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.
Crout
Christopher A
CA
Duke University Medical Center, Department of Medicine, Division of Oncology and Stem Cell Transplantation, Adult Bone Marrow Transplantation Program, Durham, NC, USA.
Koh
Liang-Piu
LP
Gockerman
Jon P
JP
Moore
Joseph O
JO
Decastro
Carlos
C
Long
Gwynn D
GD
Diehl
Louis
L
Gasparetto
Christina
C
Niedzwiecki
Donna
D
Edwards
Jon
J
Prosnitz
Leonard
L
Horwitz
Mitchell
M
Chute
Jon
J
Morris
Ashley
A
Davis
Patricia
P
Beaven
Anne
A
Chao
Nelson J
NJ
Ali-Osman
Francis
F
Rizzieri
David A
DA
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