Non-malignant Diseases (non-malignant + disease)

Distribution by Scientific Domains

Selected Abstracts

Polyclonal anti-T-cell globulin as part of the preparative regimen for pediatric allogeneic stem-cell transplantation

Mats Remberger
Abstract: To prevent graft rejection and graft-versus-host disease (GvHD) after allogeneic stem-cell transplantation (ASCT), 56 children were given polyclonal anti-T-cell globulin (ATG) as part of the conditioning regimen. Of the 56 children in the cohort, 27 had a non-malignant disease and 29 had different hematological malignancies. Eight were in first remission of leukemia and the remainder in later stages. Donors were in 16 cases a human leucocyte antigen (HLA)-identical sibling and in 40 a matched unrelated donor (MUD). The control group comprised 16 patients with an HLA-identical donor; the children in this group were not treated with ATG. Side-effects related to the ATG treatment occured in 63% of the patients and included fever, chills, headache, dyspnoea, nausea/vomiting, body pain, fall in blood pressure, and transient respiratory arrest. Engraftment occured in 55 (98%) of the ATG-treated patients at a median of 17 (11,27) days after ASCT. One rejection occured at 23 days post-SCT. The probabilities of acute graft-versus-host disease (GvHD) of grades II,IV were 6% for patients with an HLA-identical donor, 12% for controls, and 26% for the MUD group. Chronic GvHD occured in 20%, 50%, and 50% of patients in the three groups, respectively. Transplant-related mortality rates at 100 days were 6%, 6%, and 7%, respectively. The 5-yr survival rate was 94% and 81% using sibling donors, with and without ATG respectively, and 53% using unrelated donors (p =,0.002). Disregarding donor type, among the ATG-treated patients 5-yr survival rates were 46% in patients with a malignant disease and 77% in non-malignant disorders. Relapse and relapse-free survival rates were 42% and 46%, respectively. Five out of 12 patients who showed an early full donor chimerism in the T-cell lineage developed acute GvHD of grades II,IV, compared to none out of 13 patients being mixed chimeras (p =,0.01). Hence, the use of polyclonal ATG as part of conditioning prior to ASCT in children is safe and the survival rate encouraging. [source]

Allogeneic bone marrow transplantation with reduced conditioning (RC-BMT)

Lars Vindeløv
Abstract: Allogeneic bone marrow transplantation with conventional conditioning (CC-BMT) has the potential of curing various malignant and non-malignant diseases. The curative mechanisms encompass 1) stem cell support for myeloablative radio-chemotherapy, 2) the graft-versus-tumor (GVT) effect, 3) gene replacement for genetic diseases and 4) immunoablation for autoimmune diseases. CC-BMT is characterized by high intensity conditioning, the requirement of prolonged and expensive hospital treatment and a treatment related mortality (TRM) of 10,50% depending on diagnosis, disease stage, patient age and donor type. Recent preclinical and clinical progress has resulted in the emergence of new concepts and procedures that allow replacement of patient bone marrow and immune system with that of the donor by a transplant procedure with markedly reduced conditioning (RC-BMT). This type of transplant, sometimes referred to as mini-BMT, activates curative mechanisms 2,4, which for a number of diseases seems sufficient for cure. It avoids the severe organ toxicity of myeloablative radio-chemotherapy and the complications of profound neutropenia. Patients beyond the age limit of conventional BMT (50,60 yr) may therefore be candidates for this type of transplant as well as patients which because of other medical conditions or the type of disease for which the transplant is needed are poor candidates for CC-BMT. The procedure can be performed in an outpatient setting. The resulting cost reduction should contribute to making allogenic BMT more readily available. This review describes basic concepts and procedures involved in RC-BMT and summarizes preliminary results obtained with RC-BMT in different transplant centers. [source]

FISH detection of chimerism in pediatric hematopoietic stem cell transplantation

Summary Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established curative therapy for various malignant and non-malignant diseases. Successful outcome after allogeneic HSCT has been associated with donor chimerism (DC). However, the detection of residual host cells or mixed hemopoietic chimerism (MC) has indicated that donor chimerism is not obligatory following HSCT. More recently, fluorescence in situ hybridization (FISH) analysis has been applied to engraftment studies for the identification of polymorphic or sex chromosomes. In this study, chimerism status was evaluated in 48 sex-mismatched HSCT pediatric patients (17 women/31 men, mean age: 9.02 ± 3.95 years, range: 2,19) by FISH and the effect of DC or MC on outcome and long-term disease-free survival was documented. The stem cell source was bone marrow in all cases. All of the donors were human leucocyte antigen-identical siblings. FISH was performed on 156 specimens between days +13 and +1878. Donor chimerism was found in 47.9% (23/48) and MC was found in 52.1% (25/48) of the patients. Fifteen of 48 (31.25%) patients died, of whom 12 (80%) were MC and three patients (20%) were DC. The difference in chimerism status (MC or DC) was statistically significant between those patients who died and those still alive (,2 = 6.813; P = 0.009). [source]

Prevalence of abnormal bone density of pediatric patients prior to blood or marrow transplant

Kathryn J. Klopfenstein MD
Abstract Osteoporosis and osteopenia are long-term side effects of bone marrow transplant (BMT). The purpose of this study was to determine the prevalence of bone mineral density (BMD) abnormalities in pediatric patients prior to BMT. Forty-four pediatric patients were evaluated with DEXA scans. The average Z -score was ,0.37. Thirty-six percent had abnormal BMD. Sixty-seven percent of ALL patients had abnormal BMD. Patients with non-malignant diseases were significantly more likely to have abnormal BMD. Patients with ALL had more defects than solid tumor patients. Females had more defects than males. These results demonstrate BMD defects are common in children prior to BMT, especially in patients with ALL. Pediatr Blood Cancer 2009;53:675,677. © 2009 Wiley-Liss, Inc. [source]

Reduced intensity and non-myeloablative allogeneic stem cell transplantation in children and adolescents with malignant and non-malignant diseases

Prakash Satwani MD
Abstract Allogeneic hematopoietic stem cell transplant (AlloSCT) from related or unrelated histocompatible donors has been well established as potentially curative therapy for children and adolescents with selected malignant and non-malignant diseases. In the malignant setting non-myeloablative (NMA)/reduced intensity (RI)-AlloSCT eradicates malignant cells through a graft versus malignancy effect provided by alloreactive donor T-lymphocytes and/or natural killer cells. In patients with non-malignant diseases NMA/RI AlloSCT provides enough immunosuppression to promote engraftment and correct underlying genetic defects. In children, myeloablative AlloSCT is not only associated with acute short-term toxicities but also long-term late complications such as growth retardation, infertility, and secondary malignancies. NMA/RI-AlloSCT in children may be associated with reduction in use of blood products, risk of infections, transplant-related mortality, and length of hospitalization. Despite the success of RI-AlloSCT in adults, large prospective and/or randomized multicenter studies are necessary in children and adolescent recipients to define the appropriate patient population, optimal conditioning regimens, cost-benefits, survival and differences in short-term and long-term effects compared to conventional myeloablative conditioning. Pediatr Blood Cancer 2008;50:1,8. © 2007 Wiley-Liss, Inc. [source]

Pulmonary function in long-term survivors of pediatric hematopoietic cell transplantation

Paul A. Hoffmeister MPH
Abstract Background The purpose of this study was to determine the prevalence of pulmonary dysfunction in pediatric hematopoietic cell transplant (HCT) survivors and to identify associated risk factors. Procedure In a cross-sectional study, patients surviving at least 5 years after pediatric HCT were requested to undergo pulmonary function testing (PFT). Risk factors for restrictive lung disease (RLD) and obstructive lung disease (OLD) were analyzed using multivariate analysis. Results Among 472 patients contacted, 260 (55%) participated and 215 were selected for analysis. These patients were transplanted at a median age of 8.3 (0.3,18.0) years; 175 for hematologic malignancies and 40 for non-malignant diseases. The preparative regimens for 133 patients included fractionated TBI (FTBI), 29 single-fraction TBI (SFTBI), and 53 non-TBI regimens. PFT was performed at a median of 10 (5.0,27.5) years after HCT. Forty percent of patients had either RLD or OLD (28% RLD, 9% OLD, 3% mixed RLD/OLD) and at least 15% had an isolated low-DLCO. Moderate-to-severe impairment was present in 45% of patients with RLD or OLD. In multivariate analysis, risk factors associated with RLD included transplant regimen, transplant diagnosis, scleroderma/contracture, and donor relation. Patients treated with SFTBI had the highest risk of RLD. Risk factors for OLD included chronic graft-versus-host disease, transplant regimen, and time after HCT. Patients surviving 20 or more years after HCT had the highest risk of OLD. Conclusions Fifty-five percent of long-term pediatric HCT survivors had pulmonary dysfunction. These findings stress the need for long-term follow-up to detect pulmonary dysfunction. Pediatr Blood Cancer 2006; 47:594,606. © 2005 Wiley-Liss, Inc. [source]

Allogeneic bone marrow transplantation with reduced intensity conditioning for chronic granulomatous disease complicated by invasive Aspergillus infection

Jairam Sastry MBBS, MRCPCH
Abstract Chronic granulomatous disease (CGD) is a rare disorder characterized by recurrent infections, often resulting in impaired quality of life and death. Allogeneic BMT provides a definitive cure for CGD, but carries a significant risk of mortality and morbidity. The risk is higher for those who have invasive fungal infection prior to transplant. Reduced intensity conditioning (RIC) is associated with less toxicity from the conditioning agents and may provide an alternative option for all non-malignant diseases. We report a case of successful allogeneic BMT after RIC for a case of X-linked CGD complicated by severe invasive aspergillosis (IA). Pediatr Blood Cancer 2006;47:327,329. © 2006 Wiley-Liss, Inc. [source]

Investigating the Feasibility of Stem Cell Enrichment Mediated by Immobilized Selectins

Nichola Charles
Hematopoietic stem cell therapy is used to treat both malignant and non-malignant diseases, and enrichment of the hematopoietic stem and progenitor cells (HSPCs) has the potential to reduce the likelihood of graft vs host disease or relapse, potentially fatal complications associated with the therapy. Current commercial HSPC isolation technologies rely solely on the CD34 surface marker, and while they have proven to be invaluable, they can be time-consuming with variable recoveries reported. We propose that selectin-mediated enrichment could prove to be a quick and effective method for recovering HSPCs from adult bone marrow (ABM) on the basis of differences in rolling velocities and independently of CD34 expression. Purified CD34+ ABM cells and the unselected CD34, ABM cells were perfused over immobilized P-, E-, and L-selectin-IgG at physiologic wall shear stresses, and rolling velocities and cell retention data were collected. CD34+ ABM cells generally exhibited lower rolling velocities and higher retention than the unselected CD34, ABM cells on all three selectins. For initial CD34+ ABM cell concentrations ranging from 1% to 5%, we predict an increase in purity ranging from 5.2% to 36.1%, depending on the selectin used. Additionally, selectin-mediated cell enrichment is not limited to subsets of cells with inherent differences in rolling velocities. CD34+ KG1a cells and CD34, HL60 cells exhibited nearly identical rolling velocities on immobilized P-selectin-IgG over the entire range of shear stresses studied. However, when anti-CD34 antibody was co-immobilized with the P-selectin-IgG, the rolling velocity of the CD34+ KG1a cells was significantly reduced, making selectin-mediated cell enrichment a feasible option. Optimal cell enrichment in immobilized selectin surfaces can be achieved within 10 min, much faster than most current commercially available systems. [source]

Alternative haematopoietic stem cell sources for transplantation: place of umbilical cord blood

Angela R. Smith
Summary Umbilical cord blood has rapidly become a valuable alternative stem cell source for allogeneic haematopoietic stem cell transplantation. Extensive research over the last 20 years has established the safety and efficacy of umbilical cord blood transplantation in both children and adults with a variety of malignant and non-malignant diseases. This research has clearly shown that this stem cell source has several unique characteristics resulting in distinct advantages and disadvantages when compared to transplantation with unrelated bone marrow or peripheral blood stem cells. This article reviews the most recent literature comparing the outcomes after umbilical cord blood transplantation with other alternative stem cell sources. [source]

Development of a dedicated risk-adjustment scoring system for colorectal surgery (colorectal POSSUM),,

P. P. Tekkis
Background: The aim of the study was to develop a dedicated colorectal Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (CR-POSSUM) equation for predicting operative mortality, and to compare its performance with the Portsmouth (P)-POSSUM model. Methods: Data were collected prospectively from 6883 patients undergoing colorectal surgery in 15 UK hospitals between 1993 and 2001. After excluding missing data and 93 patients who did not satisfy the inclusion criteria, 4632 patients (68·2 per cent) underwent elective surgery and 2107 had an emergency operation (31·0 per cent); 2437 operations (35·9 per cent) for malignant and 4267 (62·8 per cent) for non-malignant diseases were scored. Stepwise logistic regression analysis was used to develop an age-adjusted POSSUM model and a dedicated CR-POSSUM model. A 60 : 40 per cent split-sample validation technique was adopted for model development and testing. Observed and expected mortality rates were compared. Results: The operative mortality rate for the series was 5·7 per cent (387 of 6790 patients) (elective operations 2·8 per cent; emergency surgery 12·0 per cent). The CR-POSSUM, age-adjusted POSSUM and P-POSSUM models had similar areas under the receiver,operator characteristic curves. Model calibration was similar for CR-POSSUM and age-adjusted POSSUM models, and superior to that for the P-POSSUM model. The CR-POSSUM model offered the best overall accuracy, with an observed : expected ratio of 1·000, 0·998 and 0·911 respectively (test population). Conclusion: The CR-POSSUM model provided an accurate predictor of operative mortality. External validation is required in hospitals different from those in which the model was developed. Copyright © 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source]