Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have developed a rapid and simple procedure for the elimination of mature T-cells from the donor marrow using a single incubation with the monoclonal antibody Campath-1 and donor complement. This resulted in a reduction of T-cell contamination to a mean of 1%. This regimen reduced the incidence of acute graft-versus-host disease significantly in 21 consecutive bone marrow grafts in 18 patients with leukaemia and non-Hodgkin's lymphoma. Purging was responsible for an increased incidence of graft rejection in HLA-identical transplants (13%).
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PMID:Ex vivo T-cell depletion with the monoclonal antibody Campath-1 plus human complement effectively prevents acute graft-versus-host disease in allogeneic bone marrow transplantation. 353 72

Using immunohistological techniques, the cellular composition of lymph nodes was assessed in 18 patients who had died 15 to 326 days after allogeneic bone marrow transplantation for leukaemia. The lymph nodes showed reduced cellularity of the cortex and paracortex, dilated sinuses and no lymphoid follicles. The majority of leucocytes were T lymphocytes with an inversion of the normal T4:T8 ratio. No cells were detected expressing immature cortical thymocyte antigens, using NA1/34 and OKT10, but an excess of T11 (E rosette receptor)+ cells over the sum of T4+, T8+ and HNK1+ cells raised the possibility of the presence of immature cells. B lymphocytes were extremely rare and present as clusters in only two patients. Despite this, plasma cells were prominent in many cases and their number increased with time post transplant. The predominant immunoglobulin heavy chain class was IgA in seven cases, IgG in three cases, IgM in two cases and IgE in one case with no relationship between dominant class and days post transplant. In patients with graft-versus-host disease (GvHD), there was a significantly lower T4:T8 ratio but no increase in expression of lymphocyte activation markers. Pyknotic leucocytes were present in half of the cases with GvHD and none of the other cases. No differences were detected in patients who had received marrow purged with monoclonal antibodies (Campath-I or UCHT1). Chimeric studies on three recipients of one haplotype matched marrow, using a monoclonal antibody specific for HLA-A2 and A28 antigens, showed a significant influx of donor cells by 56 days but this did not appear to be an immediate prelude to full morphological reconstitution.
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PMID:The cellular composition of human lymph nodes after allogenic bone marrow transplantation: an immunohistological study. 354 75

Serial cytogenetic studies of bone marrow and blood cells were made in leukaemic patients who had received an allogeneic bone marrow graft from a donor of unlike sex. The donor marrow was treated with the monoclonal antibody Campath-1 before infusion. The persistence of a significant proportion of dividing recipient cells in marrow and blood was observed after grafting. These recipient cells showed evidence of radiation damage of both the stable and unstable types. More than one transient clone of chromosomally abnormal recipient cells was observed in three cases. The differences between the cytogenetic findings in patients receiving donor marrow from which T cells have been removed and those cases previously studied in our Leukaemia Unit who had received untreated donor marrow are discussed.
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PMID:Cytogenetic follow-up studies of recipients of T-cell depleted allogeneic bone marrow. 354 98

One hundred and forty-six patients with acute leukaemia (81 with ANLL and 65 with ALL) received allogeneic bone marrow transplantation from their fully matched siblings. 121 patients underwent T-cell depletion (TCD) using Campath 1 monoclonal rat anti-human lymphocyte (CDw52) antibodies; 67 with Campath 1M and 54 with Campath 1G isotypes. Patients were conditioned for transplant using either total body irradiation combined with chemotherapy (125 patients) or busulfan and cyclophosphamide (21 patients). 112 recipients of T-cell depleted allografts received in addition total lymphoid irradiation (TLI) for prevention of rejection. Engraftment of neutrophils (> 0.5 x 10(9)/l) and platelets (> 25 x 10(9)/l) occurred on days 15 and 18, and on days 18 and 20 in recipients of Campath 1M and Campath 1G treated marrows respectively. Rejection was documented in 6.8% of T-cell depleted transplants. Leukaemia relapse-free survival at 2 years was 83% for patients transplanted in first CR, 76% in second CR (P2 = 0.34) and 42% in advanced leukaemia (P2 = 0.009). 81 marrow recipients, 38 with Campath 1M and 43 with Campath 1G treated marrow, received post-transplant graded increments of donor's peripheral blood lymphocytes (PBL) to induce graft-versus-leukaemia (GVL) effects. Administration of donor's PBL was associated with clinically significant GVHD and with decreased relapse rate especially in patients with ALL. Our data suggest that in patients receiving marrow allografts depleted of T cells by Campath 1 monoclonal antibodies, rejection can be reduced by adequate pregrafting immunosuppression. In patients with advanced disease, post-transplant cell-mediated immunotherapy (CMI) using donor's PBL may be beneficial; however, further studies are needed to define the optimal schedule of CMI for safe and effective prevention of relapse following TCD bone marrow transplantation in malignant haematological diseases.
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PMID:T-cell-depleted allogeneic bone marrow transplantation for acute leukaemia using Campath-1 antibodies and post-transplant administration of donor's peripheral blood lymphocytes for prevention of relapse. 773 48

Between May 1989 and February 1994, we performed 48 volunteer unrelated donor BMTs for first chronic phase chronic myeloid leukemia using in vivo T cell depletion for acute graft-versus-host disease (aGvHD) prophylaxis. In 40 cases, adequate material was available to measure the frequency of antirecipient MHC cytotoxic T lymphocyte precursor (CTLp) cells in the blood of potential donors. This supplemented standard serological typing, one-dimensional isoelectric focusing for class I proteins, and allogenotyping for DR and DQ alleles using DNA RFLP analysis in the donor selection process. All recipients were conditioned with cyclophosphamide 120 mg/kg, TBI 1320 cGy, and intravenous Campath 1G. GvHD prophylaxis consisted of CsA, short-course methotrexate, and intravenous Campath 1G. Minimum follow-up in all surviving recipients was 100 days. The development of aGvHD and the probability of leukemia-free survival were compared between the high frequency group (CTLp > 1 in 100,000) (n = 15) and the low frequency group (CTLp < 1 in 100,000) (n = 25). There was a trend for increasing grade of aGvHD, which was statistically significant in the high frequency group when compared with the low frequency group (P = 0.003). Both a high frequency of CTLp (relative risk [RR] = 9.0, P = 0.016) and HLA mismatch (RR = 6.7, P = 0.023) were predictors of severe aGvHD (grade III or IV). Multivariate analysis showed that CTLp group (RR = 3.4, P = 0.015) and CMV status (RR = 3.9, P = 0.008) were predictors of leukemia-free survival. Further investigation showed an interaction between the two, such that CMV seropositive recipients in the high frequency group had a relative risk of 9.4 (P = 0.0001) of treatment failure (death or relapse) when compared with other combinations. We conclude that with our present GvHD prophylaxis regimen, CTLp frequency analysis predicts post-BMT outcome and is a valuable aid in donor selection.
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PMID:Cytotoxic T lymphocyte precursor frequency analyses in bone marrow transplantation with volunteer unrelated donors. Value in donor selection. 776 66

Campath-1G is an immunosuppressive monoclonal antibody directed against human lymphocytes. Its effectiveness in preventing graft-versus-host disease (GVHD) by simple opsonisation of bone marrow T-cells has been studied in 36 consecutive allografts: in 17 for leukaemia, one for essential thrombocytosis and four for myeloma this was the sole means of GVHD prophylaxis. A further eight patients with aplastic anaemia received 3 months post-transplantation cyclosporin A (CsA) for this purpose whereas in the ninth and tenth the preparative regimen has been modified with this immunosuppressive agent now discontinued. Nucleated cells were harvested and after quantitative recovery of the mononuclear population on the Cobe 2997 separator they were exposed to 20 mg Campath-1G for 30 min at room temperature and then infused. Following standard conditioning, which included total lymphoid irradiation, the median days to reach 0.5 and 1.0 x 10(9)/l neutrophils were respectively 18 (range 9-34) and 28 (range 10-59); to 25 and 100 x 10(9)/l platelets the corresponding times were 17 days (range 5-32 days) and 27 days (range 13-127 days). In all, the day 14 trephine biopsy showed engraftment. At median follow-up of 20 months (range 5-44 months) only one patient has developed possible grade I cutaneous GVHD that responded promptly to corticosteroids: no chronic GVHD or CMV pneumonitis has been encountered. Of those with haematological malignancy transplanted in remission only two with acute leukaemia have relapsed. In aplastic anaemia graft loss initially occurred but this has been overcome by adding Campath-1G in vivo and omitting CsA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:T cell depletion by exposure to Campath-1G in vitro prevents graft-versus-host disease. 1045 57

Campath-1 (CDw52) antibodies (IgM and IgG2b) have been used in vitro and in vivo for control of GVHD and prevention of rejection following bone marrow transplantation. Results of 951 patients with malignant disease transplanted from HLA-matched siblings are reported. Both Campath-1M and Campath-1G are shown to be effective when used in vitro for prevention of graft-versus-host disease (GVHD). Graft failure was reduced by addition of cyclosporin A (CsA) post-transplant and possibly also by total lymphoid irradiation (TLI) pre-transplant. However, treatment of the recipient with Campath-1G to deplete residual lymphocytes was more effective, reducing the incidence of graft failure from 21% to 9% (in the absence of CsA). GVHD was virtually eliminated and leukaemia-free survival was improved. However, the risk of relapse was increased by T cell depletion, certainly in CML and to a lesser extent in AML. Addition of donor T cells to the depleted bone marrow or early post-transplant restored the risks of GVHD, graft failure and relapse to much the same as without T cell depletion. One problem associated with the use of Campath-1G in vivo was a significant delay (by up to 7 days) in neutrophil engraftment. This was unlikely to be caused by toxicity to progenitor cells and we argue that small numbers of lymphocytes may be required to assist early engraftment, possibly by cytokine production. If this problem can be overcome, T cell depletion of donor and recipient may be a good alternative to conventional GVHD prophylaxis for matched sibling transplants, resulting in a superior quality of life for the survivors. It is also likely to be particularly beneficial in transplants for non-malignant diseases and transplants from unrelated donors.
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PMID:Control of graft-versus-host disease and graft rejection by T cell depletion of donor and recipient with Campath-1 antibodies. Results of matched sibling transplants for malignant diseases. 777 29

Transplant related mortality and relapse after bmt have a negative influence on the outcome of patients transplanted for acute leukaemia in first remission. Transplant related mortality includes graft-versus-host disease, infections and graft failure. To prevent gvhd and associated infections without increased graft rejection, a protocol of combined in vivo/ex vivo T-cell depletion (Campath IgG 20 mg i.v. for 5 days and Campath IgM T-cell depleted graft) with no further immunosuppression was initiated. Up to now 22 adult patients (median age 39 years, range 21 to 51) have been transplanted. One graft failure most probably due to persistent leukaemia, three acute gvhd (grade I) and no chronic gvhd occurred. Two patients relapsed after bmt and died. Two further patients died due to idiopathic interstitial pneumonitis and acute liver failure, respectively. Eighteen patients are alive in complete remission. With a median follow up of 13 months (1-30) the probability of survival is 78%, disease free survival is 80% and transplant related mortality is 10%. We compared these results with 3 historical control groups with different regimens of gvhd prophylaxis. 1. MTX group (n = 15): With a median follow up of 135 (115-147) months after bmt the probability of survival is 40%, disease free survival is 40% and transplant related mortality is 60% (mainly gvhd and infection). 2. Campath group (only ex vivo T-cell depletion n = 25): With a median follow up of 86 (62-102) months probability of survival is 52%, disease free survival is 43% and transplant related mortality is 36% (mainly rejection and infection).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vitro and in vivo depletion of T cells. 812 50

Between January 1985 and March 1992, 48 patients with chronic phase CML underwent BMT from volunteer unrelated donors (MUD) serologically identical at HLA-A, B and DR loci. 19 patients received donor marrow ex vivo T-cell depleted (EX-TCD) with Campath monoclonal antibodies. 29 patients received unmanipulated donor marrow with CsA/MTX GVHD prophylaxis; 28 received additional intravenous antilymphocyte therapy from day +1 to +5 (IN-TCD). Overall 26 patients survive at median follow up of 362 days; actuarial survival at 3 years is 50%. 3 patients have sustained haematological relapse; actuarial leukaemia-free survival is 38%. There is no difference in overall survival between the EX-TCD and IN-TCD groups, but primary graft failure (n = 4) occurred only in the EX-TCD group, while GVHD (grade II or greater) occurred more frequently in the IN-TCD group (61% vs. 29%, p = 0.084). The optimum method for GVHD prophylaxis in MUD BMT remains uncertain.
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PMID:Matched unrelated donor bone marrow transplantation for chronic myeloid leukaemia in chronic phase: comparison of ex vivo and in vivo T-cell depletion. 844 31

We report on 24 patients with leukemia (19 pts), congenital disorders (4 pts) or severe aplastic anemia (1 pt) who received bone marrow transplantation from unrelated volunteer donors in 8 Italian Institutions. All the donor/recipient pairs were serologically HLA-A,B,DR matched; MLR was non reactive in 21 out of 24 cases. Preparative regimens were in accord with standards for diagnosis and disease status and included TBI in 15 patients, busulfan in 8, cyclophosphamide alone in one patient with SAA. GvHD prophylaxis consisted of cyclosporine/methotrexate in the majority of cases; 6 patients received additional immunotherapy with anti-lymphocyte globulin and 1 patient in vivo Campath-1G. The bone marrow was T-cell depleted in 2 cases. Acute GvHD grade II-IV occurred in 87% of patients (gr.III-IV: 57%) and was the main cause of death in 8 cases. Six patients (25%) survive with a median follow-up of 9 months, (16% actuarial survival at 3 years). A trend in favour of a better outcome has been found for age < 20 yrs at BMT (33% vs 22%), intensified GvHD prophylaxis (33% vs 22%) and transplants performed in more recent years (31% vs 18%).
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PMID:Bone marrow transplantation from unrelated donors: the Italian experience. GITMO, AIEOP and IBMDR. 844 60


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