A dose escalation study for salvage chemotherapy in patients with refractory lymphoma prior to high-dose myeloablative therapy with stem cell transplantation.
Chemosensitive response prior to transplantation has been shown to be most significant for survival post transplant. To estimate toxicity of a dose-intensive regimen that was to improve chemosensitive response rate, 15 patients with primary refractory lymphoma were enrolled in dose escalation of pre-transplant salvage chemotherapy. The first cycle had a fixed dose of ifosfamide 6 g/m2 and mitoxantrone 12 mg/m2, with arabinosyl cytosine (Ara-C) 2 g/m2, and methylprednisolone 2.0 g. Each cycle of the second and third had cisplatin 90 mg/m2, Ara-C 6 g/m2, methylprednisolone 2.0 g, and escalated doses of ifosfamide from 7.5 g/m2 to 15 g/m2 and mitoxantrone from 16 to 28 mg/m2. Blood stem cells were collected before the second cycle and > or = 3 x 10(6) CD34 cells/kg were infused 2 days after the second and third cycles, respectively. The maximum tolerated doses of ifosfamide and mitoxantrone were 11.25 g/m2 and 16 mg/m2, respectively. Acute renal failure and bacterial infection occurred as non-hematologic dose limiting toxicities. Eleven patients completed therapy. Five patients achieved complete remission and five had partial remission. Nine patients received autologous and four received allogeneic transplants. Currently, six are alive without evidence of disease, with a 3-year survival of 40%. Although preliminary, the regimen suggests acceptable toxicity and significant activity that warrants further study.
Department of Internal Medicine, Division of Hematology, Oncology, Blood and Marrow Transplantation, University of Iowa, College of Medicine, Iowa City, IA, USA.
C K
CK
Lee
M
M
de Magalhaes-Silverman
M
M
Hayashi
A
A
Schlueter
R G
RG
Strauss
R J
RJ
Hohl
R D
RD
Gingrich
D058186:Acute Kidney Injury / Q000139:chemically induced; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001424:Bacterial Infections / Q000209:etiology; D003561:Cytarabine / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D004361:Drug Tolerance; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000628:therapy*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000628:therapy*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage / Q000009:adverse effects; D009503:Neutropenia / Q000139:chemically induced; D016879:Salvage Therapy
D003561:Cytarabine; D008942:Mitoxantrone; D007069:Ifosfamide; D008775:Methylprednisolone