Improved results of allogeneic bone marrow transplantation for advanced hematologic malignancy using busulfan, cyclophosphamide and etoposide as cytoreductive and immunosuppressive therapy.
Twenty-four patients between the ages of 8 and 48 years (median 27.5) with high-risk for relapse hematologic malignancy received a marrow transplant from an HLA and MLC compatible sibling donor after chemotherapy with busulfan, 4 mg/kg/day for 4 days by mouth, cyclophosphamide 60 mg/kg/day i.v. for 2 days, and etoposide 60 mg/kg i.v. over 4 h on the first day of cyclophosphamide treatment (BU/CY/VP). Toxicity consisted of mucositis, skin rash, and nausea and vomiting in all patients, transient fever thought to be due to etoposide administration in 16/24 (67%) patients, and clinical veno-occlusive disease (VOD) of the liver in 4/24 (17%). There were nine deaths from causes other than recurrent disease in the first 100 days after transplant and two deaths after day 100, a total transplant mortality of 11/24 (46%). Three patients relapsed, but 10/24 (40%) remain alive and disease free 26-182 weeks (median 60 weeks) from transplant. These results compare favorably with results in a group of 12 similar risk patients treated with total body irradiation (TBI) containing regimens during an overlapping time period. Six of the TBI patients have had persistent or recurrent disease and only two (17%) are currently alive and disease free. The probability of disease persistence or relapse is 67% in the TBI group and 20% in the BU/CY/VP group (p less than 0.02).
Vaughan
W P
WP
Department of Internal Medicine, College of Pharmacy, University of Nebraska Medical Center, Omaha.
Dennison
J D
JD
Reed
E C
EC
Klassen
L
L
McGuire
T R
TR
Sanger
W G
WG
Kumar
P P
PP
Warkentin
P I
PI
Gordon
B G
BG
Bierman
P J
PJ
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology*; D002066:Busulfan / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005047:Etoposide / Q000009:adverse effects / Q000627:therapeutic use*; D006086:Graft vs Host Disease / Q000453:epidemiology; D006504:Hepatic Veno-Occlusive Disease / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D007938:Leukemia / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D008875:Middle Aged; D013997:Time Factors; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000276:immunology*
D007166:Immunosuppressive Agents; D005047:Etoposide; D003520:Cyclophosphamide; D002066:Busulfan