Efficacy and safety of high‐dose chemotherapy with autologous stem cell transplantation in senior versus younger adults with newly diagnosed multiple myeloma

We retrospectively studied 340 fit patients with multiple myeloma (MM) who underwent autologous stem cell transplantation (ASCT). We hypothesized that progression‐free survival (PFS) of older patients was non‐inferior to that of younger patients after ASCT. Our null hypothesis was that the PFS hazard ratio (HR) for a 5‐year increase in age was ≥1.05; the alternative (non‐inferiority) hypothesis was that the HR was ≤1. The observed HR was 0.94 (95% confidence interval [CI] 0.86‐1.03); since the CI upper bound was <1.05, we reject the null hypothesis and conclude that PFS in older patients was at least as good as in younger patients. We cannot reject an analogous null hypothesis for overall survival (HR 1.06 [95% CI 0.94‐1.19]), since the CI upper bound >1.05. Toxicity was similar across ages and transplant‐related mortality was minimal. 28% of subjects <65 versus 45% of those ≥65 received maintenance therapy. In summary, ASCT prolongs PFS equally well in older vs. younger adults. Although we cannot exclude maintenance as a confounder, these data support ASCT for fit seniors with MM.     

Alternating R‐CHOP and R‐cytarabine is a safe and effective regimen for transplant‐ineligible patients with a newly diagnosed mantle cell lymphoma

Implementation of cytarabine into induction therapy became standard of care for younger patients with mantle cell lymphoma (MCL). On the basis of its beneficial impact, many centers incorporated cytarabine at lower doses also into first‐line treatments of elderly patients. We conducted a multicenter observational study that prospectively analyzed safety and efficacy of alternating 3 + 3 cycles of R‐CHOP and R‐cytarabine for newly diagnosed transplant‐ineligible MCL patients. A total of 73 patients were enrolled with median age 70 years. Most patients had intermediate (39.7%) and high‐risk (50.7%) disease according to MCL international prognostic index. Rituximab maintenance was initiated in 58 patients. Overall response rate reached 89% by positron emission tomography–computed tomography, including 75.3% complete remissions. Two patients (2.7%) did not complete the induction therapy because of toxicity. Three patients (4.1%) were considered nonresponders, which led to therapy change before completion of induction. Estimated progression‐free survival and overall survival were 51.3% and 68.6% at 4 years, respectively. Mantle cell lymphoma international prognostic index, bulky disease (≥ 5 cm), and achievement of positron emission tomography–negativity independently correlated with progression‐free survival. Grade 3 to 4 hematologic and nonhematologic toxicity was documented in 48% and 20.5% patients, respectively. Alternation of R‐CHOP and R‐cytarabine represents feasible and very effective regimen for elderly/comorbid MCL patients. This study was registered at GovTrial ( clinicaltrials.gov ) NCT03054883.     

Zevalin and BEAM (Z‐BEAM) versus rituximab and BEAM (R‐BEAM) conditioning chemotherapy prior to autologous stem cell transplantation in patients with mantle cell lymphoma

Early relapse is common in patients with mantle cell lymphoma (MCL) highlighting the unmet need for further improvement of therapeutic options for these patients. CD20 inhibition combined with induction chemotherapy as well as consolidation with high‐dose chemotherapy (HDCT) is increasingly considered cornerstones within current therapy algorithms of MCL whereas the role of radioimmunotherapy is unclear. This retrospective single center study compared 46 consecutive MCL patients receiving HDCT in first or second remission. Thirty‐five patients had rituximab and BEAM (R‐BEAM), and 11 patients received ibritumomab tiuxetan (Zevalin®), an Yttrium‐90 labeled CD20 targeting antibody, prior to BEAM (Z‐BEAM) followed by autologous stem cell transplantation (ASCT). We observed that the 5‐year overall survival (OS) in the R‐BEAM and Z‐BEAM groups was 55% and 71% (p = 0.288), and the 4‐year progression free survival (PFS) was 32% and 41%, respectively (p = 0.300). There were no treatment related deaths in both groups, and we observed no differences in toxicities, infection rates or engraftment. Our data suggest that the Z‐BEAM conditioning regimen followed by ASCT is well tolerated, but was not associated with significantly improved survival compared to R‐BEAM. Copyright © 2015 John Wiley & Sons, Ltd.     

Hematopoietic stem cell transplantation for diffuse large B‐cell lymphoma having 8q24/MYC rearrangement in Japan

The prognosis of diffuse large B‐cell lymphoma (DLBCL) having MYC rearrangement (MYC‐R), including double hit lymphoma (DHL), is poor by standard immunochemotherapy. To evaluate the significance of hematopoietic stem cell transplantation (SCT) for DLBCL with MYC‐R, we retrospectively analyzed Japanese SCT registry data. In total, 54 patients with DLBCL with MYC‐R were identified from 4336 registered adult DLBCL patients. Detailed clinical and cytogenetic information was obtained for 48 patients. The median age at diagnosis of the 48 patients was 54.5 (range 21–67) years. Twenty‐six (54%) patients had MYC‐R only (single hit), and 22 (46%) had MYC‐R and BCL2, and/or BCL6 rearrangement (double/triple hit). In 12 patients who received auto‐SCT during the first complete response (CR), both the 2‐year overall survival (OS) and progression‐free survival (PFS) rates were 75.0% (95% confidence interval [CI], 40.8%–91.2%). In 20 patients who received auto‐SCT after relapsed or refractory state, the 2‐year OS and PFS rates were 68.2% (95% CI, 41.9%–84.5%) and 59.6% (95% CI, 35.1%–77.4%), respectively. In 17 patients who received allo‐SCT, only 4 patients underwent SCT in CR. The 2‐year OS and PFS rates were 29.4% (95% CI, 10.7%–51.1%) and 17.6% (95% CI, 4.3%–38.3%), respectively. The rate of non‐relapse mortality at 1 year was 41.2% (95% CI, 17.1%–64.0%) in this group. The outcomes of single hit and double or triple hit were not different. These findings suggest that auto‐SCT may be effective for MYC‐R DLBCL, including DHL patients of chemosensitive relapsed or refractory state. Since most patients received allo‐SCT not in CR, the outcome of allo‐SCT was unsatisfactory due to high non‐relapse mortality and early relapse. To clarify the role of allo‐SCT for MYC‐R DLBCL, further accumulation of patients is necessary.     

A multicenter retrospective comparison of induction chemoimmunotherapy regimens on outcomes in transplant‐eligible patients with previously untreated mantle cell lymphoma

Mantle cell lymphoma (MCL) is an uncommon and typically aggressive form of lymphoma. Although often initially chemosensitive, relapse is common. Several induction and conditioning regimens are used in transplant‐eligible patients, and the optimal approach remains unknown. We performed an international, retrospective study of transplant‐eligible patients to assess impact of induction chemoimmunotherapy and conditioning regimens on clinical outcomes. We identified 228 patients meeting inclusion criteria. Baseline characteristics were similar among the induction groups except for some variation in age. The type of induction chemoimmunotherapy received did not influence overall response rates (ORRs) (0.43), progression‐free survival (PFS) (P > .67), or overall survival (OS) (P > .35) on multivariate analysis (PFS and OS). Delivery of autologous stem cell transplant (ASCT) was associated with favorable PFS and OS (0.01) on univariate analysis only; this benefit was not seen on multivariate analysis—PFS (0.36) and OS (0.21). Compared with busulfan and melphalan (BuMel), the use of the carmustine, etoposide, cytarabine, melphalan (BEAM)–conditioning regimen was associated with inferior PFS (HR = 2.0 [95% CI 1.1‐3.6], 0.02) but not OS (HR = 1.1 [95% CI 0.5‐2.3], 0.81) on univariate analysis only. Within the limits of a retrospective study and modest power for some comparisons, type of induction therapy did not influence ORR, PFS, or OS for transplant‐eligible patients with MCL. International efforts are required to perform randomized clinical trials evaluating chemoimmunotherapy induction regimens.     

Multicenter phase II study of bendamustine for relapsed or refractory indolent B‐cell non‐Hodgkin lymphoma and mantle cell lymphoma

Bendamustine is a unique cytotoxic agent that has demonstrated efficacy in the treatment of indolent B‐cell non‐Hodgkin lymphomas (B‐NHLs). In this multicenter phase II trial, the efficacy and safety of bendamustine were evaluated in Japanese patients with relapsed or refractory indolent B‐NHL or mantle‐cell lymphoma (MCL). Patients received bendamustine (120 mg/m²) on days 1–2 of a 21‐day cycle, for up to six cycles. The primary endpoint was the overall response rate (ORR) as assessed by an extramural committee according to International Workshop Response Criteria (IWRC). Secondary endpoints included complete response (CR) rate, ORR according to Revised Response Criteria (revised RC), progression‐free survival (PFS), and safety. Fifty‐eight patients with indolent B‐NHL and 11 with MCL were enrolled. By IWRC, bendamustine produced an ORR of 91% (95% confidence interval [CI], 82–97%; 90% and 100% in patients with indolent B‐NHL and MCL, respectively), with a CR rate of 67% (95% CI, 54–78%). ORR and CR rates according to revised RC were 93% (95% CI, 84–98%) and 57% (95% CI, 44–68%), respectively. After a median follow‐up of 12.6 months, median PFS had not been reached. Estimated PFS rates at 1 year were 70% and 90% among indolent B‐NHL and MCL patients, respectively. Bendamustine was generally well tolerated. Reversible myelosuppression, including grade 3/4 leukopenia (65%) and neutropenia (72%), was the most clinically significant toxicity observed. Common non‐hematologic toxicities included mild gastrointestinal events and fatigue. These results demonstrate the high efficacy and tolerability of single‐agent bendamustine in relapsed patients with indolent B‐NHL or MCL histologies. (ClinicalTrials.gov ID: NCT00612183). (Cancer Sci 2010;)     

含利妥昔单抗化疗方案治疗套细胞淋巴瘤效果分析

目的探讨含利妥昔单抗化疗方案治疗套细胞淋巴瘤(MCL)患者效果及预后影响因素。方法回顾性分析2007年6月至2018年11月苏州大学附属第一医院血液科收治的56例≤65岁MCL患者临床资料,化疗方案中均包括利妥昔单抗,观察临床特征、治疗方案及生物学指标对总生存(OS)和无进展生存(PFS)的影响。结果56例患者中位发病年龄57岁,男性43例,女性13例。24例接受R-CHOP方案化疗;29例接受含阿糖胞苷方案化疗,其中15例接受R-hyper CVAD/R-MA方案化疗,14例接受R-CHOP/R-DAHP交替治疗;3例接受其他方案化疗。19例接受自体造血干细胞移植(ASCT)巩固治疗。56例患者中位OS时间74个月,2年OS率83.8%,3年OS率70.9%,2年PFS率72.0%,3年PFS率49.7%。国际预后指数(IPI)评分和治疗中是否接受ASCT是MCL患者OS和PFS的独立影响因素。含阿糖胞苷治疗组总有效率(ORR)93.1%,优于R-CHOP方案组(83.3%),差异无统计学意义(χ²=0.465,P=0.495);两组间OS及PFS差异均无统计学意义(OS:χ²=0.291,P=0.590;PFS:χ²=0.912,P=0.339)。诱导化疗达缓解的MCL患者中,ASCT巩固治疗可延长中位OS时间(72个月比124个月,χ²=3.973,P=0.040)及中位PFS时间(34个月比90个月,χ²=3.984,P=0.046)。简化MCL国际预后指数(sMIPI)评分中高危组患者中接受ASCT巩固治疗患者OS和PFS优于未接受ASCT治疗者(OS:χ²=5.037,P=0.025;PFS:χ²=6.787,P=0.009),而sMIPI评分低危组患者中,是否接受ASCT组间OS、PFS差异均无统计学意义(均P>0.05)。结论含阿糖胞苷的化疗方案对改善MCL患者的预后和生存并不理想。对于诱导化疗达缓解及sMIPI评分中高危组的MCL患者,ASCT巩固治疗可改善其预后,可作为年轻患者的一线巩固治疗方案。     

LACE‐conditioned autologous stem cell transplantation for relapsed or refractory diffuse large B‐cell lymphoma: treatment outcome and risk factor analysis from a single centre

High‐dose chemotherapy followed by autologous stem cell transplantation (ASCT) is a recognized treatment option for patients with relapsed diffuse large B‐cell lymphoma. We have analysed 51 patients who underwent ASCT after LACE (lomustine (CCNU), cytarabine (Ara‐C), cyclophosphamide, etoposide) conditioning for relapsed (n = 34, 67%) or primary refractory (n = 17, 33%) diffuse large B‐cell lymphoma. With a median follow‐up of 60 months (range 2–216) the probabilities of overall survival (OS) and progression‐free survival (PFS) at 5 years were 47 and 42%, respectively. The cumulative treatment‐related mortality was 10% (n = 5). Probabilities for OS and PFS at 5 years were 56 and 50% for patients with chemosensitive and 29 and 27% for patients with chemorefractory disease. In multivariate analysis abnormal pre‐ASCT levels of C‐reactive protein (>5 mg/L) were identified as a risk factor for worse OS, whereas abnormal pre‐ASCT levels of C‐reactive protein and chemoresistance predicted inferior PFS. LACE followed by ASCT is an effective treatment for approximately half of patients with chemosensitive relapsed diffuse large B‐cell lymphoma, and a proportion of chemorefractory patients also benefit. Copyright © 2010 John Wiley & Sons, Ltd.     

Outcome of mantle cell lymphoma patients treated at a single institution over the past decade

Mantle cell lymphoma (MCL) is a rare non‐Hodgkin's lymphoma entity with a heterogeneous clinical presentation. Various therapeutic considerations in MCL for younger and elderly patients were used over the past decade. We retrospectively analyzed all 44 patients consecutively treated in a tertiary hospital between 2000 and 2010 with newly diagnosed MCL. Patient characteristics, treatment regimens and biological markers were evaluated with regard to overall survival (OS). Treatment regimens were categorized into internationally accepted intensive standard therapies and less intensive alternative treatment regimens given with palliative intent. Biological markers were correlated with clinical outcome by univariate analysis. The median age of the entire study group was 66 years (range: 42–88), with 23 (52%) patients ≥65 years. Thirty‐one (70%) patients received standard regimens, the remaining 13 (30%) patients were treated with other, less intensive regimens with palliative intent. With a median follow‐up of 5.25 years, the three‐year OS rate was 60% [95% confidence interval (CI) 0.47–0.77]. Patients treated with standard regimens had a three‐year survival rate of 77% (range: 64–94%). Of these, patients younger than 65 years were observed to have better OS (83% at 3 years; 95% CI 68–100%) than those older than 65 years (69% at 3 years; 95% CI 48–99%). In univariate analysis, the only parameters with a statistically significant prognostic impact on OS were absolute monocyte count as a continuous variable, lactate dehydrogenase and absolute lymphocyte count (>0.5 × 10⁹/l) at diagnosis. In conclusion, our data of an unselected group of patients with newly diagnosed MCL treated at a single centre tertiary hospital are in line with results from larger randomized trials demonstrating an improved OS rate of younger as well as elderly MCL patients within the last decade. Copyright © 2013 John Wiley & Sons, Ltd.     

Autologous stem-cell transplantation in patients with mantle cell lymphoma beyond 65 years of age: a study from the European Group for Blood and Marrow Transplantation (EBMT)

BackgroundLimited experience is available on the feasibility and efficacy of autologous stem-cell transplantation (ASCT) in patients with mantle cell lymphoma (MCL) beyond 65 years.Design and methodsWe analysed 712 patients with MCL treated with ASCT from 2000 to 2007 and reported to the European Group for Blood and Marrow Transplantation registry. Patients >65 years were compared with patients <65 years for the end points non-relapse mortality (NRM), relapse incidence, progression-free survival (PFS), and overall survival (OS).ResultsSeventy-nine patients were ≥65 years old. Median time from diagnosis to ASCT was longer in the elderly patients (11 versus 9 months, P = 0.005); they had more commonly received at least two treatment lines (62.0% versus 47.9%, P = 0.02) and were less commonly in first complete remission at ASCT (35.4% versus 51.2%, P = 0.002). Median follow-up after ASCT was 19 and 25 months, respectively. NRM was comparable at 3 months (3.8% versus 2.5%) and at 5 years (5.6% versus 5.0%). There were no differences in relapse rate (66% versus 55% at 5 years), PFS (29% versus 40%) and OS (61% versus 67%) between both populations of patients.ConclusionsASCT beyond 65 years of age is feasible in selected patients with MCL and results in similar disease control and survival as in younger patients.     

Disease characteristics of diffuse large B-cell lymphoma predicting relapse and survival after autologous stem cell transplantation: A single institution experience

While various tools such as the International Prognostic Index (IPI) and its derivatives exist for risk-stratification of diffuse large B-cell lymphoma (DLBCL) at diagnosis, patient and disease characteristics capable of predicting outcome after high-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT) are not clearly defined. We retrospectively analyzed medical records of 111 DLBCL patients (78 relapsed and 33 refractory) who underwent HDC/ASCT at our institution from 2010-2015. After a median follow-up time of 4.6 years (interquartile range [IQR] 2.2-8.1), the likelihood of 5-year progression-free survival (PFS) was 62.2% (95% CI, 53.4%-72.4%) and the likelihood of 5-year overall survival (OS) was 68.9% (95% CI, 60.7%-78.2%). More than three chemotherapy regimens prior to ASCT was the only variable associated with lower likelihood of PFS (P = .004) and OS (P = 0.026). Male gender and high IPI score at time of ASCT were also associated with lower likelihood of PFS (P = .043; P = .013). NCCN IPI and age-adjusted IPI at time of ASCT were not predictive of outcome following ASCT. Patients with refractory and relapsed disease had similar outcomes post-ASCT (P = .207 for PFS, P = .073 for OS).     

Response and survival benefit with chemoimmunotherapy in Epstein‐Barr virus‐positive diffuse large B‐cell lymphoma

Epstein‐Barr virus (EBV)‐positive diffuse large B‐cell lymphoma (DLBCL) is a haematologic malignancy with poor prognosis when treated with chemotherapy. We evaluated response and survival benefits of chemoimmunotherapy in EBV‐positive DLBCL patients. A total of 117 DLBCL patients were included in our retrospective analysis; 33 were EBV‐positive (17 treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R‐CHOP] and 16 with CHOP), and 84 were EBV‐negative (all treated with R‐CHOP). The outcomes of interest were complete response (CR) and overall survival (OS) in EBV‐positive DLBCL patients (R‐CHOP versus CHOP) and in DLBCL patients treated with R‐CHOP (EBV‐positive vs EBV‐negative). There were no differences in the clinical characteristics between EBV‐positive and EBV‐negative DLBCL patients. Among EBV‐positive DLBCL patients, R‐CHOP was associated with higher odds of CR (OR 3.14, 95% CI 0.75‐13.2; P = .10) and better OS (hazard ratio 0.30, 95% confidence interval [CI] 0.09‐0.94; P = .04). There were no differences in CR rate (OR 0.52, 95% CI 0.18‐1.56; P = .25) or OS (hazard ratio 0.93, 95% CI 0.32‐2.67; P = .89) between EBV‐positive and EBV‐negative DLBCL patients treated with R‐CHOP. Based on our study, the addition of rituximab to CHOP is associated with improved response and survival in EBV‐positive DLBCL patients. Epstein‐Barr virus status does not seem to affect response or survival in DLBCL patients treated with R‐CHOP.     

Frontline treatment of diffuse large B‐cell lymphoma: Beyond R‐CHOP

Although the majority of patients with diffuse large B‐cell lymphoma (DLBCL) can be cured with the standard immunochemotherapy R‐CHOP, one‐third of them relapses with a dismal outcome in most cases. In the recent years, remarkable advances have been achieved based on the discovery of molecular genetics in DLBCL. In addition to the major cell‐of‐origin designations of germinal center B‐cell and activated B‐cell subtypes, next‐generation sequencing has unveiled the remarkable complexity of DLBCL and identified potential molecular targets for tailored therapies. Despite these findings, the current standard of care for DLBCL patients is still R‐CHOP, and optimization of frontline therapy remains an important goal. In this review, we summarize recent updates on the evolution of frontline therapies for DLBCL.     

Outcomes of Autologous Stem Cell Transplantation as a Consolidative Strategy for the Treatment of Primary and Isolated Secondary Central Nervous System Diffuse Large B Cell Lymphomas

IntroductionStandard consolidation for primary diffuse large B cell lymphoma (DLBCL) of the central nervous system (CNS) (PCNSL) is not established. This single center, retrospective observational study aims to define the outcomes of consolidative high dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) in patients with PCNSL and isolated secondary CNS DLBCL (SCNSL) and evaluate the prognostic factors.Patients and MethodsAll consecutive patients performed an HDC/ASCT for PCNSL or isolated SCNSLs between October 2012 and February 2022 were identified. Primary endpoints were progression-free survival (PFS) and overall survival (OS).ResultsAmong 35 patients included, 28 had PCNSL and 7 had isolated SCNSL. Median age was 51 (16-78). Males constituted 48.6%. Median follow-up after HDC/ASCT was 42.0 months. MATRIX (51.4%) and TEAM (80.0%) were the most frequent regimens of induction and conditioning, respectively. OS and PFS 1- and 2-year after HDC/ASCT were 68.0%, 57.0%, 58.0%, 48.0%, respectively. Increasing age, poor performance and comorbidities were associated with lower OS and PFS and higher non-relapse mortality (NRM). Complete response (CR) 1 at HDC/ACST was independently associated with higher OS and PFS [hazard ratio (HR): 4.67 and 6.99, respectively].ConclusionIn patients < 60 years consolidative HDC/ASCT yields promising OS and PFS. Patients ≥ 60 years may less likely benefit from consolidative HDC/ASCT and should be studied further in trials of novel agents, lower doses of consolidative radiotherapy and dose-adjusted conditioning regimens. Not only age, but also comorbidities, clinical performance and response to induction correlate with outcomes. Patients with isolated SCNSL may achieve similar outcomes.     

Serum albumin level at diagnosis of diffuse large B‐cell lymphoma: an important simple prognostic factor

This study compared the value of several simple laboratory parameters with known prognostic models for predicting survival in patients with diffuse large B‐cell lymphoma (DLBCL). The data of 157 adult patients with DLBCL diagnosed at Rabin Medical Center in 2004–2008 and treated with R‐CHOP immunochemotherapy were retrospectively reviewed. Main clinical features of the cohort were as follows: mean age 63.0 years, 43% male, 63% stage III/IV disease, 28% ECOG performance status > 2, 60% elevated lactate dehydrogenase level. Median duration of follow‐up was 6.6 years. The NCCN‐International Prognostic Index (IPI) was found to be a more powerful prognosticator than the IPI. Five‐year overall survival (OS) was 69.6; 73.6% for patients with intermediate NCCN‐IPI and 38.4% for patients with poor NCCN‐IPI. On univariate analysis, pretreatment hemoglobin and albumin levels were significantly associated with survival. By albumin level, 5‐year OS was 77.6 + 4% in patients with >3.5 g/dl and 53 + 7% in patients with < 3.5 g/dl (p < 0.001); 5‐year progression‐free survival (PFS) was 69.9% and 50.9%, respectively (p = 0.002). By hemoglobin level, 5‐year OS was 82.9 + 4.5% in patients with >12 g/dl and 58.8 + 5% in patients with < 12 g/dl (p = 0.007); 5‐year PFS was 75.5% and 54.1%, respectively (p = 0.008). On multivariate analysis with Cox regression, pretreatment albumin level was a significant independent predictor of OS. Furthermore, 5‐year OS of patients with a high NCCN‐IPI and albumin < 3.5 g/dl was 29.2% compared with 60% in patients with albumin > 3.5 g/dl (p = 0.022). In conclusion, pretreatment albumin level is a strong prognostic factor for OS in patients with DLBCL and can discriminate high‐risk patients for good and poor prognosis. Copyright © 2015 John Wiley & Sons, Ltd.     

Consolidation with 90Yttrium‐ibritumomab tiuxetan after bendamustine and rituximab for relapsed follicular lymphoma

Bendamustine and rituximab (BR) are widely used in patients with follicular lymphoma (FL) previously treated with conventional immunochemotherapy, but the role of consolidation radioimmunotherapy in these patients is unknown. This study evaluated the efficacy and safety of consolidation with ⁹⁰Yttrium‐ibritumomab tiuxetan (⁹⁰Y‐IT) after re‐induction therapy with BR in patients with previously treated FL. This study included adult patients with relapsed FL who had undergone one or two prior therapies. Re‐induction therapy with BR was administered every 4 weeks up to 4–6 cycles. If patients achieved at least partial response, ⁹⁰Y‐IT was administered as consolidation therapy. The primary endpoint was 2‐year progression‐free survival (PFS) after consolidation. A total of 24 FL patients (median age 60 years) who had undergone one (n = 17) or two (n = 7) prior treatments received BR. After BR therapy, 22 patients proceeded to consolidation with ⁹⁰Y‐IT, resulting in an overall 88% response rate to the protocol treatment. Within a median observation period of 46.8 months, the estimated 2‐year PFS rate after the consolidation among the 22 patients receiving ⁹⁰Y‐IT was 59% (95% confidence interval [CI], 38%–77%). Patients whose remission after previous treatment had lasted ≥2 years had a significantly higher 2‐year PFS rate than patients whose remission after previous treatment had been <2 years (68% vs. 33%, Wilcoxon p = 0.0211). Major adverse events during the protocol treatment and within 2 years after the consolidation were hematological toxicities, but they were generally acceptable. Consequently, the estimated 2‐year overall survival after the consolidation was 95% (95% CI, 74%–99%). In conclusion, in a subset of patients with previously treated FL, ⁹⁰Y‐IT consolidation after BR re‐induction conferred a durable remission, indicating that consolidation therapy using ⁹⁰Y‐IT may be a novel therapeutic option for patients with relapsed FL (UMIN000008793).     

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.     

Immune reconstitution of B‐cell lymphoma patients receiving CHOP‐based chemotherapy containing rituximab

Sixty‐six B‐cell lymphoma patients were treated with a CHOP‐based chemotherapy containing rituximab (R‐CHOP‐like regimen). Immune reconstitution was assessed by measuring lymphocyte subsets and immunoglobulins. Fifty‐five patients (83.3%) underwent six cycles of the R‐CHOP‐like regimen. CD19⁺ and CD20⁺ cells were completely eliminated from the peripheral blood after one cycle of the R‐CHOP‐like regimen; they were detected again 6 months after the therapy. One year after the therapy, B‐cell numbers recovered to their level at diagnosis and almost doubled 2 years after the therapy. The lowest numbers of CD3⁺, CD8⁺ and CD56⁺ cells were seen after three cycles of the regimen, but continued to increase until 1 year after the therapy, remaining stable thereafter. CD4⁺ T‐cells were at their lowest after six cycles of the regimen and recovered slowly for 2 years after the therapy; however, their numbers were still lower than that at diagnosis. Immunoglobulins decreased over six cycles of the R‐CHOP‐like regimen and then recovered gradually for 2 years after the therapy. The percentage of IgG, IgA and IgM 2 years after the therapy compared with those at diagnosis was 93.9%, 90.1%, 76.3%, respectively. Twelve infectious complications occurred which consisted of three febrile neutropenia, three Herpes Zoster, two tympanitis, two Pneumocystis jiroveci pneumonia and two hepatitis B virus reactivation. B‐cells required 1 year and CD4⁺ T‐cells and immunoglobulins needed 2 years to recover after the therapy. Copyright © 2010 John Wiley & Sons, Ltd.     

Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failure, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG).

PURPOSE: Mantle cell lymphoma (MCL) is characterized by a poor prognosis with a low to moderate sensitivity to chemotherapy and a median survival of only 3 to 4 years. In an attempt to improve outcome, the German Low Grade Lymphoma Study Group (GLSG) initiated a randomized trial comparing the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and rituximab (R-CHOP) with CHOP alone as first-line therapy for advanced-stage MCL. PATIENTS AND METHODS: One hundred twenty-two previously untreated patients with advanced-stage MCL were randomly assigned to six cycles of CHOP (n = 60) or R-CHOP (n = 62). Patients up to 65 years of age achieving a partial or complete remission underwent a second randomization to either myeloablative radiochemotherapy followed by autologous stem-cell transplantation or interferon alfa maintenance (IFNalpha). All patients older than 65 years received IFNalpha maintenance. RESULTS: R-CHOP was significantly superior to CHOP in terms of overall response rate (94% v 75%; P = .0054), complete remission rate (34% v 7%; P = .00024), and time to treatment failure (TTF; median, 21 v 14 months; P = .0131). No differences were observed for progression-free survival. Toxicity was acceptable, with no major differences between the two therapeutic groups. CONCLUSION: The combined immunochemotherapy with R-CHOP resulted in a significantly higher response rate and a prolongation of the TTF as compared with chemotherapy alone. Hence, R-CHOP may serve as a new baseline regimen for advanced stage MCL, but needs to be further improved by novel strategies in remission.     

Maintenance rituximab after autologous stem cell transplantation in patients with mantle cell lymphoma

BackgroundHigh-dose therapy and autologous stem cell transplantation (ASCT) improves outcomes for patients with mantle cell lymphoma (MCL), but relapse ultimately occurs in most patients. Recently presented interim results from a phase III prospective trial suggest maintenance rituximab (MR) after ASCT for MCL improves progression-free survival (PFS). The maturation of these data and any benefit of MR on overall survival (OS) remain to be defined.Patients and methodsIn this retrospective study, we examined a cohort of consecutive patients with MCL that underwent ASCT for MCL at our center and evaluated their outcomes according to whether they received MR after ASCT (n = 50) or did not (n = 107). MR was treated as a time-dependent covariate to account for variation in timing of its initiation.ResultsMR was associated with an improved PFS [hazard ratio (HR) 0.44; confidence interval (CI) (0.24–0.80), P = 0.007] and overall survival (OS; HR 0.46; CI 0.23–0.93, P = 0.03) following a multivariate adjustment for confounding factors with a median follow-up of ∼5 years. Grade 4 neutropenia was increased (34% versus 18%, P = 0.04) in the MR group, but no effect on the rate of mortality unrelated to relapse was observed.ConclusionsThese data support that MR after ASCT for MCL confers a benefit in PFS and additionally suggest it may improve OS. General application of this strategy will require confirmation of benefit in prospective randomized trials.