The addition of rituximab (R) to CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) -like therapy has improved survival in primary mediastinal B-cell lymphoma (PMBCL) patients. However, ...these results were obtained in young low risk patients and a reevaluation in an unselected patient cohort is warranted.
In this study, we analyzed 80 PMBCL patients treated with a CHOP-based regimen with and without rituximab.
In the non-rituximab cohort 10-year progression free survival (PFS) was 67% and 10-year overall survival (OS) was 72% versus a PFS of 95% and a OS of 92% in the rituximab group, PFS P = 0.001, OS P = 0.023. A subgroup PFS analysis by international prognostic index (IPI) risk revealed that all risk groups benefit from addition of rituximab to induction chemotherapy. In addition, OS probability was higher in the group of non-low risk patients who were treated with rituximab compared to those patients who did not receive rituximab (P = 0.035). In multivariate analysis, only addition of rituximab to induction chemotherapy and reaching complete remission (CR) after first line therapy had a beneficial effect on both PFS and OS, whereas IPI, age, upfront high dose (HD) chemotherapy/autologous blood stem cell transplantation (ABSCT) and rituximab maintenance had no impact on survival.
Our data demonstrate a survival benefit in unselected PMBCL patients treated with CHOP-like induction regimen and additional rituximab independently of the IPI risk score.
In this phase I/II study, we explored the combination of Temsirolimus with Bendamustine and Rituximab (BeRT) in patients with r/r follicular lymphoma (FL) or mantle cell lymphoma (MCL). Patients with ...1-3 prior therapies received Bendamustine (90 mg/m(2), day 1+2) and Rituximab (375 mg/m(2), day 1) with Temsirolimus in doses from 25 to 75 mg added on day 1, 8, 15 of a 28-day cycle. Fifteen (11 MCL, 4 FL) patients were included in the phase I. Median age was 73 years and median pretreatment number was 2. No formal dose-limiting toxicity was observed. Dominant non-hematological side effects were fatigue in 11 (73%), nausea in 9 (60%), mucositis in 7 (47%) and vomiting in 6 patients (40%). Cough, diarrhea, pyrexia and rash were observed in five patients (33%) each. Grade 3/4 events included leukopenia in 6 (40%), neutropenia in 4 (27%) and thrombocytopenia in 2 patients (13%). An objective response was observed in 14/15 patients (93%), including 5 complete response (33%; all MCL). After a median follow-up of 19 months, 67% of patients are without signs of progression. Temsirolimus can be safely added to BR with promising preliminary activity. Recruitment in phase II is ongoing.
To improve outcome of elderly patients with diffuse large B-cell lymphoma, dose-dense rituximab was evaluated in the prospective DENSE-R-CHOP-14 trial.
Rituximab (375mg/m2) was given on days 0, 1, 4, ...8, 15, 22, 29, 43, 57, 71, 85, and 99 together with six CHOP-14 cycles. Results were to be compared with patients who had received the same chemotherapy in combination with eight 2-week applications of rituximab in RICOVER-60.
One hundred twenty-four patients are assessable. Dose-dense rituximab resulted in considerably higher serum levels during the first 50 days of treatment, but rituximab exposure time was not prolonged. Grade 3 and 4 infections were exceptionally high in the first 20 patients without anti-infective prophylaxis, but decreased after introduction of prophylaxis with aciclovir and cotrimoxazole in the remaining 104 patients (from 13% to 6% per cycle and from 35% to 18% per patient; P = 0.007 and P = 0.125, respectively). Patients with international prognostic index = 3–5 had higher complete response/complete response unconfirmed rates (82% versus 68%; P = 0.033) than in the respective RICOVER-60 population, but this did not translate into better long-term outcome, even though male hazard was decreased (event-free survival: from 1.5 to 1.1; progression-free survival: from 1.7 to 1.1; overall survival: from 1.4 to 1.0).
Dose-dense rituximab achieved higher rituximab serum levels, but was not more effective than eight 2-week applications in the historical control population, even though minor improvements in poor-prognosis and male patients cannot be excluded. The increased, though manageable toxicity, precludes its use in routine practice. Our results strongly support anti-infective prophylaxis with aciclovir and cotrimoxazole for all patients receiving R-CHOP.
Based on centroblast frequency, follicular lymphoma (FL) is subdivided into grades 1-2, 3A, and 3B. Grade FL3A frequently coexists with FL1-2 (FL1-2-3A). Based on clinical trials, FL1-2 is treated ...with rituximab (R) or obinutuzumab plus bendamustine (B) or CHOP, while FL3B is treated with R-CHOP. In contrast, there are little data guiding therapy in FL3A. We present a retrospective, multicenter analysis of 95 FL3A or FL1-2-3A and 203 FL1-2 patients treated with R-CHOP or R-B first-line. R-CHOP facilitated a higher response rate (95% versus 76%) and longer overall survival (OS) (3-year OS 89% versus 73%,
P
= 0.008) in FL3A or FL1-2-3A, whereas the difference in progression-free survival (PFS) did not reach statistical significance. While transformation rates into aggressive lymphoma were similar between both groups, there were more additional malignancies after R-B compared with R-CHOP (6 versus 2 cases). In FL1-2, R-B achieved a higher 3-year PFS (79% versus 47%,
P
< 0.01), while there was no significant difference regarding OS or transformation. With the limitations of a retrospective analysis, these results suggest a benefit for R-CHOP over R-B in FL3A or FL1-2-3A. Confirmatory data from prospective clinical trials are needed.
To elucidate factors contributing to the effectiveness of allogeneic hematopoietic stem cell transplantation (alloHCT) in high-risk CLL, immune interventions, GvHD and clinical outcome of 77 ...consecutive patients allografted for CLL were analyzed. Immune modulation (immunosuppression tapering, rituximab-augmented donor lymphocyte infusions) was guided by minimal residual disease (MRD) monitoring and commenced at a median of 91 (22-273) days after alloHCT, resulting in a probability of being event free and MRD-negative 1 year after transplant of 57% (84% in those encountering chronic GvHD). Patients who were event free and MRD-negative at the 12-month landmark had a 4-year PFS of 77% and largely remained durably MRD-negative if MRD clearance had occurred subsequent to immune modulation. Three-year overall survival, PFS, relapse incidence and non-relapse mortality of all 77 patients were 69, 57, 26 and 24%, respectively. Survival was not affected by EBMT risk category but by active disease at alloHCT, which could not be overcome by intensification of conditioning. Twenty-three patients who experienced relapse post alloHCT had a survival of 56% at 2 years after CLL recurrence. In conclusion, MRD-guided immune modulation after alloHCT for high-risk CLL can provide durable MRD clearance in more than half of the patients.
SUMMARY
Background
Collection of peripheral blood stem cells (PBSCs) for autologous transplantation is a well‐established process. As a new generation of leukapheresis (LP) machines has been ...launched, measures of benchmarking and quality control need to be defined in order to ensure consistent collection performance.
Objectives
The goal of this project was to establish and evaluate a benchmarking system for autologous PBSC collection.
Methods
This retrospective study evaluated PBSC collection data of 198 patients with symptomatic multiple myeloma in first‐line therapy who underwent LP in 2013 and 2014 at our institution. Half the patients in 2014 were assigned randomly to undergo LP with the new Terumo BCT Spectra Optia (Terumo BCT, Garching, Germany), while the COBE Spectra (Terumo BCT) was used in all other cases. In 2014, we implemented a previously described formula for predicting daily CD34+ cell collection. As a benchmark, we developed the performance ratio: collected/predicted CD34+ cells.
Results
There was no significant difference in the number of collected CD34+ cells, the collection efficiency (collected/processed CD34+ cells) and performance ratio between the two collection devices and between LP procedures in 2013 and 2014.
Conclusions
We present a comprehensive benchmarking tool that is easy to implement, requires minimal expense and allows specific adjustment of LP parameters for optimisation of LP performance. With this approach, we could confirm the equal efficiency of the two compared apheresis systems.
Background: Pattern and outcome of disease recurrence after autologous stem-cell transplantation (autoSCT) for follicular lymphoma (FL) is not well known. Patients and methods: Relapse cases were ...identified from 241 consecutive patients autografted for disseminated untransformed FL from 1990 to 2002 in three institutions. Prognostic factors for relapse and outcome after relapse were analyzed by log-rank comparisons and Cox regression analyses. Results: One hundred and three relapses occurred. The 10-year relapse probability was 47%. Median time from autoSCT to relapse was 20 (2–128) months. Only three relapses were observed later than 6 years posttransplant. Median survival after relapse was 8.3 years. Patients with disease recurrence within 1 year from transplant and those who had received autoSCT as second-line treatment had significantly reduced survival by multivariate analysis, whereas Follicular Lymphoma International Prognostic Index score, age, remission status at autoSCT, high-dose regimen, and ex vivo purging had no impact. Conclusions: FL recurrence after autoSCT follows a biphasic pattern with continuing relapse during the first 6 years and only few events thereafter. The prognosis after relapse is relatively good and appears to be comparable to that of disease recurrence after standard treatment. The situation is less favorable for patients who relapse within the first posttransplant year.
Chemotherapy-associated ovarian damage comprises not only infertility, but also premature menopause. The latter has been reported as a consequence of alkylating chemotherapy for breast cancer or ...Hodgkin's lymphoma. In this study, we assessed the long-term impact of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimens on ovarian function in patients with aggressive non-Hodgkin lymphoma (NHL).
Long-term survivors after CHOP or CHOP plus etoposide (CHOEP) treatment within the Mabthera International Trial or the NHL-B1 trial of the German NHL Study Group were requested to respond to a questionnaire and to consent to blood sampling for hormone assessment.
A total of 46 of 81 contacted patients with a median age of 32.5 years at the time of enrolment into the aforementioned clinical trials responded to the questionnaire. The median follow-up after completion of treatment was 14 years. Last menstrual bleeding occurred significantly earlier in patients compared with the general population (47 versus 51 years, P < 0.0001). In comparison to the distribution of menopausal symptoms in the general population, the percentage of women with moderate or severe menopausal symptoms was increased. In 23 patients who agreed to participate in laboratory analyses, anti-Muller hormone as a marker of ovarian reserve was decreased when compared with correspondent age groups of the general population.
Although most female patients regain fertility after CHOP-like chemotherapy, late ovarian impairment occurs frequently. Therefore, awareness of such delayed side-effects at the time of counselling is of importance.
In a single-center retrospective donor versus no-donor comparison, we investigated if allogeneic stem cell transplantation (alloSCT) can improve the dismal course of poor-risk chronic lymphocytic ...leukemia (CLL).
All patients with CLL who were referred for evaluation of alloSCT within a 7-year time frame and had a donor search indication according to the EBMT criteria or because of Richter's transformation were included. Patients for whom a matched donor could be found within 3 months (matches) were compared with patients without such a donor (controls). Primary end point was overall survival measured from the 3-month landmark after search initiation.
Of 105 patients with donor search, 97 (matches 83; controls 14) were assessable at the 3-month landmark. Matches and controls were comparable for age, gender, time from diagnosis, number of previous regimens, and remission status. Disregarding if alloSCT was actually carried out or not, survival from the 3-month landmark was significantly better in matches versus controls hazard ratio 0.38, 95% confidence interval (CI) 0.17–0.85; P = 0.014. The survival benefit of matches remained significant on multivariate analysis.
This study provides first comparative evidence that alloSCT may have the potential to improve the natural course of poor-risk CLL as defined by the EBMT criteria.
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