Interaction between BCL2 and Interleukin-10 Gene Polymorphisms Alter Outcomes of Diffuse Large B-Cell Lymphoma following Rituximab Plus CHOP Chemotherapy

Background: Reactivation of hepatitis B virus (HBV) and hepatitis C virus (HCV) and febrile neutropenia (FN) are common in diffuse large B-cell lymphoma (DLBCL) patients undergoing cyclophosphamide, hydroxyrubicin, Oncovin, and prednisolone (CHOP) or cyclophosphamide, hydroxyrubicin, Oncovin, prednisolone - rituximab containing (R-CHOP) chemotherapy. This ultimately leads to delaying the therapy, increasing hospital stay, and raising the pharmacoeconomic burden on patients. Aim and Objective: The aim of this study was to determine the incidence of HBV and HCV infection and febrile neutropenia in DLBCL patients treated with R-CHOP and CHOP. Methodology: This was an institutional approved study in which patient records from a private hospital, specialized in hematology and oncology (Karachi, Pakistan), were reviewed retrospectively from 2014 to 2016. Patients aged above 18 years with known diagnosis of DLBCL who underwent CHOP-21 or R-CHOP-21 chemotherapy regimen were included. Baseline blood chemistry and liver function tests along with the data regarding HBV (hepatitis B surface antigen [HBsAg], hepatitis B surface antibody [anti-HBs]), HCV (antibody anti-HCV), and febrile neutropenia were collected from patient records. Results: In total, 35 cases of DLBCL were treated during a 3-year period (ie, from 2014 to 2016), of which 16 were on CHOP-21 regimen whereas 19 were treated with R-CHOP-21. Of the 19 patients who underwent R-CHOP chemotherapy, only 2 (10%) patients were HBsAg reactive. Before commencing the second cycle, 2 (10%) patients reported to hospital with fever and had hematological (low neutrophil count) and microbiological ( Escherichia coli) proven febrile neutropenia. The incidence of HBV infection post treatment was lower in group treated with CHOP (1 patient showed HBsAg reactivity).

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A multi-institutional and case-matched control study on treatment outcomes of consolidative radiotherapy after a full course of R-CHOP compared with R-CHOP alone in Stage I–II diffuse large B-cell lymphoma (KROG 17-02)

Journal of Radiation Research ◽

10.1093/jrr/rrz043 ◽

2019 ◽

Vol 60 (5) ◽

pp. 677-684

Author(s):

Mi Joo Chung ◽

Won Kyung Cho ◽

Dongryul Oh ◽

Keun-Yong Eom ◽

Jin Hee Kim ◽

...

Keyword(s):

B Cell ◽

Treatment Outcomes ◽

Tumor Size ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Stage I ◽

Chop Chemotherapy ◽

Bulky Disease ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract We compared treatment outcomes between rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy alone with R-CHOP followed by consolidative radiation therapy (RT) in diffuse large B-cell lymphoma (DLBCL). We analyzed 404 patients with Stage I–II DLBCL who received six to eight cycles of R-CHOP and achieved a good response after a full course of chemotherapy. Propensity-score matching was used to assess the role of consolidative RT. The R-CHOP alone group (n = 184) was matched in a 1:2 ratio with the R-CHOP plus RT group (n = 92). Twenty-four (13.0%) of 184 patients receiving R-CHOP alone and 8 (8.7%) of 92 patients receiving R-CHOP plus RT had bulky diseases (>7.5 cm). A Deauville score of 1–2 was achieved for 159 (86.4%) of 184 patients receiving R-CHOP alone and 84 (91.3%) of 92 patients receiving R-CHOP plus RT. After a median follow-up time of 42 months, the recurrence-free survival (RFS) rate (86.7% vs 93.0%, P = 0.464) and overall survival rate (88.3% vs 95.1%, P = 0.295) at 5 years did not differ significantly between the R-CHOP alone and R-CHOP plus RT arms. In the additional multivariate analyses, large tumor size (>7.5 cm) was significantly associated with decreased RFS (hazard ratio, 2.368 and confidence interval, 1.837–6.697; P = 0.048). Consolidative radiation was not a significant factor for RFS (P = 0.563). Tumor size was a significant factor for RFS in the rituximab era. The outcome of omitting consolidative RT for good responders after six to eight cycles of R-CHOP chemotherapy was acceptable in early-stage DLBCL without a bulky disease.

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The interleukin-10 gene promoter polymorphism (-1082) does not correlate with clinical outcome in diffuse large B-cell lymphoma

Blood ◽

10.1182/blood-2004-12-4814 ◽

2005 ◽

Vol 105 (12) ◽

pp. 4894-4895 ◽

Cited By ~ 18

Author(s):

Mattias Berglund ◽

Ulf Thunberg ◽

Göran Roos ◽

Richard Rosenquist ◽

Gunilla Enblad

Keyword(s):

Clinical Outcome ◽

B Cell ◽

Cell Lymphoma ◽

Gene Promoter ◽

B Cell Lymphoma ◽

Interleukin 10 ◽

Promoter Polymorphism ◽

Large B Cell Lymphoma ◽

Large B Cell ◽

Gene Promoter Polymorphism

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FcγRIIIa Gene Polymorphisms May Correlate with Response to Frontline R-CHOP Therapy for Diffuse Large B-Cell Lymphoma.

Blood ◽

10.1182/blood.v108.11.2457.2457 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2457-2457

Author(s):

Dong Hwan Kim ◽

Hee Du Jung ◽

Sang Kyun Sohn ◽

Je-Jung Lee ◽

Deok-Hwan Yang ◽

...

Keyword(s):

B Cell ◽

Gene Polymorphisms ◽

Response Rate ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Effector Cells ◽

Large B Cell Lymphoma ◽

The Impact ◽

Large B Cell ◽

Chop Therapy

Abstract Background: The precise mechanism of rituximab (R) plus CHOP (R-CHOP) therapy in diffuse large B-cell lymphoma (DLBCL) is not fully elucidated. Besides overcoming bcl-2 mediated chemoresistance, antibody-dependent cellular cytotoxicity (ADCC), which is activated by effector cells via IgG fragment C receptors (FcR), was also proposed as a mechanism of Rituximab. The current study evaluated the impact of FcR polymorphism on the response to R-CHOP therapy for DLBCL with the basis that FcR polymorphism can affect R’s affinity for ADCC effector cells. Patients and Methods: The FcγRIIIa and FcγRIIa gene polymorphisms were determined in DLBCL patients receiving R-CHOP (n=113) comparing to CHOP therapy (n=85). Results: The FcγRIIIa valine (V) allele was significantly correlated with higher complete response rate to R-CHOP compared to phenylalalnine (F) allele (88% in V/V versus 79% in V/F versus 50% in F/F, p=0.002), while no difference was found between FcγRIIa polymorphism. In addition, V/V allele was associated with faster achievement of response than other alleles. The impact of FcγRIIIa gene polymorphism on response rate was not noted in CHOP group. In terms of overall or event-free survival, no difference was found according to FcγRIIIa or FcγRIIa alleles. Conclusion: The FcγRIIIa SNP is predictive of response to R-CHOP, but does not correlate with survival in DLBCL patients.

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Association between Drug-Metabolizing Enzymes Polymorphisms and Diffuse Large B-Cell Lymphoma Risk in the Middle Eastern Population.

Blood ◽

10.1182/blood.v108.11.2043.2043 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2043-2043

Author(s):

Abdul K. Siraj ◽

Rong Bu ◽

Maha Al-Rasheed ◽

Muna Ibrahim ◽

Prashant Bavi ◽

...

Keyword(s):

B Cell ◽

Gene Polymorphisms ◽

Cell Lymphoma ◽

Middle Eastern ◽

B Cell Lymphoma ◽

Control Group ◽

Healthy Population ◽

Environmental Carcinogens ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract The last four decades have seen significant increase in the incidence of non-Hodgkin’s lymphoma (NHL) as a possible result of increasing environmental carcinogens exposure. Based on the increasing evidence for the association between carcinogens exposure related cancer risk and xenobiotic gene polymorphisms. We have undertaken a case control study on xenobiotic gene polymorphisms in Saudi individuals with a diagnosis of diffuse large B-cell lymphoma (DLBCL). Polymorphisms in five genes (CYP1A1, GSTT1, GSTP1, GSTM1 and NQO1) were characterized in 187 individuals with DLBCL and 513 normal controls using polymerase chain reaction (PCR) based method. We chose the Saudi population as our study population because of its high consanguinity and its relative genetic homogeneity. The CYP1A1*2C, GSTT1 null and GSTP1 TT genotype were all found to be significant predictors of DLBCL risk (odds ratio 6.62, 11.94 and 3.42 respectively). None of the other alleles tested for proved to be significant indicators of DLBCL risk. These results suggest that the risk of DLBCL may indeed be associated with xenobiotics - metabolism and thus with environmental exposures. Table 1 Distribution of polymorphisms in healthy population and lymphoma patients. Polymorphism Genotype Control group Lymphoma patients p OR CYP1A1 −/− 384(76.5%) 104(78.8%) *2A −/2A 105(20.9%) 24(18.18%) 0.543 0.844 2A/2A 13(2.6%) 3(2.27%) 1.000 0.852 2A allele 13% 11.36% 0.659 0.839 CYP1A1 −/− 443(88.2%) 121(91.66%) *2B −/2B 50(10%) 10(7.58%) 0.505 0.732 2B/2B 9(1.8%) 1(0.76%) 0.697 0.407 2B allele 6.8% 4.55% 0.424 0.646 CYP1A1 −/− 497(99%) 125(94.7%) *2C −/2C 5(1%) 4(3.03%) 0.090 3.181 2C/2C 0 3(2.27%) 0.008 ND 2C allele 0.5% 3.8% 0.011 6.627 NQO1 C609T CC 295 (58.5%) 94 (62.7%) CT 177 (35.1%) 37 (24.7%) 0.051 0.656 TT 32 (6.4%) 19 (8.7%) 0.059 1.863 CT+TT 209 (41.5%) 56 (37.3%) 0.395 0.841 GSTP1 2293 CC 389 (76.3%) 113 (77.9%) CT 113 (22.2%) 24 (16.6%) 0.240 0.731 TT 8 (1.5%) 8 (5.5%) 0.017 3.422 CT+TT 121 (23.7%) 32 (22%) 0.739 0.910 GSTP1 A1578G AA 170 (33.5%) 56 (35%) AG 271 (53.5%) 96 (60%) 0.772 1.075 GG 66 (13%) 8 (5%) 0.013 0.368 AG+GG 337 (66.5%) 104 (65%) 0.774 0.937 GSTT1 P 385 (75%) 36 (20.1%) D 128 (25%) 143 (79.9%) <0.001 11.948 GSTM1 P 233 (45.4%) 91 (50%) D 280 (54.6%) 91 (50%) 0.300 0.832 Table 2 Distribution of combined GSTT1 and GSTM1 polymorphisms in case and control group. Genotype Control Case p OR Null: Complete deletion of GSTT1 and GSTM1 allele Present 423 (82.8%) 109 (60.9%) Double Null 88 (17.2%) 70 (39.1%) <0.001 3.087

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