Imatinib-induced fulminant liver failure in chronic myeloid leukemia: role of liver transplant and second-generation tyrosine kinase inhibitors: a case report.

BACKGROUND: There is a worldwide problem of acute liver failure and mortality associated with remaining on the waiting for a liver transplant. In this study, we highlight results published in recent years by leading transplant centers in evaluating imatinib-induced acute liver failure in chronic myeloid leukemia and follow-up in liver transplantation. CASE PRESENTATION: A 36-year-old brown-skinned woman (mixed Brazilian race) diagnosed 1 year earlier with chronic myeloid leukemia was started after delivery of a baby and continued for 6 months with imatinib mesylate (selective inhibitor of Bcr-Abl tyrosine kinase), which induced liver failure. We conducted a literature review using the PubMed database for articles published through September 2017, and we demonstrate a role of liver transplant in this situation for imatinib-induced liver failure. We report previously published results and a successful liver transplant after acute liver failure due to imatinib-induced in chronic myeloid leukemia treatment. CONCLUSIONS: We report a case of a successful liver transplant after acute liver failure resulting from imatinib-induced chronic myeloid leukemia treatment. The literature reveals the importance of prompt acute liver failure diagnosis and treatment with liver transplant in selected cases.

Updating ECP action mechanisms.

Extracorporeal Photochemotherapy (ECP) consists in illumination of the patient's leukocytes in the presence of 8-Methoxy Psoralen (8-MOP) and its reinjection to the same patient. ECP is responsible for many cellular events, the most important being the induction of cell apoptosis. Apoptosis appears first in lymphocytes and activated lymphocytes (allo or auto) which are more sensitive and undergo faster apoptosis rather than other cells. Monocytes develop apoptosis later. The injection of apoptotic cells induces tolerance in patients with graft versus host disease (GvHD) and acute heart or lung graft rejection. In these patients, phagocytosis of apoptotic cells by antigen-presenting cells (APCs) and in particular dendritic cells is responsible for a shift from Th1 to Th2 immune response, an increase in anti-inflammatory cytokines such as interleukine 10 (IL-10) and Tumor Growth Factor Beta (TGF-ß), a decrease in pro-inflammatory cytokines and finally, for the proliferation of regulatory cells. Among CD4/CD25 positive cells, only CD4(+)CD25(hi) are T-regulatory cells (T-regs). One subpopulation of T-regs produces IL-10 and inhibits Th1 CD4 cells, whereas other populations act as suppressors and inhibit the cytotoxic T-cells responsible for organ rejection and GvHD in an antigen specific fashion. It is not clear why the injection of early apoptotic cells induces tolerance in GvHD and organ graft rejection, but in Sézary syndrome, it induces up-regulation of anti-tumor immune response. Immune response modulation (up- or down-regulation) after ECP depends on many factors: early apoptotic cell injection; anti-inflammatory environment; impaired function of dendritic cells; dendritic type 2 cell dominance, lead to immune tolerance, whereas late apoptotic or necrotic cell injection and pro-inflammatory cytokines enhance immune response. Therefore, immune response to ECP depends on various factors responsible for the diversity of its mode of action in different diseases and further investigations are required.

Transplantable liver production plan: "Yamaton"--liver project, Japan.

Organ grafts developed in the xenogeneic pig scaffold are expected to resolve most issues of donor safety and ethical concerns about living-donor liver transplantation in Japan. We have been working on so-called "Yamaton" projects to develop transplantable organs using genetically engineered pigs. Our goal is to produce chimeric livers with human parenchyma in such pigs. The Yamaton-Liver project demonstrated the proof of concept by showing that rat-mouse chimeric livers could develop in mice and be successfully transplanted into syngeneic or allogeneic rats. Under conventional immunosuppression, the transplanted livers showed long-term function and protection against rejection. Because chimeric liver grafts have xenogeneic components, additional strategies, such as humanization of pig genes, induction of hematopoietic chimeras in donors, and replacement of pig endothelial cells with human ones, might be required in clinical use. Our projects still need to overcome various hurdles but can bring huge benefits to patients in the future.

Allogeneic single lung transplantation in 7 cases / 中国组织工程研究

The present case report was designed to summarize the clinical experience of operative technique. lung preservation, lung perfusion, and perioperative management. Of 7 cases who underwent allogenic single lung transplantation (LT), 3 were idiopathic pulmonary fibrosis, 2 were chronic obstructive pulmonary disease, 1 was silicosis, emphysema, and bulla, and I was tuberculosis in both sides and presented with destroyed lung in one side. All donors were already brain death. Donor lungs were well preserved utilizing Euro-Colins liquid or low-potassium dextran solution. Donors and recipients were matched in blood type. Of 7 cases selected,5 received single right lung transplantation, and 2 received single left LT. End-to-end anastomosis was performed for pulmonary branches and pulmonary arteries. while atrium-to-atrium anastomosis was performed for pulmonary vein. Antibiotics and immunosuppressants were routinely used prior to and subsequent to LT. Following LT, heart and lung function, usage of antibiotics, and adjustment of immunosuppressant were monitored. Stomal complications regarding bronchus and pulmonary artery and vein did not appear in any patient. Five cases survived for about 2 months, one for approximately 1 year, and one for nearly 2 years. Four cases died of multi-organ failure caused by pulmonary infection, and one of severe pulmonary hemorrhage caused by aspergillus sydowi infection. Rejection occurred in 6 cases. One case sufiered from rejection three times. Selection of indication, selection and preservafton of donor lung, LT operation and pre-and post-operative management of LT have acquired satisfactory achievements. High mortality occurred in patients with preoperative poor cardiac and pulmonary functions and postoperative severe infections accompany with application of immunosuppressant.