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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)

It has previously been demonstrated that graft-versus-host disease can be overcome in patients receiving HLA-mismatched bone marrow transplants by prior in vitro depletion of T lymphocytes from the marrow. In this report we describe the use of monoclonal antibodies and magnetic microspheres for the depletion of T cells from peripheral blood and bone marrow. The target cells are sensitized with antibodies directed against the CD2, CD3, CD4 and/or CD8 cell surface antigens, captured by magnetic beads coated with sheep anti-mouse IgG antibody and collected by placing the cell suspension in a magnetic field. This simple, rapid procedure results in the efficient removal of T cells from peripheral blood and from bone marrow without affecting the colony-forming potential of normal hematopoietic stem cells. The procedure is capable of being scaled up for the treatment of larger volumes of marrow that are required for clinical transplantation.
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PMID:T lymphocyte depletion of human peripheral blood and bone marrow using monoclonal antibodies and magnetic microspheres. 290 78

Twelve patients with acute nonlymphoblastic leukemia (ANL, n = 6) or acute lymphoblastic leukemia (ALL, n = 6) in first complete remission received cyclophosphamide 120 mg/kg and total body irradiation (TBI) 12 Gy followed by HLA-identical sibling marrow that had been depleted of T cells by incubation with anti-CD2 (with or without anti-CD8) monoclonal antibody and rabbit complement. These 12 patients were compared historically to 25 patients with ANL (n = 15) or ALL (n = 10) in first remission given cyclophosphamide 120 mg/kg and TBI 12 Gy followed by non-T cell depleted HLA-identical sibling marrow for parameters of relapse and survival. Thirty-six of the 37 patients received cyclosporin as post transplant prophylaxis for graft-versus-host disease (GVHD). All surviving patients have been followed for a minimum of one year from transplant. The actuarial rate of leukemic relapse in the T-depleted group was 62% compared to 37% in the non-depleted group (p less than 0.02). Additionally, relapse occurred significantly earlier post transplant in the T-depleted recipients (p = 0.012). Actuarial survival at two years post transplant was 24% for the T-depleted recipients and 41% at six years post transplant for the non-depleted recipients (not significant, p = 0.37). We have previously shown that GVHD is less severe in patients given T cell depleted transplants. Taken together, these findings suggest that (under the protocol conditions used) a graft-versus-leukemia effect is not separable from a GVHD effect in man.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High incidence of early leukemic relapse in patients given cyclosporin and T cell depleted HLA-identical sibling marrow transplants for acute leukemia in first remission. 305 4

Sixteen patients with hematological malignancy received cyclophosphamide (120 mg/kg), fractionated total body irradiation (12 Gy), oral cyclosporin, and an HLA-identical sibling marrow transplant depleted of T cells by incubation with the monoclonal antibody anti-HuLy-m1 (CD2) and rabbit complement with (five patients) or without (11 patients) anti-HuLy-m8). These 16 patients were compared historically to 84 patients with hematological malignancy receiving cyclophosphamide (120 mg/kg), fractionated total body irradiation (12 or 14 Gy), oral cyclosporin, and unmanipulated HLA-identical sibling marrow, for parameters of engraftment and graft-versus-host disease (GVHD). Graft failure occurred in one of the 16 T-cell depleted recipients and in one of the 84 nondepleted recipients. Engraftment was slightly but significantly slower in the T-cell depleted group and bacterial infections significantly more frequent and severe than in the unmanipulated group. There was a suggestion that the severity of acute GVHD was reduced in those receiving T depleted marrow. Randomized trials will be necessary to determine if marrow T-cell depletion results in superior long-term leukemia-free survival.
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PMID:A comparative study of T-cell depleted and non-depleted marrow transplantation for hematological malignancy. 330 40

The efficacy of bone marrow transplant (BMT) T-cell depletion for the prevention of acute graft-versus-host disease (GVHD) has been demonstrated in animal models and in clinical studies. The importance of T-cell depletion has to be evaluated with standardized methods suitable for routine purposes. We report herein an in vitro mature T-cell depletion using a cocktail of three monoclonal antibodies (CD2, CD5, and CD7) and baby rabbit complement in 38 histocompatibility leucocyte antigen (HLA)-identical BMT with no more than grade II acute GVHD. The T-cell depletion was quantified using three prestandardized immunological methods: immunofluorescence (IF) analysis, SRBC-rosetting assay, and PHA proliferation assay. A mean of 97.5% IF-assessed T-cell depletion was achieved in the 38 BMT. The immediate IF analysis using three distinct sets of anti-T-cell monoclonal antibodies allowed us to detect a mean of 1.2% residual T cells. The SRBC-rosetting assay was not useful to quantify T-cell depletion because no residual SRBC-rosette-forming cells could be detected in every case. The results of a prestandardized PHA-induced proliferation assay gave a mean 96.7% inhibition of proliferation, and they were correlated with the IF results although the IF threshold of detection was higher. From these data we conclude that our in vitro T-cell-depletion procedure is reproducible and that standardized simple immunological methods such as immediate immunofluorescence analysis and PHA proliferation assay provide good tools to assess a T-cell depletion effective in the prevention of acute GVHD.
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PMID:T-cell depletion of bone marrow transplants: assessment of standard immunological methods of quantification. 331 22

Sixteen patients with haematological malignancy received high-dose chemotherapy or chemotherapy and total body irradiation followed by an HLA-identical sibling marrow transplant from which the T lymphocytes had been depleted prior to infusion by incubation with an anti-CD2 anti-T cell antibody with (seven patients) or without (nine patients) an anti-CD8 anti-T cell antibody together with rabbit complement. Additionally, all patients received cyclosporin. The number of T cells present in the donor marrow was determined by limiting dilution analysis, and was found to correlate with the subsequent incidence and severity of acute graft-versus-host disease (GVHD). The number of T cells infused into patients with no acute GVHD or with minimal acute GVHD of the skin (skin rash present for 14 days or less) was 1.3 +/- 1.0 x 10(5)/kg, while the number infused into those with moderate acute GVHD or with skin acute GVHD present for 15 days or more was 12.3 +/- 11.5 x 10(5)/kg (p less than 0.001). Thus a dose of 10(5) (or less) T cells/kg was associated with minimal or no acute GVHD, while 10(6) T cells/kg (or more) caused significant disease.
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PMID:Human marrow T cell dose correlates with severity of subsequent acute graft-versus-host disease. 333 57

We evaluated the inhibitory effects of two immunotoxins (IT) synthesized by linking two different anti-CD2 (T, p50) murine monoclonal antibodies (MoAb) to intact ricin (R). Pretreatment with 1000 ng ml-1 35.1-R or OKT 11a-R inhibited PHA-induced T-cell proliferation by 93% and 86%, respectively. At this IT concentration generation of alloreactive cytotoxic T-cells (CTL) was inhibited by more than 99% by either IT. 35.1-R and OKT 11a were minimally toxic to natural killer (NK) effectors or pluripotent bone marrow progenitor cells (CFU-GEMM). Blocking experiments suggested that 35.1-R and OKT 11a-R might recognize different epitopes of the CD2 (T, p50) surface determinant. Our findings show that anti-CD2 IT may be useful for T-cell depletion in allogeneic bone marrow transplantation. We compared TU3, an equimolar mixture of T101 [anti-CD5]-R, UCHT-1 [anti-CD3]-R and 35.1 [anti-CD2]-R with the TUT-cocktail (a mixture of T101-R, UCHT-1-R and TA-1 [anti-CDw18]-R. TUT is currently under evaluation in Phase 1 clinical trials as a T-cell depletion regimen for GVHD prophylaxis. TU3 was as effective as TUT-cocktail in inhibition of PHA response and CTL generation but unlike TUT spared NK effectors. Cocktails of immunotoxins directed against subpopulations of lymphocytes may be useful for more effective anti-GVHD strategies, and to circumvent problems of graft failure/rejection associated with current purgation regimens.
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PMID:Anti-CD2 (T, p50) intact ricin immunotoxins for GVHD-prophylaxis in allogeneic bone marrow transplantation. 351 22

A cooperative study was done on ex vivo treatment of bone marrow for the prevention of acute graft-versus-host disease (GvHD), in which either CD2-CD5-CD7 (14 patients) or CD2-CD3 (15 patients) monoclonal antibody cocktail and complement were used. In this study, 29 patients (12 female, 17 male; average age, 22-1/2 yr) received T-cell-depleted allograft through complement cytolysis, 26 from HLA-identical donors and 3 from HLA-mismatched donors. All of the patients had malignant disease with poor prognosis; 21 had acute leukemia, 7 had chronic granulocytic leukemia, and 1 had multiple myeloma. After bone marrow transplantation (BMT), GvHD prophylaxis was maintained in 12 patients (group 1), was stopped at day 11 in 6 patients (group 2), and was not administered to 11 patients (group 3). The treatment removed 92.65 +/- 5.36% of donor bone marrow T-cells with one round of complement lysis. Of 3 patients who received mismatched transplant, 2 did not achieve engraftment. Engraftment was achieved in all of the patients who had matched BMT. Two patients had acute GvHD, 1 with grade 2 in group 1, and 1 with grade 3 in group 3. No patient has developed chronic GvHD; for 9 patients, the follow-up is longer than 6 months. Five patients relapsed within 6 months after BMT. Eighteen patients are alive and well in complete remission, with an average follow-up of 7.5, 10.6, and 2.7 months for patients in groups 1, 2, and 3, respectively.
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PMID:Depletion of T-lymphocytes in donor marrow with pan-T monoclonal antibodies and complement for prevention of acute graft-versus-host disease: a pilot study on 29 patients. 352 74

We have retrospectively analyzed the outcome of bone marrow transplantation (BMT) in 14 patients with leukocyte adhesion deficiency (LAD) performed in two centers between 1981 and 1993. Five patients received BMT from HLA-identical donors. Nine received T-depleted marrow from two HLA antigen- or haplotype-incompatible parents. Conditioning regimen consisted of chemotherapy exclusively in 13 patients and associated with total body irradiation (TBI) in one patient. In five cases, failure of engraftment occurred as a result of either insufficient myeloablation (n = 3) or, possibly, graft rejection in two cases of moderate phenotype of LAD. The second conditioning regimen consisted of TBI and chemotherapy with the use of anti-lymphocyte function-associated antigen 1 (LFA-1) and anti-CD2 monoclonal antibodies for patients with the moderate phenotype of LAD. These patients were successfully retransplanted. Eight patients developed acute graft-versus-host disease (GVHD). Chronic GVHD occurred in five cases. GVHD led to the death of three patients. Ten patients are alive and well 12 months to 12 years after BMT. Chimerism is full in six of these patients and mixed but stable in four with variable proportion of donor leukocytes. One patient with less than 15% donor leukocytes has mild gingivitis, while the others are well. Sequelae from BMT are limited in two cases to growth retardation caused by TBI. Success of BMT in cases of LAD including seven of nine recipients of HLA nonidentical marrow indicates that this procedure can be proposed as a curative approach to LAD regardless of an available HLA-identical donor. Great care should be taken in GVHD prophylaxis and treatment.
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PMID:Results of allogeneic bone marrow transplantation in patients with leukocyte adhesion deficiency. 763 73

We previously demonstrated the potential of anti-IL-2R and anti-TNF alpha moAbs in the treatment of acute graft-versus-host disease (GVHD). However, one major problem was the recurrence of acute GVHD on treatment discontinuation. To target the two main effectors of acute GVHD lesions, T and NK cells on the one hand and TNF alpha on the other, we combined anti-CD2 and anti-TNF alpha moAbs. Then to prevent acute GVHD recurrence, we administered anti-IL-2R moAbs known for their inhibitory effect on activated cells. We included 15 patients with steroid-resistant acute GVHD. Seven were grafted from a genotypically-identical sibling, 5 from HLA-matched unrelated donors and 3 from partially-matched related donor. Prophylaxis of acute GVHD consisted of cyclosporin A +/- methotrexate or corticosteroids. Before treatment 6 patients had grade II, 2 patients grade III and 7 patients grade IV acute GVHD. Anti-TNF alpha (B-C7) moAbs (10 mg/day/4 days) were combined with anti-CD2 (B-E2) moAbs (10 mg/day/10 days) on the fifth day (day 5), anti-IL-2 receptor (B-B10) moAbs were given at 10 mg/day/10 days followed by 5 mg every other day for another 50 days. On day 15, 5 patients achieved a complete remission, 4 a very good partial response (62% a good response), 2 had a partial response and 4 did not respond. GVHD recurred in 4 of the 9 responders, although anti-IL-2R moAb treatment was maintained. Three patients are long-term survivors without chronic GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sequential use of three monoclonal antibodies in corticosteroid-resistant acute GVHD: a multicentric pilot study including 15 patients. 767 Mar 94

Acute graft-versus-host disease is a common complication of allogeneic bone marrow transplantation, but the mechanisms resulting in tissue injury are uncertain. In order to probe the effector phase of upper gastrointestinal acute GVHD, we performed immunopathologic studies of duodenal biopsies obtained from patients with or without GVHD. We evaluated the infiltrating mononuclear cells in both epithelium and lamina propria for expression of CD2, CD4, CD8, CD25, T alpha/beta and gamma/delta receptors, CD16, CD56, CD57 and also studied the distribution of cell adhesion molecules (ELAM-1, VCAM-1, ICAM-1, PECAM-1). In the epithelium, only a minimal T cell infiltrate was observed. In the lamina propria, GVHD tissue (vs. control) had an infiltrate of CD2+ (17.7 +/- 2.9% vs. 7.2 +/- 1.8%; P < 0.04), CD8+ (15.5 +/- 4.4% vs. 4.8 +/- 1.9%, P < 0.04) T lymphocytes. GVHD-positive and control tissues contained similar numbers of CD4+ T cells and natural killer cells (CD56+ or CD57+). ICAM-1 staining of endothelial cells was prominent in GVHD tissues (13.5 +/- 1.1 capillaries/field) and was significantly increased over non-GVHD specimens (7.5 +/- 1.8; P < 0.02). ELAM-1, VCAM-1, and PECAM-1 were similarly distributed in both biopsy groups. These data suggest that effectors of upper GI GVHD include CD2+, CD8+, T lymphocytes infiltrating the lamina propria. Inflammatory cell activation and resultant secretion of cytokines might directly damage the mucosa, but may also upregulate ICAM-1 on local endothelium leading to perpetuation of inflammation by recruitment of additional cytotoxic lymphocytes.
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PMID:The immunopathology of upper gastrointestinal acute graft-versus-host disease. Lymphoid cells and endothelial adhesion molecules. 768 Dec 25


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