Results of intensive chemotherapy followed by hematopoietic stem-cell rescue in 22 patients with refractory or recurrent primary CNS lymphoma or intraocular lymphoma.
OBJECTIVE
To assess the feasibility and efficacy of intensive chemotherapy with hematopoietic stem-cell rescue (IC + HCR) in patients with refractory or recurrent primary CNS lymphoma (PCNSL) or intraocular lymphoma (IOL).


METHODS
IC consisted of thiotepa 250 mg/m(2)/d days -9 through -7, busulfan 10 mg/kg (total dose) days -6 through -4, and cyclophosphamide 60 mg/kg/d days -3 and -2. Intravenous clonazepam 2 mg/d was given prophylactically from the day before initiation of busulfan therapy to the day after completion of busulfan therapy. Patients with refractory or recurrent PCNSL underwent IC + HCR only if they were chemosensitive to two cycles of salvage treatment with cytarabine (2 g/m(2)/d days 2 through 5 and 50 mg/m(2)/d days 1 through 5 in a 12-hour infusion) and etoposide (VP-16; 200 mg/m(2)/d days 2 through 5) (CYVE). Patients with IOL refractory to high-dose methotrexate (MTX) and cytarabine entered the IC + HCR program directly.


RESULTS
Twenty-two patients (10 with relapses, 12 with refractory disease) were enrolled. Twenty patients entered the IC + HCR program: twelve entered after CYVE treatment, seven entered directly, and one had previously been retreated with high-dose MTX. Before IC, eight patients were in complete remission (CR), four were in partial remission (PR), one had stable disease, and seven had refractory disease. After IC + HCR, 16 patients entered CR, two remained in PR, one had stable disease, and one had disease progression. Fourteen patients remained alive (median follow-up time, 41.5 months). The overall probability of survival at 3 years was 63.7%. After IC, that probability was 60% and the 3-year probability of event-free survival was 53%. Seven patients had neurologic adverse events during the entire procedure.


CONCLUSIONS
IC + HCR proved feasible and effective in patients with refractory or recurrent PCNSL or IOL. The entire procedure seemed to be most toxic in patients > or = 60 years. A prospective multicenter study is ongoing.
Soussain
C
C
Service d'Hématologie, Hôpital de Meaux, Meaux, France. c-soussain@ch-meaux.fr
Suzan
F
F
Hoang-Xuan
K
K
Cassoux
N
N
Levy
V
V
Azar
N
N
Belanger
C
C
Achour
E
E
Ribrag
V
V
Gerber
S
S
Delattre
J Y
JY
Leblond
V
V
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002066:Busulfan / Q000008:administration & dosage; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000628:therapy*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage; D005134:Eye Neoplasms / Q000188:drug therapy / Q000628:therapy*; D005240:Feasibility Studies; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000628:therapy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy / Q000628:therapy; D016400:Lymphoma, Large-Cell, Immunoblastic / Q000188:drug therapy / Q000628:therapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000628:therapy*; D016399:Lymphoma, T-Cell / Q000188:drug therapy / Q000628:therapy; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000628:therapy*; D009422:Nervous System Diseases / Q000139:chemically induced; D016879:Salvage Therapy; D013852:Thiotepa / Q000008:administration & dosage
D003561:Cytarabine; D005047:Etoposide; D003520:Cyclophosphamide; D013852:Thiotepa; D002066:Busulfan; D008727:Methotrexate