High-dose etoposide in allogeneic stem cell transplantation.
The anti-leukemic effect of etoposide is well documented. High-dose etoposide 60 mg/kg in combination with fractionated total body irradiation (TBI), usually single fractions of 1.2 Gy up to a total of 13.2 Gy, is used as conditioning therapy for allogeneic stem cell transplantation. Most studies of this conditioning regimen have included patients with acute leukemia receiving bone marrow or mobilized stem cell grafts derived from family or matched unrelated donors, and the treatment is then effective even in patients with high-risk disease. The most common adverse effects are fever with hypotension and rash, nausea and vomiting, sialoadenitis, neuropathy and metabolic acidosis. A small minority of patients develop severe allergic reactions. Etoposide has also been tested in a wide range of combination regimens, but for many of these combinations, relatively few patients are included, and some combinations have only been tested in patients who have undergone autologous transplants. However, the general conclusion is that many of these combinations are effective in patients with high-risk malignancies and the toxicity often seems acceptable. Thus, etoposide-based conditioning therapy should be further evaluated in patients having allogeneic transplants, but randomized trials are needed and the design of future trials should be based on the well-characterized TBI + high-dose etoposide regimen.
Department of Medicine, Section of Hematology, Haukeland University Hospital, Bergen, Norway.
Oystein
O
Bruserud
Håkon
H
Reikvam
Astrid Olsnes
AO
Kittang
Aymen Bushra
AB
Ahmed
Tor Henrik Anderson
TH
Tvedt
Malvin
M
Sjo
Kimberley Joanne
KJ
Hatfield
D000227:Adenine Nucleotides / Q000008:administration & dosage; D018943:Anthracyclines / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000008:administration & dosage; D002066:Busulfan / Q000008:administration & dosage; D016190:Carboplatin / Q000008:administration & dosage; D002330:Carmustine / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D000077866:Clofarabine; D003520:Cyclophosphamide / Q000008:administration & dosage; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007938:Leukemia / Q000188:drug therapy / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D008130:Lomustine / Q000008:administration & dosage; D052016:Mucositis / Q000139:chemically induced; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy; D018714:Radiotherapy, Adjuvant; D012720:Severity of Illness Index; D033581:Stem Cell Transplantation; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
D000227:Adenine Nucleotides; D018943:Anthracyclines; D000972:Antineoplastic Agents, Phytogenic; D001087:Arabinonucleosides; D005047:Etoposide; D000077866:Clofarabine; D008130:Lomustine; D003520:Cyclophosphamide; D016190:Carboplatin; D002066:Busulfan; D002330:Carmustine; D007069:Ifosfamide