Treatment of refractory lymphoma with high dose cytarabine, cyclophosphamide and either TBI or VP-16 followed by autologous bone marrow transplantation.
This study was designed to test the efficacy and toxicity of combining high-dose cytarabine (3 g/m2 every 12 h x 8 doses day -7 to day -4, total dose 24 g/m2), methyl prednisolone (0.5 mg/kg every 4 h day -7 to day -1), and cyclophosphamide (CY) (60 mg/kg day -3 and day -2) with either total body irradiation (TBI) (900 cGy in a single fraction on day -1) or VP-16 (600 mg/m2/days -7, -5, and -3) in patients not eligible for TBI secondary to prior radiotherapy. We treated 14 patients (eight male, six female) with either non-Hodgkin's lymphoma (n = 5) or Hodgkin's disease (n = 9). All patients had failed prior conventional chemotherapy (median two regimens range 1-5). Five patients were treated with TBI and nine with VP-16. There were eight complete remissions, two partial remissions, four were inevaluable for response due to early death. Overall survival is 21% (3/14) and relapse-free survival is 7% (1/14) with the sole disease-free survivor now 40 months from transplant. Very significantly, among patients receiving TBI, there were no survivors (median survival 24 days, range 17-330 days) and 4/5 had pulmonary complications. Median DLCO in these four patients was 61% (range 50-67) prior to transplant and none had an infectious etiology established by bronchoalveolar lavage. Median time to an absolute granulocyte count of 500 x 10(6)/l was 16 days (range 10-37 days) and to a platelet count of 20 x 10(9)/l was 12 days (range 7-22 days). In conclusion, the addition of high-dose cytarabine (24 g/m2) to CY and single-dose TBI or VP-16, while being very active, produced excessive pulmonary toxicity in this group of patients with lymphoma.
Broun
E R
ER
Indiana University Hospital, Indianapolis 46202-5250.
Tricot
G
G
Akard
L
L
Nichols
C
C
Cheerva
A
A
Jansen
J
J
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D003131:Combined Modality Therapy / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006689:Hodgkin Disease / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D014916:Whole-Body Irradiation
D003561:Cytarabine; D005047:Etoposide; D003520:Cyclophosphamide