The Genotype of MLH1 Is An Independent Predictor of Outcome In Diffuse Large B-Cell Lymphoma Treated with R-CHOP: a Training-Validation Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 992-992
Author(s):  
Davide Rossi ◽  
Silvia Rasi ◽  
Alice Di Rocco ◽  
Alberto Fabbri ◽  
Francesco Forconi ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
Independent Predictor ◽  
Excision Repair ◽  
B Cell Lymphoma ◽  
Salvage Treatment ◽  
Genotype 4 ◽  
Bulky Disease ◽  
Clinical Endpoints ◽  
Large B Cell Lymphoma ◽  
Validation Series

Abstract Abstract 992 Several drugs utilized in diffuse large B cell lymphoma (DLBCL) rely on DNA damage for tumor killing. This study aimed at verifying whether single nucleotide polymorphisms (SNPs) of genes involved in DNA repair may contribute to prognostication of DLBCL treated with R-CHOP. The study utilized a training-validation design. The training cohort (n=163) was a mono-institutional, prospectively collected, consecutive series of DLBCL homogeneously treated with the same chemotherapeutic regimen both at diagnosis (R-CHOP21) and at relapse/progression (R-DHAP ± BEAM conditioned autologous stem cell transplant, ASCT). The validation cohort (n=156) was a multi-institutional retrospective series of DLBCL treated with R-CHOP at diagnosis. Candidate SNPs (n=35) were selected by an educated guess approach, and included SNPs belonging to genes involved in: i) mismatch repair (MLH1); ii) base excision repair (XRCC1, OGG1); iii) nucleotide excision repair (ERCC1, ERCC2, ERCC4, ERCC5, ERCC6, XPA, XPC); iv) double strand break repair (BRCA1, BRCA2, LIG4, XRCC2, XRCC3, XRCC4, XRCC6); and v) direct reversal (MGMT). Clinical endpoints were progression free survival (PFS) after R-CHOP, overall survival (OS) from diagnosis, and OS from salvage treatment. Univariate analysis controlled for multiple comparisons identified MLH1 rs1799977 as the sole SNP predicting DLBCL OS in the training series (AG/GG genotype: HR: 3.23; 4-year OS: 55.5% vs AA genotype: 4-year OS: 80.9%; p<.001; q=.009) (Fig. 1A). Multivariate analysis identified the MLH1 rs1799977 AG/GG genotype (HR: 3.14; p<.001) as an independent predictor of OS, along with IPI score (HR: 1.38; p=.037) and bulky disease (HR: 2.56; p=.004). The prognostic relevance of MLH1 rs1799977 in the DLBCL training series was due to the impact on risk of failing both R-CHOP21 (AG/GG genotype; HR: 2.02; 4-year PFS: 47.5%; AA genotype: 4-year PFS: 65.6%; p=.007) (Fig. 1B) and second line treatment (AG/GG genotype: HR: 3.04; 2-year OS from salvage: 16.0%; AA genotype: 2-year OS from salvage: 57.3%; p=.007) (Fig. 1C). Multivariate analysis identified the MLH1 rs1799977 AG/GG genotype (HR: 1.96; p=.010) as an independent predictor of PFS after R-CHOP21, along with IPI score (HR: 1.41; p=.002) and bulky disease (HR: 1.96; p=.012). By bivariate analysis, MLH1 predicted OS from salvage treatment independent of having (p=.002) or having not (p=.049) consolidated with ASCT. The DLBCL validation series did not differ from the training series in terms of clinical features at presentation, median follow-up (p=.429), OS (p=.331), PFS (p=.416), OS from salvage (p=.987), and prevalence of MLH1 rs1799977 genotypes (p=.378). The MLH1 rs1799977 AG/GG genotype was confirmed as a predictor of poor outcome in the DLBCL validation series when considering all clinical endpoints, including: i) OS (unadjusted HR: 3.22, p=.001; adjusted HR: 3.15; p=.001); ii) PFS (unadjusted HR: 1.98, p=.017; adjusted HR: 1.86, p=.018); and iii) OS from salvage treatment (unadjusted HR: 2.95, p=.027). Pooling of the training and validation series (n=319) revealed that MLH1 AG/GG predicts DLBCL OS within subgroups defined by IPI. The biologic plausibility of the association between MLH1rs1799977 genotype and DLBCL outcome is supported by four lines evidence: i) MLH1rs1799977 is a nonsynonymous SNP causing the I219V amino acidic substitution in MLH1, a gene of the mismatch repair pathway; ii) in silico, MLH1rs1799977 is predicted to have deleterious consequences; iii) in vitro, the G variant allele of MLH1rs1799977 associates with reduced MLH1 protein expression; iv) loss of MLH1 expression in tumor cells is known to induce refractoriness to doxorubicin and platinum compounds. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Impact of Genetic Polymorphism of Myeloid Differentiation Primary Response Gene 88, Enhancer of Zeste Homolog 2, and B-cell Lymphoma 2 like 11 in Patients with Diffuse Large B Cell Lymphoma Treated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristin

2021 ◽  
Vol 9 (A) ◽  
pp. 98-105
Author(s):  
Hussam Zawam ◽  
Noha E. Ibrahim ◽  
Rasha Salama ◽  
Mai Samir ◽  
Walaa Abdelfattah ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Poor Response ◽  
Cell Of Origin ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Younger Age ◽  
Extranodal Disease ◽  
Large B Cell

BACKGROUND: Despite the growing landscape of genetic drivers in Diffuse Large B-cell Lymphoma, yet their clinical implication is still unclear and R-CHOP regimen remains a “one size fits all” therapy. We aimed in this study to examine the prevalence of EZH2, BCL211 and MYD 88 genetic polymorphisms in DLBCL patients and correlate the results with various clinical and survival outcomes. METHODS: Genotyping of MYD88 (rs387907272 T/C), EZH2 (rs3757441 C/T), and BCL2L11 (rs3789068 A/G) polymorphisms were conducted using real time polymerase chain reaction analysis in a total of 75 DLBCL patients. RESULTS: Most of our cases carried the wild TT genotype of MYD88 gene (64%), the mutant TT genotype of EZH2 gene (52%) and the wild AA genotype of BCL2L11 gene (48%). Regarding cell of origin, Germinal Centre (GC) phenotype was present in 56% of cases while 44% expressed the Post-GC (PGC) phenotype. Poor response outcome to first line R-CHOP was significantly correlated with the mutated CC genotype of MYD 88 (p=0.02), while better response to R-CHOP was significantly associated with younger age <50 years (p <0.0001), good PS (p=0.046), normal LDH level (p=0.003), earlier stage (p <0.0001), good IPI score (p=0.009), absence of extranodal disease (p <0.0001) and absence of bulky disease (p=0.004). The median PFS and the 2 year OS were significantly higher in younger age, earlier stage, good IPI score, absence of extranodal disease, absence of bulky disease and in GC phenotype. CONCLUSIONS: Our results emphasized that the mutated genotype of MYD 88 gene polymorphism is significantly associated with poor response to R-CHOP therapy.

scholarly journals 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)

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.

DHAP in combination with rituximab vs DHAP alone as salvage treatment for patients with relapsed or refractory diffuse large B-cell lymphoma: a matched-pair analysis

2006 ◽  
Vol 47 (12) ◽  
pp. 2558-2566 ◽  
Author(s):  
Ulrich J. M. Mey ◽  
Attilio Olivieri ◽  
Katjana S. Orlopp ◽  
Christian Rabe ◽  
John W. Strehl ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Salvage Treatment ◽  
Matched Pair ◽  
Matched Pair Analysis ◽  
Large B Cell Lymphoma ◽  
Pair Analysis ◽  
Large B Cell

Acquired Immunodeficiency and Malnutrition in Patients Treated with Bi-Weekly CHOP-Based Chemotherapy for Diffuse Large B-Cell Lymphoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2443-2443
Author(s):  
Dorte Tholstrup ◽  
Mads Hansen ◽  
Peter De Nully Brown ◽  
Jesper Jurlander
Keyword(s):  
T Cell ◽  
B Cell ◽  
Opportunistic Infections ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Preliminary Evaluation ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract During the recent years CHOP-14/CHOEP-14 in combination with the monoclonal anti-CD20 antibody Rituximab has become the standard choice of treatment for non-localized, poor risk Diffuse Large B-Cell Lymphoma. We, and others, have observed a relative high incidence of opportunistic infections not normally associated with the short neutropenic periods of CHOP-based treatment. We therefore introduced a prospective risk-assessment study in February 2005. The aim of the study is to assess the degree of malnutrition and immunodeficiency that may be associated with bi-weekly regimens. This is a preliminary evaluation of the first 27 patients included. Median age was 60 (31–80), 21 (78%) had CS III/IV disease, 14 (52%) extranodal involvement, 19 (70%) elevated LDH, 9 (33%) a Performance Score ≥2, i.e.13 (48%) presented with IPI 3–5 disease. Furthermore, 7 (26%) had bone marrow involvement, 8 (30%) bulky disease and 17 (63%) B-symptoms. All patients received 6 or 8 cycles of CHOP-14/CHOEP-14, and 15 patients received Rituximab at day 1 of each cycle. Patients were examined four times: 1) before 1st cycle, 2) 14 days after 4th cycle, 3) 14 days after last cycle (i.e. 6th or 8th), and 4) 3 months after treatment. Examination included blood tests, bodyweight and DEXA-scans. 20 patients (74%) had a significant weight loss during treatment. However, 3/4 had regained normal weight three months later. Consistently, DEXA-scans demonstrated a significant reduction in total lean body mass in 12 (44%) patients. P-protein, p-albumin, and selected trace elements were decreased in about 1/4 of patients during treatment. However, most patients had significant declines in T-cell levels during treatment, and interestingly about 1/4 presented with very low T-cell levels at diagnosis. Thus, total CD3-count was low in 7 (26%) patients at diagnosis, and reduced under treatment in 23 (85%). Both CD4- and CD8-count was low in 6 patients at diagnosis, while CD4 was reduced under treatment in 24 and CD8 in 16 patients. Likewise, a significant decrease of IgA, IgM, and IgG subclasses developed during treatment (Table 1). We conclude that patients treated with bi-weekly CHOP-chemotherapy may develop severely decreased levels of T-cells and severe hypogammaglobulinemia, which may be related to an increased incidence of opportunistic infections such as PCP or CMV reactivation.

Favorable Results of Rituximab in Combination with CHOP in the Front-Line Treatment of Follicular Lymphoma Grade 3.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2770-2770
Author(s):  
Luis Fayad ◽  
Michael Overman ◽  
Barbara Pro ◽  
Peter McLaughlin ◽  
Felipe Samaniego ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Grade 3 ◽  
Large B Cell

Background: Follicular lymphoma grade 3 has a natural history that is more akin to that of diffuse large B-cell lymphoma. The addition of rituximab to standard CHOP has resulted in improved response and survival in diffuse large B-cell lymphoma. Information about outcomes in follicular lymphoma grade 3 is lacking. Methods: A single institution retrospective review of patients with follicular grade 3 lymphoma evaluated at the UTMDACC from 1999 to 2004. Patients were located from the UTMDACC lymphoma database. All patients were initially treated with R-CHOP. Results: Forty-five patients were identified: 51% male, 47% ≥60 years, and 87% follicular grade 3b. The LDH was elevated in 24%, ECOG performance status was >1 in 2%, and >1 site of extranodal involvement was present in 10%. Stage distribution was 11% stage I, 11% stage II, 42% stage III, and 36% stage IV, bulky disease (>7cm) was present in 11%, and B symptoms occurred in 13%. Beta-2 microglobulin was elevated in 57% with values >3 μg/dL in over 50%. IPI distribution was: 46% IPI Low, 38% LI, 11% IH, and 4% IPI High. Overall response rate was 100% with 96% complete responses. Relapse rate by IPI category was 24% for Low IPI, 18% for IPI LI, and 40% for IPI IH, and 100% for the two patients with High IPI. With median follow-up of 33 months, three year failure-free survival (FFS) is 73% (95% CI: 59 to 87%). One patient died (2%) with an overall survival (OS) at three years of 97% (95% CI: 93 to 100%). Conclusion: The addition of rituximab to CHOP provided a high response rate and excellent early survival in this group of mostly good prognosis patients. Relapses were still seen; longer follow-up is needed.

Treatment of Diffuse Large B-Cell Lymphoma with Rituximab, Intensive Induction and High-Dose Consolidation: The Final Analysis of the Czech Lymphoma Study Group (CLSG) R-MegaCHOP-ESHAP-BEAM (R-MEB) Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 21-21
Author(s):  
Marek Trneny ◽  
Robert Pytlik ◽  
David Belada ◽  
Katerina Kubackova ◽  
Ingrid Vasova ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Performance Status ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background. Combined immunochemotherapy with CHOP and rituximab have improved the outcome of patients with diffuse large B-cell lymphoma (DLBCL). and related diseases. However, the cure rate of patients with IPI 3–5 or aaIPI 3 is still only about 50% with this regimen. Given the feasibility of previous CLSG regimens based on high-dose CHOP-ESHAP induction and BEAM consolidation, we have conducted a phase II trial combining this approach with rituximab immunotherapy. Patients and methods. Patients aged 18–65 years with DLBCL and age-adjusted IPI (aaIPI) 2–3 were treated with three cycles of high-dose CHOP (MegaCHOP - cyclophosphamide, 3 g/m2, vincristine 2 mg, adriamycin, 75 mg/m2, and prednisone, 300 mg/m2) with G-CSF every 3 weeks, followed by three cycles of ESHAP (etoposide, 240 mg/m2, cisplatin, 100 mg/m2, methylprednisolone, 2000 mg and Ara-C 2000 mg/m2) every 3 weeks. Four to six doses of rituximab 375 mg/m2 were administered on day 1 of each cycle of induction therapy. High-dose therapy (BEAM) followed by autologous stem cell transplant (ASCT) was used as consolidation. Radiotherapy was given to residual masses or sites of bulky disease. Primary endpoint was progression-free survival (PFS), while secondary endpoints were overall survival (OS) and feasibility of the treatment. Results. From April 2002 to October 2006, 105 consecutive patients from 10 centers were recruited. 58% were men and 42% women with median age 46 years (19–63 years). 74% of patients had stage IV disease, 92% had elevated LDH, 53% had performance status &gt;1, 55% had B symptoms and 19% had bone marrow involvement. aaIPI was 2 in 62% of patients and 3 in 38% of patients. 68% of patients received the whole treatment according to the protocol, including ASCT and radiotherapy. Stem cells mobilization according to the protocol was performed in 90% of patients and was successful in 86% of mobilized patients (77% of all patients). 73% of patients ultimately received ASCT (including 3 patients transplanted after ammended treatment) and 51% of patients received planned radiotherapy. Complete remission (CR) was achieved in 83% of all patients and partial remission (PR) in 2%. Early toxic death rate was 6% and 9% patients had primary refractory disease. Of patients who achieved CR or PR, only 6 subsequently relapsed (7%) and two suffered late toxic death (2%). With a median follow-up of 32 months for living patients, the estimated 2-year PFS is 77% and 2-year OS is 81%. Age less than median (46 years) was strongest predictor of favorable outcome (p = 0,00006 for PFS and p = 0,00013 for OS), while there was no effect of stage, LDH, performance status or aaIPI (2-year PFS 79% for aaIPI 2 and 77% for aaIPI 3, 2-year OS 81% for aaIPI 2 and 80% for aaIPI 3). Delivery of ASCT or radiotherapy did not significantly affected PFS in patients who did not suffered early progression or early toxic death, but radiotherapy modestly improved OS of these patients (p = 0,03). Conclusion. R-MEB has proved to be an effective treatment strategy for younger patients with high-risk aggressive B-cell lymphoma. Currently, CLSG is testing whether utilization of early PET scan may decrease toxicity and improve treatment tolerance while maintaining the efficacy of this regimen.

The Efficacy of R-ICE Therapy as a Salvage Treatment for Relapse and Refractory Diffuse Large B-Cell Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4441-4441
Author(s):  
Makoto Kodaira ◽  
Masahiro Yokoyama ◽  
Hiroaki Asai ◽  
Shuhei Yamada ◽  
Kyoko Ueda ◽  
...  
Keyword(s):  
B Cell ◽  
De Novo ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Salvage Chemotherapy ◽  
Salvage Treatment ◽  
Large B Cell Lymphoma ◽  
Grade 3 ◽  
Large B Cell

Abstract <Background> Patients with relapsed and refractory diffuse large B-cell lymphoma are usually treated with platinum-based salvage chemotherapy. We retrospectively analyzed the efficacy of adding rituximab with ICE as a salvage treatment for relapsed and refractory diffuse large B-cell lymphoma. <Method>From November 2003 to December 2006, patients with relapsed or refractory de novo diffuse large B-cell lymphoma represented CD20 positivty who received R-ICE (rituximab375mg/m2, Ifosfamide 1200mg/m2, calboplatin 400mg/m2 and etopside100mg/m2 ), were analyzed retrospectively. <Result>23 patients (19 relapse and 4 reflactory) (M:F=14:9) (median age 69, 28–77) were included. At starting treatment, twelve patients received rituximab and 11 patients were rituximab naive. In all 23 patients, responses were 11 Complete remission (CR), and 6 partial response (PR), resulting in overall response (ORR) was 74.9%. With median follow up of 10.5 months, estimated 1yr-progression free survival (PFS) was 49% and 1yr-overall survival (OS) was 70%.In patients received rituximab, ORR was 66.7% and 5 patiets achieved CR (41.7%).In the without rituximab, ORR was 90.9% and 7 patiets achieved CR (63.6%). No statistical differences were observed in response even with retuximab pretreatment. Estimated 1yr-PFS was 23% and 70% (p=0.0752) and 1yr-OS was 59% and83% (P=0.0049),respectively. NCI-CTC grade 3/4 neutropenia and thrombocytopenia were reported 100% and 91%, For non-hematological adverse event, there were grade 3 liver dysfunction (2/23) and grade 3 arrythmia (1/23). No toxic death was reported in this study. <Conclusion> R-ICE showed promising efficacy with tolelable toxicity. Available date suggested adding rituximab to ICE is more effective for patients not received rituximab in the pretreament.

The Immunohistochemical Pattern of Indoleamine 2,3-Dioxygenase in Tumor Tissue Indicates the Prognosis of Patients with Diffuse Large B-Cell Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2924-2924 ◽  
Author(s):  
Soranobu Ninomiya ◽  
Nobuhiro Kanemura ◽  
Hisashi Tsurumi ◽  
Takeshi Hara ◽  
Naoe Goto ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Poor Prognosis ◽  
Tumor Tissue ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Bulky Disease ◽  
Indoleamine 2,3 Dioxygenase ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 2924 Poster Board II-900 Introduction : Indoleamine 2,3-dioxygenase (IDO) is an enzyme that degrades the essential amino acid tryptophan along the kynurenine pathway. Pro-inflammatory cytokines, such as IFN-g, induce IDO during the inflammatory response in many human cell types. The induction of IDO is synergistic in the presence of TNF-a, IL-1 or IL-6, and might be mediated by a signaling pathway from NF-κB and/or MAPKs. Furthermore, some metabolites derived from tryptophan by IDO, such as L-kynurenine, block antigen-driven specific T-cell proliferation and induce T-cell death. Thus, IDO activity might play an important role in regulation of the immune response exerted by antigen presenting cells and also provide transformed cells with a potent tool to help escape from assault by the immune system. Indeed, we have previously reported that high serum L-kynurenine level is associated with poor prognosis of diffuse large B-cell lymphoma (DLBCL) (ASH 2008 abstract 2812). Here, we investigated the IDO expression of patients with DLBCL. Patients and methods : The study protocol comprised a prospective, consecutive entry design that was approved by our Institutional Review Board. We investigated 119 patients between December 2003 and June 2008 who were histologically diagnosed with DLBCL according to the WHO classification. We performed immunohistochemical (IHC) analysis for IDO expression by mouse anti-human IDO monoclonal antibody. Patients aged <70 y received 8 cycles of either R-CHOP or R-THP-COP therapy. Each regimen consisted of rituximab (R: 375 mg/m2), cyclophosphamide (CPA: 750 mg/m2), doxorubicin (DOX) or tetrahydropyranyl-adriamycin (THP; 50 mg/m2), vincristine (VCR; 1.4 mg/m2, maximal dose 2.0 mg), and prednisolone (PSL; 100 mg daily). The R-THP-COP regimen included THP, an anthracycline derivative of DOX. Patients aged ≥70 y received 6 cycles of R-CHOP or R-THP-COP therapy. The chemotherapy cycles were repeated at 14-day intervals in patients aged <70 y, and at 21-day intervals in patients aged ≥70 y. Patients with bulky disease received radiotherapy ranging from 30 to 40 Gy. Responses to treatment were categorized as defined by Cheson et al. Results : The median age was 65.2 year (range, 24 - 88 y) and the median follow-up was 22.9 month (range, 0.60 – 55.4 mo). The IDO expression patterns were classified into 3 categories; diffuse positive, focal positive and negative patterns. The diffuse positive IDO expression in tumor tissue was found in 38 cases (32%). The focal positive and negative expression of IDO was 16 cases (13.4%) and 65 cases (54.6%), respectively. The diffuse IDO positive cells were lymphoma cells and the focal IDO positive cells were dendritic cells (DC) confirmed by IHC analysis. The CR rates of patients with diffuse positive IDO expression, focal positive and negative were 55.3%, 62.5% and 83.1%, respectively (P<0.05). The 3-year overall survival rates for patients with diffuse positive, focal positive and negative were 49.8%, 66.3% and 81.4%, respectively (p=0.001). IDO expression was not significantly associated with the classification of germinal center (GC) type nor non-GC type. Discussion : A poor prognosis of patients with positive IDO expression might suggest that local immunity in tumor tissue is depressed by increasing L-kynurenine levels. Hence, IDO expression contributes to refractory to chemotherapy for DLBCL. Interestingly, expression pattern of IDO was significantly related with response to the treatment and prognosis of DLBCL. In conclusion, IDO activity might play an important role in DLBCL and the cells which express IDO are important for the response to treatment and prognosis of this malignancy. IDO, therefore, might be a candidate of therapeutic targets for DLBCL patients who are resistance to chemotherapy. Disclosures: No relevant conflicts of interest to declare.

R-CHOP21 Vs R-CHOP14 in 950 Diffuse Large B-Cell Lymphoma Patients: Results of a Multicentre Retrospective Study Form Italian Lymphoma Foundation (FIL)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1615-1615
Author(s):  
Luigi Rigacci ◽  
Benedetta Puccini ◽  
Maria Giuseppina Cabras ◽  
Luca Nassi ◽  
Alberto Fabbri ◽  
...  
Keyword(s):  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Univariate Analysis ◽  
B Cell Lymphoma ◽  
Hematological Toxicity ◽  
Bulky Disease ◽  
Symptomatic Disease ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 1615 Background: Diffuse large B cell lymphoma (DLBCL) is one of the most common types of non-Hodgkin's lymphoma. R-CHOP21 (C21) is considered the standard therapy but a large number of studies have tested R-CHOP14 (C14). Aims: The aim of our study was to evaluate retrospectively a cohort of patients (pts) treated with C21 or C14 and to compare the efficacy of the therapy. Methods: All pts with diagnosis of DLBCL or follicular grade IIIb lymphoma, treated with curative intent in 9 Italian Hematological Centers, were accrued. All patients treated with C14 used G-CSF as primary prophilaxis, and only elderly (over 70 years) patients treated with C21 used G-CSF as primary prophilaxis. Results: From january 2002 to june 2011, 950 pts were accrued, 643 pts were treated with C21 and 307 were treated with C14. The median age was 63 (range 19–89). The two cohorts of pts were balanced for all clinical characteristics a part for age (<60 or >60 years) with more aged pts in C21 arm (p 0.001), bone marrow positivity and more than 3 lymph node stations involved that were higher in C14 arm (p: 0.05 and p: 0.001). After induction therapy 751 pts (79%) obtained a complete remission: 501/643 (78%) after C21 and 250/307 (81%) after C14. The remaining pts obtained partial response in 110 and 48 or no response in 32 and 9 respectively for C21 and C14. After a median period of observation of 38 months 104 pts relapsed (14%), 68 (65%) in the C21 arm and 36 (35%) in the C14 arm. After a median observation period of 3 years, considering the two therapies, C21 vs C14, no differences were reported in OS (Figure 1), PFS (Figure 2) and DFS: 80% vs 84%, 69% vs 71% and 54% vs 56% respectively. In univariate analysis OS was lower in older pts (azard ratio (ar): 2.57), IPI 2 (ar: 2.09), IPI 3 (ar: 4.36), IPI 4–5 (ar: 6.36), bulky disease (ar: 1.70), symptomatic disease (ar: 2.23). In multivariate analysis factors which mantained significantly worst prognosis were older age (ar: 1.35), IPI 2 (ar: 1.95), IPI 3 (ar: 3.76), IPI 4–5 (ar: 5.01) and bulky disease (ar: 1.43). As expected hematological grade III/IV toxicity was more frequent in pts treated with C14. No differences in extra-hematological toxicity were observed. Secondary malignancies were reported: 7 in C21 and 3 in C14. After 3 years of median observation 188 pts are dead: 137 (73%) in C21 and 51 (27%) in C14 (not statistically significant, p:0.08). The large majority of pts are dead for disease progression or relapse. Conclusions: In conclusion our results confirm that C14 do not improve the results of the standard C21 in the whole lymphoma population. Dose dense therapy did not affect OS or PFS also analysing sub group of pts. As expected a higher frequency of neutropenia was observed in C21 arm but did not translate in increasing infection rate. Further prospective randomized studies are needed to verify this preliminary observations. Disclosures: No relevant conflicts of interest to declare.

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