Assessment of Motor Unit Potentials Duration as the Biomarker of DT-DEC01 Cell Therapy Efficacy in Duchenne Muscular Dystrophy Patients up to 12 Months After Systemic-Intraosseous Administration.

Duchenne muscular dystrophy (DMD) is a lethal X-linked disease caused by mutations in the dystrophin gene, leading to muscle degeneration and wasting. Electromyography (EMG) is an objective electrophysiological biomarker of muscle fiber function in muscular dystrophies. A novel, DT-DEC01 therapy, consisting of Dystrophin Expressing Chimeric (DEC) cells created by fusing allogeneic myoblasts from normal donors with autologous myoblasts from DMD-affected patients, was assessed for safety and preliminary efficacy in boys of age 6-15 years old (n = 3). Assessments included EMG testing of selected muscles of upper (deltoideus, biceps brachii) and lower (rectus femoris and gastrocnemius) extremities at the screening visit and at 3, 6, and 12 months following systemic-intraosseous administration of a single low dose of DT-DEC01 therapy (Bioethics Committee approval no. 46/2019). No immunosuppression was administered. Safety of DT-DEC01 was confirmed by the lack of therapy-related Adverse Events or Serious Adverse Events up to 22 months following DT-DEC01 administration. EMG of selected muscles of both, ambulatory and non-ambulatory patients confirmed preliminary efficacy of DT-DEC01 therapy by an increase in motor unit potentials (MUP) duration, amplitudes, and polyphasic MUPs at 12 months. This study confirmed EMG as a reliable and objective biomarker of functional assessment in DMD patients after intraosseous administration of the novel DT-DEC01 therapy.

Pattern of immunoglobulin and T-cell receptor (Ig/TCR) gene rearrangements in Polish pediatric acute lymphoblastic leukemia patients--implications for RQ-PCR-based assessment of minimal residual disease.

We studied 23 Polish children with precursor-B-ALL, using PCR-heteroduplex analysis and DNA sequencing, to determine the availability of Ig/TCR gene rearrangements as patient-specific MRD-RQ-PCR targets. We found IGH, IGK-Kde, incomplete TCRD, Vdelta2-Jalpha, TCRG and TCRB rearrangements in 83%, 39%, 61%, 35%, 61% and 13% of patients, respectively. Comparison of Ig/TCR gene rearrangements pattern (frequency and characteristics of rearrangements) in Polish patients with those reported for patients of other European nationalities did not show major differences. These results are the first promising step for further development of MRD study in Polish patients according to current diagnostic standards.

[Molecular methods for diagnostics and assessment of treatment effectiveness in modern pediatric hematooncology]. / Molekularne metody diagnostyki i oceny efektywnosci terapii we wspólczesnej hematoonkologii pediatrycznej.

This paper is a review of current diagnostic applications of molecular methods in pediatric hematooncology, including analyses performed at disease presentation, evaluation of prognosis as well as those for assessment of treatment effectiveness. Here we present the examples of important fields of application of molecular methods in pediatric hematooncology, i.e. identification of clinically significant fusion genes in acute lymphoblastic leukemia and monitoring of minimal residual disease in this most frequent childhood malignancy. Moreover, we present the methodology and clinical significance of quantitative analysis of hematopoietic chimerism after allogeneic stem cell transplantation. The methods presented include fluorescent in situ hybridization, reverse transcription, conventional and quantitative polymerase chain reaction, as well as methods of genotyping based on analysis of microsatellite marker polymorphism, single nucleotide polymorphism, and Indel markers.