Tirosin Kinase Inhibitors in Chronic Graft versus Host Disease: From Bench to Bedside

Olivieri, Jacopo; Coluzzi, Sabrina; Attolico, Imma; Olivieri, Attilio

doi:10.1100/2011/924954

Cited by 28 publications

(19 citation statements)

References 164 publications

(194 reference statements)

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“…A reasonable interpretation of this result is that 3/4 patients who died of DLI-related complications received DLI on a bulk-dose, which results in a high incidence and mortality of GVHD and marrow aplasia [16]. In addition, we observed that 2 patients with chronic GVHD obtained a complete remission after imatinib-based treatments, which might be caused by imatinib regulating GVHD [39].…”

Section: Discussionsupporting

confidence: 54%

Is Imatinib Maintenance Required for Patients with Relapse Chronic Myeloid Leukemia Post-Transplantation Obtaining CMR? A Pilot Retrospective Investigation

et al. 2013

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Imatinib can induce complete molecular remission (CMR) in relapse chronic myelogenous leukemia (CML) after allogeneic hematopoietic stem cell transplantation, but it is indefinite whether imatinib is required to maintain CMR. We retrospectively reviewed 37 relapse CML post-transplants treated with imatinib (n = 20) or donor lymphocyte infusion (DLI) (n = 17). The rate of CMR was 85% and 76.47% (P = 0.509) and treatment-related mortality was 0% and 29.4% (P = 0.019), respectively, in imatinib and DLI groups. Fifteen patients obtaining CMR voluntarily ceased imatinib, and did not experience relapse. The 8-year overall survival (OS) after relapse was 85%±8% and 40.3±12.1% (P = 0.017), and disease-free survival (DFS) after relapse was 85%±8% and 40.3±12.1% (P = 0.011), respectively, in imatinib and DLI groups. Imatinib resulted in higher OS and DFS than that of DLI in relapse CML. Imatinib maintenance might not be required for patients with relapse CML post-transplants after they achieved full donor chimerism and CMR.

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Section: Discussionsupporting

confidence: 54%

Is Imatinib Maintenance Required for Patients with Relapse Chronic Myeloid Leukemia Post-Transplantation Obtaining CMR? A Pilot Retrospective Investigation

et al. 2013

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“…8 Imatinib showed promising responses in 2 small cohorts of patients with SR-cGVHD, without major toxicities 9,10 ; other studies have shown less favorable results. [11][12][13] Imatinib is a potent dual inhibitor of both transforming growth factor-b and platelet-derived growth factor receptor (PDGF-R) pathways 14 ; these 2 cytokines are both involved in the fibrogenic and inflammatory processes of several fibrotic diseases, 15 as suggested by a murine model of cGVHD 16 and by recent data on cGVHD with fibrotic features (ScGVHD) and systemic scleroderma (SS). 17,18 Moreover, imatinib inhibits T-cell proliferation, 19 as suggested by clinical improvement in patients with chronic myelogenous leukemia and concomitant autoimmune diseases who are receiving imatinib treatment.…”

Section: Introductionmentioning

confidence: 99%

Long-term outcome and prospective validation of NIH response criteria in 39 patients receiving imatinib for steroid-refractory chronic GVHD

Olivieri

Cimminiello

Corradini

et al. 2013

Blood

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Key Points• Efficacy of imatinib in steroidrefractory chronic GVHD was prospectively compared across 3 different response systems, with high agreement.• Validity of quantitative-based assessment of response with NIH criteria was confirmed by its prognostic impact on longterm survival.Forty adults aged 28 to 73 years were entered into a prospective trial of imatinib for the treatment of steroid-refractory chronic graft-versus-host disease (SR-cGVHD). After 6 months, intention-to-treat (ITT) analysis of 39 patients who received the drug, regardless of the duration of treatment, revealed 14 partial responses (PR), 4 minor responses (MR) with relevant steroid sparing (46%) according to Couriel criteria, and 20 ‡ PR (51.3%), as per the National Institutes of Health (NIH) criteria and NIH severity score changes. The best responses were seen in the lungs, gut, and skin (35%, 50%, and 32%, respectively). After a median follow-up of 40 months, 28 patients were alive, with a 3-year overall survival (OS) and event-free survival of 72% and 46%, respectively. The 3-year OS was 94% for patients responding at 6 months and 58% for nonresponders according to NIH response, suggesting that these criteria represent a reliable tool for predicting OS after second-line treatment. Monitoring of anti-platelet-derived growth factor receptor (PDGF-R) antibodies showed a significant decrease in PDGF-R stimulatory activity in 7 responders, whereas it remained high in 4 nonresponders. This study confirms the efficacy of imatinib against SR-cGVHD and suggests that the response at 6 months significantly predicts long-term survival. This study is registered at https://eudract.ema.europa.eu/ (EUDRACT

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“…1 Cutaneous cGVHD can simulate a wide variety of autoimmune skin diseases and classically has 2 major phenotypes: lichenoid (flat-topped, pink or violaceous, scaly papules) and sclerodermoid (areas of sclerotic skin). Skin is the most common organ affected in cGVHD (75%) at the time of diagnosis.…”

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confidence: 99%

Chronic Graft-Versus-Host Disease Presenting as Eosinophilic Fasciitis

Ganta

Chatterjee²,

Pohlman³

et al. 2015

JCR Journal of Clinical Rheumatology

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Chronic graft-versus-host disease (cGVHD) is one of the main late complications of allogeneic hematopoietic stem cell transplant and a major contributor to the mortality and morbidity in surviving recipients. Skin is the most common involved organ in cGVHD and may mimic a wide spectrum of dermatological conditions in its clinical and histopathologic manifestations. Some of the commonly simulated diseases are scleroderma, morphea, and lichen sclerosus. Chronic GVHD simulating eosinophilic fasciitis (EF) is relatively rare, frequently presenting with skin induration, a typical "peau d'orange" appearance, peripheral blood eosinophilia, myalgia, arthralgia, and arthritis leading to joint contractures in severe cases.Diagnosis is based on clinical manifestations and histopathology. Treatment is challenging because most cases are refractory to first-line therapy of glucocorticoids and calcineurin inhibitors (CNIs), and there is no standard second-line therapy.We report a comprehensive review of literature on all reported cases of CGVHD presenting as EF. We also describe an additional interesting case of cGVHD presenting as EF that was resistant to traditional therapy of high-dose glucocorticoids and cyclosporin A, but showed complete resolution of skin manifestations after addition of imatinib.Chronic GVHD presenting as EF is a rare variant of sclerodermatous cGVHD. Diagnosis is difficult, and treatment of cGVHD mimicking EF remains a therapeutic challenge because of obscure pathogenesis and poor response to traditional immunosuppressive medications. Emerging insights into the pathogenesis of cGVHD have resulted in the development of novel targeted therapies, which may improve outcomes and should be attempted in this subset of the disease. Larger studies are warranted to substantiate these preliminary findings.

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Tirosin Kinase Inhibitors in Chronic Graft versus Host Disease: From Bench to Bedside

Cited by 28 publications

References 164 publications

Is Imatinib Maintenance Required for Patients with Relapse Chronic Myeloid Leukemia Post-Transplantation Obtaining CMR? A Pilot Retrospective Investigation

Is Imatinib Maintenance Required for Patients with Relapse Chronic Myeloid Leukemia Post-Transplantation Obtaining CMR? A Pilot Retrospective Investigation

Long-term outcome and prospective validation of NIH response criteria in 39 patients receiving imatinib for steroid-refractory chronic GVHD

Chronic Graft-Versus-Host Disease Presenting as Eosinophilic Fasciitis

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