Myeloablative intensified conditioning regimen with in vivo T-cell depletion (ATG) followed by allografting in patients with advanced multiple myeloma. A phase I/II study of the German Study-group Multiple Myeloma (DSMM).

We investigated toxicity and efficacy of in vivo T-cell depletion with anti-thymocyte globulin (ATG) as part of an intensified myeloablative conditioning regimen followed by allogeneic stem cell transplantation in patients with advanced multiple myeloma. The conditioning regimen consisted of modified total body irradiation, busulfan and cyclophosphamide (n=15) or in the case of prior dose-limiting radiotherapy of busulfan and cyclophosphamide (n=3). The median age was 44 years (range, 29-53) and the median time from diagnosis to transplant was 12 months (range, 6-144).

Protein levels of genes encoded on chromosome 21 in fetal Down syndrome brain: challenging the gene dosage effect hypothesis (Part II).

Down syndrome (DS) is the most common genetic cause of mental retardation. To explain the impact of extra chromosome 21 in the pathology of DS, gene dosage effect hypothesis has been proposed, but several investigators including our group have challenged this hypothesis. Although analysis of the sequence of chromosome 21 has been essentially completed, the molecular and biochemical mechanisms underlying the pathology are still unknown.

Long-term follow-up of allogeneic stem cell transplantation in patients with severe aplastic anemia after conditioning with cyclophosphamide plus antithymocyte globulin.

We investigated the efficacy of an antithymocyte globulin/cyclophosphamide preparative regimen prior to allogeneic stem cell transplantation from HLA-identical siblings in patients with severe aplastic anemia. Since 1990, 21 patients, 6 males and 15 females, with a median age of 25 years (range: 7-43) have been enrolled in the protocol consisting of 200 mg/kg cyclophosphamide and 90-120 mg/kg antithymocyte globulin (ATG, rabbit, Fresenius, Bad Homburg, Germany). For further graft-versus-host disease (GVHD) prophylaxis all patients received cyclosporin A and a short course of methotrexate (MTX).

Methylthioadenosine phosphorylase, a gene frequently codeleted with p16(cdkN2a/ARF), acts as a tumor suppressor in a breast cancer cell line.

The human methylthioadenosine phosphorylase (MTAP) gene is located on 9p21 and is frequently homozygously deleted, along with p16(cdkN2a/ARF), in a wide variety of human tumors and human tumor-derived cell lines. The function of MTAP is to salvage methylthioadenosine, which is produced as a byproduct of polyamine metabolism. We have reintroduced MTAP into MCF-7 breast adenocarcinoma cells and have examined its effect on the tumorigenic properties of these cells.

In vivo T cell depletion with pretransplant anti-thymocyte globulin reduces graft-versus-host disease without increasing relapse in good risk myeloid leukemia patients after stem cell transplantation from matched related donors.

One-hundred and two patients with good risk myeloid leukemia (CML first chronic phase or AML first CR) were transplanted from HLA-related donors after conditioning with (n = 45) or without anti-thymocyte globulin (ATG) (n = 57). One graft failure was observed in the non-ATG and none in the ATG group. The median time to leukocyte engraftment (> 1 x 10(9)/l) was 16 (range 12-33) in the ATG group and 17 days (range 11-29) in the non-ATG group (NS) and for platelet engraftment (> 20 x 10(9)/l) 24 and 19 days (P = 0.

[Unrelated donor stem cell transplantation in children: low toxicity using a GvHD-prophylaxis regimen with CSA, MTX, metronidazole,iv-immunoglobulin and ATG].

Background: Unrelated donor (UD) hematopoietic stem cell transplantation (HSCT) is accepted as a therapy for leukaemic diseases and varying inborn diseases if a suitable related donor cannot be found. The goal of immunosuppressive therapy with UD-HSCT is an effective prevention of graft-versus-host-disease (GvHD) on one hand. On the other hand an optimal balance with immunocompetence of the transplanted bone marrow is desirable in order to prevent graft failure, infection and, in the case of leukaemic diseases, potentially control the underlying disease.

S-adenosylhomocysteine, but not homocysteine, is toxic to yeast lacking cystathionine beta-synthase.

Elevated plasma homocysteine is associated with a variety of diseases in humans including coronary heart disease, stroke, peripheral vascular disease, and birth defects. However, the mechanism by which plasma homocysteine affects cells is unknown. We have examined the growth of isogenic wild-type and cystathionine beta-synthase (CBS) deficient yeast in response to homocysteine and its immediate metabolic precursor, S-adenosylhomocysteine (SAH).

Stem cell mobilisation with 16 microg/kg vs 10 microg/kg of G-CSF for allogeneic transplantation in healthy donors.

We compared two doses of recombinant human granulocyte-stimulating factor (G-CSF) for stem cell mobilisation in 90 healthy donors for allogeneic stem cell transplantation in a retrospective analysis. Group I (n = 46) received 10 microg/kg G-CSF (filgrastim) given as 5 microg/kg twice daily, and group II (n = 44) received 16 microg/kg, given as 8 microg/kg twice daily with a 12-h interval. The groups were well-balanced for age and body-weight.

Functional and comparative bioinformatic analysis of expressed genes from wheat spikes infected with Fusarium graminearum.

Fusarium head blight, caused by the fungus Fusarium graminearum, is a major disease on wheat (Triticum aestivum L.). Expressed sequence tags (ESTs) were used to identify genes expressed during the wheat-F.

Correlation of time to platelet engraftment with amount of transplanted CD34+CD41+ cells after allogeneic bone marrow transplantation.

A major problem after autologous or allogeneic stem cell transplantation is prolonged thrombocytopenia. There are several studies published about correlations of the composition of the graft and time to platelet engraftment for autologous transplantation but only a few studies for allogeneic transplantation. In our study, we wanted to find out whether the correlation between the time to platelet engraftment and amount of transplanted CD34(+)CD41(+) cells described previously after autologous peripheral blood stem cell transplantation could be reproduced in the allogeneic bone marrow transplantation setting.

Busulfan, cyclophosphamide, and etoposide as high-dose conditioning regimen in patients with malignant lymphoma.

We investigated the efficacy and toxicity of the combination of busulfan, cyclophosphamide, and etoposide (Bu/Cy/VP-16) as a preparative regimen prior to autologous hematopoietic stem cell transplantation (ASCT) in patients with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL). Fifty-three patients with recurrent ( n=30), refractory ( n=20), or high-risk ( n=3) lymphoma were enrolled. The 10 patients with HD and 43 with NHL (median age: 46 years, range: 18-64) received busulfan (16 mg/kg), cyclophosphamide (120 mg/kg), and etoposide (30 or 45 mg/kg) followed by ASCT.

Short-term folic acid supplementation induces variable and paradoxical changes in plasma homocyst(e)ine concentrations.

Folic acid is presently the mainstay of treatment for most subjects with elevated plasma homocyst(e)ine concentrations [Plasma or serum homocyst(e)ine, or total homocysteine, refers to the sum of the sulfhydryl amino acid homocysteine and the homocysteinyl moieties of the disulfides homocystine and homocystein-cysteine, whether free or bound to plasma proteins.] Changes in homocyst(e)ine in response to folic acid supplementation are characterized by considerable interindividual variation. The purpose of this study was to identify factors that contribute to heterogeneity in short-term responses to folic acid supplementation.

Practices of infectious disease prevention and management during hematopoietic stem cell transplantation: a survey from the European group for blood and marrow transplantation.

Protocols for the prevention of infections after allogeneic or autologous hemopoietic stem cell transplantations are usual. A questionnaire was sent out to the members of the European Group for Bone and Marrow Transplantation (EBMT) in the spring of 1999. A total of 308 questionnaires from 180 centers were returned.

Interference of cytokeratin-20 and mammaglobin-reverse-transcriptase polymerase chain assays designed for the detection of disseminated cancer cells.

Several reverse-transcriptase polymerase chain reaction (rtPCR) assays have been designed for the detection of disseminated cancer cells. The specificity of these discussed molecular approaches is controversial. Biological interference of the cytokeratin-20 and mammaglobin rtPCR assays has been investigated.

A fludarabine-based dose-reduced conditioning regimen followed by allogeneic stem cell transplantation from related or unrelated donors in patients with myelodysplastic syndrome.

We investigated the feasibility and efficacy of a fludarabine-based dose-reduced conditioning regimen followed by stem cell transplantation from related (n = 5) or unrelated HLA-matched donors (n = 7) in 12 patients with high risk MDS, who were not eligible for a standard myeloablative conditioning regimen. The conditioning regimen consisted of fludarabine 30 mg/m(2) daily for 6 days, busulfan 4 mg/kg daily for 2 days and anti-thymocyte globulin (ATG, rabbit) 10 mg/kg daily for 4 days in 11 patients, while one patient received fludarabine, ATG, cyclophosphamide and thiotepa. Graft-versus-host disease prophylaxis consisted of cyclosporine and a short course of methotrexate.

Disseminated breast cancer cells prior to and after high-dose therapy.

Women with breast cancer in a distinct stage of disease can benefit from high-dose therapy (HDT) with autologous stem cell support; however, a significant number of these patients relapse despite this intensive treatment. This study investigates the persistence of malignancy on the single-cell level. A total of 194 data sets consisting of bone marrow and blood samples obtained prior to and after HDT and of aliquots of apheresis products were searched with immunocytochemistry and reverse transcriptase polymerase chain reaction (RT-PCR) for disseminated cancer cells.

Real-time quantitative Y chromosome-specific PCR (QYCS-PCR) for monitoring hematopoietic chimerism after sex-mismatched allogeneic stem cell transplantation.

Y chromosome-specific sequences can be used to detect remaining male cells after sex-mismatched allogeneic blood stem cell transplantation (HSCT) involving a male patient and female donor, which represents approximately 25% of all cases. We developed a quantitative Y chromosome-specific PCR assay (QYCS-PCR) based on the DFFRY gene for the determination of hematopoietic donor chimerism. We analyzed blood and marrow samples from more than 40 patients at various time points after both standard and nonmyeloablative allogeneic HSCT.

Patient cytomegalovirus seropositivity with or without reactivation is the most important prognostic factor for survival and treatment-related mortality in stem cell transplantation from unrelated donors using pretransplant in vivo T-cell depletion with anti-thymocyte globulin.

We evaluated the cytomegalovirus (CMV) serostatus as a risk factor for survival and treatment-related mortality (TRM) in 125 patients allografted from an unrelated donor between 1994 and 1999. All patients received pretransplant in vivo T-cell depletion using rabbit anti-thymocyte globulin (ATG). Only one patient had primary graft failure and severe grade III/IV graft-versus-host disease occurred in 14% of the patients.

Anti-thymocyte-globulin as part of the preparative regimen prevents graft failure and severe graft versus host disease (GvHD) in allogeneic stem cell transplantation from unrelated donors.

To reduce the incidence of GvHD and the rate of graft failure in unrelated stem cell transplantation, we incorporate anti-thymocyte globulin in the preparative regimen in 98 patients with hematological or inherited storage disease. The median age was 32 years (range: 1-56) and 84 patients underwent transplantation from HLA-A,-B and DR identical donor, while in 14 patients the donor were mismatched either in HLA- A, -B or -DR locus. Only one patient with chronic myelocytic leukemia (CML) and blast crisis had a primary graft failure (1%).

Disposition of homocysteine in subjects heterozygous for homocystinuria due to cystathionine beta-synthase deficiency: relationship between genotype and phenotype.

We have investigated 31 subjects from five unrelated families with one or more members with cystathionine beta-synthase (CBS) deficiency. On the basis of their CBS genotype, the subjects were grouped as normal (n = 11) or heterozygotes (n = 20). Based on pyridoxine effect in the probands, the heterozygotes were further classified as pyridoxine-responsive (n = 9) or non-responsive (n = 11).

Comparison of total body irradiation vs busulfan in combination with cyclophosphamide as conditioning for unrelated stem cell transplantation in CML patients.

We compared fractionated total body irradiation (12 Gy)/cyclophosphamide (120 mg/kg) with busulfan (16 mg/kg)/cyclophosphamide (120 mg/kg) as preparative therapy in unrelated donor stem cell transplantation of CML patients. Fifty patients with CML (1.CP = 46; aP = 4) and a median age of 36 years (range 16-52) were enrolled in this sequential trial between 1994 and 1999.