Squalene Peroxidation and Biophysical Parameters in Acne-Prone Skin: A Pilot "In Vivo" Study.

Nowadays, acne vulgaris therapies are often unsuccessful. One of the responsible factors for the formation of comedones and inflammatory lesions could be the peroxidation of squalene, a hydrocarbon representing one of the major components of human sebum. This peroxidation is increased by solar irradiation. The purpose of this work was to set up an in vivo method for the extraction and quantification of squalene from acne skin and to correlate the results with biophysical skin parameters such as sebum amount, protein content and TEWL. Healthy volunteers were used as control. The results obtained demonstrated that acne-prone skin had a major quantity of squalene, and, in the stratum corneum area, its peroxide form is present. Moreover, Spearman's rank correlation showed a positive correlation between sebum content and peroxide squalene and between porphyrin intensity and peroxide squalene.

Prevention and Treatment of Acute Myeloid Leukemia Relapse after Hematopoietic Stem Cell Transplantation: The State of the Art and Future Perspectives.

Allogeneic hematopoietic stem cell transplantation (HSCT) for high-risk acute myeloid leukemia (AML) represents the only curative option. Progress has been made in the last two decades in the pre-transplant induction therapies, supportive care, selection of donors and conditioning regimens that allowed to extend the HSCT to a larger number of patients, including those aged over 65 years and/or lacking an HLA-identical donor. Furthermore, improvements in the prophylaxis of the graft-versus-host disease and of infection have dramatically reduced transplant-related mortality. The relapse of AML remains the major reason for transplant failure affecting almost 40-50% of the patients. From 10 to 15 years ago to date, treatment options for AML relapsing after HSCT were limited to conventional cytotoxic chemotherapy and donor leukocyte infusions (DLI). Nowadays, novel agents and targeted therapies have enriched the therapeutic landscape. Moreover, very recently, the therapeutic landscape has been enriched by manipulated cellular products (CAR-T, CAR-CIK, CAR-NK). In light of these new perspectives, careful monitoring of minimal-residual disease (MRD) and prompt application of pre-emptive strategies in the post-transplant setting have become imperative. Herein, we review the current state of the art on monitoring, prevention and treatment of relapse of AML after HSCT with particular attention on novel agents and future directions.

Venetoclax penetrates in cerebrospinal fluid of an acute myeloid leukemia patient with leptomeningeal involvement.

Relapse at the central nervous system (CNS) in acute myeloid leukemia (AML) carries a dismal prognosis. Treatment options are limited to intrathecal therapy, high-dose cytarabine, high-dose methotrexate, and radiotherapy. Novel strategies are needed. Venetoclax has recently been approved by the FDA, in combination with hypomethylating agents or low-dose cytarabine, for elderly adults or patients ineligible for intensive chemotherapy affected by AML. However, little is known on its efficacy in patients with leptomeningeal involvement. Here, we present a case of a 52-year-old patient affected by AML relapsed at CNS after allogeneic bone marrow transplantation who was treated with venetoclax. We evaluated the concentration of the drug in cerebrospinal fluid (CSF) by HPLC MS/MS method on three different occasions to verify the penetration of the drug through the brain-blood barrier and we observed that the concentration in CSF was similar to the IC50 established in vitro.

Low content of clonogenic progenitors on day+18 is associated with acute graft-versus-host disease and predicts transplant-related mortality.

A marrow reaction associated with acute-graft-versus-host disease (a-GVHD) has been demonstrated in experimental models; its existence in human transplantation is controversial. The aim of the present study was to investigate whether clonogenic marrow precursors are an early marker for a-GVHD and transplant-related mortality (TRM). We prospectively studied 133 patients for colony-forming units-granulocyte-monocyte (CFU-GM) at day +18/+19 posttransplantation. CFU-GM frequency below the 25th percentile was predictive of an acute GVHD score I°-IV° when evaluated in multivariate logistic regression analysis (odds ratio = 13.551, 95% confidence interval [CI]: 1.583-116.031, p = 0.01). In the group with a clonogenic frequency below the 25th percentile, the cumulative incidence of GVHD grades II-IV was significantly more frequent with respect to the group with a frequency greater than the 25th percentile, 86% versus 54% (Gray test: p = 0.02). In multivariate Cox proportional analysis, a CFU-GM frequency below the 25th percentile at day +18 was associated with reduced overall survival (OS) (hazard ratio = 1.778, 95% CI: 1.022-3.093, p = 0.04). Patients with a frequency of CFU-GM greater than the 25th percentile had increased TRM with respect to patients with a clonogenic cell frequency greater than the 25th percentile (33.5% vs. 13.0%, p = 0.01). Patients were divided based on median content of viable CD34+ cells, and measurement of viable CD34+ cells was predictive for OS (p = 0.005) and TRM (p = 0.003). A weak correlation was observed between CFU-GM frequency in marrow at day +18 and levels of IL-2 receptor (IL-2R) in plasma (r = -0.226, p = 0.03). We conclude that marrow progenitor cell counts, on day +18 may be a useful marker for identifying patients at risk for severe a-GVHD, TRM, and inferior survival.

Plerixafor on-demand in association with low-dose cyclophosphamide and G-CSF in the mobilization of patients with multiple myeloma: High effectiveness, low toxicity, and affordable cost.

In CD34+ cells mobilization of patients with multiple myeloma (MM), the use of Cyclophosphamide (CTX) at a dose of 2 g/m2 has low efficacy although also lower toxicity. The suboptimal mobilizing effect of low-dose CTX, however, may be overcome by plerixafor (PLX) on demand. We conducted a prospective multicenter study in 138 patients with MM to evaluate CTX 2 g/m2 in association with granulocyte-colony stimulating factor (G-CSF) and on-demand PLX. We compared results with a historical group of MM patients (n = 138) mobilized using CTX at a dose of 4 g/m2. CD34+ cells greater than 2 × 106/kg in max three aphereses were harvested in 98.6% of patients in the on-demand PLX study group while in 84.0% in the historical group, (p = 0.0001). In the on-demand-PLX study group, a successful harvest greater than 5 × 106/kg in max three aphereses was observed in 85.5% of patients versus 62.3% of patients in the historical control group, (p=0.0001). In the on-demand-PLX study group, 4.3% (6/138) of patients had febrile complications. Salvage mobilization in the on-demand PLX study group was 1.4%. In conclusions, on-demand PLX + CTX 2 g/m2 + G-CSF 10 µg/kg has higher efficacy and lower toxicity compared with CTX 4 g/m2 + G-CSF. An analysis of costs is presented.