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Biomedical subjects

W Friedrich

Publications and source records attributed to W Friedrich.

At least 55 records · Page 3Linked to original sources
PubMed1997

Allogeneic bone marrow transplantation for chronic myelomonocytic leukemia in childhood: a report from the European Working Group on Myelodysplastic Syndrome in Childhood.

PURPOSE: To evaluate the role of allogeneic bone marrow transplantation (BMT) in children with chronic myelomonocytic leukemia (CMML). PATIENTS AND METHODS: Forty-three children with CMML given BMT and reported to the European Working Group on Myelodysplastic Syndrome in Childhood (EWOG-MDS) data base were evaluated. In 25 cases, the donor was a human leukocyte antigen (HLA)-identical or a one-antigen-disparate relative, in four cases a mismatched family donor, and in 14 a matched unrelated donor (MUD). Conditioning regimens consisted of total-body irradiation (TBI) and chemotherapy in 22 patients, whereas busulfan (Bu) with other cytotoxic drugs was used in the remaining patients. RESULTS: Six of 43 patients (14%), five of whom received transplants from alternative donors, failed to engraft. There was a significant difference in the incidences of chronic graft-versus-host disease (GVHD) between children transplanted from compatible/one-antigen-mismatched relatives and from alternative donors (23% and 87%, respectively; P < .005). Probabilities of transplant-related mortality for children given BMT from HLA-identical/one-antigen-disparate relatives or from MUD/ mismatched relatives were 9% and 46%, respectively. The probability of relapse for the entire group was 58%, whereas the 5-year event-free survival (EFS) rate was 31%. The EFS rate for children given BMT from an HLA-identical sibling or one-antigen-disparate relative was 38%. In this latter group, patients who received Bu had a better EFS compared with those given TBI (62% v 11%, P < .01). CONCLUSION: Children with CMML and an HLA-compatible relative should be transplanted as early as possible. Improvement of donor selection, GVHD prophylaxis, and supportive care are needed to ameliorate results of BMT from alternative donors.

Bone Marrow Transplantation↗
PubMed1996

RAG mutations in human B cell-negative SCID.

Patients with human severe combined immunodeficiency (SCID) can be divided into those with B lymphocytes (B+ SCID) and those without (B- SCID). Although several genetic causes are known for B+ SCID, the etiology of B- SCID has not been defined. Six of 14 B- SCID patients tested were found to carry a mutation of the recombinase activating gene 1 (RAG-1), RAG-2, or both. This mutation resulted in a functional inability to form antigen receptors through genetic recombination and links a defect in one of the site-specific recombination systems to a human disease.

B-Lymphocytes↗
PubMed1996

Two novel missense and frameshift mutations in exons 5 and 6 of the purine nucleoside phosphorylase (PNP) gene in a severe combined immunodeficiency (SCID) patient.

Four percent of human severe combined immunodeficiency cases are caused by a deficiency of the enzyme purine nucleoside phosphorylase (PNP). In this study we investigated the molecular basis for this rare autosomal recessive disease. Sequence analyses led to the identification of two new mutations in the PNP gene: an A to G transition in exon 5, which leads to the substitution of tyrosine 192 by a cysteine residue, and a 1-bp deletion in exon 6, which causes premature translation termination of the PNP protein. Both PNP mutations affect predicted major structural motifs of the protein and result in post-translation instability of the enzyme.

Alleles↗
PubMed1996

Surface tension measurements on pharyngeal and tracheal aspirate samples from newborns without and with respiratory distress syndrome.

A rapid test determining surfactant deficiency or dysfunction might help in controlling therapy of respiratory distress syndrome (RDS). Forty tracheal aspirate samples (TA) from 40 newborns with RDS (group 1) and 46 pharyngeal from 46 newborns without RDS (reference group) were analyzed by surface tension measurement with the pulsating bubble surfactometer. Five surface tension parameters were compared. Marked differences between both groups could be noted for the parameters: minimum surface tension (gamma min) and stability index (S), while maximum surface tension (gamma max), surface tension after a 10-second adsorption period and hysteresis area did not have striking differences. The parameters gamma min and S have the highest diagnostic value for determining surfactant deficiency or dysfunction. For a rapid test it is sufficient to compare gamma min with reference values, because S is calculated from gamma min and gamma max.

Body Fluids↗
PubMed1996

Comparison of biochemical markers of bone resorption in patients with metabolic and malignant bone diseases.

The clinical usefulness of the urinary excretion of three bone resorption markers is compared in patients after renal transplantation and in tumour patients with and without bone metastases. The markers were the 3-hydroxypyridinium derivatives pyridinoline and deoxypyridinoline (pyridinium cross-links; measured by a polyclonal enzyme immunoassay), the cross-linked N-telopeptid-to-helix domain of type I collagen and the destruction products of type I collagen metabolism cross-reacting with a peptide sequence of the alpha 1-chain of the C-terminal telopeptide region of type I collagen (CrossLapsTM). In patients receiving renal transplantation the discriminating power of N-telopeptides was superior to that of pyridinium cross-links and CrossLapsTM, with Z scores (number of SDs from apparently healthy controls) of 6.61, 2.17 and 1.35, respectively. However, the pyridinium cross-links were the only markers for bone resorption which showed a significant increase with time (P < 0.001). Receiver operating-characteristic analysis for discriminating patients with bone metastases from those without revealed that the accuracy was 0.81 for pyridinium cross-links, 0.76 for the N-telopeptides and 0.61 for CrossLapsTM. The discriminating power for patients with bone metastases was higher for pyridinium cross-links and N-telopeptides than for CrossLapsTM, with Z scores (number of SDs from patients without bone metastases) of 4.38, 3.00 and 1.24, respectively. Linear correlation coefficients for the different markers were between +0.35 and +0.65 in patients receiving renal transplants, and between +0.58 and +0.84 in patients with bone metastases. In conclusion, in patients with metabolic and malignant bone diseases there are marked differences in the diagnostic performance of different biochemical markers of bone resorption. It is suggested that this may reflect the different facets of bone resorption or the different metabolic fates of the marker substances examined.

Biomarkers↗
PubMed1996

Bone marrow transplantation in immunodeficiency diseases.

Bone marrow transplantation (BMT) has become the treatment of choice in an increasing number of primary immunodeficiency disorders. In many of these otherwise lethal genetic diseases, BMT can completely reverse the immunological abnormality and patients may be permanently cured. In this review, current approaches in the application of this treatment and results obtained in various entities of primary immunodeficiencies are presented. A significant prognostic factor for the outcome is the clinical condition of the patient at the time of BMT, and prompt recognition of these rare disorders remains an important prognostic factor for BMT.

Bone Marrow Transplantation↗
PubMed1996

Combined CD34 positive plus CD2 negative selection for effective T-cell depletion as GvHD-prophylaxis in HLA-nonidentical blood progenitor cell transplantation.

G-CSF mobilized, T-cell-depleted peripheral blood progenitor cells (PBPC) and T-cell-depleted bone marrow (BM) were given to seven children (6 AL, 1 SCID) to prevent severe graft-versus-host-disease (GvHD) as well as graft rejection after transplantation from HLA-nonidentical parental donors. BM was T-cell-depleted by lectin agglutination and E-rosetting. For T-cell-depletion of the PBPC grafts a combination of CD34+ selection with the Ceprate SC immunoadsorption system and a subsequent depletion of CD2+ cells with immunomagnetic Dynabeads was used. The overall recovery was 0.3 (0.1-1.2)% for nucleated cells, 29 (18-45)% for CD3+ cells, respectively. The purity of CD34+ cells was 87 (68-97)% with a 0.3(0.05-0.7)% residual CD3+ T-cell contamination. In spite of the large T-cell number in the PBPC grafts the combination of CD34 positive and subsequent CD2 negative selection achieved a more than 4 log T-cell depletion and prevents severe GvHD even in HLA-nonidentical transplantation. In addition, if a high dose of progenitor cells ensures stable engraftment, this new approach could increase the possibility of wider use of HLA-mismatched family donors for transplantation.

Adult↗
PubMed1996

Improved lectin agglutination method for T-cell depletion of HLA-mismatched bone marrow grafts in children.

For T-cell depletion in HLA-nonidentical bone marrow transplantation of children with malignant diseases, we improved the original lectin/rosetting method described in 1981 by adding anti-CD2/3 coated donor red blood cells to the combination to achieve lectin agglutination in one step. Further improvements in handling led to a shortened and simplified method and better quality of the graft. Five bone marrow grafts prepared with this modified protocol contained a median number of 6 (0-28) x 10(4) T-cells per kg, corresponding to 0.02 (0-0.08)% CD3+ cells and 6 (3.7-10.5) x 10(6) CD34+ cells per kg at a median body-weight of 7 (5-38)kg. The overall recoveries after T-cell depletion were: NC 17 (10-44)%, CD34+ cells 61 (22-100)%, and CFU-GM 55 (29-212)%.

Agglutination↗
PubMed1995

Bone marrow transplantation for Fanconi anemia.

Fanconi anemia is a genetic disorder associated with diverse congenital abnormalities, progressive bone marrow failure, and increased risk of leukemia and other cancers. Affected persons often die before 30 years of age. Bone marrow transplantation is an effective treatment, but there are few data regarding factors associated with transplant outcome. We analyzed outcomes of HLA-identical sibling (N = 151) or alternative related or unrelated donor (N = 48) bone marrow transplants for Fanconi anemia performed between 1978 and 1994 and reported to the International Bone Marrow Transplant Registry. Fanconi anemia was documented by cytogenetic studies in all cases. Patient, disease, and treatment factors associated with survival were determined using Cox proportional hazards regression. Two-year probabilities (95% confidence interval) of survival were 66% (58% to 73%) after HLA-identical siblings transplants and 29% (18% to 43%) after alternative donor transplants. Younger patient age (P .0001), higher pretransplant platelet counts (P = .04), use of antithymocyte globulin (P = .005), and use of low-dose (15 to 25 mg/kg) cyclophosphamide plus limited field irradiation (P = .009) for pretransplant conditioning and cyclosporine for graft-versus-host disease prophylaxis (P = .002) were associated with increased survival. Bone marrow transplants are effective therapy for Fanconi anemia. The adverse impact of increasing age and lower pretransplant platelet count on transplant outcome favors earlier intervention, especially when there is an HLA-identical sibling donor.

Adolescent↗
PubMed1995

Results of allogeneic bone marrow transplantation in patients with leukocyte adhesion deficiency.

We have retrospectively analyzed the outcome of bone marrow transplantation (BMT) in 14 patients with leukocyte adhesion deficiency (LAD) performed in two centers between 1981 and 1993. Five patients received BMT from HLA-identical donors. Nine received T-depleted marrow from two HLA antigen- or haplotype-incompatible parents. Conditioning regimen consisted of chemotherapy exclusively in 13 patients and associated with total body irradiation (TBI) in one patient. In five cases, failure of engraftment occurred as a result of either insufficient myeloablation (n = 3) or, possibly, graft rejection in two cases of moderate phenotype of LAD. The second conditioning regimen consisted of TBI and chemotherapy with the use of anti-lymphocyte function-associated antigen 1 (LFA-1) and anti-CD2 monoclonal antibodies for patients with the moderate phenotype of LAD. These patients were successfully retransplanted. Eight patients developed acute graft-versus-host disease (GVHD). Chronic GVHD occurred in five cases. GVHD led to the death of three patients. Ten patients are alive and well 12 months to 12 years after BMT. Chimerism is full in six of these patients and mixed but stable in four with variable proportion of donor leukocytes. One patient with less than 15% donor leukocytes has mild gingivitis, while the others are well. Sequelae from BMT are limited in two cases to growth retardation caused by TBI. Success of BMT in cases of LAD including seven of nine recipients of HLA nonidentical marrow indicates that this procedure can be proposed as a curative approach to LAD regardless of an available HLA-identical donor. Great care should be taken in GVHD prophylaxis and treatment.

Adolescent↗
PubMed1995

Addison disease 10 years after bone marrow transplantation for Wiskott-Aldrich syndrome.

UNLABELLED: We report a 10-year-old boy with familial Wiskott-Aldrich syndrome (WAS) who underwent successful bone marrow transplantation (BMT) at the age of 9 months. With the exception of auto-immune haemolytic anaemia due to warm antibodies lasting 15 months there had not been any complication after BMT. Ten years later the patient presented with diarrhoea, hyperpigmentation of skin and oral mucosa, fatigue and polyuria. Diagnosis of Addison disease was confirmed by typical electrolyte imbalance and absent cortisol response to adrenocorticotrophic hormone. Adrenal antibodies were positive. On therapy with oral gluco- and mineralocorticoids, the symptoms disappeared and electrolytes normalized. To our knowledge auto-immuno endocrinopathy after BMT for WAS has not yet been reported. CONCLUSION: This is the first report of auto-immune adrenal insufficiency after BMT for WAS. The aetiopathogenesis of this condition remains unknown since auto-immune diseases as toxic side-effects of the ablative treatment before BMT have not yet been reported, and a relapse of WAS and cotransplantation of auto-immune adrenal insufficiency have been ruled out.

Addison Disease↗
PubMed1995

Intact survival with transfusion-associated graft-versus-host disease proved by human leukocyte antigen typing of lymphocytes in skin biopsy specimens.

A transient transfusion-associated graft-versus-host disease occurred in a premature infant of 30 weeks of gestation. We demonstrated donor lymphocytes in a skin biopsy specimen with a two-step immunoperoxidase technique using monoclonal antibodies against human leukocyte antigen determinants specific for the donor. The girl survived and is immunocompetent.

Antibodies, Monoclonal↗
PubMed1994

Evidence for engraftment of donor-type multipotent CD34+ cells in a patient with selective T-lymphocyte reconstitution after bone marrow transplantation for B-SCID.

Severe combined immunodeficiencies (SCID), a heterogeneous group of disorders of infancy, are fatal without treatment directed at immunologic reconstitution. Allogeneic bone marrow transplantation (BMT), which is such a treatment presents some unique features in SCID, especially when T-lymphocyte-depleted HLA haploidentical allografts are used. Donor-type T lymphopoiesis, less often B lymphopoiesis, develops, whereas myelopoiesis remains the recipient-type. Little is known about the engrafting cells in this peculiar lymphohematopoietic chimerism and the pathophysiology of the frequent failure of B-lymphocyte reconstitution. To address these issues, we purified CD34+ BM cells from a patient with selective T-lymphocyte reconstitution after HLA haploidentical BMT for B-SCID. Phenotypic analysis of CD34+ cells was performed by flow cytometry, and functional studies of donor- and recipient-type CD34+ cells were performed in vitro. Donor-type CD34+ cells, constituting approximately 2% of the CD34+ cells, were detected; both CD34+ HLA-DR- cells and CD34+ cells coexpressing B-(CD10 and CD19) and T-(CD2 and CD7) lymphocyte-associated cell surface molecules. Donor-type CD34+ cells coexpressing myeloid-associated molecules (CD13, CD14, CD15, and CD33) were undetectable. However, donor-type CD34+ myeloid progenitors could be shown in functional assays. Recipient-type CD34+ cells coexpressing B- and T-lymphocyte- as well as myeloid-associated molecules were detected, but recipient-type CD34+ cells could not be driven into T-lymphocyte differentiation in vitro. These findings provide evidence for engraftment of multipotent stem cells in our patient with B-SCID. Furthermore, the failure of B-lymphocyte reconstitution cannot be explained by lack of donor-type B-lymphocyte progenitors. Donor-type B lymphopoiesis and myelopoiesis are prevented by an unidentified mechanism.

Antibodies, Monoclonal↗
PubMed1994

Bone marrow transplantation (BMT) in Europe for primary immunodeficiencies other than severe combined immunodeficiency: a report from the European Group for BMT and the European Group for Immunodeficiency.

Bone marrow (BM) transplantations performed between 1977 and 1991 at 13 European centers in 149 patients with 11 different primary immunodeficiency (ID) diseases (excluding severe combined immunodeficiency) were analyzed retrospectively. Overall survival among recipients of HLA genetically identical BM (n = 56) was 66%. Since October 1985, the date of a previous survey, a significant improvement in survival has been achieved in most ID diseases (overall survival, 81.5% v 51.7%; P < .01), primarily because of a decrease in the frequency of infectious complications. In long-term survivors, disease correction is excellent, with minimal sequelae in most patients. In 22 patients who received closely matched BM (ie, from phenotypically identical related donors, matched unrelated donors, or one HLA-ag-mismatched related donors), the survival rate (45.5%) was not significantly better than among 71 recipients of BM with 2 or 3 mismatched HLA antigens (38%). In the latter group, favorable outcome was associated with younger age, with transplantation since October 1985 (47% v 25%; P < .0001), and with a diagnosis of leukocyte adhesion deficiency. The improvement in outcome was mainly because of a higher engraftment rate and a decrease in the frequency of infections, although Epstein-Barr virus-induced B-lymphocyte proliferative disorders occurred in 16 patients (mainly those with Wiskott-Aldrich syndrome), 10 of whom died. The improvement in engraftment corresponded to the introduction of treatment in vivo with anti-LFA-1 antibody to prevent rejection of T-cell-depleted grafts (74% engraftment and 45% survival in 38 treated patients versus 37.5% and 21%, respectively, in 24 untreated patients.

Adult↗
PubMed1994

The efficacy of time-limited play therapy with maltreated preschoolers.

Despite recognition of child maltreatment as a major national problem, there have been no controlled studies that evaluated the efficacy of individual psychotherapy with maltreated children. Thirty-six preschoolers who were attending a therapeutic nursery were provided with either 15 weeks of directive individual play therapy to supplement their ongoing milieu therapy or with their milieu therapy only. Of 13 outcome measures, children in the treatment group were superior to control children at posttest on amount of isolated play, and there were no significant differences at a 10-week follow-up assessment. Possible explanations for the general lack of significant results were discussed.

Attention↗
PubMed1994

High-dose consolidation with local radiation and bone marrow rescue in patients with advanced neuroblastoma.

Twenty-six children with advanced neuroblastoma were consolidated with cisplatin, BCNU, etoposide, melphalan, 21 Gy of local radiotherapy, and bone marrow rescue in a multicenter study. All patients were over 1 year of age at diagnosis. Twenty-two patients were treated in first complete or partial remission and four in second complete or partial remission. Hematologic rescue was autologous (n = 23), allogeneic (n = 2), or syngeneic (n = 1). Extrahematological toxicity involved primarily the gastrointestinal mucosa. Among five fatal toxicities, three included intestinal hemorrhage. Fourteen patients relapsed after BMT, four of them at the primary site. Seven children survive progression-free after 16-56 months. These results are essentially not different from a single-center study with the same protocol or from other published studies. The value of megatherapy for patients with advanced neuroblastoma or for a subgroup of them can only be established on a larger number of patients than most national trials accrue.

Antineoplastic Combined Chemotherapy Protocols↗