scholarly journals Updates in chronic graft-versus-host disease

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 648-654
Author(s):  
Betty K. Hamilton
Keyword(s):  
Clinical Trials ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Host Disease ◽  
Graft Versus Host ◽  
Late Morbidity ◽  
Prevention And Treatment

Abstract Chronic graft-versus-host disease (GVHD) is the leading cause of late morbidity and mortality after allogeneic hematopoietic cell transplantation. Symptoms and manifestations of chronic GVHD are heterogeneous and pleomorphic, and there are no standard treatments beyond corticosteroids. Therapy is typically prolonged, and chronic GVHD and its treatment are associated with adverse effects that have a significant impact on long-term quality of life and functional status. Several advances have been made over the last 2 decades to define the diagnosis of chronic GVHD as well as its severity and response criteria for clinical trials. Further understanding into the biologic mechanisms of the development of chronic GVHD has led to the investigation of several novel immunomodulatory and targeted therapies. Multi-institutional collaboration and pharmaceutical support in the development of therapies based on sound biologic mechanisms and clinical trials with defined end points and responses have led to several promising agents on the horizon of approval for treatment of chronic GVHD. This article reviews advances in our knowledge of chronic GVHD and its biologic framework to improve approaches to prevention and treatment.

scholarly journals Acute graft-versus-host disease: a bench-to-bedside update

Blood ◽  
2014 ◽  
Vol 124 (3) ◽  
pp. 363-373 ◽  
Author(s):  
Shernan G. Holtan ◽  
Marcelo Pasquini ◽  
Daniel J. Weisdorf
Keyword(s):  
Small Molecules ◽  
Graft Versus Host Disease ◽  
Host Disease ◽  
Multiple Modalities ◽  
Graft Versus Host ◽  
The Past ◽  
Prevention And Treatment ◽  
Near Future ◽  
Acute Graft

Abstract Over the past 5 years, many novel approaches to early diagnosis, prevention, and treatment of acute graft-versus-host disease (aGVHD) have been translated from the bench to the bedside. In this review, we highlight recent discoveries in the context of current aGVHD care. The most significant innovations that have already reached the clinic are prophylaxis strategies based upon a refinement of our understanding of key sensors, effectors, suppressors of the immune alloreactive response, and the resultant tissue damage from the aGVHD inflammatory cascade. In the near future, aGVHD prevention and treatment will likely involve multiple modalities, including small molecules regulating immunologic checkpoints, enhancement of suppressor cytokines and cellular subsets, modulation of the microbiota, graft manipulation, and other donor-based prophylaxis strategies. Despite long-term efforts, major challenges in treatment of established aGVHD still remain. Resolution of inflammation and facilitation of rapid immune reconstitution in those with only a limited response to corticosteroids is a research arena that remains rife with opportunity and urgent clinical need.

Immune Mediated Cerebellar Ataxia: An Unknown Manifestation of Graft-versus-Host Disease

2018 ◽  
Vol 141 (1) ◽  
pp. 19-22
Author(s):  
Liat Shargian-Alon ◽  
Pia Raanani ◽  
Uri Rozovski ◽  
Tali Siegal ◽  
Shlomit Yust-Katz ◽  
...  
Keyword(s):  
Cerebellar Ataxia ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Cerebellar Atrophy ◽  
Acid Decarboxylase ◽  
High Dose ◽  
Host Disease ◽  
Graft Versus Host ◽  
Aged Woman

Neurologic complications of allogeneic hematopoietic cell transplantation (allo-HCT) include infections, cerebrovascular events, therapy-induced neurotoxicity, recurrent malignancies, and neurologic manifestations of graft-versus-host disease (GVHD). Anti-glutamic acid decarboxylase (GAD) antibody-associated cerebellar ataxia is a well-established disorder of autoimmune origin, but there are no reports in the literature of its occurrence following allo-HCT. We describe a middle-aged woman with chronic GVHD after allo-HCT who presented with a rapidly progressive cerebellar syndrome. Thorough investigation revealed only cerebellar atrophy on brain imaging and positive anti-GAD65 antibodies in serum and cerebrospinal fluid suggesting the diagnosis of anti-GAD antibody-associated cerebellar ataxia. Despite prompt treatment with high-dose corticosteroids, intravenous immunoglobulins, and rituximab, the patient’s condition rapidly deteriorated, and she died 4 months later. This case suggests that anti-GAD antibody-associated cerebellar ataxia may be a rare manifestation of chronic GVHD.

scholarly journals Uva1 Phototherapy in the Management of Sclerodermatous Graft-Versus-Host Disease (Gvhd): a report of two cases / Uva1 fototerapija u lečenju sklerodermatoznog oblika hronične Gvhd: Prikaz dva slučaja

2009 ◽  
Vol 1 (4) ◽  
pp. 147-152 ◽  
Author(s):  
Hiva Fassihi ◽  
Kamran Iqbal ◽  
Trish Garibaldinos ◽  
Robert Sarkany ◽  
Julia Scarisbrick ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Skin Diseases ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Allogeneic Hsct ◽  
Graft Versus Host ◽  
Uva1 Phototherapy ◽  
Matched Sibling

Abstract Chronic graft-versus-host disease (GVHD) is a frequent complication after allogeneic hematopoietic stem cell transplantation (HSCT). Approximately 10% of patients with GVHD develop sclerodermatous changes, which can cause significant morbidity and are often refractory to standard systemic immunosuppression. We present two cases of sclerodermatous GVHD. The first is a 39-year-old man, who had a matched sibling, undergoing allogeneic HSCT for severe aplastic anemia. The second patient is a 7-year-old boy, who had an allogeneic HSCT from his HLA-identical mother for acute myeloid leukemia (AML). Both patients presented with widespread sclerotic changes, resulting in joint contractures and significant functional difficulties. Studies have shown UVA1 phototherapy to be a promising and well tolerated treatment modality in patients with sclerotic skin diseases. Both of our patients were treated with UVA1, which resulted in a significant skin softening, improvement in joint mobility and quality of life. UVA1 appears to be an effective treatment for refractory sclerodermatous GVHD; however, long-term clinical studies in larger groups are needed to accurately evaluate its efficacy and safety.

Chronic graft versus host disease is associated with long-term risk for pneumococcal infections in recipients of bone marrow transplants

Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 3683-3686 ◽  
Author(s):  
Samar Kulkarni ◽  
Ray Powles ◽  
Jennie Treleaven ◽  
Unell Riley ◽  
Seema Singhal ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Pneumococcal Infection ◽  
Pneumococcal Infections ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Penicillin Prophylaxis

Abstract Incidences of and risk factors for Streptococcus pneumoniaesepsis (SPS) after hematopoietic stem cell transplantation were analyzed in 1329 patients treated at a single center between 1973 and 1997. SPS developed in 31 patients a median of 10 months after transplantation (range, 3 to 187 months). The infection was fatal in 7 patients. The probability of SPS developing at 5 and 10 years was 4% and 6%, respectively. Age, sex, diagnosis, and graft versus host disease (GVHD) prophylaxis did not influence the development of SPS. Allogeneic transplantation (10-year probability, 7% vs 3% for nonallogeneic transplants; P = .03) and chronic GVHD (10-year probability, 14% vs 4%; P = .002) were associated with significantly higher risk for SPS. All the episodes of SPS were seen in patients who had undergone allograft or total body irradiation (TBI) (31 of 1202 vs 0 of 127;P = .07). Eight patients were taking regular penicillin prophylaxis at the time of SPS, whereas 23 were not taking any prophylaxis. None of the 7 patients with fatal infections was taking prophylaxis for Pneumococcus. Pneumococcal bacteremia was associated with higher incidences of mortality (6 of 15 vs 1 of 16;P = .04). We conclude that there is a significant long-term risk for pneumococcal infection in patients who have undergone allograft transplantation, especially those with chronic GVHD. Patients who have undergone autograft transplantation after TBI-containing regimens also appear to be at increased risk. These patients should receive lifelong pneumococcus prophylaxis. Consistent with increasing resistance to penicillin, penicillin prophylaxis does not universally prevent SPS, though it may protect against fatal infections. Further studies are required to determine the optimum prophylactic strategy in patients at risk.

scholarly journals Effectiveness of immunosuppression minimisation, conversion or withdrawal strategies in paediatric solid organ and haematopoietic stem cell transplantation: a protocol of a systematic review and meta-analysis

BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e037721
Author(s):  
Carlos Martin Saborido ◽  
Alberto M Borobia ◽  
Javier Cobas ◽  
Lorenzo D'Antiga ◽  
Esteban Frauca ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Systematic Review ◽  
Blood Pressure ◽  
Clinical Trials ◽  
Graft Versus Host Disease ◽  
Graft Rejection ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

IntroductionPaediatric transplantation is the only curative therapeutic procedure for several end-stage rare diseases affecting different organs and body systems, causing altogether great impact in European children’s health and quality of life. Transplanted children shift their primary disease to a chronic condition of immunosuppression to avoid rejection. Longer life expectancy in children poses a greater risk of prolonged and severe side effects related to long-term immunosuppressive (IS) disabilities and secondary cancer susceptibility. The goal remains to find the best combination of IS agents that optimises allograft survival by preventing acute rejection while limiting drug toxicities. This systematic review will aim to determine the optimal IS strategy within the so-called minimisation, conversion or withdrawal strategies.Methods and analysisWe will search the following databases with no language restrictions: Cochrane Central Register of Controlled Trials in the Cochrane Library, OvidSP Medline and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily; OvidSP Embase Classic+Embase; Ebsco CINAHL Plus, complete database; WHO International Clinical Trials Registry Platform search portal. We will include controlled and uncontrolled clinical trials along with any prospective or retrospective study that includes a universal cohort (all participants from a centre/region/city over a certain period). Cases series and cross-sectional studies are excluded. Two review authors will independently assess the trial eligibility, risk of bias and extract appropriate data points. The outcomes included in this review are: patient survival, acute graft rejection, chronic graft rejection, diabetes, graft function, graft loss, chronic graft versus host disease, acute graft versus host disease, surgical complications, infusion complications, post-transplant lymphoproliferative disease, liver function, renal function, cognition, depression, health-related quality of life, hospitalisation, high blood pressure, low blood pressure, cancer—other, cancer—skin, cardiovascular disease, bacterial infection, Epstein-Barr infection, cytomegalovirus infection, other viral infections and growth.

Serious Acute or Chronic Graft-Versus-Host Disease after Hematopoietic Cell Transplantation: A Comparison of Myeloablative and Non-Myeloablative Conditioning Regimens.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 755-755
Author(s):  
Olga Sala-Torra ◽  
Paul J. Martin ◽  
Barry Storer ◽  
Mohamed Sorror ◽  
Rainer F. Storb ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Hematopoietic Cell ◽  
Host Disease ◽  
Graft Versus Host ◽  
Co Morbidity

Abstract We have previously described serious graft-versus-host disease (GVHD) as a highly undesirable outcome after allogeneic hematopoietic cell transplantation (HCT). Serious GVHD encompasses death, lengthy hospitalization, major disability, or recurrent major infections related to either acute or chronic GVHD. In a previous study, we found a 25% incidence of serious GVHD among 171 consecutive patients who had HCT after non-myeloablative (NMA) conditioning between January 1998 and May 2002. To put this observation into perspective, we applied the same criteria for serious GVHD in a cohort of 264 consecutive patients who had HCT after myeloablative (MA) conditioning during the same period of time and compared results with those of the previous study. The overall incidence of serious GVHD was 17% (44/264) in the MA group, compared to 25% (43/171) in the NMA group. There were no statistically significant differences in the incidence of grades III–IV GVHD, extensive chronic GVHD or nonrelapse mortality between the two groups (Table). Patients in the NMA group were older and had higher comorbidity scores than those in the MA group. In the univariate analysis, the hazard ratio (HR) of serious GVHD for the NMA group compared to the MA group was 1.71 (95% C.I., 1.1–2.6) (p = 0.01). After adjusting for patient age, patient and donor gender, donor type, HLA-mismatch, aggressive versus indolent malignancy at HCT, remission versus relapse at HCT, myeloid versus non–myeloid malignancy, HCT co–morbidity index, and prior donor lymphocyte infusion, the HR of serious GVHD was 1.50 (95% C.I., 0.8–2.7) (p = 0.17). After censoring for recurrent or progressive malignancy after HCT, the cumulative incidence of serious GVHD at 3 years was 21% for the NMA group and 14% for the MA group, and the HR was 1.33 (95% C.I., 0.7–2.6) (p = 0.40). Reasons for categorization of GVHD as serious (i.e., death, lengthy hospitalization, major disability, or recurrent major infections) were similar between the MA and NMA cohorts. Among the 44 patients with serious GVHD in the MA group, 19 (43%) had serious acute GVHD, and 25 (57%) had serious chronic GVHD. Among the 43 patients with serious GVHD in the NMA group, 20 (46%) had serious acute GVHD, and 30 (70%) had serious chronic GVHD. Among the 264 MA patients, 28 (11%) had grade III–IV acute GVHD and 147 (56%) had extensive chronic GVHD that did not meet the criteria for serious GVHD, compared to 7 (4%) and 84 (49%) of the 171 NMA patients, respectively. We conclude that the type of pretransplant conditioning regimen does not have a large effect on the incidence of serious GVHD after HCT. Assessment of serious GVHD provides additional useful information to acute GVHD grades and the classification of limited and extensive chronic GVHD in describing overall GVHD-related outcomes after HCT. MA NMA Outcome, n (%) n = 264 n = 171 Serious GVHD 44 (17) 43 (25) Grades III–IV acute GVHD 54 (20) 27 (16) Extensive chronic GVHD 174 (66) 114 (68) 2-year nonrelapse mortality 66 (25) 43 (25)

Treatment of Established Graft-Versus-Host Disease by PG490-88.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3243-3243
Author(s):  
Benny J. Chen ◽  
Congxiao Liu ◽  
Nelson J. Chao
Keyword(s):  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Single Agent ◽  
Chinese Herb ◽  
Clinical Signs ◽  
Vehicle Control ◽  
Control Group ◽  
Host Disease ◽  
Graft Versus Host

Abstract Graft-versus-host disease (GVHD) is a major complication following hematopoietic cell transplantation. While prophylaxis of GVHD has improved, treatment for GVHD remains unsatisfactory. PG490–88, a semi-synthetic derivative of a novel compound purified from a Chinese herb, is very effective in prevention of both acute and chronic GVHD. In this study, we tested whether PG490–88 is effective in treating established GVHD. The study was performed in a clinically relevant MHC-matched and minor mismatched model (B10.D2 to BALB/c). BALB/c (H2d, Mls-2a, Mls-3a) mice were lethally irradiated (8.5 Gy) and transplanted with 1x107 bone marrow cells and 1x108 spleen cells obtained from B10D.2 (H2d, Mls-2b, Mls-3b) mice. PG490–88 was administered intraperitoneally (i.p.) daily at a dose of 0.0535 mg/kg/day starting on day +15 post transplantation when the clinical signs of GVHD were first observed. Therefore, all animals in both vehicle control and PG490–88-treated groups developed GVHD before the treatment was started. After treatment, there was no difference in the severity of clinical GVHD between the treated and the control groups. However, PG490–88-treated mice survived significantly longer than the mice in the vehicle control group (Figure, median survival time: 50 vs. 65 days, P<0.0001). These data suggest that PG490–88 as a single agent is active in the therapy of established GVHD. Further preclinical studies will determine optimal schedules and combinations that could be utilized in clinical studies. Figure Figure

Chronic graft versus host disease is associated with long-term risk for pneumococcal infections in recipients of bone marrow transplants

Blood ◽  
2000 ◽  
Vol 95 (12) ◽  
pp. 3683-3686 ◽  
Author(s):  
Samar Kulkarni ◽  
Ray Powles ◽  
Jennie Treleaven ◽  
Unell Riley ◽  
Seema Singhal ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Chronic Gvhd ◽  
Pneumococcal Infection ◽  
Pneumococcal Infections ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Penicillin Prophylaxis

Incidences of and risk factors for Streptococcus pneumoniaesepsis (SPS) after hematopoietic stem cell transplantation were analyzed in 1329 patients treated at a single center between 1973 and 1997. SPS developed in 31 patients a median of 10 months after transplantation (range, 3 to 187 months). The infection was fatal in 7 patients. The probability of SPS developing at 5 and 10 years was 4% and 6%, respectively. Age, sex, diagnosis, and graft versus host disease (GVHD) prophylaxis did not influence the development of SPS. Allogeneic transplantation (10-year probability, 7% vs 3% for nonallogeneic transplants; P = .03) and chronic GVHD (10-year probability, 14% vs 4%; P = .002) were associated with significantly higher risk for SPS. All the episodes of SPS were seen in patients who had undergone allograft or total body irradiation (TBI) (31 of 1202 vs 0 of 127;P = .07). Eight patients were taking regular penicillin prophylaxis at the time of SPS, whereas 23 were not taking any prophylaxis. None of the 7 patients with fatal infections was taking prophylaxis for Pneumococcus. Pneumococcal bacteremia was associated with higher incidences of mortality (6 of 15 vs 1 of 16;P = .04). We conclude that there is a significant long-term risk for pneumococcal infection in patients who have undergone allograft transplantation, especially those with chronic GVHD. Patients who have undergone autograft transplantation after TBI-containing regimens also appear to be at increased risk. These patients should receive lifelong pneumococcus prophylaxis. Consistent with increasing resistance to penicillin, penicillin prophylaxis does not universally prevent SPS, though it may protect against fatal infections. Further studies are required to determine the optimum prophylactic strategy in patients at risk.

Genomic instability after allogeneic hematopoietic cell transplantation is frequent in oral mucosa, particularly in patients with a history of chronic graft-versus-host disease, and rare in nasal mucosa

Blood ◽  
2010 ◽  
Vol 116 (10) ◽  
pp. 1803-1806 ◽  
Author(s):  
Faisal M. Khan ◽  
Sarah Sy ◽  
Polly Louie ◽  
Alejandra Ugarte-Torres ◽  
Noureddine Berka ◽  
...  
Keyword(s):  
Genomic Instability ◽  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Host Disease ◽  
Graft Versus Host ◽  
Allogeneic Hct ◽  
History Of

Abstract Genomic instability (GI) of cells may lead to their malignant transformation. Carcinoma after hematopoietic cell transplantation (HCT) frequently involves some (eg, oral) but not other (eg, nasal) epithelia. We examined GI in oral and nasal mucosal specimens from 105 subjects, including short-term (7-98 days, n = 32) and long-term (4-22 yrs, n = 25) allogeneic HCT survivors. Controls included autologous HCT survivors (n = 11), patients treated with chemotherapy without HCT (n = 9) and healthy controls (n = 27). GI was detected in 60% oral versus only 4% nasal specimens in long-term allogeneic HCT survivors (P < .001). None of the controls showed GI. In oral specimens, GI was significantly associated with history of oral chronic graft-versus-host disease (cGVHD). We conclude that GI after HCT is frequent in some (oral) but rare in other (nasal) epithelia. This may explain why some epithelia (especially those involved with cGVHD) are prone to develop cancer.

scholarly journals Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria

Blood ◽  
2011 ◽  
Vol 117 (11) ◽  
pp. 3214-3219 ◽  
Author(s):  
Mary E. D. Flowers ◽  
Yoshihiro Inamoto ◽  
Paul A. Carpenter ◽  
Stephanie J. Lee ◽  
Hans-Peter Kiem ◽  
...  
Keyword(s):  
Risk Factors ◽  
Graft Versus Host Disease ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Human Leukocyte ◽  
National Institutes Of Health ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

Abstract Risk factors for grades 2-4 acute graft-versus-host disease (GVHD) and for chronic GVHD as defined by National Institutes of Health consensus criteria were evaluated and compared in 2941 recipients of first allogeneic hematopoietic cell transplantation at our center. In multivariate analyses, the profiles of risk factors for acute and chronic GVHD were similar, with some notable differences. Recipient human leukocyte antigen (HLA) mismatching and the use of unrelated donors had a greater effect on the risk of acute GVHD than on chronic GVHD, whereas the use of female donors for male recipients had a greater effect on the risk of chronic GVHD than on acute GVHD. Total body irradiation was strongly associated with acute GVHD, but had no statistically significant association with chronic GVHD, whereas grafting with mobilized blood cells was strongly associated with chronic GVHD but not with acute GVHD. Older patient age was associated with chronic GVHD, but had no effect on acute GVHD. For all risk factors associated with chronic GVHD, point estimates and confidence intervals were not significantly changed after adjustment for prior acute GVHD. These results suggest that the mechanisms involved in acute and chronic GVHD are not entirely congruent and that chronic GVHD is not simply the end stage of acute GVHD.

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