Recent Advances in Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia.

Allogeneic hematopoietic stem cell transplantation remains an important treatment modality for patients with acute myeloid leukemia (AML). Recent advances have extended donor availability for patients without matched donors. Transplantation is now increasingly offered to older patients, including those above 70 years and less fit individuals. Better prognostic models are being developed. Proceeding faster to transplantation with haploidentical donors if an urgent transplant is needed, such as in patients with detectable minimal residual disease, may allow more patients to get to transplant, and it is hoped more will be cured from their disease. With continuous improvements in treatment-related toxicity and mortality, relapse has become the most important cause of treatment failure, and novel approaches are needed to make the next big leap in the treatment of this disease with transplantation. In this review we aim to summarize recent advances and provide future research directions in the transplantation for patients with AML.

Haploidentical transplantation for acute myeloid leukemia patients with minimal/measurable residual disease at transplantation.

There have been conflicting results regarding the impact of minimal/measurable disease at transplant on acute myeloid leukemia (AML) outcomes after haploidentical transplantation (haplo-SCT). We assessed the impact of pre-transplant disease status on post-transplant outcomes of 143 patients treated with haplo-SCT using fludarabine-melphalan (FM) conditioning and post-transplant cyclophosphamide (PTCy). With a median follow-up of 29 months, the two-year PFS for all patients was 41%. Compared to patients in complete remission (CR) at transplant, those with active disease (n = 29) and CR with incomplete count recovery (CRi) (n = 39) had worse PFS. They had hazard ratios (HR) of 3.5 (95% CI: 2.05-6.1; P < .001) and 2.3 (95% CI: 1.3-3.9; P = .002), respectively. Among patients who were in CR at transplant, there were no differences in PFS between those who had minimal residual disease (MRD) positive (n = 24), and MRD negative (n = 41) (HR 1.85, 95%CI: 0.9-4.0; P = .1). In multivariable analysis for patients in CR, only age was predictive for outcomes, while MRD status at transplant did not influence the treatment outcomes. Our findings suggest that haplo-SCT with FM conditioning regimen and PTCy-based GVHD prophylaxis has a protective effect, and may potentially abrogate the inferior outcomes of MRD positivity for patients with AML. Patients with positive MRD may benefit from proceeding urgently to a haplo-SCT, as this does not appear to negatively impact transplant outcomes.

Kinins and microglial responses in bipolar disorder: a neuroinflammation hypothesis.

Bipolar disorder (BD) is a severe psychiatric disorder that affects up to 15% of the worldwide population. Characterized by switches in mood between mania and depression, its etiology is still unknown and efforts have been made to elucidate the mechanisms involved in first episode, development and progression of the disorder. Microglia activation, abnormal activity of GSK-3ß and reduction in neurotrophic factor expression related to neuroinflammatory processes have been indicated to be part of the disorder's pathophysiology. Lithium, the main mood stabilizer used for the treatment and prevention of relapses, acts as an anti-inflammatory agent. Based on that, here we suggest a neuroinflammatory pathway for would be BD progression, in which microglia activation states modulated via constitutive induction of kinin-B1 receptor and reduction of kinin-B2 receptor expression and activity.