One single bone marrow harvesting from donors under 3 years of age: assessing safety and efficacy of the procedure.

To candidate children as bone marrow donors raises two main concerns: donor safety and adequate marrow cell dose. Data in the field are limited and guidelines for child donor care management are lacking. In this context, we herein report the experience collected in our center by comparing very-young donors (defined as age ≤ 3 years) with young donors (defined as age > 3 years) who donated bone marrow (BM) for patients affected by beta-globin disorders.

Haploidentical HSCT for hemoglobinopathies: improved outcomes with TCRαβ/CD19-depleted grafts.

We examined outcomes of haploidentical hematopoietic cell transplantation (haplo-HCT) using T-cell receptor αβ (TCRαβ)/CD19-depleted grafts (TCR group, 14 patients) in children with hemoglobinopathies. Patients received a preparative regimen consisting of busulfan, thiotepa, cyclophosphamide, and antithymocyte globulin preceded by fludarabine, hydroxyurea, and azathioprine. The median follow-up among surviving patients was 3.

Posterior Reversible Encephalopathy Syndrome after Hematopoietic Cell Transplantation in Children with Hemoglobinopathies.

Posterior reversible encephalopathy syndrome (PRES) is a serious adverse event associated with calcineurin inhibitors used for graft-versus-host disease (GVHD) prophylaxis. We compared the incidence of PRES in children with thalassemia (n = 222, 1.4 to 17.

Structural and Functional Insights on an Uncharacterized Aγ-Globin-Gene Polymorphism Present in Four β0-Thalassemia Families with High Fetal Hemoglobin Levels.

Introduction: Several DNA polymorphisms have been associated with high production of fetal hemoglobin (HbF), although the molecular basis is not completely understood. In order to identify and characterize novel HbF-associated elements, we focused on five probands and their four families (from Egypt, Iraq and Iran) with thalassemia major (either β(0)-IVSII-1 or β(0)-IVSI-1) and unusual HbF elevation (>98 %), congenital or acquired after rejection of bone marrow transplantation, suggesting an anticipated favorable genetic background to high HbF expression.

Methods: Patient recruitment, genomic DNA sequencing, western blotting, electrophoretic mobility shift assays, surface plasmon resonance (SPR) biospecific interaction analysis, bioinformatics analyses based on docking experiments.

Optimal Outcomes in Young Class 3 Patients With Thalassemia Undergoing HLA-Identical Sibling Bone Marrow Transplantation.

Background: Bone marrow transplantation (BMT) for class 3 patients with thalassemia is challenging due to high rates of graft rejection and transplant-related mortality. Since the first studies of BMT in the late 1980s, a number of conditioning regimens have been designed to improve outcomes, but with suboptimal results. Here we report the outcome of transplantation in class 3 patients using a modified protocol.

Haematopoietic stem cell transplantation in Nigerian sickle cell anaemia children patients.

Background: Sickle cell anaemia (SCA) remains associated with high risks of morbidity and early death. Children with SCA are at high risk for ischaemic stroke and transient ischaemic attacks, secondary to intracranial arteriopathy involving carotid and cerebral arteries. Allogeneic haematopoietic stem cell transplantation (HSCT) is the only curative treatment for SCA.

Invasive pulmonary aspergillosis in a haematopoietic stem cell transplant recipient with sickle cell disease: a successful treatment.

Sickle Cell Anaemia (SCA) is the most common inherited blood disorder and is associated with severe morbidity and decreased survival. Allogeneic Haematopoietic Stem Cell Transplantation (HSCT) is the only curative approach. Nevertheless the decision to perform a bone marrow transplant includes the risk of major complications and transplant-related mortality.

New insights into the pharmacokinetics of intravenous busulfan in children with sickle cell anemia undergoing bone marrow transplantation.

Background: Busulfan (Bu) is an integral part of conditioning regimens for patients with sickle cell anemia (SCA) undergoing transplantation. Patients with SCA might predispose to transplant-related neurological and pulmonary toxicities due to pre-existing disease-related cerebrovascular and lung injury. Bu therapy appears to be an important contributing factor in this context.

Peripheral red blood cell split chimerism as a consequence of intramedullary selective apoptosis of recipient red blood cells in a case of sickle cell disease.

Allogeneic cellular gene therapy through hematopoietic stem cell transplantation is the only radical cure for congenital hemoglobinopathies like thalassemia and sickle cell anemia. Persistent mixed hematopoietic chimerism (PMC) has been described in thalassemia and sickle cell anemia. Here, we describe the clinical course of a 6-year-old girl who had received bone marrow transplant for sickle cell anemia.

Reduction of intramedullary apoptosis after stem cell transplantation in black african variant of pediatric sickle cell anemia.

Background And Purpose: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for sickle cell anemia (SCA). We report our experience with transplantation in children with the Black African variant of SCA and the effects of transplant on erythroid compartment in bone marrow (BM).

Patients And Methods: Twenty-seven consecutive patients who underwent BM transplantation from HLA-identical donors following a myeloablative conditioning regimen were included.

Bone marrow transplantation for thalassemia from alternative related donors: improved outcomes with a new approach.

Bone marrow transplantation (BMT) performance can be limited by a lack of ideal donors, and the role of alternative donor hematopoietic cell transplantation in thalassemia is not well established. Here we used a new treatment protocol (Pc 26.1) in 16 thalassemia patients to perform BMT using phenotypically HLA-identical or 1-antigen-mismatched relatives (related donors [RDs]).

Immunohematologic reconstitution in pediatric patients after T cell-depleted HLA-haploidentical stem cell transplantation for thalassemia.

To analyze immunohematologic reconstitution, particularly of natural killer (NK) cells, we evaluated 13 β-thalassemia patients after 20 and 60 days and 1 year posttransplantation with T cell-depleted HLA-haploidentical stem cells. We assessed lymphocyte and bone marrow (BM) progenitor cell phenotype and differentiation capacity, spontaneous BM cytokine production, stromal cells, and stromal cell interleukin (IL)-7 production. A reduced clonogenic capability manifested at day +20.

Late-onset hemorrhagic cystitis in children after hematopoietic stem cell transplantation for thalassemia and sickle cell anemia: a prospective evaluation of polyoma (BK) virus infection and treatment with cidofovir.

Little is known about late-onset hemorrhagic cystitis (HC) in children, its relationship to BK virus, and treatment with cidofovir (CDV) following hematopoietic stem cell transplantation (HSCT). We prospectively investigated BK virus reactivation in children who underwent HSCT from a matched related donor for thalassemia or sickle cell anemia following busulfan-cyclophosphamide-based conditioning regimens and analyzed risk factors for development of HC and its treatment with CDV. Grade 2-4 HC occurred in 30 patients with a cumulative incidence of 26% (95% confidence interval [CI] = 18%-34%).

Purified T-depleted, CD34+ peripheral blood and bone marrow cell transplantation from haploidentical mother to child with thalassemia.

Fetomaternal microchimerism suggests immunological tolerance between mother and fetus. Thus, we performed primary hematopoietic stem cell transplantation from a mismatched mother to thalassemic patient without an human leukocyte antigen-identical donor. Twenty-two patients with thalassemia major were conditioned with 60 mg/kg hydroxyurea and 3 mg/kg azathioprine from day -59 to -11; 30 mg/m(2) fludarabine from day -17 to -11; 14 mg/kg busulfan starting on day -10; and 200 mg/kg cyclophosphamide, 10 mg/kg thiotepa, and 12.

Sustained and full fetal hemoglobin production after failure of bone marrow transplant in a patient homozygous for beta 0-thalassemia: a clinical remission despite genetic disease and transplant rejection.

An adult patient affected by beta(0)-thalassemia major underwent allogeneic bone marrow transplant (BMT) from a matched related donor. Forty days after transplant, allogeneic engraftment failure and autologous beta(0)-thalassemic bone marrow recovery were documented. Red blood cell transfusions were required until 118 days post-transplant.

Expansion of natural killer cells with lytic activity against autologous blasts from adult and pediatric acute lymphoid leukemia patients in complete hematologic remission.

Background And Objectives: Natural killer (NK) cells constitute an important area of research for hematologic malignancies. The anti-leukemic activity of NK cells against acute myeloid leukemia (AML) blasts has been described, but very few data are available for acute lymphoid leukemia (ALL). The present study was designed to investigate whether: (i) NK effectors could be expanded from adult and pediatric ALL patients in complete remission; (ii) the signal transduction machinery of these cells was preserved; (iii) NK cells showed cytotoxic activity against autologous blasts; (iv) interleukin (IL)-2, IL-12 and IL-15 were able to increase lytic activity in our in vitro model; (v) any differences in cytotoxic activity could be found between expanded effectors from adult and pediatric patients.