Biomedical subjects

H J Laws

Publications and source records attributed to H J Laws.

23 records · Page 2Linked to original sources

PubMedDate not supplied

Intensification of chelating-therapy in patients with thalassemia major.

With the introduction of "hypertransfusion" regimens the extent of disease- and therapy-related hemosiderosis has become the survival limiting factor for patients with beta-thalassemia major as iron transferred with transfusions cannot be excreted by physiological means. Subsequent introduction of deferoxamine therapy for iron elimination and prophylaxis of hemosiderosis has improved prognosis and life quality of these patients considerably. We report our experience with seven adolescent patients with beta-thalassemia and ineffective subcutaneous therapy and severe hemosiderosis-related organ complications. For that reason they received i. v. intensified chelate therapy. The patients were given 70 to 120 mg/kg DFO 7 days a week continuously via a Port-a-cath or Hickman central venous line. Under high-dose i. v. DFO therapy, serum ferritin levels significantly decreased in all patients. Target serum ferritin levels of 3 000 ng/ml were reached after 12 to 20 months of treatment. In 3 of the 5 patients that were treated for longer than 43 months serum ferritin levels even dropped below 2 000 ng/ml. Serum ferritin levels also correlated well with SQUID examinations. Therefore, monitoring of serum ferritin may be useful to monitor patient's compliance and control intensified DFO therapy. Continuous administration of the intensified DFO therapy induced normalization of liver function and left ventricular cardiac function in all patients who are still alive. Two patients died due to cardiac decompensation. In five patients 19 episodes of central catheter-related infections were observed (1.5 infections per 1 000 catheter days). No DFO-associated allergic reactions nor irreversible organ dysfunction were observed. Our results indicate that intensified i. v. DFO therapy is an effective and safe method for treatment of severe organ dysfunction in patients with thalassemia major. The most severe problems are catheter-related infections and inconsistent long-term compliance.

Adolescent↗

PubMedDate not supplied

Similar survival following HLA-identical sibling transplantation for standard indication in children with haematologic malignancies: a single center comparison of mobilized peripheral blood stem cell with bone marrow transplantation.

BACKGROUND: Peripheral blood stem cell (PBSC) grafts are increasingly used for autologous and allogeneic haematopoietic stem cell transplantation (alloHSCT) with the aim to hasten neutrophil and platelet engraftment and thereby to reduce transplant-related complications due to infections, bleeding and graft failure. Based on the paucity of data on PBSC transplantation in children we performed a retrospective single-center analysis comparing the outcome of children receiving mobilized PBSC from human leukocyte antigen (HLA)-identical sibling donors to bone marrow (BM) transplant recipients. PATIENTS AND METHODS: Between 1996 and 2004, 16 children with haematologic malignancies and standard indication for alloHSCT underwent PBSC transplantation from HLA-identical sibling donors. The outcome of these children was compared to a historic control group of 19 bone marrow (BM) transplant recipients. Time to neutrophil engraftment, incidence of acute and chronic graft-versus-host disease (GvHD), relapse rate, transplant-related mortality, event-free and overall survival were analyzed. RESULTS: Neutrophil engraftment was achieved significantly faster after PBSC compared to BM transplantation with a median time to neutrophil engraftment of 11 (range: 8-21) and 19 (16-44) days for the PBSC and BM cohort, respectively (p < 0.001). Two of 19 (11 %) BM recipients did not achieve primary neutrophil engraftment and both patients died due to infectious complications. The rate of clinically significant acute GvHD > or = grade II was higher in the PBSC compared to the BM group (75 vs. 39 %; p = 0.045). Incidences of chronic GvHD (PBSC vs. BM: 60 vs. 44 %), death of disease (13 vs. 21 %) and death of complication (13 vs. 16 %) were comparable between both groups (p = ns). With a median follow up of 4.7 years (PBSC) and 10.2 years (BM) overall survival (PBSC vs. BM: 68.6 +/- 13.5 vs. 63.2 +/- 11.1 %; p = 0.65) and event-free survival (67.0 +/- 12.1 vs. 63.2 +/- 11.1 %; p = 0.80) is without demonstrable difference in both groups. CONCLUSIONS: Transplantation of PBSC compared to BM is associated with faster neutrophil engraftment and a higher rate of > or = grade II acute GvHD. As overall survival and event-free survival is similar when using PBSC and BM, PBSC is an alternative stem cell source for HLA-identical sibling transplantation. Further prospective analyses with higher number of patients stratified according to well established risk factors are required to define the precise role of both stem cell sources for children with haematologic malignancies.

Adolescent↗

PubMedDate not supplied

[Immune stimulation with interleukin-2 after autologous stem cell transplantation in children and adolescents with solid tumors].

Children with solid tumors of poor prognosis have benefitted from autologous bone marrow transplantation as a treatment modality. Adjuvant interleukin-2 (IL2) therapy has previously been shown to improve prognosis in adults with some solid tumors. In this setting improved survival probability has been attributed to IL2-mediated augmentation of antineoplastic activity of the immune system. In this study 8 pediatric patients in complete remission after autologous stem cell transplantation were treated with recombinant IL2 administered in 3 cycles of 5 days continuous intravenous infusions and a two week rest in between. We demonstrated that IL2 therapy increased transplantation-related activation of the immune system both on cellular and humoral levels. Peripheral blood T and NK cell number increased by the factors 1.7 and 6.0 respectively. NK and T cell activation were further enhanced as indicated by elevated levels of soluble IL2 receptor. The production of tumor cytotoxic cytokines like alpha TNF and gamma INF was stimulated. The elevated aTNF and gamma INF cytokine synthesis seemed to be mainly related to the activation and proliferation of NK cells, as T cells obtained from patients after IL2 therapy showed a definite cytokine production deficiency after T cell specific stimulation.

Adolescent↗

PubMedDate not supplied

[Hereditary heterozygote factor VII deficiency].

Hereditary Factor VII deficiency is one of the rare congenital coagulopathies. Prolonged prothrombin time (PT) with normal partial prothrombin time (PTT) may be an indicator for Factor VII deficiency. A family with hereditary heterozygous Factor VII deficiency is presented in whom no symptoms of a bleeding disorder were clinically detectable. A discussion of the therapeutic options follows.

Blood Coagulation Tests↗

PubMedDate not supplied

Circulating CD34+ cell counts as predictive parameter for the efficacy of peripheral stem cell apheresis in Ewing tumor patients.

The parameters used by different centers for starting peripheral stem cell apheresis following mobilization with chemotherapy and G-CSF are diverse. We retrospectively analysed 62 leukaphereses performed on eleven patients with Ewing Tumors and one patient with Synovial Sarcoma, all after treatment with standardized chemotherapy (according to the EICESS protocol) and subsequent administration of G-CSF. Blood samples, drawn before the apheresis and samples of the apheresis products were analysed by flow cytometry for their content of CD34+ cells, furthermore, the peripheral leukocyte count was determined. Our aim was to define a parameter that reliably predicts the efficacy of leukapheresis in these patients. We found a significant correlation (r = 0.85; p < 0.0001) between the absolute CD34 positive cell count prior to leukapheresis and the yield of CD34+ cells/kg body weight (bw) in the apheresis product. No correlation was observed between the leukocyte count prior to apheresis and CD34+ cells/kg bw in the apheresis product (r = 0.14; p < 0.28). In addition, we found no correlation between the number of CFU-GM in the apheresis product and the CD34+ cells/kg bw (r = 0.22; p < 0.35). Our data indicate that the peripheral CD34 positive cell count prior to leukapheresis is the best parameter for predicting the efficacy of peripheral stem cell apheresis in Ewing Tumor patients after treatment with standardized chemotherapy.

Adolescent↗