bluuebunny/crossref_metadata_2025_split huggingface dataset:
High incidence of symptomatic methemoglobinemia (metHb) in Asian patients (pts) treated with 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, triapine) and gemcitabine (GEM) in a second-line phase II trial of metastatic non-small cell lung cancer
Authors: Ma B. , Tan E. H. , Mok T. , Lam K. C. , Soo R. , Leong S. S. , Wang L. Z. , Mo F. , Chan A. T. , Goh B. C. 
Published: March 2020

18207 Background: Triapine (Vion Pharmaceuticals) is an inhibitor of ribonucleotide reductase that can enhance GEM uptake in GEM- resistant cell lines. Clinically significant metHb has been rarely reported with triapine & G6PD-deficient pts maybe more susceptible. This multicenter study evaluated the activity & safety of combined triapine-GEM in pts with metastatic NSCLC who had progressed despite prior response or disease stabilization to 1st line platinum-GEM regimen. Methods: Eligible pts were treated with triapine (105mg/m2) as 4-hr IV infusion, followed by GEM (1g/m2) over 30-min on days 1, 8 & 15, repeating every 28 days for 6 cycles. G6PD-deficient pts were excluded. Results: 6 males & 6 female Asian pts (median age: 65 yrs) received a median no. of 2 cycles (range 1–6 cycles). At a median follow-up of 4.6 mos, no response was seen. 4 pts had stable disease. Median time to progression was 3 mos (95% CI: 1.7–9.1 mos). Gr 3–4 toxicities included neutropenia (gr 3, 2 pts), hypoxia (gr 3, 3 pts) & dyspnea (gr 3, 1 pt). There were no treatment-related deaths & all pts remained alive at analysis. 4 pts developed symptomatic metHb during, or ≤ 4 hrs of stopping triapine. This was manifested as dyspnea &/or hypoxia, associated with an oxygen saturation of ≤90% at room air. Arterial metHb assay performed during the hypoxic episode showed a metHb level of up to 15% of total concentration of hemoglobin ([Hb]), which fell to < 5% of [Hb] within 4–6 hrs of stopping triapine. All pts recovered with conservative treatment & none required reversal with methylene blue. 3 out of the 4 pts were able to continue treatment after dose-reduction of triapine. Conclusions: The cause of the relatively high incidence of triapine-related symptomatic metHb was unclear in this Asian cohort. This study was terminated prematurely due to lack of response. No significant financial relationships to disclose.
Correlation between anemia before treatment with survival in patients with advanced non-small cell lung cancer
Authors: Bella S. R. , Richardet M. E. , Gomez Storniolo P. , Celiz P. , Lingua A. , Mascheroni B. , Mangeaud A. , Richardet E. A. 
Published: March 2020

18211 Background: Prognostic factors identified in advanced non small cell lung cancer are: age, gender, PS, h. SWOG univariable analysis in patients with chemotheraphy; confirmed these factors and show a relationship between the hemoglobin level and the overall survival; in addition the metastasic site number and cisplatin- based chemotheraphy (7). To analyse and compare the hemoglobin level before cisplatin- based chemotheraphy with survival in patients with advanced non- small cell lung cancer. Methods: Retrospective study conducted at the IONC of the 179 clinical record were analized, over a 5 year period. The collected data were: age, gender, PS, histologic type, stage, chemotheraphy cycles number, smooke history, number and metastasic site. We analyzed median and overal survival using Kaplan Meier, and the anemia as a prognostic implication factor with univariable and multivariable Cox regression analysis. Istologic type and TNM (1–6). Results: The mean age was 59 (40–79); 146 (81.5%) male and 33 (18.5%) women; histological types found were squamous cell carcinomas in 66 (37%), and adenocarcinoma in 113 (63%); stage IIIB in 61 (34%) and IV in 118 (66%). 147 (82%) were smokers and 32 (18%) were never smokers. All the patients had PS 0–1. Median overall survival time was 11.53 months and 13.88 months in the haemoglobin level < or > 11 gr/ 100 ml, respectively. (p=0.3). In univariable Cox regression analysis, smoking rates and chemotheraphy cycles number were predictors of survival (p=0.05 y p=0.018, respectively). Hemoglobine (p=0.55). In multivariable Cox regression analysis, only the number of cycles was predictor of survival (p=0.026). Hemoglobine (p=0.34). Conclusions: In our experience, a greater survival tendency was observed in patients with advanced non- small cell lung cancer who presented levels of Hemoglobine greater than 11 gr/dl, previous to cisplatin- based chemotherapy without statistical significance. [Table: see text]
Autologous transplantation for relapsed non-Hodgkin lymphoma using intravenous busulfan and cyclophosphamide as conditioning regimen: A single center experience
Authors: Stefanovic A. , Escalon M. P. , Pereira D. L. , Santos E. S. , Goodman M. , Byrnes J. J. , Fernandez H. F. 
Published: March 2020

18508 Background: High-dose chemotherapy followed by autologous stem cell transplanatation has become standard of care for patients with relapsed, chemosensitive non-Hodgkin’s lymphoma (NHL). In an effort to improve safety and efficacy of this therapeutic approach, new conditioning regimens are being developed. Methods: We retrospectively reviewed the clinical data of 44 consecutive patients with relapsed NHL who had been treated with intravenous Busulfan and Cyclophosphamide (BU/CY) as conditioning regimen for autologous stem cell transplantation between January 2000 and April 2005. Busulfan was administered at a total dose of 3.2 mg/kg on days -7 to -4 (given in two or four divided doses), followed by Cyclophosphamide at a dose of 120 mg/kg intravenously on days -3 and -2. We determined treatment-related morbidity and mortality, event-free survival (EFS, defined as time period between transplantation and occurrence of serious morbidity, disease relapse, disease progression, or death), disease-free survival (DFS), and overall survival (OS). Results: The distribution by histologic type of the 44 patients was as follows: 29 diffuse large B-cell lymphoma, 8 follicular lymphoma, 4 mantle cell lymphoma, and 3 peripheral T-cell lymphoma. Median age was 50 (range 20 to 68 years). At the time of transplantation, 27 patients had attained a complete response (CR or CRu) to salvage chemotherapy, 13 had achieved a partial response, and 4 had stable disease. Median time to neutrophil recovery post transplantation was 11 days. Treatment-related toxicities included nausea/vomiting (77%), diarrhea (43%), and mucositis (66%), which were mild in the majority of cases. Neutropenic fever occurred in 82% of patients. The 100-day mortality rate was 4 (9%) of patients: sepsis (n=1), pneumonia (n=1), and hepatic veno-occlusive disease (n=2). After a median follow-up of 52 months, 3-year Kaplan-Meier estimates of EFS, DFS, and OS were 35%, 41% and 44% respectively. Conclusions: Intravenous BU/CY is a safe and effective conditioning regimen as part of autologous transplantation for relapsed NHL. Our outcomes are comparable to those of other published regimens. Further investigation of this treatment approach is warranted. No significant financial relationships to disclose.
Oral vorinostat (suberoylanilide hydroxamic acid, SAHA) in relapsed diffuse large B-cell lymphoma (DLBCL): Final results of a phase II trial
Authors: Crump M. , Coiffier B. , Jacobsen E. D. , Sun L. , Ricker J. L. , Xie H. , Frankel S. R. , Randolph S. S. , Cheson B. D. 
Published: March 2020

18511 Background: Vorinostat (Zolinza™) is a histone deacetylase inhibitor (HDACI) approved in the US for the treatment of cutaneous manifestations in patients (pts) with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following 2 systemic therapies. Clinical responses with vorinostat have been reported in other lymphoma subtypes. Methods: Open-label, single-arm, nonrandomized Phase II trial of oral vorinostat 300 mg bid (initially 14 d/3 wks; amended to 3 d/wk) until disease progression or intolerable toxicity. Eligibility: measurable, relapsed/refractory DLBCL; = 2 prior systemic therapies; adequate hematologic, hepatic and renal function. Pts who had prior HDACI treatment, allogeneic transplant, or had failed > 3 prior therapies were excluded. Primary endpoint: objective response rate (ORR) measured by CT/PET. Secondary endpoints: assessment of response duration (DOR), time to progression (TTP), time to response (TTR) and safety. Results: Eighteen pts (median age, 66 y [range, 59–86 y]; median 2 prior systemic therapies) were enrolled from 5/05 - 3/06 at 8 centers. Seven pts were initially treated with 300 mg bid 14 d/3 wks, but 4 had DLT (Gr 3 muscle spasms; Gr 4 thrombocytopenia, n = 3). The schedule was amended to 300 mg bid 3 d/wk and no other pt had DLT. One pt on the 3d/wk schedule achieved a CR (TTR = 85 d; DOR = 225+ d) and the ORR was 5.6%. One pt had SD for 301 d. Sixteen pts discontinued (DC) due to PD; median TTP for all pts was 44 d. Median number of treatment cycles was 2 (range, 1–14+). Two pts received > 6 cycles (126 d). Common drug-related adverse experiences (AE; mostly = Gr 2) were diarrhea (61%), fatigue (50%), nausea (39%), anemia (33%) and vomiting (33%). Three pts had dose reduction (300 -> 200 mg bid 14 d/3 wks) and none DC due to a drug-related AE. Drug-related AE = Gr 3 included thrombocytopenia (n = 3; 300 mg bid 14 d/3 wk) and asthenia (n = 2; 300 mg bid 3 d/wk). Two pts died on study of causes unrelated to drug: PD + GI hemorrhage (d 40) and acute myocardial infarction (d 95). Conclusion: Vorinostat has modest activity in pts with relapsed DLBCL and is well tolerated at 300 mg bid 3 d/wk or 200 mg bid 14 d/3 wks. The optimal dose/schedule and predictive response biomarkers require further study. No significant financial relationships to disclose.
A phase I-II study to assess the safety, pharmacokinetics, and potential efficacy of intravenous SB-743921 on days 1 and 15 of a 28-day cycle in patients with non-Hodgkin lymphoma
Authors: Goy A. , Feldman T. , Dessanti M. , Hainsworth J. , Weaver C. , Ungerleider R. , Wolff A. , Escandon R. 
Published: March 2020

18516 Background: Kinesin spindle protein (KSP) is required for mitotic spindle bipolarity and cell cycle progression. SB-743921 (SB- 921), a selective KSP inhibitor, blocks mitotic spindle assembly, causing cell cycle arrest in mitosis and subsequent cell death. Neutropenia was the dose-limiting toxicity (DLT) in the first-in-humans study of SB-921 given Q21 days. Methods: Cohort 1 of the Phase I portion of a study determining the safety, pharmacokinetics and MTD of SB-921 without prophylactic GCSF in patients (pts) with Non-Hodgkin’s Lymphoma (NHL) or Hodgkin’s Disease is reported. Pts with relapsed or refractory disease were eligible if they had received at least one prior chemotherapy regimen, had failed high-dose therapy with autologous stem cell transplant (ASCT), or were not candidates for ASCT. SB-921 is given to dose-escalating cohorts of 3 pts as a 1 hr IV infusion, Q14 days. Dosing began at 2 mg/m2 and escalated in 1 mg/m2 increments after 3 pts tolerated 1 cycle. Pts without dose-limiting toxicity (DLT) not completing Cycle 1 are replaced. Cohort expansion to 6 pts occurs if 1/3 pts experiences DLT, defined as any drug-related toxicity = grade 3 or drug-related grade 4 hematologic toxicity. Results: Cohort 1 (2 mg/m2) enrolled 6 NHL pts (5 indolent, 1 aggressive). 4 were female; median age = 59 (52–73); 5 Caucasian, 1 African-American; median no. of cycles = 2 (1–6). 5/6 pts were evaluable; 1 dropped out before dosing. The most common Grade 1–2 AEs, in decreasing order, were fatigue, dysgeusia, paresthesia, leukopenia, and diarrhea. Grade 3 AEs of note were 1 each of hemolytic anemia, leukopenia, thrombocytopenia and dyspnea; 1 Grade 4 anemia was reported. Conclusions: SB-921 was well tolerated without prophylactic GCSF in Cohort 1 of the Phase I portion of this study, which continues to dose-escalate. If neutropenia is the DLT, dose escalation will continue with prophylactic GCSF. No significant financial relationships to disclose.
Combined treatment with high-dose methotrexate and whole brain radiation improves survival in primary central nervous system lymphoma (PCNSL)
Authors: Abdelsalam M. A. , Hussainy G. , Akhtar S. , Maghfoor I. , Elweshi A. , Khafaga Y. , Alhuseini H. , Rahal M. , Alshabana M. 
Published: March 2020

18520 Background: Primary CNS lymphoma (PCNSL) is an aggressive primary brain tumor, cranial irradiation alone rarely result in long term disease control or prolonged survival. We analyzed our data for the impact of adding high dose methotrexate (HDMTX) prior to whole brain irradiation (WBI). Methods: All patients with PCNSL diagnosed and managed during 1991–2004 were identified from Oncology Data Unit. Patient’s characteristics, prognostic factors, details of treatment and outcome were reviewed. Sixty-two patients were identified, 10 were excluded (4 had WBI < 40 Gy and 6 had no treatment). Radiation alone was considered curative with a dose ≥ 40 Gy. Combined modality therapy included 3–4 cycles of HDMTX (3gm/m2) followed by WBI Results: 52 patients were analyzed for outcome. 36 had WBI, dose ≥40 Gy, 16 received 3–4 cycle of HDMTX followed by WBI (chemo-radiotherapy (CRT)). Median age was 48.2 years; 42 years in CRT group, 51 years in WBI. Patients characteristics were comparable between two groups except for higher multifocal tumor in CRT group (92% vs. x22%, p=0.029). Median follow is 12.83±6.4 months. Results are shown in Table . HR for event is 0.64 (95% CI was 0.52–0.98) and for death 0.58 (95% CI was 0.48–0.92), both in favor of CRT. Univariate regression analysis using one-way analyses of variance (ANOVA) and multivariate Cox regression analysis for prognostic factors including age (< 60 vs. ≥60), ECOG PS (0–2 vs. 3–4), extent of surgery (biopsy vs. debulking), solitary vs mutifocal tumor and dose of radiation therapy (< 50Gy vs. ≥50Gy) failed to identify any prognostic factor. Conclusions: This retrospective comparison supports other phase II trials results that high dose methotrexate followed by WBI in PCNSL improves outcome. [Table: see text] No significant financial relationships to disclose.
Cyclooxygenase-2 inhibition induces oxidative stress and decreases intracellular glutathione to reduce survival of human B lymphoma/leukemia cells
Authors: Ryan E. P. , Rahman I. , Phipps R. P. 
Published: March 2020

18522 We recently reported that inhibition of Cox-2 reduced human B-CLL proliferation and survival. Herein, we investigated the mechanisms whereby a small molecule Cox-2 selective inhibitor (SC-58125) blunts survival of human B cell lymphomas and chronic lymphocytic leukemia B cells. SC-58125 (a celecoxib analogue) and OSU03012 (a celecoxib analogue that lacks Cox-2 inhibitory activity) both decreased intracellular glutathione (GSH) content in malignant human B cells, as well as in Cox-2 deficient mouse B cells. This new finding supports Cox-2 independent effects of SC-58125. Interestingly, SC-58125 also significantly increased B cell reactive oxygen species (ROS) production, suggesting that ROS are a pathway that reduces malignant cell survival. Addition of GSH ethyl ester protected B lymphomas from the increased mitochondrial membrane permeability and reduced survival induced by SC-58125. Moreover, the SC-58125-mediated GSH depletion resulted in elevated steady-state levels of the glutamate cysteine ligase catalytic subunit mRNA and protein. These new findings of increased ROS and diminished GSH levels following SC-58125 exposure support novel mechanisms whereby a Cox-2 selective inhibitor reduces malignant B cell survival. These observations also support the concept that certain Cox-2 selective inhibitors may have therapeutic value in combination with other drugs to kill malignant B lineage cells. No significant financial relationships to disclose.
Ocular adnexal lymphoma subtyped according to the REAL classification: A 12-year experience from a single institution
Authors: Herrada J. , Campos-Gines A. F. , Gupta A. , Vazquez C. W. 
Published: March 2020

18541 Background: The Revised European and American Lymphoma (REAL) classification (1994) provided a useful and practical tool to define lymphomas. The aim is to report our experience with this unusual malignancy diagnosed since the REAL classification was implemented. Methods: Retrospective review was performed on patients (pts) with ocular adnexal lymphoma between 1994 and 2006. Medical records, diagnostic imaging procedures, and pathology reports, including immunophenotyping studies, were reviewed. Histologic definition of lymphoma was based on the REAL Classification. Results: 10 pts were identified. All but one were females. Median age at diagnosis was 69 years (54–84). Primary sites included conjunctiva (5), orbital soft tissue (3), and eyelid (2). No lacrimal gland location was found. Ann Arbor stage at diagnosis was IE in most cases (7). One patient (pt) had stage IIE (conjunctival and maxillary sinus) and 2 pts had simultaneous bone marrow involvement (stage IV). 6 pts had marginal zone B-cell subtype, and the remaining 4 pts had small lymphocytic B-cell lymphoma. Radiation as single treatment modality was given to all 7 pts with stage IE, and all those achieved a complete remission (CR). CR was also achieved using chemotherapy with cyclophosphamide (C), vincristine (V), doxorubicin, prednisone (P), and rituximab followed by radiation in the pt with stage IIE. Of the 2 pts with stage IV, 1 achieved a CR with rituximab-based chemotherapy, and 1 never achieved a CR despite chemotherapy (chlorambucil, CVP). With a median follow-up of 23 months (9–70), the 9 pts that achieved a CR after initial treatment remain alive and disease-free. The only pt that did not achieve a CR lost follow-up at 18 months. Conclusions: In our patient population, radiation alone appears to be an effective treatment modality for stage IE. Achieving a CR seems to be a crucial factor for long-term control of the disease. No significant financial relationships to disclose.
Phase II: Combination of cladribine, cyclophosphamide, mitoxantrone, rituximab (R-CCM) in patients with relapsed and refractory follicular and mantle cell lymphoma, results of a prospective study at Kitasato University
Authors: Suzuki Y. , Danbara M. , Hayama M. , Togano T. , Ohsaka M. , Miyazaki K. , Horie R. , Higashihara M. 
Published: March 2020

18542 Background: Indolent non-Hodgkin’s lymphoma (I-NHL) account for 20% of all of NHL in Japan, and they are increasing in number. More than 80% of the patients who achieve a complete remission with the initial treatment, will require salvage therapy. Recently, cladribine (2-CdA), a purine analogue is receiving much attention, because, even as a single agent, it has shown a high efficacy for I-NHL. The aim of our study was to determine the effectiveness and toxicity of combined chemotherapy consisting of 2-CdA, cyclophosphamide (CYP), mitoxantrone (MIT), rituximab (R-CCM) in the treatment of refractory or relapsed I-NHL. Methods: Patient eligibility criteria were: Previously treated patients with I-NHL, refractory or relapsed disease, no chemotherapy or irradiation within 4 weeks prior to the study, life expectancy of at least 3 months, age: 20–75, perfomance status of 0–3, adequate function ( bone marrow, liver, kidney, lung, heart) and written informed consent. The treatment regimen was: 2-CdA given at a dose of 0.09 mg/kg/day in a 2-h intravenous infusion from day 2–4, CYP 200 mg/m2/day from day 2–4, MIT 8 mg/m2/day on day 2 and rituximab 375 mg/m2/day on day .Primary end point was overall response rate. Results: 9 patients were enrolled, 7 (2 with mantle cell lymphoma, MCL; and 5 with follicular lymphoma, FL) were eligible. Mean Age was 63(51–72). The mean observation time was 121 days(47–314). Overall response rate (complete and partial) just after this therapy was 85.7%, one was progressive disease. One of PR one relapsed and died ten months after this regimen. The major toxicity was myelosuppression. Grade-III and -IV neutropenia was seen in 7 patients, grade-III thrombocytopenia in one and grade-III hemorrhagic cystitis in one, but all of them recovered from these toxicity. After the treatment, Grade-IV pneumonia and grade-III left-ventricular diastolic dysfunction was seen in the PD patient and passed away. Conclusions: the R-CCM is effective and safe in a combined regimen for relapsed and refractory I-NHL patients. We have just begun this new regimen, therefore, further investigations with larger population are warranted. No significant financial relationships to disclose.
Usefulness of low-dose thalidomide for Japanese patients with refractory and relapsed multiple myeloma
Authors: Kanamori H. , Hashino S. , Takahashi S. , Onozawa M. , Kahata K. , Kondo T. , Asaka M. 
Published: March 2020

18543 Background: Thalidomide is not licensed in Japan, and many patients with multiple myeloma (MM) are therefore taking thalidomide that is imported from other countries. In this study, the effectiveness and side effects of thalidomide in patients with MM who took the drug from 2003 to November 2006 were retrospectively analyzed. Methods: Forty-one patients with refractory and relapsed MM were treated with thalidomide. The median age of the patients was 67.6 years (range,48 to 90 years) Most patients (88%) were treated at a dose of 100 mg/day, but the dose was later modified due to toxities, responses and monetary matters. Thalidomide was administered alone (n=21) and in combination with other drugs (n=20) such as dexamethasone. Results: Seventeen patients (41%) responded to thalidomide (nine patients (22%) showed a reduction in myeloma protein of over 50% and eight patients (19%)showed a reduction of 25–50%.). Kaplan-Meier estimates of overall survival were 68.6% at 1 year and 38.4% at 2 years.The 2-year overall survival rate was higher in ten patients who underwent autologous stem cell transplantation(P<0.001). Low-dose thalidomide was tolerated well but thalidomide treatment had to be discontinued in two patients because of life-threatening interstitial pneumonitis (Onozawa et al. JCO 2005,23). Conclusions: Low-dose thalidomide is useful for treatment of advanced myeloma and can improve prognosis. However, thalidomide, even when administered at a low dose, can caese life-threatening toxicities, and attention must therefore be given to safe use of the drug. No significant financial relationships to disclose.