Digital PCR-based quantification of miR-181a in the cerebrospinal fluid aids patient stratification in pediatric acute lymphoblastic leukemia.

Despite remarkable improvements in the survival of pediatric acute lymphoblastic leukemia (ALL), sensitive detection and clinical management of central nervous system leukemia (CNSL) are still immensely challenging. Blast cells residing in the CNS but not circulating in the cerebrospinal fluid (CSF) remain undetected by current diagnostic methods, preventing a truly risk-adapted anti-leukemic treatment in this compartment. We examined the clinical applicability of the molecular marker microRNA (miR)-181a quantified in the cell-free CSF to evaluate the level of CNS involvement and to optimize patient stratification based on CNS status.

Chromosomal breakage tests in the differential diagnosis of Fanconi anemia and aplastic anemia.

Background: FA patients are hypersensitive to preconditioning of bone marrow transplantation.

Objective: Assessment of the power of mitomycin C (MMC) test to assign FA patients.

Methods: We analysed 195 patients with hematological disorders using spontaneous and two types of chromosomal breakage tests (MMC and bleomycin).

Bone Turnover Marker for the Evaluation of Skeletal Remodelling in Autosomal Recessive Osteopetrosis after Haematopoietic Stem Cell Transplantation: A Case Report.

: Autosomal recessive osteopetrosis (ARO) is a rare genetic disorder of bone metabolism, primarily affecting the remodelling function of osteoclasts. Haematopoietic stem cell transplantation (HSCT) is the first-line treatment for ARO. Traditional tools for the assessment of therapeutic response, such as measuring donor chimerism, do not provide information on bone remodelling.

Next-Generation Sequencing-Based Genomic Profiling of Children with Acute Myeloid Leukemia.

Pediatric acute myeloid leukemia (AML) represents a major cause of childhood leukemic mortality, with only a limited number of studies investigating the molecular landscape of the disease. Here, we present an integrative analysis of cytogenetic and molecular profiles of 75 patients with pediatric AML from a multicentric, real-world patient cohort treated according to AML Berlin-Frankfurt-Münster protocols. Targeted next-generation sequencing of 54 genes revealed 17 genes that were recurrently mutated in >5% of patients.

Peripheral Bone Relapse of Paediatric TCF3-HLF Positive Acute Lymphoblastic Leukaemia during Haematopoietic Stem Cell Transplantation: A Case Report.

The present case report features a highly uncommon form of a paediatric TCF3-HLF positive acute lymphoblastic leukaemia (ALL) relapse, an extramedullary, peripheral bone manifestation. Following complete remission, during the conditioning for haematopoietic stem cell transplantation (HSCT), our sixteen-year-old male patient complained of fever, pain and swelling of the right forearm. Radiography suggested acute osteomyelitis in the right ulna with subsequent surgical confirmation.

Case Report: A Child With Hemophilia A Serves as Donor for Hematopoietic Stem Cell Transplantation to Cure His Brother's Severe Aplastic Anemia.

The first-line treatment of severe aplastic anemia is allogeneic hematopoietic stem cell transplantation with a matched sibling donor. However, co-morbidities of the identical donor can make donation difficult. We present a transplantation where in parallel with the patient's conditioning treatment, the preparation of the donor with severe hemophilia A required a special management with perioperative factor VIII substitution.

Bispecific Antibodies and Other Non-CAR Targeted Therapies and HSCT: Decreased Toxicity for Better Transplant Outcome in Paediatric ALL?

This review will address the place of innovative, non-chemotherapy, non-CAR-T targeted therapies in the treatment of Acute Lymphoblastic Leukaemia (ALL), focusing on their use in the hematopoietic stem cell transplant (HSCT) context. The focus will be on the agent with the most experience to date, namely the bispecific T-cell engater (BiTE) blinatumomab, but references to antibody-drug conjugates (ADCs) such as inotuzumab ozogamicin and monoclonal antibodies such as daratumamab will be made as well. Specific issues to be addressed include: (1) The use of these agents to reduce measurable residual disease (MRD) prior to HSCT and their potential for improved transplant outcomes due to reduced toxicity compared to traditional chemotherapy salvage, as well as potentially increased toxicity with HSCT with particular agents; (2) the appropriate sequencing of innovative therapies, i.

Recent Advances in the Management of Pediatric Acute Myeloid Leukemia-Report of the Hungarian Pediatric Oncology-Hematology Group.

Outcome measures of pediatric acute myeloid leukemia (AML) improved considerably between 1990 and 2011 in Hungary. Since 2012, efforts of the Hungarian Pediatric Oncology-Hematology Group (HPOG) included the reduction in the number of treatment centers, contemporary diagnostic procedures, vigorous supportation, enhanced access to hematopoietic stem cell transplantation (HSCT), and to targeted therapies. The major aim of our study was to evaluate AML treatment results of HPOG between 2012 and 2019 with 92 new patients registered (52 males, 40 females, mean age 7.

Inotuzumab ozogamicin in infants and young children with relapsed or refractory acute lymphoblastic leukaemia: a case series.

No data on inotuzumab ozogamicin (InO) in infant acute lymphoblastic leukaemia (ALL) have been published to date. We collected data internationally on infants/young children (<3 years) with ALL treated with InO. Fifteen patients (median 4.

Safety and efficacy of rivaroxaban in pediatric cerebral venous thrombosis (EINSTEIN-Jr CVT).

Anticoagulant treatment of pediatric cerebral venous thrombosis has not been evaluated in randomized trials. We evaluated the safety and efficacy of rivaroxaban and standard anticoagulants in the predefined subgroup of children with cerebral venous thrombosis (CVT) who participated in the EINSTEIN-Jr trial. Children with CVT were randomized (2:1), after initial heparinization, to treatment with rivaroxaban or standard anticoagulants (continued on heparin or switched to vitamin K antagonist).

Synonymous GATA2 mutations result in selective loss of mutated RNA and are common in patients with GATA2 deficiency.

Deficiency of the transcription factor GATA2 is a highly penetrant genetic disorder predisposing to myelodysplastic syndromes (MDS) and immunodeficiency. It has been recognized as the most common cause underlying primary MDS in children. Triggered by the discovery of a recurrent synonymous GATA2 variant, we systematically investigated 911 patients with phenotype of pediatric MDS or cellular deficiencies for the presence of synonymous alterations in GATA2.

[Hereditary haematological malignancies].

The majority of haematological malignancies represent sporadic diseases, but hereditary entities with predisposing genetic alterations have also been described. Diseases of the myeloid and lymphoid cell lineages with genetic predispositions are associated with heterogeneous clinical manifestations, with many symptoms being specific for certain cytogenetic and molecular aberrations. Apart from the myeloid predisposition syndromes with clear Mendelian inheritance patterns, cases with ambiguous predisposing factors are also known, but their role in hereditary leukemogenesis is still poorly understood.

Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial.

Background: Treatment of venous thromboembolism in children is based on data obtained in adults with little direct documentation of its efficacy and safety in children. The aim of our study was to compare the efficacy and safety of rivaroxaban versus standard anticoagulants in children with venous thromboembolism.

Methods: In a multicentre, parallel-group, open-label, randomised study, children (aged 0-17 years) attending 107 paediatric hospitals in 28 countries with documented acute venous thromboembolism who had started heparinisation were assigned (2:1) to bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20-mg equivalent dose or standard anticoagulants (heparin or switched to vitamin K antagonist).