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

Eight patients with aplastic anemia were transplanted with marrow from HLA-identical donors. Two patient rejected their grafts and died while 5 patients (71%) show no ill effects 3 months, 10 months, and more than 1, 2 and 4 years after the transplantation. Three of the patients who received unirradiated donor buffy coat after transplantation developed chronic graft-versus-host disease (GVHD) which, however, resolved following treatment with Prednisolone and Azathioprine. One patient with end-stage acute myeloid leukemia, who was transplanted with marrow from an identical twin, died 6 days after the transplantation of bleedings and sepsis. Eight patients with acute non-lymphoblastic leukemia (ANL) were transplanted, while in remission, with marrow from HLA-identical siblings. One patient died of interstitial pneumonia 3 months after transplantation, while another patient recovered from GVHD of the gut at 5 months after the transplantation. Seven out of 8 patients with ANL (88%) are home and well between 2 and 12 months after the transplantation.
 ...
PMID:Bone marrow transplantation for aplastic anemia and acute leukemia at Huddinge Hospital. 675 85

Bone marrow transplantation offers two potential therapeutic advantages over more conventional therapy of leukemia. It allows more intensive treatment to be given without regard to marrow toxicity and allows in the case of allogeneic marrow an additional immunotherapeutic effect through graft-versus-host disease (GVHD). Initially, allogeneic transplants in HLA matched sibling donors were only employed in end-stage patients. Although there were encouraging results in terms of long-term therapeutic effects, the overall mortality was prohibitive. Subsequently, patients were transplanted in remission with a marked improvement in overall survival in both acute lymphocytic leukemia and acute non-lymphocytic leukemia. The major obstacles to further improvement in the therapeutic effects of this procedure have been identified (i.e., GVHD, viral infection, and relapse in ALL) and are subject to intensive investigations that already show encouraging results. Syngeneic marrow transplantation is limited for obvious reasons, but early results have shown significant therapeutic effects, in particular, in chronic myelogenous leukemia. These results have encouraged others to use autologous bone marrow. Marrow contamination with unseen tumor cells is being approached by pharmacologic and immunologic techniques designed to "purge" marrow of tumor cells. Animal and initial clinical studies have been encouraging.
 ...
PMID:Bone marrow transplantation: current results in leukemia. 676 16

Eighty consecutive patients were transplanted with human leukocyte antigen (HLA)-identical sibling marrow for acute myelogenous leukemia (AML, N = 29), acute lymphoid leukemia (ALL, N = 23), or chronic myelogenous leukemia (CML, N = 28). Donor marrow was depleted of lymphocytes using counterflow centrifugation. Median age of the recipients was 31 years. Pretransplant conditioning consisted of cyclophosphamide and fractionated total body irradiation (TBI). Graft failure occurred in 4 of 77 evaluable patients (5%). The probability of acute graft-versus-host disease (GVHD) > or = grade 2 at day 100 after transplantation was 15%. The projected 3-year estimate of extensive chronic GVHD was 12%. The projected 3-year probability of relapse was 30% in transplants for AML in first complete remission (CR1), 35% after transplantation for ALL in CR1, and 38% after transplantation for CML in first chronic phase (CP1). The projected 3-year probability of leukemia-free survival (LFS) was 56% after transplantation for AML-CR1, 42% in patients transplanted for ALL-CR1, and 49% after transplantation for CML-CP1. The chance of relapse was significantly reduced in a cohort of 72 standard risk patients conditioned with a regimen intensified by the addition of anthracyclines. This resulted in DFS at 4 years after BMT of 63% compared to 39% in a historical control group. Enrichment of the donor marrow with NK-cells did not increase the incidence of GVHD, but did neither decrease the relapse rate after BMT. In bone marrow transplantation for leukemia, counterflow centrifugation is a useful technique for the prevention of GVHD. Further efforts should be made to reduce relapse-rate, particularly in high risk patients.
 ...
PMID:Allogeneic bone marrow transplantation for leukemia with marrow grafts treated by counterflow centrifugation. 812 52

We have treated 28 patients (pts) with malignant hematological diseases with allogeneic bone marrow transplantation (BMT). 18 pts had acute lymphoblastic (ALL) and non lymphoblastic leukemia (ANLL), 5 chronic myeloid leukemia (CML), 2 severe aplastic anemia (SAA), 1 myelodisplasia, 1 Fanconi's anemia and 1 advanced Non Hodgkin's lymphoma. All but three received the graft from HLA identical sibling donors. We used conditioning with total body irradiation and chemotherapy (cyclophosphamide, cytarabine and etoposide) in 17 pts and chemotherapy alone in 11. 24 pts had full hematological recovery 18 to 25 days post BMT. 15 pts died after BMT as a consequence of toxicity or early infection (4), graft failure (2), graft versus host disease (4) or relapse (5). Actuarial event free survival for the group with favorable prognosis (SAA, ALL and ANLL in first or second remission and CML in chronic phase) is 57% at 36 months. Allogeneic BMT is an effective and feasible therapeutic procedure for selected patients with hematological malignancies.
 ...
PMID:[Allogenic bone marrow transplantation in the treatment of malignant hematologic disease]. 852 7

Thirty-one patients (median age, 44 years) with advanced hematologic malignancies were given thiotepa 15 mg/kg, and cyclophosphamide 120 (n = 14) or 150 (n = 17) mg/kg followed by unfractionated peripheral blood stem cell transplants (PBSCT) from genotypically identical siblings (n = 28) or one antigen mismatched family donor (n = 3). Donors were mobilized with granulocyte colony-stimulating factor 5 to 10 microgram/kg/d for 6 days and underwent two to three leukapheresis on days +5, +6, +7. The median cell yield per donor expressed/kg of recipients body weight was as follows: nucleated cells 13 x 10(8)/kg; CD34+ cells 6 x 10(6)/kg; colony-forming unit-granulocyte macrophage 38 x 10(4)/kg, and CD3+ cells 449 x 10(6)/kg. The diagnoses were chronic myeloid leukemia (n = 4), acute myeloid (n = 9) or lymphoid leukemia (n = 2), acute myelofibrosis (n = 2), multiple myeloma (n = 1), lymphoma (n = 6), chronic lymphocytic leukemia (n = 1) myelodysplasia (n = 6). Twenty-eight patients had advanced disease, 29 patients were first grafts, and 2 were second transplants 3 and 9 years after the first. Neutrophil counts of 0.5 x 10(9)/L and platelet counts of 30 x 10(9)/L platelets were both achieved on day +14 (median). Engraftment could be proven by sex markers or DNA polymorphism in 29 of 31 patients: one had early leukemia relapse and one patient was unevaluable because of early death. Acute graft-versus-host disease (GVHD) was scored as minimal or absent (grade 0 to 1) in 14 patients, moderate (grade II) in 13, and severe (grade III to IV) in four. Causes of death were leukemia (n = 4), acute GVHD (n = 4, with associated cytomegalovirus infections in three), sepsis (n = 1), liver failure (n = 1), multiorgan failure (n = 1), and hemorrhage (n = 1). The actuarial transplant mortality is 29%, the actuarial relapse rate 22%. Nineteen patients survive with a median follow up of 288 days (100-690). The actuarial 2-year survival is 57%. Three patients received PBSCT from family donors mismatched for one class II antigen: all engrafted, one developed grade I aGVHD; one died of leukemia on day +155; two are alive disease free 267 to 290 days postgraft. This study suggests that thiotepa cyclophosphamide followed by unfractionated PBSC allograft may be an alternative form of transplant for adults with advanced leukemia, also in the setting of one antigen mismatched donor. The engraftment is rapid with acceptable GVHD and relatively low transplant-related mortality.
 ...
PMID:Thiotepa cyclophosphamide followed by granulocyte colony-stimulating factor mobilized allogeneic peripheral blood cells in adults with advanced leukemia. 870 95

Peripheral blood progenitor cells (PBPCs) are increasingly being used to replace bone marrow cells (BMCs) as a source of hematopoietic stem cells also in the field of allogeneic transplantation. Whereas it is well known that PBPC grafts and BM differ significantly in progenitor cell content and lymphocyte dose, the clinical consequences of these differences with respect to engraftment, graft-versus-host disease (GVHD), and the graft-versus-leukemia (GVL) effect are more difficult to assess. We present a murine model that allows us to evaluate engraftment, GVHD, and GVL effect of allogeneic PBPC transplantation (PBPCT). Balb/c mice (H-2d) served as recipients. Donors were major histocompatibility complex-matched DBA/2 mice or syngeneic Balb/c mice, respectively. Experiments with increasing numbers of BMCs or Filgastrim-mobilized PBPCs showed that the number of progenitor cells in the graft was correlated with the probability to engraft, irrespective of the graft type. With identically high cell numbers transferred (1 x 10(9) nucleated cells/kg body weight [BW]), the mortality rates due to GVHD (25%) were about the same after allogeneic BM transplantation (BMT) and allogeneic PBPCT, although PBPC grafts contained four times more CD3+ T cells as compared with BM grafts (6.2 x 10(8) v 1.4 x 10(8)/kg BW). For investigation of GVL activity, Balb/c recipients were injected with syngeneic cells of the B-lymphocytic leukemia cell line A20 2 days before transplantation. After total body irradiation to a dose of 7.5 Gy, 1 x 10(9)/kg BW Balb/c PBPCs, DBA BMCs, or DBA PBPCs were infused. The relapse rates observed were 80% after syngeneic PBPCT (n = 22), 60% after allogeneic BMT (n = 23), and 34% after allogeneic PBPCT (n = 26) (allogeneic BMT v PBPCT, P = .032). We conclude that transplantation of allogeneic PBPCs instead of BM may enhance the GVL effect without an increase of GVHD.
 ...
PMID:Allogeneic peripheral blood progenitor cell transplantation in a murine model: evidence for an improved graft-versus-leukemia effect. 926 90

A 26-year-old man, affected by acute non-lymphocytic leukemia, received a bone marrow transplantation from his HLA identical sister. A mild (grade 1) acute graft-versus-host disease (GVHD) developed during the first month after BMT. A moderate (grade 2) muco-cutaneous GVHD was present from the 4th month on, in association with recurrent oral herpes simplex infection. A typical clinical and electromyographic picture of myasthenia gravis (MG) developed 46 months after BMT, requiring continuous medication with pyridostigmine. A high titer of antibiotics against the acetylcholine receptor was found in the serum of the patient but not in the serum of the donor. Since the donor had no evidence of MG or other autoimmune disorders, this is likely to be an autoimmune complication of chronic GVHD. Other cases described in the literature are reviewed: a recurrent expression or coexpression of some HLA antigens was recorded, indicating that some genetic factors could predispose to this acquired disorder.
 ...
PMID:Myasthenia gravis after allogeneic bone marrow transplantation. A case report and a review of the literature. 932 79

We report a 1-year-old boy with infantile lymphoblastic leukemia in first complete remission who received a cord blood stem cell transplantation (CBSCT) from an HLA identical sibling. We collected 120 ml of cord blood when his brother was born, which contained 4.2 x 10(8) mononuclear cells (4.2 x 10(7)/kg) and 3.1 x 10(5) CFU-GM (3.1 x 10(4)/kg). One month prior to transplantation, he showed persistent fever and liver dysfunction, and was finally diagnosed as having primary cytomegalovirus (CMV) infection which was demonstrated by elevation of serum anti-CMV-IgM. The administration of ganciclovir dramatically improved the clinical symptoms and abnormal laboratory findings, and was continued up to 1 month after transplantation to suppress the CMV reactivation. The preconditioning regimen consisted of busulfan (16 mg/kg/4 days) and cyclophosphamide (120 mg/kg/2 days), and cyclosporin A (CyA) alone was used for graft-versus-host disease (GVHD) prophylaxis. Fever suspicious of grade I GVHD developed on day 19, but subsided by increasing the dose of CyA. The WBC and platelet counts reached greater than 1,000/microliter and 50 x 10(3)/microliter on days 12 and 42, respectively. It is now at 13 months since transplantation, and he remains in a disease free state.
 ...
PMID:[Cord blood stem cell transplantation for infantile acute lymphoblastic leukemia after primary cytomegalovirus infection]. 942 43

Using a murine transplantation model, we simulated a clinical situation in which major histocompatibility complex (MHC)-identical allogeneic peripheral blood progenitor cells (PBPCs) are transplanted for the treatment of a malignant disease that is resistant to resting natural killer (NK) cells but sensitive to cytokine-activated NK cells and T cell-mediated antitumor activity. We determined the influence of selective T cell depletion of allogeneic PBPC grafts on graft-vs.-leukemia (GVL) activity and investigated the effectiveness of ex vivo treatment with NK cell-activating cytokines to compensate for the putative loss of T cell-derived factors stimulating natural cytotoxicity. After pretreatment of Balb/c (H-2d) recipients with 7.5 Gy of total body irradiation, 2x10(7) rhG-CSF-mobilized PBPCs of splenectomized syngeneic or MHC-identical DBA (H-2d) mice were transferred. Selective T cell depletion (TCD) was performed by immunomagnetic purging with a mononoclonal antibody directed against CD3. In some experimental groups, T cell-depleted PBPCs were incubated with 200 U/mL interleukin (IL)-2 and 100 U/mL IL-12 for 24 hours. To investigate antileukemic activity in vivo, recipient mice were inoculated with 1x10(5) A20 cells (a B-lymphoblastic leukemia of Balb/c origin) 2 days before PBPC transplantation (PBPCT). After transplantation of unmanipulated allogeneic cells, 25% of the animals died with signs of graft-vs.-host disease (GVHD) but 71% were free from relapse 100 days after PBPCT. After TCD of allogeneic grafts with anti-CD3, the incidence of GVH-related mortality was below 5% but the leukemia-free survival rate was significantly (p < 0.05) decreased to 25% and thus was similar to that observed after syngeneic PBPCT (17%). When CD3-depleted grafts were incubated with IL-2 and IL-12, 45% of the animals remained free from leukemia; however, the difference was not statistically significant. Our results suggest that ex vivo activation of residual NK cells with IL-2 and IL-12 does not fully compensate for the abrogation of GVL activity after depletion of CD3+ T cells from MHC-matched PBPCT.
 ...
PMID:Abrogation of graft-vs.-leukemia activity after depletion of CD3+ T cells in a murine model of MHC-matched peripheral blood progenitor cell transplantation (PBPCT). 947 98

In a newly developed murine model of allogeneic peripheral progenitor transplantation (PBPCT) we investigated the immunotherapeutic potential of allogeneic peripheral stem cells. The following topics were addressed by our experiments: (1) comparison of the graft-versus-leukemia effect exerted by allogeneic PBPCT compared to allogeneic BMT; (2) the influence of T-lymphocytes on GVL activity; (3) the possibility to enhance the GVL activity of allogeneic PBPCT grafts by ex vivo cytokine incubation. Balb/c mice received cells of the syngeneic B-lymphatic leukemia A20 2 days prior to TBI (7.5 Gy) and the respective graft. The recipients received allogeneic bone marrow grafts or allogeneic peripheral progenitor cells obtained after mobilization of the donors (DBA/2) with either G-CSF in a dose of 250 microg/kg/day for 5 days. In some experiments T lymphocytes were removed by immunomagnetic depletion with CD3-coated beads. An additional group received T cell-depleted and IL-2/IL12-activated PBPCT grafts. The antileukemic activity of an allogeneic PBPCT graft was significantly greater than the antileukemic activity of an allogeneic BMT graft of the same size. Relapse rates were 80% in syngeneic PBPCT, 60% after allogeneic BMT and 34% after allogeneic PBPCT. This rise in antileukemic activity is not accompanied by a rise in GVHD mortality. Depletion of T lymphocytes by CD3-coated beads resulted in a nearly complete loss of the GVL activity with a relapse rate of 75%. Incubation of the T-depleted graft with IL-2 and IL-12 to enhance NK-based GVL activity has only limited success after MHC-matched transplantation with a relapse rate of 55%. Allogeneic PBPC exert a pronounced antileukemic effect. After MHC-matched PBPCT, this GVL effect resides mostly on the T cells of the graft. Ex vivo activation of T cell-depleted grafts by IL-2 and IL-12 is accompanied by an only limited reduction of relapse rate. PBPC are a valuable modality for primary transplantation in situations with high risk of relapse and for the treatment of relapse after BMT.
 ...
PMID:Immunotherapeutic aspects of allogeneic peripheral progenitor cells. 971 83


<< Previous 1 2 3 4 5 6 7 8 Next >>