PURPOSE: To improve the effect of allogeneic stem-cell transplantation by sequential use of intensive chemotherapy, reduced-intensity conditioning (RIC), and prophylactic donor lymphocyte transfusions (pDLTs) in high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). PATIENTS AND METHODS: In a prospective study of 75 consecutive patients (median age, 52.3 years), high risk was defined by progressive or refractory disease (n = 59), second remission after early relapse (n = 8), or first remission with poor prognosis based on cytogenetics or delayed response to induction therapy (n = 8). Unfavorable karyotypes were found in 49% of informative patients, and 68 patients had medical contraindications against standard conditioning. Fludarabine (30 mg/m2), cytarabine (2 g/m2), and amsacrine (100 mg/m2) for 4 days were used for cytoreduction. After 3 days of rest, RIC consisted of 4 Gy total-body irradiation, antithymocyte globulin, and 80 to 120 mg/kg cyclophosphamide. Thirty-one patients had an HLA-identical sibling donor; 44 patients had an unrelated and/or HLA-mismatched donor. pDLT was given from day +120 in patients who were not receiving immunosuppression and were free of graft-versus-host disease (GvHD). RESULTS: Complete remission was induced in 66 patients (88%). With a median follow-up of 35.1 months (range, 13.6 to 47.6 months), 2-year overall and leukemia-free survival were 42% and 40%, respectively. Outcome of patients with refractory disease or with complex cytogenetic aberrations was identical to that of better prognostic subgroups. Survival was best in patients who received high CD34+ cell numbers, and in patients with limited GvHD. CONCLUSION: Sequential use of intensive chemotherapy, RIC transplantation, and pDLT represents a promising approach to the treatment of high-risk AML and MDS, particularly in patients with most unfavorable prognoses.
PURPOSE: To improve the effect of allogeneic stem-cell transplantation by sequential use of intensive chemotherapy, reduced-intensity conditioning (RIC), and prophylactic donor lymphocyte transfusions (pDLTs) in high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). PATIENTS AND METHODS: In a prospective study of 75 consecutive patients (median age, 52.3 years), high risk was defined by progressive or refractory disease (n = 59), second remission after early relapse (n = 8), or first remission with poor prognosis based on cytogenetics or delayed response to induction therapy (n = 8). Unfavorable karyotypes were found in 49% of informative patients, and 68 patients had medical contraindications against standard conditioning. Fludarabine (30 mg/m2), cytarabine (2 g/m2), and amsacrine (100 mg/m2) for 4 days were used for cytoreduction. After 3 days of rest, RIC consisted of 4 Gy total-body irradiation, antithymocyte globulin, and 80 to 120 mg/kg cyclophosphamide. Thirty-one patients had an HLA-identical sibling donor; 44 patients had an unrelated and/or HLA-mismatched donor. pDLT was given from day +120 in patients who were not receiving immunosuppression and were free of graft-versus-host disease (GvHD). RESULTS: Complete remission was induced in 66 patients (88%). With a median follow-up of 35.1 months (range, 13.6 to 47.6 months), 2-year overall and leukemia-free survival were 42% and 40%, respectively. Outcome of patients with refractory disease or with complex cytogenetic aberrations was identical to that of better prognostic subgroups. Survival was best in patients who received high CD34+ cell numbers, and in patients with limited GvHD. CONCLUSION: Sequential use of intensive chemotherapy, RIC transplantation, and pDLT represents a promising approach to the treatment of high-risk AML and MDS, particularly in patients with most unfavorable prognoses.
Authors: Charles Craddock; Sandeep Nagra; Andrew Peniket; Cassandra Brookes; Laura Buckley; Emmanouil Nikolousis; Nick Duncan; Sudhir Tauro; John Yin; Effie Liakopoulou; Panos Kottaridis; John Snowden; Donald Milligan; Gordon Cook; Eleni Tholouli; Tim Littlewood; Karl Peggs; Paresh Vyas; Fiona Clark; Mark Cook; Stephen Mackinnon; Nigel Russell Journal: Haematologica Date: 2009-11-30 Impact factor: 9.941
Authors: A-K Zoellner; S Fritsch; D Prevalsek; N Engel; M Hubmann; R Reibke; C T Rieger; J C Hellmuth; M Haas; F Mumm; T Herold; G Ledderose; W Hiddemann; M Dreyling; A Hausmann; J Tischer Journal: Bone Marrow Transplant Date: 2015-02-02 Impact factor: 5.483
Authors: J M Middeke; R Herbst; S Parmentier; G Bug; M Hänel; G Stuhler; K Schäfer-Eckart; W Rösler; S Klein; W Bethge; U Bitz; B Büttner; H Knoth; N Alakel; M Schaich; A Morgner; M Kramer; K Sockel; M von Bonin; F Stölzel; U Platzbecker; C Röllig; C Thiede; G Ehninger; M Bornhäuser; J Schetelig Journal: Leukemia Date: 2015-08-18 Impact factor: 11.528