scholarly journals Incidence, Risk Factors and Prognosis of Transformation in Follicular Lymphoma: a Multicentre Retrospective Analysis of 1763 Patients from the Geltamo Spanish Lymphoma Cooperative Group

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3944-3944 ◽  
Author(s):  
Sara Alonso* ◽  
Miguel Alcoceba* ◽  
Laura Magnano ◽  
Marcio Andrade ◽  
María García-Álvarez ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Follicular Lymphoma ◽  
Autologous Transplantation ◽  
B Cell Lymphoma ◽  
Aggressive Lymphoma ◽  
Prognostic Impact ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Abstract INTRODUCTION Follicular lymphoma (FL) may, over time, transform into an aggressive lymphoma, usually diffuse large B-cell lymphoma (DLBCL). Transformed follicular lymphomas (tFL) have a worse prognosis due to poorer response to treatment than primary DLBCL. The incidence of transformation is estimated in ~3% per year, although it varies largely between different studies (24%-70% overall). These differences are mainly due to different criteria to define tFL, to lack of evidence of tFL by biopsy, absence of clonality studies discarding secondary de novo NHL, studies performed in the pre-Rituximab era, or different follow-up times among studies. With all this pitfalls, the actual incidence of transformation remains an open question. The aim of the present study is to analyse the incidence and prognostic impact of transformation in patients with FL in a large retrospective series of the Spanish group of Lymphomas (GELTAMO). PATIENTS&METHODS A total of 1763 patients from 19 Spanish centres diagnosed of FL between 2000 and 2011 were recruited in the study. Data were obtained from the database of centres willing to participate in this study. True tFL (FL to DLBCL) were recorded. From the original cohort, FL IIIb, composite FL+DLBCL, discordant FL (FL in bone marrow and DLBCL in adenopathy or viceversa), and downgrading tFL (DLBCL at diagnosis and relapse of FL) were excluded. Patients with inadequate follow-up were not considered. Therefore, 1611 patients (grade I, II, and IIIa) were finally included. This study was approved by the Salamanca University Hospital Ethic Committee. RESULTS One hundred and ten patients (median follow up of 6 years) were transformed to DLBCL. Cumulative incidence of transformation at 5, 10, and 15 years was of 5%, 9%, and 14%, respectively. With a median follow up of 75.9 months (2 to 179), median time to transformation was 66 months, ranged 1-179. Considering survival from diagnosis of FL, tFL patients had a shorter OS than non-transformed (19% vs. 69%, p<0,0001). Most of the tFL patients (92%) have previously received treatment for FL, 63% of them with Rituximab. Median number of treatment lines before transformation was 2 (1-7). Factors influencing risk of tFL in the multivariate analysis included non-response to first line therapy (PR, p<0.001, HR:2,5 95% CI:1.5-4.2; others, p<0.0001, HR: 8,1 95% CI: 4.1-16.0), and FLIPI>2 (p=0.002, HR: 2,1 95% CI: 1.3-3.4). In the multivariate analysis, factors predicting decreased OS after transformation included non-achievement of CR after first line therapy (p<0,001, HR:4.3 95% CI:2-9.1), and elevated LDH at the moment of transformation (p=0,003, HR:3 95% CI:1.5-6.3). We analyzed separately the role of autologous stem cell transplantation (ASCT) in transformed FL patients. Patients that received ASCT were significantly younger (<70 years) p<0,001, had a better performance status (ECOG <2) (p=0,008) and had achieved a better response (CR) (p<0,001) than those who did not receive ASCT. All of them in our series were treated with rituximab based regimens at transformation. When we analyzed those patients that were eligible for ASCT (younger than 70), patients that received ASCT showed a better OS after transformation than those who did not (51% vs 26% at 5 years, p=0,004). Interestingly, patients who achieve CR to first line therapy at transformation did not beneficiate of ASCT (54% vs 66% at 5 years, p=0,8) while those who do not achieve CR did (50% vs 16% at 5 years, p=0,008). CONCLUSIONS In this series, one of the largest reported in the rituximab era, high risk FLIPI (>=2) and non-response to FL first line therapy were associated with a higher risk of transformation.Only non-response to transformed FL treatment therapy and a high LDH at transformation were associated with a worse OS after transformation in the multivariate analysis. Autologous transplantation in transformed patients could have a benefit in terms of OS after transformation, but after the introduction of immunochemotherapy strategies, perhaps patients responding to treatment after transformation do not beneficiate from this strategy. *Equal contribution; ‡Equal senior contribution Disclosures Sancho: CELLTRION, Inc.: Research Funding.

High-Dose Bi-Weekly THP-COP Induction Treatment Followed by High-Dose Therapy with Autologous Peripheral Blood Stem Cell Transplantation for Advanced-Stage Follicular Lymphoma as First-Line Therapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5207-5207
Author(s):  
Sadao Aoki ◽  
Jun Takizawa ◽  
Masutaka Higashimura ◽  
Akihito Momoi ◽  
Nobuhiro Tsukada ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Cell Transplantation ◽  
High Dose ◽  
Advanced Stage ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Abstract Introduction: Most patients with advanced-stage follicular lymphoma(FL) cannot be cured by conventional chemotherapy and have median survival of 7 to 10 years. High-dose chemotherapy (HDT) supported by autologous stem cell transplantation(ASCT) gives a survival benefit for patients with aggressive lymphoma. Recent several multicenter studies have shown that clinical and molecular remissions can be attained in patients with FL receiving intensified high-dose sequential chemotherapy and autografting. We have reported the efficacy and safety of high-dose bi-weekly THP-COP with G-CSF support (HDBW-TCOPG) for non-Hodgkin’s lymphoma. Therefore, we performed a pilot clinical trial to evaluate the efficacy and toxicity of HDBW-TCOPG followed by HDT with ASCT as first-line therapy in patients with advanced-stage FL. Patients and methods: Between August 1998 and December 2003, 10 Japanese patients with previously untreated FL from whom informed consent was obtained were included in this single-center pilot study. Median age was 48 years. All patients had stage 3 or 4 disease, aaIPI LI 8 and HI 2. Histological subtypes of FL included grade 1 4; grade 2 4; grade 3a 2. HDBW-TCOPG consisted of pirarubicin 70 mg/m2 on day 1; cyclophosphamide 1000 mg/m2 on day 1; vincristine 1.4 mg/m2 on day 1; predonisolone 50 mg/m2 from day 1 to 5; lenograstim 2.0 mg/kg/day from day 3. Five patients who enrolled after rituximab was approved for indolent B-cell lymphoma in Japan received induction therapy combined HDBW-TCOPG with rituximab 375mg/m2 on day -2 (R-HDBW-TCOPG). Six cycles were administered at intervals of two weeks. PBSC were collected during the later cycles of HDBW-TCOPG or on the recovery of high-dose etoposide regimen (500mg/m2 for 3 days) administered after the completion of HDBW-TCOPG. Leukaphereses were performed until a minimum of 2.0x106/kg CD34+ cells had been collected. The conditioning regimen consisted of ranimustine 200mg/m2 on day-7 and -2; paraplatin 300mg/m2 on day -6, -5, -4, -3; etoposide 500mg/m2 on day −5, −4, −3; cytarabine 2.5 g/m2 every 12 hours on day −2, −1 (MCE-CA regimen) in 2 patients or cyclophosphamide 50mg/kg on day −2, −1 (MCEC regimen) in 8 patients. Results: Sufficient numbers of PBSC were collected in 5 of 7 patients mobilized with HDBW-TCOPG and in all 5 patients with high-dose etoposide. The median time to reach total number of leukocytes of 1.0 x109/l was nine days (range 8–11). All 10 patients who were in PR at the end of HDBW-TCOP(G) achieved CR post APBSCT. After a median follow up of 36.6 months (range 7–66 months) PFS and OS are 90% and 90%, respectively, for all patients. One patient developed secondary myeloid leukemia with t(3;21) and died at 35 months after APBSCT without signs of recurrence of lymphoma. Another patient who relapsed at 35 months after transplantation. IgH or BCL2 rearrangement was detected by PCR analysis prior to therapy in three patients and one of them still showed detectable disease after HDBW-TCOPG induction. However, all three patients demonstrated MRD negativity after HDT with ASCT. Conclusion: HDBW-TCOPG as induction therapy followed by HDT with ASCT is feasible for advanced-stage FL with acceptable toxicity, and this short term highly intensified therapy may induce cure of the disease by minimizing MRD, but longer follow up is needed to evaluate the impact on survival.

Rituximab Fails to Reduce Histologic Transformation (HT) Rate of Follicular Lymphoma (FL) to Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 837-837 ◽  
Author(s):  
Ariel E Marciscano ◽  
Neel Gupta ◽  
Zhigang Zhang ◽  
Julie Teruya-Feldstein ◽  
Ariela Noy
Keyword(s):  
Follicular Lymphoma ◽  
Lower Risk ◽  
Cell Lymphoma ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
P Value ◽  
First Line ◽  
First Line Therapy ◽  
Large B Cell Lymphoma

Abstract Background: Histologic Transformation (HT) of indolent follicular lymphoma to aggressive lymphoma is a critical and sometimes fatal event in a patient’s disease course. It is unclear if rituximab influences HT. We have previously shown that single agent rituximab is used earlier in the disease course than traditional chemotherapy likely due to rituximab’s high therapeutic index (Cohler et al., ASH 2007). Others have shown rituximab also improves the complete response rate, disease free and overall survival of follicular lymphoma when used as a single agent and in combination with chemotherapy. Theoretically, this could reduce the disease burden over a patient’s lifetime and consequently the transformation rate. Methods: We retrospectively screened 3500 patients and identified 584 eligible patients at Memorial Sloan Kettering Cancer Center (MSKCC) with newly diagnosed, treatment naïve, indolent follicular lymphoma. We compared two cohorts of rituximab usage: 1998– 2000 and 2001–2006. In the former, patients received rituximab predominantly in the relapsed setting. In the latter, patients liberally received rituximab even as single agent first line therapy. Histologic transformation to diffuse large B cell lymphoma (DLBCL) was the primary study endpoint. All therapy was recorded. Results: Median follow-up time was 92 months for the 1998–2000 cohort and 41 months for the 2001–2006 cohort. Patients in the latter cohort received rituximab both earlier in the course of follow up and more often as a first line therapy. The median time from diagnosis to first rituximab was 21 months vs. 2 months, respectively. Rituximab was given alone or in combination as first line systemic therapy to 36% of the 1998–2000 cohort, but to 93% of the 2001–2006 cohort. The comparative risks of transformation between the two cohorts were not statistically significant (P-value = 0.41 by log rank comparison). The cumulative incidence of transformation 36 months after diagnosis was 8.1% for the 1998– 2000 cohort and 4.4% for the 2001–2006 cohort. Furthermore, patients receiving rituximab first line, either single agent or in combination, compared to patients receiving rituximab as salvage therapy, showed essentially no difference in risk of histologic transformation. (P-value = 0.68) Surprisingly, patients never receiving rituximab had a significantly lower risk of transformation than those who received rituximab at any point (p-value = 0.0095), however, these rituximab naïve patients had lower risk FLIPI scores accounting for the difference (p-value = 0.15). Notably, 173/584 patients never received systemic therapy, and 102 of these were expectantly monitored without any local therapy, such as radiotherapy or therapeutic surgery). None of these 102 patients had transformation within the first 36-months of follow up. Finally, we confirm Ginè et al.’s earlier finding that a higher risk FLIPI score confers a higher risk of transformation. (Annals of Oncology, 2006) For each unit increase of FLIPI risk score (e.g., 3 à 4), the probability of histologic transformation at any time point increases 1.72 fold. Moreover, high-risk FLIPI patients (3–5 risk factors) have a 3.3-fold increase in risk of HT (p-value <0.0001). Conclusions: Patients diagnosed with FL in 2001–2006 received rituximab earlier in their disease and more frequently than those diagnosed in 1998–2000. However, in contrast to our hypothesis, this did not translate to a lower risk of transformation for the 2001– 2006 cohort. The 36-month risk of transformation was lower in patients with lower FLIPI scores. This data supports the clinical decision to expectantly monitor low-risk FLIPI patients.

Re-Treatment with Rituximab Plus Chemotherapy in Patients with Aggressive Lymphoma Treated Previously with CHOP or CHOP-Like Combinations Plus Rituximab.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4707-4707 ◽  
Author(s):  
Andres Palacios ◽  
Mayda Navarrete ◽  
Laura Gallur ◽  
Javier Zuazu ◽  
Cristina Barrenetxea ◽  
...  
Keyword(s):  
Salvage Therapy ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Aggressive Lymphoma ◽  
Event Free Survival ◽  
Therapy Failure ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Abstract Introduction. CHOP plus Rituximab has become the standard treatment for patients with aggressive B-cell lymphoma - particularly DLBCL -, after having shown a better response rate and event free survival over CHOP. However, a number of patients are resistant or relapse (R/R) after a good response. The aim of this study is to assess the efficacy of different Rituximab-containing regimens as salvage therapy in refractory/relapsed (R/R) patients with aggressive lymphoma who had been treated with R-CHOP or R-CHOP-like regimens as first-line therapy. Patients and Methods. Thirty-six consecutive patients (34 evaluable for response) from the the same institution were reviewed. Twenty-five patients had diffuse large B-cell lymphoma, 4 mantle-cell lymphoma, and 7 Grade 3b follicular lymphoma. Patients received R-CHOP (n=21), DA-R-EPOCH (n=12) orR-Hyper-CVAD (n=3) as first-line therapy. The following salvage regimens were used in this study: R-ESHAP (n=1), R-ICE (n=10), R-TT (n=4), R-GemOx (n=13), Rituximab monotherapy (n=7), and R-MC (n=1). The first three of these regimens were considered ‘aggressive’ (AG) and the three remaining regimens were considered ‘less aggressive’ (LAG). Results. Median patient age was 59.6 years (range: 31–84 years). The overall response rate (ORR) was 53% (38% complete response [CR]; 15% partial response {PR]. CR directly correlated with IPI score at relapse or therapy failure. ORR was similar in both types of regimen, however the response quality (determined as % CR) was 45% with the LAG regimen and 22% with the AG regimen.With a median follow-up of 29 months the overall survival (OS) was 53% and the event free survival (EFS) was 22%. EFS correlated inversely with IPI at relapse or therapy failure (P=0.015) and directly with response to salvage therapy (P=0.0002). in addition, EFS was slightly higher in patients treated with LAG regimen (42% vs 20%); however this was not statistically significant. Conclusion. Some authors have hypothesised that ORR appears to decrease when patients who had previously received Rituximab + chemotherapy for first-line therapy were treated with Rituximab + chemotherapy as salvage therapy at relapse. However, our data indicate that responses to Rituximab + chemotherapy continue to occur in these patients. In addition, ‘aggressive’ salvage regimens do not achieve better responses. Large, prospective studies are requires in order to verify the findings of this study.

Lymphoma Patients Secondary to Congenital and Acquired Immunodeficiency Syndroms in a Turkish Pediatric Oncology Center

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5445-5445
Author(s):  
Nurdan Tacyildiz ◽  
Gulsah Tanyildiz ◽  
Gulsan Yavuz ◽  
Emel Unal ◽  
Handan Dincaslan ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Progressive Disease ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Lymphoproliferative Syndrome

Abstract PURPOSE An increased incidence of lymphoma is seen in various types of immune deficiency syndromes,including congenital immune deficiency diseases, organ transplantation with iatrogenic immunosuppression and autoimmune disorders. Prognosis of the lymphomas secondary to immunodeficiencies is stil poor. We aimed to analyse clinical features and treatment results of our patients that diagnosed as lymphoma and have immundeficiency syndrom. PATIENTS Between 2002-2014, we have seen 12 (7male, 5 female) childhood lymphoma that related immunodeficiencies. Ages of patients were between 4-15 years (median 8 years).The follow up period is 1-140 months (median: 38.5 months) and survival rate is %58. Five of patients died because of the progressive disease. The characteristics of patients are summarized in the table. TABLE- Clinical characteristics of patients Patient Age (year) Gender Diagnosis Follow up (months) Survival 1. G.C 10 Male T-NHL + AT 6 Alive (lost to follow up) 2. İ.D 4 Male T-NHL + ALPS 9 Eksitus 3. M.K 12 Female T cell rich B cell lymphoma+ CVID 2 Eksitus 4. S.K 9 Female B cell lymphoblastic lymphoma+AT 54 Alive 5. B.C 5 Male BL + Renal transplantation 1 Eksitus 6. S.K 7 Female BL + AT 6 Eksitus 7. C.G 12 Male BL + WAS 48 Eksitus 8. K.B 11 Female BL+EBV associated lymphoproliferative syndrome 29 Alive 9. M.Y 15 Female HL + CVID 140 Alive 10. B.Ç 4 Male HL + selective IgA deficiency 132 Alive 11. S.S 7 Male HL + AT 70 Alive 12. B.K 5 Male HL + AT 48 Alive TOTAL n = 12 4-15 years Median : 8 4 female 8 male 8 NHL (survival % 37.5) 4 HL (survival% 100) 1-140 months Median : 38.5 Survival %58 RESULTS Two of 5 Ataxia Telangiectasia (AT) patients diagnosed as Hodgkin's lymphoma (HL) while other three diagnosed as non-Hodgkin's lymphoma (NHL) (1 Burkitt's lymphoma-BL,1 B cell lymphoblastic lymphoma-BCLL,1 T-cell NHL). One of 2 common variable immunodeficiency (CVID) patient diagnosed as HL and the other one diagnosed T-cell rich B-cell lymphoma (TCRBCL). Wiscott-Aldrich syndome (WAS), autoimmune lymphoproliferative syndrome (ALPS ) and selective immunoglobulin A deficiency patients diagnosed as large B-cell lymphoma (LBCL), T-cell NHL and HL, respectively. In one patient, EBV associated BL developed secondary to renal transplantation. Another EBV associated BL patient has been diagnosed recently who has DNA instability defect. Follow-up period of patients were between 1-140 months (median 38.5 months). Almost half of the patients ( 42%) were diagnosed as BL,BCLL or TCRBCL. Although, survival of our patients for median 38.5 months is 58% (5 patients died with progressive disease) ,four of the 5 BL&TCRBCL patients have been died. Two patients who are living after BL and BCLL diagnosis in that group are treated with Rituximab as first line therapy. CONCLUSİON BL is most common lymphoma type in immundeficient lymphoma patients which may be subject for future research . Although special attention has been given to these patients, especially survival of BL lymphoma secondary to immunodeficiencies are poor. Special treatment modalities, like targeted terapies may be necessary as first line therapy to improve survival of these patients. Disclosures No relevant conflicts of interest to declare.

Progression of Follicular Lymphoma within 24 Months of First Treatment (POD -24) As a Predictor of Overall Survival - a Single Center Retrospective Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1534-1534
Author(s):  
Guy Bitansky ◽  
Elena Vasilev ◽  
Maya Zlotnick ◽  
Elena Ribakovsky ◽  
Ohad Benjamini ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Real World ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Early Progression ◽  
Progression Of Disease ◽  
Routine Imaging

Background: Follicular lymphoma (FL) is the most common indolent lymphoma in the western world with a median survival approaching 20 years. However, the course of the disease is extremely heterogeneous and therefore, at diagnosis it is difficult to predict survival. Roughly 20% of patients experience rapid progression of disease post first line treatment. Progression of disease within 24 months of first treatment (POD24) was previously identified a robust predictor of reduced overall survival (OS) (Casulo et al., JCO, 2015). Aims: We aimed to validate POD24 as a predictor of poor OS in a real-world cohort of patients, which was not uniformly treated, including patients that were initially treated with radiation or observed at least 6 months prior to first line therapy. Methods: We thoroughly reviewed 635 patient's records that were diagnosed between 1987 and 2018. Patients with FL grade 3B or de-novo transformation, as well as those that were never treated, treated prior to the rituximab era or had missing relevant clinical data were excluded. POD24 was defined as time from first therapy (systemic or radiation therapy) to first documented progression (either clinical or by imaging). Overall Survival was defined as time from diagnosis to either last follow-up or death. Progression Free Survival (PFS) was defined as the time from first treatment to first documented progression, death or last follow-up. Survival was analyzed with Kaplan-Meier method and comparison of survivals was done with Log-Rank test. Multivariate analysis was conducted with Cox regression. Results: A total of 317 patients met the study inclusion criteria and were included in our analysis. Median age was 57 (23-87), 162 (51%) were male and 155(49%) female .Median follow-up was 7.5 years (0.24-24.4). FLIPI (available in n=149) was high in 41 (27%) patients, intermediate in 37 (25%) and low in 71 (48%). Eighty seven patients (27.4%) received radiation as their first treatment and 86 (27%) were initially observed. Systemic therapy regimens included alkylator based regimens (n=152, RCHOP-88), bendamustine based (45), fludarabine Based (32), and Rituximab alone (2). Maintenance therapy administration was documented in 119 patients. Progression was documented in 133 (42%) patients, and transformation in 34 (11%). Thirty four patients (11%) deceased. Median OS was not reached in our study cohort, and median PFS was 109 months (CI:68-150). Early progression (POD24) was captured in 68 (21.5%) patients. The OS of those patients was significantly lower than those whom did not progress within 24 months of first therapy (figure 1A, p&lt;0.0001). High FLIPI score also predicted lower OS (p=0.001). In multivariate analysis both factors remained significant (POD24 p=0.013, FLIPI p=0.023). In the group of patients that were initially observed (86), 18 had early progression after first treatment. In this group, OS did not differ between the patients that had POD24 vs those who did not (p=0.095). The same was true for patients that had radiation as their first line therapy (p=0.36). The impact of POD24 on OS was observed in patients that were treated with alkylator based regimens (p=0.02) as well as with bendamustine based regimens (p=0.028). In the Fludarabine treated patients no significant difference in OS was observed in the different POD24 groups, probably due to small sample size. Interestingly, POD24 did not predict inferior OS in 69 patients in whom progression was diagnosed by routine imaging (PET/CT or CT) (Figure 1B). However, it was borderline predictive (p=0.1) when progression was clinically diagnosed (n=38). Conclusions: Our real-world analysis validated the importance of POD24 as predictor of OS in patients who were treated at diagnosis with alkylator or bendamustine based regimens. POD24 did not predict survival in patients treated with radiation or in those initially observed, a result that may reflect their superior outcome. Notably, POD24 did not predict OS in patients that were diagnosed with progression by routine imaging. As we, and others use imaging studies frequently in the follow-up of FL patients, especially in first two years after therapy, the scenario of positive findings in imaging is relatively frequent. Our data suggest that random findings in imaging that do not have clinical expression may not predict inferior outcome which is of major clinical implications. Disclosures No relevant conflicts of interest to declare.

Gray Zone Lymphoma (GZL) With Features Intermediate Between Classical Hodgkin Lymphoma (cHL) and Diffuse Large B-Cell Lymphoma (DLBCL): A Large Retrospective Multicenter Analysis Of Clinical Characteristics, Treatment, Outcomes, and Prognosis In The Current Era

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 847-847
Author(s):  
Andrew M Evens ◽  
Jennifer A. Kanakry ◽  
Laurie H. Sehn ◽  
Tatyana Feldman ◽  
Aimee Kroll ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Stage I ◽  
Stage Iii ◽  
Clinical Factors ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Mediastinal Involvement

Abstract Background The WHO recognizes a category of B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and cHL, which is commonly referred to as GZL. This is an uncommon entity that is reported to present primarily with mediastinal involvement; there is a paucity of data describing non-mediastinal presentations. Furthermore, treatment of this entity is challenging due to disease heterogeneity, lack of data regarding prognostication, and no standard guidelines for management. Methods We performed a multicenter retrospective analysis of newly diagnosed GZL patients (pts) treated from 2001-2012 at 18 North American academic centers. Inclusion criteria included availability of clinical information as well as minimum follow up of 12 months for non-relapsing pts. Diagnosis was established by institutional expert pathology review. We examined detailed pt characteristics, treatment and outcome, and we determined prognostic factors associated with survival on univariate and multivariate Cox regression analyses. Results 100 pts with GZL were identified; 4 were excluded for inadequate follow-up. Of 96 cases, median age was 39 years (19-86) with 23% of pts age ≥ 60 years; M:F ratio was 1.5:1. Clinical characteristics at diagnosis were as follows: 52% stage III/IV; 56% B symptoms; 89% ECOG PS 0-1; 38% elevated LDH; 31% hypoalbuminemia, 62% anemia; 13% bone marrow involvement; 24% bulky disease >10cm (26% stage I/II and 20% stage III/IV had bulk disease); and 23% of pts had IPI 3-5 and 18% IPS 4-7. Notably, 44% of pts presented with mediastinal involvement (MGZL), while 56% had systemic disease without mediastinal involvement (NMGZL). Compared with NMGZL, pts with MGZL were younger (37 vs 50 years, P<0.0001) and more frequently had stage I/II disease (77% vs 17%, P=0.0001). Further, MGZL had lower IPS (12% 3-7) and IPI scores (12% 3-5) compared with NMGZL (44% IPS 3-7, P=0.0002; and 33% IPI 3-5, P=0.0006). The most common first-line therapy for all pts was R-CHOP (n=48), followed by ABVD (n=25), R-EPOCH (n=10), CHOP (n=5), BEACOPP or hyperCVAD (n=5), and other (n=2); 69% of pts received rituximab as part of first-line therapy and 31% received consolidative radiotherapy (RT) (RT: 70% of MGZL and 13% of NMGZL). The overall response rate (ORR) to first-line therapy was 70% with 58% achieving a complete remission (CR); 27% of pts had primary refractory disease. While there was a trend for improved CR rate for pts who received rituximab as part of first-line therapy (65% vs 40% for those not receiving rituximab, P=0.07), there were no significant differences in response based on other individual treatment regimens or modalities. At a median follow-up of 25 months (8-109), the 2-year progression-free survival (PFS) and overall survival (OS) for all pts were 41% and 84%, respectively (Figure 1). PFS and OS were superior for pts with stage I/II disease compared with stage III/IV (PFS: 52% vs 32%, respectively, P=0.02; OS: 97% and 71%, respectively, P=0.001). On univariate analysis, clinical factors that predicted PFS and OS are detailed in Table 1. Interestingly, despite having lower risk features, the PFS or OS for MGZL did not differ from NMGZL. On multivariate regression analysis for PFS, elevated LDH was the only factor that predicted poorer outcome (HR 2.01 (95% CI 0.99-4.09), P=0.05). Several factors were significant for inferior OS including: presence of B symptoms (HR 17.41 (95% CI 1.53-197.57), P=0.02), hypoalbuminemia (HR 8.09 (95% CI 1.37-47.83), P=0.02), and stage 4 vs 1-3 disease (HR 21.39 (95% CI 2.90-157.74), P=0.003). Conclusions To the best of our knowledge, this is the largest series of GZL reported to date. We describe a new clinical subtype (NMGZL), which has distinct characteristics, but similar outcomes as MGZL. Within the limitations of a retrospective analysis, overall PFS appeared inferior to that observed in cHL and DLBCL, though OS was excellent, suggesting in part the success of salvage therapy. An elevated LDH was associated with worse PFS, while there were no differences seen based on clinical presentation or initial therapy. Further, there were several clinical factors identified (i.e., B symptoms, albumin, and stage) that strongly predicted OS. Continued examination both biologically and clinically of this unique subset of lymphoma is warranted. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Risk-adapted FDG–PET/CT-based follow-up in patients with diffuse large B-cell lymphoma after first-line therapy

2010 ◽  
Vol 21 (8) ◽  
pp. 1694-1698 ◽  
Author(s):  
U. Petrausch ◽  
P. Samaras ◽  
S.R. Haile ◽  
P. Veit-Haibach ◽  
J.D. Soyka ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
First Line ◽  
First Line Therapy ◽  
Large B Cell Lymphoma ◽  
Line Therapy ◽  
Pet Ct ◽  
Fdg Pet Ct ◽  
Large B Cell

Superiority of Double over Single Autologous Stem Cell Transplantation as First-Line Therapy for Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 536-536 ◽  
Author(s):  
Michele Cavo ◽  
Claudia Cellini ◽  
Elena Zamagni ◽  
Patrizia Tosi ◽  
Delia Cangini ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Complete Remission ◽  
Autologous Transplantation ◽  
High Dose ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Significant Difference ◽  
The Impact

Abstract The “Bologna 96” clinical trial was designed in an attempt to prospectively compare a single autologous transplantation (Tx-1) versus double autologous transplantation (Tx-2) as part of first-line therapy for patients with symptomatic multiple myeloma (MM) and less than 60 years of age. Tx-1 was given to support melphalan 200 mg/m2 (MEL-200); Tx-2 was given to support a first course of MEL-200 followed, within 3 to 6 months, by melphalan 120 mg/m2 + busulfan 12 mg/kg. In both arms of the study, autologous transplantation was preceded by 4 courses of VAD and subsequent collection of peripheral blood stem cells with high-dose cyclophosphamide 7 g/m2. An analysis was performed using an intent-to-treat approach on 228 patients who were randomly assigned to Tx-1 (n=115 patients, median follow-up of living patients: 45 months) or Tx-2 (n=113 patients, median follow-up of living patients: 54 months). In comparison with Tx-1, Tx-2 prolonged event-free survival (EFS) of 12 months (P=0.001) and time to progression (TTP) of 17 months (P=0.0001). Six-year projected probability of survival (OS) was 44% for Tx-1 and 63% for Tx-2 (P=0.3). The probability of attaining stringently defined complete remission (CR) or near complete remission (nCR) was 35% for Tx-1 and 48% for Tx-2; the sample size analyzed was not powered to detect a statistically significant difference between the two groups. Among patients randomized to Tx-1, attainment of CR or nCR was an essential prerequisite for extended OS (P=0.0001), EFS (P=0.000002) and TTP (P=0.000007). At the opposite, the benefits of double autologous transplantation were the greatest among patients who failed at least nCR. In particular, patients who did not attain CR or nCR after the first autologous transplantation and by study randomization received a second transplantation had a significantly longer duration of OS (P=0.01), EFS (P=0.000006) and TTP (P=0.000001) than patients who had the same response status but were assigned to receive a single autologous transplantation. Compared to Tx-1, Tx-2 significantly extended OS (P=0.04), EFS (P=0.000006) and TTP (P=0.000001) also among patients who failed Cr or nCR after receiving the entire treatment program to whom they were assigned (Tx-1 or Tx-2). At the opposite, for patients who were in CR or nCR after the first transplantation, there was no significant benefit from receiving a second autologous transplantation. In conclusion, data from the present analysis show that in comparison with a single autologous transplantation, i) double transplantation significantly prolonged EFS and TTP among younger (< 60 years) patients with previously untreated MM; ii) double autologous transplantation was of particular benefit for patients who failed at least nCR. Mature data derived from the final analysis of the study must be awaited before definite conclusions can be given concerning the impact of double autologous transplantation on the outcome of patients with MM. Supported by Università di Bologna, Progetti di Ricerca ex-60% (M.Cavo); Ministero dell’Università e Ricerca Scientifica, progetto FIRB, RBAU012E9A_001 (M. Cavo); and Fondazione Carisbo.

Evaluation in the Context of Daily Practice of Follicular Lymphoma patients' Outcome Before and After Approval of Rituximab in First Line Therapy in This Indication: Results of a Retrospective Analysis of 247 Unselected Patients with a 5-Year Median of Follow-up,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3698-3698
Author(s):  
Emmanuelle Nicolas Virelizier ◽  
Celine Segura-Ferlay ◽  
Izabela-Irina Domnisoru ◽  
Philippe Rey ◽  
Thérèse Gargi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Follicular Lymphoma ◽  
Retrospective Analysis ◽  
Response Rate ◽  
Daily Practice ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Before And After

Abstract Abstract 3698 Background: Randomized trials had demonstrated that rituximab improved outcome in newly diagnosed follicular lymphoma (FL) and this anti-CD20 monoclonal antibody was approved in France since 2004 in combination of chemotherapy (CT) for LF in first line therapy. As these results were obtained in selected patients with strict inclusion and exclusion criteria used in clinical trials, whether the improvement of patient's outcome is valuable in unselected population of FL patients with various medical history, different CT regimens is questionable. We performed a retrospective analysis to evaluate if the management and the outcome of FL have significantly changed in our institution before and after rituximab approval in 2004. Patients and Methods: all adult patients referred for first line LF were included and separated into cohort 1 diagnosis between 1996 and 2003 (103 patients) and cohort 2 between 2004 and 2010 (144 patients). Baseline clinical and biological datas, Follicular Lymphoma International prognostic Index (FLIPI), type of therapy, treatment response, progression free survival (PFS) and overall survival (OS) were compared. Results: There were no statistical differences in patients' characteristics between the 2 cohorts, including FLIPI score. In cohort 2, 71% received in first line therapy a rituximab based regimen (19% in monotherapy and 52% with CT). In cohort 1, 58% of patients were treated with CT and 10% with rituximab, 2% in monotherapy and 8% in combination with CT. Response rate were significantly improved in cohort 2 compared to cohort 1: complete response rate was 74.3% versus 57.8%, P <.001. With a median follow-up of 115.5 and 46.5 months in cohort 1 and 2, the 2-year PFS was 67% for cohort 1 and 82% for cohort 2 (P =.0039), respectively. The 2-year OS was also improved between the two periods (98% versus 87%, P =.0007). We could confirm the prognostic value on OS of the FLIPI score in whole series, in cohort 1 before the rituximab era but not in cohort 2. In fact, the 2-year OS was respectively 100% in low risk, 98% in intermediate risk and 95% in high risk (P =.14)/ Conclusions: These datas confirms the improvement of FL patients' outcome observed in clinical trials after the approval of rituximab in first line therapy prescript in a context of daily practice whatever age, medical history, and type of CT. Disclosures: No relevant conflicts of interest to declare.

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