Achievement of Durable and Complete Remission of Graft-versus-host Disease After Liver Transplantation With Ruxolitinib: A Case Report

Endo, Yutaka; Oshima, Go; Hibi, Taizo; Shinoda, Masahiro; Sakurai, Masatoshi; Koda, Yuya; Izawa, Yoshikane; Obara, Hideaki; Kitago, Minoru; Yagi, Hiroshi; Abe, Yuta; Murakami, Kentaro; Yamada, Yasuaki; Fukushima, Ayano; Yokose, Takahiro; Mori, Takehiko; Kuroda, Takeshi; Kitagawa, Yuko

doi:10.1097/tp.0000000000002904

Cited by 9 publications

(16 citation statements)

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“…After the discovery of TNF-α inhibitor, which activates regulatory T cells and suppresses GVHD progression [ 19 ], recent studies have used TNF-α inhibitor combined with steroid for GVHD-LT patients and shown better survival rates [ 6 , 20 ]. Another case report has shown that using Ruxolitinib, a JAK I/II inhibitor, can improve survival of GVHD-LT patients who have steroid and TNF-α inhibitor resistance [ 21 ], but these results were obtained from a small number of cases in heterogeneous patients [ 1 , 6 ]. A standard treatment regimen for GVHD-LT has not been established yet.…”

Section: Discussionmentioning

confidence: 99%

“…After reviewing previous chimerism studies of GVHD-LT, STR-PCR was found to be the most commonly used method ( Table 3 ), with almost all reports showing chimerism level above the detection sensitivity of STR-PCR [ 9 ]. Among patients with clinical progression in previous reports, surviving patients showed relatively low levels of chimerism or high levels of chimerism detected at a relatively late period (chimerism level 34%, detected at POD #48) [ 21 ]. To the best of our knowledge, our case series is the first report of GVHD-LT proven by INDEL-qPCR assay, a relatively powerful and new method compared to STR-PCR.…”

Section: Discussionmentioning

confidence: 99%

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Detecting Donor-Derived DNA by Real-Time PCR in Recipients Suspected of Graft-Versus-Host-Diseases After Liver Transplantation: A Case Series and Literature Review

Kim

et al. 2023

Ann Transplant

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Background Graft-versus-host disease (GVHD) after liver transplantation (LT) is a rare but fatal complication. GVHD diagnosis is usually based on clinical symptoms and pathologic confirmation. However, it is often misdiagnosed due to its non-specific symptoms. Here, we report the detection of donor-cell chimerism using peripheral blood (PB) donor-derived deoxyribonucleic acid (ddDNA) for 3 cases with suspected GVHD after LT (GVHD-LT) through real-time quantitative polymerase chain reaction (qPCR) assay targeting 39 insertions and/or deletions of chromosomes. Material/Methods The qPCR assay for detecting donor-cell chimerism was performed for 3 post-LT patients with suspected GVHD using KMRtype ® and KMRtrack ® assays (GenDx, Netherlands). The mean recipient/donor-cell fraction of informative markers unique to each recipient or donor was calculated. Results In Case 1, who received living donor LT (LDLT) from his daughter, initial sign was diarrhea at post-operative day (POD) #23. Case 2 received unrelated deceased donor LT and initial sign was cytopenia at POD #29. Case 3 received LDLT from her son and GVHD associated cytopenia was developed at POD #80. Average PB ddDNA fractions in post-transplant samples of cases 1, 2, and 3 were 39.68%, 78.38%, and 4.76%, respectively. Despite an active treatment including steroid and tumor necrosis factor-α inhibitor, 2 patients (cases 1 and 2) died due to multiple organ failures. Conclusions Early detection of donor-cell chimerism may help halt fatal progression of GVHD-LT. A qPCR test targeting INDEL of chromosomes would be a helpful procedure for timely diagnosis of GVHD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Detecting Donor-Derived DNA by Real-Time PCR in Recipients Suspected of Graft-Versus-Host-Diseases After Liver Transplantation: A Case Series and Literature Review

Kim

et al. 2023

Ann Transplant

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“…The activity of therapeutic JAK 1/2 blockade in GvHD has already been reported. 4,5 In our experience, ruxolitinib has exhibited an overall favorable safety profile and appears to be a viable option in treating cutaneous grade 2 GvHD after LT. Nevertheless, synergy between lowered immunosuppression and ruxolitinib cannot be ruled out.…”

mentioning

confidence: 89%

“…[1][2][3] We report the complete remission of a cutaneous grade 2 GvHD after LT treated with ruxolitinib, a Janus kinase (JAK)-1/2 inhibitor recently proposed in this field. 4,5 A 30-year-old female with cryptogenic cirrhosis underwent super-urgent ABO-incompatible deceased donor retransplantation for hepatic artery thrombosis. Given the rapid onset, worsening clin-Italy…”

mentioning

confidence: 99%

“…F I G U R E 1 (A) the generalized erythematous maculopapular rash involved any part of the body, including palms (1), feet (2), and the volar surfaces of extremities (3,4). (B) the skin biopsy demonstrating the basal cell layer vacuolization with lymphocytic infiltration in the dermis, and no evidence of eosinophil infiltration [hematoxylin-eosin (EE); ×10] (1), and the epidermal apoptotic keratinocyte (arrow) (EE; ×40) (2).…”

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confidence: 99%

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Complete resolution of a cutaneous grade 2 graft‐versus‐host disease after liver transplantation using ruxolitinib

Lauterio¹,

Carlis²,

Pugliano

et al. 2021

Clinical Transplantation

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Although graft-versus-host disease (GvHD) remains rare (1%-2%) and different therapeutic approaches have been proposed, mortality rates for this complication after liver transplantation (LT) remain extremely high. [1][2][3] We report the complete remission of a cutaneous grade 2 GvHD after LT treated with ruxolitinib, a Janus kinase (JAK)-1/2 inhibitor recently proposed in this field. 4,5 A 30-year-old female with cryptogenic cirrhosis underwent super-urgent ABO-incompatible deceased donor retransplantation for hepatic artery thrombosis. Given the rapid onset, worsening clin-Italy

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JAK Inhibitors in Solid Organ Transplantation

Assadiasl

Mojtahedi

Nicknam

2023

The Journal of Clinical Pharma

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Janus kinase (JAK) inhibitors are a novel group of immunosuppressive drugs approved to treat certain rheumatic and allergic disorders; however, their efficacy in the regulation of alloimmune responses after solid organ transplantation has not yet been elucidated. In the present review, we have summarized the results of in vitro, in vivo, experimental, and clinical trial studies about the efficacy and safety of JAK inhibitors in improving allograft survival in solid organ transplantations, including kidney, heart, lung, and liver transplants. Moreover, reports on administering JAK inhibitors to steroid‐resistant patients with graft versus host disease (GvHD) after solid organ transplantation have been reviewed. Overall findings are suggestive of a beneficial role for JAK inhibitors in organ transplantation: for example, they have been shown to improve allograft function, reduce the rate and score of acute rejection, downregulate the expression of proinflammatory cytokines and adhesion molecules, and decrease oxidative stress. However, the adverse effects of these drugs, in particular bone marrow suppression and infection, remain an obstacle.

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Achievement of Durable and Complete Remission of Graft-versus-host Disease After Liver Transplantation With Ruxolitinib: A Case Report

Cited by 9 publications

References 4 publications

Detecting Donor-Derived DNA by Real-Time PCR in Recipients Suspected of Graft-Versus-Host-Diseases After Liver Transplantation: A Case Series and Literature Review

Detecting Donor-Derived DNA by Real-Time PCR in Recipients Suspected of Graft-Versus-Host-Diseases After Liver Transplantation: A Case Series and Literature Review

Complete resolution of a cutaneous grade 2 graft‐versus‐host disease after liver transplantation using ruxolitinib

JAK Inhibitors in Solid Organ Transplantation

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