bluuebunny/crossref_metadata_2025_split huggingface dataset:
Second cancer risk 40 years after cure for Hodgkin lymphoma.
Authors: Schaapveld Michael , Aleman Berthe M , Eggermond Anja M , Janus Cecile P , Krol Augustinus , Maazen RWM Van Der , Raemaekers John M. M. , De Boer J. P. , Zijlstra Jose M , Van Imhoff Gustaaf Willem , Beijert Max L , Poortmans Philip M. , Lybeert Marnix L. , Mulder Ina , Visser Otto , Louwman Marieke J. , Sombroek Cherita , Lugtenburg Pieternella , van Leeuwen Flora E. 
Published: March 2020

8039 Background: During the last decades Hodgkin Lymphoma (HL) treatment changed towards less toxic chemotherapy schemes and smaller radiation fields. The impact of these changes on second cancer (SC) risk is still unknown. Methods: We calculated standardized incidence ratios (SIR), comparing SC risk after HL treatment with expected risk, based on cancer incidence in the general population, and compared SC risk between treatment modalities, accounting for competing events, in a large Dutch cohort comprising 3,390 5-years HL survivors, aged 15-51 years at HL treatment and diagnosed between 1965-2000. Results: The median follow-up was 18.2 years; 23% of the patients was followed ≥25 years. During follow-up 734 SCs and 92 third cancers (TC) occurred. The SIR for any SC was 4.5 (95% confidence interval (95%CI) 4.1-4.9). SC risk was still elevated after 35 years of follow-up (SIR 3.9; 95%CI 2.5-5.8) and cumulative incidence (CI) reached 47.1% (95%CI 43.6-50.5) at 40 years follow-up. For TCs the SIR was 5.5 (95%CI 4.4-6.9); the 20-year CI was 22.3% (95%CI 17.8-27.2). Risks of NHL and leukemia strongly decreased in more recent treatment periods (P-trend <0.001). The CI of solid tumors (ST) between 5-19 years after HL treatment did not differ for patients treated between 1965-1979, 1980-1989 or 1990-2000 (P=0.21; 19-year CI 9.1%, 11.6% and 11.4%, respectively). Radiotherapy (RT) above the diaphragm increased risk of STs above the diaphragm (hazard ratio (HR) 2.4, P<0.001), while subdiaphragmatic RT was associated with a 1.7-fold increased HR of a subdiaphragmatic ST (P=0.001). An incomplete mantle field was associated with significantly lower breast cancer (BC) risk (hazard ratio (HR) 0.4, 95%CI 0.2-0.8). A cumulative procarbazine dose >4.2 g/m2 yielded a 1.3-fold increased HR (95%CI 1.0-1.7) for non-breast STs and a 2-fold (95%CI 1.2-3.1) increased HR for gastrointestinal STs, but was associated with a strongly decreased BC risk (HR 0.3, 95%CI 0.2-0.6). Conclusions: SC risk after HL has decreased with treatment changes over the last decades, due to strongly decreasing risk of leukemia and NHL. Smaller radiation fields and procarbazine doses >4.2 g/m2 are associated with lower breast cancer risk, while high procarbazine doses increase risk of gastrointestinal STs.
Long-term follow-up results of a phase I/II study of concurrent chemoradiotherapy for localized nasal NK/T-cell lymphoma (NKTCL): JCOG0211.
Authors: Yamaguchi Motoko , Tobinai Kensei , Oguchi Masahiko , Ishizuka Naoki , Kobayashi Yukio , Isobe Yasushi , Ishizawa Kenichi , Maseki Nobuo , Itoh Kuniaki , Usui Noriko , Wasada Izumi , Ishikura Satoshi , Kagami Yoshikazu , Kinoshita Tomohiro , Hotta Tomomitsu , Tsukasaki Kunihiro , Oshimi Kazuo ,   Japan Clinical Oncology Group - Lymphoma Study Group (JCOG-LSG)
Published: March 2020

8050 Background: Concurrent chemoradiotherapy has been regarded as one of the standard management for localized nasal NKTCL. However, its long-term efficacy and toxicity is not known. Methods: The JCOG0211 trial is a phase I/II study of concurrent chemoradiotherapy consisting of radiotherapy (RT) of 50 Gy and 3 cycles of DeVIC (carboplatin, etoposide, ifosfamide, dexamethasone) for newly diagnosed, localized nasal NKTCL (JCO 2009). Patients (Pts) with newly diagnosed, localized diseases (IE & contiguous IIE with cervical node involvement) who were 20-69 yrs of age with PS 0-2 were eligible. 3-D conformal RT planning with a wide margin (+ 2 cm to the gross tumor, the entire nasal cavity and the nasopharynx) and a 2-step cone down were required. 33 pts were enrolled in the study, 27 of whom were treated with RT and a 2/3-dose of DeVIC, which was selected as the recommended phase II dose in the preceding phase I portion of the trial. All pts completed RT without any protocol violations. Long-term follow-up results on overall survival (OS), progression-free survival (PFS) and toxicity were evaluated. Results: The median follow-up was 69 months (range, 62-96). The pt (N=33) characteristics were as follows: median age 54 yrs (range, 21-68); stage IIE 33%; B symptom (+) 36%; elevated serum LDH 21%. %5-yr OS and PFS were 73% (95%CI, 54-85%) and 67% (95%CI, 48-80%), respectively. 11 pts (33%) experienced disease recurrence. Two achieved a 2nd CR by salvage chemotherapies followed by allogeneic stem cell transplantation, and the remaining 9 pts died of disease. There was no observed death and disease progression after 34 and 31 months, respectively. One pt experienced Grade 3 irregular menstruation for 3 years. No other Grade 3 or 4 late non-RT-associated adverse events (AEs) were observed. One pt received plastic surgery due to Grade 4 RT dermatitis. No other Grade 3 or greater RT-associated late AEs were encountered. Conclusions: Both survival benefit and disease control from concurrent chemoradiotherapy with RT and DeVIC are maintained during a 5-yr follow-up, indicating the excellent efficacy of this approach as a first-line therapy for localized nasal NKTCL. Long-term toxicity is acceptable.
Determinants of and outcomes associated with chemoimmunotherapy dose density in elderly subjects with diffuse large B-cell lymphoma (DLBCL).
Authors: Perepu Usha S. , Weibel Kelcy C , Button Anna M , Jacobus Laura S. , Smith Brian , Cerhan James R. , Link Brian K. 
Published: March 2020

8061 Background: RCHOP is the standard first line therapy for DLBCL but elderly patients often receive suboptimal doses. Relative dose intensity (RDI) less than 70-90% has previously been associated with inferior survival in CHOP treated patients. We now investigate the clinical determinants of immunochemotherapy dose delivery and comparative effectiveness of dose intensity on lymphoma-specific outcomes in persons over the age of 60. Methods: SPORE MER (Molecular Epidemiology Resource) is a prospectively accrued observational study in which University of Iowa and Mayo Clinic patients with a diagnosis of Non Hodgkins lymphoma have been enrolled since 2003. We reviewed data from the Iowa patients along with medical records from DLBCL patients over the age of 60 treated with anthracycline based chemo immunotherapy consecutively enrolled up through to December 2009. Statistical tests of associations between RDI and clinicopathologic factors, as well as survival outcomes, were performed. Results: We identified 92 patients over the age of 60. The median age was 70. 47 subjects experienced at least 1 dose reduction, 26 subjects had dose delays, and 20 subjects were unable to complete therapy. RDI ranged from 0.30-1.70 (median 0.92) for doxorubicin and from 0.29-1.70 (median 0.97) for cyclophosphamide. 24 and 19% of subjects received < 80% of RDI for dox and cy respectively. Age (p< 0.001 for both dox and cy) and performance status (p=0.04 for dox) but not number of medications, ACE27 co-morbidity score, body surface area, nor need for acute care visits were associated with decreased RDI. Adjusted for IPI, RDI did NOT have a significant effect on event-free or lymphoma-specific survival. Conclusions: Among clinical variables, age is the dominant variable associated with delivery dose intensity for chemotherapy in elderly patients treated for DLBCL; and among elderly patients receiving chemo immunotherapy, we did not find an association between dose intensity and lymphoma-specific outcomes. [Table: see text]
Brentuximab vedotin for relapsed or refractory non-Hodgkin lymphoma: Preliminary results from a phase II study.
Authors: Advani Ranjana , Oki Yasuhiro , Shustov Andrei R. , Grove Laurie E. , Bartlett Nancy 
Published: March 2020

8070 Background: Brentuximab vedotin is a CD30-directed antibody-drug conjugate approved for the treatment of Hodgkin lymphoma and systemic anaplastic large cell lymphoma (ALCL) after failure of other therapies. Based on the high objective response rate observed in patients with systemic ALCL, a type of non-Hodgkin lymphoma that is characterized by homogeneous CD30 expression, a study was initiated in other non-Hodgkin lymphomas that express the CD30 target. Methods: A phase 2 open-label single-arm study is underway in patients with relapsed or refractory CD30-positive non-Hodgkin lymphoma, excluding ALCL (NCT01421667). Brentuximab vedotin is administered IV at 1.8 mg/kg every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint is objective response rate assessed by the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). Tumor specimens are assessed by central lab in order to characterize the relationship of CD30 expression with antitumor activity. Results: Ten patients (age range 28–83; 5 M, 5 F) have enrolled to date. Diagnoses include diffuse large B-cell lymphoma (DLBCL, n=2), EBV-positive DLBCL of the elderly (n=3), primary mediastinal B-cell lymphoma (n=2), peripheral T-cell lymphoma NOS (n=2), and angioimmunoblastic T-cell lymphoma (AITL). Patients had received 1–6 prior chemotherapy regimens; 3 patients had prior stem cell transplants. Of 6 patients who have completed the cycle 2 response assessment, 2 attained complete remission, 1 with DLBCL (90% CD30+) and 1 with AITL (8% CD30+), 1 had stable disease, and 3 had progressive disease. Treatment-related serious adverse events observed to date were rash, febrile neutropenia, and mastoiditis. Conclusions: Preliminary results suggest that brentuximab vedotin may have antitumor activity in patients with relapsed or refractory CD30-expressing non-Hodgkin lymphomas, in addition to the efficacy previously observed in systemic ALCL. Updated study results will be presented.
Use of exon-based transcriptome profiling to identify novel signaling pathways and survival-associated genes in diffuse large B-cell lymphoma.
Authors: Leppa Sirpa , Taskinen Minna , Koivula Satu , Chen Ping , Louhimo Riku , Delabie Jan , Karjalainen-Lindsberg Marja-Liisa , Bjorkholm Magnus , Fluge Oystein , Pedersen Lars Moeller , Rydstrom Karin , Jerkeman Mats , Eriksson Mikael , Hautaniemi Sampsa , Holte Harald ,   Nordic Lymphoma Group
Published: March 2020

8074 Background: Identification of biological prognostic factors that could be used to define poor risk diffuse large B-cell lymphoma (DLBCL) patients is a main concern. Methods: Study population consisted of 38 de novo high risk DLBCL patients less than 65 years old. The patients were treated in the Nordic phase II protocol with six courses of R-CHOEP14 followed by systemic central nervous system prophylaxis with one course of high dose methotrexate and one course of high dose cytarabine. Exon array-based profiling was used to screen signaling pathways and differentially expressed genes between the clinically high risk patients, who had relapsed or remained in remission in response to dose dense chemoimmunotherapy. At the time of the analysis, median follow up was 34 months, progression free survival (PFS) 78% and overall survival (OS) 78%. Results: The screen between relapsed patients and the patients in remission using criteria of p ≤ 0.05 and fold change ≥ 1.6 revealed 566 differentially expressed genes (131 protein coding), of which 24 were likely to be involved in conventional signaling pathways, including those regulating antigen processing and presentation (CIITA, HLA-DQA2, HLA-DQB1, RFXAP), Jak-STAT signaling (SOCS3), Notch signaling (NOTCH1) and Toll-like receptor signalling (IRF5). In cox univariate analysis, 12 of 24 genes were found to associate with PFS (p<0.05). Of these, high expression of CIITA, DLL4, HLA-DQA2, HLA-DQB1, IRF5, NOTCH1, PER1, RFXAP, SEMA4D and ZFP36 had a favorable impact on PFS, whereas high levels of ENPP3 and PRKAR2B were associated with adverse outcome. Differential expression of four genes was confirmed by quantitative PCR, and prognostic value of six genes validated using Lymphoma/Leukemia Molecular Profiling Project microarray data set. Immunohistochemical validation of the findings in a larger patient cohort is ongoing. Germinal centre B-cell signature did not predict survival in this cohort. Conclusions: The results provide evidence that exon-based transcriptome profiling can identify biologically relevant signaling pathways and genes that discriminate the outcome of homogenously treated young high risk DLBCL patients.
Prevention of adverse events during treatment of HIV-associated Hodgkin lymphoma with ritonavir and zidovudine.
Authors: Sandhu Sonia , Gupta Shweta , Itokazu Gail , Braik Tareq , Jain Shivi , French Audrey L. , Rubinstein Paul G. 
Published: March 2020

8085 Background: In response to very high rates of neurologic and hematologic adverse events (AE) when ABVD was used in combination with ritonavir (RTV) or zidovudine (AZT) in HIV-associated Hodgkin (HL) we instituted a policy to use alternative antiretroviral agents during HL therapy in our HIV patients. In this study, we examined all AE in HIV-HL since the exclusion of RTV and AZT over 2 years ago. We also evaluated the AEs when HAART and chemotherapy for NHL were taken together in an expanded cohort of 52 pts. Methods: A screen of pharmacy and hospital databases between 1998-2012 identified all HIV-associated HL and NHL patients. Adverse events during chemotherapy were assessed by chart review and graded per the NCI Common Terminology Criteria for Adverse Events. Statistics: Fisher's exact test was used to examine the differences in AE incidence associated with use of specific antiretrovirals. Results: HAART use during chemotherapy was identified in 35/36 (96%) pts with HL and 52/108 (48%) of pts with NHL. Before RTV and AZT were prohibited, G3/4 neuropathy, neutropenia, and anemia developed in 31, 68, and 57% of 23 pts with HIV-HL respectively. Since then, 12 patients were treated with non-RTV and AZT based HAART. 0% neuropathy and only 20% G3/4 neutropenia and 10% anemia was observed, each statistically significant (p<0.01). Of the 54 patients with NHL, 64% received CHOPR like, HYPERCVADR (18%), and daEPOCHR (11%). All AEs for each NHL regimen were similar to historical controls and no anti HIV medication was found to correlate with any AE, despite 28% of the HAART regimens containing RTV. Conclusions: No relationship between any AE and anti HIV medications was identified during treatment for NHL. But, excluding RTV or AZT-based HIV therapy during HL treatment, decreased neuropathy, neutropenia, and anemia by 100%, 38%, and 28% respectively. We suggest that exclusion of ritonavir and zidovudine from HAART regimens used with ABVD become the standard.
Predictive value of baseline serum MIP-1α and CRP on symptom burden and tumor response to induction therapy in patients with multiple myeloma.
Authors: Cleeland Charles S. , Wang Xin Shelley , Thomas Sheeba K. , Liu Ping , Sailors Mary H , Mendoza Tito R. , Reuben James M. , Cohen Evan N. , Gilmore Katherine R. , Ilagan Venus M , Williams Loretta A. , Johnson Valen E. 
Published: March 2020

8091 Background: Macrophage inflammatory protein-1α(MIP-1α) is a growth factor for human multiple myeloma (MM) cells. As an osteoclastic factor, its presence provides pathophysiological evidence of the development of lytic bone lesions in MM. C-reactive protein (CRP) indicates systemic inflammation. The relationship between disease-driven inflammatory markers and both patient-experienced symptoms and tumor response to induction therapy is unknown. Methods: MM patients (N=39) who were either newly diagnosed or had received fewer than 2 cycles of chemotherapy, and who also were to receive induction therapy, were enrolled. To test concentrations of MIP-1α and CRP, serum samples were collected before and after induction and assayed by Luminex. Multiple symptoms were measured twice a week via the M. D. Anderson Symptom Inventory MM module (MDASI-MM) from -8 to +112 days of induction. The MM-specific items of the MDASI-MM are bone aches, constipation, muscle weakness, diarrhea, sore mouth or throat, rash, and difficulty paying attention. Correlation between symptom severity and inflammatory markers at baseline was examined by linear regression modeling. Kruskal-Wallis significance test and Wilcoxon test were used to examine association between MIP-1α and tumor response. Results: Patients received either bortezomib-based (89%) or lenalidomide-based induction therapy. Baseline MIP-1α and CRP were significantly inversely related to the mean severity component score of the 5 most-severe symptoms (fatigue, pain, bone aches, poor sleep, drowsiness) (p=.03; p=.02), and significantly inversely related to the severity of a component score of the module-specific symptoms (p=0.04; p=.002). Change over time in MIP-1α differed significantly by tumor response category (p=.04), with the partial response group having a higher median score than the complete response group (1.483 vs. 0.016, p=.01). Conclusions: Our data suggest that higher baseline levels of serum MIP-1α and CRP predict effective chemotherapy-induced reduction of disease-related symptoms in MM patients. Higher serum MIP-1α expression after induction therapy was related to less-ideal tumor response.
Prognostic value of serum lactate dehydrogenase in symptomatic multiple myeloma.
Authors: Patel Krina K. , Orlowski Robert Z. , Weber Donna M. , Wang Michael , Thomas Sheeba K. , Shah Jatin J. , Turturro Francesco , Alexanian Raymond , Delasalle Kay 
Published: March 2020

8093 Background: In patients with symptomatic multiple myeloma, the clinical features, responses to treatment, and survival times vary. Well established predictors of survival include the International Staging System (ISS), cytogenetic abnormalities, and response to therapy. Long recognized has been the association of high serum lactate dehydrogenase (LDH) with advanced disease and shorter survival. We focused here on the impact of high LDH on staging and prognosis in order to guide the role of recent advances in therapy. Methods: We evaluated 1,247 patients with newly diagnosed, symptomatic myeloma from 10/74 to 7/11. Our goal was to determine the prognostic value of high LDH (>300 IU/L) in relation to ISS stage. We also compared the frequencies of anemia, hypercalcemia, and response to therapy in patients with high LDH with those of patients with Stage III disease and normal LDH values. Results: All 1,139 patients with normal LDH lived significantly longer than the 108 patients with elevated values (47 vs. 16 months, p <.01). LDH was elevated in 9% of all patients, but in 2%, 6%, and 18% of patients with ISS-I, II, and III disease, respectively. Their survival times were also significantly shorter than those of comparable patients in each stage with normal LDH (table). Among the 108 patients with high LDH, the frequencies of hemoglobin <8.5 g/dl (54 vs. 41%, p=.03), and serum calcium>11.5 mg/dl (41 vs. 27%, p<.01) were significantly higher than those of 292 patients with Stage III disease and normal LDH, and the frequency of response to therapy was less (40 vs. 62%, p<.01). Conclusions: Serum lactate dehydrogenase provides a convenient and dependable prognostic indicator in patients with multiple myeloma. An elevated LDH value indicates a poor prognosis regardless of ISS stage, confirming the report by Gkotzamanidou, Terpos, and Dimopoulos et al, and should be included in the definition of stage III disease. Such patients require rapid control of disease with sequential combinations of effective drugs and intensive therapy in order to improve their outcome. [Table: see text]
Clinical profile of multiple myeloma in Asia: An Asian Myeloma Network (AMN) study.
Authors: Lee Jae Hoon , Kim Kihyun , Kim Jin Seok , Min Chang Ki , Shimizu Kazuyuki , Chou Takaaki , Kosugi Hiroshi , Suzuki Kenshi , Hata Hiroyuki , Chen Wenming , Hou Jian , Huang Shang-Yi , Chng Wee Joo , Tan Daryl C.L. , Teoh Gerrard , Chim James , Liang Raymond , Nawarawong Weerasak , Siritanaratkul Noppadol , Durie Brian G. 
Published: March 2020

8097 Background: The incidence of multiple myeloma (MM) is known to be variable according to ethnicity. However the difference of clinical characteristics between ethnic groups is not well-defined. In Asian countries the incidence of MM has been lower compared with Western countries. However, there are growing evidences that MM is increasing very rapidly in this region. Until now, only few data of Asian patients has been reported. Asian myeloma network (AMN) decided to analyze the first multinational project to explore clinical characteristics of Asian MM patients and clinical practice performed in Asian countries. Methods: Data were collected from 21 centers from 7 countries and regions were collected retrospectively. Clinical characteristics of 2969 symptomatic MM patients at diagnosis were described. Overall survival (OS) and prognostic factors were analyzed for 2273 patients who have survival data. Results: Median OS was 54 months (95% CI 48.0-60.0). Patients who were diagnosed before 2000 were shorter survival. Transplantation was performed to 513 patients with better survival (84 vs. 45 months, p<0.001). First line treatment of 2339 evaluable patients was analyzed. Overall response rate was 71% with 30%, VGPR or better. New drugs including bortezomib, thalidomide or lenalidomide were combined for 32.5% of all 2339 patients without difference in response rate or OS according to combination. Conclusions: We successfully described clinical characteristics of Asian MM patients and this project will be the base for future studies or clinical trials for Asian MM patients. Updated analyses and comparison with Western data will be presented. AMN, supported by the International Myeloma Foundation (IMF) IMWG initiative.
Survival outcomes of early autologous stem cell transplant (ASCT) followed by lenalidomide, bortezomib, and dexamethasone (RVD) maintenance in patients with high-risk multiple myeloma (MM).
Authors: Kaufman Jonathan L. , Nooka Ajay K. , Muppidi Samatha , Heffner Leonard T. , Gleason Charise , Boise Lawrence , Lonial Sagar 
Published: March 2020

8100 Background: Despite markedly improved survival rates for MM pts in the last decade, 15-20% of pts with high risk genetics continue to have dismal outcomes with a median PFS of 18.5 months (Kapoor P et al). In this subset of pts, efforts are needed to improve response rates and prolong the response duration, but doing so without genotoxic therapy as this has been shown not to improve outcomes (Barlogie et al). Methods: We evaluated 37 pts with high risk features [del17p (n=16), t(4;14) (n=1), t(14;16) (n=4) by FISH/CTG; hypodiploidy (n=9), del 13 (n=16); complex karyotype (n=14) by CTG; PCL (n=7) and atypical presentation (n=4)]. After completing induction therapy, all pts underwent ASCT followed by RVD maintenance. 60 days after ASCT following hematological recovery, pts began maintenance [lenalidomide 10 mg/day (days1–21), bortezomib 1.3 mg/m2 and dexamethasone 40 mg once a week (days 1, 8, 15) every 28 days]. Results: The response rates are summarized in the table. 7/36 pts progressed while on RVD maintenance. The median PFS and OS for pts on RVD maintenance has not been reached. Pts with <VGPR pre-ASCT and with <VGPR on RVD maintenance have median PFS of 28 months and 11 months, respectively. 4 pts with prior h/o DVT received anticoagulation, while all others received ASA for DVT prophylaxis. No thrombotic events were seen. There were no grade 3/4 toxicities or treatment-related mortality. The most common toxicities during maintenance schedule were: PN-40% (G1: 26%; G2:14%); G1 rash-10% and G1 fatigue in 78% pts. Cytopenias were seen in 25% pts and dose reductions were made in 50% pts. There is no report of secondary malignancies. Conclusions: Early ASCT followed by RVD maintenance delivers superior response rates in this high risk segment achieving sCR in 47% and ≥VGPR in 73% pts and prevents early relapses. The median PFS and OS have not been reached. RVD maintenance regimen is well tolerated and promising. [Table: see text]