Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seventy-three BMT procedures (42 allogeneic-BMT, 30 autologous-BMT, 1 syngeneic transplant) were undertaken at the Shariati Hospital in Tehran between March 1991 and November 1993. Allogeneic-BMT was performed for thalassaemia major (n = 23), AML in complete remission (n = 3), severe aplastic anaemia (n = 7), CML (n = 7), dyskeratosis congenita (n = 2) and Fanconi anaemia (n = 1). Conditioning regimens comprised busulphan (BU) plus cyclophosphamide (CY) or CY only. Thirty-two (78%) of the 43 patients remain alive 1-34 months after BMT. Twelve patients died: the causes of death were haemorrhagic cystitis (n = 1), CMV pneumonitis (n = 1), GVHD (n = 3), infection (n = 3), rejection (n = 1), VOD (n = 2) and hepatitis (n = 1). Autologous-BMT was performed for patients with AML in CR (n = 16), ALL in CR (n = 9), lymphoma in relapse (n = 3), Ewing sarcoma (n = 1) and multiple myeloma (n = 1). The median age was 18 years. Conditioning regimens were Ara C plus CY, etoposide plus CY and high-dose melphalan. Sixteen (54%) of the 30 patients survive, 14 in continuous complete remission. The causes of death were relapse (AML (n = 7), ALL (n = 4), lymphoma (n = 1)), VOD (n = 1) and infection (n = 1).
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PMID:Bone marrow transplantation in Iran. 792 Mar 8

Allogeneic bone marrow transplantation (BMT) is associated with a severe complication--graft-versus-host disease (GVHD). Although effectively preventing GVHD, ex vivo T-lymphocyte marrow depletion unfortunately increases graft rejection and reduces the graft-versus-leukemia (GVL) effect. The ex vivo transfer of the herpes simplex thymidine kinase (HS-tk) suicide gene into T cells before their infusion with hematopoietic stem cells could allow for selective in vivo depletion of these T cells with ganciclovir (GCV) if subsequent GVHD was to occur. Thus, one could preserve the beneficial effects of the T cells on engraftment and tumor control in patients not experiencing severe GVHD. To obtain T cells specifically depleted by GCV, we transduced primary T cells with a retroviral vector containing the HS-tk and neomycin resistance (NeoR) genes. Gene transfer was performed by coculturing PHA +/- CD3- or alloantigen-stimulated purified T cells on an irradiated retroviral vector producer cell line or by incubating the T cells in supernatant from the producer. Subsequent culture in G418 for 1 week allowed for the selection of transduced cells. GCV treatment of interleukin-2-responding transduced and selected cells resulted in greater than 80% growth inhibition, whereas GCV treatment of control cells had no effect. Similarly, the allogeneic reactivity of HS-tk-transduced cells was specifically inhibited by GCV. Combining transduced and nontransduced T cells did not show a bystander effect, thus implying that all of the cells inhibited by GCV were indeed transduced. Lastly, studies involving the transduction of the HUT-78 (T-lymphoma) cell line suggest that stable expression of HS-tk can be maintained over 3 months in vitro in the absence of G418. In summary, we have established the feasibility of generating HS-tk-transduced T cells for subsequent in vivo transfer with hematopoietic stem cells and, if GVHD occurs, specific in vivo GCV-induced T-cell depletion in allogeneic BMT recipients.
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PMID:Ganciclovir treatment of herpes simplex thymidine kinase-transduced primary T lymphocytes: an approach for specific in vivo donor T-cell depletion after bone marrow transplantation? 804 49

To explore the augmentation of cyclosporin-induced graft-versus-host disease (GVHD) in autologous bone marrow transplantation (BMT), we conducted a phase I dose escalation trial of interferon (IFN)-alpha 2a. A dose of either 1 or 3 x 10(6) units of IFN-alpha 2a was given by daily sc injection starting on day 0 of BMT and continuing for 28 days. Cyclosporine (CYA) was also started on day 0 of BMT at a dose of 1 mg/kg/day for 28 days. We enrolled 22 patients (median age 43 years, range 19-55 years, male/female ratio = 9/13) which included 11 patients with lymphoma, 5 patients with Hodgkin's disease, 4 patients with AML and 1 patient each with acute lymphoblastic leukemia (ALL) and myeloma. Patients were divided into four groups: two control groups received either CYA or IFN-alpha 2a alone and the other two groups received IFN-alpha 2a at a dose of either 1 x 10(6) or 3 x 10(6) units/day sc concomitantly with CYA for 28 days. IFN-alpha 2a treatment was terminated early in 5 patients: 2 patients receiving IFN-alpha 2a at a dose of 3 x 10(6) units/day developed intractable fatigue, nausea and vomiting and 3 other patients had life-threatening transplant-related complications not related to IFN-alpha 2a (1 patient receiving 3 x 10(6) units/day, and 2 receiving 1 x 10(6) units/day). These patients were considered not evaluable. Of the 17 evaluable patients, all 13 who received IFN-alpha 2a developed GVHD regardless of whether they received CYA whereas only 2 of the 4 patients who received CYA alone developed detectable GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase I study of alpha-interferon augmentation of cyclosporine-induced graft versus host disease in recipients of autologous bone marrow transplantation. 805 15

Treatment of lethally irradiated mice with a short course of high-dose interleukin (IL)-2 markedly inhibits acute and chronic graft-versus-host disease (GVHD), while preserving a graft-versus-leukemia (GVL) effect of allogeneic T-cells. We recently demonstrated that this GVL effect, observed with the EL4 leukemia/lymphoma in the A/J-->B10 strain combination, was mediated by CD8+ A/J T-cells in a CD4-independent fashion. IL-2 inhibited only the activity of CD4+ cells, and not that of CD4-independent CD8+ T-cells in A/J spleen cell inocula. This inhibition of CD4 function was sufficient to markedly inhibit GVHD, thus explaining the dissociation of GVHD and GVL in IL-2-treated mice. We have now performed studies to determine the capacity of IL-2 to inhibit GVHD induced across a variety of different histocompatibility barriers. IL-2 significantly delayed GVHD mortality in three of four additional fully major histocompatibility complex (MHC) plus minor-disparate strain combinations when CD4+ T-cells were given. Numbers of CD8+ T-cells comparable to those that might contaminate human marrow demonstrated a relatively poor capacity to produce acute GVHD when given without CD4+ cells in all of three additional strain combinations evaluated. In one of these strain combinations (B10-->BALB/c), IL-2 protected against acute but not chronic GVHD mortality when CD4+ cells were given with or without CD8+ cells. In one fully allogenic strain combination, B10-->A/J, IL-2 did not inhibit the GVHD produced by CD4+ cells given with or without CD8+ cells. IL-2 was unable to inhibit CD8-mediated GVHD in strain combinations differing at isolated class I MHC loci. In a strain combination differing only at multiple minor histocompatibility antigen (HA) loci, B10-->C3H.SW, GVHD was largely CD8-dependent, but IL-2 did not inhibit the small CD4-mediated component of GVHD. Together, these results suggest that IL-2 inhibits a restricted subset of CD4 cells or functions, and that the type of CD4 activities mediating GVHD is determined by the particular histoincompatibilities between donor and host.
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PMID:Strain dependence of interleukin-2-induced graft-versus-host disease protection: evidence that interleukin-2 inhibits selected CD4 functions. 811 Jul 26

A group of 330 oncological patients were supported throughout a 7-year period with central venous catheters (Broviac/Hickman catheters) and underwent standard oncological chemotherapy, because of hematological malignancies or solid tumors (156 children), or a myeloablative conditioning regimen followed by bone marrow transplantation because of leukemia or lymphoma (174 patients: 110 adults, 64 children). Of these, 17 patients (8 after bone marrow transplantation) developed a catheter-related bacteremia and were treated by at least two antibiotics according to the sensitivity of the bacteria. In 1 patient the catheter (infected by Bacillus cereus) was removed on day 25 of antibiotic treatment because of persistent high fever and further positive blood cultures. After bone marrow transplantation, 2 other patients, with a Pseudomonas or a Staphylococcus infection respectively, did not respond to the combined antibiotic treatment and died 1 week and 7 weeks later, respectively, from transplant-related severe graft-versus-host disease. In the other 14 patients antibiotic treatment was successful and removal of the central-vein catheter could be avoided.
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PMID:Results of antibiotic treatment of Hickman-catheter-related infections in oncological patients. 815 60

In recent years, the soluble Interleukin-2 Receptor (sIL-2R) has gained recognition as a valuable marker of in vivo activated immune functions in a variety of diseases. We studied sIL-2R levels in patients with cytomegalovirus (CMV) disease, and/or graft versus host disease (GVHD) following bone marrow transplantation (BMT). Our study included 36 patients after T-cell depleted allogenic BMT and 11 healthy controls. Mean sIL-2R serum levels were significantly higher after BMT than before (1273 u/ml vs. 629 u/ml, respectively, p < 0.007). In the patients who developed CMV disease, with or without GVHD, mean sIL-2R levels increased significantly (2866 u/ml p < 0.004); there was a drop after recovery (1949 u/ml), but not a return to pre-CMV onset levels. Similar elevated sIL-2R levels were found in patients during CMV disease only, GVHD only, or both. In patients who developed GVHD, sIL-2R levels were positively correlated with the severity of GVHD (Pearson's correlation coefficient .8322, p < 0.003). We conclude that sIL-2R may serve as a valuable nonspecific marker for the presence of CMV disease and severity of GVHD following T-lymphocyte depleted BMT.
Leuk Lymphoma 1994 Jan
PMID:Soluble interleukin-2 receptor levels in cytomegalovirus disease and graft versus host disease after T-lymphocyte depleted bone marrow transplantation for hematological neoplasias. 816 58

87 patients underwent bone marrow transplantation (BMT) in Innsbruck between 1983 and 1992. 81 patients were suffering from hematologic malignancies and severe aplastic anemia and six patients had advanced solid tumours/sarcoma. 56% of the patients undergoing HLA-identical sibling BMT were in an advanced or refractory stage of disease at the time of BMT. 19 patients underwent autologous BMT and 5 patients received a graft from an HLA-matched unrelated donor. Patients were treated with standard conditioning regimens according to the underlying disease. Cyclosporine A (CsA) was given prophylactically against graft-versus-host disease (GVHD) either alone or in combination with methotrexate. Probability of survival for patients transplanted in the first chronic phase of chronic myelogenous leukemia (CML) was 85%, whereas the disease free survival (DFS) for patients transplanted in accelerated phase or blast crisis was only 40%. DFS for acute myelogenous leukemia (AML) in first complete remission and acute lymphoblastic leukemia (ALL) standard-risk (i.e., first or second complete remission) was 71% and 60%, respectively. All patients transplanted for non-Hodgkin's lymphoma (NHL) or Hodgkin's disease had refractory or advanced disease. Probability of survival for lymphoma patients was 60%. Acute GVHD > grade II developed in 35% of patients undergoing HLA-identical sibling BMT (46% in the high-risk group vs. 21% in the standard-risk group). Main causes of death in the high-risk group were relapse (31%), severe bacterial or fungal infections (17%), interstitial pneumonia (11%) and acute GVHD (6%).
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PMID:[Innsbruck results of bone marrow transplantation in treatment of hematologic neoplasms and solid tumors]. 819 54

The management of chronic myeloid leukemia (CML) patients who relapse after allogeneic bone marrow transplantation (BMT) is difficult. Hydroxyurea, alpha interferon, second BMT and leukocytes infusion are various options but none of these approaches is clearly optimal. Hydroxyurea controls the symptoms in most patients without any apparent survival benefit. Alpha interferon (IFN) results in haematological remission in most cases with partial or total Philadelphia negativity in 20-30% of patients. Whether IFN therapy prolongs survival is not yet certain. Second BMT results in successful outcome in about half of the patients, however toxicity to the preparatory regimen, post transplant venocclusive disease and acute graft versus host disease are all major complications. An interval of less than 6 months between the initial and second BMT is generally associated with a poor outcome. Buffy coat infusions from the original donor have resulted in a cytogenetic remission in most patients. Less intensive preparatory regimes, donor buffy coat infusion and the use of biological response modifiers post transplant in order to augment the graft versus leukemia effect in high risk patients may indeed be possible areas of improvement in future studies.
Leuk Lymphoma 1993 Jun
PMID:Chronic myeloid leukemia: management of relapse after allogeneic bone marrow transplantation. 822 Jan 14

Cyclosporine and prednisone were administered as graft-versus-host disease (GVHD) prophylaxis to nine patients undergoing marrow transplant from HLA matched, unrelated donors. RhGM-CSF was administered at a dose of 250 micrograms/m2 daily to all patients. The median day of neutrophil recovery to > or = 500/mm3 was Day 16. Four patients developed Grade II acute GVHD and four developed Grade III acute GVHD. One patient, who survived only 25 days, did not develop GVHD at all. One patient developed systemic infection within the first 28 days after marrow infusion. Comparison of these data to a prior series of patients undergoing bone marrow transplant (BMT) from unrelated donors who were treated with rhGM-CSF along with methotrexate and cyclosporine for GVHD prophylaxis suggests that rhGM-CSF is well-tolerated, neutrophil recovery may be earlier but the severity of GVHD does not appear reduced. Selection of the GVHD prophylaxis regimen may affect the hematopoietic response to cytokine therapy. Further trials with rhGM-CSF in patients undergoing BMT from unrelated donors are required.
Leuk Lymphoma 1993 Jun
PMID:rhGM-CSF after allogeneic bone marrow transplantation from unrelated donors: a pilot study of cyclosporine and prednisone as graft-versus-host disease prophylaxis. 822 Jan 15

Chronic myelogenous leukemia (CML) is a uniformly lethal malignant disorder of the hematopoietic stem cell. Although CML cannot be cured with conventional therapy, recent results suggest that therapy with marrow transplantation may prolong survival and, in some cases, provide curative therapy. Approximately 30% of otherwise eligible marrow transplant candidates have an HLA matched or one antigen mismatched related donor. Related donor marrow transplantation therapy for patients in the chronic phase of CML results in 45-70% long-term, disease-free survival. Younger recipient age, transplant in chronic rather than advanced phase and transplant within one year of diagnosis provide a better outcome. Graft versus host disease (GVHD), pneumonia and systemic infections are commonly encountered complications. T-lymphocyte depletion of donor marrow reduces the incidences of acute and chronic graft versus host disease but is associated with a higher relapse rate and lower overall incidence of disease-free survival than use of non-T-depleted marrow. The use of HLA matched or one antigen mismatched unrelated donors allow successful marrow transplantation in approximately 30% of CML cases where a suitably matched related donor is not available. Unrelated donor marrow transplantation can provide stable engraftment in the majority of recipients and lead to leukemia-free survival in many cases. The beneficial effects of unrelated donor marrow transplantation are particularly apparent in young, chronic phase recipients and when performed using donor/recipient pairs identical at the HLA A, B and DR loci. A higher incidence of graft failure and GVHD than observed in sibling marrow transplant as well as prolonged convalescence in some cases can be anticipated.(ABSTRACT TRUNCATED AT 250 WORDS)
Leuk Lymphoma 1993
PMID:Treatment of CML with unrelated donor marrow transplant. 825 98


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