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Journal of Clinical Oncology, Vol 19, Issue 3 (February), 2001: 742-749
© 2001 American Society for Clinical Oncology

Results of Intensive Chemotherapy Followed by Hematopoietic Stem-Cell Rescue in 22 Patients With Refractory or Recurrent Primary CNS Lymphoma or Intraocular Lymphoma

By Carole Soussain, Florence Suzan, Khê Hoang-Xuan, Nathalie Cassoux, Vincent Levy, Nabih Azar, Coralie Belanger, Eddine Achour, Vincent Ribrag, Sophie Gerber, Jean-Yves Delattre, and Véronique Leblond

From the Service d’Hématologie, Hôpital de Meaux, Meaux; Service d’Hématologie, Hôpital de Versailles, Versailles; Services de Neuro-Oncologie, d’Ophtalmologie, de Neuro-Radiologie, and d’Hématologie and Centre de Transfusion, Hôpital Pitié-Salpêtrière, Paris; Département de Biostatistique et d’Informatique Médicale, Hôpital Saint-Louis, Paris; Service d’Hématologie, Hôpital Necker Paris, Paris; Service d’Hématologie, Hôpital de Colmar, Colmar; and Service d’Hématologie, Institut Gustave Roussy, Villejuif, France.

Address reprint requests to Carole Soussain, MD, Service d’ Hématologie, CHG Meaux, 6-8 rue Saint-Fiacre, BP 218, 77104 Meaux Cedex, France; email: c-soussain{at}ch-meaux.fr

PURPOSE: 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).

PATIENTS AND METHODS: IC consisted of thiotepa 250 mg/m2/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/m2/d days 2 through 5 and 50 mg/m2/d days 1 through 5 in a 12-hour infusion) and etoposide (VP-16; 200 mg/m2/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.

CONCLUSION: 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 >= 60 years. A prospective multicenter study is ongoing.


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