Intensive methotrexate and cytarabine followed by high-dose chemotherapy with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma: an intent-to-treat analysis.
OBJECTIVE
To assess the safety and efficacy of intensive methotrexate-based chemotherapy followed by high-dose chemotherapy (HDT) with autologous stem-cell rescue in patients with newly diagnosed primary CNS lymphoma (PCNSL).


METHODS
Twenty-eight patients received induction chemotherapy using high-dose systemic methotrexate (3.5 g/m2) and cytarabine (3 g/m2 daily for 2 days). Fourteen patients with chemosensitive disease evident on neuroimaging then received high-dose therapy using carmustine, etoposide, cytarabine, and melphalan with autologous stem-cell rescue.


RESULTS
The objective response rate to the induction-phase chemotherapy was 57%, and median overall survival is not yet assessable, with a median follow-up time of 28 months. The overall median event-free survival time is 5.6 months for all patients and 9.3 months for 14 patients who underwent transplantation. Six of these 14 patients (43%) remained disease-free at last follow-up. Treatment was well tolerated; there was one transplantation-related death. Prospective neuropsychologic evaluations have revealed no evidence of treatment-related neurotoxicity.


CONCLUSIONS
This treatment approach is feasible in patients with newly diagnosed PCNSL without evidence of significant related neurotoxicity. Although the transplantation results are similar to those achieved in patients with aggressive or poor-prognosis systemic lymphoma, the low response rate to induction chemotherapy and the significant number of patients who experienced relapse soon after HDT suggest that more aggressive induction chemotherapy may be warranted.
Abrey
Lauren E
LE
Departments of Neurology and Medicine and the Office of Clinical Research, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. abreyl@mskcc.org
Moskowitz
Craig H
CH
Mason
Warren P
WP
Crump
Michael
M
Stewart
Douglas
D
Forsyth
Peter
P
Paleologos
Nina
N
Correa
Denise D
DD
Anderson
Nicole D
ND
Caron
Dawn
D
Zelenetz
Andrew
A
Nimer
Stephen D
SD
DeAngelis
Lisa M
LM
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002330:Carmustine / Q000008:administration & dosage; D016543:Central Nervous System Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D011446:Prospective Studies; D012074:Remission Induction; D012449:Safety; D016879:Salvage Therapy; D015996:Survival Rate; D014182:Transplantation, Autologous; D016896:Treatment Outcome
D003561:Cytarabine; D005047:Etoposide; D008558:Melphalan; D002330:Carmustine; D008727:Methotrexate