Follicular Large Cell Lymphoma: An Aggressive Lymphoma That Often Presents With Favorable Prognostic Features

Blood ◽  
1999 ◽  
Vol 93 (7) ◽  
pp. 2202-2207 ◽  
Author(s):  
J. Rodriguez ◽  
P. McLaughlin ◽  
F.B. Hagemeister ◽  
L. Fayad ◽  
M.A. Rodriguez ◽  
...  

Abstract It is debated whether follicular large cell lymphoma (FLCL) has a clinical behavior that is distinct from indolent follicular lymphomas, and whether there is a subset of patients who can be potentially cured. We report here our experience with 100 FLCL patients treated at our institution since 1984 with three successive programs. We evaluated the predictive value of pretreatment clinical features, including two risk models, the Tumor Score System and the International Prognostic Index (IPI). With a median follow-up of 67 months, the 5-year survival is 72% and the failure-free survival (FFS) is 67%, with a possible plateau in the FFS curve, particularly for patients with stage I-III disease. Features associated with shorter survival included age ≥60, elevated lactic dehydrogenase (LDH) or beta-2-microglobulin (β2M), advanced stage, and bone marrow involvement. Stage III patients had significantly better survival than stage IV patients (P < .05). By the IPI and Tumor Score System, 80% of the patients were in the lower risk groups; both systems stratified patients into prognostic groups. Patients with FLCL have clinical features and response to treatment similar to that reported for diffuse large cell lymphoma. Prognostic risk systems for aggressive lymphomas are useful for FLCL. A meaningful fraction of patients may possibly be cured when treated as aggressive lymphomas.

Blood ◽  
1999 ◽  
Vol 93 (7) ◽  
pp. 2202-2207
Author(s):  
J. Rodriguez ◽  
P. McLaughlin ◽  
F.B. Hagemeister ◽  
L. Fayad ◽  
M.A. Rodriguez ◽  
...  

It is debated whether follicular large cell lymphoma (FLCL) has a clinical behavior that is distinct from indolent follicular lymphomas, and whether there is a subset of patients who can be potentially cured. We report here our experience with 100 FLCL patients treated at our institution since 1984 with three successive programs. We evaluated the predictive value of pretreatment clinical features, including two risk models, the Tumor Score System and the International Prognostic Index (IPI). With a median follow-up of 67 months, the 5-year survival is 72% and the failure-free survival (FFS) is 67%, with a possible plateau in the FFS curve, particularly for patients with stage I-III disease. Features associated with shorter survival included age ≥60, elevated lactic dehydrogenase (LDH) or beta-2-microglobulin (β2M), advanced stage, and bone marrow involvement. Stage III patients had significantly better survival than stage IV patients (P < .05). By the IPI and Tumor Score System, 80% of the patients were in the lower risk groups; both systems stratified patients into prognostic groups. Patients with FLCL have clinical features and response to treatment similar to that reported for diffuse large cell lymphoma. Prognostic risk systems for aggressive lymphomas are useful for FLCL. A meaningful fraction of patients may possibly be cured when treated as aggressive lymphomas.


1990 ◽  
Vol 8 (8) ◽  
pp. 1370-1379 ◽  
Author(s):  
R S Stein ◽  
J P Greer ◽  
J M Flexner ◽  
J D Hainsworth ◽  
R D Collins ◽  
...  

We reviewed the clinical and pathologic features in 186 patients with large-cell lymphomas seen at Vanderbilt University Hospital between 1970 and 1986. Ninety-two cases (49%) were large noncleaved-cell lymphoma (LNCCL), 61 cases (33%) were large-cleaved-cell lymphoma (LCCL), 17 cases (9%) were peripheral T-cell lymphoma (PTCL), and 16 cases (9%) were immunoblastic sarcoma of B cells (IBS-B). These subsets of large-cell lymphoma did not differ with respect to median age, distribution by stage, or incidence of bone marrow involvement. Significant differences between groups were noted with regard to male:female ratio, incidence of symptoms, incidence of extranodal disease, and pattern of adenopathy. However, when LCCL was excluded from the analysis, none of these differences were significant. By univariate analysis, age, stage, marrow involvement, extranodal disease, B symptoms, elevated serum lactic dehydrogenase (LDH), and diffuse pattern were unfavorable prognostic features in large-cell lymphoma. However, when cases were stratified by cell of origin, nodular versus diffuse pattern was of no prognostic significance. Nodularity was favorable only because 71% of nodular and nodular-diffuse cases were LCCL, while the majority of diffuse cases were LNCCL. Although IBS-B is considered a "high-grade" lymphoma, we found no evidence for inferior survival in these patients compared with LNCCL or LCCL. In fact, survival was better in IBS-B than in LNCCL or LCCL, although this difference was not significant. However, survival was significantly inferior in PTCL (median, 11 months) compared with the other subsets of large-cell lymphoma (median, 46 months; P = .038, log-rank test). Since the association of PTCL and an inferior survival has most often been noted in the context of "second-generation" chemotherapy, we believe that this association may be therapy-dependent and may be minimized by the use of more aggressive chemotherapy regimens.


2002 ◽  
Vol 20 (1) ◽  
pp. 197-204 ◽  
Author(s):  
Tamara N. Shenkier ◽  
Nicholas Voss ◽  
Randall Fairey ◽  
Randy D. Gascoyne ◽  
Paul Hoskins ◽  
...  

PURPOSE: To evaluate clinical outcome of patients with limited-stage diffuse large-cell lymphoma (DLCL) treated with three cycles of chemotherapy followed by involved-region irradiation (IRRT). PATIENTS AND METHODS: Adults with limited-stage DLCL were treated with brief doxorubicin-containing chemotherapy regimens between 1980 and 1998. IRRT was administered 3 to 4 weeks after the third chemotherapy treatment in a dose equivalent to 30 Gy in 10 fractions. RESULTS: Three hundred and eight patients (median age, 64 years) were included, and 299 experienced complete remission. After a median follow-up of 86 months, 64 patients developed progressive disease, and 104 patients died (43 from lymphoma, three from toxicity, and 58 from other causes). Actuarial overall and progression-free survival (PFS) rates were, respectively, 80% and 81% at 5 years and 63% and 74% at 10 years. For subgroups identified using the Miller modification of the International Prognostic Index (IPI), the overall survival rates at 5 and 10 years were, respectively, 97% and 89% (no factors), 77% and 56% (one or two factors), and 58% and 48% (three or four factors), and the 5-year and 10-year PFS rates were, respectively, 94% and 89% (no factors), 79% and 73% (one or two factors), and 60% and 50% (three or four factors). Men with testicular presentation, had a definitely inferior outcome. CONCLUSION: Long-term outcome with three cycles of doxorubicin-based chemotherapy and IRRT confirms that this is a successful approach for the majority of patients with limited-stage DLCL. Subgroups with worse prognoses can be identified, and these patients should be offered alternative treatment approaches.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10599-10599
Author(s):  
M. A. Rodriguez ◽  
S. Temple ◽  
L. Fayad ◽  
F. Hagemeister ◽  
P. McLaughlin ◽  
...  

10599 Background: The International Prognostic Index (IPI), the standard tumor risk model in patients (pts) with diffuse large cell lymphoma (DLCL), has 5 factors (age, LDH, performance status, extra nodal sites, and stage). We previously proposed a simpler two-factor model, based on LDH and B2M (JCO10;1989). B2M is a component of HLA class I antigens, expressed in lymphocytes, and a known prognostic indicator in some lymphoid malignancies. The benefits of this model are: objective measures; lab method widely available; simplicity; biologic marker. Methods: We applied the model to a large cohort of DLCL patients with prospective baseline B2M, and treated with doxorubicin-based (chemo) regimens, with and without rituximab. 718 pts with DLCL were sequentially treated at MDACC by IRB approved chemo protocols from 1988–2000. In 2001, rituximab plus chemo (RCHOP) became standard. 311 DLCL pts were sequentially treated with RCHOP from 2001–2005. Cox regression analyses for univariate and multivariate models of IPI factors and B2M were done. Kaplan-Meier survival projections were in three risk categories: low (normal [nl] LDH and B2M); intermediate (either LDH or B2M > nl); or high (LDH and B2M > nl). Results: In both treatment groups, IPI factors and B2M were significant as univariate factors. In the RCHOP group, however, the IPI multivariate model showed age, stage, and extra-nodal sites were not significant risk factors, while B2M and LDH remained highly significant (p<0.01). The 5 year survival projections by risk category were: (*) combines intermediate low and intermediate-high categories Conclusions: This simple two-factor model predicts risk for patients with DLCL, treated with or without rituximab, comparably to the IPI. B2M should be considered an important prognostic indicator in DLCL, particularly in rituximab treated patients. Exploratory analyses to revise the IPI model are indicated. [Table: see text] No significant financial relationships to disclose.


1992 ◽  
Vol 10 (2) ◽  
pp. 219-227 ◽  
Author(s):  
U Vitolo ◽  
M Bertini ◽  
E Brusamolino ◽  
G B Cavallero ◽  
B Comotti ◽  
...  

PURPOSE The prognosis of advanced-stage diffuse large-cell lymphoma (DLCL) has improved with the use of the third-generation regimens such as methotrexate with leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B). However, different results have been reported. Therefore, we started a cooperative study to confirm the efficacy of MACOP-B. An analysis of prognostic factors was also performed to identify poor-prognosis patients. PATIENTS AND METHODS Between June 1986 and March 1989, 180 patients with advanced-stage DLCL were treated with MACOP-B. MACOP-B was given according to the original scheme. Numerous clinical features possibly predictive for complete response (CR), disease-free survival (DFS), and survival were analyzed in univariate and multivariate analyses. RESULTS One hundred twenty-seven patients (71%) achieved a complete remission, 20 (11%) achieved a partial remission, 24 (13%) had unchanged or progressive disease, and nine (5%) died due to toxicity. With a median follow-up of 28 months, 71% of 127 CRs remain in first remission. Predicted 3-year survival for all 180 patients is 60%, and 3-year DFS for the 127 CRs is 67%. Overall toxicity was acceptable, with mucositis being the most frequent severe side effect. A multivariate regression analysis identified lactate dehydrogenase (LDH) level, bone marrow involvement, and tumor burden as independent risk factors for survival. These factors were also important for achievement of remission and DFS and allowed us to identify three distinct risk groups of patients with good, intermediate, and poor prognosis, with 3-year survival rates of 80%, 59%, and %29, respectively. CONCLUSIONS These results confirm the effectiveness of MACOP-B in advanced-stage DLCL at low or intermediate risk; however, high-risk patients are in urgent need of new therapeutic approaches. A better definition of prognostic features would allow a more reliable comparison of different treatment regimens, as well as an effective tailoring of therapy by prognostic groups.


1991 ◽  
Vol 9 (2) ◽  
pp. 236-242 ◽  
Author(s):  
L E Robertson ◽  
J R Redman ◽  
J J Butler ◽  
B M Osborne ◽  
W S Velasquez ◽  
...  

From 1975 to 1988, 50 patients with lymph node biopsy-documented diffuse large-cell lymphoma (DLCL) presented with bone marrow involvement. Twenty-four patients (48%) had large-cell lymphoma (LCL) in the bone marrow and were compared with 19 (38%) patients who had small cleaved-cell lymphoma (SCCL) in the marrow. Additionally, seven patients (14%) had mixed small- and large-cell lymphoma (ML) in the marrow. Patients who had LCL marrow involvement were younger (P less than .02) and more frequently had elevated lactic dehydrogenase (LDH) levels (P less than .001), high tumor burden (P less than .01), and more sites of extranodal disease (P less than .05) than those with SCCL in the marrow. The complete response (CR) rate to multiagent chemotherapy was 16.7% in the LCL group and 89.4% in the SCCL group (P less than .001). One third of the patients with LCL in the marrow developed CNS involvement, compared with only one patient in the SCCL group (P = .06). Overall 5-year survival was 79% in patients with SCCL marrow involvement, compared with only 12% in patients with LCL in the marrow (P = .002). Despite a high CR rate, patients with marrow involved by SCCL were at a high continuous risk of relapse with only a 30% failure-free survival at 5 years. We conclude that bone marrow involvement with LCL predicts for extremely poor prognosis with low response rate and short survival. Patients with SCCL in the bone marrow have a high rate of CR and a high rate of 5-year survival; however, there is a high risk of late relapse, and only 15% are in a continuous remission at 8 years.


2003 ◽  
Vol 14 (2) ◽  
pp. 273-276 ◽  
Author(s):  
J.K. Campbell ◽  
J.P. Matthews ◽  
J.F. Seymour ◽  
M.M. Wolf ◽  
S.K. Juneja

2020 ◽  
Author(s):  
Diwen Pang ◽  
Ling Huang ◽  
Xinmiao Jiang ◽  
Feili Chen ◽  
Hanguo Guo ◽  
...  

Abstract Background Relapsed/refractory (R/R) anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) respond to ALK inhibitors, but resistance bears a poor prognosis. No biomarkers predict a long duration of response to ALK inhibitors. The ALK gene was first identified as the fusion partner of the nucleophosmin (NPM1) gene in recurrent t(2;5)(p23;q35) found in an ALCL subset. However, several distinct ALK fusions that result in highly different characteristics have also been described in lymphomas. Methods We retrospectively reviewed 43 patients with pathologically confirmed ALK-positive ALCL at Guangdong Provincial People’s Hospital from February 2007 through February 2020, including seven R/R patients who received ALK inhibitors (six with crizotinib and one with alectinib). We performed next-generation sequencing (NGS) with paraffin-embedded tissue for these seven R/R patients and one patient with a peripheral blood sample. We evaluated clinical characteristics and survival status. Results The median age of all patients was 29 (range 15–66) years. Most patients were male with advanced stage and B symptoms. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 60% and 70%, respectively with a median follow-up of 52.2 (range 2.4–168.6) months. Multivariate analyses revealed that only bone marrow involvement was an independent prognostic factor for PFS (P = 0.03) and OS (P = 0.03). Of the seven R/R patients, the median line number of therapies was four (range 3–7) and that of ALK inhibitor usage was three (range 2–5). The overall response rate was 100% (n = 7). The NGS identified four patients with the NPM1-ALK fusion and two with tumor necrosis factor receptor-associated factor 1 gene (TRAF1)-ALK fusion; the latter quickly developed resistance to chemotherapy and ALK inhibitors. Conclusions ALK inhibitors improved survival of patients with R/R ALK-positive ALCLs. TRAF1-ALK fusion may predict a poor clinical outcome to chemotherapy and ALK inhibitors. This ALK fusion may reflect a trend toward the aggressive behavior of lymphomas.


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