Comparative regimens for the ex vivo chemopurification of B cell lymphoma-contaminated marrow.
The success of autologous bone marrow transplantation for B cell lymphoma may depend on the efficacy of in vitro purification of patients' tumor cell-contaminated marrow. In this study, we tested the toxicity of seven different chemotherapeutic agents against two B cell lymphoma lines (LY-16 and SK-DHL-2) as compared to normal human bone marrow granulocyte-macrophage progenitor cells (CFU-GM). 4-Hydroperoxycyclophosphamide (4-HC), VP-16-213 (VP-16), nitrogen mustard, and vincristine showed a highly selective toxicity against cultured lymphoma cells; i.e., at doses sufficient to induce a 4-log clonogenic tumor cell reduction (4-HC 21 micrograms/ml, VP-16 50 micrograms/ml, nitrogen mustard and vincristine 5 micrograms/ml), 10.0 +/- 6.7, 3.0 +/- 3.2, 23.2 +/- 22.7 and 24.0 +/- 17.0% (mean +/- 1 SD), respectively, of normal bone marrow CFU-GM were preserved. The differential sensitivity of tumor cells and normal hematopoietic precursors was less prominent after exposure of cells to cis-diamminechloroplatinum II (cis-platinum); thus, at a drug dose of 100 micrograms/ml, all detectable lymphoma cells could be eradicated (i.e., greater than or equal to 4 log reduction) while a CFU-GM recovery of only 0.2 +/- 0.2% was observed. In contrast, adriamycin and bleomycin, at the highest tumoricidal concentrations tested (5 and 100 micrograms/ml, respectively) did not exhibit a selective toxicity toward lymphoma cell lines. In summary, our results suggest that nitrogen mustard and vincristine, as well as 4-HC and VP-16, may be useful agents for the ex vivo treatment of bone marrow grafts form B cell lymphoma patients.
Gulati
S C
SC
Laboratory of Hematopoietic Cell Kinetics, Memorial Sloan-Kettering Cancer Center, New York.
Atzpodien
J
J
Langleben
A
A
Shimazaki
C
C
Jain
K
K
Yopp
J
J
Ng
R P
RP
Colvin
O M
OM
Clarkson
B D
BD
D000970:Antineoplastic Agents / Q000633:toxicity*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000473:pathology; D001761:Bleomycin / Q000633:toxicity; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D002460:Cell Line; D002469:Cell Separation / Q000379:methods; D002945:Cisplatin / Q000633:toxicity; D003520:Cyclophosphamide / Q000031:analogs & derivatives / Q000633:toxicity; D004317:Doxorubicin / Q000633:toxicity; D005047:Etoposide / Q000031:analogs & derivatives / Q000633:toxicity; D006801:Humans; D008223:Lymphoma / Q000473:pathology*; D008466:Mechlorethamine / Q000633:toxicity; D014750:Vincristine / Q000633:toxicity
D000970:Antineoplastic Agents; C051505:3',4'-dihydroxyetoposide; D001761:Bleomycin; C012358:4-hydroxycyclophosphamide; D008466:Mechlorethamine; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin