bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating the impact of rituximab on bcl-2-associated resistance to CHOP using competing risks in elderly patients with diffuse large B-cell lymphoma (DLBCL)
Authors: Mounier N. , Briere J. , Gisselbrecht C. , Lederlin P. , Berger F. , Bosly A. , Tilly H. , Reyes F. , Gaulard P. , Coiffier B. 
Published: March 2020

7514 Background: In diffuse large B-cell lymphoma, the combination of rituximab and CHOP (R-CHOP) has been proved to reduce bcl-2-associated treatment failure in elderly patients. However, some deaths could be due to age-associated morbidity such as cardio-vascular events. Patients and Methods: We therefore, addressed the question of its long-term impact by a competing risks analysis of 292 patients from the previously updated LNH-98–5 trial by the Groupe d’Etude des Lymphomes de l’Adulte (GELA) (Feugier et al, J Clin Oncol 2005). Using the competing risk formulation of Cox model regression, we investigated the effect of the explanatory variables on different competing events during the disease’s course such as progression, relapse, or death. Results: With a median follow-up of 5 years, R-CHOP was associated with a better survival than CHOP in 193 bcl-2-positive patients (56 ± 9% vs 42 ± 11%, P = 0.01), whereas in 99 bcl-2-negative patients there was no difference (58 ± 14% vs 52 ± 15% vs, P = 0.6). Results of competing risks analysis are given in table. Of particular interest, R-CHOP significantly decreased the risk of progression or relapse in both bcl-2-positive (RR = 2.6, P < 0.001) and bcl-2 negative (RR = 2.2, P = 0.01) and had no impact on the risk of death in complete remission patients (age over 70 remained an adverse factor). After relapse, aa-IPI 2–3 (RR = 2.9, P < 0.0001) and bcl-2 overexpression (RR = 1.5, P = 0.03) had still a significant effect on the risk of death but not front-line R-CHOP and age above 70. Conclusion: These findings highlight the role of rituximab in the sensitization to drug-induced apoptosis without inducing long-term sequel. However, Bcl2 positive patients failed to salvage treatment after relapse. [Table: see text] No significant financial relationships to disclose.
Anti-tumor activity of mTOR inhibitor temsirolimus for relapsed mantle cell lymphoma: A phase II trial in the North Central Cancer Treatment Group
Authors: Ansell S. M. , Geyer S. M. , Kurtin P. J. , Inwards D. J. , Kaufmann S. H. , Flynn P. J. , Morton R. F. , Luyun R. F. , Dakhil S. R. , Gross H. , Witzig T. E. 
Published: March 2020

7532 Background: Mantle Cell Lymphoma (MCL) is characterized by t(11;14) resulting in over expression of cyclin D1, a member of the phosphatidylinosital 3-kinase (PI3K) pathway. Temsirolimus is a novel inhibitor of the mammalian target of rapamycin (mTOR) kinase. Previous studies with weekly temsirolimus at a dose of 250mg demonstrated a 38% overall response rate in 35 patients (JCO 23 (23); 5347–56, 2005). Thrombocytopenia was frequently observed and was dose limiting. The current study tested whether low-doses (25mg) of temsirolimus could produce a similar overall response rate (ORR) with less toxicity. Methods: Eligible patients had biopsy proven cyclin D1 positive MCL and had relapsed or were refractory to therapy. Patients received temsirolimus 25mg IV weekly as a single agent. Patients were restaged after 1 cycle (4 doses), after 3 cycles, and every 3 cycles thereafter. Patients with a tumor response after 6 cycles were eligible to continue drug for a total of 12 or 2 cycles after complete remission (CR) and then were observed without maintenance. The goal was to achieve an ORR of at least 20%. Results: Twenty-nine patients were enrolled between March and August 2005. Twenty-two patients have completed therapy. One patient with a major protocol violation on cycle-1 and one ineligible patient were excluded, leaving 27 evaluable patients. The ORR was 41% (11/27), with 1 CR and 10 PRs. Early evaluation of TTP showed a median of 5.5 months (95% CI: 3.3–7.7) and the duration of response for the 11 responders was 6.2 months (95% CI: 3.6 to not yet reached). These results compare favorably with the 6.5 months and 6.9 months, respectively, found in previous trials that used 250 mg. The median dose delivered per month was 80 mg (range, 10–100 mg). Sixteen (59%) of patients required a dose reduction. The median time on treatment was 4.4 months (95% CI, 3.3–7.7). The incidence of grade 3 and 4 thrombocytopenia was 12% and 0%, respectively. One patient experienced grade 5 infection without neutropenia, which was considered unrelated to CCI-779. Conclusions: Single agent CCI-779 at a dose of 25mg has anti-tumor activity in relapsed MCL similar to the 250 mg dose. This study indicates that combinations of temsirolimus with other agents should be feasible. [Table: see text]
Long term outcome of 135 high grade non-Hodgkin’s lymphoma of the head and neck (HN NHL) treated with high dose CHOP regimen and involved field radiotherapy
Authors: Laccourreye L. , Desablens B. , Le Maignan C. , Le Mevel A. , Berthou C. , Lamy T. , Gandour C. , Guilhot F. , Ifrah N. , Colombat P. , Goelams  
Published: March 2020

7550 Background: We present the results of a prospective study conducted by the GOELAMS group and evaluating long-term clinical outcome in a series of 135 patients with a HN NHL undergoing chemotherapy and radiotherapy. Methods: From 1986 through 1998, 135 patients aged from 17 to 69 years were enrolled in a prospective multicenter study for primary treatment of HN localized stage I/II high-grade NHL. Treatment regimen consisted in 3 VCAP + 40 Gy locoregional irradiation. Results: The median age was 48.5 years (17–69) with 36 patients being 60 or over. The main localization was Waldeyer’s ring (57) including tonsil (35), nasopharynx (14), whole Waldeyer (8), neck (49), nasal cavities (14), thyroid (8) salivary gland (5), mandibular bone (2). According to the WFC, histological subtype were as F (21%), G (57%) and H (20%) and unclassified (2%). Ann Harbor classification included 80 stage 1 and 55 stage II. The IPI score was 0 (49.7%), 1 (22.3%), 2 (10.4%), 3 (2.3%) undetermined (16.3%). PS>2 and bulk (≥ 5 cm) were observed in 7.5% and 43% of patients respectively. 94% achieved CR. 2 patients died during treatment. Relapses occurred in 23/127 (18.1%) at a median time of 31 months (5.5–80). 16 of these relapses occurred before 3 years of CR, 5 between 3 and 6 years and 2 after 6 years of CR. With a median follow up of 65 month (7–146) OS and EFS were 81.5% and 77% respectively. In univariate analysis age≥ 60, extension, PS≥2, Bulk≥5 cm, erythrocyte sedimentation rate≥ 40, high serum LDH,IPI≥2 and salivary gland or panwaldeyer localization significantly decrease EFS (P = 0.055, 0.017, 0.006, 0.0001, 0.04, 0.028, 0.014 and 0.043 or 0.0001 respectively). In multivariate analysis only the bulk≥5 cm, the erythrocyte sedimentation rate≥40 and the localization to salivary gland significantly decrease EFS (P = 0.004, 0.004 and 0.033 respectively). Conclusions: This study underlines the high efficiency of this protocol in treating HN NHL. HN NHL localized to the salivary glands or with a bulk ≥ 5 cm should be included in new therapeutic trials in order to improve their outcome. No significant financial relationships to disclose.
Influence of parent age and gender on anticipation in familial B-cell malignancies
Authors: Alexandrescu D. T. , Brown K. , Dutcher J. P. , Wiernik P. H. 
Published: March 2020

7553 Background: Anticipation (A) occurs when a disease manifests at an earlier age or with increased severity in the next generation. Dependence of A on parent age and sex has not been previously investigated in B-cell malignancies. Methods: 144 pairs [45 mixed Hodgkin’s/non-Hodgkin’s (HD/NHL) and NHL/HD, 44 NHL, 24 HD and 31 CLL] were analyzed retrospectively for presence of anticipation in overall, paternal (PT) and maternal transmission (MT). 90 pairs belong to our familial hematological malignancies database, and 54 were pooled from the literature. A among diseases, as well as PT and MT were compared by t-test. Parent age at conception was correlated with A by Pearson correlation (PC). Results: Age at conception was similar among all malignancies, and overall anticipation varied between −18.93 and −26.61 yr, with no significant difference among diseases, except between CLL and mixed HD/NHL-NHL/HD (−18.93 vs. −26.61 yr, mean difference −7.68 yr, p = 0.03, 95% CI −14.74 to −0.62). A significant PC between the parent age at conception and A was found for all malignancies, with the exception of borderline significance in the case of mixed HD/NHL-NHL/HD MT. No difference in overall A was observed between PT and MT, except for HD (−27.25 vs. −14.25 yr, mean difference −13.00 years, P = 0.02, 95% CI −23.68 to −2.32). However, higher PCs were observed with PT than MT for all diseases (Table). Conclusions: A is present in all familial B-cell malignancies analyzed and it correlates with parent age of conception. Although mean absolute A was more prominent with PT than MT only in the case of HD, all diseases showed a tendency towards a higher PC with PT. Although less prominent than with neurological disease, this phenomenon points towards a germline inheritance of B-cell malignancies and a common genetic basis for HD and NHL. [Table: see text] No significant financial relationships to disclose.
Prediction of outcome using positron emission tomography (PET) compared to standard response criteria and potential role in treatment decisions in diffuse large B-cell lymphoma (DLBCL) patients
Authors: Trneny M. , Jaeger U. , Belohlavek O. , Skrabs C. , Koren J. , Hanswirth A. , Pytlik R. , Klener P. 
Published: March 2020

7565 Background: PET has been demonstrated to give valid information about viable tumor residua. There are however only limited data regarding the combination of classical response criteria with PET and there is a lack of information on the impact of additional therapy (add-Th) on the outcome of PET neg. or PET pos. pts. Methods: One hundred thirty-nine pts (median age 50y) with newly diagnosed DLBCL who were examined by PET during (after 2–4 cycles CHT - ‘early PET’) or/and at the end of therapy (‘end PET’) were analyzed retrospectively. IPI risk distribution were as follows: L 28%, LI 24%, IH 33% and H 15% pts. All pts were treated with anthracyclin based CHT. “Early PET” was performed in 84 pts. and “end PET” in 103 pts before add-Th, PET at both time points was performed in 48 pts. Add-Th (HDT with ASCT or/and radiotherapy), was given as planned or as a result of response evaluation (conventional methods - CT, trephine biopsy). No treatment modification was made on PET result only, except for 2 cases when planned RT was skipped because of PET neg. RT was performed in 59 pts (42.4%) and HDT with ASCT as consolidation in 54 pts (38.8%). Median follow up was 30 m. Results: CR or CRu was achieved after CHT in 102 (74%) pts, PR in 24 (17%) pts, stable or progress dis. in 13 (9%). ‘Early PET’ was neg. in 60% pts and ‘end PET’ was neg in 67% pts. PET neg. was achieved at least once in 97 (70%) pts, and PET pos. at least once was found in 50 pts (36%). The PFS at 30 m according to the combination of conventional and PET response was as follows: for CR PET-neg. pts 89%, for PR PET-neg. pts 90%, for CR PET-pos. pts 45% and for PR PET-pos. pts 64% (p=0.0001). OS was 93%, 63%, 90% and 83%, respect.(p=0.004). The analysis of impact of add-Th showed PFS at 30 m: for PET-neg pts with Add-Th 96%, for PET-neg. pts without Add-Th 82%. PET-pos. pts without Add-Th had a PFS of only 10% and PET-pos. pts with add-Th had PFS 58% (p=0.0001). The OS was 92%, 98%, 38% and 74% respect. (p=0.0001). Conclusions: Our data demonstrate that PET give more powerful information than standard response criteria. The second analysis support the the idea that pts with DLBCL in CR who remain PET pos. should undergo the additional therapy. Partial support: Grant MSM 0021620808 No significant financial relationships to disclose.
A multi-center, open-label study to evaluate the safety and efficacy of pentostatin, cytoxan, and rituxan (PCR) in the treatment of previously untreated or treated, stage III or IV, low-grade B-Cell NHL
Authors: Mena R. R. , Christiansen N. P. , Nyman D. W. , Markan Y. , Chowhan N. M. 
Published: March 2020

7591 Background: The decision to treat indolent B-cell NHL is often based on progressive disease, worsening symptoms, and increasing hematological derangement. When treatment is indicated, these lymphoproliferative disorders are very sensitive to combination chemotherapies. Combination therapy with these agents, pentostatin (P), a purine analog, cyclophosphamide (C), a DNA alkylator, and rituximab (R), an anti-CD20 monoclonal antibody, represents a promising approach in the treatment of these patients. Most regimens have utilized fludarabine (F) as the purine analog but the myelosuppression and immunosuppression of (F) combinations frequently results in severe infections. Methods: Eligibility criteria allow previously treated and treatment-naïve patients diagnosed with low-grade stage III/IV NHL (REAL classification) to be enrolled. Treatment consisted of intravenous infusions of P (4 mg/m2), C (600 mg/m2), and R (375 mg/m2) on day 1 of a 21-day cycle for a total of 8 cycles. Clinical evaluation was performed after cycles 2, 4, 6 and 8. Patients were stratified by disease and by prior treatment status. Results: The intent-to-treat (ITT) population consisted of 54 NHL patients (median age 65, range 30–86) who received a total of 330 cycles (median 6 per patient). The ECOG status was 0 (31%), 1 (58%) and 2 (12%). The overall objective response rate was 71% (CR 15%, Cru 13%, PR 43%). Eight grade 4 neutropenias were documented along with a single grade 4 leukopenia. There were a total of 3 deaths which occurred within 30 days of the last dose. The first death was due to a second primary, NSCLC, diagnosed after treatment began. The second death occurred in an 81 year-old female, who had achieved PR, and her death was due to CHF. The last death, due to MI/CAD, occurred in an 84 year-old woman with SD. Conclusions: This immunochemotherapeutic regimen is active in indolent Grade III/IV NHL and the incidence of significant toxicities was low. Updated trial results will be presented at the ASCO annual meeting. Future trials evaluating the use of R as maintenance therapy following this PCR regimen may also be warranted with an eye toward increasing the overall survival of patients with NHL. No significant financial relationships to disclose.
Effect of complete response pre- and post- autologous stem cell transplantation in multiple myeloma
Authors: Sayani F. , Stewart D. , Kmet L. , Faris P. , Savoie M. L. , Chaudhry A. , Brown C. , Russell J. , Bahlis N. 
Published: March 2020

7604 Background: The value of achieving a complete response (CR) pre or post high dose therapy and autologous stem cell transplant (HDT-ASCT) in multiple myeloma is still uncertain. Knowing the impact of achieving a CR prior to HDT-ASCT on survival, may lead to the incorporation of novel therapeutic agents into the front line treatment of this disease. The aim of our study was to determine whether achieving a CR before or after HDT-ASCT affects overall survival (OS) in multiple myeloma patients. Methods: We performed a retrospective analysis of 88 consecutive myeloma patients receiving HDT-ASCT at our center from 1993 to 2004. The OS of patients achieving at least 90% reduction in their M-protein, i.e. complete response and very good partial response (CR/VGPR), pre or post HDT-ASCT, was compared to that of patients achieving a partial response or less (<90% reduction in M-protein). OS, defined as the number of months from HDT-ASCT to death or last follow up, was estimated by the Kaplan-Meier method. Response status was evaluated pre and at 100 days post HDT-ASCT. Results: Prior to HDT-ASCT, twenty-two (25%) patients achieved a CR/VGPR. Median follow-up time was 39 months for patients in CR/VGPR and 18 months for non-CR/VGPR group. OS at 5 years was 58% (95% CI: 21%-82%) for patients in CR/VGPR, compared to 69% (95% CI: 51%-81%) for all patients in PR or less prior to stem cell collection. Post HDT-ASCT, 48 (55%) patients achieved a CR/VGPR. Their OS estimate at 5 years was 67% (95% CI: 44%-82%) compared to 71% (95% CI: 27%-92%) for all other patients. Overall, 30% more patients achieved CR/VGPR post HDT-ASCT. However, the survival curves did not differ by response status pre or post HDT-ASCT (log-rank test p=0.58 and 0.57 respectively). Conclusions: Our results suggest that achieving a clinical CR/VGPR pre or post HDT-ASCT does not appear to impact OS. These results might have been influenced by the small sample size and the possible need for a longer follow-up time. A more robust definition of CR at the molecular level, plus the use of novel therapeutic agents in front-line treatment, may better define the impact of achieving CR in multiple myeloma. No significant financial relationships to disclose.
Extended follow-up of outcome measures and analysis of prognostic factors in multiple myeloma patients treated on a phase I study with bortezomib and pegylated liposomal doxorubicin
Authors: Biehn S. E. , Moore D. T. , Voorhees P. M. , Garcia R. A. , Lehman M. J. , Dees E. C. , Orlowski R. Z. 
Published: March 2020

7617 Background: Preclinical studies of bortezomib (bort) with pegylated liposomal doxorubicin (PLD) showed enhanced anti-tumor efficacy compared with either single agent. This led to a phase I trial in patients (pts) with advanced hematologic malignancies who received bort on days 1, 4, 8 and 11 at 0.9–1.5 mg/m2, and PLD on day 4 at 30 mg/m2, every three weeks (Blood 105:3058, 2005). Significant activity was seen, with 36% of relapsed/refractory multiple myeloma (MM) pts achieving a complete or near-complete response, while 73% attained at least a partial response. It was therefore of interest to define time to progression (TTP) and overall survival (OS) with this regimen. Methods: Additional follow-up was obtained on all 22 evaluable MM pts. TTP and OS were determined from day 1 of bort/PLD, and the Kaplan-Meier method was used to calculate time-to-event estimators. The log-rank test was used to compare TTP and time to retreatment (TTR) on bort/PLD vs. the prior therapy. Cox regression was used to evaluate covariates for association with TTP and OS. Results: Median TTP with bort/PLD was 9.3 months (mos)(95% confidence interval (CI) 8.3–22.4) versus 3.8 mos (95% CI 2.3–10.0) on the pt’s prior therapy (p=0.04). Similarly, the median TTR after bort/PLD was prolonged (p=0.04) compared with TTR after the prior regimen, with 3 pts having not yet received their next therapy. With a median follow-up of 36 mos, 13 of these patients (59%) remain alive, and the median OS has not yet been reached. Karnofsky performance status was significantly associated with TTP (p=0.02), while the hematocrit (hct; p=0.06) and IgA subtype (p=0.08) had borderline significance. Hct was significantly associated with OS (p=0.03), while the number of prior regimens (p=0.07) and the platelet count (p=0.06) had borderline significance. Conclusions: Bort alone induced a median TTP of 6.6 mos and OS of 16 mos in MM (N Engl J Med 348: 2609, 2003). The current results support the possibility that the bort/PLD regimen may improve upon TTP, and especially OS, compared with bort alone. This hypothesis is being studied in a randomized, international phase 3 trial ( NCT00103506 ) comparing bort and bort/PLD. No significant financial relationships to disclose.
FDG-PET predicts disease burden in multiple myeloma
Authors: Kostakoglu L. , Niesvizky R. , Liu M. , Goldsmith S. J. , Christos P. , Jayabalan D. S. , Coleman M. 
Published: March 2020

7619 Background: Because of the clinical and biologic heterogeneity of multiple myeloma, staging systems have been developed based on recognition of various prognostic factors. The recent integration of FDG-PET into the diagnostic algorithm may also have prognostic implications. Our aim was to evaluate the value of FDG-PET in determining the extent of disease as a staging tool in MM and to compare PET results with the established staging systems and laboratory data. Methods: Thirty seven patients with MM (mean age: 62±12) underwent a whole body FDG-PET scan at initial staging prior to therapy. FDG uptake was qualitatively scored in the following patterns: minimally diffuse (score 1), focal (score 2), multifocal (score 3), diffuse (score 4) and extramedullary (score 5). Standardized uptake values (SUVmax) were obtained in 780 osseous and extramedullary sites for quantitative evaluation. Additionally, mean SUVmax was calculated in 14 representative anatomic sites in the axial and appendicular skeleton in 20 age-matched control patients with no osseous malignancy. Ratios of the mean lesion SUVmax to the mean SUVmax of corresponding osseous sections from the control group were calculated. A score was obtained for each patient to reflect disease severity by adding the ratio for each lesion. Qualitative and quantitative results were correlated with the tumor burden (paraproteins, free light chains in the serum) and staging scores of Durie-Salmon (D-S) and the international staging systems (ISS). Results: There was good correlation between the quantitative score and both D-S staging and the ISS. However, correlation was stronger with the D-S system compared to that with ISS (r=0.44, p=0.007 vs. r=0.33, p=0.06). There was also good correlation between the quantitative score and the tumor burden (r=0.37, p<0.05). The qualitative scoring system produced a good correlation with the tumor burden (r=0.35, p<0.05). There was no correlation between the qualitative scoring system and D-S staging or ISS (P>0.05). Conclusions: FDG-PET is useful in assessing the extent of disease as a staging tool at initial diagnosis in MM. The scoring system we have developed appears to correlate with the established staging systems and the level of free light chains which may contribute to the prognostic evaluation of patients with MM. No significant financial relationships to disclose.