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Biomedical subjects

U W Schaefer

Publications and source records attributed to U W Schaefer.

At least 55 records · Page 3Linked to original sources
PubMed1999

Detection of TT virus DNA in specimens other than blood.

BACKGROUND: Recently, a new infective agent of humans, TT virus (TTV), was identified. Very high prevalence rates of TTV in different population groups, including apparently healthy individuals, were reported for several countries. OBJECTIVES, STUDY DESIGN: In order to investigate whether or not non-parenteral transmission routes can contribute to TTV spread, we have tested saliva, urine, and stool samples from eight TT viraemic individuals for the presence of TTV DNA by polymerase chain reaction. RESULTS: TTT DNA was detected in saliva of five subjects and stools of four patients. None of the urine samples contained TTV DNA. Viral titres in saliva were close to those found in serum. In feces, TTV DNA could only be detected in low concentrations. CONCLUSIONS: Our findings on the presence of TTV DNA in saliva and stool suggest that TTV might be transmitted non-parenterally.

DNA Virus Infections↗
PubMed1999

Induction of a graft-versus-leukemia reaction by cyclosporin A withdrawal as immunotherapy for leukemia relapsing after allogeneic bone marrow transplantation.

We studied the immunomodulating effect of withdrawal of immunosuppression with cyclosporin A (CsA) in 42 patients with leukemic relapse of chronic myelogenous leukemia (CML) (n = 24), acute myeloid leukemia (AML) (n = 13) and acute lymphoblastic leukemia (ALL) (n = 5) after allogeneic unmanipulated bone marrow (BMT) or peripheral blood stem cell transplantation (PBSCT). Response to CsA withdrawal was monitored molecularly by the polymerase chain reaction for elimination of CML cells containing the bcr-abl messenger RNA (mRNA) transcript (n = 24), or mll-af4 mRNA transcript characteristic of leukemic cells with a 11q23 chromosomal abnormality (n = 1). Rapid tapering of CsA resulted in subsequent achievement of cytogenetic remission in 11 of 14 CML patients (79%) who relapsed in early disease phase (n = 9 cytogenetic relapse, n = 2 hematological relapse) after a median of 57 days. Three of 13 AML patients and one of five ALL patients achieved complete remission. CsA withdrawal was accompanied by the development of acute graft-versus-host disease (GVHD) grade II in most of the 24 patients with CML. Two patients who achieved remission of AML or ALL died from severe GVHD grade III-IV. We calculated a probability of 84% for achieving and remaining in remission with early relapse of CML 4 years after relapse post BMT, whereas patients with AML have only a probability of about 10% of achieving and remaining in remission after 3 years. Patients with advanced CML and ALL had no chance of achieving and remaining in remission in the same time period.

Adolescent↗
PubMed1999

Opportunistic CNS infection after bone marrow transplantation.

We retrospectively identified opportunistic CNS infections in 655 patients who had undergone allogeneic, syngeneic or autologous BMT or PBSCT between 1990 and 1997. Twenty-seven patients (4%) developed CNS infections. All CNS infections occurred in allogeneic BMT or PBSCT patients. The most common CNS infections were toxoplasma encephalitis (74%) and cerebral aspergillosis (18%). Furthermore, we identified one patient with candida encephalitis and one patient with viral encephalitis. Overall mortality of patients with opportunistic CNS infection was 67%. There were two different groups of toxoplasma encephalitis with a different appearance on MR imaging. The first group showed edema, but no gadolinium enhancement, whereas the second group exhibited typical MRI appearances with the exception of frequent hemorrhagic transformation. The first group had a significant shorter latency between BMT and onset of CNS infection (mean 45 days vs 180 days, P = 0.02), a significant higher daily dose of corticosteroids as treatment for graft-versus-host disease (GVHD) (P = 0.01), more severe GVHD and a higher mortality (71% vs 36%). This study shows that the most common CNS infections in our patient population are toxoplasma encephalitis and cerebral aspergillosis, that there are two distinct subgroups of toxoplasma encephalitis and that CNS infections occur after allogeneic BMT only.

Adolescent↗
PubMed1999

Content of long-term culture-initiating cells, clonogenic progenitors and CD34 cells in apheresis harvests of normal donors for allogeneic transplantation, and in patients with acute myeloid leukaemia or multiple myeloma.

Using a limiting dilution assay the frequency of long-term culture-initiating cells (LTC-IC) in the apheresis products following mobilization by granulocyte-colony stimulating factor (G-CSP) with or without chemotherapy from 14 normal donors (ND) for allogeneic bone marrow transplantation, 16 patients with multiple myeloma (MM) and 15 patients with acute myeloid leukaemia (AML), where the aphereses were intended for autologous transplantation, were compared. The estimated median incidences of LTC-IC in the first apheresis products from ND, MM and AML were 1/3289, 1/1775 and 1/13075 mononuclear cells (MNC) respectively. The patients with AML had a significantly lower incidence compared with the other two groups (P < 0.0001). There was a positive correlation between the incidence of LTC-IC and the number of CD34+ cells, the number of GM-CFC, and the number of BFU-E. The positive association with GM-CFC or BFU-E was weaker. In these experiments the percentage of CD34+ cells was the best predictor for the frequency of LTC-IC in the peripheral blood progenitor cells (PBPC). In eight cases of MM the LTC-IC assay was performed for both the first and second harvest. All cases had a lower LTC-IC frequency in the second harvest compared with the first, an average of 23% (13-42%, 95% confidence interval) and this reduction was statistically significant (P<0 001); CD34+ cells were also lower (P< 0.001).

Acute Disease↗
PubMed1998

Alveolo-capillary protein permeability and lung function in patients with late pulmonary complications after allogeneic bone marrow transplantation.

A prospective study was performed to identify markers predictive for the development of pulmonary complications in the early (<50 days) and late (>50 days) phase after bone marrow transplantation (BMT). The characterization of BMT patients with early or late pulmonary complications revealed clear-cut differences. Early and long term increase of alveolo-capillary protein permeability was associated with smoking and was found in 20 patients developing pulmonary complications within 50 days after BMT (group 1). The 22 patients who developed such complications thereafter (group 2) had more acute graft vs host disease than 66 patients who remained free of these complications for a minimum of 1 year. Concentrations of bronchoalveolar lavage (BAL) fluid albumin (alb) and serum beta2-microglobulin (S-beta2m) were determined 10 days before BMT, on days 1, 30, and 40 after BMT, whereas lung function tests were performed before BMT, after discharge from the hospital, and 6 months as well 1 year after BMT. Using cut-off values for BAL fluid alb (>2.3 mg/dl) and S-beta2m (>0.8 mg/liter) we could significantly discriminate 12 patients out of 19 group 1 patients (early pulmonary complications) as well as 9 out of 21 group 2 patients (late pulmonary complications) from 12 out of 64 group 3 patients (without such complications) 1 day after BMT. Our results demonstrate that early increased alveolo-capillary protein permeability defines a patient population at risk to develop pulmonary complications later than 50 days after BMT with up to 1 year significantly decreased lung volumes (FEV1, 73% predicted, VC, 85% predicted).

Adolescent↗
PubMed1998

Detection of CBFbeta/MYH11 fusion transcripts in patients with inv(16) acute myeloid leukemia after allogeneic bone marrow or peripheral blood progenitor cell transplantation.

We evaluated the occurrence of the CBFbeta/MYH11 fusion transcripts by PCR analysis in 10 patients with inv(16)(p13;q22) acute myeloid leukemia (AML) who underwent allogeneic bone marrow transplantation (BMT) (n = 5), peripheral blood progenitor cell transplantation (PBPCT) (n = 3), or autologous transplantation (n = 2). In addition to the analysis of minimal residual disease (MRD), the chimerism status of patients after allogeneic transplant was studied by PCR. The CBFbeta/MYH11 fusion transcript was not detectable in six of seven patients who remained in remission after allogeneic BMT or PBPCT. Two of these patients in remission were monitored for 50 months and 64 months post-BMT. One patient in remission was PCR-positive for CBFbeta 3 months post-BMT in a single BM sample, but not in a simultaneously examined blood sample, suggesting that analyses from BM samples are more sensitive than those from blood samples. Sequential PCR assays performed 6 and 12 months post-BMT obtained from the same patient were negative. Another patient with a positive PCR assay 3 months post-allogeneic PBPCT, remained PCR positive for the CBFbeta/MYH11 fusion transcript when tested 6 months post-PBPCT. A chimerism analysis by PCR revealed a mixed chimerism status in this patient. He relapsed 7 months post-transplant. Before transplant, in all nine patients who were in complete remission of AML (eight patients in 1CR, one patient in 2CR), the CBFbeta/MYH11 transcript was detectable. In one patient in relapse, the fusion transcript was not only detectable in blood and bone marrow, but also in a cerebrospinal fluid sample prior to transplant. Two patients who received autologous BMT were monitored for CBFbeta/MYH11 transcripts 3 months after BMT. The CBFbeta/MYH11 was detected in these patients. Both patients subsequently relapsed 3 months and 23 months post-autologous BMT. The results study show that analysis of the CBFbeta/MYH11 fusion transcript by PCR seems to be a suitable method for monitoring minimal residual disease in AML patients with inv (16).

Adolescent↗
PubMed1998

Influence of protective isolation on outcome of allogeneic bone marrow transplantation for leukemia.

Various isolation strategies are used to prevent infections during bone marrow transplantation; data on their efficacy are lacking. We studied whether use of high efficiency particulate air filtration (HEPA) and/or laminar airflow (LAF) units affect transplant-related mortality (TRM) or survival in the first year after allogeneic transplantation. 5065 patients with leukemia receiving bone marrow transplants from an HLA identical sibling (n = 3982) or alternative related or unrelated donors (n = 1083) between 1988 and 1992 were reported to the International Bone Marrow Transplant Registry by 222 teams. Two types of isolation were considered: (1) conventional protective isolation with single patient room and any combination of hand-washing, gloves, mask and gown; and (2) HEPA and/or LAF. Cox proportional hazards regression models were used to determine the relative risks (RRs) of transplant-related mortality (TRM) and of deaths from any cause in patients treated in HEPA/LAF units compared to patients treated in conventional isolation. HLA-identical sibling and alternative donor transplants were analyzed separately. Risks of TRM and overall mortality in the first 100 days post-transplant were significantly lower among patients treated in HEPA/LAF units than in those treated conventionally. RRs of TRM were 0.76 (P = 0.009) for recipients of HLA-identical sibling transplants and 0.65 (P = 0.003) for recipients of alternative donor transplants. Correspondingly RRs of overall mortality were 0.80 (P = 0.02) and 0.65 (P = 0.0006). Decreased risks of TRM and of death in the first 100 days post-transplant resulted in significantly higher 1-year survival rates in patients treated in HEPA/LAF rather than in conventional isolation units. Use of HEPA and/or LAF to prevent infections decreases TRM and increases survival after allogeneic bone marrow transplants for leukemia.

Adolescent↗
PubMed1997

Transplantation of filgrastim-mobilized peripheral blood stem cells from HLA-identical sibling or alternative family donors in patients with hematologic malignancies: a prospective comparison on clinical outcome, immune reconstitution, and hematopoietic chimerism.

The clinical results, cellular immune reconstitution, and hematopoietic chimerism obtained after transplantation of recombinant human granulocyte colony-stimulating factor mobilized allogeneic peripheral blood stem cells (PBSCs) from genotypically human leukocyte antigen (HLA)-identical sibling (n = 36) or alternative family donors (n = 24) were prospectively compared in patients with hematologic malignancies. Thirty-two of 34 evaluable patients with HLA-identical sibling donors and all patients with alternative family donors achieved trilineage engraftment. The median time intervals to reach peripheral neutrophil counts <500/microL (13 v 17 days) or <1,000/microL (16 v 19 days) and unsupported platelet counts <20,000/microL (11 v 15 days) or <50, 000/microL (19 v 24 days) as well as red blood cell and platelet transfusion requirements were not significantly different between both patient subsets. The cumulative probability of grades II through IV acute graft-versus-host disease (GVHD) for the 60 study patients was 48% +/- 10% but ranged between 86% +/- 12% in patients whose donors had at least one HLA-A,B,DR,DQ,DP antigen disparity in direction to acute GVHD, and 25% +/- 9% in recipients of GVHD-matched transplants (P < .003). The 2-year survival estimates were 54% +/- 10% for patients with alternative family donors and 65% +/- 9% for patients with HLA-identical sibling donors. Multivariate analysis identified the pretransplantation disease stage, patient age, and acute GVHD as independent predictors of overall and disease-free survival, whereas alternative family donors alone had no adverse effect on these clinical endpoints. Monthly monitoring of peripheral blood T-helper cell subsets, B cells, and monocytes during the first year posttransplantation showed a nearly identical course of immune cell reconstitution in both patient subsets. In addition, no differences in the proportions of complete chimeric patients were detectable between the two patient subsets by sex chromosome and variable number of tandem repeats analysis up to 12 months posttransplantation. In conclusion, PBSCs from alternative family donors represent an attractive source for allogeneic transplantation in patients lacking HLA-identical sibling donors and should be further evaluated in comparison with marrow transplants from alternative family donors.

Adolescent↗
PubMed1997

[Transplantation of hematopoietic stem cells. II: Indications for transplantation of hematopoietic stem cells after myeloablative therapy].

The destruction of hematopoiesis and lymphopoiesis by total body irradiation or high dose chemotherapy for the treatment of malignancy can be reversed by the transplantation of allogeneic or autologous hematopoietic stem cells. In primary disorders of bone marrow or immune system, allogeneic stem cells replace deficient cells. Acute leukemias can be cured, with in 50 to 80% disease free survival after 5 to 8 years. The allogeneic graft versus leukemia effect by immunoreactive cells reduces the relapse rate in myeloid and lymphoid malignancies. 40 to 70% of patients with chronic myeloid leukemia remain disease free after more than 5 years. Patients with malignant lymphoma have a 40 to 70% chance of cure with autologous transplantation, which is not increased by allogeneic cells, because of a higher incidence of severe complications. An increasing number of patients without option for cure is treated with the aim of prolonging remission or retarding disease progression, such as in chronic myeloid leukemia, multiple myeloma and certain solid tumors. New studies suggest in breast cancer with axillary lymph node metastases, that adjuvant high dose chemotherapy with autologous stem cell support will significantly improve disease free survival from 30 to over 60% after 3 to 5 years. In congenital metabolic and storage diseases deficient enzymes are substituted by the allogeneic cells. Clinical trials explore the use of stem cell transplantation after myeloablative therapy in autoimmune disorders as well as in gene therapy with transfected hematopoietic stem cells.

Combined Modality Therapy↗
PubMed1997

[Transplantation of hematopoietic stem cells. I: Definitions, principle indications, complications].

The transplantation of hematopoietic and lymphopoetic stem and progenitor cells has become a standard procedure for the treatment of many malignant diseases. Autologous stem cells are derived from the patient himself, allogeneic cells from an HLA-identical or HLA-compatible family or unrelated donor. Hematopoietic stem cells can be obtained from bone marrow, blood and fetal cord blood. After 3 to 5 days treatment, the granulocyte-colony stimulating factor (G-CSF) mobilizes stem- and progenitor cells from the marrow into the blood. This method is now standard in autologous transplantation and is increasingly preferred in allogeneic transplantation. The time to hematopoietic recovery is shorter with blood stem cells than with bone marrow cells. With myeloablative high dose therapy followed by stem cell transplantation, long term disease free survival is possible in many cases and great proportions of patients can be cured (see part II). Improvements of supportive care have reduced toxicity of treatment substantially, however severe complications still occur at oropharynx, gastrointestinal tract, liver, lung, skin, kidney, urinary tract and nervous system. After allogeneic transplantation immunocompetent donor cells can react with the recipients tissue. In HLA-identical donor and recipients differences in the minor histocompatibility antigens account for this graft-versus-host-reaction (GvH), which is mainly mediated by transplanted T-cells. The GvH-reaction can affect skin, liver, gut and other organs and cause clinically relevant GvH-disease (GvHD). The GvHD is more severe in HLA-mismatched or unrelated transplantations. Immunodeficiency and organ dysfunction due to GvHD may predispose infections and impair the outcome of transplantation. Unrelated cord blood stem cells may have a minor risk of inducing acute GvHD, as stem and T-cells are immature. After allogeneic stem cell transplantation, the relapse rate of leukemia or lymphoma is significantly reduced by immunoreactive cells:graft-versus-tumor (GvT) or graft-versus-leukemia effect (GvL).

Graft vs Host Disease↗
PubMed1997

A retrospective single centre study of the outcome of five different therapy approaches in 48 patients with relapse of chronic myelogenous leukemia after allogeneic bone marrow transplantation.

In a retrospective single centre study we examined the outcome of five different therapy approaches in 48 patients in whom a relapse of CML (13 cytogenetic relapses, 35 hematological relapses: 10 chronic phase (CP), nine accelerated phase, 16 blast crisis) occurred after allogeneic BMT. Cyclosporin A (CsA) withdrawal, interferon alpha-2b (IFN-alpha) therapy, donor leukocyte transfusions (DLT), second transplantation (2nd BMT), and chemotherapy (CTX) alone were used and studied for their response rates. Patients who achieved a complete hematologic and cytogenetic remission (CR) were studied for BCR-ABL transcripts and for their chimerism status by PCR. A strong antileukemic effect was observed after abrupt CsA withdrawal, with 10 of 20 patients achieving a CR (50%). All 10 patients with early stage (nine cytogenetic and one CP), but none of the patients with advanced disease recurrence, responded to CsA withdrawal. IFN-alpha induced in five of 11 patients (45%) a stable cytogenetic remission, whereas treatment with DLT induced a CR in only two of 14 patients (14%). A second transplant was performed in six patients. Three of six patients (50%) survive disease-free at a median of 19 months after the 2nd BMT (range 10-25). The use of CTX alone did not induce a remission.

Adolescent↗
PubMed1996

Improved immune reconstitution after allotransplantation of peripheral blood stem cells instead of bone marrow.

Clinical studies are evaluating possible advantages of allogeneic peripheral blood stem cell transplantation (PBSCT) over bone marrow transplantation (BMT). We compared immune reconstitution after PBSCT (n = 20) and BMT (n = 20) in terms of lymphocyte subset counts and proliferative in vitro responses to mitogens and recall antigens (follow-up: 5 to 11 months posttransplant). Additionally, 10 PBSC harvests and 10 marrow harvests were analyzed for their composition of immunocompetent cells. Compared with BMT patients, PBSCT recipients had PB counts of naive (CD4+CD45RA+) and memory (CD4+CD45RO+) helper T cells and of B cells (CD19+) that were elevated (P < .003, P < .001, and P < .004, respectively) and proliferative responses to phytohemagglutinin (P < .0001), pokeweed mitogen (P < .02), Tetanus toxoid (P < .0005), and Candida (P < .004) that were increased. PBSCT recipients received a mean of 188 (range, 44 to 280) x 10(6) naive helper T cells and 169 (range, 18 to 296) x 10(5) memory helper T cells per kilogram; the corresponding numbers for BMT recipients were 11 (range, 4 to 24) and 10 (range, 1 to 22) x 10(5) cells per kilogram, respectively. The question of whether the documented improved in vitro immune competence after PBSCT is associated with a lower incidence of infectious complications in vivo still needs further study.

Adult↗
PubMed1996

Bone marrow transplantation from partially HLA-matched related donors in adults with leukaemia: the experience at the University Hospital of Essen, Germany.

The Seattle group has demonstrated that bone marrow transplantation (BMT) using partially HLA-mismatched related donors is feasible in principal. However, it was unclear whether these results can also be achieved at smaller-sized BMT units. Therefore a matched pair analysis enrolling 52 BMTs from partially HLA-mismatched relatives and 52 control BMTs from HLA-identical siblings was performed at the University Hospital of Essen. Overall survival (OS) and incidence of graft-versus-host disease (GVHD) did not differ significantly after study and control BMTs (OS: 52% v 63% 1 year, 46% v 48% 5 years post transplant; acute GVHD: 37% v 35%, chronic GVHD: 67% v 55%). After study BMTs, however, therapy-related mortality (P=0.018) and incidence of graft failure (P=0.002) were increased, whereas relapse rate was reduced (11% v 27%). Two or three mismatches in HVG direction implied the same risk of graft failure as one mismatch. Therefore, (i) OS after BMT from one HLA antigen mismatched relative and from HLA-identical siblings does not differ significantly even when performed at a 'smaller' centre; (ii) two or even three HLA mismatches in host-versus graft (HVG) direction might be acceptable in family BMT for leukaemia.

Acute Disease↗
PubMed1996

Molecular studies of chimerism and minimal residual disease after allogeneic peripheral blood progenitor cell or bone marrow transplantation.

We investigated 23 patients for their chimerism status who underwent allogeneic transplantation using peripheral blood progenitor cells (PBPCT) for chronic myelogenous leukemia (CML) (n = 14), acute myelogenous leukemia (AML) (n = 5), acute lymphoblastic leukemia (n = 1), myelodysplasia (MDS) (n = 1), and Hodgkin's disease (HD) (n = 2). These data were compared with those of patients after allogeneic BMT after matching them for disease and disease stage, sex of donor and recipient, GVHD prophylaxis, conditioning therapy and degree of HLA disparity. Patients were studied monthly up to 16 months post-transplant. In 11 of 23 (48%) patients who were transplanted with PBPCs and in 18 of 23 (78%) patients after BMT a mixed chimerism was detected at 1 month post-transplant. After 3 months, six of 21 (29%) evaluable patients after PBPCT remained mixed chimeric as opposed to 12 of 21 (57%) patients after BMT. We also assessed minimal residual disease using detection of the chimeric BCR/ABL transcripts by PCR of CML patients in this study. In four of 14 (29%) patients who underwent PBPCT, the BCR/ABL chimeric transcript was detected, while after BMT eight of 14 (57%) CML patients remained BCR/ABL positive. In two of these BMT patients, a cytogenetic relapse developed subsequently, and one other patient suffered a hematological relapse, whereas one of the CML patients relapsed after PBPCT. The present data may indicate that after PBPCT the incidence of leukemic relapse is similar or even lower than after BMT.

Adolescent↗