With this protocol the ALL-SCT BFM international study group wants * to evaluate whether hematopoietic stem cell transplantation (HSCT) from matched family or unrelated donors (MD) is equivalent to the HSCT from matched sibling donors (MSD). * to evaluate the efficacy of hematopoietic stem cell transplantation (HSCT)from mismatched family or unrelated donors (MMD) as compared to HSCT from matched sibling donors or matched donors. * to determine whether therapy has been carried out according to the main HSCT protocol recommendations. The standardisation of the treatment options during HSCT from different donor types aims at the achievement of an optimal comparison of survival after HSCT with survival after chemotherapy only. * to prospectively evaluate and compare the incidence of acute and chronic Graft-versus-Host-Disease (GvHD) after HSCT from matched sibling donor (MSD), from matched donor (MD) and from mismatched donor (MMD).
Patients with high risk or relapsed acute lymphoblastic leukaemia (ALL) have a worse prognosis compared to all other patients with ALL. For these patients additional therapy approaches are required after they have achieved remission with multimodal chemotherapy. Allogeneic haematopoetic stem cell transplantation shows promising results mainly due to an immunological antileukaemic control by the graft-versus-leukaemia effect but treatment related mortality and morbidity remains a serious problem.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
405
patients with MSD receive as conditioning VP16 60mg/kg/d on day -3
patients with a MSD receive TBI (12Gy in 6 fractions) as conditioning
patients with a HLA matched unrelated Donor (9/10 oder 10/10) receive VP16 60mg/kg/d on day -3 and ATG fresenius 20mg/kg/d on day -3,-2,-1
patients with a HLA matched unrelated Donor (9/10 oder 10/10) receive TBI (12Gy in 6 fractions)
patients with a MMD (haploidentical or cord blood) receive Fludarabine 30mg/m²/d on day -9 to -5, ATG fresenius 20mg/kg/d on day -3,-2,-1, Treosulfan 14g/m²/d on day -7 to -5 and Thiotepa 2x5mg/kg/d on day -4
patients with MMD-transplantation (8/10)receive VP16 60mg/kg/d on day -4, ATG from day -3 to day-1 20mg/kg/d
patients with a MMD-transplantation (8/10) receive 12 Gy in 6 fractions
Universitätsklinik für Kinder- und Jugendheilkunde, Klin. Abt. f. Hämato-Onkologie
Graz, Austria
Universitätsklinik für Kinder- und Jugendheilkunde
Innsbruck, Austria
St. Anna Children's Hospital
Vienna, Austria
Department of Paediatric Haematology and Oncology HSCT-Unit
Prague, Czechia
Pediatric Clinic II, Rigshospitalet
Copenhagen, Denmark
Event free survival
Event-free and overall survival after allogeneic HSCT
Time frame: 10 years
number of patients with GvHD acute and chronic Graft-versus-Host-Disease (GvHD)
evaluation of the incidence and severity of acute Grade I-IV graft versus Host disease and of limited or extensive chronic graft versus host disease
Time frame: 10 years
occurrence and course of late effects after chemotherapy with subsequent allogeneic HSCT
evaluation of organ dysfunctions according to WHO Toxicity score
Time frame: 10 years
occurrence and course of late effects after chemotherapy with subsequent allogeneic HSCT
evaluation of growth retardation and endocrine dysfunction
Time frame: 10 years
occurrence and course of late effects after chemotherapy with subsequent allogeneic HSCT
Evaluation of incidence of aseptic bone necrosis.
Time frame: 10 years
occurrence and course of subsequent malignancies after chemotherapy with subsequent allogeneic HSCT
Evaluation of incidence of secondary cancer after total body irradiation and/or chemotherapy
Time frame: 10 years
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