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)

A 38-year-old female with acute myelogenous leukemia (M2) received an allogeneic bone marrow graft from an HLA-DR one locus-mismatched sister during the first remission. The conditioning regimen consisted of busulfan and cyclophosphamide. Acute graft-versus-host disease (GVHD) developed on day 11 after transplantation. Although the GVHD was successfully treated with methylprednisolone, peripheral blood neutrophils that had begun to increase disappeared in association with improvement of the GVHD and graft rejection was eventually diagnosed. The second bone marrow transplantation from the same donor ended up with engraftment failure. She died of sepsis due to Candida albicans following the development of Epstein-Barr virus-associated B-lymphoproliferative disorder. The clinical course of this patient indicates that successful therapy of severe GVHD with methylprednisolone may lead to marrow graft rejection.
 ...
PMID:-Rejection of an allogeneic bone marrow graft following successful treatment of severe graft-versus-host disease (GVHD). 885 31

Allogeneic BMT is the treatment of choice for patients with SAA who have an HLA-identical sibling donor. The results, however, have been relatively poor for transplants from partially matched family donors or unrelated donors because of the high incidence of graft rejection and/or GVHD. Six multiply transfused patients received a novel conditioning regimen of CY 200 mg/kg and TBI 800 cGy prior to receiving marrow from their HLA-haploidentical family donors. Three recipient-donor pairs were mismatched for one HLA locus, one for two loci and two for three loci. A combination of MTX and CsA was used for GVHD prophylaxis. Engraftment was noted in all six patients. Acute GVHD occurred in four patients, two each for grade I and II, respectively. One patient, who was ABO-compatible with her donor had delayed onset of pure red cell aplasia (PRCA) which completely recovered 6 months after additional immunotherapy with prednisolone. There were two deaths; both occurred while patients were on treatment for GVHD. One was from systemic fungemia and the other probably from cytomegalovirus interstitial pneumonitis (CMV-IP). Four patients (66.7%) have been alive and disease-free for more than 8.2, 27.3, 38.4 and 47.2 months after BMT, respectively. The results suggest that CY/TBI-800 may be a simple and effective conditioning regimen for SAA patients receiving BMT from family members other than HLA-identical siblings.
 ...
PMID:CY/TBI-800 as a pretransplant regimen for allogeneic bone marrow transplantation for severe aplastic anemia using HLA-haploidentical family donors. 886 34

Acute graft-versus-host disease (GVHD) is thought to be initiated by alloreactive type 1 T cells that secrete gamma-interferon (IFN-gamma). IFN-gamma induces the production of inflammatory cytokines, e.g., tumor necrosis factor-alpha and interleukin (IL)-1, which are the distal mediators of GVHD. We demonstrate that the transplantation of polarized type 2 murine T cells (i.e., cells secreting IL-4 but not IFN-gamma) together with T-cell-depleted bone marrow results in a significant increase in survival (P<0.001) after bone marrow transplantation across minor histocompatibility barriers (B10.BR-->CBA/J). Further analysis demonstrated that increased survival in recipients of polarized type 2 T cells correlated with diminished production of both IFN-gamma and tumor necrosis factor-alpha but with increases in IL-4 2 weeks after transplantation. Despite improved survival, histologic changes of GVHD were evident in oral mucosal and hepatic tissues at 7 weeks after bone marrow transplantation. These data provide further evidence that inflammatory cytokines in the immediate posttransplant period are pivotal to the development of mortality but that they do not correlate with individual target organ damage.
 ...
PMID:Transplantation of polarized type 2 donor T cells reduces mortality caused by experimental graft-versus-host disease. 893 72

Myeloablative treatment followed by allogeneic transplantation of peripheral blood hemopoietic progenitors (alloPBT) was administered to five leukemia patients with a high risk of relapse. The donors subcutaneously received 10 micrograms/kg/day of G-CSF for five days. The tolerance to this medication was good with only complaints of moderate bone pain. Two of the peripheral blood donors had previously been bone marrow donors and both expressed their preference for the new method. The product of peripheral blood leukapheresis contained from one to four-fold more hemopoietic progenitors and approximately ten-fold more T-lymphocytes than the bone marrow received from normal donors. Prophylaxis of the graft versus host disease (GVHD) consisted of cyclosporine A (CsA) in one case and CsA and methotrexate (MTX) in four cases. The bone marrow implantation was verified with a neutrophil count of up to more than 0.5 x 10(9)/l between days 12 to 21 after transplant and a platelet count higher than 20 x 10(9)/l from days 11 to 41 after transplant. Acute GVHD was clinical grade O (two cases), II (one case) and grade III (two cases). In conclusion, alloPBT may be more safely and comfortably performed to the donor. This method may provide rapid recovery of neutrophils and platelets in patients without an apparent increase in the risk of developing graft versus host disease.
 ...
PMID:[Allogeneic transplant of peripheral blood hematopoietic progenitors. Preliminary experience]. 894 58

We have carried out an analysis of 44 patients undergoing allogeneic PBSC transplants from fully HLA-matched related donors with particular emphasis on engraftment kinetics and the incidence and severity of GVHD. The recipients had a median age of 37 years (range 5-56 years), 16 patients had standard-risk disease and 28 had poor-risk disease. GVHD prophylaxis was with cyclosporin A and methotrexate (n = 41), cyclosporin A alone (n = 2) or cyclosporin A and methyl-prednisolone (n = 1). Stem cells were mobilised using G-CSF, collecting a median of 5.75 x 10(6) CD34+ cells/kg recipient weight (range 0.94-35 x 10(6) CD34+ cells/kg). Engraftment times to a neutrophil count > 0.5 x 10(9)/1 and platelets > 20 x 10(9)/1 were achieved at a median of day +14 (range 10-25) and day +14 (range 9-130) respectively. Patients receiving > or = 4 x 10(6) CD34+ cells/kg had significantly accelerated neutrophil and platelet engraftment and this number of CD34+ cells would appear to be a prerequisite for maximum engraftment using PBSC. Acute GVHD occurred in 25 of 43 evaluable patients although in only 12 was this clinically significant (grades II-IV). Chronic GVHD has occurred in 17 out of 36 evaluable patients, there was no significant difference between the standard- and poor-risk groups in incidence of either acute or chronic GVHD. In conclusion, these results confirm the feasibility of using PBSC for allogeneic transplantation without evidence for increased risk of either acute or chronic GVHD and provide further evidence supporting the potential of PBSC to replace bone marrow as the major source of haemopoietic cells for allogeneic transplantation.
 ...
PMID:Allogeneic peripheral blood stem cell transplantation for haematological malignancies--an analysis of kinetics of engraftment and GVHD risk. 901 25

In our BMT Unit, we have observed a high frequency of skin rash associated with fever and other clinical findings during engraftment of autologous BM and/or PBSC. Thirty patients with breast cancer and 12 patients with Hodgkin's or non-Hodgkin's lymphoma, treated with the same regimen, were analyzed retrospectively or prospectively to characterize the clinical syndrome, its frequency, and its clinical course, as well as to define the factors affecting its incidence. In patients developing skin rash, the median and range for time to onset of skin rash and for time to increase in WBC after reinfusion of stem cells were identical (8 days, range 5-13) and did not differ significantly (P = 0.533). Twenty-three patients (55%) had skin rash, 18 patients had fever. Other, less frequent manifestations include platelet transfusion refractoriness (PTR), diarrhea, diffuse alveolar hemorrhage, and autoimmune thrombocytopenia or hemolytic anemia. A higher proportion of breast cancer patients developed the syndrome in comparison to lymphoma patients (67% vs 25%, P = 0.051). Acute GVHD grade I-II was established histologically in six patients with the syndrome. Comparison of the incidence of the syndrome by different variables using Fisher's exact test revealed significance for disease category (P = 0.02) and number of previous treatment regimens (P = 0.002) as predictive factors for developing the autoaggression syndrome. In other words, patients with breast cancer and those with only one previous treatment regimen were more likely to develop the syndrome. This study suggests that an autoaggression GVHD-like syndrome accompanies the early phase of autologous engraftment and that a higher frequency of the syndrome might be seen in breast cancer patients undergoing high-dose chemotherapy and autologous stem cell transplantation.
 ...
PMID:Increased frequency of autoaggression syndrome associated with autologous stem cell transplantation in breast cancer patients. 911 5

We have previously demonstrated that syngeneic marrow mixed with H-2 haploidentical marrow transplantation could provide not only protection against graft-versus-host disease (GVHD) but also anti-leukemic (GVL) effects in mice. In the present studies, we report clinical observations using autologous marrow mixed with HLA-haploidentical allogeneic marrow transplantation for treatment of patients with malignant blood diseases. Sixteen cases, including 12 with acute leukemia and four with advanced malignant lymphoma, were treated by autologous marrow, which was purged in vitro by hyperthemia (42.5 degrees C for 70 min) following incubation for 5 days with interleukin 2 (IL-2) in liquid culture and mixed with HLA haploidentical marrow cells from their sibling or parent. Acute GVHD was not observed in any patient after transplantation. Hematological rescue in the clinical setting was demonstrated in all cases but one who died early from hepatic veno-occlusive disease (VOD). Five cases who were transplanted at the time of CR2 or CR3 and in advanced phase of lymphoma, relapsed 4 to 7 months after transplantation. The relapse rate was 31.3%. None of eight patients who received allogeneic BMT within 2 h after ABMT relapsed with median follow-up of 12 months and two of them died from procedure-related complications. Seven cases are still alive and disease-free with a median follow-up of 12 months. Mixed chimerism was found in 3/6 cases, who had different sex donors, by analysis of sex chromosomes. These results show that mixed transplantation is a safe, effective and new approach to treating patients with malignant tumors. In order to detect the effects of GVL, studies are now in progress in our clinic.
 ...
PMID:Autologous bone marrow mixed with HLA-haploidentical allogeneic marrow transplantation for treatment of patients with malignant blood diseases. 911 6

In order to analyze the incidence and risk factors for invasive fungal infection (IFI) after allogeneic BMT, 142 consecutive adult BMT recipients (131 sibling donors, 11 unrelated donors) transplanted in 1989-1993 were retrospectively analyzed. There were 21 cases with definite or probable IFI (incidence 15%) (Aspergillus, 15; Candida, four; Fusarium, one; Absidia, one). The median time to the diagnosis of IFI was 136 days after BMT (range 6-466 days). Only 14% of the IFIs were found during the neutropenic period post-BMT. Of the pretransplant characteristics, hematological disease (MDS vs other) (P = 0.001) and unrelated donor (P = 0.01) were risk factors for IFI. Acute GVHD grade III-IV (P = 0.03) and extensive chronic GVHD (P = 0.0002) were also found to be significant risk factors. Only three patients with IFI (14%) became long-term survivors. Invasive fungal infections tended to develop late after BMT, were usually caused by Aspergillus sp., and were strongly associated with GVHD and its treatment. Better prophylaxis and treatment of IFI are needed. More effective prophylaxis for GVHD might decrease the risk of IFI after allogeneic BMT.
 ...
PMID:Incidence and risk factors for invasive fungal infections in allogeneic BMT recipients. 913 72

Donor lymphocyte infusions (DLI) were given between June 1990 and March 1996 to 18 patients with chronic myeloid leukemia (CML) for the treatment of cytogenetic (n = 6) or hematologic relapse (n = 12) following an allogeneic bone marrow transplant (BMT). Patients were divided in two groups: patients in group A (n = 8) received a large dose of donor lymphocytes (> or = 1 x 10(8)/kg), whereas patients in group B (n = 10) received escalating numbers of cells (2 x 10(5) up to 2 x 10(8)/kg). The median number of DLI in group A was 2 (range 1-3); the median number of infusions in group B was 7 (range 3-9). Acute GVHD occurred in 12 patients (grades I-III) and was a major cause of death in two. The risk of developing GVHD correlated with the number of cells infused: 37%, 14%, 5% and 0% for DLI with cells > or = 1 x 10(8), 2 x 10(7)/kg, 2 x 10(6)/kg, and 2 x 10(5)/kg, respectively (P = 0.01). Median transaminase levels were found to be significantly increased in patients with, as compared to patients without, acute GVHD (GPT 412 vs 28 IU/l; P = 0.03). Severe aplasia occurred in four and was a contributing cause of death in two patients. Overall, four patients died as a consequence of DLI and all received > 1 x 10(8)/kg cells: the actuarial risk was 38% in group A and 14% in group B (P = 0.1). There were 10 complete and three partial cytogenetic responses: the actuarial probability at 5 years of being Ph negative was 69%: it was 46% for group A and 85% for group B (P = 0.1). The longest patient is now 6 years post-DLI, Ph negative, BCR-ABL negative. The actuarial 3 year survival is 38% in group A and 86% in group B (P = 0.06). The study confirms that DLI post-BMT is not innocuous and that there is a definite long-lasting antileukemic effect in patients with CML. It also suggests that: (1) the risk of developing GVHD correlates with the number of infused cells; (2) that significant elevations of serum GPT levels are associated with GVHD; and (3) that the use of escalating doses of cells may allow the identification of side-effects and discontinuation of infusions before life-threatening GVHD has developed.
 ...
PMID:Donor lymphocyte infusions (DLI) in patients with chronic myeloid leukemia following allogeneic bone marrow transplantation. 915 68

The immune-mediated graft-versus-leukemia effect is important to prevent relapse after allogeneic progenitor cell transplantation. This process requires engraftment of donor immuno-competent cells. The objective of this study was to assess the feasibility of achieving engraftment of allogeneic peripheral blood or bone marrow progenitor cell after purine analog containing nonmyeloablative chemotherapy. Patients with advanced leukemia or myelodysplastic syndromes (MDS) who were not candidates for a conventional myeloablative therapy because of older age or organ dysfunction were eligible. All patients had an HLA-identical or one-antigen-mismatched related donor. Fifteen patients were treated (13 with acute myeloid leukemia and 2 with MDS). The median age was 59 years (range, 27 to 71 years). Twelve patients were either refractory to therapy or beyond first relapse. Eight patients received fludarabine at 30 mg/m2/d for 4 days with idarubicin at 12 mg/m2/d for 3 days and ara-c at 2 g/m2/d for 4 days (n = 7) or melphalan at 140 mg/m2/d (n = 1). Seven patients received 2-chloro-deoxyadenosine at 12 mg/m2/d for 5 days and ara-C 1 at g/m2/d for 5 days. Thirteen patients received allogeneic peripheral blood stem cells and 1 received bone marrow after chemotherapy. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methyl-prednisolone. Treatment was generally well tolerated, with only 1 death from multiorgan failure before receiving stem cells. Thirteen patients achieved a neutrophil count of greater than 0.5 x 10(9)/L a median of 10 days postinfusion (range, 8 to 17 days). Ten patients achieved platelet counts of 20 x 10(9)/L a median of 13 days after progenitor cell infusion (range, 7 to 78 days). Eight patients achieved complete remissions (bone marrow blasts were < 5% with neutrophil recovery and platelet transfusion independence) that lasted a median of 60 days posttransplantation (range, 34 to 170+ days). Acute GVHD grade > or = 2 occurred in 3 patients. Chimerism analysis of bone marrow cells in 6 of 8 patients achieving remission showed > or = 90% donor cells between 14 and 30 days postinfusion, and 3 of 4 patients remaining in remission between 60 and 90 days continued to have > or = 80% donor cells. We conclude that purine analog-containing nonmyeloablative regimens allow engraftment of HLA-compatible hematopoietic progenitor cells. This approach permits us to explore the graft-versus-leukemia effect without the toxicity of myeloablative therapy and warrants further study in patients with leukemia who are ineligible for conventional transplantation with myeloablative regimens either because of age or concurrent medical conditions.
 ...
PMID:Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. 919 77


<< Previous 1 2 3 4 5 6 7 8 9 10