Allogeneic hematopoietic stem cell transplantation from matched related donors for acute myeloid leukemia.

INTRODUCTION: In patients with acute myeloid leukemia (AML), allogeneic hematopoietic stem cell transplantation (HSCT) remains the priority treatment option as the most effective prevention of relapse. When an HLA-matched sibling is available, these transplants are preferred. OBJECTIVES: We stratificated patients according to risk, disease state (an active disease, the 1st or 2nd complete remission ‒ CR1, CR2, which was achieved after the 1st or 2nd induction) and type of graft (from brother or sister). Finally, the overall survival (OS) of patients in individual groups was evaluated. MATERIAL AND METHODS: The retrospective single-center study included 104 transplantations in 97 adult patients with AML who underwent HSCT from matched sibling donor in a period of 10 years between January 2011 and December 2020. RESULTS: 54 patients (55.7%) were alive as of the January 1, 2022. The median OS of the entire group, as well as the cohort with favorable (5y-OS 75.0%) and intermediate prognosis risk (5y‒OS 78.5%) was not reached. We found that patients, who required second induction therapy to achieve CR, had poorer OS after allogeneic HSCT, median 20.7 months (95% CI, 6.5-35.5) than those who achieved CR after first induction, median not reached (95% CI, 63.5‒63.5, p=0.0048). Statistically significant effect on OS shows transplantation in CR2 (HR 6.76, CI 95% 2.19‒20.80, p=0.0009), In addition, this parameter influenced OS more than achieving CR up to the 2nd induction course (HR 2.44, CI 95% 1.17‒5.11; p=0.0180) or entry to transplantation without CR (HR 2.81, CI 95% 1.09‒7.26; p=0.0326). CONCLUSION: The results presented in the work show the high efficiency of HSCT in each risk group. The number of induction therapies required to achieve CR is a good prognostic factor. The gender of a sibling has no impact on OS (Tab. 11, Fig. 7, Ref. 18). Text in PDF www.elis.sk Keywords: acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation, overall survival, remission status, donor tender.

Implementation of Modern Therapeutic Drug Monitoring and Lipidomics Approaches in Clinical Practice: A Case Study with Colistin Treatment.

Nowadays, lipidomics plays a crucial role in the investigation of novel biomarkers of various diseases. Its implementation into the field of clinical analysis led to the identification of specific lipids and/or significant changes in their plasma levels in patients suffering from cancer, Alzheimer's disease, sepsis, and many other diseases and pathological conditions. Profiling of lipids and determination of their plasma concentrations could also be helpful in the case of drug therapy management, especially in combination with therapeutic drug monitoring (TDM). Here, for the first time, a combined approach based on the TDM of colistin, a last-resort antibiotic, and lipidomic profiling is presented in a case study of a critically ill male patient suffering from Pseudomonas aeruginosa-induced pneumonia. Implementation of innovative analytical approaches for TDM (online combination of capillary electrophoresis with tandem mass spectrometry, CZE-MS/MS) and lipidomics (liquid chromatography-tandem mass spectrometry, LC-MS/MS) was demonstrated. The CZE-MS/MS strategy confirmed the chosen colistin drug dosing regimen, leading to stable colistin concentrations in plasma samples. The determined colistin concentrations in plasma samples reached the required minimal inhibitory concentration of 1 µg/mL. The complex lipidomics approach led to monitoring 545 lipids in collected patient plasma samples during and after the therapy. Some changes in specific individual lipids were in good agreement with previous lipidomics studies dealing with sepsis. The presented case study represents a good starting point for identifying particular individual lipids that could correlate with antimicrobial and inflammation therapeutic management.

A simple and green capillary electrophoresis-mass spectrometry method for therapeutic drug monitoring of colistin in clinical plasma samples.

Colistin and other polymyxin antibiotics have become increasingly used in clinical settings as a result of treating multidrug-resistant infections in critically ill patients. The highly variable pharmacokinetics of colistin in these patients is accompanied by a high risk of toxicity or underdosing. An effective tool that allows rational optimization of the drug dosage regimen is therapeutic drug monitoring. Therefore, there is a need to dispose with appropriate, sensitive, and accurate analytical methods. Here, a simple, specific, and accurate on-line capillary electrophoresis - tandem mass spectrometry method was developed and applied for the first time to determine colistin in human plasma. Protein precipitation using acidified acetonitrile was the solitary procedure used to achieve sample pretreatment. A bare fused silica capillary was employed for the separation process, and the background electrolyte used was 50 mM formic acid (pH 2.54). The FDA's bioanalytical method validation guidelines were followed in the validation of the proposed method. For colistin A and colistin B, favorable performance and validation parameters were obtained (such as linearity, limit of detection, lower limit of quantitation, intra-day and inter-day precision, accuracy, and stability).The validated method was then effectively used to analyze real clinical samples taken from patients who were in critical condition. Our newly developed method is comparable with previously published liquid chromatography approaches and has the potential to be applied in the therapeutic monitoring of colistin in routine clinical laboratories. Moreover, according to the greenness assessment, the developed capillary electrophoresis - mass spectrometry method represents a very interesting green and sustainable tool in the field of bioanalysis.

Treatment of Adults and Young Adults with Acute Lymphoblastic Leukemia: Real Life Data from Two Centers in Slovakia.

INTRODUCTION: The results of treatment of acute lymphoblastic leukemia (ALL) from the low population countries are missing in the literature. PATIENTS AND METHODS: We retrospectively examined biological characteristics and survival of 90 patients with ALL. RESULTS: At median follow-up 17 months, 52 men and 38 women were eligible for the analysis with median age 43 years (18-74). As for the risk stratification, 25.6% of patients were in standard risk, 46.7% in high risk and 27.8% in very high-risk group. Complete remission achieved 88.9% of patients. We observed 5.6% of induction deaths and 4.5% of resistant disease. 47.8% of the patients underwent allogeneic stem cell transplantation (alloSCT), 59% in the young adults (YA; < 40 years) and 40% in adult group (≥ 40 years). We noticed 32.6% relapses overall with median survival of relapsed patients 3.9 months. YA patients had longer survival than adults: 3-year overall survival (OS) 65.0% vs 30.2%; (HR = 0.36; 95% CI 0.2-0.64; P = .001) and event free survival (EFS) 51.5% vs 21.9%; (HR = 0.45; 95% CI 0.26-0.78; P = .005). There was significant difference in 3-year EFS between risk groups in YA patients 90.9%, 48.0%, 11.4%; (P = .001). OS after alloSCT individually for the YA was 62.6% and for adults 39.1%, hazard ratio (HR) = 0.49 (95% CI 0.20-1.21); (P = .095). We observed 14% early deaths, 25.6% late deaths and 3 relapses (7%) after allogeneic stem cell transplantation. CONCLUSIONS: Our data proved that even in a low population country similar result can be achieved as in larger ones while using well designed adapted protocols from leukemic study groups.