G Model
ARTICLE IN PRESS
LR-5450; No. of Pages 5
Leukemia Research xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Leukemia Research journal homepage: www.elsevier.com/locate/leukres
Beta-2 microglobulin is a strong prognostic factor in patients with DLBCL receiving R-CHOP therapy Kazuho Miyashita a , Naoto Tomita a,∗ , Masataka Taguri b , Taisei Suzuki c , Yasufumi Ishiyama d , Yoshimi Ishii e , Yuki Nakajima a , Ayumi Numata e , Yukako Hattori d , Wataru Yamamoto e , Takuya Miyazaki a , Takayoshi Tachibana a , Hirotaka Takasaki d , Kenji Matsumoto e , Chizuko Hashimoto f , Sachiya Takemura g , Etsuko Yamazaki a , Katsumichi Fujimaki h , Rika Sakai d , Shigeki Motomura d , Yoshiaki Ishigatsubo a a Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan b Department of Biostatistics and Epidemiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan c Department of Hematology, Yokosuka City Hospital, 1-3-2 Nagasaka, Yokosuka 240-0195, Japan d Department of Medical Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama 241-8515, Japan e Department of Hematology, Yokohama City University Medical Center, 4-57 Urafune, Minami-ku, Yokohama 232-0024, Japan f Department of Hematology/Oncology, Yamato Municipal Hospital, 8-3-6 Fukaminishi, Yamato 242-8602, Japan g Department of Internal Medicine, Yokohama Ekisaikai Hospital, 1-2 Yamada-cho, Naka-ku, Yokohama 231-0036, Japan h Department of Hematology/Immunology, Fujisawa City Hospital, 2-6-1 Fujisawa, Fujisawa 251-8550, Japan
a r t i c l e
i n f o
Article history: Received 20 June 2015 Received in revised form 22 August 2015 Accepted 25 August 2015 Available online xxx Keywords: Diffuse large B-cell lymphoma Non-hodgkin lymphoma Beta 2-microglobulin R-CHOP Progression-free survival
a b s t r a c t Useful prognostic markers for patients with diffuse large B cell lymphoma (DLBCL) have been reported. To identify which biomarker best predicts the prognosis of patients with DLBCL, we performed a retrospective study that included 319 DLBCL patients who had received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy between 2003 and 2012. We assessed the prognostic significance of six biomarkers [lactate dehydrogenase, soluble interleukin-2 receptor, thymidine kinase activity, beta-2 microglobulin (B2M), C-reactive protein, and ferritin] and representative clinical characteristics using progression-free survival (PFS) as the endpoint. The study group included 181 men and 138 women with a median age of 63 years (range, 22–89 years). In a multivariate analysis, the serum B2M level most strongly correlated with PFS (hazard ratio, 2.11; P = 0.04). In a univariate analysis, patients with serum B2M levels >1.75 g/mL (n = 210) had a worse 3-year PFS rate (71.2%) than those with B2M levels 20% owing to major comorbidities, who were not evaluated for all six biomarkers, or who were not observed during chemotherapy were excluded. Dose reduction or termination at subsequent cycles owing to toxicity did not preclude participation. Patients with human immunodeficiency virus infection were also excluded from this study. 2.2. Treatment First-line treatment consisted of six to eight cycles of standard R-CHOP therapy [750 mg/m2 cyclophosphamide, 50 mg/m2 doxorubicin, and 1.4 mg/m2 (maximum 2.0 mg/body) vincristine on day 1, 100 mg/body prednisolone on days 1–5, and 375 mg/m2 rituximab for 21 days per cycle] for all DLBCL patients regardless of Ann Arbor stage. 2.3. Prognostic factors Associations between prognosis and (1) the serum levels of the six biomarkers and (2) the clinical characteristics of the patients were determined. Clinical characteristics included age, sex, Ann Arbor clinical stage (CS), PS, the presence of B symptoms, a bulky mass, and more than one extra-nodal lesion. A bulky mass was defined as any mass exceeding 10 cm in diameter in a horizontal plane or a mediastinal mass with a maximum diameter exceeding one-third of the maximum chest diameter as observed on computed tomography scans.
Table 1 Patients characteristics. Total, n (%)
B2M (g/mL)
P-value
60
123 (39) 196 (61)
63 46
60 150
1 >2.3 mg/dL >179 ng/mL >UNL × 1.4 >1660 U/mL >19 U/L >1.75 g/mL HI, H
Univariate
Multivariate
P-value
P-value
HR
95% CI
0.765 0.627
ARTICLE IN PRESS
LR-5450; No. of Pages 5
Leukemia Research xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Leukemia Research journal homepage: www.elsevier.com/locate/leukres
Beta-2 microglobulin is a strong prognostic factor in patients with DLBCL receiving R-CHOP therapy Kazuho Miyashita a , Naoto Tomita a,∗ , Masataka Taguri b , Taisei Suzuki c , Yasufumi Ishiyama d , Yoshimi Ishii e , Yuki Nakajima a , Ayumi Numata e , Yukako Hattori d , Wataru Yamamoto e , Takuya Miyazaki a , Takayoshi Tachibana a , Hirotaka Takasaki d , Kenji Matsumoto e , Chizuko Hashimoto f , Sachiya Takemura g , Etsuko Yamazaki a , Katsumichi Fujimaki h , Rika Sakai d , Shigeki Motomura d , Yoshiaki Ishigatsubo a a Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan b Department of Biostatistics and Epidemiology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan c Department of Hematology, Yokosuka City Hospital, 1-3-2 Nagasaka, Yokosuka 240-0195, Japan d Department of Medical Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama 241-8515, Japan e Department of Hematology, Yokohama City University Medical Center, 4-57 Urafune, Minami-ku, Yokohama 232-0024, Japan f Department of Hematology/Oncology, Yamato Municipal Hospital, 8-3-6 Fukaminishi, Yamato 242-8602, Japan g Department of Internal Medicine, Yokohama Ekisaikai Hospital, 1-2 Yamada-cho, Naka-ku, Yokohama 231-0036, Japan h Department of Hematology/Immunology, Fujisawa City Hospital, 2-6-1 Fujisawa, Fujisawa 251-8550, Japan
a r t i c l e
i n f o
Article history: Received 20 June 2015 Received in revised form 22 August 2015 Accepted 25 August 2015 Available online xxx Keywords: Diffuse large B-cell lymphoma Non-hodgkin lymphoma Beta 2-microglobulin R-CHOP Progression-free survival
a b s t r a c t Useful prognostic markers for patients with diffuse large B cell lymphoma (DLBCL) have been reported. To identify which biomarker best predicts the prognosis of patients with DLBCL, we performed a retrospective study that included 319 DLBCL patients who had received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy between 2003 and 2012. We assessed the prognostic significance of six biomarkers [lactate dehydrogenase, soluble interleukin-2 receptor, thymidine kinase activity, beta-2 microglobulin (B2M), C-reactive protein, and ferritin] and representative clinical characteristics using progression-free survival (PFS) as the endpoint. The study group included 181 men and 138 women with a median age of 63 years (range, 22–89 years). In a multivariate analysis, the serum B2M level most strongly correlated with PFS (hazard ratio, 2.11; P = 0.04). In a univariate analysis, patients with serum B2M levels >1.75 g/mL (n = 210) had a worse 3-year PFS rate (71.2%) than those with B2M levels 20% owing to major comorbidities, who were not evaluated for all six biomarkers, or who were not observed during chemotherapy were excluded. Dose reduction or termination at subsequent cycles owing to toxicity did not preclude participation. Patients with human immunodeficiency virus infection were also excluded from this study. 2.2. Treatment First-line treatment consisted of six to eight cycles of standard R-CHOP therapy [750 mg/m2 cyclophosphamide, 50 mg/m2 doxorubicin, and 1.4 mg/m2 (maximum 2.0 mg/body) vincristine on day 1, 100 mg/body prednisolone on days 1–5, and 375 mg/m2 rituximab for 21 days per cycle] for all DLBCL patients regardless of Ann Arbor stage. 2.3. Prognostic factors Associations between prognosis and (1) the serum levels of the six biomarkers and (2) the clinical characteristics of the patients were determined. Clinical characteristics included age, sex, Ann Arbor clinical stage (CS), PS, the presence of B symptoms, a bulky mass, and more than one extra-nodal lesion. A bulky mass was defined as any mass exceeding 10 cm in diameter in a horizontal plane or a mediastinal mass with a maximum diameter exceeding one-third of the maximum chest diameter as observed on computed tomography scans.
Table 1 Patients characteristics. Total, n (%)
B2M (g/mL)
P-value
60
123 (39) 196 (61)
63 46
60 150
1 >2.3 mg/dL >179 ng/mL >UNL × 1.4 >1660 U/mL >19 U/L >1.75 g/mL HI, H
Univariate
Multivariate
P-value
P-value
HR
95% CI
0.765 0.627
