High-dose treosulfan in patients with relapsed or refractory high-grade lymphoma receiving tandem autologous blood stem cell transplantation.
This phase I/II study evaluated high-dose treosulfan in patients with high-grade lymphoma. In all, 21 patients (median age 51, 25-60 years) with primary refractory disease (n=3) or early (n=11) or late (n=7) relapse received DexaBEAM and one course etoposide for cytoreduction and PBPC mobilization. Subsequently, 16 patients received 30 g/m2 treosulfan and 140 mg/m2 melphalan, followed by autologous transplantation. Nine patients received a 2nd high-dose treatment (HDT) with 30 g/m2 treosulfan and 750 mg/m2 thiotepa. Recovery time to >1/nl leukocytes and >25/nl thrombocytes was 8.9 (range 8-11) and 11.9 (8-16) days after 1st and 9.6 (7-13) and 13 (9-19) days after 2nd HDT. Reversible grade 3 or 4 nonhematologic toxicities included mucositis (n=7), infection (n=7) and one episode of re-entry tachycardia. Two treatment-related deaths occurred after 2nd HDT. Since three dose-limiting toxicities occurred among nine patients receiving tandem HDT, 30 g/m2 of treosulfan was considered MTD in this setting. Patients with late compared to early relapse or refractory disease had a higher probability of CR (6/7 vs 3/14 patients, P=0.017) and overall survival (71 vs 21%, P<0.05, 24-49 months follow-up). In conclusion, high-dose treosulfan as major therapy component induces sustained complete remissions in relapsed high-grade lymphoma with acceptable toxicity.
Clinic of Hematology/Oncology, Germany. michael.koenigsmann@medizin.uni-magdeburg.de
M
M
Koenigsmann
M
M
Mohren
K
K
Jentsch-Ullrich
A
A
Franke
E
E
Becker
M
M
Heim
M
M
Freund
J
J
Casper
D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D002066:Busulfan / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D033581:Stem Cell Transplantation; D014182:Transplantation, Autologous / Q000276:immunology
D018906:Antineoplastic Agents, Alkylating; D005047:Etoposide; C018404:treosulfan; D002066:Busulfan