C(H)OP refractory chronic lymphocytic leukemia patients in whom salvage chemotherapy chosen by evaluating multiple chemotherapeutic drug-resistant factors was remarkably effective.
It is well known that the expression of anticancer drug-resistant factors is elevated in patients with primary refractory or relapsed chronic lymphocytic leukemia (CLL) who have been treated with chemotherapy. We report here two C(H)OP refractory patients with CLL in whom salvage chemotherapy chosen by evaluating anticancer drug-resistant factors (glutathione-S-transferase-Pi [GST-Pi], glycoprotein [GP]-170, multidrug resistance-associated protein [MRP], and lung resistance protein [LRP]) was remarkably effective. A 71-year-old male patient was refractory to induction therapy with cyclophosphamide, vincristine, and prednisone (COP), and his leukemic cells at diagnosis displayed overexpression of GST-Pi and GP-170. A 74-year-old female patient's condition had been stable; she had received ten courses of COP over 9 years. However, because systemic lymphadenopathies recurred, she was treated with chemotherapy consisting of cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) or dexamethasone, etoposide, ifosphamide, and carboplatin (DeVIC). However, she did not respond at all, and her leukemic cells at recurrence displayed overexpression of GST-Pi. Therefore, we chose for these patients a salvage therapy consisting of dexamethasone and high-dose cytosine arabinoside (Ara C), to which neither GST-Pi nor GP-170 show any drug resistance. In both patients, this salvage therapy proved effective.
Matsunaga
Takuya
T
Fourth Department of Internal Medicine, Sapporo Medical University, South-1, West-17, Chuo-ku, 060-8543, Sapporo, Japan. matunaga@sapmed.ac.jp
Kogawa
Katsuhisa
K
Fujimi
Akihito
A
Takizawa
Kohei
K
Takahira
Naoki
N
Takemoto
Naofumi
N
Tanaka
Ikuta
I
Akiyama
Takehide
T
Sato
Tsutomu
T
Takayama
Tetsuji
T
Terui
Takeshi
T
Sakamaki
Sumio
S
Niitsu
Yoshiro
Y
D018435:ATP Binding Cassette Transporter, Subfamily B; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D005982:Glutathione Transferase / Q000032:analysis; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000032:analysis; D009363:Neoplasm Proteins / Q000032:analysis; D011241:Prednisone / Q000008:administration & dosage; D016879:Salvage Therapy; D017211:Treatment Failure; D020394:Vault Ribonucleoprotein Particles; D014750:Vincristine / Q000008:administration & dosage; D000099187:Major Vault Protein
D018435:ATP Binding Cassette Transporter, Subfamily B; D003520:Cyclophosphamide; D004317:Doxorubicin; D005982:Glutathione Transferase; D006023:Glycoproteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D011241:Prednisone; D020394:Vault Ribonucleoprotein Particles; D014750:Vincristine; D000099187:Major Vault Protein; C513055:ABCB1 protein, human