Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome.
OBJECTIVE
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).


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.


CONCLUSIONS
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.
Schmid
Christoph
C
José Carreras Unit for Hematopoietic Stem Cell Transplantation, Department of Medicine III, Ludwig-Maximilians-University Hospital, Marchioninistr 15, 81379 Munich, Germany. Christoph.Schmid@med.uni-muenchen.de
Schleuning
Michael
M
Ledderose
Georg
G
Tischer
Johanna
J
Kolb
Hans-Jochem
HJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000677:Amsacrine / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016009:Chi-Square Distribution; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D016015:Logistic Models; D017710:Lymphocyte Transfusion; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000628:therapy*; D010865:Pilot Projects; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012074:Remission Induction; D033581:Stem Cell Transplantation; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
D000677:Amsacrine; D003561:Cytarabine; D014740:Vidarabine; C024352:fludarabine