Nongastric marginal zone B-cell lymphoma: a prognostic model from a retrospective multicenter study

The International Prognostic Index (IPI) and Follicular Lymphoma Prognostic Index (FLIPI) are used as prognostic indices for NHL and indolent lymphoma. However, marginal zone B-cell lymphoma (MZL) evidences a distinctive clinical presentation and a natural course; thus, in this study, we attempted to devise an adequate prognostic index for MZL. Two-hundred and five patients diagnosed with MZL were retrospectively reviewed. After analysis of the prognostic factors, progression-free survival (PFS), and overall survival (OS), we constructed a prognostic index of MZL (MZLPI) via the summation of each factor. We then compared PFS and OS with IPI, FLIPI, and MZLPI. According to our multivariate analysis, nodal MZL, ECOG performance > or = 2, and advanced stage were composed of MZLPI. MZLPI was grouped as follows: score 0 as a low-risk group, score 1 as an intermediate risk group, and score 2 as a high-risk group. The PFS curve, according to MZLPI results, evidenced a more discriminated pattern than IPI and FLIPI, and this was especially true in the intermediate risk group. In OS, MZLPI (P=0.0007) evidenced a more discriminated pattern than IPI (P=NS) or FLIPI (P=0.0044). MZLPI, which is constructed of relatively simple factors, may represent a useful prognostic index for the prediction of PFS and OS in MZL, and may also be used as a substitute for IPI or FLIPI.     

Predictive value of prognostic indices in patients with follicular lymphomas

PURPOSE: The aim of this study was to compare which of three indices--International Prognostic Index (IPI), Italian Lymphoma Intergroup (ILI) index, Follicular Lymphoma adapted International Prognostic Index (FLIPI)--is the most useful in predicting outcome in follicular lymphoma (FL) patients and to identify other clinical and laboratory prognostic factors that influence survival. PATIENTS AND METHODS: Clinical and prognostic studies were carried out in 99 patients with FL. RESULTS: The distribution of patients in IPI risk groups was 44.4%, 19.2%, and 36.4% of cases classified as low, intermediate, and high risk. According to ILI, low-, intermediate-, and high-risk scores were present in 34.3%; 27.3%, and 38.4% of FL patients. After applying the FLIPI index, the patients were divided into three risk groups: low (21.2% of cases), intermediate (39.4%), and high (39.4%) of FL patients. Survival curves demonstrated a high significant difference for the low- and high-risk group according to IPI and FLIPI (log rank=91.13 and 82.17 respectively; p < 0.0001). Difference in overall survival (OS) and failure-free survival (FFS) among low-, intermediate-, and high-risk groups according to ILI was statistically significant (log rank test p < 0.0001). CONCLUSION: All three indices are important tools for prognostic evaluation of FL patients, as well as useful in identifying FL patients with poor outcome. IPI and FLIPI classify patients into two risk groups (low/intermediate- and high-risk groups) with significance difference in OS and FFS, but ILI is more reliable in stratifying patients in low-, intermediate-, and high-risk groups.     

Is the follicular lymphoma international prognostic index better than the international prognostic index to identify high-risk follicular lymphoma patients?

The aims of this study are to validate follicular lymphoma international prognostic index (FLIPI) prognostic score and to compare it with the international prognostic index (IPI) in a cohort of 57 Brazilian patients. According to IPI, 24 patients (42%) were in the low-risk, 28 (49%) in the intermediate-risk, and 4 (7%) in the high-risk group. The distribution according to FLIPI was: 20 (35%) in the low-risk, 8 (14%) in the intermediate-risk, and 29 (51%) in the high-risk group. According to IPI score, median OS was not reached for the low-risk, it was 45 months for the intermediate-risk and 25 months for the high-risk group (p < 0.001). When FLIPI score was applied, median OS was not reached for the low and intermediate-risk, and was 42 months for the high-risk group (p = 0.0064). These findings suggest that: (1) FLIPI score could be validated in a Brazilian population; (2) FLIPI is more accurate than IPI to identify FL patients having worse prognosis (51%); (3) IPI seems to be a better tool for clinical decisions because it selected a smaller high-risk group (7%) having worse prognosis. In our opinion, IPI high-risk patients are the real candidates for more aggressive therapies, avoiding unnecessary over-treatment.     

Prognostic indexes in follicular lymphoma: a comparison of different prognostic systems.

BACKGROUND: The International Prognostic Index (IPI), initially designed for aggressive lymphomas, is also used in follicular lymphoma (FL) and other indolent lymphomas. Two new prognostic indexes have recently been proposed for FL [the Italian Lymphoma Intergroup (ILI) Index and the Follicular Lymphoma International Prognostic Index (FLIPI)]. PATIENTS AND METHODS: Three indexes, IPI [age >60 years, extranodal involvement two or more sites, elevated lactate dehydrogenase (LDH), Eastern Cooperative Oncology Group performance status > or =2, stage > or =3], ILI (age >60 years, extranodal involvement two or more sites, elevated LDH, male sex, B symptoms, erythrocyte sedimentation rate > or =30 mm first hour) and FLIPI (age >60 years, stage > or =3, elevated LDH, nodal involvement five or more, haemoglobin level < or =12 g/dl) were calculated in 411 patients with FL. RESULTS: Overall concordance between the three indexes was 54%. A total of 126 (31%) patients were included in the high-risk group according to IPI, 131 (32%) according to ILI and 157 (38%) after FLIPI application. Ten-year overall survival rates after applying the prognostic indexes (IPI, ILI and FLIPI) were, respectively: 72%, 71% and 72%, in the low-risk group; 51%, 60% and 49% in the intermediate-risk group; and 24%, 16% and 31% in the high-risk group. CONCLUSIONS: In this series, all three indexes, IPI, ILI and FLIPI, were useful to classify FL patients into differentiated risk groups, although the FLIPI identified a larger proportion of high-risk patients than the IPI and ILI.     

Examination of the follicular lymphoma international prognostic index (FLIPI) in the National LymphoCare study (NLCS): a prospective US patient cohort treated predominantly in community practices

BackgroundBecause follicular lymphoma (FL) patients have heterogeneous outcomes, the FL international prognostic index (FLIPI) was developed to risk-stratify patients and to predict survival. However, limited data exist regarding the role of FLIPI in the era of routine first-line rituximab (R) and R-chemotherapy regimens and in the setting of community oncology practices.Patients and MethodsWe evaluated the outcome data from the National LymphoCare Study (NLCS), a prospective, observational cohort study, which collects data on patients with FL in the United States (US) community practices.ResultsAmong 1068 male and 1124 female patients with FLIPI data, most were treated in US community practices (79%); 35% were FLIPI good risk, 30% intermediate risk, and 35% poor risk. FLIPI risk groups were significant predictors of overall survival (OS) and progression-free survival (PFS) for patients who undergo watchful waiting (WW), and those who receive non-R-containing regimens, R-alone, and R-chemotherapy combinations.ConclusionsIn the setting of contemporary practice with routine R use, stratifying patients into good, intermediate, and poor FLIPI risk groups predicts distinct outcomes in terms of OS and PFS. FLIPI remains an important prognostic index in the R era and should be used in clinical practices to support discussions about prognosis.     

Follicular lymphoma: an Institutional Analysis

Background: Follicular lymphoma (FL) is second most common lymphoma in adult, constituted 20% of all lymphoma cases in the west. There is limited information is available on FL from India. Methods: The clinico-pathological profile, treatment outcome and prognostic factors for survival were assessed retrospectively in 181 patients of FL seen at our center over a period of 17 years ( 1996-2012). Results: There were 120 males and 61 females. The median age was 51 years (24-80 years). The common presenting features were lymphadenopathy 71%, fatigue 23% and fever 20%. Ann Arbor stage distribution was: stage I - 9%, stage II - 11%, stage III -22 % and stage IV - 58%. Extra nodal involvement and bulky disease were present in 22% and 19% patients respectively. Follicular Lymphoma International Prognostic Index (FLIPI) 1 score : Low -25%, Intermediate-45% and high risk in 30% of cases. One forty five patients (80%) received treatment at presentation or during follow-up. Chemotherapeutic regimen used were: CHOP-45 , CVP-51, chlorambucil and prednisolone -7 , BR ( bendamustine and rituximab)-12, RCHOP- 14 RCVP – 7 and other regimen were used in 5 cases. The overall response (ORR) and complete remission (CR) rates were 70% and 35% respectively. Median overall survival (OS) and event free survival (EFS) was 5.5 years and 2.5 years respectively, with median follow up period of 3.0 years. Grade 3 histology, failure to attain CR, low serum albumin, and high risk FLIPI were significantly associated with lower event free survival. High risk FLIPI (HR 1.46, 95% CI 1.03-2.10, p=0.003) and failure to attain CR (HR 2.64, CI 1.10-4.30, p=0.001) were predictors of poor OS. Conclusions: FL represents 9 % of all lymphoma in adult. This is the largest data from single institute from India. Eighty percentage of patients presented in stage III/IV disease. High risk FLIPI and failure to attain CR were important prognostic variables for OS.     

Comparison of four prognostic scores in peripheral T-cell lymphoma

BackgroundTo compare the usefulness of four prognostic scores in patients with peripheral T-cell lymphoma (PTCL) from a single institution.Patients and methodsOne hundred twenty-one patients (77 male/36 female, median age 53 years) with PTCL [anaplastic large-cell lymphoma (ALCL) 21, PTCL not otherwise specified 56 and other 44)]. Complete response (CR) rate and 5-year overall survival (OS) were 41% and 31%, respectively. International Prognostic Index (IPI), Prognostic Index for T-cell lymphoma (PIT), International peripheral T-cell lymphoma Project score (IPTCLP) and modified Prognostic Index for T-cell lymphoma (mPIT) were calculated as in the original references. mPIT was only assembled to 41 patients in whom Ki-67 immunostaining was available. ALCL patients were analyzed separately.ResultsConcordance among IPI, PIT and IPTCLP was 52% for low-risk group, 27% for low/intermediate-risk group, 20% for high/intermediate-risk group and 14% for high-risk group. IPI, PIT and IPTCLP predicted CR, with IPI being the best score in logistic regression. Neither Ki-67 immunostaining nor mPIT predicted CR. Five-year OS (low-risk versus intermediate- or high-risk categories) according to IPI, PIT, IPTCLP and mPIT were 52% versus 45%, 75% versus 49%, 58% versus 20% and 39% versus 0%, respectively. IPTCLP was the best score for OS in multivariate analysis.ConclusionAll the scores demonstrated their usefulness to assess the outcome of patients with PTCL, with IPTCLP being the most significant to predict OS.     

改良国际预后指数（NCCN-IPI）对R-CHOP方案治疗弥漫大B 细胞淋巴瘤的预后评估（附168 例临床分析）

目的:验证改良国际预后指数（NCCN-IPI）对弥漫大B 细胞淋巴瘤（DLBCL ）患者免疫化疗后的预后评估价值。方法:回顾性分析天津医科大学肿瘤医院2008年1 月至2013年1 月收治的168 例初治DLBCL 患者的临床特征及预后,采用NCCN-IPI和国际预后指数（IPI）进行危险度分层和预后评估。结果:全组患者中位年龄58（24～80）岁,男性92例（54.8%）,AnnArbor分期Ⅲ～Ⅳ期94例（56.0%）,ECOGPS ≥ 2 分19例（11.3%）;发病时LDH 水平升高（> 245 U/L）占71.4% 。中位随访42（15～88）个月,3年和5 年生存率（OS）分别为（75.9 ± 3.4）% 、（65.1 ± 5.2）% 。全组患者根据IPI 评分系统,低危组占30.4% ,中低危27.4% ,中高危25.0% ,高危17.3% ;3 年OS分别为91.8% 、76.7% 、67.9% 和47.1% 。根据NCCN-IPI评分,低危组19.0% ,中低危38.1% ,中高危31.5% ,高危11.3% 。3 年OS分别为94.5% 、85.4% 、61.2% 和38.1% 。与IPI 评分相比,NCCN-IPI评分区分高危和低危患者的能力更强（NCCN-IPI:3 年OS:94.5% vs . 38.1% ;IPI:91.8% vs . 47.1%）。 结论:在利妥昔单抗一线治疗中,与IPI 指数相比,NCCN-IPI更好地整合了年龄和LDH 水平两个变量的预后作用,可作为DLBCL 患者强有力的预后分层工具。      

The role of anthracyclines in combination chemotherapy for the treatment of follicular lymphoma: retrospective study of the Intergruppo Italiano Linfomi on 761 cases

In order to elucidate the role of anthracycline based combination chemotherapy regimens for the treatment of follicular lymphoma we conducted a retrospective study on a large series of patients with a histologically confirmed diagnosis of follicular lymphoma. The Italian lymphoma intergroup (ILI) promoted a retrospective study of patients with follicular lymphoma treated in cooperative trials between 1985 and 1996. Six hundred and thirty three cases were treated with an anthracycline-containing regimen and 128 patients were treated without anthracyclines. The two groups were prognostically comparable; in particular, no difference was observed according to both IPI and ILI prognostic index. Results showed a complete remission (CR) rate for patients treated with anthracyclines was 69.2% and overall response rate was 92.5%. After a median follow-up of 51 months (54 months for patients still alive), the 5- and 10-year overall survival (OS) rates were 80 and 66%, respectively. Disease-free survival (DFS) and failure-free survival (FFS) rates at 5 years were 61 and 49%, respectively. In the group of patients treated with combination chemotherapy not including anthracyclines, the CR rate was 67.5% and the overall response rate was 85.4%. A longer OS (80% at 5 years) was observed in patients treated with anthracyclines compared to 67% OS rate in patients treated without anthracyclines (p = 0.0004). FFS was significantly longer in patients treated with anthracyclines (49 vs. 34% p = 0.006). Patients treated with anthracyclines with low or intermediate risk according to ILI prognostic index showed a significantly longer OS (p = 0.0001 andp = 0.0009, respectively); those in the high-risk group showed a trend for a longer survival. In conclusion, this retrospective study shows that patients with follicular lymphoma treated with an anthracycline containing regimen had a better outcome compared to patients treated with other combination regimens non including anthracyclines in terms of CRs, OS and FFS. On the basis of these results anthracycline-containing regimens (ACR) should be considered as the standard treatment of patients with advanced follicular lymphoma.     

The Follicular Lymphoma International Prognostic Index (FLIPI) and the histological subtype are the most important factors to predict histological transformation in follicular lymphoma.

BACKGROUND: Histological transformation (HT) is a well-known event in patients with follicular lymphoma (FL) conferring an unfavorable prognosis. The aim of the study was to analyze incidence and risk factors for HT in a large series of FL patients. PATIENTS AND METHODS: 276 patients (median age: 54 years; M139/F137) diagnosed with FL (42% grade 1, 51% 2, 7% 3) in a single institution were studied. Initial treatment consisted of combined chemotherapy in most cases. Median survival was 11.3 years. Main clinic and biological variables were assessed for HT and survival. RESULTS: 30 of 276 patients (11%) presented HT after a median follow-up of 6.5 years, with a risk of 15% and 22% at 10 and at 15 years, respectively. All HT corresponded to diffuse large B-cell lymphoma (DLBCL). Grade 3 histology, nodal areas >4, increased LDH and beta(2)-microglobulin, and high-risk IPI and FLIPI were associated with HT. In multivariate analysis, grade 3 histology and FLIPI retained prognostic significance. Only FLIPI predicted HT in grade 1-2 patients. 28 patients received salvage treatment for HT, with a CR rate of 52%. Median survival from transformation was 1.2 years, with 6/13 CR patients being alive >5 years after HT. CONCLUSION: FLIPI and histology were the most important variables predicting HT. Upon HT, only patients achieving CR reached prolonged survival, thus emphasizing the need for effective therapies once this event occurs.     

Prognostic value of the Follicular Lymphoma International Prognostic Index score in marginal zone lymphoma

BACKGROUND:

In marginal zone lymphoma (MZL), clinical and follow‐up data on large cohorts of patients are difficult to obtain. The objective of this single‐center, retrospective analysis of a large cohort of 144 patients with MZL was to elucidate the role of prognostic markers, treatments, and outcomes in this disease.

METHODS:

In total, 144 patients were identified who were diagnosed with MZL at the authors' institution between 2003 and 2010. Data on clinical parameters, treatments, response, and survival were analyzed. In addition, the validity of the International Prognostic Index (IPI) and Follicular Lymphoma International Prognostic Index (FLIPI) prognostic scores were tested in patients with MZL.

RESULTS:

Among 144 patients with MZL, 96 patients (67%) had extralymph node (extranodal) MZL, 32 patients (22%) had lymph node (nodal) MZL, and 16 patients (11%) had splenic MZL. The 5‐year progression‐free survival rate was 82% in the nodal MZL group, 88% in the extranodal MZL group, and 74% in the splenic MZL group and did not different between the 3 groups (P = .60). The 5‐year overall survival rate was excellent in all 3 MZL groups (nodal MZL, 89%; extranodal MZL, 92%; splenic MZL, 82%; P = .46). In our cohort, the FLIPI score was a significant prognostic marker: The 5‐year progression‐free survival rate for patients who had FLIPI scores of 0 to 2 (low or intermediate risk) was excellent at 92%, whereas it was only 62% for patients who had FLIPI scores of 3 to 5 (poor risk; P = .003). Similarly, the 5‐year overall survival rate for patients who had FLIPI scores of 0 to 2 was 95%, whereas it was only 62% for patients who had FLIPI scores of 3 to 5 (P = .0009).

CONCLUSIONS:

The FLIPI score had strong prognostic value in patients with MZL. Patients who have low‐risk or intermediate‐risk FLIPI scores have an excellent prognosis, whereas patients with poor‐risk FLIPI scores are candidates for novel treatment approaches. Cancer 2013. © 2012 American Cancer Society.     

Refractoriness to immunochemotherapy in follicular lymphoma: Predictive factors and outcome

Follicular lymphoma is characterized by a good response to immunochemotherapy (ICT). However, a small percentage of patients responds poorly to treatment and seems to have a worse outcome. This study attempted to identify the predictive factors and outcome of refractoriness to first‐line ICT. All patients diagnosed with stage II to IV follicular lymphoma between 2002 and 2014 and treated with first‐line ICT in 4 Spanish institutions were analyzed. Those with no response or progression or relapse within 6 months of first‐line response assessment were considered ICT refractory. Three hundred forty‐three patients were included (median age 58 years, 48% male), of whom 53 (15%) were ICT refractory. On multivariate analysis, high‐risk follicular lymphoma international prognostic index (FLIPI) score, B symptoms, and elevated β2‐microglobulin were correlated with refractoriness, and refractoriness, high‐risk FLIPI score, and β2‐microglobulin were correlated with overall survival (OS). Compared with ICT‐sensitive, ICT‐refractory patients had a higher incidence of histological transformation (5‐year cumulative incidence 25% [14%‐39%] vs. 6% [3%‐10%], P < .001), a higher rate of refractoriness to second‐line therapy (16/33 [48%] vs. 13/57 [23%], P = .01), and a lower OS (5‐year OS probability 38% [95% CI 23%‐53%] vs. 87% [82%‐92%%], P < .001). In conclusion, refractoriness to ICT was seen in 15% of patients and was predicted by high‐FLIPI scores, B symptoms, and elevated serum β2‐micrglobulin. Immunochemotherapy‐refractory patients had a worse prognosis than ICT‐sensitive patients, and current treatment options for this subgroup are not satisfactory.     

m7FLIPI and targeted sequencing in high‐risk follicular lymphoma

Patients with follicular lymphoma (FL) refractory to front‐line immunochemotherapy (ICT) have a poor overall survival (OS). Gene mutation analysis may be more accurate than classical risk factors to pick out these patients before treatment. This study aimed to describe the prevalence of selected genetic mutations in a cohort of patients with high‐risk FL. Twenty‐five patients with FL refractory to front‐line ICT and 10 non‐refractory patients matched for age, sex, and FLIPI score were included. We sequenced 18 genes (custom targeted sequencing panel) previously reported to potentially have prognostic impact, including the seven genes necessary to determine m7FLIPI risk. The 35 patients had a median age of 62. The FLIPI and FLIPI2 were high in 27 (84%) and 14 (48%), respectively. Three‐year progression‐free survival (PFS) and OS probabilities were 25% (95% CI, 13%‐41%) and 53% (34%‐69%), respectively. There were 73 variants in the 18 genes among the 35 patients. The median number of mutations per patient was 1 (interquartile range, 0‐3). The most commonly mutated genes were CREBBP (11 of 35, 31%) and EP300 (10 of 35, 29%). EP300 mutations were associated with refractoriness to treatment (10 of 25 among refractory and 0 of 10 among non‐refractory). In conclusion, in this study, patients with high‐risk follicular lymphoma were genetically heterogeneous.     

Different age limits for elderly patients with indolent and aggressive non-hodgkin lymphoma and the role of relative survival with increasing age

BACKGROUND: There is no consistent definition at what age patients with non-Hodgkin lymphoma (NHL) are considered "elderly." This might hamper well balanced decisions with respect to treatment. METHODS: From a population-based NHL registry the age groups younger than 60 years, 60-64 years, 65-69 years, 70-74 years, and 75 years and older were analyzed in relation to the revised European-American lymphoma classification and to the age-adjusted International Prognostic Index (IPI). The prognostic value of the variables from the age-adjusted IPI was determined. The relative survival probabilities were calculated. RESULTS: The incidence of diffuse large B-cell lymphoma (DLBL) increased with advancing age, as was the case for small lymphocytic lymphomas. Follicular lymphomas were less frequently encountered with advancing age. With respect to the so-called indolent lymphomas, a decreasing complete remission rate and overall survival rate (5-year) was observed for patients older than 70 years, whereas patients with DLBL fared worse when older than 65 years and 60 years, respectively. The age-adjusted IPI score was discriminative for prognosis. However, even with an IPI score nil, the age group older than 75 years fared significantly worse (P < 0.009), but less so with the relative survival model. The relative survival at 5 years was 60%, 53%, 48%, 35%, and 32% for the 5 respective age groups. CONCLUSIONS: Patients with indolent lymphomas become elderly when they are older than 70 years, but when aggressive lymphoma is concerned this occurs when patients are older than 65 years. For patients with an IPI score nil, age older than 75 years is the dominant prognostic factor. The negative influence of concomitant disease on overall survival, although continuously increasing in older age groups, seems to diminish for patients older than 75 years when compared with the general Dutch population.     

淋巴瘤国际预后指征对中国进展型非霍奇金氏淋巴瘤的适用性研究

目的 观察进展型ＮＨＬ国际预后指征（ＩＰＩ）对用标准方案治疗的中国进展型非堆奇金氏淋巴瘤预后的预测作用。方法 分析１９９１年－１９９３年间病理组织学和免疫组化确诊的进展型ＮＨＬ２１例,按ＩＰＩ分组,全组分成低度危险,中度危险组,高中度危险组和高度危险组。结果：低危组,低中度危组和高危组患者的ＣＲ率分别是５９．１％,４７．２％,３１．８％和９．７％,结论：ＩＰＩ对选择常规化疗效差的高色进展型ＮＨＬ病     

External Validation of the FLIPI Risk Score Measured at Diagnosis and POD24 Among Individuals With Follicular Lymphoma at the Time of Subsequent Relapse

BackgroundThe Follicular lymphoma international prognostic index (FLIPI) risk score and POD24 have previously been shown to have prognostic value in follicular lymphoma (FL), but the extent to which they can inform prognosis at the time of subsequent relapse is uncertain.Patients and MethodsWe conducted a longitudinal cohort study of individuals diagnosed with FL between 2004 and 2010 in Alberta, Canada who received front-line therapy and subsequently relapsed. FLIPI covariates were measured prior to the initiation of front-line therapy. Median overall survival (OS), progression-free survival (PFS2), and time to next treatment (TTNT2) were estimated from the time of relapse.ResultsA total of 216 individuals were included. The FLIPI risk score was highly prognostic at the time of relapse for OS (c-statistic = 0.70; HR_{[High vs. Low]} = 7.38; 95% CI: 3.05-17.88), PFS2 (c-statistic = 0.68; HR_{[High vs. Low]} = 5.84; 95% CI: 2.93-11.62) and TTNT2 (c-statistic = 0.68; HR_{[High vs. Low]} = 5.72; 95% CI: 2.87-11.41). POD24 was not prognostic at the time of relapse for either OS, PFS2, or TTNT2 (c-statistic = 0.55).ConclusionThe FLIPI score measured at diagnosis may help with the risk stratification of individuals with relapsed FL.     

Low-grade stage III-IV follicular lymphoma: multivariate analysis of prognostic factors in 484 patients--a study of the groupe d'Etude des lymphomes de l'Adulte.

PURPOSE: To identify the prognostic factors that influence overall survival (OS) in patients with stage III-IV follicular lymphomas and evaluate the clinical usefulness and the prognostic value of the International Prognostic Index (IPI). PATIENTS AND METHODS: Four hundred eighty-four patients with Ann Arbor stage III-IV follicular lymphomas treated in two phase III trials from 1986 to 1995 were screened for this study. All histologic slides were reviewed by two hematopathologists. The influence of the initial parameters on survival was defined by univariate (log-rank test) and multivariate (Cox model) analyses. RESULTS: The poor prognostic factors for OS (age > 60 years, "B" symptom(s), > or = two extranodal sites, stage IV disease, tumor bulk > 7 cm, at least three nodal sites > 3 cm, liver involvement, serous effusion-compression or orbital/epidural involvement, and erythrocyte sedimentation rate > 30 mm/h) that were significant in univariate analysis were subjected to multivariate analysis. Three factors remained significant: B symptom(s) (risk ratio = 1.80), age greater than 60 years (risk ratio = 1.60), and at least three nodal sites greater than 3 cm (risk ratio = 1.71). When the IPI was applied to these patients, the score was 1, 2, 3, and 4-5 in 49%, 39%, 11%, and 2%, respectively, and it was significant for progression-free survival (P =.002) and OS (P =.0001). CONCLUSION: Three prognostic factors for poor OS were identified: B symptoms, age greater than 60 years, and at least three nodal sites greater than 3 cm. The IPI was prognostic for OS, but in this population, a very low number of patients belonged to the high-risk groups.     

Presence of t(14;18) positive cells in blood and bone marrow does not predict outcome in follicular lymphoma

Follicular Lymphoma International Prognostic Index—FLIPI is an established clinical predictor for outcome in follicular lymphoma. The role of molecular abnormalities in blood and bone marrow of follicular lymphoma patients including t(14;18) is less clear. Seventy-five patients from a single institution diagnosed with follicular lymphoma between1999 and 2005 were included into the study. Diagnosis was based on lymph node biopsy in 62 cases (83%). Thirty-nine patients (52%) had G1 histological grade and 47 (63%) had entirely follicular growth pattern, as well as 9 patients (12%) had systemic symptoms and 33 (44%) were assigned to a good risk according to FLIPI. Median age of patients was 53 years. During a median observation time of 3 years 63 patients (84%) required initiating anti-lymphoma treatment. Seventy-five samples of peripheral blood and 65 samples of bone marrow were collected at the diagnosis. Bcl2 rearrangements including major breakpoint region and minor breakpoint cluster region were investigated using nested polymerase chain reaction technique. The primary end points of the study were time to first line lymphoma treatment and progression-free survival. Cells carrying t(14;18) were found in 31 cases (41%) including 29 samples of peripheral blood and 26 samples of bone marrow. Detection of t(14;18) in blood and bone marrow at diagnosis had no influence on clinical outcome. Age, follicular growth pattern systemic symptoms, and FLIPI score above 1 were predictive for initiation of the first lymphoma therapy. Follicular growth pattern, initial nodal involvement, serum LDH level, and FLIPI score above 1 were predictive for longer progression-free survival.     

Long-term follow-up of advanced-stage low-grade lymphoma patients treated upfront with high-dose sequential chemotherapy and autograft.

Long-term outcome, after first line intensified high-dose sequential (i-HDS) chemotherapy, was evaluated in 46 patients, aged < or =65 years, with advanced low-grade lymphoma. Seventeen patients had small lymphocytic lymphoma (SLL), 29 had follicular lymphoma (FL), 10 of them with histologic transformation. I-HDS included: (1) tumor debulking, by 2 APO+2 DHAP courses; (2) sequential administration of high-dose (hd) etoposide, methotrexate, and cyclophosphamide, followed by peripheral blood progenitor cell (PBPC) harvest; (3) hd-mitoxantrone + melphalan with PBPC autograft. Ten FL patients had their PBPC immunologically purged ex vivo. There were two treatment-related deaths; five FL patients had short-lasting response followed by disease progression, five SLL reached a stable PR; overall, 34 patients (74%) reached CR. At a median follow-up of 4.3 years, the estimated 9-year OS and EFS were 84% and 45%, respectively. No significant differences were observed in the OS among patients at low, intermediate or high IPI score, with an estimated OS projection of 95%, 78%, and 75%, respectively. FL had longer survival without evidence of residual disease (9-year EFS: 59%) as compared to SLL patients (8.8-year EFS: 17%); however, both groups had prolonged survival and no need of salvage treatment, as shown by the time to disease progression curve, projected to 66% and 62% for SLL and FL, respectively. The results indicate that hd-approach in low-grade lymphoma: (1) is associated with longer progression-free survival as compared to conventional therapies; (2) may imply higher tumor mass reduction in FL as compared to SLL patients; (3) offers long life expectancy, with potential survival benefits at least for patients at intermediate/high IPI score.     

滤泡性淋巴瘤的临床特点、预后及治疗

 滤泡性淋巴瘤的发生率居非霍奇金淋巴瘤发病率的第二位,临床上疾病发展呈惰性,主要表现为无痛性淋巴结肿大。预后因素包括滤泡淋巴瘤国际预后指数（FL IPI）、肿瘤组织免疫微环境。免疫化疗已成为滤泡淋巴瘤的一线治疗方法,滤泡淋巴瘤一经诊断即应开始治疗,观察等待策略仅限于少数选择病例。造血干细胞移植适用于复发、难治的病例。