High-Dose Melphalan Followed by Busulfan and Fludarabine Conditioning Prior to Allogeneic Stem Cell Transplantation in Elderly Patients with Active Acute Myeloid Leukemia-A Retrospective Single-Center Study.

In patients with relapsed or refractory (r/r) acute myeloid leukemia (AML), long-term survival in most cases can only be achieved with allogeneic hematopoietic stem cell transplantation. The introduction of sequential conditioning regimens has contributed to the steadily improving prognosis of r/r AML patients. As most studies mainly included younger patients, feasibility of sequential conditioning in elderly or comorbid patients remains subject of debate.

Early blast clearance during sequential conditioning prior to allogeneic stem cell transplantation in patients with acute myeloid leukaemia.

For patients with relapsed or refractory AML, sequential conditioning prior to allogeneic stem cell transplantation (alloSCT) is an established and potentially curative treatment option. Early response to treatment during conditioning indicates chemotherapy-responsive disease and may have prognostic value. We retrospectively evaluated blast clearance on day 5 after melphalan, administered 11 days prior to alloSCT as part of a sequential conditioning in 176 patients with active AML.

Enzymatic Activity Is Not Required for Phospholipase D Mediated TNF-α Regulation and Myocardial Healing.

Phospholipase D1 is a regulator of tumor necrosis factor-α expression and release upon LPS-induced sepsis and following myocardial infarction (MI). Lack of PLD1 leads to a reduced TNF-α mediated inflammatory response and to enhanced infarct size with declined cardiac function 21 days after ischemia reperfusion (I/R) injury. Deficiency of both PLD isoforms PLD1 and PLD2 as well as pharmacological inhibition of the enzymatic activity of PLD with the PLD inhibitor FIPI protected mice from arterial thrombosis and ischemic brain infarction.

Phospholipase D1 regulation of TNF-alpha protects against responses to LPS.

Sepsis is a systemic inflammatory disorder with organ dysfunction and represents the leading cause of mortality in non-coronary intensive care units. A key player in septic shock is Tumor Necrosis Factor-alpha (TNF-α). Phospholipase (PL)D1 is involved in the regulation of TNF-α upon ischemia/reperfusion injury in mice.