Overcoming drug resistance in mantle cell lymphoma using a combination of dose-dense and intense therapy.
We present a study of the prevalence of genetic polymorphisms and expression of genes encoding the drug-resistance proteins glutathione S-transferases (GSTs) in order to gain insights into the pattern of failure evident in mantle cell lymphoma. We note a high preponderance of genetic alterations conferring resistance to standard chemotherapy in this illness. Concurrent with this investigation, we present a series of patients who were provided dose-dense and intense chemotherapy to circumvent these drug-resistance mechanisms. High responses were noted, though durable remissions were few, indicating non-traditional chemotherapy options are important to investigate in this illness.
Duke University Medical Center, Department of Medicine, Division of Oncology and Stem Cell Transplantation, Adult Bone Marrow Transplantation Program, Durham, NC, USA.
Christopher A
CA
Crout
Liang-Piu
LP
Koh
Jon P
JP
Gockerman
Joseph O
JO
Moore
Carlos
C
Decastro
Gwynn D
GD
Long
Louis
L
Diehl
Christina
C
Gasparetto
Donna
D
Niedzwiecki
Jon
J
Edwards
Leonard
L
Prosnitz
Mitchell
M
Horwitz
Jon
J
Chute
Ashley
A
Morris
Patricia
P
Davis
Anne
A
Beaven
Nelson J
NJ
Chao
Francis
F
Ali-Osman
David A
DA
Rizzieri
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002330:Carmustine / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005787:Gene Frequency; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D036102:Peripheral Blood Stem Cell Transplantation; D011110:Polymorphism, Genetic; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D002330:Carmustine; D003520:Cyclophosphamide; D003561:Cytarabine; D005047:Etoposide; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D016179:Granulocyte Colony-Stimulating Factor; D008942:Mitoxantrone; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human