Single Nucleotide Polymorphism (SNP) Approach of Multiple Candidate Pathways Predicting the Risk of Acute / Chronic Graft-Versus-Host Disease or Transplant Outcomes Following Allogeneic Hematopoietic Stem Cell Transplantation: Potential Involvement of Nuclear Factor Kappa-B (NFKB), Platelet-Derived Growth Factor (PDGF) and Transforming Growth Factor-Beta (TGF-β) Pathway with Chronic Graft-Versus-Host Disease Graft-Versus-Host Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2221-2221
Author(s):  
Dong Hwan (Dennis) Kim ◽  
Jina Yun ◽  
Jee Hyun Kong ◽  
Chul Won Jung ◽  
Ahmed Galal ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Growth Factor ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Transforming Growth Factor ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Cytokine Activation

Abstract Abstract 2221 Poster Board II-198 Background: Acute graft-versus-host disease (GVHD) was known to be involved in the Th1 cytokine activation and alloreactive T-cell cytotoxicity, while the pathogenesis of chronic GVHD is yet revealed fully although in which Th2 cytokine activation or transforming growth factor (TGF) mediated pathway was suggested to be involved. The current study is a hypothesis generating study in order to identify potential predictive surrogate associated with the risk of acute or chronic GVHD in addition with transplant outcomes after allogeneic hematopoietic stem cell transplantation (HSCT). Methods: The current study was performed to identify genetic surrogates predicting the risk of acute / chronic GVHD, relapse free survival, non-relapse mortality and overall survival in 394 pairs transplanted at the Princess Margaret Hospital, Toronto, ON, Canada. In addition, the predictive markers for organ specific incidence of acute / chronic GVHD were also evaluated (i.e. for skin/liver/gut acute GVHD or skin, eye, oral, lung or liver chronic GVHD). Total of 261 single nucleotide polymorphisms (SNPs) in 56 genes were determined for donor/recipients' genotypes using MALDI-TOF based platform, involving in the pathways of 1) cytokines (i.e. IL1A, IL1B and its receptor, IL1R1, IL2 & IL2RA, IL4 & IL4R, IL6 & IL6R, IL8, IL10 & IL10RA, RB, IL12A/BandIL12RB1, IFNG & IFNGR1/2, TNFTI/II/II), 2) NFKB (NFKB1/2/A, NFKBIA/B, IKB, IKK1, IKBKB, RelB), 3) apoptosis (FAS, TRAIL & TRAILR1), 4) endothelium nitric oxide regulation (EDN1, NOS1/2A/3), 5) PDGF (PDGFB/C/D & PDGFRA/B), 6) TGF-β (TGFB1/2 & TGFBR1/2/3, TGFRB1), 7) Toll-like receptor (TLR4/5), 8) NOD2/CARD15 and 9) prostaglandin-endoperoxide synthase (PTGS1/2). The candidate genotypes have been selected by choosing the SNPs in non-synonymous SNPs in exon region with minor allele frequency of > 0.05 to 0.1. Results: Followings are the lists of recipients' and donors' genotypes with p-value<0.05 thus associating with clinical outcomes following allogeneic HSCT: In summary, the risk of chronic GVHD was significantly associated with SNP of the genes involved in the pathway of NFKB, PDGF, TGF-β, and some of cytokines (esp. type II, IL6 & IL4), while that of acute GVHD associates with the genotypes in the pathway of TNF and apoptosis. In addition, survival after allogeneic transplantation was associated with the genotypes in NOS (nitric oxide synthase, endothelial nitric oxide synthesis pathway), IL-2 and TGF pathway. Conclusion: Because of complex nature of GVHD pathogenesis, multiple candidate pathway SNPs has been explored targeting SNPs in the pathway of cytokines, NFKB, apoptosis, endothelium nitric oxide regulation, NOD2/CARD15, PDGF, PTGS1/2, TGF-β and TLR. Different involvements were noted of TGF-β, PDGF or NFKB with chronic GVHD versus TNF and apoptosis-associated SNPs with acute GVHD. Further study will help us to reach more clear conclusion which genotype is the predictor of the risk of GVHD. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Acute and chronic graft versus host disease after hematopoietic stem cell transplant

JBMTCT ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 53-66
Author(s):  
Vaneuza A. M. Funke ◽  
Maria Claudia Rodrigues Moreira ◽  
Afonso Celso Vigorito
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Primary Therapy ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Graft versus host disease is one of the main complications of Hematopoietic stem cell, in­volving about 50% to 80% of the patients. Acute GVHD clinical manifestations and therapy is discussed, as well as new NIH criteria for the diagnosis and classification of chronic GVHD. Therapy for both refractory chronic and acute GVHD is an important field of discussion once there is no superiority for the majority of the agents after primary therapy has failed. Hence, this review is meant to be a useful tool of consultation for clinicians who are dealing with this complex complication.

Does Donor Epstein-Barr Virus (EBV) Seropositivity Affect Recipient's Risk of Graft Versus Host Disease (GVHD) in Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT)?

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5766-5766
Author(s):  
Erden Atilla ◽  
Esmanur Kaplan ◽  
Pinar Ataca Atilla ◽  
Selami Kocak Toprak ◽  
Pervin Topcuoglu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Abstract Introduction: EBV seropositivity in general population is 80%. Reactivation of latent infection in pre-transplant seropositive patients causes post-transplant lenfoproliferative disease (PTLD) following Allo-HSCT. The effect of donor EBV positivity on recipient's risk of graft versus host disease is not clear. Our aim is to present EBV seroprevalence and PTLD incidence as well as demonstrating the relation of EBV seropositivity with GVHD. Patients and Methods: A total of 364 allogeneic stem cell transplant recipients and donors were evaluated retrospectively from 2006 to 2015. During Allo-HSCT preparation procedures all recipients and donors were serologically tested. EBV specific IgG (VCA-IgG, EBNAIgG, EA-IgG) and IgM (VCA-IgM) antibodies were determined by Chemiluminescence by ARCHITECT lab analyzers using commercially available kits (Abbott, USA). All patients were followed for reactivation. Results: EBV IgG positivity was detected in 338 of recipients (92.8%) and 283 of donors (77.7%). There was no statistically difference detected between related or unrelated transplants. The mean age was 37 (range 16-67). 217 recipients were male (60%). 295 (81%) patients were transplanted for malign hematological diseases. The majority of patients were grafted from full-matched related donors (258, 71%). The most common source of stem cell was peripheral blood in 299 patients (82%) followed by bone-marrow in 56 patients (15%), bone-marrow plus peripheral blood in 9 patients (3%). 273 (75%) patients received myeloablative conditioning regimen. All patients received prophylactic acyclovir (in related transplants 400mg 3 times daily, in un-related transplants 800mg 3 times daily) starting from conditioning and up to three months posttranplant period. One pretransplant seropositive 26 year-old aplastic anemia patient had PTLD with EBV IgM positivity within 3 months posttransplant. He received 4 cycles of rituximab and prednisolone and achieved complete response. Three patients had EBV IgM positivity in posttransplant 4, 9 and 24th months with symptoms of infectious mononucleosis. The seropositivity resolved without treatment. Acute GVHD developed in 223 patients (61%) whereas chronic GVHD was detected in 285 (78%) of patients. The incidence of acute GVHD was similar when donor was EBV seropositive compared to seronegative (78% vs 22%, p=0.72). Chronic GVHD incidence was similar between donor EBV seropositive group compared to seronegative group (80% vs 20%, P=0.199). Conclusion: EBV seropositivity is common detected in 92.8% of our allo-HSCT recipient cohort. Donor EBV status did not have an effect on developing acute or chronic GVHD. Disclosures No relevant conflicts of interest to declare.

Chronic Graft-Versus-Host Disease after Tacrolimus Versus Cyclosporine for Graft-Versus-Host Disease Prophylaxis in Pediatric Patients Undergoing Matched Unrelated Donor Hematopoietic Stem Cell Transplantation. A Pediatric Blood and Marrow Transplant Consortium Study..

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4984-4984
Author(s):  
Mark P. Atlas ◽  
Greg Yanik ◽  
Kirk R. Schultz ◽  
Rakesh K. Goyal
Keyword(s):  
Hematopoietic Stem Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Chronic graft versus host disease (GVHD) is a significant cause of morbidity and mortality in matched unrelated donor hematopoietic stem cell transplantation. Incidence of acute GVHD is a major risk factor for chronic GVHD. Calcineurin inhibitors form the backbone of graft versus host disease (GVHD) prophylaxis in hematopoietic stem cell transplantation. When comparing cyclosporine to tacrolimus for GVHD prophylaxis, we previously reported a trend toward superiority of cyclosporine as prophylaxis against acute GVHD. We now analyze their effect on the incidence and severity of chronic GVHD. In a multi-institutional trial, we prospectively collected the clinical data on 141 evaluable patients receiving either cyclosporine/methotrexate or tacrolimus/methotrexate based prophylactic regimens for 6/6 matched unrelated donor, transplant. Conditioning regimens were fully ablative; no T-cell depletion was permitted; cord blood donors were excluded. Patients were required to receive either cyclosporine or tacrolimus, but the choice was per investigator preference. The two arms were reasonably balanced: 60.1% of patients received cyclosporine and 39.9% of patients received tacrolimus. Rates for acute GVHD were 60.4% for cyclosporine and 73.8% for tacrolimus (p = 0.086). Rates for chronic GVHD were 44.2% for cyclosporine and 47.3% for tacrolimus (p = 0.7). In the 61 patients with chronic GVHD, extensive disease was present in 82.9% of cyclosporine group and 80.8% of the tacrolimus group (p = 1.0) Those graded as moderate or severe comprised 80% of the cyclosporine group and 56% of the tacrolimus group (p = 0.46) and those both extensive and moderate or severe were 71.4% and 52%, respectively (p = 0.12). In pediatric matched unrelated donor transplantation, the incidence and severity of chronic graft versus host disease in patients receiving either tacrolimus/methotrexate or cyclosporine/methotrexate based regimens for prophylaxis of GVHD are not significantly different.

Proteomic Screening Applied to the Diagnosis of Chronic Graft-Versus-Host-Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1164-1164
Author(s):  
Eva M. Mischak-Weissinger ◽  
Michael Stadler ◽  
Ernst Holler ◽  
Michael Schleuning ◽  
Hildegard Greinix ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Correct Classification ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Peptide Pattern ◽  
Conditioning Regimens

Abstract Abstract 1164 Poster Board I-186 Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for many hematologic malignancies or hematopoietic dysfunction syndromes, but the application is still limited due to major complications, such as severe graft versus host disease (GvHD) and infectious complications. Diagnosis chronic GvHD is based on clinical features and biopsies, a non invasive, unbiased laboratory test does not exist. We used the urine collected from 20 patients (10 with limited cGvHD, 10 with extensive cGvHD) to establish a proteomic pattern that allowed the diagnosis of cGvHD development and tested the resulting set of polypeptide markers (27 differentially excreted peptides) on more than 200 patients prospectively and blinded for the correct classification of cGvHD samples. The majority of the patients included were transplanted for hematological malignancies (n=209), 6 for hematopoietic failure syndromes. Conditioning regimens included dose reduced conditioning regimens (FLAMSA and ClaraC for the majority of the patients of MHH), as well as standard conditioning regimens (TBI+Cy or Busulfan+Cy) for about 35% of the patients, with GvHD-prophylaxis including cyclosporine A and mycophenolate (MMF) or metothrexate (MTX) as appropriate. Eighty percent of the patients received ATG (antithymocyte globulin) prior to HSCT. A peptide pattern of 27 peptides, differentiating chronic from acute GvHD was developed. Controls were patients at least 100 days post HSCT, with no GvHD in the history, no infections and without relapse at the time of sampling. Prospective and blinded evaluation of the patients revealed the correct classification of patients developing cGvHD with a sensitivity of 85% and specificity of 95%.Further evaluation of the cGvHD patterns specific for particular organ manifestations of cGvHD are currently ongoing. Interestingly, the cGvHD pattern seems to be predictive for GvHD developing post DLI, while the aGvHD-specific proteomic pattern only predicts GvHD of the intestine, which may be more similar to “late acute GvHD”. Disclosures Krons: mosaiques-diagnostics GmbH: Employment. Metzger:mosaiques-diagnostics GmbH: Employment.

Tregs In Graft-Versus-Host Disease: A Task Force In Trouble?.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3748-3748
Author(s):  
Sya N. Ukena ◽  
Jens Grosse ◽  
Stefanie Buchholz ◽  
Michael Stadler ◽  
Arnold Ganser ◽  
...  
Keyword(s):  
T Cells ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Peripheral Tolerance ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
The Impact

Abstract Abstract 3748 Graft-versus-host disease (GvHD) remains the major clinical complication in hematopoietic stem cell transplantation (SCT) resulting in severe morbidity and significant mortality. This alloreactive immune response is mainly induced by donor T cells transplanted with the graft. Regulatory T cells (Tregs) play an essential role in the induction and maintenance of peripheral tolerance. In addition, data from murine models have shown that Tregs can prevent GvHD while preserving the graft-versus-leukemia effect. In order to functionally and dynamically characterize human Tregs after allogeneic SCT, we analyzed CD4+CD25highCD127dim T cells isolated from the peripheral blood of more than 80 patients with hematological malignancies every 30 days over half a year following SCT. Patients were divided into the following clinical groups: (A) no signs of acute or chronic GvHD, (B) acute GvHD, (C) chronic GvHD and (D) acute GvHD passed into chronic GvHD. Human peripheral blood lymphocytes were separated by Ficoll gradient and CD4+CD14−CD25highCD127dim T cells were isolated by MoFlow cell sorting. Isolated RNA was pooled and microarray analysis was performed by using Affymetrix HG_U133_Plus2.0 Arrays. Results were verified by using quantitative realtime RT-PCR. Additionally, Tregs were phenotypically analyzed by FACS. We monitored a continous but slower recovery of Tregs in GvHD within the first 6 months following PBSCT. Manifestation of acute and chronic GvHD correlated with significantly reduced frequencies of peripheral Tregs in the first month after PBSCT compared to patients without GvHD. Microarray data revealed a high stability of the Treg transcriptome in the first half year representing the most sensitive time window for tolerance induction. Moreover, comparison of the Treg gene expression profiles from patients with and without GvHD point to a reduced suppressive function of Tregs with diminished migration capacity to the target organs likely contributing to the development of GvHD. Our findings corroborate the impact of human Tregs in the pathophysiology of GvHD and identify novel targets for the manipulation of Tregs to optimize strategies for prophylaxis and treatment of life-threatening GvHD. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Association between human leukocyte antigens and graft-versus-host disease occurrence after allogenic hematopoietic stem cell transplantation

2012 ◽  
Vol 130 (4) ◽  
pp. 219-224 ◽  
Author(s):  
Daniela Máira Cardozo ◽  
Sofia Rocha Lieber ◽  
Silvia Barbosa Dutra Marques ◽  
Francisco José Aranha ◽  
Afonso Celso Vigorito ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Human Leukocyte ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

CONTEXT AND OBJECTIVE: Graft-versus-host disease (GVHD) is one of the complications following allogenic stem cell transplantation. This study investigated an association between human leukocyte antigen (HLA) and the occurrence of acute and chronic GVHD in patients who had received stem cell transplantations from HLA-identical siblings. DESIGN AND SETTING: Retrospective study at Hematology and Hemotherapy Center, Universidade Estadual de Campinas (Unicamp). METHODS: The participants were 176 patients whose first transplant was between 1997 and 2009. HLA genotyping was performed serologically and using the polymerase chain reaction with specific primer sequence. RESULTS: Acute GVHD was positively associated with HLA-A10 (P = 0.0007), HLA-A26 (P = 0.002), B55 (P = 0.001), DRB1*15 (P = 0.0211) and DQB1*05 (P = 0.038), while HLA-B16 (P = 0.0333) was more frequent in patients without acute GVHD. Chronic GVHD was positively associated with HLA-A9 (P = 0.01) and A23 (P = 0.0292) and negatively with HLA-A2 (P = 0.0031) and B53 (P = 0.0116). HLA-B35 (P = 0.0373), B49 (P = 0.0155) and B55 (P = 0.0024) were higher in patients with acute GVHD grade 3 or above, than in other patients. In patients with extensive chronic GVHD, HLA-A9 (P = 0.0004), A24 (P = 0.0059) and A26 (P = 0.0411) were higher than in other patients, while HLA-A2 was lower (P = 0.0097). CONCLUSION: This study suggests that HLA can influence the incidence and severity of acute and chronic GVHD. However, a study with a better design and more patients will be needed to confirm these results.

Positive Impact of Chronic Graft-Versus Host Disease on Survival in 928 Allogeneic Hematopoietic Stem Cell Transplant Recipients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1952-1952 ◽  
Author(s):  
Gunhan Gurman ◽  
Pinar Ataca ◽  
Erden Atilla ◽  
Sinem Civriz Bozdag ◽  
Selami Kocak Toprak ◽  
...  
Keyword(s):  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Lower Risk ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Immune Mediated

Abstract Introduction: Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is a standard curative treatment option in hematological diseases. The anti-leukemic activity relies not only the effects of conditioning regimen but also the immune mediated graft-versus leukemia (GVL) effect. Donor T cells are responsible for the GVL and causes complications namely acute and chronic graft versus host disease (GVHD). Herein, we aim to present the relation of graft versus host disease with survival and relapse. Patients and Methods: We retrospectively evaluated 928 Allo-HSCT between 1989 and 2015 followed in our institution. Chi-square test and student's t test were used in comparison. P <0.05 was considered statistically significant. Results: 551 patients were male (59%) and 377 patients (41%) were female. The median age of the group was 34 (range 15 -71). Patients received stem cell from related donors more frequently (85%) with HLA full match (66%). Peripheral blood was the source of stem cells in 645 recipient (70%) followed by bone marrow (28%). 75 patients were diagnosed as benign hematological disorders. The most common malign hematological diagnosis was acute myeloid leukemia in 366 patients (39%). Patients received 80% of myeloablative conditioning regimen prior to transplantation. 43% of the patients diagnosed as acute GVHD and 45% had chronic GVHD. 798 achieved engraftment (86%) neutrophil engraftment median of 16 days, platelet engraftment median of 14 days. Relapse was detected in 6% of patients. The overall survival (OS) was 59 months and progression free survival (PFS) was 33 months. Acute GVHD had no impact on OS, PFS, relapse rate. The OS in patients with chronic GVHD was significantly higher than in GVHD negative patients (68.8 vs 56.9, P=0.009). Although chronic GVHD patients had lower risk of relapse and higher PFS, the results were not statistically significant. Conclusion: GVHD is a serious complication and important cause of post transplant morbidity. Chronic GVHD is associated with lower risk of relapse in previous studies. In this study, we have concluded the improved OS in patients with chronic GVHD. The immune mediated GVL effect may be the reason for anti-leukemia effect and improved survival. Disclosures No relevant conflicts of interest to declare.

scholarly journals SOCS3 regulates graft-versus-host disease

Blood ◽  
2010 ◽  
Vol 116 (2) ◽  
pp. 287-296 ◽  
Author(s):  
Geoffrey R. Hill ◽  
Rachel D. Kuns ◽  
Neil C. Raffelt ◽  
Alistair L. J. Don ◽  
Stuart D. Olver ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Transforming Growth Factor ◽  
Chronic Gvhd ◽  
Cytokine Signaling ◽  
Host Disease ◽  
Graft Versus Host ◽  
Donor T Cells

Abstract Suppressor of cytokine signaling-3 (SOCS3) is the main intracellular regulator of signaling by granulocyte colony-stimulating factor, an immune-modulatory cytokine used to mobilize stem cells for transplantation. We have therefore studied the contribution of SOCS3 to the spectrum of graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (SCT). Grafts from SOCS3−/Δvav donor mice in which SOCS3 deficiency is restricted to the hematopoietic compartment had an augmented capacity to induce acute GVHD. With the use of SOCS3−/ΔLysM and SOCS3−/Δlck donors in which SOCS3 deficiency was restricted to the myeloid or T-cell lineage, respectively, we confirmed SOCS3 deficiency promoted acute GVHD mortality and histopathology within the gastrointestinal tract by effects solely within the donor T cell. SOCS3−/Δlck donor T cells underwent enhanced alloantigen-dependent proliferation and generation of interleukin-10 (IL-10), IL-17, and interferon-γ (IFNγ) after SCT. The enhanced capacity of the SOCS3−/Δlck donor T cell to induce acute GVHD was dependent on IFNγ but independent of IL-10 or IL-17. Surprisingly, SOCS3−/Δlck donor T cells also induced severe, transforming growth factor β– and IFNγ-dependent, sclerodermatous GVHD. Thus, the delivery of small molecule SOCS3 mimetics may prove to be useful for the inhibition of both acute and chronic GVHD.

scholarly journals Mast Cell Involvement in Fibrosis in Chronic Graft-Versus-Host Disease

2021 ◽  
Vol 22 (5) ◽  
pp. 2385
Author(s):  
Ethan Strattan ◽  
Gerhard Carl Hildebrandt
Keyword(s):  
Wound Healing ◽  
Mast Cell ◽  
Mast Cells ◽  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Fibrotic Disease ◽  
Acute Leukemias ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Allogeneic hematopoietic stem cell transplantation (HSCT) is most commonly a treatment for inborn defects of hematopoiesis or acute leukemias. Widespread use of HSCT, a potentially curative therapy, is hampered by onset of graft-versus-host disease (GVHD), classified as either acute or chronic GVHD. While the pathology of acute GVHD is better understood, factors driving GVHD at the cellular and molecular level are less clear. Mast cells are an arm of the immune system that are known for atopic disease. However, studies have demonstrated that they can play important roles in tissue homeostasis and wound healing, and mast cell dysregulation can lead to fibrotic disease. Interestingly, in chronic GVHD, aberrant wound healing mechanisms lead to pathological fibrosis, but the cellular etiology driving this is not well-understood, although some studies have implicated mast cells. Given this novel role, we here review the literature for studies of mast cell involvement in the context of chronic GVHD. While there are few publications on this topic, the papers excellently characterized a niche for mast cells in chronic GVHD. These findings may be extended to other fibrosing diseases in order to better target mast cells or their mediators for treatment of fibrotic disease.

scholarly journals Ruxolutinib in Steroid Refractory Graft Versus Host Disease (SR-GVHD): Systemic Literature Review

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5682-5682
Author(s):  
Mostafa F. Mohammed Saleh ◽  
Shahrukh K. Hashmi
Keyword(s):  
Adverse Events ◽  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Infectious Complications ◽  
Systemic Review ◽  
Close Monitoring ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Steroid Refractory

Background: Graft versus host disease (GVHD) is a main cause of morbidity and mortality in patients having undergone allogeneic hematopoietic stem cell transplantation (HSCT). About 30-40% of patients have steroid‐refractory GVHD (SR‐GVHD) after the first‐line use of high doses of corticosteroids with a poor prognosis .Ruxolitinib is a promising treatment for SR-GVHD. However, data regarding optimum dosing, response rates and associated adverse events are scarce. Herein, we provide the first systemic review of literature for the use ruxolutinib in GVHD. Methods: A Medline (PubMed), google scholar, OVID and Cochrane Database of Systematic Reviews search using key words "Ruxolutinib and GVHD", "Ruxolutinib and SR-GVHD" was undertaken in June 2019. Only peer reviewed databases were searched and search was restricted to human studies of acute and chronic GVHD only. Results: 16 publications, as listed in Table 1. Only one was a prospective trial, all others were retrospective studies, case series (5), and case reports (2). Overall response, ranged 45% - 100%, complete response was noted in 5.2% -80% patients. Time to response was variable from 1-12 weeks. Cytopenias and infectious complications were frequently reported with dose reduction or interruptions needed in most studies. Maintained responses were reported in a small proportion after ruxolutinib discontinuation. Conclusion Ruxolutinib has promising efficacy in SR-GVHD , however cytopenias and infectious complications reported frequently mandate close monitoring. Results of ongoing prospective trials could provide answers for optimum dosing and response assessment, and management of related adverse events. Table Disclosures No relevant conflicts of interest to declare.

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