bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and risk factors for central nervous system relapse in patients with diffuse large B-cell lymphoma: The impact of the addition of rituximab to CHOP chemotherapy
Authors: Villa D. , Savage K. J. , Sehn L. H. , Connors J. 
Published: March 2020

8037 Background: The addition of rituximab to CHOP (CHOP-R) chemotherapy improves outcome in patients with diffuse large B- cell lymphoma (DLBCL). However, limited data suggests that it may not impact the risk of central nervous system (CNS) relapse. We evaluated the risk of CNS relapse and associated predictive factors in a large population-based cohort of patients with DLBCL. Methods: All patients with DLBCL diagnosed from September 1, 1999 to January 14, 2005 at the British Columbia Cancer Agency were identified, including those from a recently published report (Sehn, J Clin Onc. 2005). Patients were included if they were ≥16 years old with advanced stage (stage III /IV, or stage I /II with B symptoms or bulky disease (≥10 cm)), or limited stage with testicular involvement and excluded if HIV-positive or known to have CNS involvement at diagnosis. From Sept 1999 to Feb 2001 patients were treated with CHOP- type chemotherapy. After March 1, 2001 patients received CHOP-R. Results: A total of 435 patients with DLBCL were identified; 125 (29%) were treated with CHOP and 310 (71%) with CHOP-R. There were 28 CNS relapses with no significant difference in frequency between CHOP-treated (11 (9%)) or CHOP-R-treated (17 (5%)) patients (p=0.202). The median time to CNS relapse (8.1 mos vs 6.7 mos) and median survival after CNS relapse (2.7 mos vs 3.8 mos, p=0.665) were similar in the CHOP and CHOP-R treated patients, respectively. In univariate analysis, testicular involvement, renal involvement, advanced stage, and LDH ≥2x ULN were associated with increased risk of CNS relapse. In a multivariate analysis, testicular (OR 7.44, p=0.013) or renal (OR 6.23, p=0.012) involvement, and stage IV disease (OR 4.43, p=0.034) were independent predictors of CNS relapse. Conclusions: Consistent with prior reports, the addition of rituximab does not appear to significantly influence the risk of CNS relapse in patients with DLBCL, possibly due to poor CNS penetration. Risk factors for CNS relapse in the rituximab era are similar to those noted in prior reports based on anthracycline-treated patients. The overall survival of patients with CNS relapse is dismal and new strategies to reduce its incidence warrant further evaluation. No significant financial relationships to disclose.
Rituximab induces long-term remissions in patients with HIV-associated multicentric Castleman's disease
Authors: Bower M. , Powles T. , Williams S. , Newsom-Davis T. , Atkins M. , Stebbing J. , Montoto S. , Nelson M. , Webb A. , Kelleher P. 
Published: March 2020

8049 Background: HIV associated multicentric Castlemans (MCD) is rare lympohproliferative disorder and most treatment options to date, have proved largely unsuccessful. This study investigated the efficacy of the anti CD20 monoclonal antibody rituximab in patients with this disease. Methods: Between 2003 and 2006, patients with histological proven HIV related MCD received a course of 4 infusions of rituximab 375mg/m2 at weekly intervals. Results: Twenty one consecutive patients (18 male) were recruited into this study and the median follow-up is 12 months (range 1–49). The median age was 37 years and all patients were either on highly active antiretroviral therapy (HAART) (62%) or started HAART at the time of MCD diagnosis (38%). The median CD4 cell count at MCD diagnosis was 275/mm3 (range 77–725). One died within 2 weeks of starting rituximab (not evaluable); 20 evaluable patients all achieved clinical remission of symptoms and 71% achieved a radiological response according to RECIST criteria. Rituximab lead to a significant fall in anaemia, thrombocytopenia, CRP, ESR, serum HHV8 viral load and IL-10. Rituximab caused transitory fall in the CD19 count, but had no effect on the CD4, CD8 and NK cell counts or plasma HIV viral load. The disease free survival at 2 years is 79% (95%CI: 49–100%) and overall survival is 95% (95%CI: 86–100%). Two patients have relapsed after 1.6 & 2.8 years and were successfully retreated with rituximab therapy. Conclusions: Rituximab therapy results in a sustained clinical, radiological and biochemical remission in patients with HIV related MCD. No significant financial relationships to disclose.
Phase I/II study of bortezomib (B) in patients with systemic AL-amyloidosis (AL)
Authors: Reece D. E. , Sanchorawala V. , Hegenbart U. , Merlini G. , Palladini G. , Fermand J. , Vescio R. A. , Liu X. , Elsayed Y. A. , Comenzo R. L. 
Published: March 2020

8050 Background: AL is characterized by deposition of monoclonal immunoglobulin light chains leading to multi-organ failure and death. B (Velcade®) is a specific inhibitor of the 26S proteasome with activity in several malignancies. This mechanism of action raises concern of enhancing the amyloidogenic protein deposition and worsening of AL. This phase I/II study is to determine the maximum tolerated dose (MTD) and toxicity profile of B in pts previously treated for AL. Secondary objectives include the rate and duration of hematologic and organ responses. Methods: A 3+3 dose escalation design was used for the phase I part. Eligibility criteria included previously treated AL with organ involvement, LVEF =40% and adequate organ function. Pts with prior B treatment, infection, significant cardiac disease, bleeding or gr. 2 neuropathy were excluded. Seven cohorts are planned to examine two administration schedules. A weekly schedule administering 0.7,1.0,1.3 or 1.6 mg/m2 of B on day 1, 8, 15, 22 of a 35-day cycle. In the bi-weekly schedule, 0.7, 1.0 or 1.3 mg/m2 are given on day 1,4,8, 11 of a 21-day cycle. Pts were assessed at specified intervals and dose-limiting toxicities (DLT) were assessed during cycle 1. Results: At this time, 15 pts were treated in the 4 weekly cohorts. Median age was 59 yrs (38–74). All pts had previously received systemic therapy; 100% had received melphalan (58% with prior SCT), 83% steroids, 58% thalidomide. 75% of pts had = 2 organs involved at baseline, renal 42%, cardiac 33%, neuropathy 33%. One DLT (worsening CHF) was observed in cohort 1.6 mg/m2. Two pts discontinued early due to CHF and hypotension. Grade 3/4 AEs were reported in 42% of pts and the most frequent were fatigue 17%, infection 17%, CHF 8% and retinal detachment 8%. The most frequent grade 1/2 AEs were diarrhea 67%, nausea 42%, fever 33%, dizziness 33% and neuropathy 8%. There were no treatment-related deaths. Of the 11 evaluable pts for response, 5 (45%) had objective hematological responses (2 CR and 3 PR) and 4 pts (36%) have stable disease > 6 months. Dose escalation on the biweekly schedule is ongoing. Conclusions: B has significant activity in patients with relapsed AL in this preliminary analysis and tolerance to B is satisfactory. The MTD for the weekly schedule is 1.6 mg/m2. Further assessment is planned in the phase II part. [Table: see text]
Preliminary results from a phase II study of lenalidomide oral monotherapy in relapsed/refractory aggressive non-Hodgkin lymphoma
Authors: Wiernik P. H. , Lossos I. S. , Tuscano J. , Justice G. , Vose J. M. , Pietronigro D. , Takeshita K. , Ervin-Haynes A. , Zeldis J. , Habermann T. 
Published: March 2020

8052 Background: Lenalidomide (Revlimid), an immunomodulatory drug of the IMiDs class, is approved in the US for treatment of relapsed/refractory multiple myeloma and myelodysplastic syndromes associated with a deletion 5q[31] cytogenetic abnormality. Lenalidomide also has activity in chronic lymphocytic leukemia and cutaneous T-cell lymphoma. This study was designed to assess the safety and efficacy of lenalidomide in patients with relapsed/refractory aggressive non-Hodgkin's lymphoma (NHL). Methods: Patients with relapsed/refractory aggressive NHL with measurable disease after at least 1 prior treatment regimen were eligible. Patients received 25 mg lenalidomide orally once daily on Days 1–21 every 28 days and continued therapy for 52 weeks as tolerated or until disease progression. Response and progression were evaluated using the IWLRC methodology. Results: As of enrollment cut-off, 50 patients were enrolled and 49 received drug. Forty-one patients were evaluable for response. The median age was 65 (46–84) and 18 were female. Histology was diffuse large B-cell lymphoma [DLBCL] (n=21), follicular center lymphoma grade 3 [FL] (n=3), mantle cell lymphoma [MCL] (n=14) and transformed [TSF] (n=3). Median time from diagnosis to lenalidomide was 3.2 (0.4–32) years and median number of prior treatment regimens was 3 (1–7). Fourteen patients (34%) exhibited an objective response (5 complete responses unconfirmed (CRu) and 9 partial responses (PR)), 12 had stable disease (SD) for a tumor control rate (TCR) of 63% and 15 progressive disease (PD). Responses were seen in each of the aggressive histologic subtypes studied: DLBCL (5/21), MCL (6/14), FL (2/3), and TSF (1/3). Five of 11 patients (45%) with a prior stem cell transplant responded. Progression free survival although ongoing is currently > 239 (>191 - >373) days in patients experiencing CRu and > 160 (>54 - >251) days in patients with PR. Most common Grade 4 adverse events were neutropenia (8.2%) and thrombocytopenia (8.2%) while most common Grade 3 adverse events were neutropenia (22%), leukopenia (14%) and thrombocytopenia (12%). Conclusion: Lenalidomide oral monotherapy is active with manageable side effects in relapsed/refractory aggressive NHL. No significant financial relationships to disclose.
Phase II trial of the oral mTOR inhibitor everolimus (RAD001) for patients with relapsed or refractory lymphoma
Authors: Johnston P. B. , Ansell S. M. , Colgan J. P. , Habermann T. M. , Inwards D. J. , Markovic S. N. , Micallef I. N. , Porrata L. F. , LaPlant B. R. , Geyer S. M. , Witzig T. E. 
Published: March 2020

8055 Background: mTOR inhibition with intravenous temsirolimus (Wyeth Pharmaceuticals) has been associated with responses in mantle cell lymphoma (J Clin Oncol 23;5347, 2005) as well as other lymphomas (Blood 108 (11) 2483; 2006). This phase II study tested the oral mTOR inhibitor everolimus (RAD001, Novartis Pharmaceuticals) in three simultaneous two-stage phase II lymphoma studies - aggressive (group 1), indolent (group 2), or uncommon (group 3). The goals were to learn the toxicity profile and to assess the anti-tumor response. Planned interim analysis for groups 1 and 3 have been completed and are the subject of this report. Methods: Patients (pts) received 10 mg PO daily for each 28 day cycle (up to 12) and restaged after 2, 6, and 12 cycles. The primary endpoint is the confirmed response rate, including CR, CRu or PR. 12 pts were enrolled in stage 1 of each study. At least 1 success in 12 is required to proceed to stage 2, to a total of 37 pts. Overall, the treatment will be considered promising if 4 or more successes are observed in all 37 pts in each group. Results: The median age of the 12 pts in group 1 was 68.5 yrs (range: 53–80), with a median of 3 (range, 1–15) prior therapies. Four pts had a prior stem cell transplant (SCT). Pts completed a median of 7 (range, 1–12) cycles of therapy. 6 confirmed responses have been achieved (1 CR, 5 PR), meeting the overall criteria for promising results in this study. Common grade 3 adverse events (AEs) include thrombocytopenia (3 pts) and anemia (2 pts). For group 3, the median age was 49 yrs (range, 27–78), with a median of 7 (range, 1–13) prior therapies and 6 pts had a prior SCT. Pts have completed a median of 6.5 cycles (range, 1–11). 5 confirmed responses have been achieved (5 PR), meeting the criteria for this regimen to be considered promising. Of these 5 patients, 3 had HD, 1 T-cell NHL, and 1 had macroglobulinemia. Common grade 3 AEs include anemia (3 pts) and thrombocytopenia (2 pts). No grade 4 AEs were reported. Conclusions: Oral everolimus has activity in a spectrum of lymphomas with acceptable toxicity. The responses observed in both group 1 and group 3 met the criteria to continue accrual. These results provide the rationale for additional studies with this novel class of agents and to integrate mTOR inhibitors into salvage treatment regimens. No significant financial relationships to disclose.
R-HCVAD/R-MTX-ARAC is an effective regimen for untreated diffuse large B-cell lymphoma (DLBCL) with aggressive features: M. D. Anderson experience in 40 patients
Authors: Fayad L. , Temple S. , Pro B. , Hagemeister F. , Cabanillas F. , Samaiego F. , McLaughlin P. , Wang M. , Kwak L. , Romaguera J. , Rodriguez M. A. 
Published: March 2020

8058 Background: R-HCVAD (rituximab-cyclphosphamide, vincristine, dexamethasone, doxorubicin) alternating with R-MTX-ARAC (rituximab, methotrexate-cytarabine) is a chemoimmunotherapy regimen with activity in ALL, mantle cell, and Burkitt’s lymphomas (BL). Histological differentiation between BL, atypical BL, and DLBCL with high-grade features can be difficult. We thus have treated patients with DLBCL with high-grade histological features and/or poor-risk IPI with R-HCVAD. Methods: Forty consecutive patients with information collected prospectively in the NCCN database, treated between 7/2002 and 10/05 at M.D Anderson Cancer Center, and who received at least one cycle are included in this cohort analysis. Characteristics: 18 (45%) male; 18 (45%) HI and High IPI; 25 (62.5%) ↑LDH; 26 (65%) with Stage III/IV; 2 (5%) with PS>1; 8 (20%) with >60 years; 25 (62%) a Ki-67 >90%. Four patients received less than 4 cycles of treatment. Results: ORR was of 100%, with 95% CR/CRu. With a median follow-up of 26 months, 6 patients failed: 1 died in CR of pulmonary embolism while on treatment; 1 patient who achieved CR, had PD before the end of treatment; 1 achieved a PR and was transplanted (is alive in remission); 1 achieved a PR and progressed died of disease; and 2 relapsed (one is in remission after an ASCT). Four patients have died: 3 of disease, 1 of pulmonary embolism. The 3-year OS is 88% (95% CI 77%-99%); 3-year FFS is 71% (95% CI 47%-95%). The 3-year FFS for patients with L/LI risk (3-failures of 22 pts) was 78% (95% CI 52%-100%); and for patients with HI/H IPI (3 failures of 18 pts) 65% (95% CI 27%-100%). Conclusions: R-HCVAD/R-MTC-ARAC is a very active regimen for DLBCL of high grade. Toxicity was mostly hematological. We are currently doing a prospective randomized phase II study comparing this regimen to standard R-CHOP in patients with poor-risk IPI scores. No significant financial relationships to disclose.
Retrospective analysis of P-STAT6 expression as a predictive marker in primary nervous system lymphoma patients assigned to high-dose methotrexate
Authors: Altavilla G. G. , Pitini V. V. , Arrigo C. C. , Marabello G. G. , Naro C. C. , Tomasello C. C. , Righi M. M. , la Torre D. D. 
Published: March 2020

8059 Background: Recent immunohistochemical data and gene expression values have demonstrated that a majority of Primary Nervous System Lymphoma (PCNSL) express both bcl-6 as well as MUM-1, suggesting an overlapping histogenetic time slot of B-cell differentiation. In addition, an increased expression of P-STAT6 seems to predict short survival in patients (pts.) treated with high-dose Methotrexate (HD-MTX)-based chemotherapy. To investigate the clinical impact of the P-STAT6 expression in this setting we have analyzed P- STAT6 expression in available tumor tissue blocks of 25 PCNSL pts. treated with HD-MTX who have had follow up for at least 2.5 years. Methods: Immunohistochemistry for P-STAT6 was performed using an indirect immunoperoxidase method. Responses were evaluated according to the International Workshop criteria for PCNSL. Progression-free survival (PFS) and overall survival (OS) were calculated according to the Kaplan-Meier Method. Results: 15 male, 10 female; mean age 52.1 years, were included in the analysis. The immunohistochemical analysis showed three different patterns of P-STAT6 expression: 7 pts. had absent P-STAT6 expression and low tumor cellular density (group A); 8 pts. had sparse positive P-STAT6 expression and low cellular density (group B), 10 pts. had strong P-STAT6 nuclear expression in tumor cells and on vascular endothelia and high cellular density (group C). The overall response rates to treatment (CR+PR) were 83% for both group A and B compared to 5% of group C. Furthermore the pts. with intense P-STAT6 expression experienced an impressive early progression (PFS median 2.5 months) and an OS very short (median 10 months). To date pts. of groups A and B have not reached median OS and PFS. Conclusions: PCNSL pts. with intense P-STAT6 expression experienced short survival when treated with HD-MTX- chemotherapy. No significant financial relationships to disclose.
The choice of first-line therapy in advanced Hodgkin lymphoma: Retrospective comparison of ABVD and escalated BEACOPP regimen
Authors: Jurczak W. , Krochmalczyk D. , Giza A. , Węgrzyn J. , Sobocinski M. , Gawelko J. , Malkowski B. , Czyz J. , Pawlega J. , Skotnicki A. B. 
Published: March 2020

8063 Background: HD patients with high risk have a relatively poor prognosis with less than 50% 5-year overall survival (OS) if treated with ABVD regimen. Methods: Therapy results of all 105 patients with advanced HL (CS IIBX -IV) treated from diagnosis at our Department in the last decade, are presented. The choice of initial 3 cycles between ABVD and escalated BEACOPP was done at the patients preferal and physician's adivice. Further 3 chemotherapy cycles depended on initial response assessment: poorly responding ABVD treated patients were offered therapy escalation. Patients with a good response (over 80% regression) after the first 3 cycles were later treated with ABVD. EFS and OS were primary endpoints of the study. Results: We divided patients into 2 treatment groups, depending on the first 3 cycles (escalated BEACOPP n = 57 or ABVD n = 48). Poor response resulting in therapy intensification was not considered as an event defined only as a relapse or progression during therapy. There was a statistically insignificant imbalance between the risk factor distribution with less favorable prognosis in patients treated with esc BEACOPP: 38 % of pts in IV th clinical stage (as compared to 31% in ABVD group), 3,08 EORTC risk factors (as compared to 2,64 in ABVD group) and 2,19 according to German Hodgkin Study Group (1.93 respectively). Increased toxicity of esc BEACOPP regimen was due to grade 3/4 cytopaenia (present in all patients) resulting in more infection episodes (according to WHO scale stage 3 - 16 pts , stage 4 - 8 pts; in ABVD group, 2 and 1 pt respectively). There were no treatment related mortalities. In esc BEACOPP projected 5 y OS was 96% and EFS 89% , which is comparable to GHSG results. 5 y OS and EFS in ABVD group are 87% and 66% respectively. The difference in EFS is statistically significant (p< 0.05). Conclusions: In our study we checked the feasibility of esc BEACOPP regimen in high risk HD pts. The results show the importance of the intensity of the first line approach. In the poor responders after the initial 3 cycles, even early treatment intensification, didn’t improve the outcome. De-escalation of therapy after the first 3 cycles, in good responders, didn’t make OS and EFS inferior to GHSG results in which they recommend 6 cycles of esc BEACOPP therapy. No significant financial relationships to disclose.
Preliminary results from a phase II study of lenalidomide oral monotherapy in relapsed/refractory indolent non-Hodgkin lymphoma
Authors: Witzig T. E. , Vose J. , Pietronigro D. , Takeshita K. , Ervin-Haynes A. , Zeldis J. , Wiernik P. H. 
Published: March 2020

8066 Background: Lenalidomide, an immunomodulatory drug, is approved in the US for treatment of relapsed/refractory multiple myeloma and myelodysplastic syndromes associated with a deletion 5q[31] cytogenetic abnormality. Lenalidomide also has activity in chronic lymphocytic leukemia and cutaneous T-cell lymphoma. This study was designed to assess the safety and efficacy of lenalidomide monotherapy in patients with relapsed/refractory indolent non-Hodgkin's lymphoma (NHL). Methods: Patients with relapsed/refractory indolent NHL with measurable disease after at least 1 prior treatment regimen were eligible. Patients received 25 mg lenalidomide orally once daily on Days 1–21 every 28 days and continued therapy for 52 weeks as tolerated or until disease progression. Response and progression were evaluated using the IWLRC methodology. Results: As of enrollment cut-off, 43 patients received drug and 27 were evaluable for response. The median age was 63 (43–82) and 12 were female. Histology was small lymphocytic lymphoma [SLL] (n=12), follicular center lymphoma grades 1,2 [FCL] (n=12) and nodal marginal B-cell lymphoma [NML] (n=3). Median time from diagnosis to lenalidomide was 4.3 (0.4- 24) years and median number of prior treatment regimens was 3 (1–17). Seven patients (26%) exhibited an objective response (2 complete responses (CR), 1 complete response unconfirmed (CRu) and 4 partial responses (PR)), 9 had stable disease (SD) for a tumor control rate (TCR) of 59% and 11 progressive disease (PD). Responses were produced in each of the indolent histologic subtypes studied: SLL (3/12), FCL (3/12) and NML (1/3). Since most responses develop at ≥ 4 months, additional responses may be seen in early SD patients with longer follow-up. Five patients (12%) exhibited Grade 4 neutropenia, and Grade 3 adverse events were neutropenia (16%) and thrombocytopenia (14%). Conclusion: Lenalidomide oral monotherapy is active with manageable side effects in relapsed/refractory indolent NHL. [Table: see text]
Non-Hodgkin lymphoma of the Waldeyer's ring: Is a higher radiotherapy dose required?
Authors: Bahl G. , Laskar S. , Muckaden M. A. , Nair R. , Gupta S. , Bakshi A. , Gujral S. , Parikh P. M. , Shrivastava S. K. , Dinshaw K. A. 
Published: March 2020

8067 Background: To evaluate the prognostic factors and treatment outcome of Indian patients with primary Non-Hodgkins Lymphoma (NHL) of the Waldeyer's Ring (WR) region treated at a single institute. Methods: 269 patients with NHL of the WR treated at Tata Memorial Hospital, Mumbai from January 1990 to December 2002 were included. The median age was 45 years and majority of the patients (67%) were males. Systemic symptoms were present in only 16% of patients, primary site was the tonsil in 58%, nasopharynx in 42% and base tongue in 5% of patients. Majority had Diffuse Large B-Cell Lymphoma (85%); 26% patients presented with stage I disease and 66% had stage II disease. Treatment comprised of a combination of chemotherapy (CTh) and radiotherapy (RT) in majority of the patients (71%). Among these patients, 63% received an RT dose of =45Gy. Results: The complete response rate was 68%. After a median follow-up of 57 months, the 5 year DFS & OS for the whole group were 62.2% and 70.1% respectively. Multivariate analysis showed that; age >30 years (HR=4.05, 95%CI=1.53–10.7, p=0.005), WHO performance score =2 (HR=2.36, 95%CI=1.12–4.95, p=0.023), T-cell lymphomas (HR=5.55, 95%CI=2.43–12.7, p<0.001), bulky tumors (HR=2.08, 95%CI=1.02–4.257, p=0.045), and nasopharyngeal primary (HR=3.26, 95%CI=1.51–7.02, p=0.003), had a negative influence on survival. Patients treated with a combination of CTh & RT had a significantly better outcome than those treated with CTh alone (OS: 78.9% vs. 48.1%, p<0.00001). The hazard ratio for death (HR) in the chemotherapy alone group was 3.50 (95% CI=2.17–5.65). The CR (p=0.01), DFS (p<0.0001) and OS (p=0.002) rates were significantly better for patients receiving a RT dose of =45Gy. The HR in the subgroup that received a RT dose of < 45Gy was 5.09 (95% CI=2.39–10.86). Conclusions: Age at diagnosis, WHO performance score, T-cell histological type, size and site of the tumor significantly influence outcome in patients with primary NHL of the Waldeyer's Ring. Combined modality treatment, comprising of CTh & RT (with an RT dose of =45Gy), results in satisfactory outcome in patients with this rare neoplasm. No significant financial relationships to disclose.