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The cellular reconstitution after childhood cancer therapy is associated with the risk of infection and efficacy of revaccination. Many studies have described the reconstitution after stem cell transplantation (SCT). The recovery after cancer treatment in children who have not undergone SCT has mainly been investigated in acute lymphoblastic leukemia (ALL), less for solid tumors. Here, we have examined the temporal evolution of total leukocyte, neutrophil and lymphocyte counts as surrogate parameters for the post-therapeutic immune recovery in a cohort of n = 52 patients with ALL in comparison to n = 58 patients with Hodgkin's disease (HD) and n = 22 patients with Ewing sarcoma (ES). Patients with ALL showed an efficient increase in blood counts reaching the age-adjusted lower limits of normal between 4 and 5 months after the end of maintenance therapy. The two groups of patients with HD and ES exhibited a comparably delayed recovery of total leukocytes due to a protracted post-therapeutic lymphopenia which was most pronounced in patients with HD after irradiation. Overall, we observed a clearly more efficient resurgence of total lymphocyte counts in patients aged below 12 years compared to patients aged 12 to 18 years. Our results underline that the kinetics of cellular reconstitution after therapy for HD and ES differ significantly from ALL and depend on treatment regimens and modalities as well as on patient age. This suggests a need for disease, treatment, and age specific recommendations concerning the duration of infection prophylaxis and the timing of revaccination., (© 2023. The Author(s).)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1-25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0-88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%-subcutaneous; 29%-intravenous; 1%-unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.

Methods for determination of genistein and its four new analogues in culture media have been developed to support studies on their potential anticancer activities. The investigated compounds were extracted from the media using liquid-liquid extraction with appropriate solvent. After evaporation of organic solvents each of the dry extracts was reconstituted in appropriate mobile phase. Reversed-phase HPLC was applied to quantitative determining of tested compounds. The methods are specific, sensitive and technically simple. They were used to evaluate concentration level of investigated compounds in experiments with human promyelocytic leukemia cells (HL-60 cell line).

The pharmacokinetics and toxicity of (-)-(S)-bromofosfamide ((2S)-(2-chloroethylamino)-3-(2-bromoethyl)-1,3,2-oxazaphosphorinae 2-oxide, CAS 146452-37-1, CBM-11) were determined in ten patients with non-small cell lung cancer following an oral dose of 1.38 g/m2 B.S.A. (Body Surface Area). The drug was given as a powder in gelatine capsules to fasting patients. Plasma samples were collected during the first 24 h after administration. All samples, after extraction with chloroform, were assayed by a reverse phase HPLC method using UV detection at 200 nm. Orally administered (-)-(S)-bromofosfamide showed relatively fast absorption kinetics. Peak concentration of 47 micrograms/ml was observed after 1 h. The average half-life was about 5 h. Toxicities associated with oral (-)-(S)-bromofosfamide therapy consisted of symptoms regarding the central nervous system, gastrointestinal tract and urinary tract. Neurotoxic symptoms were the most common clinically significant side effects and probably dose limiting.

(-)-(S)-Bromofosfamide ((2S)-(2-chloroethylamino)-3-(2-bromoethyl)-1,3,2-oxazaphosphorinane 2-oxide, CAS 146452-37-1, CBM-11) is a new potential anti-cancer drug, currently under investigation. Its pharmacokinetics and bioavailability were studied in female mice following intravenous and oral administration of the dose of 50 mg/kg. The compound was extracted from plasma samples using chloroform and analyzed by high-performance liquid chromatography with UV detection at 200 nm. Orally administered (-)-(S)-bromofosfamide was absorbed quickly, attaining a maximum level of 33.9 micrograms/ml at 5 min, and was eliminated with a half-life (t1/2) of about 0.9 h. The average half-life of intravenously administered (-)-(S)-bromofosfamide was about 0.7 h. The total plasma clearance (CL) and volume of distribution (Vd) were found to be 0.14 l/h and 4.92 l/kg, respectively. The absolute bioavailability of (-)-(S)-bromofosfamide after oral administration was 105%.

In this open, randomized, two way crossover, bioequivalence study, two 5 mg tablet preparations of glipizide (Glipizyd tabl. 5 mg, Tarchomińskie Zakłady Farmaceutyczne POLFA S.A., and Glibenese tabl. 5 mg, Pfizer), were compared in 24 healthy male volunteers. Pharmacokinetic variables (mean maximum plasma concentration, mean time to reach maximum plasma concentration, and the mean area under the plasma concentration-time curve) were not statistically significantly different for the two formulations. It can be concluded that the two tablet preparations of glipizide are likely to be bioequivalent.

A high-performance liquid chromatographic method for the determination of miconazole in human plasma is described. A solid-phase extraction was performed on an octadecyl (C18) cartridge. Miconazole was eluted with methanol, separated on a reversed-phase column and was measured by ultraviolet detection at 230 nm. The absolute extraction recovery from plasma samples was 85%. The limit of detection was established as 5 ng/ml. The coefficient of variation of the determination of plasma levels by this method over the standard curve concentration range was less than 10%, except with the concentration of 10 ng/ml. The plasma levels of miconazole in twelve healthy volunteers given a 250-mg oral dose of two tablet forms were determined by this method.