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Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene are detected in approximately 30% of acute myeloid leukemia (AML). The high frequency of FLT3 mutations, along with their adverse effect on prognosis, makes FLT3 a promising therapeutic target, and has spurred development of FLT3 inhibitors. First-generation inhibitors, including midostaurin and sorafenib, lack specificity for FLT3 and act on multiple kinases, whereas second-generation inhibitors, including gilteritinib, and quizartinib, are highly specific to FLT3 and are more potent than first-generation inhibitors. Several FLT3 inhibitors have recently gained regulatory approval worldwide, and several others are under development. The advent of FLT3 inhibitors has changed the standard treatment for FLT3-mutated AML in the frontline and relapsed/refractory settings and contributed to improved outcomes for this formidable AML subtype. However, numerous unresolved issues remain owing to rapid changes in practice. These include identification of optimum FLT3 inhibitors and combination therapies, the role of maintenance therapy, and the indication for allogeneic hematopoietic cell transplantation. Furthermore, strategies to overcome resistance to FLT3 inhibitors must be pursued. Results of ongoing and future studies will improve our ability to use FLT3 inhibitors more effectively, which should provide significant benefits to a wider range of patients.

The present study analyzed the incidence and clinical features of disseminated intravascular coagulation (DIC) developed in association with non-Hodgkin lymphoma (NHL). Two hundred thirty-six patients with newly diagnosed NHL were admitted to our institute since Jul. 2008 to Dec. 2014. Coagulation markers were evaluated in 161 of 236 patients at the time of diagnosis. DIC was diagnosed in 18 patients (11.2 %) based on the criteria established by Ministry of Health, Labor, and Welfare of Japan. All of the 18 patients had Ann-Arbor Stage IV advanced disease, and 17 patients were in poor performance status. Liver function panels, such as bilirubin, aminotransferases, serum choline esterase, and albumin levels, were worse in patients with DIC than those without DIC, indicating impaired production of coagulation factors. Importantly, DIC exerts significantly negative impact on prognosis of NHL; median survival of both groups was 176 versus 2430 days. The difference remains significant after statistically adjusting for age, performance status, Ann-Arbor stage, international prognostic index, and liver function panels. Nine of 18 patients with DIC received anti-coagulants, which failed to improve clinical outcome. Nevertheless, early recognition and intervention to DIC state may contribute to improve prognosis of NHL.

A 39-year-old man was admitted to our hospital to initiate highly active anti-retroviral therapy (HAART) for documented acquired immune deficiency syndrome. The HIV load was 2.5 million copies/mL and the CD4-positive lymphocyte count was only 52 cells/µL at presentation. The HAART regimen consisted of lamivudine and abacavir as the backbone, plus raltegravir and lopinavir/ritonavir as the base. The day after initiating HAART, his body temperature rose to 102.4 °F (39.1 °C), accompanied by elevated levels of liver enzymes, neutropenia, coagulopathies, and an extremely high serum ferritin level, prompting us to suspect hemophagocytic lymphohistiocytosis (HLH) and disseminated intravascular coagulation (DIC). To correct the coagulation abnormalities, recombinant thrombomodulin (rTM) was initiated at 375 U/kg. Surprisingly, fever resolved almost immediately, in parallel with dramatic decreases in serum levels of ferritin and liver enzymes and prompt normalization of coagulopathy with only two doses of rTM. The patient subsequently developed amebiasis, which was successfully treated using metronidazole. In summary, the use of rTM dramatically improved not only DIC, but also HLH, suggesting potent anti-inflammatory effects of the agent. Although further clinical reports and trials are needed, rTM appears to provide an additional therapeutic option in the management of HLH.