Effect on cytokine release and graft-versus-host disease of different anti-T cell antibodies during conditioning for unrelated haematopoietic stem cell transplantation

Abstract

Summary:Three different types of anti-T cell antibody were used in patients undergoing haematopoietic stem cell transplantation (HSCT) with an HLA-A, -B and -DR compatible unrelated donor: ATG-Fresenius (ATG-F) (n = 26), Thymoglobuline (TMG) (n = 61) and OKT-3 (n = 45). The groups were comparable regarding diagnosis, stage, age, conditioning and GVHD prophylaxis, Adverse events were less frequent after ATG-F treatment. Levels of IL-2, IL-6, IFN-␥, TNF-␣ and GM-CSF were increased after OKT-3 infusion. In multivariate analysis OKT-3 treatment (P = 0.01), G-CSF treatment (P = 0.02) and a cell dose у2.7 ؋ 10 8 /kg (P = 0.03) gave a faster engraftment. Acute GVHD grades II-IV occurred in 25% of the ATG-F patients, 12% of the TMGpatients and 43% (P Ͻ 0.001 vs TMG) of the OKT-3 patients. OKT-3 was associated with acute GVHD in multivariate analysis. TRM was 26% using TMG as compared to 43% in the OKT-3 group (P = 0.03). Patient survival at 4 years was 63%, 50% and 45% in the ATG-F, TMG and OKT-3-treated patients, respectively (NS). Relapses were 8%, 49% and 34%, respectively (ATG-F vs TMG, P = 0.03). Relapse-free survivals were 61%, 40% and 37% (NS). Among CML patients the probability of relapse was 61% in TMG-treated patients, while no patients relapsed in the other two groups. To conclude, the type of anti-T cell antibody affects GVHD and relapse after HSCT using unrelated donors.

The clinical importance of bronchoalveolar lavage in allogeneic SCT patients with pneumonia

“…All patients with unrelated donors or non-malignant disorders were administered anti-thymocyte globulin for 2-5 days before transplantation. 12 As GVHD prophylaxis, 348 patients were administered CsA and four doses of MTX. During the first month, the blood CsA levels were kept at 100-150 ng/ml in patients with sibling donors and at 200-300 ng/ml in patients with matched unrelated donors.…”

Unrelated donor BMT recipients given pretransplant low-dose antithymocyte globulin have outcomes equivalent to matched sibling BMT: a matched pair analysis

“…6 In recent years, a number of European centers have reported relatively low rates of acute GVHD and early TRM using a variety of ATG products and schedules of administration. [7][8][9][10][11][12][13][14][15] Total doses of pretransplant thymoglobulin have ranged between 8 and 20 mg/kg. 8,9,12,13 An IBMTR analysis of alternative donor transplants between 1987 and 1993 indicated that the influence of donors on outcome was not apparent in high risk patients but quite significant with low and intermediate risk disease.…”

“…[7][8][9][10][11][12][13][14][15] Total doses of pretransplant thymoglobulin have ranged between 8 and 20 mg/kg. 8,9,12,13 An IBMTR analysis of alternative donor transplants between 1987 and 1993 indicated that the influence of donors on outcome was not apparent in high risk patients but quite significant with low and intermediate risk disease. 20 The current analysis indicates that equivalent outcomes may be seen at all stages.…”

“…[1][2][3][4][5][6] In addition, some uncontrolled studies have indicated that pretransplant serotherapy with antithymocyte globulin (ATG) or other antibodies appears to reduce acute GVHD and early mortality of closely matched UD BMT to levels comparable to matched related donor (MRD) BMT. [7][8][9][10][11][12][13][14][15] Since 1995 we have used a relatively low dose of rabbit ATG in the pretransplant conditioning protocol for all UD transplants. Outcomes of 57 of these patients are compared with those of 57 MRD BMT recipients matched for important prognostic factors.…”

Immune reconstitution after haematopoietic transplantation with two different doses of pre-graft antithymocyte globulin

“…[5][6][7] Different types of pre-graft serotherapy have been used including monoclonal antibodies such as OKT3, or Campath 1G anti-CD52, or rabbit or horse polyclonal antibodies directed against thymocytes or T lymphocytes. 2,[5][6][7][8] The type of antibody used during the conditioning regimen affects the rate of GVHD, infection and relapse. 8 A recent study reported that 15 mg/kg, but not 7.5 mg/kg, of rabbit antithymocyte globulin (ATG), reduces the incidence of grade III-IV acute GVHD.…”