Pretreatment EBV-DNA copy number is predictive of response and toxicities to SMILE chemotherapy for extranodal NK/T-cell lymphoma, nasal type.
OBJECTIVE
Extranodal NK/T-cell lymphoma, nasal type (ENKL) is an Epstein-Barr virus (EBV)-associated lymphoma for which a new chemotherapeutic regimen called SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) recently showed promising results.


METHODS
The amount of EBV-DNA was prospectively measured in whole-blood and plasma samples by real-time quantitative PCR from 26 patients registered in the SMILE phase II study.


RESULTS
Before treatment, the EBV-DNA was detected in 22 samples of whole blood with a median number of 3,691 copies/mL (range: 0-1.14 × 10(7)), but 15 samples of plasma with a median of 867 copies/mL (range: 0-1.27 × 10(7)). Results of these 2 measurements of EBV-DNA well correlated (R(2) = 0.994, P < 0.001). The overall response rate to SMILE was significantly higher in patients with less than 10(5) copies/mL of EBV-DNA in whole blood at enrollment (90% vs. 20%, P = 0.007) and in patients with less than 10(4) copies/mL of EBV-DNA in plasma (95% vs. 29%, P = 0.002). The incidence of grade 4 toxicity of SMILE other than leukopenia/neutropenia was significantly higher in patients with 10(5) copies/mL of EBV-DNA or more in whole blood (100% vs. 29%, P = 0.007) than that of others and in patients with 10(4) copies/mL or more in plasma (86% vs. 26%, P = 0.002).


CONCLUSIONS
These findings suggest that whole blood is more sensitive for clinical use than plasma. The EBV-DNA amount in whole blood was useful for predicting tumor response, toxicity, and prognosis after SMILE chemotherapy for ENKL.
Department of Pediatrics, Nagoya University Graduate School of Medicine, Higashi-ku, Nagoya, Japan.
Yoshinori
Y
Ito
Hiroshi
H
Kimura
Yoshinobu
Y
Maeda
Chizuko
C
Hashimoto
Fumihiro
F
Ishida
Koji
K
Izutsu
Noriyasu
N
Fukushima
Yasushi
Y
Isobe
Jun
J
Takizawa
Yuichi
Y
Hasegawa
Hajime
H
Kobayashi
Seiichi
S
Okamura
Hikaru
H
Kobayashi
Motoko
M
Yamaguchi
Junji
J
Suzumiya
Rie
R
Hyo
Shigeo
S
Nakamura
Keisei
K
Kawa
Kazuo
K
Oshimi
Ritsuro
R
Suzuki
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects; D004279:DNA, Viral / Q000097:blood / Q000235:genetics*; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D007970:Leukopenia / Q000139:chemically induced; D054391:Lymphoma, Extranodal NK-T-Cell / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009297:Nasal Mucosa / Q000187:drug effects / Q000473:pathology / Q000821:virology; D009503:Neutropenia / Q000139:chemically induced; D011379:Prognosis; D011446:Prospective Studies; D013256:Steroids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
D004279:DNA, Viral; D013256:Steroids; D005047:Etoposide; D001215:Asparaginase; D007069:Ifosfamide; D008727:Methotrexate