PubMed Health⌕ Search

Biomedical subjects

G Vogelsang

Publications and source records attributed to G Vogelsang.

At least 19 recordsLinked to original sources
PubMed2006

Chronic graft-versus-host disease: implications of the National Institutes of Health consensus development project on criteria for clinical trials.

Chronic graft-versus-host disease (GVHD) has been a difficult problem to address and clinical research in this area lags behind other innovations in hematopoietic stem cell transplantation (HCT). Recently the international transplant community has focused more on chronic GVHD. This new focus is well represented by the development of the National Institutes of Health sponsored chronic GVHD consensus project, which has unified the transplant community's approach to chronic GVHD through the activities of focused working groups. From December 2005 through May 2006, a series of consensus documents have been published addressing the areas of diagnosis and staging, histopathology, strategies for the development and validation of biomarkers, response criteria, ancillary therapy and supportive care and the design of clinical trials. This paper summarizes and discusses these reports, focusing specifically on diagnosis and scoring and response criteria. Although these documents represent a huge effort by the research community, they must be prospectively implemented and validated. These new criteria should advance the standards and uniformity of chronic GVHD clinical research. The ultimate success of this project is dependent on whether these recommendations move the field forward. This is an opportunity for the transplant community to unite and make a significant impact in chronic GVHD.

Chronic Disease↗
PubMed2003

Phase I study of escalating doses of low-dose-rate, locoregional irradiation preceding Cytoxan-TBI for patients with chemotherapy-resistant non-Hodgkin's or Hodgkin's lymphoma.

PURPOSE: In patients in whom bone marrow transplantation (BMT) fails, recurrence often occurs at sites known to have contained disease before initiating BMT. The purpose of this study was to find the maximal tolerable dose of locoregional irradiation (LRT) between 1000 and 2000 cGy that could be integrated with our Cytoxan-total body irradiation (TBI) BMT conditioning regimen in the treatment of lymphoma. METHODS AND MATERIALS: Patients had Hodgkin's or non-Hodgkin's lymphoma in chemotherapy-refractory relapse. All patients received LRT to a maximum of three sets of fields encompassing either all current or all previously known sites of disease. Cytoxan-TBI consisted of cyclophosphamide 50 mg/kg daily for 4 days followed by TBI of 1200 cGy given in four fractions. RESULTS: Twenty-one patients were enrolled. Radiation Therapy Oncology Group Grade 3 in-field acute toxicity was observed in 1 patient at each dose level up to 1500 cGy and in 3 of 6 patients receiving 2000 cGy. Clinically evident late toxicities were limited to hypothyroidism and one second malignancy occurring outside the LRT fields. CONCLUSION: Low-dose-rate, LRT with concurrent Cytoxan-TBI before BMT has acceptable rates of in-field toxicity for doses up to 1500 cGy in five fractions. This regimen safely permits the use of a total combined radiation dose of up to 2700 cGy during 2 weeks, with encouraging in-field response rates in treatment-refractory patients.

Adolescent↗
PubMed2002

Thalidomide-induced neuropathy.

BACKGROUND: Thalidomide is effective for the treatment of some refractory dermatologic and oncologic diseases. Toxic neuropathy limits its use, as embryopathy can be avoided by contraceptive measures. OBJECTIVE: To describe the clinical, electrophysiologic, and pathologic features of thalidomide-induced peripheral neuropathy. METHODS: Clinical and electrophysiologic examinations were performed in seven patients with thalidomide-induced peripheral neuropathy. Thalidomide was used for graft-vs-host disease, pyoderma gangrenosum, and discoid lupus with dosages ranging from 100 to 1,200 mg/day for 5 to 16 months (cumulative dosages of 24 to 384 g). RESULTS: All seven patients had clinical and electrophysiologic evidence of a sensory more than motor, axonal, length-dependent polyneuropathy that presented as painful paresthesias or numbness. Sural nerve biopsies, done in three patients, showed evidence of Wallerian degeneration and loss of myelinated fibers. The symptoms, signs, and electrophysiologic data correlated with total cumulative dose of thalidomide. CONCLUSIONS: Thalidomide induces a dose-dependent sensorimotor length-dependent axonal neuropathy; it should be judiciously used with close neurologic monitoring.

Adult↗
PubMed2002

Bone marrow transplantation in Shwachman-Diamond syndrome.

Shwachman-Diamond syndrome is a rare autosomal recessive disorder characterized by exocrine pancreatic dysfunction, metaphyseal dysostosis and bone marrow dysfunction with a predilection towards severe hematologic complications. Allogeneic bone marrow transplantation has been used as a therapeutic approach for SDS patients with serious hematologic abnormalities with mixed results. There is some concern that these patients may be more susceptible to early (<100 days) transplant-related complications than other transplant groups. We report a patient who received a matched allogeneic transplant without developing serious early transplant-related complications, but eventually died from relapse of his disease. Although experience is limited, a review of the reported cases suggests patients with SDS may be transplanted without significant short-term morbidity and mortality.

Adult↗
PubMed2002

Endoscopic findings predict the histologic diagnosis in gastrointestinal graft-versus-host disease.

BACKGROUND AND STUDY AIMS: Graft-versus-host disease (GvHD) of the gastrointestinal tract is a major cause of morbidity and mortality after allogeneic bone marrow transplantation (BMT). Whether endoscopic findings predict the histologic diagnosis of GvHD in the gastrointestinal tract remains controversial. We performed a study to determine the diagnostic accuracy of macroscopic endoscopy findings in the diagnosis of acute and chronic histologically proven gastrointestinal GvHD (GI-GvHD). PATIENTS AND METHODS: Endoscopic images from the intestinal mucosa of post-BMT patients were blindly graded as positive or negative for GI-GvHD and compared with corresponding histological findings, which were used as the gold standard. RESULTS: 44 BMT patients were referred for 96 endoscopic evaluations. Using 162 endoscopy-biopsy pairs, a positive association between endoscopic grading and histologic grading of GI-GvHD (odds ratio [OR] = 11.97, 95% CI 3.86, 37.16) was observed. Endoscopic diagnosis correctly predicted histologic diagnosis in both acute and chronic GI-GvHD (OR = 9.3 vs. 23.1, P = 0.31). CONCLUSIONS: The diagnostic accuracy of endoscopy was high in both acute and chronic histologically proven GI-GvHD. Accurate diagnosis of GI-GvHD might be obtained with mucosal biopsies from either the upper or lower gastrointestinal tract. Endoscopy may play a significant role in establishing early diagnosis and treatment for GI-GvHD in patients following BMT, but histologic evaluation of the gastrointestinal mucosa is needed to confirm the final diagnosis.

Adult↗
PubMed2000

Fludarabine and cyclophosphamide with filgrastim support in patients with previously untreated indolent lymphoid malignancies.

To evaluate the response rate and potential toxicities, a phase II trial was conducted of fludarabine and cyclophosphamide with filgrastim support in patients with previously untreated low-grade and select intermediate-grade lymphoid malignancies. Symptomatic patients with preserved end organ function received cyclophosphamide 600 mg/m(2) intravenous (iv) day 1 and fludarabine 20 mg/m(2) iv days1 through 5, followed by filgrastim 5 microg/kg subcutaneous starting approximately day 8. Treatment was repeated every 28 days until maximum response or a maximum of 6 cycles. Sixty patients, median age 53.5 years, were enrolled. Thirty-seven patients with non-Hodgkin lymphoma (NHL) were stage IV and 6 were stage III. Eleven of 17 patients with chronic lymphocytic leukemia (CLL) were Rai intermediate risk and 6 were high risk. The overall complete response (CR) rate was 51% and the partial response (PR) rate was 41%. Of patients with CLL, 47% achieved a CR and the remaining 53% achieved a PR. Of patients with follicular lymphoma, 60% achieved CR and 32% achieved a PR. Although the toxicity of this regimen was mainly hematologic, significant nonhematologic toxicities, including infections, were seen. Twenty-four patients subsequently received an autologous or allogeneic stem cell transplant. Engraftment was rapid, and there were no noticeable procedure toxicities in the immediate posttransplant period attributable to the fludarabine and cyclophosphamide regimen. Fludarabine, cyclophosphamide, and filgrastim make up a highly active and well-tolerated regimen in CLL and NHL.

Adult↗
PubMed2000

[Circulatory support with the mechanical heart, "HeartMate"].

Treatment with the mechanical heart, HeartMate, has been introduced in Denmark. Short-term circulatory support can be obtained by intraaortic balloon counterpulsation, an external centrifugal pump and the total artificial heart. Long-term circulatory support can be established by treatment with the HeartMate. The principle of the mechanical heart is simple--a pump is implanted in parallel to the existing heart and connected to external, portable batteries. The patient quickly improves and is brought in an optimal state for transplantation. A few patients have been able to omit the subsequent heart transplantation. The patient's own heart improved during the treatment and the native heart functioned again after the system was explanted. The main complications during treatment are bleeding, infection, thromboembolic events and systemic failure. Permanent, fully implantable mechanical circulatory pumps are under development--which may herald the beginning of a whole new era for treatment of cardiac failure.

Assisted Circulation↗
PubMed2000

[Economic aspects of implementation of the mechanical heart, "HeartMate"].

This economic evaluation was performed to assess the economic consequences for society and for the Danish health care sector of replacing the traditional treatment with Biomedicus assist device with The Mechanical Heart, HeartMate, as a bridge to transplantation for patients with severe cardiac failure. A cost-effectiveness analysis showed that the use of HeartMate is more cost-effective than the use of Biomedicus assist device. Using HeartMate one life-year gained costs DKK 225,000. Using Biomedicus one life-year gained costs DKK 270,000. The use of HeartMate results in an additional expenditure of DKK 615,000 per patient. By this additional expenditure the patients gain 3.6 extra life-years on average. The marginal expenditure by replacing the Biomedicus treatment with HeartMate is DKK 170,000 per extra life-year gained.

Cost-Benefit Analysis↗
PubMed2000

Immunotherapy with rituximab during peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.

Peripheral blood stem cell grafts from patients with lymphoma are often contaminated with neoplastic cells. Administration of a lymphoma-specific monoclonal antibody before collecting stem cells may be one way of reducing the contamination. Similarly, an antibody after transplantation at a time of minimal residual disease may increase the efficacy of the procedure. The objective of this study was to determine the safety of using rituximab as both an in vivo purging agent and a posttransplantation adjuvant. Eligible patients with lymphoma received 375 mg/m2 rituximab intravenously IV) on day 1, 2.5 g/m2 cyclophosphamide IV on day 4, and 10 microg/kg per day filgrastim starting on day 5 and continuing until completion of leukapheresis. Patients subsequently received a standard preparative regimen and then received 375 mg/m2 rituximab IV 7 days after platelet independence was achieved. Twenty-five patients (14 men, 11 women; median age, 51 years) were enrolled. Of the 25 patients, 23 received transplants after at least 2.0 x 10(6) CD34+ cells/kg were harvested. As determined with a sensitive polymerase chain reaction assay, 6 of 7 stem cell products tested were free of tumor contamination. All patients engrafted promptly, and the rituximab infusions were well tolerated. Transient neutropenia of uncertain etiology occurred in 6 patients a median of 99.5 days post-transplantation. An additional patient developed progressive pancytopenia. Rituximab used as an in vivo purging agent and adjuvant immunotherapy with peripheral blood stem cell transplantation for non-Hodgkin's lymphoma is a well-tolerated regimen. However, the ultimate determination of efficacy will require the results of ongoing studies.

Adult↗
PubMed2000

Autologous graft-versus-host disease induction in advanced breast cancer: role of peripheral blood progenitor cells.

The purpose of the present study was to investigate the impact of the use of peripheral blood progenitor cells (PBPCs) on the induction of autologous graft-versus-host disease (GVHD) in patients with advanced breast cancer. 14 women with stage IIIB and 36 women with stage IV breast cancer received cyclosporine (CsA) 2.5 mg kg-1 i.v. daily, d 0-28, and interferon-gamma (IFNg) 0.025 mg/m2 s.c. qod, d7-28, following PBPC-T +/- bone marrow transplantation (BMT). Preceding high-dose chemotherapy consisted of cyclophosphamide 6 g/m2 and thiotepa 800 mg/m2. Histologically proven > or = grade II cutaneous GVHD was induced in18/50 (36%) of patients and was independent of the source of haematopoietic support. In vitro studies showed that post-transplant, 76% of patients had developed auto-cytotoxicity against their own pre-transplant PHA-lymphoblasts. A significant correlation between the occurrence of GVHD > or = grade II and cytolysis was observed in the NK cell-line K562 and the T47D breast cancer cell-line. With a median follow-up of 2(1/2) years, the overall survival (OS) is 58%, the disease-free survival (DFS) 26%, both independent of the development of GVHD and similar to what has been observed in other studies on high-dose chemotherapy in advanced breast cancer. It therefore remains unclear whether the induction of autologous GVHD with the occurrence of auto-cytotoxic lymphocytes can result in an anti-tumour effect in this group of patients.

Adult↗
PubMed2000

An old drug for a new disease: pentostatin (Nipent) in acute graft-versus-host disease.

Bone marrow transplantation has become the modality of choice for a number of malignant conditions. One of the primary causes of morbidity and mortality following bone marrow transplantation is graft-versus-host disease (GVHD). Moderate to severe acute GVHD affects 9% to 35% of patients undergoing standard allogeneic bone marrow transplantation. The incidence of chronic GVHD is approximately 40% to 50%. In our experience at Johns Hopkins Oncology Center, patients with stages 2, 3, and 4 acute GVHD had median survivals of only 5.4, 3.6, and 2.5 months, respectively, despite treatment. Patients with chronic GVHD do not fare much better. Their overall 10-year mortality rate remains high at 42%. Significant failure rates and toxicities have been associated with all available therapeutic options for GVHD. Pentostatin (Nipent; SuperGen, San Ramon, CA) is currently used to treat a variety of hematologic malignancies. In addition to its antineoplastic effects, considerable immunosuppressive properties have been reported. Pentostatin affects the immune system by decreasing lymphocyte number and function. Its immunosuppressive effect has promise for the treatment of GVHD and warrants further study.

Acute Disease↗
PubMed1999

Salvage therapy for refractory chronic graft-versus-host disease with mycophenolate mofetil and tacrolimus.

Chronic graft-versus-host disease (GVHD) is a common late complication of allogeneic bone marrow transplantation (BMT) and is the principal cause of morbidity and non-relapse mortality. The improved management of acute GVHD has not translated into lower rates of chronic GVHD as older patients undergo allogeneic BMT, more patients receive unrelated or related mismatched allogeneic BMT, and donor lymphocyte infusion is increasingly used for treatment of post-BMT relapses. Patients with high risk chronic GVHD or those who fail on standard therapy have a bad prognosis. Salvage therapies have produced disappointing results. Here, we present a retrospective analysis of 26 patients where a steroid sparing synergistic combination of mycophenolate mofetil (MMF) and tacrolimus was used in refractory chronic GVHD. 46% patients showed an objective response, 11.5% had stable disease, 34.6% had progression and 7.7% were not evaluable. The combination was well tolerated. This promising preliminary result has prompted a trial to assess the safety and efficacy of this regimen in patients with chronic GVHD who have failed prior therapy and to determine if it would improve survival as well as quality of life in such patients.

Adult↗
PubMed1999

Immune modulation in autologous bone marrow transplantation: cyclosporine and gamma-interferon trial.

From March 1994 to November 1994, 16 patients with high risk hematological malignancies were entered in a phase I clinical trial, designed to confirm the toxicity of cyclosporine and gamma interferon given to induce autologous graft-versus-host disease (GVHD) after autologous bone marrow transplantation (ABMT). This trial was based on the results in a rodent model, in which cyclosporine given after ABMT induces an autoimmune syndrome (autologous GVHD) identical to allogeneic GVHD. Further, this autologous GVHD is associated with a graft-versus-tumor effect augmented by interferon that upregulates MHC class II expression on normal and tumor cells, the target of the cytolytic T cells in autologous GVHD. In this trial, cyclosporine 1 mg/kg/day was given from the day of bone marrow reinfusion until the completion of the interferon and gamma-interferon. Gamma-interferon at 0.025 mg/m2 every other day was started when the total white cell count was >200 cells/ml for 2 consecutive days and continued for a total of 10 doses after ABMT. The preparative regimens were busulfan and cyclophosphamide, or cyclophosphamide with total body irradiation. All patients received 4HC-purged marrow grafts. Median age was 45 years (range 19-68). The diagnoses included chemo-resistant non-Hodgkin's lymphoma (10), acute lymphoblastic leukemia (two), chemo-resistant Hodgkin's disease (two), acute myeloid leukemia (one), and multiple myeloma (one). Median absolute neutrophil count recovery was 25.5 days (range 19-46 days). Median platelet count recovery was 40.5 days (range 28-279 days). There were nine deaths, two were related to transplant toxicity (infection), while the other seven were due to relapse. Event-free survival with a median of 964 days (range 19-1441 days of follow-up was 44%. In conclusion, treatment with cyclosporine, and gamma-interferon after ABMT was well tolerated and did not impair engraftment. Further studies with a larger number of patients are required to document any beneficial anti-tumor effect of autologous GVHD induction after ABMT.

Adolescent↗
PubMed1998

Bone marrow transplantation for chronic lymphocytic leukemia.

The use of bone marrow transplant (BMT) for patients with chronic lymphocytic leukemia (CLL) is a relatively new approach when compared to the use of this therapy for other hematologic malignancies. The long natural history of CLL and significant procedure-related mortality initially deterred the use of BMT for CLL. However, improvement in transplantation procedures and supportive care paved the way for the use of BMT in patients with CLL. There are now multiple reports showing complete remissions with both autologous and allogeneic BMT. The follow-up remains short, therefore, the durability of these remissions remains to be determined. Several innovative approaches to BMT for CLL are now being explored and include non-myeloablative preparative regimens for allogeneic transplants, purging autologous grafts, and induction of graft-versus-leukemia effects. Ultimately, however, long-term disease-free and overall survival will need to be shown before BMT for CLL will gain widespread acceptance.

Bone Marrow Purging↗
PubMed1997

Human herpes virus-6 encephalitis after bone marrow transplantation: successful treatment with ganciclovir.

Here we report a case that presented with sudden onset of neurological symptoms and was treated with ganciclovir. Polymerase chain reaction analysis for human herpes virus-6 (HHV-6) from his cerebrospinal fluid was later found to be positive. He subsequently recovered with minimal residual neurological symptoms. Encephalitis secondary to this virus may be more common than previously thought in patients undergoing bone marrow transplantation. This condition should be considered in the differential diagnosis of sudden onset neurological symptoms after bone marrow transplantation.

Adult↗
PubMed1996

Erythroderma after autologous bone marrow transplantation modified by administration of cyclosporine and interferon gamma for breast cancer.

BACKGROUND: Allogeneic graft-versus-host disease is associated with decreased rates of tumor relapse. The addition of interferon gamma to cyclosporine, given to induce graft-versus-host disease after autologous bone marrow transplantation, increases the extent of the cutaneous eruption. OBJECTIVE: Our purpose was to describe the clinical and histologic cutaneous changes in 10 patients with breast cancer who received interferon gamma to potentiate graft-versus-host disease after autologous bone marrow transplantation modified by cyclosporine. METHODS: Ten women receiving autologous bone marrow transplantation modified by the administration of cyclosporine and interferon gamma were observed clinically with sequential biopsy of the skin weekly and at the time of cutaneous eruptions. RESULTS: Erythroderma (stage 3) developed in five women after the first or second administration of interferon gamma. At least on skin biopsy specimen from 7 of the 10 women showed grade 2 changes of graft-versus-host reaction, including all patients with erythroderma. Epidermal intercellular edema was prominent in these specimens with expression of keratinocyte HLA-DR and intercellular adhesion molecule 1. Induction of keratinocyte HLA-DR and intercellular adhesion molecule 1 expression was not observed in specimens from normal skin during administration of interferon gamma. CONCLUSION: This protocol causes a more widely distributed cutaneous eruption, including erythroderma (50%), than autologous bone marrow transplantation and cyclosporine administration alone (3%). Whether it will affect survival is unknown.

Adult↗
PubMed1995

Thalidomide as replacement for steroids in immunosuppression after lung transplantation.

Steroids have been implicated in postoperative complications after lung transplantation: infections, delayed wound healing, and poor bronchial anastomotic healing. Thalidomide (alpha-phthalimidoglutarimide), a sedative drug with known immunomodulatory properties, was used to replace corticosteroids after canine lung transplantation. Fifteen mongrel dogs underwent single-lung transplantation: group I (n = 5) received cyclosporin A (20 mg/kg twice a day), azathioprine (2.5 mg/kg once a day), and thalidomide (50 mg/kg twice a day). Group II (n = 5) received standard immunosuppression of cyclosporin A (20 mg/kg twice a day), azathioprine (2.5 mg/kg once a day), and prednisone (2 mg/kg once a day), and group III (n = 5) received cyclosporin A (10 mg/kg twice a day), azathioprine (2.5 mg/kg once a day), and thalidomide (50 mg/kg twice a day). Open lung biopsy and bronchoscopy were performed weekly until sacrifice on day 28. Serum thalidomide and cyclosporin A levels were followed up weekly. Group I showed essentially no rejection until week 2 and minimal rejection (grade 1) until day 28. Group II had moderate rejection (grade 2) of the graft at all time points. Group III animals had moderate to severe rejection (grades 3 to 4) after 21 days (p < 0.05 for group I versus groups II and III). The number of clinically evident episodes of pneumonia was also significantly lower in group I than in groups II and III (p < 0.05). We conclude that thalidomide appears to replace corticosteroids effectively in early postoperative immunosuppression after lung transplantation and is associated with a decreased incidence of pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗