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Background: Metabolic dysfunction-associated fatty liver disease has been linked to negative outcomes in patients with end-stage liver disease following liver transplantation. However, the influence of immunosuppressive regimens on it has not been explored. Methods: A retrospective analysis was conducted using the preoperative and postoperative data from patients with end-stage liver disease. The study compared three different groups: tacrolimus-based group, sirolimus-based group, and combined tacrolimus- and sirolimus-based regimens. Binary logistic regression analysis was employed to identify risk factors for metabolic dysfunction-associated fatty liver disease. Results: A total of 171 patients participated in the study, consisting of 127 males and 44 females, with a mean age of 49.6 years. The prevalence of posttransplant metabolic dysfunction-associated fatty liver disease was 29.23%. Among the three groups, there were 111 liver transplant recipients in the tacrolimus-based group, 28 in the sirolimus-based group, and 32 in the combination group. A statistically significant difference was observed in the incidence of metabolic dysfunction-associated fatty liver disease (P < 0.05), whereas the other preoperative and postoperative parameters showed no significant differences. Multivariate analysis revealed that a low-calorie diet (95% confidence intervals: 0.15-0.90, P = 0.021) and a combination of tacrolimus- and sirolimus-based immunosuppressive regimen (95% confidence intervals: 1.01-2.77, P = 0.046) were associated with lower risk of posttransplant metabolic dysfunction-associated fatty liver disease. Conclusions: Our study indicates that implementing a low-calorie diet and utilizing a combination of tacrolimus- and sirolimus-based immunosuppressive regimen can effectively lower the risk of posttransplant metabolic dysfunction-associated fatty liver disease following liver transplantation.

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As the most prominent and ideal modality in female fertility preservation, ovarian tissue cryopreservation, and transplantation often confront the challenge of ischemic damage and follicular loss from avascular transplantation. To surmount this impediment, we engineered a novel platelet-derived factors-encapsulated fibrin hydrogel (PFH), a paradigmatic biomaterial. PFH encapsulates autologous platelet-derived factors, utilizing the physiological blood coagulation cascade for precise local delivery of bioactive molecules. In our study, PFH markedly bolstered the success of avascular ovarian tissue transplantation. Notably, the quantity and quality of follicles were preserved with improved neovascularization, accompanied by decreased DNA damage, increased ovulation, and superior embryonic development rates under a Low-concentration Platelet-rich plasma-derived factors encapsulated fibrin hydrogel (L-PFH) regimen. At a stabilized point of tissue engraftment, gene expression analysis mirrored normal ovarian tissue profiles, underscoring the effectiveness of L-PFH in mitigating the initial ischemic insult. This autologous blood-derived biomaterial, inspired by nature, capitalizes on the blood coagulation cascade, and combines biodegradability, biocompatibility, safety, and cost-effectiveness. The adjustable properties of this biomaterial, even in injectable form, extend its potential applications into the broader realm of personalized regenerative medicine. PFH emerges as a promising strategy to counter ischemic damage in tissue transplantation, signifying a broader therapeutic prospect. (197 words).

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A critical shortage of donor corneas exists worldwide. Hydrogel patches with a biological architecture and functions that simulate those of native corneas have garnered considerable attention. This study introduces a stromal structure replicating corneal patch (SRCP) composed of a decellularized cornea-templated nanotubular skeleton, recombinant human collagen, and methacrylated gelatin, exhibiting a similar ultrastructure and transmittance (above 80 %) to natural cornea. The SRCP is superior to the conventional recombinant human collagen patch in terms of biomechanical properties and resistance to enzymatic degradation. Additionally, SRCP promotes corneal epithelial and stromal cell migration while preventing the trans-differentiation of stromal cells into myofibroblasts. When applied to an ocular surface (37 °C), SRCP releases methacrylated gelatin, which robustly binds SRCP to the corneal stroma after activation by 405 nm light. Compared to gelatin-based photocurable hydrogel, the SRCP better supports the restoration of normal corneal curvature and withstands deformation under an elevated intraocular pressure (100 mmHg). In an in vivo deep anterior-corneal defect model, SRCP facilitated epithelial healing and vision recovery within 2 weeks, maintained graft structural stability, and inhibited stromal scarring at 4 weeks post-operation. The ideal performance of the SRCP makes it a promising humanized corneal equivalent for sutureless clinical applications.

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In several ocular diseases, degeneration of retinal neurons can lead to permanent blindness. Transplantation of stem cell (SC)-derived RGCs has been proposed as a potential therapy for RGC loss. Although there are reports of successful cases of SC-derived RGC transplantation, achieving long-distance regeneration and functional connectivity remains a challenge. To address these hurdles, retinal organoids are being used to study the regulatory mechanism of stem cell transplantation. Here we present a modified protocol for differentiating human embryonic stem cells (ESCs) into retinal organoids and transplanting organoid-derived RGCs into the murine eyes.

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ABSTRACT Purpose: To determine the clinical outcomes in patients after type 1 Boston keratoprosthesis surgery and the significance of ultrasound biomicroscopy imaging for postoperative follow-up. Methods: This retrospective analysis included 20 eyes of 19 patients who underwent corneal transplantation with type 1 Boston keratoprosthesis between April 2014 and December 2021. Data on patient demographics, preoperative diagnosis, visual acuity, and postoperative clinical findings were analyzed. Results: Type 1 Boston keratoprosthesis implantation resulted in intermediate- and long-term positive outcomes. However, blindness and other serious complications such as glaucoma, retroprosthetic membrane formation, endophthalmitis, or retinal detachment also occurred. The use of ultrasound biomicroscopy imaging allowed for better evaluation of the back of the titanium plate, anterior segment structures, and the relationship of the prosthesis with surrounding tissues, which provided valuable postoperative information. Conclusion: Regular lifetime monitoring and treatment are necessary in patients who undergo Boston type 1 keratoprosthesis implantation for high-risk corneal transplantation. ultrasound biomicroscopy imaging can be a valuable imaging technique for the evaluation of patients with Boston type 1 keratoprosthesis, providing important information on anterior segment anatomy and potential complications. Further studies and consensus on postoperative follow-up protocols are required to optimize the management of patients with Boston type 1 keratoprosthesis.

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BACKGROUND: The use of mobilizing agents for hematopoietic stem cell (HSC) transplantation is insufficient for an increasing number of patients. We previously reported lipid made endocannabinoid (eCB) ligands act on the human bone marrow (hBM) HSC migration in vitro, lacking long term stability to be therapeutic candidate. In this study, we hypothesized if a novel 2-AG-loaded polycaprolactone (PCL)-based nanoparticle delivery system that actively targets BM via phosphatidylserine (Ps) can be generated and validated. METHODS: PCL nanoparticles were prepared by using the emulsion evaporation method and characterized by Zetasizer and scanning electron microscopy (SEM). The encapsulation efficiency and release profile of 2-AG were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The presence of cannabinoid receptors (CBRs) in HSCs and monocytes was detected by flow cytometry. Cell morphology and viability were assessed using transmission electron microscopy (TEM), SEM, and the WST-1 viability assay. The migration efficacy of the 2-AG and 2-AG-loaded nanoparticle delivery system on HSCs and HPSCs (TF-1a and TF-1) and monocytes (THP-1) was evaluated using a transwell migration assay. RESULTS: The 140-225 nm PCL nanoparticles exhibited an increasing polydispersity index (PDI) after the addition of Ps and 2-AG, with a surface charge ranging from - 25 to -50 mV. The nanoparticles released up to 36% of 2-AG within the first 8 h. The 2-AG-Ps-PCL did not affect cellular viability compared to control on days 5 and 10. The HSCs and monocytes expressed CB1R and CB2R and revealed increased migration to media containing 1 µM 2-AG-Ps-PCL compared to control. The migration rate of the HSCs toward monocytes incubated with 1 µM 2-AG-Ps-PCL was higher than that of the monocytes of control. The 2-AG-Ps-PCL formulation provided a real time mobilization efficacy at 1 µM dose and 8 h time window via a specific CBR agonism. CONCLUSION: The newly generated and validated 2-AG-loaded PCL nanoparticle delivery system can serve as a stable, long lasting, targeted mobilization agent for HSCs and as a candidate therapeutic to be included in HSC transplantation (HSCT) protocols following scale-up in vivo preclinical and subsequent clinical trials.

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The incidence of Acute myeloid leukemia (AML) increases with advancing age, and the prognosis for elderly patients is significantly poorer compared to younger patients. Although the combination therapy of venetoclax and hypomethylating agents has demonstrated improved prognosis in patients unable to tolerate intensive chemotherapy, there remains a therapeutic blank for those who fail to achieve remission with current treatment regimens. Here, we report the successful clinical utilization of autogenous CLL1 CAR-T therapy combined with hematopoietic stem cell transplantation in a 73-year-old patient diagnosed with refractory AML. The patient achieved morphological complete remission (CR) with incomplete marrow recovery and a slight presence of minimal residual disease (MRD) after receiving CLL1 CAR-T therapy. To further enhance the treatment and promote the recovery of hemopoiesis, we performed bridged allogenic hematopoietic stem cell transplantation (allo-HSCT) 20 days after the infusion of CLL1 CAR-T cells. The patient achieved MRD-negative CR following HSCT treatment. His primary disease maintained a complete remission status during the 11-month follow-up period. The patient encountered grade 2 cytokine release syndrome and grade 4 granulocytopenia subsequent to the infusion of CAR-T cells, while several rounds of infection and graft-versus-host disease were observed following allo-HSCT. Nevertheless, all these concerns were successfully addressed through comprehensive provision of supportive treatments. We have successfully demonstrated a highly effective and safe combination strategy involving CLL1 CAR-T therapy and allo-HSCT, which has exhibited remarkable tolerability and holds great promise even for elderly patients with AML.

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Walter Brendel was a physiologist who headed the Institut of Experimental Surgery at the University of Munich (LMU) from 1961 until 1989. His legendary career began with the development of an anti-human lymphocyte globulin (ALG) at his Institute during the late 1960s. The initial successful treatment of a small number of patients culminated in the co-treatment of the first successfully heart-transplanted patient in Capetown, South Africa (successful reversal with ALG of an acute allograft rejection). Walter Brendel was a pioneering personality whose work has laid a wide platform for the promotion of interdisciplinarily conducted innovative research programs in various domains of translational science and medicine. Among the many innovative achievements, the most notable are: discovery of involvement of the alternative pathway of complement activation in hyperacute xenograft rejection; induction of immunological tolerance to horse IgG as a means to prevent anaphylactic reactions during ALG therapy; development and clinical implementation of the extracorporeal shock wave lithotripsy for extracorporeal destruction of renal and ureteral calculi. The legacy of Brendel continues with the foundation of the Walter-Brendel Kolleg für Transplantationsmedizin (i.e., the German Transplant School for Transplantation Medicine), which has been held annually since 1994.

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Purpose: Meniscal injuries are common in the young and active population. There is increasing utilization of surgical interventions like meniscal allograft transplantation (MAT) to restore the protective function of menisci following injury leading to meniscal deficiency. Extensive research and publications exist on the management of meniscal injury and the sequalae of meniscal deficiency. However, a comprehensive synthesis of the existing evidence through an umbrella review is lacking. This study aims to fill this gap by providing a current examination of the literature on MAT. Methods: A comprehensive search was conducted in the MEDLINE, Embase and Scopus databases to identify relevant systematic reviews and meta-analyses. Studies were screened based on predefined inclusion and exclusion criteria. The quality of the included studies was assessed using the AMSTAR-2 tool. Results: A total of 41 studies were included in the review, with most published within the last decade. The majority of studies (56.1%) received a 'Critically Low' confidence rating, 26.8% were rated as 'Low', and only 14.6% were rated as 'High' confidence. From the included studies, 51.2% reported on PROMs, with the Lysholm score being the most common. Transplant failure and reoperation rate were reported in 34.1% and 19.5% of studies respectively. Studies on MAT reported favourable short-term outcomes in terms of patient-reported outcome measures (PROMs) but were limited by the lack of randomized control trials and consistent comparison groups. Conclusions: This umbrella review highlights an increase in interest in MAT but underscores the need for higher-quality reviews with standardized reporting and rigorous methodologies. Future research should focus on long-term outcomes, optimal surgical techniques, patient selection criteria and risk factors for transplant failure. There is also a need for more studies focusing on MAT in pediatric populations. Overall, this review provides a comprehensive assessment of the current state of research in MAT and identifies areas for improvement in future studies. Level of Evidence: Level IV.

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Simultaneous liver-kidney transplantation (SLK) is a feasible option for patients with end-stage liver disease and concomitant renal dysfunction or end-stage renal disease. SLK has gained significant attention primarily due to multiple alterations in the allocation criteria over the past two decades. This review aims to summarize the most recent updates and outcomes of the SLK allocation policy, comparing SLK outcomes with those of liver transplantation alone and exploring the implications of donation after cardiac death in SLK procedures.

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Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe, potentially life-threatening, drug-induced hypersensitivity reaction that involves hematological abnormalities (atypical lymphocytosis, eosinophilia), lymphadenopathy, skin eruption, and internal organ involvement (lung, liver, kidney). The 36-year-old female patient was followed by bloody diarrhea, diffuse skin rashes and hepatitis. She was diagnosed with psoriatic arthritis, and Leflunomide 20 mg was added to the treatment six weeks ago. Upon developing hepatic encephalopathy and deepening the fulminant liver failure during the follow-up, a living donor liver from her son was transplanted on the 4th day of hospitalization. The patient had deceased on the second day after liver transplantation due to multiple organ failures. In the literature, mortality in DRESS syndrome is mostly secondary to hepatic failure. Liver transplantation cannot be effective due to systemic involvement and recurrence in the transplanted liver.

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The use of marginal grafts is very challenging and is associated with post-reperfusion syndrome and early allograft dysfunction. The outcomes of machine perfusion for the preservation of marginal grafts have been compared with that of static cold storage, with studies reporting a reduced risk of ischemic cholangiopathy and graft loss. We performed this systematic review and meta-analysis of randomized controlled trials (RCTs) comparing outcomes of machine perfusion of liver grafts to static cold storage (SCS) of liver grafts during liver transplantation. Two independent researchers thoroughly searched for literature in the following databases: PubMed (Medline), Cochrane Central Register of Controlled Studies (CENTRAL), clinical trial registry, ResearchGate, Google Scholar, and Scopus (ELSEVIER) databases (last search: November 2023). The search terms used were: "dynamic perfusion," "normothermic perfusion," "hypothermic perfusion," "liver transplantation," "static cold storage," "NMP," "HOPE," "extended criteria grafts," "marginal grafts," "RCTs," "randomized controlled trials," "warm ischemia," and "cold ischemia." Eight RCTs published between 2019 and 2023 were included in the data synthesis and meta-analysis. The primary outcome considered was the overall incidence of early allograft dysfunction (EAD) between the two methods of graft perfusion after liver transplantation. The secondary outcome considered was the rate of retransplantation. Our meta-analysis revealed that SCS is associated with more EAD when compared with machine perfusion, with a p-value of <0.00001. We also found that the rate of retransplantation is higher among patients who received a liver preserved by SCS, with a p-value of 0.02. The use of machine perfusion in the preservation of liver grafts showed a significant reduction in early allograft dysfunction and retransplantation.

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Myeloablative Total Body Irradiation (TBI) used in our Institution, as part of the conditioning scheme for haematopoietic stem cell transplantation, is an extended-distance supine technique that has been implemented using a 15 MV LINAC beam, lead lung compensators, PMMA, and water bolus to improve homogeneity. This study reviews in-vivo dosimetry (IVD) over 10 years of treatments, assessing the technique's robustness, accuracy, and efficiency. A 2-lateral opposite fields plan was calculated from planning CT with validated Oncentra TPS (Elekta AB, Sweden). Monitor units (MUs), lung compensators shape and thickness were calculated to deliver the prescription dose (12 Gy in 6 bi-daily fractions or 9.9 Gy in 3 daily fractions) to the patient's abdomen midline at the umbilical level, maintaining lung dose within ±5 % range of prescription. Data from 103 patients, of which more than 87 % were pediatric, were retrieved and analyzed for a total of 537 treatment fractions. The impact of IVD omission was evaluated, supposing doing it only once or in the first two fractions, if necessary. Median ΔMU from planned was -1.2 %. Median percentage dose deviation from prescription in 6 anatomical regions was below 2 %. IVD omission could have resulted in an increase of 7 patients registering at least one anatomical region outside the ±5 % dose range at the end of treatment. It is possible to confirm the implemented technique's robustness and accuracy in delivering the prescribed dose under IVD monitoring. Nevertheless, this technique and associated IVD are time-consuming and IVD omission could be assessed with limited drawbacks.

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Single antigen bead (SAB) assays are the most common and sensitive method used to detect and monitor post-transplant donor specific HLA antibodies (DSA). However, a direct comparison across traditional and modified SAB assays to improve routine DSA monitoring using pre-treated IgG sera to eliminate interference has not been performed. We performed a technical comparison of 251 post-transplant DSA from n = 91 serum samples tested neat (pre-treated, undiluted), at a single 1:16 dilution, in the C1q bead assay, and for IgG subclasses (IgG1, IgG2, IgG3, IgG4) with IgG-enriched sera. We found that DSAs that are detectable by 1:16 dilution and/or C1q are associated with higher IgG MFI values and results could be predicted by testing neat sera. DSA detected at 1:16 dilution correlated with >7000 IgG MFI in neat sera and identified DSA that exceeded the SAB linear range for semiquantitative measurements. C1q positive DSA correlated with >15,000 IgG MFI in neat sera. C1q binding correlated most strongly with total IgG MFI (Spearman r = 0.82, p = 0.002) and not specific subclasses, demonstrating that DSA C1q binding capacity in this cohort is driven by HLA-specific IgG concentration. Evaluation of engineered pan-HLA class I-specific human IgG1 and IgG2 subclass monoclonal antibodies by SAB C1q and C3d assays revealed that IgG2 antibodies can bind complement at higher concentrations. The strengths and limitations of modified SAB assays must be considered to optimize efficient testing and accurate clinical interpretation.

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OBJECTIVE: The aim of this study is to compare outcomes of single lung retransplantation (SLRTx) to double lung retransplantation (DLRTx) after an initial double lung transplantation. METHODS: The Organ Procurement and Transplantation Network/United Network for Organ Sharing database between May 2005 and December 2022 was retrospectively analyzed. Multiorgan transplantation, repeated retransplantation, and lung retransplantation when the status of the initial transplantation was unknown were excluded. RESULTS: 891 patients were included in the analysis: 698 cases (78.3%) were DLRTx and 193 cases (21.7%) were SLRTx. Mean lung allocation score was higher among DLRTx (59.6±20.7 vs 55.1±19.3, p = 0.007). Extracorporeal membrane oxygenation (ECMO) bridge to lung transplantation use was similar between groups (p=0.125), as was waitlist time (p=0.610). Need for mechanical ventilation (54.6% vs 35.8%, p = 0.005) and ECMO (17.9% vs 9.0%, p = 0.069) at 72 hours after transplantation was more frequent in DLRTx group. However, median post-transplant hospital stay (21.5 [IQR 12-35] vs 20 days [IQR 12-35], p=0.119) and in-hospital mortality (10.9% [76/698] vs 12.4% [24/193], p=0.547) were comparable between groups. Long-term survival was significantly better among DLRTx (log-rank test p < 0.001). In the propensity-score weighted multivariable model, DLRTx had 28% lower risk of mortality at any point during follow-up compared to SLRTx (HR: 0.72, 95% confidence interval: 0.57-0.91, p=0.006). CONCLUSIONS: Less invasiveness of single lung transplantation in the retransplant setting has minimal short-term benefit and is associated with significantly worse long-term survival. Double lung retransplantation should remain the standard for lung retransplantation after initial double lung transplantation.

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OBJECTIVE: Thoraco-abdominal normothermic regional perfusion (TA-NRP) has emerged as a strategy for evaluating and recovering the heart in controlled donation after the circulatory determination of death (cDCDD). However, its impact on lung grafts remains largely unknown. We aimed to assess the impact of TA-NRP on the outcomes of recipients of cDCDD lungs. METHODS: This is a retrospective, multicenter, nationwide study describing the outcomes of cDCDD lung transplants (LTs) performed in Spain from January 2021 to November 2023. Patients were divided in two groups based on the recovery technique: TA-NRP with the simultaneous recovery of the heart versus abdominal NRP (A-NRP) without simultaneous heart recovery. The primary endpoint was the incidence of Primary Graft Dysfunction (PGD) grade 3 at 72 hours. Secondary endpoints included the overall incidence of PGD, days on mechanical ventilation, ICU and hospital length of stay, early survival rates, and mid-term outcomes. RESULTS: 283 cDCDD LTs were performed during the study period, 28 (10%) using TA-NRP and 255 (90%) using A-NRP. No differences were observed in the incidence of PGD grade 3 at 72 hours between the TA-NRP and the A-NRP group (0% vs. 7.6%; p=0.231), though the overall incidence of PGD was significantly lower with TA-NRP (14.3%% vs. 41.5%; p=0.005). We found no significant differences between the groups regarding other post-transplant outcome variables. CONCLUSIONS: TA-NRP allows the simultaneous recovery of both the heart and the lungs in the cDCDD scenario with appropriate LT outcomes comparable to those observed with the A-NRP approach.

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OBJECTIVE: To investigate how individual social determinants of health (SDOH) and cumulative social disadvantage (CSD) affect survival and receipt of liver transplant (LT) in patients with hepatocellular carcinoma (HCC). METHODS: We enrolled 139 adult patients from two Indianapolis hospital systems between June 2019 and April 2022. Structured questionnaires collected SDOH and social risk factor data. We compared SDOH and CSD by race, gender and disease aetiology, assigning one point per adverse SDOH. Multivariable competing risk survival analysis assessed associations between SDOH, CSD, survival and LT receipt. RESULTS: Black patients experienced higher CSD than white patients in the cohort (5.4±2.5 vs 3.2±2.1, p<0.001). Black patients were significantly more likely to have household incomes

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This survey aimed to reveal the actual preventing exposure for handling of clothing and sweat of patients treated with anticancer drugs, following the publication of "Guideline for Preventing Occupational Exposure in Cancer Chemotherapy Drugs, 2019 Edition" (Guideline 2019). A survey was conducted among nurses working at 95 hematopoietic stem cell transplantation promotion base hospitals from September 1, 2023 to October 31, 2023. The response rate was 84.2% (80 facilities). Of the respondents, 45% wore gloves when touching patients' skin to administer anticancer drugs. Almost the nurses identified "urine" and "feces" as fluids on contaminated linen, while 14.1% also identified "sweat." For new staff, the results for preventing exposure education on "if touching the patients' skin" and "if handling clothing and linen" were 23.8% and 34.9%, respectively. This survey shows that nurses may not be following the Guideline 2019 for use of personal protective equipment and handling of clothes. Medical institutions handling anticancer drugs need to educate their staff for preventing occupational exposure.

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Mantle cell lymphoma (MCL) is a type of lymphoid malignancy that is rare in Japan. MCL is refractory to conventional chemotherapy and has dismal outcomes. Nonetheless, the prognosis of MCL has gradually improved with the advent of autologous stem cell transplantation and BTK inhibitors. First-line therapies incorporating BTK inhibitors are currently under development, and are expected to further improve the prognosis. Nevertheless, subsets with poor prognosis have been identified, including p53 abnormalities (TP53 mutations or deletions), blastoid variant, high MIPI-c, and POD24, and these show resistance to conventional treatments including BTK inhibitors. To overcome these challenges, novel therapies such as CAR-T therapy and combination therapy with BTK and BCL2 inhibitors are being developed, and should soon become clinically available in Japan. The therapeutic landscape for MCL is evolving dynamically, and this article will discuss the future of MCL treatment strategies in Japan.

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Treatment for chronic graft-versus-host disease, the most important long-term complication of allogeneic hematopoietic cell transplantation, has changed significantly over the past decade. Development of novel targeted therapies has advanced as objective criteria for the diagnosis and evaluation of chronic GVHD have been established and understanding of the biological pathways to pathogenesis has increased. This paradigm shift is driving chronic GVHD practice significantly toward individualized therapy while minimizing exposure to steroids. Treatment using a variety of novel agents, tailored to each individual patient's condition, is expected to improve quality of life and overall survival by preventing chronic GVHD, controlling disease progression, and maintaining motor and occupational functions. This article reviews the pathogenesis of chronic GVHD and discusses prospects for the treatment of chronic GVHD, along with recently approved drugs and promising drugs in development.

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