement in 5 cases, gastrointestinal tract involvement in 4 cases and liver involvement in 3 cases. All 12 patients developed severe respiratory failure caused by cGVHD before lung transplantation, including 9 cases of typeⅡ respiratory failure and 3 cases of type Ⅰ respiratory failure. Two patients underwent right lung transplantation, 2 cases of left lung transplantation and 8 cases of bilateral lung transplantation. The interval from HSCT to lung transplantation was 75 (19-187) months. Upon the date of submission, postoperative follow-up time was 18 (7-74) months. Ten patients survived, 1 died from severe hepatitis at postoperative 22 months, and 1 died from gastrointestinal bleeding at postoperative 6 months. No recurrence of primary diseases was reported in surviving patients. <b>Conclusions</b> Lung transplantation is an efficacious treatment for lung cGVHD after HSCT, which may prolong the survival time and improve the quality of life of the recipients.

Low-dose ATG combined with low-dose PTCY in preventing GVHD after haploidentical transplantation:a retrospective analysis of 90 cases / 陆军军医大学学报

Objective To retrospectively analyze the efficacy and safety of low-dose antithymocyte globulin(ATG)combined with low-dose post transplantation cyclophosphamide(PTCY)in prevention of graft versus host disease(GVHD)after haploidentical transplantation.Methods Clinical data of 90 patients receiving haplotype matched transplantation in No.920 Hospital of PLA Joint Logistic Support Force from January 2022 to February 2023 were collected,and they were divided into study group(n=47)and control group(n=43)according to different GVHD prevention programs.The patients of the study group were given low-dose ATG combined with low-dose PTCY,and those of the control group received standard dose of PTCY.The implantation status,occurrence of GVHD,survival status and other indicators were analyzed between the 2 groups.Results ① Both groups of patients were successfully implanted,the median duration for neutrophil implantation(11 vs 17 d,P＜0.05)and platelet implantation(12 vs 20 d,P＜0.05)was significantly shorter in the study group than the control group.The incidence of grade Ⅱ～Ⅳ aGVHD(12.8％vs 34.9％,P＜0.05)and grade Ⅲ～Ⅳ aGVHD(6.4％ vs 20.9％,P＜0.05)was significantly lower in the study group than the control group,so was the non-recurrent mortality rate(6.4％vs 20.9％,P＜0.05)and the incidence of hemorrhagic cystitis(12.8％ vs 34.9％,P＜0.05).② By the end of the study,there were no significant differences in the incidence of mild and moderate and severe cGVHD,recurrence rate,reactivation rates of EBV and CMV,overall survival rate or progression-free survival rate between the 2 groups.Conclusion For haploidentical transplantation,low-dose ATG combined with low-dose PTCY has the advantages of lower incidence of GVHD,non-recurrent mortality,incidence of hemorrhagic cystitis and faster implantation.

Association of intestinal and oral microbiota with acute graft versus host disease of the gastrointestinal tract in patients after allogeneic hematopoietic stem cell transplantation / 陆军军医大学学报

Objective To preliminarily investigate the association between changes in intestinal microbiota and oral microbiota of allogeneic hematopoietic stem cell transplantation(allo-HSCT)patients and early gastrointestinal acute graft versus host disease(aGVHD),and try to explore potentially effective biomarkers and provide theoretical basis for early prediction and intervention of gastrointestinal aGVHD.Methods Ten acute leukemia patients who developed gastrointestinal aGVHD within 1 month after receiving allo-HSCT in Department of Hematology of Sichuan Provincial People's Hospital from September 2021 to June 2023 were enrolled,and their fecal samples and saliva samples before and after the aGVHD were collected.16S rRNA sequencing analysis was applied for the differential changes in intestinal and oral microbiota before and after the development of early gastrointestinal aGVHD.Results ① A decrease in Bacteroides spp.and an increase in Enterococcus spp.and Enterobacteriaceae spp.in the intestinal microbiota were positively correlated with the occurrence of early upper gastrointestinal aGVHD(P＜0.05),whereas no significant difference was observed in the overall microbial diversity of the oral microbiota(P＞0.05).② LEfSe analysis of the intestinal microbiota before and after gastrointestinal aGVHD revealed an increase in Klebsiella spp.and Enterococcus spp.and a decrease in Escherichia coli;In the oral microbiota,LEfSe analysis revealed 10 microbial markers with significant difference,of which Gamma proteobacteria was the most significant.③ The difference in β-diversity of the intestinal microbiota was significant(P=0.03),whereas there was no significant difference in the α-and β-diversity of the oral microbiota.Conclusion Significant differences are found in intestinal microbiota before and after the occurrence of early gastrointestinal aGVHD in patients after Allo-HSCT,and the occurrence may have a correlation with the chang in oral microbiota.

Analysis of risk factors for short-term death after allogeneic hematopoietic stem cell transplantation / 中国组织工程研究

BACKGROUND:Allogeneic hematopoietic stem cell transplantation is an effective and even the only way to cure various hematological diseases,but the short-term mortality rate is relatively high after transplantation. OBJECTIVE:To investigate the risk factors affecting the overall survival of patients with hematological diseases in the short term(within 100 days)after allogeneic hematopoietic stem cell transplantation,so as to reduce mortality and effectively prevent related risks in the short term(within 100 days)after allogeneic hematopoietic stem cell transplantation. METHODS:Clinical data of 585 patients with hematological diseases who underwent allogeneic hematopoietic stem cell transplantation at the Hematopoietic Stem Cell Transplantation Center of First Affiliated Hospital of Zhengzhou University from January 1,2018 to June 30,2021 were retrospectively analyzed.The risk factors that affected overall survival within 100 days after allogeneic hematopoietic stem cell transplantation were explored. RESULTS AND CONCLUSION:A total of 585 patients with hematologic diseases underwent allogeneic hematopoietic stem cell transplantation.92 patients died within 100 days after transplantation,with a mortality rate of 15.7%(92/585).The median age of death cases was 26.5 years old(1-56 years),and the median survival time of death cases was 48 days(0-97 days).Univariate analysis exhibited that age≥14 years old,acute graft-versus-host disease,grade IV acute graft-versus-host disease,bacterial bloodstream infection,as well as carbapenem-resistant organism bloodstream infection,were risk factors for overall survival within 100 days after allogeneic hematopoietic stem cell transplantation(P<0.05).Multivariate regression analysis showed that age≥14 years old,grades Ⅲ-Ⅳ acute graft-versus-host disease,bacterial bloodstream infection,and carbapenem-resistant organism bloodstream infections were independent risk factors for overall survival(within 100 days)in patients after allogeneic hematopoietic stem cell transplantation.Hazard ratios were 1.77(95%CI 1.047-2.991),7.926(95%CI 3.763-16.695),2.039(95%CI 1.117-3.722),and 3.389(95%CI 1.563-7.347),respectively.In conclusion,all-cause mortality rate after allogeneic hematopoietic stem cell transplantation is relatively high in the short term.A timely diagnosis and effective treatment of bacterial bloodstream infection and acute graft-versus-host disease are essential to improving allogeneic hematopoietic stem cell transplantation outcomes.

Efficacy of umbilical cord mesenchymal stem cells replacing donor bone marrow cells in haploidentical hematopoietic stem cell transplantation / 中国组织工程研究

BACKGROUND:HLA haploid allogeneic hematopoietic stem cell transplantation provides a chance of survival for patients with high-risk hematologic malignancies.In recent years,the research on the transplantation mode and graft selection of haploidentical transplantation is still ongoing.At present,the mixed transplantation model of non-extracorporeal T-cell removal bone marrow and peripheral blood stem cells established by the Hematology Research Center of Peking University is gradually becoming popular in China,but this model requires the collection of donor bone marrow fluid,which increases the pain and risk of the donor. OBJECTIVE:To explore the curative effect of infusion of umbilical cord mesenchymal stem cells replacing donor bone marrow cells in haploidentical peripheral blood hematopoietic stem cell transplantation for malignant hematological diseases. METHODS:Fifty hematological malignancies patients who underwent haploidentical hematopoietic stem cell transplantation from January 2019 to May 2022 were selected and randomly assigned to two study groups at a ratio of 2:3.Among them,19 patients received umbilical cord mesenchymal stem cell combined with peripheral blood stem cell transplantation,and 31 patients were treated with bone marrow cells combined with peripheral blood stem cells.The study was approved by the Ethics Committee of Henan Provincial People's Hospital.The recipients of umbilical cord mesenchymal stem cells were first transfused with third-party umbilical cord mesenchymal stem cells(1×106/kg)on the day of transplantation,followed by peripheral blood hematopoietic stem cells 6 hours later.In the bone marrow group,donor bone marrow cells were transfused +1 day after transplantation and peripheral blood stem cells were transfused +2 days after transplantation.After transplantation,rabbit anti-human thymocyte immunoglobulin,cyclosporine A,mycophenolate mofetil,and a short-course methotrexate were used for graft-versus-host disease prophylaxis for all recipients. RESULTS AND CONCLUSION:No adverse events occurred during the reinfusion of umbilical cord mesenchymal stem cells.There were no significant differences between the mesenchymal stem cell group and the bone marrow group in the engraftment rate[100%(19/19)vs.96.8%(30/31),P>0.05],median duration for neutrophil engraftment(14 days vs.15 days,P>0.05)and median duration for platelet engraftment(20 days vs.19 days,P>0.05).The incidence of grade Ⅱ-Ⅳ acute graft-versus-host disease in the mesenchymal stem cell group was significantly lower than in the bone marrow group[21.1%(4/19)vs.58.1%(18/31),P = 0.01].There were no significant differences between the two groups in the incidence of chronic graft-versus-host disease[21.1%(4/19)vs.25.8%(8/31),P>0.05],the relapse rates[15.8%(3/19)vs.16.1%(5/31),P>0.05]and the incidence of early cytomegalovirus viremia[42.1%(8/19)vs.35.5%(11/31),P>0.05],and the 2-year overall survival rate[68.4%(10/19)vs.70.9%(16/31),P>0.05].It is indicated that umbilical cord mesenchymal stem cells replace donor bone marrow cells in haploidentical peripheral blood stem cell transplantation for malignant hematological diseases,which reduced the incidence of acute graft-versus-host disease after transplantation,did not increase the incidence of chronic graft-versus-host disease,recurrence rate and early cytomegalovirus viremia,and reduced the pain and risk of donor pulp extraction.

Characteristics of acute graft-versus-host disease of the intestine after unrelated cord blood transplantation / 中国组织工程研究

BACKGROUND:Despite unrelated cord blood transplantation is expected to become an important method for treating malignant hematological diseases,the manifestation and clinical characteristics of acute graft-versus-host disease in the gastrointestinal tract still require further in-depth investigation. OBJECTIVE:To analyze the clinical characteristics of intestinal acute graft-versus-host disease after unrelated cord blood transplantation. METHODS:A retrospective analysis was conducted on 668 malignant hematological disease patients after unrelated cord blood transplantation who underwent hematopoietic stem cell transplantation subspecialty in the Department of Hematology,First Affiliated Hospital of University of Science and Technology of China from December 2016 to December 2020.Among them,clinical data of 138 patients with intestinal acute graft-versus-host disease were analyzed,including 76 males and 62 females,with a median age of 13(1-62)years.All patients were treated with a myeloablative regimen(without antihuman thymocyte globulin)and cyclosporin A combined with mycophenolate mofetil to prevent graft-versus-host disease. RESULTS AND CONCLUSION:(1)The patients with intestinal acute graft-versus-host disease had diarrhea of varying degrees,most of which were yellow-green,yellow-brown watery stools or mucous stools.53 patients(38.4%)had blood stools,82 patients(57.9%)had skin involvement,18 patients(13.0%)had a secondary intestinal bacterial infection,and 90 patients(65.2%)had cytomegaloviremia.(2)The clinical characteristics of patients(70 cases,50.7%)with grade 1-2 intestinal acute graft-versus-host disease were compared with those(68 cases,49.3%)with grade 3-4 intestinal acute graft-versus-host disease.It was found that the age of grade 3-4 intestinal acute graft-versus-host disease patients was higher than that of grade 1-2 intestinal acute graft-versus-host disease patients(P<0.001),and they were complicated with cytomegaloviremia probably(P=0.035).Diarrhea lasted longer(P=0.00)and the length of hospital stay increased substantially(P<0.001).However,there were no significant differences in recipient gender,pre-transplant disease status,HLA matching,diagnosis,combined skin graft-versus-host disease,and secondary intestinal infection rate in patients of the two groups.(3)These findings conclude that the clinical characteristics of intestinal acute graft-versus-host disease after unrelated cord blood transplantation are complex,which affects the prognosis and quality of life of patients seriously and requires early identification and precise treatment.

Effect of ropivacaine combined with dexmedetomidine in transversus abdominis plane block on postoperative stress hormone and cognitive function in patients undergoing laparoscopic radical gastrectomy / 新乡医学院学报

Objective To explore the effect of ropivacaine combined with dexmedetomidine in transversus abdominis plane block(TAPB)on postoperative stress hormones and cognitive function in patients undergoing laparoscopic radical gastrectomy.Methods A total of 80 patients undergoing laparoscopic radical gastrectomy at the First Affiliated Hospital of Xinxiang Medical University from April to October 2023 were selected as the research subjects.According to different anesthesia methods,the patients were divided into the observation group and the control group,with 40 patients in each group.Patients in the observation group were injected bilaterally with 2.5 g·L-1 ropivacaine and 0.5 μg·kg-1 dexmedetomidine for TAPB,with 20 mL injection on each side.Patients in the control group were injected bilaterally with 2.5 g·L-1 ropivacaine for TAPB,with 20 mL injection on each side.Mean arterial pressure(MAP)and heart rate(HR)were recorded at the time of admission to the operating room(T1),immediately after endotracheal intubation(T2),40 minutes after pneumoperitoneum(T3),and 15 minutes after extubation(T4).Radioimmunoprecipitation was used to detect serum cortisol(COR)level,and enzyme-linked immunosorbent assay was used to measure serum norepinephrine(NE)and epinephrine(E)levels at 1,6,12,and 24 hours after surgery.Visual analog scale(VAS)was used to assess pain at rest,and Ramsay sedation scale(RSS)was used to evaluate sedation depth.The doses of propofol and sufentanil were compared between the two groups.Serum β-amyloid(Aβ)and S100β protein levels at 1 day before surgery,1 and 3 days after surgery were detected by using the enzyme-linked immunosorbent assay,and cognitive function was assessed at the same time points by using the mini-mental state examination(MMSE).Results At T,and T2,there was no significant difference in MAP and HR between the control group and the observation group(P＞0.05).At T3 and T4,MAP and HR in the observation group were significantly lower than those in the control group(P＜0.05).At 1,6,and 12 hours postoperatively,VAS score in the observation group was significantly lower than that in the control group(P＜0.05).At 24 hours postoperatively,there was no significant difference in VAS score between the control group and observation group(P＞0.05).At 1 and 6 hours postoperatively,RSS score in the observation group was significantly higher than that in the control group(P＜0.05).At 12 and 24 hours postoperatively,there was no significant difference in RSS score between the control group and observation group(P＞0.05).At 1,6,and 12 hours postoperatively,COR,NE,and E levels in the observation group were significantly lower than those in the control group(P＜0.05).At 24 hours postoperatively,there was no significant difference in COR,NE,and E levels between the control group and observation group(P＞0.05).The doses of propofol and sufentanil in the observation group were significantly lower than those in the control group(P＜0.05).One day before surgery,there was no significant difference in MMSE score between the control group and observation group(P＞0.05).At 1 and 3 days postoperatively,MMSE score in the observation group was significantly higher than that in the control group(P＜0.05).One day before surgery,there was no significant difference in serum Aβ and S100β protein levels between the control group and observation group(P＞0.05).At 1 and 3 days postoperatively,serum Aβ and S100β protein levels in the observation group were significantly lower than those in the control group(P＜0.05).Conclusion Ropivacaine combined with dexmedetomidine in TAPB in radical gastrectomy can significantly reduce postoperative pain,increase sedative effect,prolong the duration of TAPB,and benefit patients'postoperative recovery with reduced cognitive impairment.

Research progress on pathology and pathogenesis of chronic ocular graft-versus-host disease / 国际眼科杂志(Guoji Yanke Zazhi)

Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is a treatment for many malignant tumors of blood system and severe immunodeficiency, and chronic graft-versus-host disease(cGVHD)is one of the major complications after transplantation, which seriously affects the life quality of patients. The cGVHD can attack all the target tissues of the eye. The more common ones are lacrimal gland, eyelid, conjunctiva, cornea and limbus, meibomian gland, etc. The pathophysiological process is inflammation and fibrosis. Although many researchers at home and abroad have gradually begun to explore the disease and obtained many new findings, its pathology and pathogenesis are still not fully understood, and there is no unified and effective treatment. Clinically, the treatment of the disease is usually when symptoms have appeared. At this time, the target tissue is likely to have irreversible and permanent damage, resulting in a protracted and refractory situation. Therefore, this thesis mainly clarifies the research progress of the pathology and pathogenesis of ocular cGVHD in recent years, in order to provide new guidance for the treatment of the disease.

Research progress on nutritional support for gastrointestinal graft-versus-host disease / 中华临床营养杂志

Gastrointestinal graft versus host disease is one of the most severe complications after hematopoietic stem cell transplantation, which can occur in patients of any age groups. Its clinical manifestations include nausea, vomit, abdominal pain, diarrhea and the like. Severe gastrointestinal graft versus host disease could directly influence the patients' clinical prognosis and therapeutic efficacy of transplantation. Here we had a review of the research progress on nutritional support and diet management strategies for gastrointestinal graft versus host disease. It is of great clinical significance to form a step-wise nutritional support model to reduce the risk of malnutrition in patients with gastrointestinal graft versus host disease, which would contribute to improving patients' general condition, relieving digestive tract symptoms, and reducing the risk of complications.

The quest for better outcomes: a randomized controlled trial comparing letrozole versus clomiphene citrate in polycystic ovarian syndrome related infertility

Background: Infertility is a widespread concern, particularly among individuals with polycystic ovarian syndrome (PCOS). Clomiphene citrate (CC) has been a primary treatment for PCOS-related infertility, despite suboptimal pregnancy rates. Letrozole, an aromatase inhibitor, presents an alternative with potential advantages for improving pregnancy outcomes. This study aimed to rigorously compare letrozole and CC in the context of PCOS-related infertility, focusing on Bangladeshi women, adopting incremental dosing protocols, and examining endpoints to contribute valuable insights.Methods: A randomized controlled trial was conducted at a tertiary care center in Bangladesh from July 2021 to June 2023. Participants included women aged 18-35 with anovulatory infertility due to PCOS. They were randomized into two groups: letrozole and CC. Treatments were administered following incremental dosing protocols, and outcomes included endometrial thickness, ovulation rate, mono-follicular development, pregnancy rate, and time to pregnancy.Results: Out of 187 patients assessed for eligibility, 102 were enrolled, with 51 in each group. Demographics were comparable between groups. While endometrial thickness did not significantly differ between the groups, letrozole demonstrated a higher rate of mono-follicular development (72.55% versus 50.98%), a significantly higher pregnancy rate (47.06% versus 23.53%), and a shorter time to pregnancy (9.23 weeks versus 11.7 weeks) compared to CC.Conclusions: This study suggests that letrozole may be a preferred option for ovulation induction in PCOS patients due to its superior pregnancy rates and shorter time to pregnancy compared to CC. However, limitations such as a relatively small sample size and variations in dosages should be considered. Further research is needed to validate these findings and address the evolving needs of patients with PCOS-related infertility.

Lower expression of NOTCH components in peripheral blood mononuclear cells of allogeneic hematopoietic cell transplant patients

ABSTRACT Introduction: Chronic graft-versus-host disease (cGvHD) not only remains the main cause of late mortality after allogeneic hematopoietic cell transplant, but also has the capacity of causing severe organ impairment in those who survive. The Notch, a highly conserved ligand-receptor pathway, is involved in many immunological processes, including inflammatory and regulatory responses. Recently, mouse models have shown that the blockage of canonical Notch signaling prevents GvHD. Objective and Method: Due to the lack of data on the Notch pathway in human chronic GvHD, we sought to study the expression of NOTCH components in primary samples of patients who received allo-HCT and presented active cGvHD or a long-term clinical tolerance to cGvHD. Results: Our results showed a significantly lower expression of NOTCH components in both groups that received allo-HCT, independently of their cGvHD status, when compared to healthy controls. Conclusion: Moreover, there were no differences in gene expression levels between the active cGvHD and clinically tolerant groups. To our knowledge, this is one of the first studies performed in human primary samples and our data indicate that much remains to be learned regarding NOTCH signaling as a new regulator of GvHD.

Dentistry consensus on HSCT - Part III: Special topics - Dentistry on HSCT

ABSTRACT Patients undergoing hematopoietic stem cell transplantation (HSCT) might present acute and late toxicities and the oral tissues are frequently affected. With the survival increasing, patients show late and long-term morbidities, and there is an important association between the general and the oral health. The first and second parts of this Consensus have showed the importance of the adequacy of oral health in the pre-HSCT, and the main alterations and oral care during the period of admission for HSCT. This third part aims to review specific themes of post-HSCT dental care, such as graft-versus-host disease (GVHD) and the pediatric patient. It also aims to review pertinent subjects, both during the HSCT period and post-HSCT, concerning quality of life, pain, cost-effectiveness, and remote care. Based on this review, it is evident the importance of the work of the dental surgeon (DS) in the follow-up and treatment of the HSCT patient, always collaborating with the whole multidisciplinary team.

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.

Assessment of stress and coping mechanisms in the 1st year MBBS students from English and Vernacular medium – An experience from a new All India Institute of Medical Sciences

Background: The stress levels among the 1st year MBBS students are high due to multiple factors. In this setting, an objective assessment of stress and coping strategies among medical students may provide a foundation to adopting specific measures to help them. Aims and Objectives: The specific objectives of the study were to compare stress levels and coping strategies among medical students from different backgrounds and mediums of instructions and to ategorize the stress level of students depending on Class X, XII marks, number of attempts, and annual family income. Materials and Methods: Forty-eight 1st year MBBS students were recruited for the study. Participants were divided into two groups, that is, Group 1 – English medium schools and Group 2 – Hindi medium schools and informed consent was taken. In a preferable time slot, the participants were given two questionnaires (Zung’s SDS and Way of Coping Revised scale) and a table of personal information to fill. Results: There were significantly higher stress scores among English medium students as compared to vernacular medium. There was no correlation between Class 10th and 12th marks with the stress. Proportion of students having high stress had AFI <1 lakh and proportion having low stress had AFI more than 5 lakh. Students having more than 3 attempts in medical qualifying examination had the least stress scores. Conclusion: Stress among medical students was found to more in students from English medium schools due to the urban background of these students. High family income acts a psychological security for the students, hence the low stress among them. Students with more than 3 attempts in qualifying examination were more mature, hence the low stress score among them.

Evaluation of GVHD And oral mucositis in patients submitted to HSCT at the STMO-CHC of UFPR

Oral graft-versus-host disease (GVHD) and oral mucositis (OM) are important complications of hematopoietic stem cell transplantation (HSCT) that significantly impact the patient's quality of life. In this context, this study aimed to evaluate the profile of patients undergoing allogeneic HSCT, assessing oral GVHD and OM occurrence. Data from medical records of patients that underwent HSCT between 2019 and 2021 were collected. Patients over 18 years old, with diseases or conditions requiring HSCT, were included. A clinical examination was performed to evaluate the occurrence of GVHD and OM. A total of 47 patients undergoing HSCT were evaluated of which 34.04% developed GVHD, and of these 81.25% have had oral involvement. As for OM, it affected 82.97% of the patients, with grades 3 and 4 being more detected. The most frequent previous disease was acute myeloid leukemia, and most of these patients received a related type of transplant (84.61%), fully compatible (53.84%), with bone marrow as a source of stem cells (53.84%). Most patients received the myeloablative conditioning regimen (69.23%). Cyclosporine was the most immunosuppressive agent used for the GVHD prevention associated with methotrexate (76.92%). Oral GVHD and OM are frequent and debilitating oral complications of HSCT, which can compromise a patient's general health and overall survival. Early diagnosis is important for a quick start of treatment and to reduce the impact on the patient's prognosis. (AU)

Prevention and treatment of chronic graft-versus-host disease by mesenchymal stem cells: advances and challenges / 器官移植

Chronic graft-versus-host disease (cGVHD) is the main complication after allogeneic hematopoietic stem cell transplantation, which is also the major cause of non-relapse -related death. Due to its complex pathophysiological process, the response rate of conventional glucocorticoids combined with immunosuppressants is less than 50%. Second-line therapy should be given for patients with glucocorticoid-resistant cGVHD. Nevertheless, no consensus has been reached on current second-line therapy and the therapeutic effect is relatively poor. Mesenchymal stem cell (MSC) is one of the most common adult stem cells. Due to multi-dimensional and multi-target immune regulating function, MSC has been widely applied in the prevention and treatment of cGVHD. In addition, accumulated studies have confirmed the safety and efficacy of MSC in the treatment of cGVHD, which is expected to become a novel strategy for the prevention and management of cGVHD. In this article, research progress, mechanism and existing problems of prevention and treatment of cGVHD by MSC were reviewed, aiming to provide novel ideas for optimizing therapeutic regimens of MSC and enhancing the prevention and treatment effect of cGVHD in subsequent research.

Prevention and treatment of high-risk acute myeloid leukemia recurrence after allogeneic hematopoietic stem cell transplantation / 器官移植

Acute myeloid leukemia (AML) is a group of highly-heterogeneous clonal diseases. Chemotherapy and hematopoietic stem cell transplantation are considered as effective treatment for AML. For high-risk AML patients, allogeneic hematopoietic stem cell transplantation is an effective therapeutic option. However, some AML patients may still face the problem of disease recurrence after hematopoietic stem cell transplantation. A majority of recurrent patients cannot be effectively treated by chemotherapy or secondary transplantation, which is the main cause of death after allogeneic hematopoietic stem cell transplantation. Therefore, it is of significance to strengthen follow-up of AML patients after allogeneic hematopoietic stem cell transplantation and implement appropriate measures to prevent postoperative recurrence. In this article, the monitoring, drug prevention and cell therapy of recurrence after allogeneic hematopoietic stem cell transplantation in high-risk AML patients were reviewed, aiming to provide reference for improving clinical prognosis of high-risk AML patients undergoing allogeneic hematopoietic stem cell transplantation.

Successful treatment of acute leukemia by secondary transplantation after the first haploidentical hematopoietic stem cell transplantation failure / 器官移植

Objective To evaluate the feasibility of secondary transplantation for patients with acute leukemia after failure of the first haploidentical hematopoietic stem cell transplantation. Methods Two acute leukemia patients underwent the first haploidentical hematopoietic stem cell transplantation from two donors with thalassemia, and the number of collected CD34+ cells was 2.57×106/kg and 1.99×106/kg per donor, respectively. The first haploidentical hematopoietic stem cell transplantation failed. Secondary transplantation was performed from two non-thalassemia donors, and the number of collected CD34+ cells was 4.28×106/kg and 5.75×106/kg per donor, respectively. A reduced-intensity conditioning regimen consisting of fludarabine (Flu), busulfan (Bu) and antithymocyte globulin (ATG) was adopted for the secondary transplantation. Results For two recipients, the time of secondary transplantation of neutrophil and platelet was +12 d and +10 d, +10 d and +10 d, respectively. Up to the final follow-up (+1 062 d and +265 d after secondary transplantation), the primary diseases of both two recipients have been completely relieved without evident post-transplantation complications. Conclusions Secondary transplantation with reduced-intensity conditioning regimen may successfully treat acute leukemia after failure of the first haploidentical hematopoietic stem cell transplantation.