Haploidentical stem cell transplantation in two children with mucopolysaccharidosis VI: clinical and biochemical outcome.

Background: Mucopolysaccharidosis VI (MPS VI) is an autosomal recessive progressive multiorgan disorder due to mutation in the gene encoding the enzyme Arylsulfatase B (ARSB). Dysfunctional ARSB causes lysosomal accumulation of glycosaminoglycans (GAG). Currently, enzyme replacement therapy (ERT) is preferred to hematopoietic stem cell transplantation (SCT) due to the treatment-related risks of the latter.

RALLE pilot: response-guided therapy for marrow relapse in acute lymphoblastic leukemia in children.

Despite improved treatment results of childhood acute lymphoblastic leukemia (ALL), 20% to 30% have a relapse, and then the outcome is very poor. We studied 40 children with ALL marrow relapse piloting an ALL relapse protocol with well-known drugs and drug combinations by using a concept of response-guided design. We also measured response in logarithmic fashion.

Small cell lung cancer in a 14-year-old girl.

Pediatric lung cancer is uncommon, and small cell lung cancer (SCLC) is exceptionally rare. A 14-year-old previously healthy girl was diagnosed with limited-stage SCLC, which was considered inoperable. She responded well to chemotherapy with carboplatin and etoposide, and surgical resection was performed after 2 cycles.

Prognostic value of PAX-FKHR fusion status in alveolar rhabdomyosarcoma: a report from the cooperative soft tissue sarcoma study group (CWS).

Background: Alveolar Rhabdomyosarcomas (RMA) are characterized by chromosomal translocations, fusing the PAX3 or PAX7 gene with FKHR in about 85%. Previous studies have suggested that the fusion type is associated with prognosis. In order to investigate the predictive value of the PAX-FKHR fusion status on disease outcome of patients with RMA treated in the CWS trials we performed a retrospective analysis.

High-dose iodine-131-metaiodobenzylguanidine with haploidentical stem cell transplantation and posttransplant immunotherapy in children with relapsed/refractory neuroblastoma.

We evaluated the feasibility and efficacy of using high-dose iodine-131-metaiodobenzylguanidine ((131)I-MIBG) followed by reduced-intensity conditioning (RIC) and transplantation of T cell-depleted haploidentical peripheral blood stem cells (designated haplo-SCT) to treat relapsing/refractory neuroblastoma (RRNB). Five RRNB patients were enrolled: 4 with relapse (3 after autologous SCT) and 1 with induction therapy failure. The preparative regimen included high-dose (131)I-MIBG on day -20, followed by fludarabine (Flu), thiotepa, and melphalan (Mel) from day -8 to -1.

Ante mortem diagnosis of amoebic encephalitis in a haematopoietic stem cell transplanted patient.

Acanthamoeba species are widely distributed free-living amoebae showing an increased role as human pathogens causing encephalitis, keratitis, pneumonitis and dermatitis. A haematopoietic stem cell transplanted (HSCT) patient developed purulent meningitis while awaiting regrafting. The meningitis was thought to be an endogenous infection arising from the mucous membranes primarily involving the cervicofacial regions, probably due to haematogenous spread facilitated by surgery.

Rapid and effective CD3 T-cell depletion with a magnetic cell sorting program to produce peripheral blood progenitor cell products for haploidentical transplantation in children and adults.

Background: Effective T-cell depletion is a prerequisite for haploidentical peripheral blood progenitor cell (PBPC) transplantation. This study was performed to investigate the performance of magnetic cell sorting-based direct large-scale T-cell depletion, which is an attractive alternative to standard PBPC enrichment procedures.

Study Design And Methods: PBPCs were harvested from 11 human leukocyte antigen (HLA)-haploidentical donors.

Pax3-fkhr and pax7-fkhr fusion genes impact outcome of alveolar rhabdomyosarcoma in children.

Rhabdomyosarcoma is a highly malignant embryonic tumor of childhood. Two specific translocations t(2;13)(q35;q14) and t(1;13)(p36;q14) have been identified in about 75-80% of ARMS cells. The aim of this multicenter study was to analyze the relationships between the identified fusion transcripts and survival including some selected clinical parameters.

Cytogenetic findings in pediatric renal cell carcinoma.

Adenocarcinomas of the kidney are rare childhood tumors. Only 30 cases with chromosomal abnormalities have been reported, and neither their karyotypic characteristics nor the molecular mechanisms behind their pathogenesis are clear, except for a special group of papillary tumors characterized by X-chromosome abnormalities. We have cytogenetically analyzed short-term cultured cells from two pediatric renal carcinomas, one papillary, and one chromophobe renal cell carcinoma, revealing the following karyotypes: 58-60,XX,-X,-1,+7,-8,-9,-11,-14,-15,+17,-18,-19,-21,-22 and 36,X,-X,-1,-2,-5,-6,-9,-10,-13,-17,-21/37,idem,+r/36,idem,-14,+1-2r, respectively.

Pathways through relapses and deaths of children with acute lymphoblastic leukemia: role of allogeneic stem-cell transplantation in Nordic data.

Purpose: Our focus was on patients with pediatric acute lymphoblastic leukemia (ALL) who experienced relapse or died without becoming transplantation candidates. The purpose was to outline measures needed to improve the outcome.

Patients And Methods: We analyzed our population-based 20-year data on 3,385 Nordic children with ALL treated on Nordic Society for Pediatric Hematology and Oncology ALL protocols, and described the flow of these patients through relapses, remissions, and deaths as a result of toxicity, demonstrating where major patient losses occurred.

Influence of donor/recipient sex matching on outcome of allogeneic hematopoietic stem cell transplantation for aplastic anemia.

Background: Increased risk of transplant related mortality in male recipients of female hematopoietic stem cell grafts and in vitro reactivity of lymphocytes against H-Y encoded gene products in females with rejected male grafts have been documented. An increased rejection of male grafts in female recipients is not reported for solid organ or stem cell transplants and the role of H-Y as transplantation antigen has been controversial.

Methods: Data from 1481 patients with a hematopoietic stem cell transplant for aplastic anemia reported from 154 centers in 28 countries were analyzed.

Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia.

The cellular targets of primary mutations and malignant transformation remain elusive in most cancers. Here, we show that clinically and genetically different subtypes of acute lymphoblastic leukemia (ALL) originate and transform at distinct stages of hematopoietic development. Primary ETV6-RUNX1 (also known as TEL-AML1) fusions and subsequent leukemic transformations were targeted to committed B-cell progenitors.

TNF-alpha and IFN-gamma are overexpressed in the bone marrow of Fanconi anemia patients and TNF-alpha suppresses erythropoiesis in vitro.

In Fanconi anemia (FA) C mice tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) have key roles in the pathogenesis of bone marrow failure. In FA subjects TNF-alpha was found to be increased in the serum and overproduced by patient-derived B-cell lines. In acquired aplastic anemia, a disease in which, similarly to FA, marrow failure occurs, TNF-alpha and IFN-gamma act as late mediators of the stem cell damage and are overexpressed in patient marrow lymphocytes.

Intravitreal sustained-release ganciclovir implants for severe bilateral cytomegalovirus retinitis after stem cell transplantation.

Purpose: To describe the treatment of cytomegalovirus (CMV) retinitis with intravitreal sustain-release ganciclovir devices in a 16-year-old patient in third remission of acute lymphoblastic leukemia after stem cell transplantation.

Methods: The patient received a stem cell transplant from an unrelated bone marrow donor after which he contracted a serious CMV infection manifested in the lungs and retinae. His immune system at this time was almost completely depleted.