We report incidence and deep molecular characteristics of lineage switch in 182 pediatric patients affected by B-cell precursor acute lymphoblastic leukemia (BCP-ALL), who were treated with blinatumomab. We documented six cases of lineage switch that occurred after or during blinatumomab exposure. Therefore, lineage conversion was found in 17.4% of all resistance cases (4/27) and 3.2% of relapses (2/63). Half of patients switched completely from BCP-ALL to CD19-negative acute myeloid leukemia, others retained CD19-positive B-blasts and acquired an additional CD19-negative blast population: myeloid or unclassifiable. Five patients had KMT2A gene rearrangements; one had TCF3::ZNF384 translocation. The presented cases showed consistency of gene rearrangements and fusion transcripts across initially diagnosed leukemia and lineage switch. In two of six patients, the clonal architecture assessed by IG/TR gene rearrangements was stable, while in others, loss of clones or gain of new clones was noted. KMT2A-r patients demonstrated very few additional mutations, while in the TCF3::ZNF384 case, lineage switch was accompanied by a large set of additional mutations. The immunophenotype of an existing leukemia sometimes changes via different mechanisms and with different additional molecular changes. Careful investigation of all BM compartments together with all molecular –minimal residual disease studies can lead to reliable identification of lineage switch.

This article discusses the potential of droplet digital polymerase chain reaction (PCR) for the diagnostic detection and monitoring of the allelic load of the BRAF V600E mutation in circulating cell-free DNA and myeloid progenitor cell population in the bone marrow of patients with Langerhans cell histiocytosis (LCH). Droplet digital PCR may serve as a useful tool for the monitoring of minimal residual disease and improve our understanding of the pathogenesis of Langerhans cells histiocytosis. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology.

Relevance. Juvenile xanthogranuloma (JXG) is the most common form of non-Langerhans cell histiocytic disorder. Cutaneous forms of the disease spontaneously regress within a few years, while systemic forms of JXG require treatment and may pose a threat to the lives of patients. Due to the lack of unified approach to the treatment of multisystem forms of JXG, the question of effective therapy tactics remains unresolved. The most common approach is to use Langerhans cell histiocytosis (LCH) treatment regimens for JXG. With the understanding of the leading role of mutations in the MEK-ERK signaling pathway in the pathogenesis of JXG, targeted therapy, BRAF- and MEK-inhibitors, are increasingly being considered in the treatment of JXG.Clinical cases. We present two cases of multisystem JXG with central nervous system (CNS) lesions. The first patient with CNS and skin lesions was treated with chemotherapy, developed for the treatment of multisystem LCH, which allowed us to obtain an effect “active disease better” (AD better). The second JXG patient with brain, lungs, bones, and adrenal gland lesions, combined targeted therapy with BRAF- and MEKinhibitors, vemurafenib and cobimetinib, resulted in a “non active disease” (NAD) effect.Conclusion. Multisystem form of JXG with CNS involvement is a rare oncological disease, the therapy of which has not been developed. With the introduction of molecular genetic profiling technology, it became possible to obtain NAD effect using targeted therapy.

No abstract

Background: Secondary immunodeficiency in recipients after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the pediatric practice is often accompanied by bacterial and viral infections of the gastrointestinal tract (GIT), resistant to conventional therapy. Fecal microbiota transplantation (FMT) promotes intestinal recolonization and eradication of gastrointestinal symptoms. Clinical case description: A 2.5-year-old patient underwent allo-HSCT from a haploidentical related donor (father) as a part of the treatment of acute myeloid leukemia. A month after the last procedure, diarrhea (up to 10 times a day) and abdominal pain appeared. The astrovirus RNA and Clostridium difficile toxin A were detected in the feces. The FMT was prescribed. After two FMT procedures, the intestinal syndrome leveled out, and the tests for the astrovirus RNA and clostridial toxins were negative. The content of cholic and, in particular, deoxycholic acids, as well as their conjugates with glycine and taurine, in the feces increased; the acetic acid content increased with a simultaneous decrease in the level of propionic acid, which indicates the restoration of the intestinal microbiotas functional potential. Conclusion: FMT contributes to the restoration of the normal intestinal microflora, the elimination of clostridial toxins, enteroinvasive E. coli and astrovirus infection in allo-HSCT recipients, as evidenced by the indicators of the intestinal microbiota activity, and can be used in allo-HSCT recipients with infections refractory to conventional therapy.