No abstract

Acute and chronic graft-versus-host disease (GVHD) remain major obstacles for successful allogeneic hematopoietic cell transplantation. Extracorporeal photopheresis (ECP) modulates immune cells, such as alloreactive T cells and dendritic cells, and improves GVHD target organ function(s) in steroid-refractory GVHD patients. We performed a systematic review to evaluate the totality of evidence regarding the efficacy of ECP for treatment of acute and chronic steroid-refractory or steroid-dependent GVHD. Nine studies, including 1 randomized controlled trial, met inclusion criteria, with a total of 323 subjects. In pooled analyses, overall response rates (ORR) were .69 (95% confidence interval [CI], .34 to .95) and .64 (95% CI, .47 to .79) for acute and chronic GVHD, respectively. In acute GVHD organ-specific responses, ECP resulted in the highest ORR for cutaneous, with .84 (95% CI, .75 to .92), followed by gastrointestinal with .65 (95% CI, .52 to .78). Similar response rates were seen in chronic GVHD involving the skin and gastrointestinal tract. Conversely, ORR for chronic GVHD involving the lungs was only .15 (95% CI, 0 to .5). In chronic GVHD, grades 3 to 4 adverse events were reported at .38 (95% CI, .06 to .78). ECP-related mortality rates were extremely low. Rates of immunosuppression discontinuation were .55 (95% CI, .40 to .70) and .23 (95% CI, .07 to .44) for acute and chronic GVHD, respectively. In summary, albeit limited by numbers of available studies, pooled analyses of prospective studies demonstrate encouraging responses after ECP treatment in acute and chronic GVHD after failing corticosteroids. Further research efforts are needed to improve organ-specific responses.

Sorafenib treatment after HSCT appears to be feasible and highly effective with dose individualization according to patient tolerability. Further analysis is needed to evaluate the immunomodulating role of sorafenib after HSCT. The data from the current support prospective controlled trials of sorafenib after HSCT. Cancer 2017;123:2867-74. © 2017 American Cancer Society.

No abstract

FMS-like tyrosine kinase 3 (FLT3) is one of the most commonly mutated genes in AML. FLT3 is mutated in ~30% of patients with AML, either by internal tandem duplications (FLT3-ITD) of the juxta-membrane domain or by a point mutation, usually involving the tyrosine kinase domain. Several FLT3 tyrosine kinase inhibitors are being evaluated in multiple studies aiming at improving outcomes. The most widely used is sorafenib, a potent multikinase inhibitor approved for hepatocellular carcinoma and renal cell carcinoma. Sorafenib monotherapy or in combination with conventional chemotherapy, has been evaluated in various settings in AML, including front-line, relapsed or refractory disease including post-allograft failures and, more recently, as post-transplant maintenance therapy. Encouraging data have emerged with several other agents like lestaurtinib, midostaurin, crenolanib, gilteritinib and quizartinib. Although transient responses to FLT3 inhibitors are often observed in case of disease relapse, the most promising approach is the use of FLT3 inhibitors either in combination with induction chemotherapy or as consolidation/maintenance therapy after allogeneic hematopoietic cell transplantation. In this review, we summarize the clinical data on sorafenib and other FLT3 inhibitors in AML.