Safety and feasibility of high-dose ranimustine (MCNU), carboplatin, etoposide, and cyclophosphamide (MCVC) therapy followed by autologous stem cell transplantation for malignant lymphoma.
High-dose chemotherapy followed by autologous stem cell transplantation (auto-SCT) is widely used as a salvage therapy in the treatment of refractory malignant lymphoma. To investigate the safety and feasibility of a high-dose MCNU, carboplatin, etoposide and cyclophosphamide (MCVC) regimen, we conducted a prospective multicenter trial. Thirty patients with relapsed/refractory/poor-risk non-Hodgkin lymphoma (NHL n = 27) or Hodgkin lymphoma (HD n = 3) were uniformly treated with an MCVC regimen and underwent auto-SCT. The median follow-up duration of the surviving patients was 67 months (56-133 months). The major toxicities were anorexia (94 %), diarrhea (80 %), nausea (79 %), febrile neutropenia (70 %), alopecia (67 %) and mucositis (60 %). Three patients developed severe left ventricular dysfunction, and two patients developed severe sinusoidal obstructive syndrome (SOS). Of these patients, two died without disease progression. Treatment-related mortality was 6.6 %. Late-onset adverse events including two cases of cytomegalovirus pneumonia and one of interstitial pneumonia were observed. In DLBCL (n = 13) and transformed FL (n = 2) patients, OS and EFS at 3 years were 72 and 46 %, respectively. These results suggest that the MCVC regimen followed by auto-SCT is a feasible and tolerable therapy for relapsed/refractory malignant lymphoma. However, cardiac toxicity due to high-dose cyclophosphamide and development of SOS can occur and should be carefully monitored. Further follow-up is needed to evaluate the long-term efficacy and safety of this regimen.
Department of Hematology, Akita University Graduate School of Medicine, Akita, Japan. ykameoka@doc.med.akita-u.ac.jp
Yoshihiro
Y
Kameoka
Naoto
N
Takahashi
Kenichi
K
Ishizawa
Yuichi
Y
Kato
Jugo
J
Ito
Osamu
O
Sasaki
Kazunori
K
Murai
Hideyoshi
H
Noji
Makoto
M
Hirokawa
Katsusi
K
Tajima
Tsutomu
T
Shichishima
Yoji
Y
Ishida
Hideo
H
Harigae
Kenichi
K
Sawada
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006689:Hodgkin Disease / Q000401:mortality* / Q000628:therapy*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009607:Nitrosourea Compounds / Q000008:administration & dosage / Q000009:adverse effects; D033581:Stem Cell Transplantation; D015996:Survival Rate; D014182:Transplantation, Autologous
D009607:Nitrosourea Compounds; D005047:Etoposide; D003520:Cyclophosphamide; D016190:Carboplatin; C020766:ranimustine