scholarly journals Eosinophilic fasciitis (Shulman syndrome), a rare entity and diagnostic challenge, as a manifestation of severe chronic graft-versus-host disease: a case report

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Thomas Chalopin ◽  
Nicolas Vallet ◽  
Marion Morel ◽  
Raphael Maguet ◽  
Louis d’Alteroche ◽  
...  
Keyword(s):  
Skin Biopsy ◽  
Graft Versus Host Disease ◽  
Soft Tissues ◽  
Rare Complication ◽  
Clinical Signs ◽  
Specific Treatment ◽  
Eosinophilic Fasciitis ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Abstract Background Shulman’s disease, or eosinophilic fasciitis (EF), is a rare autoimmune disease, characterized by sclerodermic skin lesions with progressive induration and thickening of the soft tissues. Chronic graft-versus-host-disease (GVHD) presenting as EF is a very rare manifestation of cutaneous GVHD. Case presentation We report an unusual case of EF in a 46-year-old Caucasian male patient who had received an allogenic hematopoietic stem cell transplantation in the context of relapsed/refractory multiple myeloma. The diagnosis was challenging, with the patient presenting hepatic dysfunction, normal eosinophils count, and incomplete clinical signs. Magnetic resonance imaging (MRI) and skin biopsy confirmed the diagnosis of EF. Early initiation of specific treatment with corticosteroids and prednisolone achieved complete response. Conclusion In practice, incomplete signs in this rare complication should lead to MRI as it is a major tool to guide decision-making based on the skin biopsy, allowing a rapid diagnosis and the initiation of treatment without delay.

Comparison of Three Minor-Mismatched Mouse Models of Chronic Graft Versus Host Disease.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3237-3237
Author(s):  
Antonia M.S. Mueller ◽  
Jessica A. Allen ◽  
David Miklos ◽  
Judith A. Shizuru
Keyword(s):  
Acute Phase ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Clinical Signs ◽  
Skin Lesions ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Mortality And Morbidity ◽  
Graft Versus Host ◽  
Igg Synthesis

Abstract Chronic graft-versus-host disease (cGVHD) is the most frequent long-term complication after allogeneic hematopoietic cell transplantation (HCT). While acute GVHD (aGVHD) is largely donor T cell (TC) driven in the setting of tissue damage, less is understood about the pathophysiology of cGVHD. There is clear evidence that besides TC, B cells (BC) contribute to this syndrome. cGVHD has not been widely studied in animal models. The existing cGVHD models use either MHC-mismatched strains, or the manifestations appear in a time frame more akin to aGVHD. To generate a comprehensive picture of cGVHD we studied 3 different MHC-matched, minor histocompatibility (miHA) mismatched strain combinations over an extended time period (day (d) 30, 60, 90, 120, 150, 300) for clinical signs, chimerism, IgG synthesis (donor/host), and histology: C57BL/6 (B6)→ BALB.B (H2Db), B10.D2→BALB/c (H2Dd), and AKR/J→BALB.K (H2Dk). Recipients were lethally irradiated and given FACS purified hematopoietic stem cells (HSC: c-Kit+Thy1.1loLin-Sca-1+). To induce GVHD titrated doses of splenocytes or purified CD4 or CD8 TC were co-transplanted. BALB.B recipients of B6 HSC + TC develop aGVHD. Morbidity as assessed by weight loss and mortality directly correlated with TC dose. Survivors of the acute phase stabilized by d50–70, with only subtle signs for months. However, they ultimately developed a full-blown burned-out picture of cGVHD, including erythrosquamous skin lesions, alopecia, cirrhotic liver changes, conjunctivitis and corneal clouding at 1 year post-HCT. Periportal liver infiltrates progressed over time to fibrosis. Intestines were primarily affected in the acute phase, whereas skin changes such as subcutaneous atrophy and infiltrative hair follicle damage were manifested late. Splenocytes or isolated CD4 TC (+HSC), but not CD8 TC, induced the full clinical and histological picture of GVHD. Despite a low barrier to engraftment, recipients of HSC only remained mixed chimeras. With addition of TC, conversion to full donor chimerism promptly occurred. However, delays in BC reconstitution correlated with the presence and degree of GVHD. Despite this lymphopenia high levels of IgG synthesis were observed post-HCT. BALB/c recipients of B10.D2 HSC grafts develop cutaneous GVHD (alopecia, erythrosquamous exanthema) between d20–50 post-HCT, which subsequently resolves. These mice had low mortality and morbidity and did not display clinical signs of systemic GVHD. Histological changes were subtle and engraftment occurred promptly. HCT of AKR/J→BALB.K required high numbers of HSC to achieve engraftment and chimerism remained mixed (beyond d100). Low numbers of co-transferred splenocytes or CD4 TC (but not CD8 TC) induced fulminant hyperacute GVHD with a very high mortality, approaching 80–100%. In contrast, CD8 cells appeared to facilitate engraftment of donor cells. Here, we characterized and compared miHA-mismatched HCT models with regard to cGVHD and engraftment. B6→BALB.B offers the most convincing histological signs of systemic cGVHD. Whereas the B10.D2→BALB/c developed an attenuated form, and AKR/J→BALB.K developed a devastating aGVHD. We believe mouse studies which allow the delineation of the GVHD-inducing (presumably CD4) TC subsets will not only yield a better understanding of the pathophysiology of GVHD, but will, together with the identification of engraftment facilitator cells (contained within the CD8 TC fraction) be the basis for the future of clinical graft engineering.

Successful Treatment of Pure Red Cell Aplasia and Chronic GVH with Rituximab after ABO Mismatched HSCT

2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Haidouri S ◽  
◽  
Mehtat EM ◽  
Jennane S ◽  
Elmaaroufi H ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Successful Treatment ◽  
Rare Complication ◽  
Pure Red Cell Aplasia ◽  
Red Cell ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Red Cell Aplasia ◽  
Disease Case

Background: Pure Red Cell Aplasia (PRCA) is a rare complication of ABO mismatched hematopoietic stem cell transplantation; there isn’t no standard of care, here we report a case of successful treatment by Rituximab in a refractory PRCA and chronic graft versus host disease. Case Presentation: A 26-year-old woman with PRCA following ABOmismatched allogeneic HSCT for chronic myeloid leukemia, associated with steroid refractory chronic hepatic graft versus host disease, treated with 4 doses of Rituximab 375mg/m² weekly, with an increase in her hemoglobin level and improvement of her liver’s enzymes. Conclusion: The interest of this case is to report the important therapeutic result of Rituximab, widely used in literature, especially if chronic Graft Versus host disease is associated.

scholarly journals Effect of Early Post-Transplantation Tacrolimus Concentration on the Risk of Acute Graft-Versus-Host Disease in Allogenic Stem Cell Transplantation

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 613
Author(s):  
Nidhi Sharma ◽  
Qiuhong Zhao ◽  
Bin Ni ◽  
Patrick Elder ◽  
Marcin Puto ◽  
...  
Keyword(s):  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Tacrolimus Concentration ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
The Impact ◽  
Risk Of Relapse ◽  
Acute Graft

Acute graft versus host disease (aGVHD) remains a leading cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HSCT). Tacrolimus (TAC), a calcineurin inhibitor that prevents T-cell activation, is commonly used as a GVHD prophylaxis. However, there is variability in the serum concentrations of TAC, and little is known on the impact of early TAC levels on aGVHD. We retrospectively analyzed 673 consecutive patients undergoing allo-HSCT at the Ohio State University between 2002 and 2016. Week 1 TAC was associated with a lower risk of aGVHD II–IV at TAC level ≥10.15 ng/mL (p = 0.03) compared to the lowest quartile. The cumulative incidence of relapse at 1, 3 and 5 years was 33%, 38% and 41%, respectively. TAC levels at week 2, ≥11.55 ng/mL, were associated with an increased risk of relapse (p = 0.01) compared to the lowest quartile. Subset analysis with acute myeloid leukemia and myelodysplastic syndrome patients showed significantly reduced aGVHD with TAC level ≥10.15 ng/mL at week 1 and a higher risk of relapse associated with week 2 TAC level ≥11.55 ng/mL (p = 0.02). Hence, achieving ≥10 ng/mL during the first week of HCT may mitigate the risk of aGVHD. However, levels (>11 ng/mL) beyond the first week may be associated with suppressed graft versus tumor effect and higher relapse.

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 Sustained remission after haploidentical bone marrow transplantation in a child with refractory systemic juvenile idiopathic arthritis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Guillaume Morelle ◽  
Martin Castelle ◽  
Graziella Pinto ◽  
Sylvain Breton ◽  
Matthieu Bendavid ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Juvenile Idiopathic Arthritis ◽  
Graft Versus Host Disease ◽  
Immune Thrombocytopenia ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Sustained Remission ◽  
Refractory Disease ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host

Abstract Background Some patients with systemic juvenile idiopathic arthritis (SJIA) and severe, refractory disease achieved remission through intensive immunosuppressive treatment followed by autologous hematopoietic stem cell transplantation (HSCT). However, disease relapsed in most cases. More recently selected SJIA patients received allogenic HSCT from a HLA-identical sibling or a HLA matched unrelated donor. While most transplanted patients achieved sustained SJIA remission off-treatment, the procedure-related morbidity was high. Case report A girl presented SJIA with a severe disease course since the age of 15 months. She was refractory to the combination of methotrexate and steroids to anti-interleukin (IL)-1, then anti-IL-6, tumor necrosis factor alpha inhibitors, and thalidomide. Given the high disease burden and important treatment-related toxicity the indication for a haploidentical HSCT from her mother was validated, as no HLA matched donor was available. The patient received a T replete bone marrow graft at the age of 3.7 years. Conditioning regimen contained Rituximab, Alemtuzumab, Busulfan, and Fludarabine. Cyclophosphamide at D + 3 and + 4 post HSCT was used for graft-versus-host-disease prophylaxis, followed by Cyclosporin A and Mycophenolate Mofetil. Post HSCT complications included severe infections, grade 3 intestinal graft-versus-host-disease, autoimmune thyroiditis, and immune thrombocytopenia. Three years after HSCT, the child is alive and well, notwithstanding persistent hypothyroidy requiring substitution. Immune thrombocytopenia had resolved. Most importantly, SJIA was in complete remission, off immunosuppressive drugs. Conclusion Allogenic HSCT may be a therapeutic option, even with a HLA haplo-identical alternative donor, in patients with inflammatory diseases such as SJIA. Despite increased experience with this treatment, the risk of life-threatening complications restrains its indication to selected patients with severe, refractory disease.

scholarly journals AB0543 CLINICAL CHARACTERISTICS OF A GROUP OF CHRONIC GRAFT-VERSUS-HOST DISEASE PATIENTS WITH POSITIVE AUTOIMMUNITY.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1568.1-1568
Author(s):  
M. E. Acosta ◽  
L. Gómez-Lechón ◽  
O. Compán ◽  
S. Pastor ◽  
C. A. Montilla-Morales ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Clinical Characteristics ◽  
De Novo ◽  
Small Sample Size ◽  
Small Sample ◽  
Eosinophilic Fasciitis ◽  
Ocular Involvement ◽  
Host Disease ◽  
Graft Versus Host ◽  
Multidisciplinary Consultation

Background:Graft-versus-host disease (GVHD) is a commonly severe multiorgan complication in patients undergoing allogeneic transplantation of hematopoietic progenitors. Its chronic form reflects a complex immune response with different degrees of inflammation, immune dysregulation and fibrosis. In some chronic graft-versus-host disease (cGVHD) patients, positive antibodies have been detected, which represent the presence of immune activity and suggest the possible involvement of B lymphocytes in the disease etiopathogenesis, but their clinical utility is controversial.Objectives:To describe the clinical characteristics of a group of cGVHD patients with positive autoimmunity treated in a multidisciplinary consultation of Rheumatology-Dermatology- Hematology of GVHD.Methods:Observational and retrospective study to describe the clinical characteristics of the patients with positive autoimmunity collected in the database of the multidisciplinary consultation of GVHD. The variables reviewed for this study, in addition to the demographic ones, were type of antibody, disease causing the transplant, presentation, severity and type of involvement. The statistical analysis was done with Epi-info 7.2.2.6.Results:Only 16 (16%) of the 100 patients included in the database had positive autoimmunity. Twelve (75%) tested positive to ANA, although 5 (31.25%) in a lower titer (1/80). The most common immunofluorescence pattern was the nucleolar in 88.89% (66.67% nucleolar and 22.22% nucleolar + cytoplasmic). Other antibodies detected were: 6 anti-Ro52, 2 anti-dsDNA, 1 anti-RP155, 1 anti-Fibrillarin, 1 anti-SAE1, 1 p-ANCA and 1 anti-NOR-90. The mean of age was 51.31±14.03 years. As for sex 4 (25%) were female and 12 (75%) were men. The most frequent disease that caused the transplant was acute myeloid leukemia (58.3%). Ten (62.5%) patients presented de novo cGVHD, 1 (6.25%) progressive and 5 (31.25%) quiescent. The time since receiving the transplant until the first visit was 14 to 79 months. Ten (62.5%) patients had nonspecific symptoms (arthralgia and myalgia), 2 (12.5%) edema, 8 (50%) contractures, 8 (50%) fasciitis and 6 (37.5%) eosinophilia. Eight (50%) patients had ocular involvement and 6 (37.5%) of the oral mucosa in the form of dry syndrome (Sjögren-like syndrome). Ten (62.5%) patients had limitation of joint mobility detected by the range of motion scale (ROM), of which 6 were mild and 4 moderate. Only 5 (31.25%) patients had general condition impairment. As for the skin involvement 10 (62.5%) patients had sclerodermiform involvement (8 of them being eosinophilic fasciitis- like), 2 (12.5%) lichenoid, and 3 (18.5%) mixed (sclerodermiform + lichenoid). Only 1 patient didn´t meet diagnostic criteria for GVHD. The sclerodermiform was the most common type of involvement in the positive ANA patients. Regarding the severity according to the of the American National Institute of Health (NIH) classification: 8 (50%) had serious affectation, 5 (31.25%) moderate and 2 (12.5%) mild, with 4 (25%) exitus.Conclusion:In our cohort of patients with cGVHD, serum detection of autoantibodies is uncommon, being the ANA with nucleolar pattern the most frequent. Although the small sample size does not allow correlations with the clinical variables it´s worth highlighting a greater positivity of autoantibodies in the sclerodermiform skin forms.References:[1]Kuzmina Z et al. Clinical significance of autoantibodies in a large cohort of patients with chronic graft-versus-host disease defined by NIH criteria. Am J Hematol. 2015 February; 90(2): 114–119.[2]Rhoades R, Gaballa S. The Role of B Cell Targeting in Chronic Graft-Versus-Host Disease, Biomedicines 2017, 5, 61: 2-10Disclosure of Interests:Maria Elisa Acosta: None declared, Luis Gómez-Lechón: None declared, Olga Compán: None declared, Sonia Pastor: None declared, Carlos A. Montilla-Morales: None declared, Olga Martínez González: None declared, Ana Isabel Turrión: None declared, Javier del Pino Grant/research support from: Roche, Bristol, Consultant of: Gedeon, Cristina Hidalgo: None declared

scholarly journals 1075. Absolute Lymphocyte Count as a Predictor of Cytomegalovirus (CMV) Infection and Recurrence in Hematopoietic Stem Cell Transplant (HSCT) Recipients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S565-S565
Author(s):  
Joanne Reekie ◽  
Marie Helleberg ◽  
Christina Ekenberg ◽  
Mark P Khurana ◽  
Isabelle P Lodding ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Lymphocyte Count ◽  
Absolute Lymphocyte Count ◽  
Cell Transplant ◽  
Cmv Infection ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Increased Risk ◽  
Acute Graft

Abstract Background Cytomegalovirus (CMV) is a serious complication following Hematopoietic Stem Cell Transplant (HSCT) and can lead to serious organ disease and mortality. This study aimed to investigate the association between absolute lymphocyte count (ALC) and CMV to determine whether ALC could help to identify those at an increased risk of CMV infection and recurrence Methods Adults undergoing HSCT between 2011 and 2016 at Rigshospitalet, Denmark were included. Cox proportional hazards models investigated risk factors, including ALC, for CMV infection in the first year post-transplant and recurrent CMV infection 6 months after clearance and stopping CMV treatment for the first infection. For the primary outcome ALC was investigated as a time-updated risk factor lagged by 7 days, and for recurrent CMV, ALC measured at the time at the time of stopping treatment for the first CMV infection was investigated (+/- 7 days). Results Of the 352 HSCT recipients included, 57% were male, 40% received myeloablative conditioning, 42% had high risk (D-R+) CMV IgG serostatus at transplant and the median age was 56 (IQR 43-63). 143 (40.6%) patients had an episode of CMV DNAemia a median of 47 days after transplant (IQR 35-62). A lower current ALC (≤ 0.3 x109/L) was associated with a higher risk of CMV infection in univariate analysis compared to a high current ALC (> 1 x109/L). However, this association was attenuated after adjustment, particularly for acute graft versus host disease (Figure). 102 HSCT recipients were investigated for risk of recurrent CMV of which 41 (40.2%) had a recurrent CMV episode a median of 27 days (IQR 16-50) after stopping CMV treatment for the first infection. A lower ALC (≤ 0.3 x109/L) at the time of stopping CMV treatment was associated with a significantly higher risk of recurrent CMV after adjustment (Figure). A higher peak viral load (> 1500 IU/ml) during the first episode of CMV infection was also associated with an increased risk of recurrent CMV (aHR 2.47, 95%CI 1.00-6.10 compared to < 750 IU/ml). Association between absolute lymphocyte count (ALC) and risk of CMV infection and recurrent CMV within 6 months. **First CMV infection multivariable model also adjusted for sex, CMV serostatus, age, year of transplant, Charlson Comorbidity Index, Anti-thymocyte globulin (ATG) given, HLA donor-recipient matching, and acute graft versus host disease (time-updated) *Recurrent CMV infection multivariable model also adjusted for conditioning regimen, sex, CMV serostatus, age, year of transplant Anti-thymocyte globulin (ATG) given, HLA donor-recipient matching, and acute graft versus host disease and peak CMV viral load during the first CMV infection Conclusion A lower ALC at the time of stopping treatment for the first CMV infection was associated with an increased risk of recurrent CMV and could be used to help guide decisions for augmented CMV surveillance and clinical awareness of CMV disease symptoms in these patients. Disclosures All Authors: No reported disclosures

scholarly journals A Novel Secondary Neoplasm Following Allogeneic Hematopoietic Stem Cell Transplant: Mixed Donor-Recipient Primitive Mesenchymal Proliferation of the Liver

2021 ◽  
pp. 109352662110016
Author(s):  
Brian Earl ◽  
Zi Fan Yang ◽  
Harini Rao ◽  
Grace Cheng ◽  
Donna Wall ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Graft Versus Host Disease ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Post Transplant

Post-hematopoietic stem cell transplant secondary solid neoplasms are uncommon and usually host-derived. We describe a 6-year-old female who developed a mixed donor-recipient origin mesenchymal stromal tumor-like lesion in the liver following an unrelated hematopoietic stem cell transplant complicated by severe graft-versus-host disease. This lesion arose early post-transplant in association with hepatic graft-versus-host disease. At 12 years post-transplant, the neoplasm has progressively shrunken in size and the patient remains well with no neoplasm-associated sequelae. This report characterizes a novel lesion of mixed origin post-transplant and offers unique insights into the contribution of bone marrow-derived cells to extra-medullary tissues.

scholarly journals Tissue immune profiles supporting response to mesenchymal stromal cell therapy in acute graft-versus-host disease—a gut feeling

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Caroline Gavin ◽  
Erik Boberg ◽  
Lena Von Bahr ◽  
Matteo Bottai ◽  
Anton Törnqvist Andrén ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Mesenchymal Stromal Cell ◽  
Stromal Cell ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Cell Profile ◽  
Acute Graft

AbstractAcute graft-versus-host disease (aGvHD), post-allogeneic hematopoietic stem cell transplantation, is associated with high mortality rates in patients not responding to standard line care with steroids. Adoptive mesenchymal stromal cell (MSC) therapy has been established in some countries as a second-line treatment.Limitations in our understanding as to MSC mode of action and what segregates patient responders from non-responders to MSC therapy remain. The principal aim of this study was to evaluate the immune cell profile in gut biopsies of patients diagnosed with aGvHD and establish differences in baseline cellular composition between responders and non-responders to subsequent MSC therapy.Our findings indicate that a pro-inflammatory immune profile within the gut at the point of MSC treatment may impede their therapeutic potential. These findings support the need for further validation in a larger cohort of patients and the development of improved biomarkers in predicting responsiveness to MSC therapy.

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