Potential Risks to Stable Long-term Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for Children With Cerebral X-linked Adrenoleukodystrophy.

Importance: Allogeneic hematopoietic stem cell transplantation is the standard intervention for childhood cerebral X-linked adrenoleukodystrophy. However, the pretransplant conditions, demyelination patterns, complications, and neurological outcomes of this therapy are not well characterized.

Objectives: To identify the risks to stable neurocognitive survival after hematopoietic stem cell transplantation and to describe subgroups of patients with distinct clinical long-term outcomes.

Androgen therapy in Fanconi anemia: A retrospective analysis of 30 years in Germany.

A substantial number of individuals with Fanconi anemia (FA) develop bone marrow failure and are treated with androgen therapy in order to increase blood counts. The authors retrospectively identified 70 patients who received androgen therapy any time between July 1976 and September 2014. Among these patients, 37 had medical records for analysis.

Risk assessment of relapse by lineage-specific monitoring of chimerism in children undergoing allogeneic stem cell transplantation for acute lymphoblastic leukemia.

Unlabelled: Allogeneic hematopoietic stem cell transplantation is required as rescue therapy in about 20% of pediatric patients with acute lymphoblastic leukemia. However, the relapse rates are considerable, and relapse confers a poor outcome. Early assessment of the risk of relapse is therefore of paramount importance for the development of appropriate measures.

Stem-cell transplantation in children with acute lymphoblastic leukemia: A prospective international multicenter trial comparing sibling donors with matched unrelated donors-The ALL-SCT-BFM-2003 trial.

Purpose: Although hematopoietic stem-cell transplantation is widely performed in children with high-risk acute lymphoblastic leukemia (ALL), the influence of donor types is poorly understood. Thus, transplantation outcomes were compared in the prospective multinational Berlin-Frankfurt-Muenster (BFM) study group trial: ALL-SCT-BFM 2003 (Allogeneic Stem Cell Transplantation in Children and Adolescents with Acute Lymphoblastic Leukemia).

Patients And Methods: After conditioning with total-body irradiation and etoposide, 411 children with high-risk ALL received highly standardized stem-cell transplantations during the first or later remissions.

Levetiracetam as a possible cause of secondary graft failure after allogenic hematopoietic stem cell transplantation.

Background: Levetiracetam is increasingly used as antiepileptic drug (AED) of choice in children as well as in adults with complex diseases due to its lack of interactions and a large spectrum of action. Secondary graft failure, i.e.

Autologous CD133+ bone marrow cells and bypass grafting for regeneration of ischaemic myocardium: the Cardio133 trial.

Aims: Intra-myocardial transplantation of CD133(+) bone marrow stem cells (BMC) yielded promising results in clinical pilot trials. We now performed the double-blinded, randomized, placebo-controlled CARDIO133 trial to determine its impact on left ventricular (LV) function and clinical symptoms.

Methods And Results: Sixty patients with chronic ischaemic heart disease and impaired LV function (left ventricular ejection fraction, LVEF <35%) were randomized to undergo either coronary artery bypass grafting (CABG) and injection of CD133(+) BMC in the non-transmural, hypokinetic infarct border zone (CD133), or CABG and placebo injection (placebo).

Total Body Irradiation (TBI) using Helical Tomotherapy in children and young adults undergoing stem cell transplantation.

Background: Establishing Total Body Irradiation (TBI) using Helical Tomotherapy (HT) to gain better control over dose distribution and homogeneity and to individually spare organs at risk. Because of their limited body length the technique seems especially eligible in juvenile patients.

Patients And Methods: The cohort consisted of 10 patients, 6 female and 4 male, aged 4 - 22 y with acute lymphoblastic- (ALL) or acute myeloic leukemia (AML).

Transplantation in patients with SCID: mismatched related stem cells or unrelated cord blood?

Pediatric patients with SCID constitute medical emergencies. In the absence of an HLA-identical hematopoietic stem cell (HSC) donor, mismatched related-donor transplantation (MMRDT) or unrelated-donor umbilical cord blood transplantation (UCBT) are valuable treatment options. To help transplantation centers choose the best treatment option, we retrospectively compared outcomes after 175 MMRDTs and 74 UCBTs in patients with SCID or Omenn syndrome.

Long-term outcome in children with relapsed acute lymphoblastic leukemia after time-point and site-of-relapse stratification and intensified short-course multidrug chemotherapy: results of trial ALL-REZ BFM 90.

Purpose: The multicenter trial ALL-REZ BFM (ie, Acute Lymphoblastic Leukemia Relapse Berlin-Frankfurt-Münster) 90 was designed to improve prognosis for children with relapsed acute lymphoblastic leukemia (ALL) by time-to-relapse- and site-of-relapse-adapted stratification and by introduction of novel chemotherapy elements and to evaluate new prognostic parameters in a large, population-based cohort.

Patients And Methods: Five hundred twenty-five patients stratified into risk groups A (early bone marrow [BM] relapses), B (late BM relapses), and C (isolated extramedullary relapses) received alternating short-course intensive polychemotherapy (in blocks R1, R2, or R3) and cranial/craniospinal irradiation followed by maintenance therapy. Block R3 (high-dose cytarabine and etoposide) was introduced to improve the outcome compared with historical controls.

Two-dimensional speckle tracking strain analysis for efficacy assessment of myocardial cell therapy.

The subtle effects of transplanted bone marrow cells (BMC) on regional myocardial behavior in patients with ischemic heart disease are difficult to assess. Novel echocardiographic techniques can quantify regional myocardial deformation (strain) and distinguish between passive and active wall motion. We hypothesized that this technique may help delineate cell therapy-induced changes in regional LV contractility that escape clinical routine studies.

A prospective, multicenter study of caspofungin for the treatment of documented Candida or Aspergillus infections in pediatric patients.

Objective: We evaluated the safety, tolerability, and efficacy of caspofungin in pediatric patients with invasive aspergillosis, invasive candidiasis, or esophageal candidiasis.

Methods: This was a multicenter, prospective, open-label study in children 3 months to 17 years of age with proven or probable invasive aspergillosis, proven invasive candidiasis, or proven esophageal candidiasis. All of the patients received caspofungin 70 mg/m(2) on day 1, followed by 50 mg/m(2) per day (maximum: 70 mg/day), as primary or salvage monotherapy.

Clinical and molecular characteristics of squamous cell carcinomas from Fanconi anemia patients.

Fanconi anemia is a recessively inherited disease that is characterized by congenital abnormalities, bone marrow failure, and a predisposition to develop cancer, particularly squamous cell carcinomas (SCCs) in the head and neck and anogenital regions. Previous studies of Fanconi anemia SCCs, mainly from US patients, revealed the presence of high-risk human papillomavirus (HPV) DNA in 21 (84%) of 25 tumors analyzed. We examined a panel of 21 SCCs mainly from European Fanconi anemia patients (n = 19 FA patients; 16 head and neck squamous cell carcinomas [HNSCCs], 2 esophageal SCCs, and 3 anogenital SCCs) for their clinical and molecular characteristics, including patterns of allelic loss, TP53 mutations, and the presence of HPV DNA by GP5+/6+ polymerase chain reaction.

Cancer risks in Fanconi anemia: findings from the German Fanconi Anemia Registry.

Background: Fanconi anemia is an inherited genomic instability syndrome associated with progressive bone marrow failure leading to death or the requirement for hematopoietic stem cell transplantation, acute myeloid leukemia, and solid tumors. Prior epidemiological studies have quantified the risks of bone marrow failure, acute myeloid leukemia and solid tumors, but these estimates have not been replicated.

Design And Methods: We assembled a cohort of 181 patients with Fanconi anemia mostly from Germany.

Intramyocardial delivery of bone marrow mononuclear cells and mechanical assist device implantation in patients with end-stage cardiomyopathy.

In end-stage heart failure, mechanical ventricular assist devices (VAD) are being used as bridge-to-transplantation, as a bridge-to-recovery, or as the definitive therapy. We tested the hypothesis that myocardial implantation of autologous bone marrow mononuclear cells (BMNC) increases the likelihood of successful weaning from left VAD (LVAD) support. Ten patients (aged 14-60 years) with deteriorating heart function underwent LVAD implantation and concomitant implantation of autologous BMNC.

Decreased platelet reactivity identified by whole blood flow cytometry in Fanconi anaemia patients.

Fanconi anaemia (FA) is a rare inherited chromosome instability disorder characterized by congenital anomalies and a high risk for bone marrow failure and cancer. Bleeding is a frequent complication in FA, leading to substantial morbidity and mortality. Thrombocytopenia is a major factor leading to this complication, but the bleeding tendency of FA patients often exceeds what one might expect based on their platelet counts.

Squamous cell carcinoma of the tongue in a 13-year-old girl with Fanconi anemia.

We report the case of a 13-year-old girl with squamous cell carcinoma (SCC) of the tongue. Fanconi anemia with a yet unknown complementation group had been diagnosed at the age of 5 years. Organ involvement included intestinal atresia, renal dysfunction due to crossed renal atopia, and tubular acidosis type II.

Superiority of allogeneic hematopoietic stem-cell transplantation compared with chemotherapy alone in high-risk childhood T-cell acute lymphoblastic leukemia: results from ALL-BFM 90 and 95.

Purpose: The role of hematopoietic stem-cell transplantation (SCT) in first complete remission (CR1) for children with very high-risk (VHR) acute lymphoblastic leukemia (ALL) is still under critical discussion.

Patients And Methods: In the ALL-Berlin-Frankfurt-Münster (BFM) 90 and ALL-BFM 95 trials, 387 patients were eligible for SCT if there was a matched sibling donor (MSD). T-cell ALL (T-ALL) patients with poor in vivo response to initial treatment represented the largest homogeneous subgroup within VHR patients.

VCAM-1-positive stromal cells from human bone marrow producing cytokines for B lineage progenitors and for plasma cells: SDF-1, flt3L, and BAFF.

The differentiation of B lymphocytes in the bone marrow is guided by the surrounding microenvironment determined by cytokines, adhesion molecules, and the extracellular matrix. These microenvironmental factors are mainly provided by stromal cells. In this paper, we report the identification of a VCAM-1-positive stromal cell population by flow cytometry.

Evaluation of whole-genome amplification of low-copy-number DNA in chimerism analysis after allogeneic stem cell transplantation using STR marker typing.

Whole-genome DNA amplification (WGA) is a promising method that generates large amounts of DNA from samples of limited quantity. We investigated the accuracy of a multiplex PCR approach to WGA over STR loci. The amplification bias within a locus and over all analyzed loci was investigated in relation to the amount of template in the WGA reaction, the specific STR locus, and allele length.

TERC mutations in children with refractory cytopenia.

Mutations in the human telomerase RNA gene (TERC) cause autosomal dominant dyskeratosis congenita and have been detected in individuals with bone marrow failure. Here, we screened for TERC mutations in a cohort of 80 children with hypocellular myelodysplastic syndrome and detected TERC alterations in two of them.

Allogeneic haematopoietic stem cell transplantation in relapsed or refractory anaplastic large cell lymphoma of children and adolescents--a Berlin-Frankfurt-Münster group report.

Patients with refractory or early relapsed anaplastic large cell lymphoma (ALCL) have a poor chance of survival. We report 20 children and adolescents with high-risk relapsed or refractory ALCL who underwent allogeneic haematopoietic stem cell transplantation (HSCT). We retrospectively analysed 20 patients who relapsed between December 1991 and April 2003 during (six patients) or soon after first-line Berlin-Frankfurt-Münster-type chemotherapy (14 patients) and underwent allogeneic HSCT.

Fatal reactivation of postnatal cytomegalovirus infection with rapid emergence of ganciclovir resistance in an infant after allogeneic stem cell transplantation.

Human cytomegalovirus (HCMV) can cause serious problems after hematopoietic stem cell transplantation. The death of a pediatric transplant recipient after reactivation of a postnatal HCMV infection with bilateral retinitis and pneumonitis is described. Sequencing of the HCMV UL97 region revealed a compartment-specific mutation (H520Q) in urine conferring ganciclovir resistance.

Immunosuppressive therapy for aplastic anemia in children: a more severe disease predicts better survival.

Severe acquired aplastic anaemia (SAA) is a life-threatening disease characterized by pancytopenia and hypoplastic bone marrow. Autologous T lymphocytes are thought to cause bone marrow failure by immune-mediated excessive apoptosis of stem and progenitor cells. The disease is subclassified into a severe (neutrophil count, > 0.