|Year : 2018 | Volume
| Issue : 1 | Page : 66-69
Diffuse large B-cell lymphoma: A retrospective study from a regional care center in South India
Suresh MC Babu, Sunny Garg, Govinda Babu Kanakasetty, Lakshmaiah Chinnagiriyappa Kuntegowdanahalli, Lokanatha Dasappa, Suparna Ajit Rao
Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
|Date of Web Publication||23-Aug-2018|
Dr. Suparna Ajit Rao
Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka
Source of Support: None, Conflict of Interest: None
Introduction: Diffuse large B-cell lymphoma (DLBCL) is an aggressive lymphoma whose outcomes have significantly improved with rituximab in addition to anthracycline-based chemotherapy. Objective: This study aimed to study the epidemiology, treatment, and outcomes of patients with DLBCL. Materials and Methods: A total of 526 patients diagnosed with DLBCL between 2006 and 2015 were retrospectively analyzed. Results: The median age was 50 years with a male preponderance. Two hundred and twenty-three (42.39%) patients presented with B symptoms. A total of 53 (10.07%) patients presented with bulky disease and 202 (31.40%) with extranodal disease. The most common extranodal sites involved were the stomach (20.79%) and the bone marrow (10.89%). Bone marrow involvement was seen in only 22 (4.18%) cases. The distribution of patients presenting in low, low-intermediate, high-intermediate, and high-risk International Prognostic Index (IPI) were 148 (28.13%), 191 (36.31%), 124 (23.57%), and 63 (11.97%), respectively. The median survival of the entire cohort was 22 months. Survival of patients that compared the two groups with respect to the IPI – one having clubbed patients in low and low/intermediate risk and the other clubbing high/intermediate and high risk showed significantly improved survival in the lower risk groups – 24 versus 18 months (P = 0). The survival of those who received chemoimmunotherapy i.e R – CHOP was significantly better than those who received chemotherapy (CHOP) alone – 33 versus 21 months (P = 2.22e–16). Conclusions: DLBCL is one of the most common lymphomas seen in our daily practice. Outcomes are significantly inferior compared to western countries. Biological and patient-related factors such as nongerminal center B subtype, higher extranodal involvement, and poor tolerability to treatment could contribute to inferior outcomes.
Keywords: CHOP, diffuse large B-cell lymphoma, outcomes, R-CHOP
|How to cite this article:|
Babu SM, Garg S, Kanakasetty GB, Kuntegowdanahalli LC, Dasappa L, Rao SA. Diffuse large B-cell lymphoma: A retrospective study from a regional care center in South India. Indian J Cancer 2018;55:66-9
|How to cite this URL:|
Babu SM, Garg S, Kanakasetty GB, Kuntegowdanahalli LC, Dasappa L, Rao SA. Diffuse large B-cell lymphoma: A retrospective study from a regional care center in South India. Indian J Cancer [serial online] 2018 [cited 2019 Aug 23];55:66-9. Available from: http://www.indianjcancer.com/text.asp?2018/55/1/66/239592
| » Introduction|| |
DLBCL is the most common non-Hodgkin's lymphoma (NHL), constituting one-third of all the cases. It is an aggressive lymphoma, with a median survival of only a year without any treatment. The introduction of CHOP chemotherapy and addition of rituximab has improved outcomes, and this regimen (R-CHOP) remains the standard for treatment. We conducted a retrospective study to describe the epidemiology, clinical presentation, and outcomes of DLBCL with or without rituximab-based chemotherapy.
| » Materials and Methods|| |
Patients diagnosed with DLBCL between 2006 and 2015 at our hospital were retrospectively analyzed. Evaluation included hemogram, biochemistry, serology, lymph node excision biopsy/core biopsy of the presenting extranodal site, unilateral bone marrow aspiration, and biopsy, with either whole-body positron emission tomography-computed tomography or CT imaging. Formalin-fixed, paraffin-embedded sections of the whole node excision biopsy or core biopsy were utilized for immunohistochemistry. These tissues were stained with conventional hematoxylin-eosin and immunostaining. Patients were studied with respect to their clinical profile including the following variables: age, sex, nodal/extranodal disease, IPI scores (including age-adjusted IPI), and treatment received, i.e., whether rituximab was added to anthracycline-based chemotherapy. Bulky disease was considered as per the standard definition of nodes measuring >10 cm in any diameter. Their outcomes were studied according to the risk in IPI score, and with respect to the addition of rituximab to chemotherapy. Follow-up was done as per the standard criteria.
The statistical analysis was performed using R-software. Survival analysis was performed by Kaplan–Meier analysis using the Log-rank test.
| » Results|| |
A total of 526 patients were studied, and their clinical characteristics are depicted in [Table 1]. The median age of the cohort was 50 years (6–83 years). The male-to-female ratio was 2.09:1. Two hundred and twenty-three (42.39%) of the patients presented with B symptoms. A total of 53 patients presented with bulky disease (10.07%). Two hundred and two (31.40%) patients presented with extranodal disease upfront; the most common site was stomach (20.79%), followed by bone marrow (10.89%). The number of patients with bone marrow involvement was only 22 (4.18%) of the entire study population. The other extranodal sites involved at presentation are shown in [Table 1]. The distribution of patients presenting with low, low-intermediate, high-intermediate, and high risk as per the IPI were 148 (28.13%), 191 (36.31%), 124 (23.57%), and 63 (11.97%), respectively.
Treatment included CHOP chemotherapy or chemoimmunotherapy with R-CHOP [Table 1]. The number of cycles administered was 6–8 in number, depending on response assessment using the RESIST criteria. The number of patients who received CHOP chemotherapy alone was 388 (73.76%), and those receiving R-CHOP were 114 (21.67%) of the entire study cohort. Those presenting with bulky disease and/or extranodal disease received radiation as per the guidelines. None of our patients underwent autologous stem cell transplantation at recurrence due to logistic issues.
The median survival of the entire study population was 22 months [Table 2]. The survival of patients that compared the two groups with respect to the IPI at presentation – one group having clubbed patients in the low and low/intermediate risk and the other group clubbing high/intermediate and high risk showed significantly improved survival in the lower risk groups – 24 versus 18 months (P = 0) [Figure 1]. Survival comparing those who received chemoimmunotherapy versus chemotherapy alone showed a significantly better survival in the arm containing rituximab – 33 versus 21 months (P = 2.22e–16) [Figure 2].
|Figure 1: Survival in those with low and low/intermediate IPI versus high/intermediate and high IPI|
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| » Discussion|| |
DLBCL accounts for one-third of all NHLs in western studies, and constitutes 60%–70% of all B cell lymphomas in Asia. The incidence in India has been documented to be 38%, similar to or slightly lower than other Asian countries.
The median age of these patients at presentation has been reported to in the 60s in western studies. The median age in our study was 50 years, which is almost 2 decades lower than most western studies. This is similar to several other studies from Asia where the median age was reported in the 50s.,,
Male-to-female ratio was 2:1, with a male predominance. This is in concordance with all studies that have documented a higher incidence in males.,,
Although etiological factors were not analyzed in our study, there are several that are prevalent and could be associated with DLBCL in our population. Tuberculosis (TB), alcohol, and smoking are rampant in our population and have been positively associated with DLBCL. DLBCL is higher among those working in farms, with factors such as planting crops, animal husbandry, and agrochemicals, including fertilizers, insecticides, and herbicides, associated with higher risks. A marked increase has also been associated with the prevalent HIV/AIDS epidemic. With India having one of the world's highest numbers of TB and HIV cases, this would only mean that the number of cases of DLBCL is on the rise. Other causative factors associated are congenital immunodeficiencies, iatrogenic immunosuppression such as solid organ transplant, long-term survivors of Hodgkin's lymphoma, autoimmune disease, HCV infection, coeliac disease, and family history of B-cell lymphomas. There is also a subset of DLBCL that occurs due to transformation from low-grade lymphomas, especially follicular lymphoma.
More than 40% of our study cohort had B symptoms at presentation, which is slightly higher than the expected 30% incidence.
The extranodal involvement in our presenting population is approximately 38%, which is slightly higher than the documented which is approximately 30%; however, stomach which is the most common extranodal site across studies was the most frequent site in ours as well. Bone marrow involvement, documented in 10%–20%cases, was only seen in 4.18% of our study population.
Most patients in this study belonged to the intermediate IPI risk group, more in the lower than the higher risk group. This is because most people presented at an earlier stage of the disease. This is much higher than the expected (30%–40% of patients with DLBCL). Survival analysis revealed a statistically significant improvement in the lower risk groups than the higher, with a median survival difference of 6 months (24 vs. 18 months).
The overall survival of our study population is much lesser (22 months) than published data documenting >50% cure rates in the rituximab era. This is despite the fact that a greater number belonged to a lower risk group, i.e., a lower stage. This finding could be due to multiple factors such as a higher incidence of nongerminal center B (GCB) subtype of DLBCL seen in Asians compared to the Western population, a substantial proportion of our population not having received rituximab-based chemotherapy, and the fact that none of our patients underwent autologous stem cell transplantation which is seen to improve survival in recurrent setting.
Those who received rituximab-based chemotherapy were seen to have a significantly better survival, the difference observed was 12 months (33 vs. 21 months). This reiterates the benefit seen with rituximab reported in various studies.
| » Conclusions|| |
DLBCL is an aggressive lymphoma and one of the most common lymphomas seen in our daily practice at our center. Despite administration of the standard therapeutic regimens, outcomes are significantly inferior in comparison to western countries. Both biological and patient-related factors such as nonGCB subtype, higher extranodal involvement, and poor tolerability to treatment could contribute to inferior outcomes.
The authors would like to thank all the staff and students of the Department of Medical Oncology, Kidwai Memorial Institute of Oncology.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Flowers CR, Fedewa SA, Chen AY, Nastoupil LJ, Lipscomb J, Brawley OW, et al.
Disparities in the early adoption of chemoimmunotherapy for diffuse large B-cell lymphoma in the United States. Cancer Epidemiol Biomarkers Prev 2012;21:1520-30.
Chen Y, Han T, Iqbal J, Irons R, Chan WC, Zhu X, et al.
Diffuse large B-cell lymphoma in Chinese patients: Immunophenotypic and cytogenetic analyses of 124 cases. Am J Clin Pathol 2010;133:305-13.
Armitage JO. How I treat patients with diffuse large B-cell lymphoma. Blood 2007;110:29-36.
Ozbalak M, Ar MC, Tuzuner N, Salihoglu A, Eskazan AE, Ongoren Aydin S, et al.
Detailed analysis of diffuse large B cell lymphoma patients: A single-center, retrospective study. ISRN Hematol 2013;2013:908191.
Lee MY, Tan TD, Feng AC, Liu MC. Clinicopathological analysis of 598 malignant lymphomas in Taiwan: Seven-year experience in a single institution. Am J Hematol 2006;81:568-75.
Fan R, Zhang LY, Wang H, Yang B, Han T, Zhao XL, et al.
Multicentre hospital-based case-control study of diffuse large B-cell lymphoma in Shanghai, China. Asian Pac J Cancer Prev 2012;13:3329-34.
Devita VT, Lawrence TS, Rosenberg SA. Devita, Hellman, and Rosenberg's Cancer: Principles and Practice of Oncology. 10th
ed. Philadephia: Wolters Kluver Health/Lippincott Williams & Wilkins; 2015.
López-Guillermo A, Colomo L, Jiménez M, Bosch F, Villamor N, Arenillas L, et al.
Diffuse large B-cell lymphoma: Clinical and biological characterization and outcome according to the nodal or extranodal primary origin. J Clin Oncol 2005;23:2797-804.
Sehn LH, Scott DW, Chhanabhai M, Berry B, Ruskova A, Berkahn L, et al.
Impact of concordant and discordant bone marrow involvement on outcome in diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol 2011;29:1452-7.
Sehn LH, Gascoyne RD. Diffuse large B-cell lymphoma: Optimizing outcome in the context of clinical and biologic heterogeneity. Blood 2015;125:22-32.
[Figure 1], [Figure 2]
[Table 1], [Table 2]