The Glasgow Prognostic Score (GPS) as a novel and significant predictor of extranodal natural killer/T‐cell lymphoma,nasal type

The Glasgow Prognostic Score (GPS), an inflammation‐based prognostic score including C‐reactive protein and albumin, shows significant prognostic value in several types of solid tumors. The prognostic value of GPS in lymphoma remains unclear. We performed this study to evaluate the prognostic significance of GPS in extranodal natural killer (NK)/T‐cell lymphoma (ENKL). We retrospectively analyzed 164 patients with newly diagnosed ENKL. The prognostic value of GPS was evaluated and compared with that of International Prognostic Index (IPI), Prognostic Index for Peripheral T‐cell lymphoma unspecified (PIT), and Korean Prognostic Index (KPI). Patients with higher GPS tended to have more adverse clinical characteristics, lower rates of complete remission (P < 0.001), inferior progression‐free survival (PFS, P < 0.001), and inferior overall survival (OS, P < 0.001). Multivariate analysis demonstrated that high GPS, age > 60 years, and elevated LDH were independent adverse predictors of OS. GPS was found superior to IPI, PIT, and KPI in discriminating patients with different outcomes in low‐risk groups (all P < 0.05). GPS is an independent predictor of survival outcomes in ENKL. Inflammatory response might play an important role in the progression of ENKL and survival of patients with ENKL. Am. J. Hematol. 88:394–399, 2013. © 2013 Wiley Periodicals, Inc.     

New prognostic model for extranodal natural killer/T cell lymphoma,nasal type

Extranodal natural killer/T cell lymphoma, nasal type (ENKTL) is an aggressive disease with a poor prognosis, requiring risk stratification in affected patients. We designed a new prognostic model specifically for ENKTL to identify high-risk patients who need more aggressive therapy. We retrospectively reviewed 158 patients who were newly diagnosed with ENKTL. The estimated 5-year overall survival rate was 39.4 %. Independent prognostic factors included total protein (TP) <60 g/L, fasting blood glucose (FBG) >100 mg/dL, and Korean Prognostic Index (KPI) score ≥2. We constructed a new prognostic model by combining these prognostic factors: group 1 (64 cases (41.0 %)), no adverse factors; group 2 (58 cases (37.2 %)), one adverse factor; and group 3 (34 cases (21.8 %)), two or three adverse factors. The 5-year overall survival (OS) rates of these groups were 66.7, 23.0, and 5.9 %, respectively (p?<?0.001). Our new prognostic model had a better prognostic value than did the KPI model alone (p?<?0.001). Our proposed prognostic model for ENKTL, including the newly identified prognostic indicators, TP and FBG, demonstrated a balanced distribution of patients into different risk groups with better prognostic discrimination compared with the KPI model alone.     

Prognostic significance of pleural or pericardial effusion and the implication of optimal treatment in primary mediastinal large B-cell lymphoma: a multicenter retrospective study in Japan

The prognosis of patients with primary mediastinal large B-cell lymphoma has improved over recent years. However, the optimal treatment strategy including the role of radiotherapy remains unknown. We retrospectively analyzed the clinical outcomes of 345 patients with newly diagnosed primary mediastinal large B-cell lymphoma in Japan. With a median follow up of 48 months, the overall survival at four years for patients treated with R-CHOP (n=187), CHOP (n=44), DA-EPOCH-R (n=9), 2^nd- or 3^rd-generation regimens, and chemotherapy followed by autologous stem cell transplantation were 90%, 67%, 100%, 91% and 92%, respectively. Focusing on patients treated with R-CHOP, a higher International Prognostic Index score and the presence of pleural or pericardial effusion were identified as adverse prognostic factors for overall survival in patients treated with R-CHOP without consolidative radiotherapy (IPI: hazard ratio 4.23, 95% confidence interval 1.48–12.13, P=0.007; effusion: hazard ratio 4.93, 95% confidence interval 1.37–17.69, P=0.015). Combined with the International Prognostic Index score and the presence of pleural or pericardial effusion for the stratification of patients treated with R-CHOP without radiotherapy, patients with lower International Prognostic Index score and the absence of effusion comprised approximately one-half of these patients and could be identified as curable patients (95% overall survival at 4 years). The DA-EPOCH-R regimen might overcome the effect of these adverse prognostic factors. Our simple indicators of International Prognostic Index score and the presence of pleural or pericardial effusion could stratify patients with primary mediastinal large B-cell lymphoma and help guide selection of treatment.     

Central nervous system involvement in diffuse large B‐cell lymphoma

Background: Malignant lymphoma with central nervous system (CNS) involvement has an extremely poor prognosis. We retrospectively studied the risk factors for CNS involvement in patients with diffuse large B‐cell lymphoma (DLBCL) treated by cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or rituximab (R) ‐CHOP chemotherapy. Patients and methods: We studied 375 consecutive patients who were newly diagnosed with DLBCL between 1996 and 2006. Patients with primary CNS involvement and patients who received CNS prophylaxis were excluded. All the patients received CHOP (n = 172) or R‐CHOP (n = 203) chemotherapy. The following variables were assessed for their potential to predict CNS involvement: gender, age, serum lactate dehydrogenase (LDH) level, performance status, clinical stage, number of extranodal involvements, International Prognostic Index (IPI), bone marrow involvement, presence of a bulky mass, presence of B symptom, and treatment. Results: CNS involvement was observed in 13 cases (3.5%). In univariate analysis, LDH more than normal range, LDH more than twice as normal range, high IPI, bone marrow involvement, and systemic relapse were the predictors for CNS involvement. In multivariate analysis, no risk factors were detected for CNS involvement. The use of rituximab did not have an impact on CNS involvement. Conclusions: The incidence of CNS involvement dose not decrease in rituximab‐era.     

老年弥漫性大B细胞淋巴瘤预后因素及治疗分析

目的探讨老年弥漫性大B细胞淋巴瘤（DLBCL）预后因素,不同治疗方案对其生存的影响。方法回顾性分析72例初发老年DLBCL的性别、年龄、临床分期、B症状、ECOG-PS评分、结外病灶、血清LDH水平、血红蛋白水平、IPI评分与预后的相关性,其中可评价的为64例。比较接受3周CHOP方案34例和接受3周R-CHOP方案30例的生存情况。结果老年DLBCL患者中位生存期40．3个月,2年OS率67．43％,3年OS率49．89％。多因素分析显示年龄、ECOG-PS、临床分期、IPI评分是影响老年DLBCL患者预后的独立危险因素（P〈0．05）。CHOP组和R-CHOP组2年及3年OS率差异均有统计学意义,2年OS率（53．3％VS72．1％,P〈0．05）,3年OS率（39．2％VS60．8％,P〈0．05）。结论年龄、ECOG-PS、临床分期、IPI评分是老年DLBCL患者的预后相关因素,R-CHOP方案疗效优于CHOP方案。     

B cell non-Hodgkin’s lymphoma: experience from a tertiary care cancer center

Information on presentation and outcome of B cell non-Hodgkin's lymphoma (B-NHL) is limited from developing countries. Data of newly diagnosed adult aggressive B-NHL (n?=?260) patients were analyzed for clinical presentation, histological subtype, response to therapy, and survival. Univariate and multivariate Cox-regression analyses were performed for identification of prognostic factors. Diffuse large B cell lymphoma was the most common subtype (71?%). Median age was 50?years (18-78?years). The most common symptom was peripheral lymphadenopathy seen in 66?% of cases. Forty-seven percent of patients had advanced stage (stage III/IV), and 41?% had ECOG performance status of II-IV. B symptoms and bulky disease were present in 47 and 26?%, respectively. Intermediate to high risk score according to the International Prognostic Index (IPI) was seen in 67?%. Cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP) and CHOP-like regimens were used in 70?% cases, while R-CHOP was used in 18?% cases. For diffuse large B cell lymphoma (DLBCL) patients, in intent-to-treat analysis, the overall response and complete remission rates were 73 and 60?%, respectively. Four-year event-free and overall survival was 54 and 64.7?%, respectively. Presence of B symptoms (p?=?0.004), stage III/IV (p?=?0.02/p?=?0.01), performance status II-IV (p?=?0.001), serum albumin (<4?g/dl; p?=?0.001), hemoglobin <10?g/dl (p?=?0.001), high-risk IPI score (0.001), use of <6 chemotherapy cycles (p?=?0.001), and failure to attain CR (p?=?0.001) were significantly associated with lower event-free and overall survival. DLBCL is the most common B cell NHL seen at our center. Intermediate to high IPI was seen in 45?% and was associated with poor survival. Majority of the patients were treated without rituximab. In comparison to western data, we observed higher proportion of DLBCL, lower median age, higher male to female ratio, and higher proportion of patients with B symptoms in our study.     

AIDS-related non-Hodgkin lymphoma: final analysis of 485 patients treated with risk-adapted intensive chemotherapy

We aimed to compare AIDS risk-adapted intensive chemotherapy in AIDS-related lymphoma (ARL) patients before and after the advent of highly active antiretroviral therapy (HAART). A total of 485 patients aged from 18 to 67 years were randomly assigned to chemotherapy after stratification according to an HIV score based on performance status, prior AIDS, and CD4(+) cell counts below 0.10 x 10(9)/L (100/mm(3)). A total of 218 good-risk patients (HIV score 0) received ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisolone) or CHOP (doxorubicin, cyclophosphamide, vincristine, and prednisolone); 177 intermediate-risk patients (HIV score 1), CHOP or low-dose CHOP (Ld-CHOP); and 90 poor-risk patients (HIV score 2-3), Ld-CHOP or VS (vincristine and steroid). The 5-year overall survival (OS) in the good-risk group was 51% for ACVBP versus 47% for CHOP (P = .85); in the intermediate-risk group, 28% for CHOP versus 24% for Ld-CHOP (P = .19); and in the poor-risk group, 11% for Ld-CHOP versus 3% for VS (P = .14). The time-dependent Cox model demonstrated that the only significant factors for OS were HAART (relative risk [RR] 1.6, P < .001), HIV score (RR 1.7, P < .001), and the International Prognostic Index (IPI) score (RR 1.5, P < .001) but not chemotherapy regimen. Our findings indicate that in ARL patients, HIV score, IPI score, and HAART affect survival but not the intensity of the CHOP-based chemotherapy.     

Prognostic factors for classifying extranodal NK/T cell lymphoma, nasal type, as lymphoid neoplasia

This study evaluated the applicability of prognostic factors commonly used for diagnosis of classical lymphoma outcomes to extranodal NK/T cell lymphoma, nasal type (NTCL). Clinical features and their associations with lactate dehydrogenase (LDH) were evaluated in 70 patients. RLDH was defined as the ratio of LDH to the upper normal limit. RLDH was associated with stage (I-II vs. III-IV), lymph node involvement (LNI), and International Prognostic Index score (<2 vs. > or =2). Poor performance status and advanced stage were common in patients with local tumor invasiveness (LTI). LDH level, classified into three levels (low, high, and very high) was associated with survival (P < 0.001). In multivariate analysis, the predictive values of LDH level, B symptom, performance status, and stage remained significant whereas those of LTI and LNI did not. Scoring was performed by weighting each factor with 0.5 or 1.0 according to its hazard ratio. Scores were classified into four groups. Groups with high scores were associated with unfavorable outcomes (P < 0.001). Current study suggests that prognostic factors for NHL may be useful to predict the outcome of NTCL but the model should take LDH level and the prognostic weight of each factor into account.     

Prospective analysis of treatment outcome and prognostic factors in patients with T-cell lymphomas treated by CEOP-B: single institutional study

The important prognostic factors were evaluated for T-cell non-Hodgkin lymphoma (NHL) patients in a prospective study using the CEOP-B protocol [a modified cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-like regimen that uses epirubicin instead of doxorubicin with the addition of bleomycin]. Fifty-two patients were enrolled in the study. The overall response rate was 63.5%. The median progression-free survival (PFS) and median overall survival (OS) was 18.0 and 39.5 months respectively. The most common toxicity was neutropenia. The factors related to poor outcome were a high International Prognostic Index (IPI) and a high 'B' score (bone marrow involvement, B symptoms, bulky disease). We developed a new prognostic model, namely the Prognostic Group for T cell NHL (PGT) that included four groups: PGT1 (low IPI/low B score), PGT2 (low IPI/high B score), PGT3 (high IPI/Low B score) and PGT4 (high IPI/Low B score). OS and PFS (not reached, 48 months) in the PGT1 group were significantly longer than those (11.5 and 4.8 months) in PGT2. The same result was observed in the PGT3 and PGT4 groups. The CEOP-B regimen was moderately active and tolerable for T-cell NHL patients, and the PGT system might be useful for the prediction of long-term survival of T-cell NHL patients.     

Primary mediastinal large B-cell lymphoma: optimal therapy and prognostic factor analysis in 141 consecutive patients treated at Memorial Sloan Kettering from 1980 to 1999

Primary mediastinal large B-cell lymphoma (PMLBL) is a distinct clinicopathological entity with unclear prognostic factors and optimal treatment approach. To elucidate an optimal treatment and identify predictive factors, a retrospective analysis of 141 consecutive patients was undertaken. Patients received cyclophosphamide, hydroxydaunomycin, Oncovin, prednisone (CHOP)-like therapy, the non-Hodgkin lymphoma (NHL)-15 regimen or upfront autologous stem cell transplantation (ASCT) on Institutional Review Board approved trials or according to the institutional guidelines. Evaluation included lactate dehydrogenase, International Prognostic Index (IPI) assessment, computed tomography scan and gallium imaging. With a median follow-up of 10.9 years, event-free survival (EFS) and overall survival (OS) was 50% and 66% respectively. EFS/OS for CHOP/CHOP-like, NHL-15 and upfront ASCT was 34/51%, 60/84% and 60/78% respectively. CHOP/CHOP-like regimens had inferior EFS and OS versus NHL-15 or upfront ASCT (P < 0.001). A total of 23% of patients received radiotherapy. Multivariate analysis revealed the following outcome predictors: for EFS, greater than or equal to two extranodal sites and initial therapy received (NHL-15 or upfront ASCT); for OS, only initial therapy with NHL-15. We conclude: (i) dose-dense chemotherapy with NHL-15 may be superior to CHOP for PMLBL; (ii) The impact of consolidative radiotherapy requires randomised controlled trials; (iii) The age-adjusted IPI did not predict survival in this analysis; (iv) high-dose chemotherapy/ASCT should be reserved for upfront anthracycline-based therapy failure or in clinical trials for high-risk patients.     

A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma

There is no generally established prognostic index for patients with mantle cell lymphoma (MCL), because the International Prognostic Index (IPI) and Follicular Lymphoma International Prognostic Index (FLIPI) have been developed for diffuse large cell and follicular lymphoma patients, respectively. Using data of 455 advanced stage MCL patients treated within 3 clinical trials, we examined the prognostic relevance of IPI and FLIPI and derived a new prognostic index (MCL international prognostic index, MIPI) of overall survival (OS). Statistical methods included Kaplan-Meier estimates and the log-rank test for evaluating IPI and FLIPI and multiple Cox regression for developing the MIPI. IPI and FLIPI showed poor separation of survival curves. According to the MIPI, patients were classified into low risk (44% of patients, median OS not reached), intermediate risk (35%, 51 months), and high risk groups (21%, 29 months), based on the 4 independent prognostic factors: age, performance status, lactate dehydrogenase (LDH), and leukocyte count. Cell proliferation (Ki-67) was exploratively analyzed as an important biologic marker and showed strong additional prognostic relevance. The MIPI is the first prognostic index particularly suited for MCL patients and may serve as an important tool to facilitate risk-adapted treatment decisions in patients with advanced stage MCL.     

The highest prognostic impact of LDH among International Prognostic Indices (IPIs): an explorative study of five IPI factors among patients with DLBCL in the era of rituximab

Although the International Prognostic Index (IPI) is considered as the current standard prognostication system for diffuse large B-cell lymphoma (DLBCL), prognostic heterogeneity is suggested to exist among the patients within the same IPI risk group. Hence, we investigated the pattern of distribution and prognostic impact of five IPI factors within the same IPI score. We retrospectively reviewed the medical records of 387 patients newly diagnosed as pathologically proven DLBCL between February 2002 and February 2010. We classified patients to IPI risk scores and categorized them according to the combinations of IPI. Then, we explored the frequency of five IPI factors and analyzed the correlation between these subgroups and efficacy outcomes: complete response (CR), event-free survival (EFS), and overall survival (OS). Survival estimates by IPI score in this cohort corresponded to the classic IPI. Elevated serum level of lactate dehydrogenase (LDH) was the most prevalently distributed factor throughout the scores, and patients with elevated serum level of LDH tended to have lower CR, inferior EFS, and/or OS irrespective of IPI scores. Particularly, among the subgroups of IPI score of 2, elevated serum level of LDH was significantly associated with inferior CR (73.1 vs 95.2 %), 3-year EFS (57 vs 87 %), and 3-year OS (58 vs 82 %). In addition, the higher serum level of LDH, particularly above 2,000 IU/L, was significantly correlated with the inferior survival outcomes (3-year EFS 78.0 vs 58.5 vs 45.5 vs 20.0 %, 3-year OS 86.0 vs 66.2 vs 58.2 vs 40.0 %). In conclusion, among five factors of IPI, elevated serum level of LDH seems to be the most frequently distributed and, more importantly, the most relevant IPI factor with the highest prognostic impact. These findings still warrant further validation in larger cohorts.     

Phase II study of CHOP-GR therapy in diffuse large B-cell lymphoma

We investigated a fixed scheme of combination chemotherapy protocol including CHOP, granulocyte colony stimulating factor (G-CSF) and rituximab (CHOP-GR) for patients with diffuse large B cell lymphoma (DLBCL) in a phase II clinical trial. Forty-four patients were registered: 21 patients <61?years of age in the low or low-intermediate International Prognostic Index (IPI) risk group and 23 patients between 61 and 70?years of age in any IPI risk group. The patients underwent two courses of CHOP chemotherapy followed by four courses of CHOP-GR, including subcutaneous G-CSF on days 11-14 and rituximab on day 15. An additional two courses of weekly rituximab were administered. Of the assessable 43 patients, complete remission occurred in 39 (91?%), partial remission in one (2?%), and progressive disease in three (7?%). In the median 53-month observation period in alive patients, the 5-year overall survival rate of the 43 patients was 77?% and the 5-year progression-free survival rate was 69?% with a subsequent plateau. There were nine deaths in the 43 patients, all of which were attributable to lymphoma progression. The most frequent adverse events were leukocytopenia (98?%), neutropenia (94?%), lymphocytopenia (91?%), and alopecia (83?%). CHOP-GR is a safe and effective therapy for patients with untreated DLBCL.     

Risk factors for poor treatment outcome and central nervous system relapse in diffuse large B-cell lymphoma with bone marrow involvement

Although several studies have described the prognostic implication of bone marrow (BM) involvement (BMI) in lymphoma, studies focused on BM-involved diffuse large B-cell lymphoma (DLBCL) are very rare and small-sized. This study was performed to examine the prognostic impact of morphologic findings of BMI by lymphoma and risk factors for central nervous system (CNS) relapse in BM-involved DLBCL. Between 1993 and 2005, 675 patients were diagnosed with DLBCL, and 88 patients who had BMI at initial diagnosis were eligible for this study. The median overall survival (OS) and failure-free survival (FFS) of 88 patients were 36.6 and 20.1 months, respectively. When three variables from BM morphologic findings (the pattern of BM infiltration, extent of BMI by lymphoma, and percentage of large cells in the infiltrate) were simultaneously included into multivariate model, the increased extent of BMI by lymphoma (≥10%) in BM area was the only negative prognostic factor, independent of the International Prognostic Index (IPI). Patients with both lower IPI scores and less extent of BMI showed an excellent prognosis with chemotherapy alone (5-year OS and FFS rates, 80% and 69%). However, morphologic BM features were not independent predictive factors for CNS recurrences. An increased lactate dehydrogenase (LDH) level at initial diagnosis was the only independent predictive factor for CNS relapse. Further efforts should be directed toward finding optimal treatment modalities based on the IPI and the extent of BMI by lymphoma. CNS prophylaxis may be considered only in patients with initial elevated LDH levels. K.-W. Lee and J. Yi equally contributed to this study.     

First-line therapy of CD20+ diffuse large B-cell lymphoma: facts and open questions

CHOP chemotherapy, administered every 21 days, has been for years the standard therapy for advanced diffuse large B-cell lymphoma, with a long-term overall survival rate of about 40%. In this perspective article, Dr. Brusamolino discusses the recent advances in the treatment of this condition. See related paper on page 1250.CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy, administered every 21 days (CHOP21), has been for years the standard therapy for advanced diffuse large B-cell lymphoma (DLBCL), with a long-term overall survival rate of about 40%.¹ Modifications of the CHOP design including its dose-intensity and dose-density, have been introduced in the attempt to improve its efficacy. The dose-intensive ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) regimen, developed by the Groupe d’Etude des Lymphomes de l’Adult (GELA) demonstrated an advantage over CHOP in terms of event-free and overall survival² and the CHOEP (CHOP plus etoposide) regimen developed by the German High-Grade non-Hodgkin’s Lymphoma (DSHNHL) group proved to be superior to CHOP in young patients with normal lactate dehydrogenase (LDH).³ Moreover, compared to CHOP21, the dose-dense two-weekly CHOP14 regimen produced longer survival in young and elderly patients.⁴In the early 1990s, the prognostic relevance of a number of clinical variables was retrospectively evaluated by the International non-Hodgkin’s Lymphoma Prognostic Factors Project in patients with diffuse lymphoma who had been given doxorubicin-containing regimens. An International Prognostic Index (IPI) was developed, based on the five most significant variables: age, clinical stage, LDH, ECOG performance status and number of extra-nodal sites.⁵ Accordingly, four categories of risk were defined: low (0–1 risk factor), low-intermediate (2 factors), high-intermediate (3 factors) and high risk (4 or 5 factors). Each prognostic group showed significantly different outcomes, with 5-year relapse-free survival rates ranging from 70% to 40% and overall survival rates ranging from 73% to 26%. An adjustment of the original IPI system was subsequently developed for patients younger than 60 years (age-adjusted IPI or aaIPI); the risk factors considered were stage, LDH and performance status and risk categories varied from aaIPI 0 to aaIPI 2–3. The IPI system was of great help in designing clinical studies for different patient categories including young patients with favorable prognosis (aaIPI 0–1), young patients with intermediate/unfavorable prognosis (aaIPI 2–3) and elderly patients.One of the facts that changed the therapeutic scenario in DLBCL was the coupling of CHOP chemotherapy with rituximab, a humanized anti-CD20 monoclonal antibody (R-CHOP). The role of rituximab was first evaluated in elderly (> 65 years) patients with DLBCL, in whom eight courses of R-CHOP every 21 days conclusively demonstrated, in a GELA study, to significantly improve the outcome compared with CHOP alone.⁶ This superiority was evident in patients with both favorable and unfavorable IPI scores and the survival benefit is maintained over time. Of importance, the addition of rituximab did not substantially increase toxicity, although a trend towards a higher risk of infections after R-CHOP compared to CHOP was observed. The US E4494 Intergroup trial comparing up-front CHOP with or without rituximab and with or without rituximab maintenance in the elderly demonstrated a significant advantage for patients receiving rituximab, either as part of induction or maintenance therapy.⁷ The impact of adding rituximab to CHOP, in both young and elderly patients with DLBCL, has been recently confirmed in a large population-based study. Comparing survival before and after the introduction of rituximab into clinical practice, the British Columbia Cancer Agency observed that in elderly patients the 2-year overall survival improved from 40% to 67% and progression-free survival from 44% to 67%, while in young patients overall survival improved from 69% to 87%, with a 10% gain in the progression-free survival.⁸     

Delineating outcomes of patients with diffuse large b cell lymphoma using the national comprehensive cancer network‐international prognostic index and positron emission tomography‐defined remission status; a population‐based analysis

The recently devised National Comprehensive Cancer Network International Prognostic Index (NCCN‐IPI) appears superior to the revised IPI (R‐IPI) in delineating outcome in diffuse large B‐cell lymphoma. We examined the outcome of a population‐based cohort of 223 consecutive patients treated with R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) or R‐CHOP‐like immuno‐chemotherapy between January 2005 and December 2011 by both the NCCN‐IPI and R‐IPI, and further stratified outcome by the achievement of both computerized tomography (CT) and positron emission tomography (PET)‐CT complete remission (CR), with the latter reassessed using blinded central review by an independent nuclear medicine and radiology specialist. The NCCN‐IPI was superior to the R‐IPI in identifying patients at very high risk of systemic and/or central nervous system relapse. Notably, both the NCCN‐IPI and the R‐IPI remained strongly predictive of relapse irrespective of CT or PET‐defined remission status following R‐CHOP. Patients with high‐risk NCCN‐IPI scores (≥6) have a dismal outcome following R‐CHOP therapy regardless of PET‐defined response to R‐CHOP. Moreover, such patients appear refractory to salvage chemotherapy and thus require alternative therapeutic approaches, although age and performance status may, for many patients, preclude the safe delivery of a primary intensified regimen. By contrast, patients with NCCN‐IPI 1–5 who achieve PET‐CR following R‐CHOP have excellent outcomes and may merit reduced follow up frequency.     

High Ki67 index and bulky disease remain significant adverse prognostic factors in patients with diffuse large B cell lymphoma before and after the introduction of rituximab

The aim of this study was to evaluate the impact of clinical variables and biologic features on response rate (RR), overall survival (OS) and progression-free survival (PFS) in 111 patients with de novo diffuse large B cell lymphoma (DLBCL). Fifty-three patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) and 58 patients were treated with R-CHOP (rituximab + CHOP). The variables predictive of RR in the CHOP group were B symptoms, age, clinical stage, bone marrow involvement, bulky disease, International Prognostic Index (IPI) and Bcl-2; in the R-CHOP group, these variables were bulky disease, bone marrow involvement, IPI and Ki67 expression >80%. Multivariate analysis showed that in patients treated with CHOP, the independent prognostic factors associated with PFS were age, bulky disease, IPI and Bcl-2 and those associated with OS were performance status, clinical stage, IPI and bone marrow involvement. In contrast, in patients treated with R-CHOP, the variable shown by multivariate analysis to be an independent prognostic factor associated with PFS was bulky disease, whereas Ki67 expression >80% was associated with OS and PFS. Our data show that a high Ki67 expression and bulky disease could represent possible predictive factors of poor prognosis, which would help to identify a high-risk subgroup of newly diagnosed DLBCL.     

The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous entity, with patients exhibiting a wide range of outcomes. The addition of rituximab to CHOP chemotherapy (R-CHOP)has led to a marked improvement in survival and has called into question the significance of previously recognized prognostic markers. Since randomized controlled trials of R-CHOP in DLBCL have included select subgroups of patients, the utility of the International Prognostic Index (IPI) has not been reassessed. We performed a retrospective analysis of patients with DLBCL treated with R-CHOP in the province of British Columbia to assess the value of the IPI in the era of immunochemotherapy. The IPI remains predictive, but it identifies only 2 risk groups. Redistribution of the IPI factors into a revised IPI (R-IPI) provides a more clinically useful prediction of outcome. The R-IPI identifies 3 distinct prognostic groups with a very good (4-year progression-free survival [PFS] 94%, overall survival [OS] 94%), good (4-year PFS 80%, OS 79%), and poor (4-year PFS 53%, OS 55%) outcome, respectively (P < .001). The IPI (or R-IPI) no longer identifies a risk group with less than a 50% chance of survival. In the era of R-CHOP treatment, the R-IPI is a clinically useful prognostic index that may help guide treatment planning and interpretation of clinical trials.     

MAGE-A3 expression is an adverse prognostic factor in diffuse large B-cell lymphoma

This study evaluates the prognostic value of MAGE-A3 expression in 28 diffuse large B-cell lymphoma (DLBCL) patients. A significant association was observed between MAGE-A3 expressions, assessed by quantitative real-time RT-polymerase chain reaction (PCR), with advanced stages of disease (P < 0.05). Elevated serum lactate dehydrogenase (LDH) levels and International Prognostic Index (IPI) score were significantly higher in MAGE-A3-positive patients (P = 0.025 and P = 0.004, respectively). Expression of MAGE-A3 was associated with poor response to treatment and a significantly shorter overall survival (P < 0.001). Our data address new information in the association of MAGE-A3 expression and poor prognosis in DLBCL patients.     

Local tumor invasiveness is more predictive of survival than International Prognostic Index in stage I(E)/II(E) extranodal NK/T-cell lymphoma, nasal type

This study was launched to determine the prognostic significance of local tumor invasiveness (LTI) in 114 patients diagnosed with stage I(E)/II(E) extranodal natural killer (NK)/T-cell lymphoma, nasal type (NTCL). LTI was defined as bony invasion or destruction or tumor invasion of the skin. Complete remission (CR), overall survival (OS), and disease-free survival (DFS) were compared between each group according to LTI, Ann Arbor stage, and International Prognostic Index (IPI). LTI was observed in 23 patients. Using multivariate analysis, factors associated with low probability of CR were the presence of LTI (P < .001), the presence of B symptoms (P = .003), and single-modality chemotherapy (P = .045). The presence of LTI (relative risk [RR] = 8.4, 95% confidence interval [CI] 3.9-17.9; P < .001) and high IPI score (RR = 2.8, 95% CI 1.2-6.8; P = .019) were also predictive of OS. The presence of LTI (RR = 7.3, 95% CI 3.2-16.5; P < .001) was an independently significant factor for reduced DFS. Ann Arbor staging system did not predict CR, OS, or DFS but IPI did have predictive power with regard to survival outcome. LTI is the most important prognostic factor in predicting low probability of CR and reduced OS and DFS in nasal stage I(E)/II(E) NTCL.