bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rituximab, gemcitabine and oxaliplatin (R-GEMOX): An effective regimen for relapsed and refractory B-cell lymphoma
Authors: El Gnaoui T. , Dupuis J. , Belhadj K. , Rahmouni A. , Copie-Bergman C. , Gaillard I. , Diviné M. , Tabah-Fisch I. M. , Reyes F. , Haioun C. 
Published: March 2020

7562 Background: High-dose therapy with autologous stem cell support (HDT) is an established treatment for chemosensitive relapse in lymphoma. However, not all patients are candidates for HDT because of age, comorbidities or previous HDT. In addition,effective and less toxic alternatives to classical Cisplatin/ARA-C-based salvage regimens are needed. Methods: Based on the clinical activity, tolerability of rituximab (R), gemcitabine (G) and oxaliplatin (Ox) and synergy between these drugs, the R-GEMOX regimen was designed with R (375mg/m2 d 1), G (1,000 mg/m2 d 2) and Ox (100 mg/m2 d 2). Treatment was given every two weeks. Between January 2002 and June 2005, 46 patients with refractory/relapsing B-cell CD20+ lymphoma not eligible for HDT were enrolled in an unicenter pilot study whose primary objective was overall response rate (ORR) after 4 cycles (induction phase). Patients were planned to receive 8 cycles if at least PR was observed after 4 cycles. Median age was 64 years (range: 43–78) and histological subtypes were: diffuse large B-cell lymphoma (n = 33), follicular (n = 8) and mantle cell (n = 5). Prior treatments included anthracyclin in 45 patients, rituximab in 26 (56%) and HDT in 14 (30%). The median number of prior treatments was 2 (range: 1 to 5) and 13 patients (28%) had received at least 3 prior regimens. Results: 315 cycles were given. The dose administered was 100% of the intended dose for the three drugs in all patients but 8, for whom the dose of oxaliplatin was reduced due to neurotoxicity (n = 7) or preexisting renal insufficiency (n = 1). Eight patients progressed during the induction phase. After 4 cycles, responses were: 10 CR, 13 CRu and 15 PR resulting in an ORR of 83%. At the end of treatment, among the 38 responder-patients, 36 patients achieved CR (78% of the entire population), one patient remained in PR and one progressed. With a median follow-up of 27 months, the 2-year progression-free and overall survivals were 53% and 66%, respectively. NCIC grade 3–4 neutropenia and thrombocytopenia were reported in 48% and 22% of the cycles. A grade 4 infection was observed in only 3% of the cycles. There was no renal toxicity. Conclusions: The R-GEMOX regimen shows promising activity with an acceptable toxicity. It is currently evaluated in a multicentric phase II study. [Table: see text]
Dose-modified oral chemotherapy for AIDS-related non-Hodgkin’s lymphoma (AR-NHL) in East Africa
Authors: Mwanda W. O. , Orem J. , Fu P. , Banura C. , Kakembo J. , Ness A. , Johnson J. , Black J. , Katongole-Mbidde E. , Remick S. 
Published: March 2020

7564 Background: Dose-modified chemotherapy for AR-NHL in the pre-HAART era has been shown to be equally efficacious and less myelotoxic [N Engl J Med 1997;336:1641 (mBACOD); J Clin Oncol 2001;19:2171 (mCHOP)]. In resource-constrained settings, intravenous chemotherapy and supportive care of the AIDS/cancer patient are challenging (J Natl Cancer Inst 2002;94:718). Methods: We embarked on a pilot feasibility trial of dose-modified oral chemotherapy [lomustine 50 mg/m2 D1 (C1 only); VP-16 100 mg/m2 D1–3; and cyclophosphamide/procarbazine 50 mg/m2 each D22–26 at 6-week intervals (1 cycle) for 2 cycles] in HIV-infected patients with biopsy-proven AR-NHL in East Africa. Results: A total of 52 pts (23 Uganda; 29 Kenya) were registered to study. The majority of pts were female (56%) with median age 39 yrs (range 18–64); poor PS (2 or 3) - 62%; high grade lymphoma (65%); advanced stage (III or IV) - 67%; and B symptoms (79%). At study entry median CD4 count was 207/μL and HIV-1 viral load 98,857 copies/ml. Nineteen pts (37%) had access to ARV. A total of 74.5 cycles of therapy were administered to 49 pts (median 2; range 0.5–2). The regimen was well tolerated. There were 4 episodes of febrile neutropenia and 3 treatment-related deaths (6% mortality rate). Overall objective response rate is 67% (CR/uCR 49%); median survival 8.2 months (range <1.0 to 52.5+ mos.); and 22 patients remain alive as of 10/7/05. Conclusions: Dose-modified oral chemotherapy is efficacious, has comparable outcome to that in the US in pre-HAART era, an acceptable safety profile, and is pragmatic in the resource-limited setting. Further investigation of the oral regimen vs. mCHOP is warranted. [Supported in part by NIH grants: CA83528, AI36219, CA70081, and TW00011. Bristol-Myers Squibb and Sigma Tau Pharmaceuticals provided the chemotherapy drugs for this trial.] (J. Black, PhD, formerly DCTD, NCI, Bethesda, MD, USA). No significant financial relationships to disclose.
BACOP/FR combination chemotherapy as front-line treatment of follicular lymphoma. A phase II study of the Gruppo Italiano Studio Linfomi (GISL)
Authors: Luminari S. , Lombardo M. , Mammi C. , Bellei M. , Merli F. , Stelitano C. , Lazzaro A. , Marasca R. , Brugiatelli M. , Federico M. 
Published: March 2020

7571 Background: Doxorubicin, fludarabine and rituximab are all considered active drugs in the treatment of follicular lymphoma (FL). Howevere, the best induction regimen is still matter of debate. In 2003 the GISL started a phase II trial to assess efficacy and tolerability of a combination of bleomycin, adriamycin, ciclophosphamide, vincristine and prednisone (BACOP) followed by fludarabine and rituximab (FR). Methods: To be included in the study pts should have: histologically confirmed diagnosis of FL, stage II-IV disease, age 18–70, active disease. Pts were assessed for t(14:18) by PCR on bone marrow at diagnosis and at time of response assessment. Treatment consisted in three courses of BACOP followed by 4 courses of FR for pts in partial remission (PR) or complete remission with persistent t(14:18) positivity (CRM+). Pts achieving molecular complete remission (CRM-) stopped therapy after BACOP. The main endpoints of the study were overall response rate (CR+PR) (ORR) and failure free survival (FFS). A final accrual of 60 assessable pts was planned, however a faster accrual than expected allowed to enrol 91 pts between May 2003 and Dec 2005. Results: At time of present analysis 61 pts were valuable for final response: Median age was 56 yrs (25–70), male gender 56%, 18% with systemic symptoms, 88% in stage III-IV disease, 13% had elevated LDH and 21% bulky disease. Molecular marker was present in 30 out of 57 pts. 19 pts achieved a CR after three courses of BACOP; four of them, being in CRM- stopped therapy. 28 pts achieved CR with four additional courses of FR. At the end of treatment CR and ORR were 77% and 90% respectively; relatively to pts with molecular marker at diagnosis CRM- was 60%. Toxicity data are available for 57 patients: grade III/IV anemia and neutropenia were observed in two (3%) and 18 (32%) cases respectively; severe infections occurred in two cases, both bacterial pneumonia. After a median follow-up of 17 months (0.5–31) 12 events were observed: Major toxicity, four; non responders, two; relapse, six. Conclusions: BACOP/FR is a feasible and safe regimen for the treatment of patients with FL with promising efficacy. More mature follow-up is required to confirm these preliminary results. No significant financial relationships to disclose.
A phase II study of bortezomib in relapsed Hodgkin lymphoma: Preliminary results of CALGB 50206
Authors: Blum K. A. , Johnson J. L. , Niedzwiecki D. , Cannellos G. P. , Cheson B. D. , Bartlett N. L. 
Published: March 2020

7576 Background: Constitutive NF-κB activation has been described in both Hodgkin lymphoma (HL) cell lines and patient-derived Reed-Sternberg cells. In vitro, therapeutic targeting of NF-κB with proteasome inhibitors like bortezomib leads to apoptosis of HL cell lines, providing a rationale for clinical trials with this agent. Methods: From 3/15/2004 until 2/23/2005, the CALGB conducted a phase II trial of bortezomib in patients (pts) with relapsed and refractory classical HL to assess response rate and toxicity. Eligibility requirements included at least one prior systemic therapy, measurable disease, absolute neutrophil count ≥ 750/μL, platelets ≥ 75,000/μl, and creatinine ≤ 2.5 mg/dl. Pts able to undergo a stem cell transplant with curative intent or with pre-existing sensory neuropathy ≥ grade 2 were not eligible. Bortezomib was administered at 1.3 mg/m2 days 1, 4, 8, and 11 every 21 days for 2–8 cycles, or until disease progression. Results: 30 pts received a median of 2 cycles (range, 1–8). For 25 pts with available data, 80% had stage IV disease with a median of 4 prior therapies (range 2–8, 92% with prior stem cell transplant). For 29 pts with complete response data, 2 pts were not evaluable due to adverse events (bleeding gastric ulcer and grade 4 dyspnea) during cycle 1 leading to a discontinuation of therapy prior to restaging. In the remaining 27, no responses were observed [95% CI (0.0, 0.13)]; 18 pts progressed, and 9 pts had stable disease. Median follow-up is 4.4 (range, 0.6 -16.4) months. The median progression-free and overall survival times are 1.4 [95% CI (1.3, 2.8)] and 11.6 months [95% CI (6.6, ongoing)], respectively. Toxicity data are available for 26 pts. Grade 3–4 events included thrombocytopenia (27%), lymphopenia (8%), dyspnea (8%), anemia (4%), diarrhea (4%), hypotension (4%), rash (4%), and hyperbilirubinemia (4%). Both instances of grade 3–4 dyspnea occurred in pts with disease progression in the lung. 27% developed grade 2 sensory or motor neuropathy. Conclusions: Although well-tolerated, bortezomib has no single agent efficacy in relapsed classical HL at the current dose and schedule. No significant financial relationships to disclose.
Absolute lymphocyte count prior to rituximab therapy predicts time to progression in patients with follicular grade 1 lymphoma
Authors: Behl D. , Markovic S. N. , Witzig T. E. , Colgan J. P. , Habermann T. M. , Inwards D. J. , Ansell S. M. , Micallef I. N. , Johnston P. B. , Porrata L. F. 
Published: March 2020

7586 Background: The immunologic mechanisms of action of rituximab have been described as complement mediated lysis, vaccine like effect, antibody-dependent cellular cytotoxicity (ADCC) and the cellular microenvironment. We hypothesized that in the treatment of follicular grade 1 lymphoma (FL), the presence of a stronger host immune status prior to rituximab therapy would result in a prolonged time to progression (TTP). As a surrogate marker for immune status, we evaluated the absolute lymphocyte count (ALC) prior to rituximab treatment. Methods: Between 1996 and 2002, 1,104 consecutive FL patients were evaluated at Mayo Clinic Rochester. Of these patients, we retrospectively analyzed a group of all FL patients who received rituximab (375 mg/m2 once a week for four weeks) alone at any time during their lymphoma treatment at the Mayo Clinic (n=79). The primary end-point was to assess the impact of ALC just prior to rituximab therapy on TTP for FL. Results: The median age of the cohort was 56.6 years (range: 25–98 years). The median follow-up was 12.5 months (range: 1–76 months). An ALC count of ≥ 890 cells/μL prior to rituximab therapy predicted a longer TTP compared with an ALC < 890 cells/μl (25 months versus 8 months, respectively, p < 0.0124). A higher complete response rate was observed in the ALC ≥ 890 cells/μL group compared with the ALC < 890 cells/μL group [15/40 (38%) vs 5/39 (13%), p < 0.035]. The groups were balanced regarding the Follicular Lymphoma International Prognostic Index (FLIPI) (p = 0.794). Multivariate analysis demonstrated ALC ≥ 890 cells/μL prior to rituximab therapy as an independent prognostic factor for TTP when compared to hemoglobin, LDH, and Ann Arbor stage. The ALC was independent of the FLIPI in multivariate analysis. Conclusions: This data supports the hypothesis that a higher lymphocyte count, as a marker of the immune status of the patient, predicts for a longer TTP following rituximab therapy. No significant financial relationships to disclose.
Patterns of mortality after prolonged follow-up of a randomized trial using granulocyte colony-stimulating factor (G-CSF) to maintain chemotherapy dose intensity in non-Hodgkin lymphoma (NHL)
Authors: Clamp A. R. , Bhattacharya S. , Ryder D. W. , Pettengell R. , Radford J. A. 
Published: March 2020

7590 Background: Recombinant G-CSF is commonly used to maintain chemotherapy dose intensity and reduce the incidence of infective complications in the management of NHL. The possible impact of this effect on mortality patterns after prolonged follow-up is worthy of investigation. We investigated the long-term survival and incidence of second malignancies in the first randomized trial utilising recombinant G-CSF in NHL (Pettengell R et al Blood 1992, 80: 1430–1436). Methods: Data on overall survival (OS), progression-free survival (PFS), freedom from progression (FFP) and the incidence of second malignancies were extracted from medical records and cancer registry databases for 80 patients with aggressive subtypes of NHL, who had previously been randomised to receive either VAPEC-B chemotherapy alone (39 patients) or VAPEC-B with G-CSF (41 patients). 10 year survival figures were extracted and Kaplan-Meier survival curves were drawn for the above parameters and compared between treatment groups using the log-rank test. Results: Median follow-up was 11.8 years for surviving patients (range 7.8–13.1 yrs). Patients receiving G-CSF achieved a 12% higher median dose intensity of chemotherapy. No significant differences were found in PFS or OS but 10 year FFP appeared to be better in the G-CSF arm (60.8%) compared with the control arm (45.6%) (log-rank test p=0.12). Eleven deaths from non-NHL causes occurred in the G-CSF arm compared with three in the control arm (log- rank test p=0.06). Five second malignancies were detected on long-term follow-up in the G-CSF arm compared with two in the control arm. Conclusions: The demonstration of different mortality patterns in the two arms may be related to the greater dose intensity of chemotherapy received in the G-CSF arm. Although, our study has insufficient statistical power to draw definite conclusions, this finding warrants further investigation. No significant financial relationships to disclose.
Manifestation and prognostic value of EBV serology in nasal/nasopharyngeal T and NK-cell lymphomas
Authors: Zhang Y. , Huang Y. , Xiao J. , Xia Y. , Lu T. , Lin T. 
Published: March 2020

7596 Background: Extranodal nasal type T and NK-cell lymphoma is highly associated with the Epstein-Barr virus (EBV) infection which is usually found in tumor cells, but the serum manifestation of EBV and its prognostic value remains unclear. Methods: 151 patients with nasal/nasopharyngeal T and NK-cell lymphomas were reviewed, the diagnoses of which were confirmed by histology and immunohistochemistry from Jan, 1992 to Nov, 2004. In 40 patients, which included 30 males and 10 females and aged 24 to 73(median 46) years old, analyses were performed of serum titers of antibodies against virus-capsid antigen (VCA-IgA) and early antigen (EA-IgA) with immunoenzyme assay, and antibody against EBV DNAase (EDAb), with immunoradiological method. Positive criteria were identified as VCA-IgA ≥ 1: 10, EA-IgA≥ 1: 10, and EDAb ≥ 30%. Clinically, 87.5% of the 40 patients were staged as Ann Arbor I and II diseases. Most patients underwent combined chemo and radiotherapy. Results: Median follow-up time for survived patients was 17(6–136) months. Median survival time for the overall patients were 12 months. Highest serum VCA-IgA, EA-IgA, and EDAb levels were 1: 1280, 1: 40, and 86% respectively. Positive rates of the three parameters were 60%, 15%, and 50% respectively. 30 patients(75%) had at least one positive parameter. Positve EA-IgA was negatively correlated with survival (p=0.0245) in Kaplan-Meier analysis, neither positive VCA-IgA or elevated EDAb level showed significant correlation with survival (p=0.134 and 0.405 ). Conclusions: Most patients with nasal/nasopharyngeal T and NK-cell lymphomas showed serum evidences of EBV infection, higher EA-IgA level can be a poor prognostic factor for survival. The importance of EBV serology in patients with nasal/nasopharyngeal T and NK-cell Lymphoma deserves further investigation. No significant financial relationships to disclose.
A phase II study of HCVIDDOXIL alternated with methotrexate-cytarabine in patients with newly diagnosed T-cell lymphoma
Authors: Pro B. , Fayad L. , Romaguera J. , Hagemeister F. H. , Samaniego F. , McLaughlin P. , Rodriguez A. M. , Kwak L. , Walker P. , Dang N. H. 
Published: March 2020

7597 Background: T cell lymphomas (TCL) generally are more aggressive and have a poorer prognosis than the corresponding B cell lymphomas. A chemotherapeutic regimen that is effective in aggressive lymphoid malignancies is HCVAD alternating with methotrexate (MTX) and cytarabine (Ara-C). Pegylated liposomal doxorubicin (DOXIL) is associated with greater tumor penetration and less toxicity. We initiated a phase II study to evaluate the efficacy of the regimen HCVIDDOXIL, using DOXIL as a substitute for doxorubicin in the HCVAD regimen, alternated with MTX-Ara-C . Methods: Previously untreated patients (pts) with Zubrod performance status ≤3, age > 18 years, and adequate organ function were eligible. Pts with skin involvement alone, CD30+, ALK +, T-anaplastic large cell lymphoma (ALCL), HIV-1 positive serology, and evidence of CNS involvement were excluded. Pts received HCVIDDOXIL ( cyclophosphamide 300 mg/m2 iv Q 12 h × 6 doses d 1–3, mesna 600 mg/m2 iv daily over 24 hours by continuous infusion d 1–3, DOXIL 25 mg/m2/day iv on d 2, vincristine 1.4 mg/m2 (max. 2 mg) iv days 4 and 11, dexamethasone 40 mg iv or po daily × 4 d 1–4 and 11–14) alternated with MTX/Ara-C ( MTX 200 mg/m2 iv over 2 hours on d 1, then 800 mg/m2 iv over 22 hours on d1, Ara-C 3 g/m2 iv Q 12 hours × 4 doses on d 3–4) every 3 weeks for a maximum of 8 cycles. Endpoints were progression-free survival and response rate. Results: Between October 2003 and November 2005, 23 pts were enrolled. Median age 53 years (range, 23–68). Twelve pts had stage IV, 6 stage III, 3 stage I, and 2 stage II disease. Fourteen (60%) pts had extranodal disease, and 8 (36%) pts had an elevated LDH. In 21 evaluable pts, the ORR was 90% [CR n=12 (57%); PR n= 7 pts (33%)]. Common Grade 3–4 adverse events were thrombocytopenia in 17 pts (77%), neutropenia in 6 (27%), anemia in 5 (23%), and febrile neutropenia in 7 (32%). With a median follow-up of 13 months, the median progression-free survival is 8.3 months (95% CI: 6.5 to 14.2 months). Conclusions: In this high-risk population the regimen HCVIDDOXIL alternated with MTX-Ara-C induced a high response rate. As expected, the most common toxicity was myelosuppression. The efficacy of this regimen should be confirmed in a larger cohort of patients. Enrollment in this study continues. No significant financial relationships to disclose.
The benefit of whole-body low-dose unenhanced multidetector computer tomography (WBLD-MDCT) for follow up and therapy response monitoring in patients with multiple myeloma: Correlation with hematologic parameters
Authors: Horger M. S. , Driessen C. , Brodoefel C. , Faul C. , Pereira P. , Vogel W. , Claussen C. D. , Kanz L. 
Published: March 2020

7607 Background: To assessthe value of whole-body low-dose multidetector computer tomography (WBLD-MDCT) as diagnostic and survey modality in multiple myeloma (MM), and as a one-stop alternative (Horger et al. EJR 2005;54:289–297) to established imaging techniques (e.g. x-ray and MRI). Methods: Between 7/2001 and 2/2005, WBLD-MDCT scans were obtained in 90 consecutive patients with histologically proven stage II-III MM, all patients having 2 or more scans (mean = 3,8; range = 2–6). CT-scans were performed using a standardized low-dose protocol and the number, size and density of focal or diffuse medullary (in the appendicular skeleton and pelvis) and extra-medullary lesions as well as osteolysis were analysed for each examination and at follow up. Results were correlated with current standard MM laboratory data and at follow up in order to assess correct temporal recognition of significant myeloma changes by both methods. Results: Detection and follow up of medullary and extra-medullary MM lesions and osteolysis by WBLD-MDCT resulted in a sensitivity of 92%, a specificity of 93%, a NPV of 95%, a PPV of 85% and a likelihood ratio for patients with CT-abnormalities to present changes in the course of their disease of 12. Results of radiologic and hematologic analysis showed high agreement at follow up (median, 3 mo). However, agreement of both techniques at the time of investigation was only moderate (κ = 0.629), with CT being correct in 60% of mismatching cases. Thus, CT enabled earlier detection of MM changes. WBLD-MDCT assessed correctly the course of disease in all 4 patients with nonsecretory MM. Evaluation of stability was optimal in all patients. Conclusions: WBLD-MD represents a reliable, widespread, quick (75s acquisition time), and cost-effective imaging technique in MM, allowing detection of bone marrow involvement, extra-medullary tumors and lytic bone lesions in different clinical settings (staging, follow up, therapy monitoring, evaluation of stability). WBLD-MDCT repeatedly allowed detection of changes in the course of the disease prior to laboratory data, especially in extramedullary MM relapse and nonsecretory MM. No significant financial relationships to disclose.
A phase I/II study of arsenic trioxide, bortezomib, and ascorbic acid in relapsed or refractory multiple myeloma
Authors: Berenson J. R. , Matous J. V. , Ferretti D. , Swift R. A. , Mapes R. A. , Morrison B. , Yeh H. S. 
Published: March 2020

7611 Background: The combination of arsenic trioxide (ATO) and bortezomib (B) has shown synergistic anti-tumor activity against human multiple myeloma (MM) cells in preclinical studies, suggesting that this combination may effectively treat patients with MM. In addition, ascorbic acid (AA) can sensitize MM cells to the cytotoxic effects of ATO. Methods: Patients with relapsed or refractory MM were enrolled in this phase I/II dose-escalation trial in 6 cohorts. Patients were given ATO (0.125 or 0.250 mg/kg), B (0.7, 1.0, or 1.3 mg/m2), and a fixed dose of AA (1000 mg) IV on days 1, 4, 8, and 11 of a 21-day cycle for a maximum of 8 cycles. The planned sample size was a maximum of 27 evaluable patients. The primary endpoint was safety and tolerability of the ATO/B/AA regimen in patients with relapsed or refractory MM. Results: At the time of this interim analysis, 22 patients (median age, 63 years) have been enrolled, and accrual has been completed on all cohorts. This group had failed a median of 4 (range, 3–9) prior therapies. One occurrence of grade 4 thrombocytopenia was observed. One occurrence of asymptomatic arrhythmia led to patient withdrawal. All other adverse events were grade 1 or 2. For the 21 patients evaluable for efficacy, objective responses were observed in 10 patients (43%), including 2 complete (CR), 2 partial (PR), and 5 minor (MR) responses. Only 1 (1 MR) of 6 patients receiving the lowest dose of B (0.7 mg/m2) showed a response, whereas 8 (2 CR, 2 PR, and 4 MR) of 15 patients receiving the higher doses (1.0 or 1.3 mg/m2) responded. Conclusions: The ATO/B/AA regimen was well tolerated by the majority of patients, and produced objective responses in 43% of the patients in this heavily pretreated group. The results of this phase I/II study warrant further clinical evaluation of the ATO/B/AA combination regimen for the treatment of patients with relapsed or refractory MM. [Table: see text]