Prognostic value of the age-adjusted International Prognostic Index in chemosensitive recurrent or refractory non-Hodgkin's lymphomas treated with high-dose BEAM therapy and autologous stem cell transplantation.

High-dose therapy (HDT) is now recommended for patients under 60 years of age with chemosensitive relapsed aggressive non-Hodgkin's lymphoma. However, approximately half of these patients will be cured by HDT. Prognostic factors are needed to predict which patients with chemosensitive lymphoma to second-line therapy could benefit from HDT. We retrospectively investigated the prognostic value of the widely used age-adjusted International Prognostic Index (AA-IPI) calculated at the time of relapse (35 patients) or just before second-line salvage therapy for primary refractory disease (5 patients). The median age was 51 years (range 18-64 years). Thirty-six patients had diffuse large B-cell lymphoma. Salvage cytoreductive therapy before HDT was DHAP/ESHAP (cytarabine, cysplatin, etoposide, steroids) in 17 patients, VIM3-Ara-c/MAMI (high-dose cytarabine, ifosfamide, methyl-gag, amsacrine) in 17 patients, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or reinforced CHOP in 4 patients, high-dose cyclophosphamide and etoposide in 2 patients. The HDT regimen consisted of BEAM (carmusine, cytarabine, etoposide, melphalan) in all cases. Eleven patients were in partial remission and 29 in complete remission at the time of HDT. Ten patients had an IPI >1, 16 had relapsed early (<6 months after first-line therapy) or disease was refractory to first-line therapy (5 of the 16 patients). The median follow-up was 6.07 years (range 1.24-9.74 years). Overall survival was not statistically different in patients with refractory disease or in those who relapsed early compared with late failures (>6 months after first-line chemotherapy) (P=1), but the AA-IPI >1 was associated with a poor outcome (P=0.03). In conclusion, the AA-IPI could have a prognostic value in patients with chemosensitive recurrent lymphoma treated with BEAM HDT.     

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.     

Impact of Conditioning Regimen on Outcome of 2-Year Disease-Free Survivors of Autologous Stem Cell Transplantation for Hodgkin Lymphoma

BackgroundAutologous stem cell transplantation is the standard of care for patients with relapsed HL and the long-term outcomes for survivors 2 years after ASCT have not been well described. No prospective trials have compared the effect of different conditioning regimens on outcomes.Patients and MethodsWe searched the Nebraska Lymphoma Study Group database to identify patients with HL who received ASCT from 1984 to 2007. Patients were conditioned with either CBV (cyclophosphamide, carmustine, and etoposide) or BEAM (carmustine, etoposide, cytarabine, and melphalan).ResultsAt a median follow-up of 8 (range, 2-26) years, 225 patients were alive and disease-free 2 years after ASCT. Analysis was limited to these patients. At 5 years, the progression-free survival (PFS) was 92% for BEAM and 73% for CBV (P = .002) and the overall survival (OS) was 95% for BEAM and 87% for CBV (P = .07). At 10 years, the PFS was 79% for BEAM and 59% for CBV (P = .01) and the OS was 84% for BEAM and 66% for CBV (P = .02).ConclusionPatients with HL who are disease-free and alive 2 years after ASCT have favorable outcomes. We observed lower risk of progression and longer survival associated with use of BEAM vs. CBV. Patients in the BEAM group received a transplant in more recent years so we cannot exclude the possibility that the superior outcomes seen in the BEAM group are because of better supportive care, use of peripheral blood stem cell grafts, or improvements in salvage therapies before transplantation.     

Favorable Long-Term Outcomes with Autologous Stem Cell Transplantation for High-Risk Multiple Myeloma Patients with a Positive Result On 18F-FDG PET/CT at Baseline

Background18F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) is a useful tool for identifying high-risk features in patients with newly diagnosed multiple myeloma (NDMM). This study evaluated the role of autologous stem cell transplantation (ASCT) in patients presenting with positive results on PET/CT scans.Materials and MethodsThe medical records of 210 patients who underwent PET/CT at diagnosis were retrospectively reviewed. Eligible patients for transplantation proceeded to upfront ASCT with high-dose chemotherapy (HDT) after induction therapy with novel agents.ResultsThe presence of a number of focal lesions (FL) >3 and extramedullary disease (EMD) occurred in 111 and 35 patients, respectively. ASCT was performed in 54 patients. Among patients with FL > 3, those treated with ASCT showed a prolonged 2-year progression-free survival (PFS) and overall survival (OS) rates compared to those not treated with ASCT (PFS, 60.2% vs. 23.5%, P < 0.001; OS, 91.7% vs. 63.6%, P = 0.005). In patients with FL ≤ 3, treatment by ASCT was associated with a higher 2-year PFS rate than no treatment by ASCT (74.0% vs. 54.9%, P = 0.040). The OS of patients treated with ASCT was not significantly longer than that of patients not treated with ASCT (P = 0.115). In multivariate analysis, FL > 3, Revised International Staging System (R-ISS), and upfront ASCT were independent prognostic factors for PFS and OS.ConclusionPresenting FL > 3 on baseline PET/CT represents a high-risk feature in patients with NDMM. Frontline ASCT with HDT prolonged the survival of patients with FL > 3.     

Chemoresistance can be overcome with high-dose chemotherapy and autologous stem-cell transplantation for relapsed and refractory Hodgkin lymphoma

BackgroundHigh-dose therapy and autologous stem-cell transplant (HDT/ASCT) is the preferred treatment of chemosensitive relapsed/refractory Hodgkin lymphoma (HL). The role for HDT/ASCT in chemoresistant HL is less well defined. We evaluated long-term outcomes of relapsed/refractory HL patients whose disease was refractory to secondary chemotherapy preceding HDT/ASCT.Patients and methodsAll HL patients who underwent HDT/ASCT in British Columbia for primary progression (PP, defined as progression within 3 months of initial therapy completion) or first relapse (REL1) were reviewed. Patients were grouped based on response to secondary chemotherapy as sensitive (S), resistant (R), and untested/unknown (U).ResultsA total of 256 patients underwent HDT/ASCT for PP (35%) or REL1 (65%) between 1985 and 2011. At median follow-up of 11.7 years, 58% were alive without HL, 36% relapsed; 6% died of transplant-related mortality, 3% secondary malignancies, and 3% unrelated causes. For PP/S, PP/R, and PP/U groups, 10-year FFS were 47%, 31%, and 38%; 10-year OS were 52%, 29%, and 37%, respectively. For REL1/S, REL1/R, and REL1/U groups, 10-year FFS were 64%, 51%, and 81%; 10-year OS were 71%, 59%, and 79%, respectively. In multivariate analysis, resistance to secondary chemotherapy predicted for post-transplant mortality in the PP (P = 0.04) but not REL1 (P = 0.16) groups.ConclusionIn this large uniformly treated cohort of HL patients with long-term follow-up, chemoresistance preceding HDT/ASCT was identified as a poor prognostic factor; however, this factor can be partially overcome by HDT/ASCT, resulting in cure in 30%–50% of patients. HDT/ASCT should therefore be considered in all transplant eligible patients, regardless of responsiveness to salvage chemotherapy.     

Stem-cell transplantation in T-cell non-Hodgkin’s lymphomas

BackgroundT-cell lymphomas are a heterogeneous group of non-Hodgkin’s lymphomas (NHLs). With the exception of anaplastic lymphoma kinase protein-positive large-cell lymphoma, standard chemotherapy provides dismal long-term outcomes when compared with NHLs with B-cell immunophenotype.DesignWe review the literature on the role of high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) in T-cell NHLs both as up-front treatment and in the salvage setting. The role of allogeneic transplantation will also be reviewed.ResultsResults from five prospective, nonrandomized and six retrospective studies evaluating the role of HDT and ASCT in the up-front setting show that patients in first complete or partial remission especially those who present with advanced disease and high prognostic index of peripheral T-cell lymphoma score may benefit from this approach. In the relapsed and/or refractory setting, most series show results that are comparable with those seen in patients with B-cell lymphomas if transplanted with chemosensitive disease. There is limited evidence to suggest that an immune-mediated graft-versus-lymphoma effect may result in long-term disease remissions in some patients after allogeneic transplantation.ConclusionsRandomized studies comparing HDT and ASCT with conventional chemotherapy are needed in T-cell lymphomas.     

The impact of total body irradiation on the outcome of patients with follicular lymphoma treated with autologous stem-cell transplantation in the modern era: a retrospective study of the EBMT Lymphoma Working Party

BackgroundThe aim of this study was to investigate the impact of the high-dose regimen on the outcome of patients with follicular lymphoma (FL) having had autologous stem-cell transplantation (ASCT) in a recent time period.PatientsBetween 1995 and 2007, 2233 patients with FL had their first ASCT with either a total body irradiation (TBI)-containing regimen or carmustin, etoposide, cytarabine and melphalan (BEAM), of which 47% were autografted in first remission.ResultsAfter a median observation time of 73 months (interquartile range 30–107), 5- and 10-year non-relapse mortality (NRM) was similar (6% and 10% in both groups). No significant NRM differences became evident after multivariate adjustment for confounders. Secondary malignancies were observed in 9.7% and 7.9% of the patients after TBI and BEAM (P = 0.19), which were treatment-related myelodysplastic syndromes/acute myelogenous leukaemia (t-MDS/AML) in 3.4% and 2.8% (P = 0.57). The median time to t-MDS/AML was around 50 months in both groups. Because of a lower relapse incidence, TBI was associated with better event-free survival reaching statistical significance in the patients transplanted in first remission but not in those transplanted beyond first remission.ConclusionsIn patients with FL who received TBI-based ASCT after 1995 increased NRM and t-MDS/AML risks did not emerge compared with BEAM while disease control was at least equivalent.     

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.     

High-dose therapy with autologous stem-cell transplantation (ASCT) after?first progression prolonged survival of follicular lymphoma patients?included?in the prospective GELF 86 protocol

Background:Among the 566 patients with follicular lymphomas (FL)included in the GELF 86 prospective trials from October 1986 to September1995, 372 with progressive/relapsing disease were analyzed retrospectively toidentify prognostic factors at first relapse. Patients and methods:For progressive FL, patients received mono-(22%) or polychemotherapy (78%) followed by high-dose therapy(HDT) with ASCT for 83 patients (22%). The median time toprogression from initial treatment was 23 months (range 3–102 months)and 24% of documented patients (52 of 217) had histologicaltransformation (HT). Salvage therapy produced an overall response in64% of patients and the five-year survival from progression was42%. Results:For patients who underwent HDT with ASCT compared tostandard treatment, five-year freedom from second failure was at 42%vs. 16% (P = 0.0001) and five-year survival was58% vs. 38% (P = 0.0005), respectively. Thebenefit of HDT and ASCT remained if we consider only patients less than 65years (five-year survival at 60% vs. 40%; P =0.001). Multivariate analysis of parameters significant according tounivariate analysis found that no ASCT at first progression, age at relapse>50 years, progression on-therapy were adversely significant onsurvival. Conclusions:HDT with ASCT compared to standard treatmentprolonged remission and survival after first progression of FL patients.     

The pretransplant Follicular Lymphoma International Prognostic Index is associated with survival of follicular lymphoma patients undergoing autologous hematopoietic stem cell transplantation

We retrospectively evaluated the association of the Follicular Lymphoma International Prognostic Index (FLIPI) and other characteristics with survival following high-dose therapy and autologous stem cell transplantation (ASCT) in 207 consecutive follicular lymphoma (FL) patients. The FLIPI was associated with OS both when evaluated as a categorical variable (0 - 1 vs. 2 vs. 3 vs. 4, p = 0.01, global test) and a continuous linear variable (p = 0.002). The association of FLIPI with survival appeared to be more relevant for patients who received standard conditioning regimens compared to those that were treated with high-dose radioimmunotherapy (p = 0.004). Among all patients, mortality was also associated with chemosensitive disease (HR = 0.47, p = 0.01) or untreated relapse (HR = 0.20, p = 0.0002) vs. chemoresistant disease, and ≥2 extranodal sites (HR = 2.82, p = 0.03) after adjusting for FLIPI. These data suggest that the FLIPI and select non-FLIPI factors after adjustment for the FLIPI are associated with survival in FL patients undergoing ASCT.     

Outcomes of Transplant-Eligible Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma After Second-Line Salvage Chemotherapy: The Gustave Roussy Experience

IntroductionAfter failure of frontline therapy, patients with relapsed/refractory diffuse large B-cell lymphoma (RR-DLBCL) that does not respond to first-line salvage chemotherapy can be recommended second-line salvage chemotherapy. The available literature in this regard is weak, although many centers routinely offer this type of second-line salvage chemotherapy to their patients.Patients and MethodsThis retrospective study included transplant-eligible patients with RR-DLBCL treated at Gustave Roussy between January 2008 and April 2020. Eligible patients were those who received second-line salvage chemotherapy using R-DHAP or R-ICE in patients who experienced an insufficient partial response, stable disease, or progressive disease in response to first-line salvage chemoimmunotherapy using an alternative regimen.ResultsForty-six RR-DLBCL patients received second-line salvage regimen, which yielded an objective response rate of 33%, median progression-free survival of 2.1 months, and overall survival of 11.4 months. Twelve patients proceeded to autologous stem-cell transplantation (ASCT), of whom 70% remained alive 1 year after ASCT. To explore the impact of transplantation, a multivariate analysis (excluding response to the first-line salvage regimen because this covariate was totally embedded within the transplantation covariate), ASCT was associated with progression-free survival (hazard ratio = 0.16; 95% confidence interval, 0.06-0.42) and overall survival (hazard ratio = 0.27; 95% confidence interval, 0.08-0.88).ConclusionSecond-line salvage chemotherapy with R-DHAP or R-ICE followed by ASCT leads to a favorable outcome in almost one third of patients with RR-DLBCL and offers a median overall survival of approximately 1 year. These data support the administration of second-line salvage chemotherapy followed by ASCT.     

Clinical characteristics and outcomes of relapsed follicular lymphoma after autologous stem cell transplantation in the rituximab era

High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a therapeutic option for patients with relapsed follicular lymphoma (FL). The clinical characteristics and outcomes of FL relapse after ASCT in the rituximab era have not yet been fully elucidated. We retrospectively reviewed 414 FL patients treated with ASCT between 2000 and 2014 in four hematology departments. All patients received rituximab as a first-line treatment. We specifically analyzed the clinical characteristics, treatment strategies at relapse, and outcomes of 95 patients (23%) who relapsed after ASCT. The patients (median age, 57 y) received a median of two lines of therapy (range, 2-6) prior to ASCT, with 92% in complete response (CR) or partial response (PR) before ASCT. Histological transformation at relapse after ASCT was observed in 20% of the patients. Treatment at relapse after ASCT consisted of chemotherapy with or without rituximab (n = 45/90, 50%), targeted agents (18%), rituximab monotherapy (14%), or consolidation allogeneic transplantation after induction chemotherapy (12%) and radiotherapy (6%). After relapse, the median progression-free survival (PFS) and overall survival (OS) were 1 year (95% CI, 0.541-1.579) and 5.5 years (95% CI, 1.910-9.099), respectively. In the multivariate analysis, histological transformation (HT) was associated with OS (P = .044; HR 2.439; 95% CI, 1.025-5.806), and a high FLIPI score at relapse was associated with PFS (P = .028; HR 2.469; 95% CI, 1.104-5.521). This retrospective study showed that the period of PFS of patients who relapsed after ASCT is short. A biopsy should be performed for these patients to document the HT. Our results indicate that new treatment strategies will need to be developed for these patients.     

Life expectancy of young adults with follicular lymphoma

BackgroundThis study was aimed at investigating the clinical features and outcomes of follicular lymphoma (FL) patients younger than 40 years, which have not been extensively investigated yet.Patients and methodsOne hundred and fifty-five patients younger than 40 years were retrospectively studied from a series of 1002 FL patients diagnosed in four different European Oncology Centres (Barcelona, Spain; Bellinzona, Switzerland; London, UK; Novara, Italy) from 1985 to 2010.ResultsPatients younger than 40 had a lower incidence of elevated LDH, high beta2-microglobulin, and a high-risk Follicular Lymphoma International Prognostic Index (FLIPI) score, whereas bone marrow involvement and bulky and disseminated lymphadenopathy were more frequent. At a median follow-up of 10 years, younger patients, in comparison with those older than 40, had significantly better overall (OS), cause-specific survival (CSS), and progression-free survival (PFS), with 10-year OS rate of 81% versus 51% (P < 0.0001), 10-year CSS rate of 82% versus 60% (P < 0.0001), and 10-year PFS of 39% versus 24% (P = 0.0098). However, there were no significant CSS and PFS differences in comparison with the patients aged 40–60. In multivariate analysis, having the lymphoma diagnosed in the last two decades and a favourable FLIPI score were associated with a significantly longer PFS and CSS in younger patients, whereas only FLIPI retained statistical significance for OS.ConclusionsIn our series, FL patients younger than 40 have a median OS of 24 years and their outcome seems to be improving over time. However, they still have a significantly shorter life expectancy than that of an age-matched general healthy population.     

The use of FDG-PET in the initial staging of 142 patients with follicular lymphoma: a retrospective study from the FOLL05 randomized trial of the Fondazione Italiana Linfomi

BackgroundThe role of [¹⁸F] fluorodeoxyglucose (FDG)-positron emission tomography (PET) in follicular lymphoma (FL) staging is not yet determined.Patients and methodsThe aim of the present study was to investigate the role of PET in the initial staging of FL patients enrolled in the FOLL05-phase-III trial that compared first-line regimens (R-CVP, R-CHOP and R-FM). Patients should have undergone conventional staging and have available PET baseline to be included.ResultsA total of 142 patients were analysed. PET identified a higher number of nodal areas in 32% (46 of 142) of patients and more extranodal (EN) sites than computed tomography (CT) scan. Also, the Follicular Lymphoma International Prognostic Index (FLIPI) score increased in 18% (26 of 142) and decreased in 6% (9 of 142) of patients. Overall, the impact of PET on modifying the stage was highest in patients with limited stage. Actually, 62% (15 of 24) of cases with limited disease were upstaged with PET.ConclusionsThe inclusion of PET among staging procedures makes the evaluation of patients with FL more accurate and has the potential to modify therapy decision and prognosis in a moderate proportion of patients. Further prospective clinical trials on FL should incorporate PET at different moments, and the therapeutic criteria to start therapy should be re-visited in the views of this new tool.     

Predictive value of Follicular Lymphoma International Prognostic Index (FLIPI) in patients with follicular lymphoma at first progression.

BACKGROUND: Different prognostic scores have been proposed to predict the outcome of follicular lymphoma (FL) patients at diagnosis. A new prognostic index specifically addressing FL patients, the Follicular Lymphoma International Prognostic Index (FLIPI), has recently been developed, which might also be useful in patients with progression. PATIENTS AND METHODS: One hundred and three patients (55 male, 48 female; median age 59 years) with FL in first relapse/progression after an initial response to therapy (50 complete responders/ 53 partial responders) were included in the study. RESULTS: Five-year survival from progression (SFP) was 55% (95% confidence interval 44%-66%). The distribution according to the FLIPI at relapse was 39% good prognosis, 24% intermediate prognosis and 37% poor prognosis. Five-year SFP for these groups were 85%, 79% and 28%, respectively (P < 0.0001). Other variables at relapse with prognostic significance for SFP were age, presence of B symptoms, performance status, bulky disease, number of involved nodal sites, lactate dehydrogenase level, hemoglobin level, histological transformation, the Italian Lymphoma Intergroup prognostic index for FL and the International Prognostic Index for aggressive lymphomas. In the multivariate analysis bulky disease (P=0.01), presence of B symptoms (P=0.03) and FLIPI at relapse (P=0.0003) were the most important variables for predicting SFP. CONCLUSIONS: In patients with FL at first relapse/progression, the FLIPI, along with the presence of bulky disease and B symptoms, are features that predict SFP and thus could be useful to select candidates for experimental treatments.     

Durable complete responses from therapy with combined epratuzumab and rituximab: final results from an international multicenter, phase 2 study in recurrent, indolent, non-Hodgkin lymphoma

BACKGROUND: In this international, multicenter trial, the authors evaluated rituximab (anti-CD20) plus epratuzumab (anti-CD22) in patients with postchemotherapy relapsed/refractory, indolent non-Hodgkin lymphoma (NHL), including long-term efficacy. METHODS: Forty-nine patients with follicular NHL (FL) (N = 41) or small lymphocytic lymphoma (SLL) (N = 7) received intravenous epratuzumab 360 mg/m2 and then intravenous rituximab 375 mg/m2 weekly x4. The regimen was tolerated well. RESULTS: Twenty-two of 41 patients with FL (54%) had an objective response (OR), including 10 (24%) complete responses (CR) (CR/unconfirmed CR [CRu]), whereas 4 of 7 patients with SLL (57%) had ORs, including 3 (43%) with CR/CRu. Rituximab-naive patients (N = 34) had an OR rate of 50% (26% CR/CRu rate), whereas patients who previously responded to rituximab (N = 14) had an OR rate of 64% (29% CR/CRu rate). An OR rate of 85% was observed in patients with FL who had Follicular Lymphoma International Prognostic Index (FLIPI) risk scores of 0 or 1 (N = 13), whereas 28 patients with intermediate or high-risk FLIPI scores (> or =2) had an OR rate of 39% (18% CR/CRu rate). In patients with FL, the median response duration was 13.4 months, and that duration increased to 29.1 months for 10 patients who had a CR/CRu, including 4 patients who had durable responses with remissions that continued for >4 years. In patients with SLL, the median response duration was 20 months, including 1 patient who had a response that continued for >3 years. CONCLUSIONS: The combination of epratuzumab and rituximab induced durable responses in patients with recurrent, indolent NHL.     

Assessing the Effectiveness of Treatment Sequences for Older Patients With High-risk Follicular Lymphoma With a Multistate Model

BackgroundDisease progression within < 2 years of initial chemoimmunotherapy and patient age > 60 years have been associated with poor overall survival (OS) in follicular lymphoma (FL). No standard treatment exists for these high-risk patients, and the effectiveness of sequential therapies remains unclear.Patients and MethodsWe studied the course of FL with first-, second-, and third-line treatment. Using large population-based data, we identified 5234 patients with FL diagnosed in 2000 to 2009. Of these patients, 71% had received second-line therapy < 2 years, and 29% had received no therapy after first-line therapy, with a median OS of < 3 years. Treatment included rituximab, R-CVP (rituximab, cyclophosphamide, vincristine), R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine), R-Other (other rituximab-containing), and other regimens. The Aalen-Johansen estimator and Cox proportional hazards models were used to quantify the outcomes and assess the effects of the clinical and sociodemographic factors.ResultsR-CHOP demonstrated the most favorable 5-year OS among first- (71%), second- (55%), and third-line (61%) therapies. First-line R-CHOP improved OS (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.50-0.64) and reduced the mortality risks after first-line (HR, 0.60; 95% CI, 0.47-0.77), second-line (HR, 0.40; 95% CI, 0.29-0.53), and third-line (HR, 0.63; 95% CI, 0.53-0.76) treatments. B-symptoms, being married, and histologic grade 1/2 were associated with the use of earlier second-line therapy. Early progression from second- to third-line therapy was associated with poor OS. The repeated use of R-CHOP or R-CVP as first- and second-line treatment yielded high 2-year mortality rates (R-CHOP + R-CHOP, 17.3%; R-CVP + R-CVP, 21.1%).ConclusionOur multistate approach assessed the effect of sequential therapy on the immediate and subsequent treatment-line outcomes. We found that R-CHOP in any line improved OS for patients with high-risk FL.     

Risk of hepatitis B reactivation and the role of novel agents and stem-cell transplantation in multiple myeloma patients with hepatitis B virus (HBV) infection

BackgroundThe purpose of the study is to analyse the prevalence of hepatitis B virus (HBV) infection and its incidence of reactivation among multiple myeloma (MM) patients treated in the era of novel therapy in an endemic Asian setting.Patients and methodsFrom 2000 to 2008, 273 patients with newly diagnosed MM were screened for the presence of hepatitis B virus surface antigen and HBV core antibody. HBV-infected patients were prospectively followed for reactivation with serial monitoring of serum alanine transferase and HBV DNA load. The patterns of HBV reactivation in relation to treatment received, exposure to high-dose therapy with autologous stem-cell transplantation (HDT/ASCT) and novel agents were studied.ResultsThe prevalence of HBV infection was 5.5%. Three cases of HBV reactivation despite lamivudine prophylaxis were reported. Two patients reactivated 3–5 months after HDT/ASCT while receiving thalidomide maintenance and one reactivated 3 years after HDT/ASCT and shortly after bortezomib salvage therapy. Emergence of a mutant HBV strain was documented in one patient.ConclusionsUse of prophylaxis may reduce but will not preclude HBV reactivation. Highest risk occurs during immune reconstitution phase of HDT/ASCT. The role of immunomodulatory agents in HBV reactivation needs to be further elucidated. Separate HBV prophylaxis and surveillance guidelines ought to be developed for patients with MM.     

Upfront Autologous Stem Cell Transplantation for Untreated High-Risk Diffuse Large B-Cell Lymphoma in Patients Up to 60 Years of Age

BackgroundAlthough rituximab added to CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) is the standard chemotherapy for untreated DLBCL, its therapeutic effect is limited in younger patients with high-intermediate risk or high-risk disease according to the age-adjusted international prognostic index. In fact, the efficacy and safety of HDT plus rituximab followed by ASCT for such patients remain unclear.Patients and MethodsWe retrospectively investigated the safety and effectiveness of HDT/ASCT in patients with untreated DLBCL. Twenty-two patients, aged 60 years and younger, with untreated DLBCL (classified as high-intermediate [n = 14 (64%)] or high [n = 8 (32%)] risk) underwent upfront HDT/ASCT between January 2004 and December 2008, achieving either a complete response (CR; n = 15 (68%)) or a partial response (PR; n = 7 (32%)).ResultsThe 5-year overall survival rate was 81.0% and the progression-free survival rate was 73.0%, with no significant difference between risk groups based on the international prognostic index. The most common nonhematologic toxicity was febrile neutropenia [n = 9 (41%)]. The cause of all 3 fatalities was exacerbation of the underlying disease, and no treatment-related mortality was observed. No variables with a significant influence on overall survival were identified, but a correlation of the treatment response before transplanation with progression-free survival was suggested (CR vs. PR: 92% vs. 30%, P = .002).ConclusionThese results suggest that adding rituximab to upfront HDT/ASCT is feasible and can improve the outcome in untreated patients with poor-prognosis DLBCL. In the future, upfront HDT/ASCT should be more extensively evaluated in clinical trials.     

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.