Blinatumomab Prior to CAR-T Cell Therapy-A Treatment Option Worth Consideration for High Disease Burden.

The optimal bridging therapy before CAR-T cell infusion in pediatric relapsed or refractory B-cell precursor acute lymphoblastic leukemia (r/r BCP-ALL) still remains an open question. The administration of blinatumomab prior to CAR-T therapy is controversial since a potential loss of CD19+ target cells may negatively impact the activation, persistence, and, as a consequence, the efficacy of subsequently used CAR-T cells. Here, we report a single-center experience in seven children with chemorefractory BCP-ALL treated with blinatumomab before CAR-T cell therapy either to reduce disease burden before apheresis (six patients) or as a bridging therapy (two patients).

Case Report: Liver as a Source of Hematopoietic Stem Cells After Liver Transplantation Following Hematopoietic Stem Cell Transplantation.

We report a child with Fanconi anemia who, after hematopoietic stem cell transplantation (HSCT) complicated by acute graft-versus-host disease (GVHD), underwent orthotopic liver transplantation (OLT). Approximately 1 month after OLT, the presence of third-party genetic material from the liver donor was noted and in the next few weeks, the chimerism assessment revealed 100% liver donor leukocytes in the peripheral blood. The rapidly progressing GVHD with gut involvement resulted in patient's death 6 months after OLT.

MicroRNA gene methylation landscape in pediatric B-cell precursor acute lymphoblastic leukemia.

Background: Aberrant DNA methylation is an important mechanism by which the normal patterns of microRNA expression are disrupted in human cancers including B-cell precursor acute lymphoblastic leukemia (BCP ALL), the most common pediatric malignancy.

Objectives: To characterize the methylation profile landscape of microRNA genes in BCP ALL patients.

Material And Methods: We employed Infinium® MethylationEPIC BeadChip Arrays to measure the methylation of microRNA genes from bone marrow samples of children with BCP ALL (n = 38) and controls without neoplasms (n = 4).

Fludarabine-Cyclophosphamide-Based Conditioning with Antithymocyte Globulin Serotherapy Is Associated with Durable Engraftment and Manageable Infections in Children with Severe Aplastic Anemia.

Severe aplastic anemia (SAA) is a bone marrow failure syndrome that can be treated with hematopoietic cell transplantation (HCT) or immunosuppressive (IS) therapy. A retrospective cohort of 56 children with SAA undergoing transplantation with fludarabine-cyclophosphamide-ATG-based conditioning (FluCyATG) was analyzed. The endpoints were overall survival (OS), event-free survival (EFS), cumulative incidence (CI) of graft versus host disease (GVHD) and CI of viral replication.

Thymic activity in immune recovery after allogeneic hematopoietic stem cell transplantation in children.

Thymic output was studied prospectively in 52 children who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Thymic activity was assessed by quantification of recent thymic emigrants (RTE) discriminated from the rest of naive T cells by immunophenotype CD3+/CD4+/CD31+/CD45RA+. Thymic output was analyzed in correlation with the kinetics of immune recovery and in relation to other potential risk factors that may influence thymopoiesis: underlying disease, type of HSCT, source of stem cells, age of recipient and donor, type of conditioning, implemented graft versus host disease (GvHD) prophylaxis, viral reactivations (herpes viruses cytomegalovirus - CMV, Epstein-Barr virus - EBV, adenovirus - ADV, BK virus - BKV), occurrence and grade of both acute and chronic graft versus host disease (aGvHD, cGvHD) and number of transplanted CD34 cells/kg.

Successful Salvage Treosulfan-Based Megachemotherapy With Allogeneic Stem Cell Transplantation in Nonsyndromic, Therapy-Resistant Disseminated Juvenile Xanthogranuloma: A Case Report.

Juvenile xanthogranuloma (JXG) is a rare histiocytic disorder classified as non-Langerhans cell histiocytosis; although it is usually a benign and self-limiting disease, it can be fatal in some cases, especially with systemic dissemination. We present a case report of a boy with therapy-resistant disseminated JXG who was treated with systemic chemotherapy and received 3 allogeneic hematopoietic stem cell transplantations (allo-HSCTs) from an unrelated donor. The post-transplant period was complicated by acute graft vs host disease and lymphoproliferative disease caused by Epstein-Barr virus.

Pediatric unmanipulated haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide and reduced intensity, TBI-free conditioning regimens in salvage transplantations.

Background: Unmanipulated haploidentical stem cell transplantation (haploSCT) with post-transplant cyclophosphamide is an option for patients with advanced hematologic malignancies. It offers a platform both for non-major histocompatibility complex-restricted alloimmunity due to killer-like immunoglobulin receptor (KIR)-mediated mechanisms of natural killer lymphocyte regulation and for classical T-cell mediated antileukemic effects.

Objectives: The devastating long-term sequelae after total body irradiation (TBI) in children are encouraging omission of irradiation techniques in pediatric stem cell transplantations (SCT).

Safety and efficacy of autologous mononuclear cell and stem cell apheresis in very low-weight children-Experience at a single center.

Background: Apheresis in children with low body weight is technically limited by their tolerance of the extracorporeal blood volume.

Study Design And Methods: This paper presents a single-center experience with 23 procedures in 12 children with weights between 5.2 and 9.

Feasibility and Safety of Treosulfan, Melphalan, and Thiotepa-Based Megachemotherapy with Autologous or Allogeneic Stem Cell Transplantation in Heavily Pretreated Children with Relapsed or Refractory Neuroblastoma.

The prognosis of resistant or relapsing children with neuroblastoma remains very poor, and the search for new therapies is ongoing. In this analysis, we assessed the toxicity of a treosulfan, melphalan, and thiotepa (TMT) regimen in 17 children with recurrent or refractory neuroblastoma who underwent stem cell transplantation (SCT). For allogeneic SCT, fludarabine and antithymocyte globulin were added.

Allogeneic Stem Cell Transplantation after Fanconi Anemia Conditioning in Children with Ataxia-Telangiectasia Results in Stable T Cell Engraftment and Lack of Infections despite Mixed Chimerism.

Ataxia-telangiectasia (A-T) syndrome is an autosomal recessive chromosomal breakage syndrome caused by mutation of the ataxia-telangiectasia mutated gene manifested by progressive neurodegeneration, telangiectasias of sclera and skin, immune deficiency with sinopulmonary infections, and increased incidence of lymphoid malignancies and solid tumors. Three children with A-T underwent allogeneic stem cell transplantation (SCT) using protocols for Fanconi anemia. All 3 patients were engrafted with a mixed donor-recipient chimerism, but the full donor engraftment was observed in the T lymphocyte compartment.

The distinguishable DNA whole genome methylation profile of 2 cases of pediatric precursor B acute lymphoblastic leukaemia (BCP ALL) with prodromal, preleukemic phase: A case report.

Rationale: A prolonged, prodromal phase before definitive paediatric precursor B acute lymphoblastic leukaemia (BCP ALL) diagnosis is rarely observed.

Patients Concerns: In the first, the patient presented with an aplastic preleukemic phase, whilst the second presented with a rheumatic-like preliminary phase.

Diagnoses: The case reports of two patients with BCP ALL with a prodromal phase lasting a few weeks are presented.

Imatinib in the treatment of chronic myeloid leukemia in children and adolescents is effective and well tolerated: Report of the Polish Pediatric Study Group for the Treatment of Leukemias and Lymphomas.

Background: Chronic myeloid leukemia (CML) constitutes only 2-3% of all leukemias in pediatric patients. Philapelphia chromosome and BCR-ABL fusion are genetic hallmarks of CML, and their presence is crucial for targeted molecular therapy with tyrosine kinase inhibitors (TKIs), which replaced hematopoietic stem cell transplantation (HSCT) as a standard first-line therapy. The disease in pediatric population is rare, and despite molecular and clinical similarities to CML in adults, different approach is needed, due to the long lifetime expectancy and distinct developmental characteristics of affected children.

Whole-genome DNA methylation characteristics in pediatric precursor B cell acute lymphoblastic leukemia (BCP ALL).

In addition to genetic alterations, epigenetic abnormalities have been shown to underlie the pathogenesis of acute lymphoblastic leukemia (ALL)-the most common pediatric cancer. The purpose of this study was to characterize the whole genome DNA methylation profile in children with precursor B-cell ALL (BCP ALL) and to compare this profile with methylation observed in normal bone marrow samples. Additional efforts were made to correlate the observed methylation patterns with selected clinical features.

Immune recovery and the risk of CMV/ EBV reactivation in children post allogeneic haematopoietic stem cell transplantation.

Immune reconstitution was studied prospectively in 86 children who underwent allogeneic haematopoietic stem cell transplantation (HSCT). We analysed the risk of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation in correlation with the kinetics of immune recovery and in relation to other potential risk factors that may influence the reactivation of these viruses including: diagnosis, type of HSCT, source of stem cells, type of conditioning, or the occurrence of graft-versus-host disease (GvHD). The absolute number of lymphocyte subpopulations in peripheral blood was evaluated in seven timepoints following HSCT.