acute graft-versus-host disease (agvhd) prophylaxis with atg-fresenius in matched unrelated donor-stem cell transplantation (mud-sct)

Conditions: Graft vs Host Disease

Summary: the study aim is to evaluate the influence of the anti-t-lymphocyte globulin atg-fresenius s given pre-transplant in addition to standard gvhd prophylaxis with cyclosporine a and a short course of methotrexate with respect to efficacy and safety.

to assess the efficacy of atg-fresenius s in addition to standard therapy (cyclosporine a / methotrexate) with respect to early treatment failure defined by the occurrence of severe acute gvhd grade iii-iv or early mortality within 100 days post transplantation compared to standard therapy alone. all patients receive myeloablative therapy. recommended regimens: for patients with all: fractionated tbi (8-12 gy) plus cyclophosphamide (1-2 x 60 mg/kg) \[etoposide/melfalan are also allowed\]. for all other indications: either tbi (8-12 gy) or busulfan (per os 14-16 mg/kg b.w. or equivalent for iv administration) plus cyclophosphamide (1-2 x 60 mg/kg) or thiotepa ≥ 15 mg/kg or bcnu ≥ 300 mg/m2. conditioning regimens may differ from centre to centre; each centre decides for constant (disease specific) regimen(s) throughout the whole study period. standard gvhd prophylaxis consists of cyclosporine a (target trough level ≥ 200 ng/ml starting from day -1 until day +100) and short course methotrexate (15 mg/m2 at day +1, 10 mg/m2 at days +3, +6 and +11).

Eligibility criteria:
inclusion criteria: participation of patients in simultaneous diagnostic and comprehensive therapeutical trials for certain entities is allowed. * patients 18-60 years of age; * patients suffering from one of the following diseases: * aml: 1st complete remission (cr1) or beyond 1st remission (cr2, cr3), in relapse, not in remission (primary refractory, induction failure); * all: 1st complete remission (cr1) or beyond 1st remission (cr2, cr3), in relapse, not in remission (primary refractory, induction failure); * mds, if transplantation is medically indicated: ra (with poor risk factors as classified by the international prognostic scoring system of mds), rars, raeb, raeb-t, cmml; * cml: beyond 1st chronic phase (cp1): accelerated phase, blast crisis, chronic phase (cp2, cp3); * omf, if transplantation is medically indicated: osteomyelofibrosis; * patients designated to undergo allogeneic bone marrow transplantation or allogeneic peripheral blood stem cell transplantation; * patients with a hla-a, -b (dna-based, 2 digits), hla-drb1, -dqb1 (dna-based 4 digits) matched (8 out of 8 alleles) unrelated donor; serological typing is not required * patients with a karnofsky performance score (kps): \> 60%; * patients who underwent all obligatory screening examinations (special examinations within the last 4 weeks); * patients who have given their written informed consent to participate in the study. exclusion criteria: * patients with significant cardiac (e.g. ejection fraction \ 1.5 mg/dl), metabolic (e.g. bilirubin \> 2.0 mg/dl) and/or cns disease, currently uncontrolled by treatment, which may interfere with the completion of the study; * patients with any bacterial, viral, or fungal infections not under adequate antimicrobial control; * patients who are known to have serum hepatitis or who are carriers of the hepatitis b surface antigen (hbs-ag), or hepatitis c antibody, or who are known to have a positive result to the test of hiv antibodies; * patients with any additional concurrent or previous malignant disease; * patients with known hypersensitivity to rabbit immunoglobulin antibodies in past patient history or with known allergy to any substance chemically related to the study medication; * pregnant (β-hcg test) or lactating women; * patients who formerly underwent transplantation including previous autologous transplants; * patients who cannot communicate reliably with the investigator or who are not likely to cope with the requirements of the study.

Keywords: gvhd agvhd prophylaxis matched unrelated donor atg sct bmt polyclonal antibody gvhd prophylaxis for patients with all, aml, cml, mds, omf patients with allogeneic bm or pbsc transplantation patients with a matched unrelated donor