Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease

Svegliati, Silvia; Olivieri, Attilio; Campelli, Nadia; Luchetti, Michele Maria; Poloni, Antonella; Trappolini, Silvia; Moroncini, Gianluca; Bacigalupo, Andrea; Leoni, Pietro; Avvedimento, Enrico V.; Gabrielli, Armando

doi:10.1182/blood-2007-01-071043

Cited by 197 publications

(163 citation statements)

References 14 publications

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“…Their actions are mainly by reducing the amount of fibrosis in conjunction by counteracting effects of TGFβ and platelet-derived growth factor (PDGF). These findings are supported by the presence of agonistic antibodies found in cGVHD to the receptors of these cytokines [133]. In a phase I/II trial, imatinib at 100 mg/ day was used to treat 19 patients, both adult and pediatric, who had refractory sclerotic cGVHD of skin, gastrointestinal tract, or cGVHD of lungs.…”

Section: Imatinibmentioning

confidence: 92%

State-of-the-art acute and chronic GVHD treatment

Jamil

Mineishi

2015

Int J Hematol

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owing to the advancement in reduced intensity conditioning (RIC) and in patients without HLA-matched donors due to the use of cord blood and haploidentical HSCT [4][5][6]. Although marked improvement has been made in supportive care, immunosuppressive therapy and DNA-based Human Leukocyte Antigen (HLA) typing, graft vs host disease (GVHD) remains a major cause of morbidity and non-relapse mortality among allogeneic HSCT recipients. It was first described by Billingham in 1966 as a syndrome where immunocompetent T cells from the donor recognize and damage the host tissue in an immunocompromised recipient. It presents with heterogeneous symptoms involving multiple organ systems including gastrointestinal tract, skin, mucosa, liver and lungs [7]. In the past clinical features occurring within 100 days after HSCT was called acute GVHD (aGVHD) and those happening after 100 days were labeled chronic GVHD (cGVHD) [8,9]. This definition was rather unsatisfactory thus National Institute of Health (NIH) consensus criteria were developed and have been revised. The criteria have added new categories such as late-onset aGVHD (acute GVHD occurring after 100 days) and overlap syndrome which includes features of both acute and chronic GVHD to the classification, and also have introduced new definitions for organ system involvement [10][11][12]. The categorization of acute vs chronic GVHD is based on the combination of clinical symptoms rather than the time of onset. Depending upon a number of variables associated with patients, donors, and types of transplant, the incidence of aGVHD varies with incidence of grade II-IV GVHD at 40 % in matched related donor (MRD) transplant to 50 % in MUD transplant. The main risk factors for aGVHD include degree of HLA mismatch, age of the patient, previous all immunization of the donor and the kind of GVHD prophylaxis used. About 30-70 % of allogeneic HSCT recipients alive after 100 days will Abstract Graft-versus-host disease (GVHD) remains as the major obstacle for successful hematopoietic stem cell transplant (HSCT). Roughly half of the patients undergoing HSCT develop GVHD which requires treatment, and above 10 % of the patient may die because of it. However, GVHD presents with anti-tumor activity, called graft-versus-tumor (GVT) effect, and it carries significant anti-tumor activity, thus suppressing GVHD completely may increase the relapse of original disease. Thus, it is important to control GVHD to the appropriate level.

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Section: Imatinibmentioning

confidence: 92%

State-of-the-art acute and chronic GVHD treatment

Jamil

Mineishi

2015

Int J Hematol

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“…1 Alone, trisomy 8 does not appear to be sufficient for leukemogenesis but may be associated with an increased risk of myeloid malignancy. 1 To investigate further the contribution of þ 8 to AML, we determined the gene expression signature associated specifically with this numerical chromosomal abnormality using large, previously reported, AML microarray data sets 2,3 and data sets derived from AML cell lines. We have identified a novel association between HOXA gene upregulation and þ 8 AML providing new insight into the potential contribution of þ 8 to AML pathogenesis.…”

Section: Conlfict Of Interestmentioning

confidence: 99%

“…1,2 On the other hand, imatinib, a potent tyrosine kinase inhibitor, is known to inhibit the activation of those pathways, 3 and has been investigated for the treatment for steroid-refractory skin cGVHD. 4,5 Although these studies showed that imatinib was effective as salvage treatment for refractory cGVHD, it remains unknown whether the prophylactic imatinib after SCT affects the incidence and severity of cGVHD.…”

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confidence: 99%

Prophylactic impact of imatinib administration after allogeneic stem cell transplantation on the incidence and severity of chronic graft versus host disease in patients with Philadelphia chromosome-positive leukemia

et al. 2010

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“…12 The fibrotic change in cGVHD, especially extensive cGVHD, was also associated with the production of autoantibodies against platelet-derived growth factor receptor. 13 Rituximab, which depletes B cells in vivo, was reported to have a preventive and curative potential for GVHD. [14][15][16] However, the optimal strategy for B-cell depletion has yet to be investigated.…”

Section: Introductionmentioning

confidence: 99%

Allogeneic HY antibodies detected 3 months after female-to-male HCT predict chronic GVHD and nonrelapse mortality in humans

Nakasone¹,

Tian

Sahaf³

et al. 2015

Blood

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Key Points• Detection of multiple HY-Abs at 3 months post-F→M HCT predicts cGVHD incidence, severity, and nonrelapse mortality.• Patients with a high HY score may be good candidates for cGVHD prevention trials, especially those targeting allogeneic B cells.Allogeneic antibodies against minor histocompatibility antigens encoded on the Y chromosome (HY-Abs) develop after hematopoietic cell transplant (HCT) of male recipients with female donors (F→M). However, the temporal association between HY-Ab development and chronic graft-versus-host disease (cGVHD) has yet to be elucidated. We studied 136 adult F→M HCT patients, with plasma prospectively collected through 3 years posttransplant, and measured immunoglobulin G against 6 H-Y antigens. Multiple HY-Abs were frequently detected beginning at 3 months posttransplant: 78 (57%) of F→M patients were seropositive for at least 1 of the 6 HY-Abs, and 3-month seropositivity for each HYAb was associated with a persistent seropositive response throughout the posttransplant follow-up period (P < .001 in each). There were no associations between pretransplant features and 3-month overall HY-Ab development. Detection of multiple HY-Abs at 3 months (represented by HY score) was significantly associated with an increased risk of cGVHD (P < .0001) and nonrelapse mortality (P < .01). Compared to clinical factors alone, the addition of HY score to clinical factors improved the predictive potential of cGVHD (P < .01). Monitoring HY-Ab development thus stratifies cGVHD risk in F→M HCT patients and may support preemptive prophylaxis therapy for cGVHD beginning at 3 months posttransplant. (Blood. 2015;125(20):3193-3201)

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Stimulatory autoantibodies to PDGF receptor in patients with extensive chronic graft-versus-host disease

Cited by 197 publications

References 14 publications

State-of-the-art acute and chronic GVHD treatment

State-of-the-art acute and chronic GVHD treatment

Prophylactic impact of imatinib administration after allogeneic stem cell transplantation on the incidence and severity of chronic graft versus host disease in patients with Philadelphia chromosome-positive leukemia

Allogeneic HY antibodies detected 3 months after female-to-male HCT predict chronic GVHD and nonrelapse mortality in humans

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