bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trend and geographic variations in the incidence of mantle cell lymphoma in the United States from 1975 to 2003
Authors: Zhou Y. , Wang H. , Zhang Y. , Du X. , Kwak L. , Romaguera J. , Wang M. 
Published: March 2020

8091 Background: Mantle cell lymphoma (MCL) is an uncommon subtype of non-Hodgkin's lymphoma (NHL). To better understand the incidence and epidemiological features of MCL in the United States, we conducted a population-based study with 3943 patients (pts) of MCL identified from the Surveillance, Epidemiology, and End Results (SEER) tumor registries over 28 years. Methods: From SEER public database, we identified 157,035 pts of all ages diagnosed with NHL between 1975 and 2003 in 9 SEER areas. Of these pts, 3,943 (2.5%) had histologically confirmed MCL, acccounting for 2.51% of NHL. The incidence with 95% confidence intervals were generated from SEER*Stat Software. Incidence was age-adjusted to the U.S. 2000 standard population. Annual percent change (APC) for the incidence was calculated and considered to be statistically significant if P<0.05. The crude 1-year survival rate was calculated as the ratio of the number of pts who survived over 1 year and the number of pts diagnosed with MCL. Results: Of 3,943 pts with MCL, 69.4% were late-stages (stages III IV), 24.2% were early-stages (stages I-II), and 7.1% were unstaged. Median age at diagnosis for MCL was 68.0. Overall incidence was 0.380/100,000/year, which increased by age from 0.02 in pts aged <40 to 2.02 for 70–79 and 1.81 in pts aged 80 or older. The age-adjusted incidence increased from 0.077 in 1975 to 0.641 in 2003. APC was 4.71% (P<0.001). Incidence of MCL was higher in men (0.555) than in women (0.250) (P<0.001). Annual increase was greater in men (5.84%) than in women (2.82%). There were also substantial geographic variations (P<0.001) in the incidence of MCL. The age-adjusted incidence was highest in Seattle (0.455) and the lowest in Hawaii (0.314). The incidence appeared to be higher in Caucasians (0.405) than in African-Americans (0.235) and other races (0.238). Annual increase was 5.1% in Caucasians, and 1.1% in African-Americans and other races. The 1-year survival rate was 85.0% for pts diagnosed in 1975–84, and increased to 90.4% for pts diagnosed in 1985–1994 and 82.0% for pts diagnosed in 1995–2003. Conclusions: The incidence of MCL increased progressively from 1975 to 2003, and was significantly higher in males and in Caucasians. There were substantial geographical variations in the incidence of MCL. No significant financial relationships to disclose.
Macrophage levels in large cell lymphoma are associated with survival
Authors: McGrath M. S. , Shagrun L. , Morris A. , Behler C. 
Published: March 2020

8097 Background: Recent studies of follicular lymphoma have suggested that the presence of high levels of tumor associated macrophages (MO) conferred a poor prognosis. The current study evaluated large cell lymphomas for the presence of MOs and “proliferative MOs” (promacs), in HIV+ and HIV- LCL. Methods: Formalin-fixed and paraffin-embedded tissues from patients with LCL (and controls) were obtained from the ACSR (URL: http://acsr.ucsf.edu ) and evaluated for expression of CD68 (MO), PCNA (proliferation) and HIVp24 via the use of 0.6mm section tissue microarrays (TMA). Survival data was also evaluated. Results: 64 cases of LCL were evaluated, 31 of which were HIV+ (33 cases were HIV-). HIV p24 staining was seen with 13 of the 31 HIV+ cases(42%) , with staining only in MOs. Promacs (CD68+/PCNA+MOs) were more frequent in cases of HIV+ LCL (median of 18) and HIV- LCL (median of 5), than normal lymph nodes and reactive tonsillar tissue (p<.001). In both HIV+ and HIV- cases of LCL, there was a trend towards shorter survival (p<0.07) with increased numbers of MOs and promacs; p24 reactivity was unrelated to survival. Conclusions: In this preliminary study of MOs in LCL, MO number per TMA core was significantly correlated with promac number in all cases of LCL (p<.001). HIV p24 localized to MOs in 42% of HIV+ LCL cases and was unrelated to survival. Increased promac numbers in cases of LCL correlated with decreased survival in all cases of LCL, but cases of HIV+LCL tended to demonstrate shorter survival than in cases of HIV- LCL. Of the latter group, higher numbers of macrophages (for example, greater than 46 macrophages/core) portend a worse prognosis, but this finding was not statistically significant in this preliminary study. No significant financial relationships to disclose.
Outcomes after autologous stem cell transplantation in relapsed or refractory Hodgkin disease: The Duke experience
Authors: Kim D. W. , Misra D. , Clough R. W. , Long G. D. , Prosnitz R. G. 
Published: March 2020

8100 Background: High dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) offers patients with relapsed or refractory Hodgkin's disease (HD) the possibility of durable long term remission. We examined the characteristics and outcomes of patients treated at Duke University Medical Center between May 1997 and May 2006. Methods: We performed a retrospective chart review on all patients with relapsed or refractory HD who received HDT followed by ASCT at our institution. Various prognostic factors were also analyzed for their impact on overall survival (OS) and disease free survival (DFS). Results: Sixty-one patients received HDT followed by ASCT for relapsed or refractory HD. Median age was 33 years (range: 16 years to 64 years). The patient population was comprised primarily of males (64%), Caucasians (80%), and patients with nodular sclerosing histology (77%). Fifty-six percent of patients had primary refractory HD. At the time of relapse, 44% of patients had stage I-II disease, and 21% had B symptoms. For patients with relapsed disease, the median time from initial diagnosis to relapse was 17 months. Most patients (64%) received cyclophosphamide, etoposide, and BCNU chemotherapy as HDT. Thirty-one percent of patients received consolidative radiotherapy after HDT. Twenty-eight percent of patients had chemotherapy- responsive disease prior to undergoing HDT. Following ASCT, 46/61 (75%) of patients achieved a complete response. Transplant-related deaths occurred in 2/61 (3%) patients. With a median follow-up of 2.5 years (range: 3 months to 8.8 years), the actuarial 5-year OS and DFS were 79% and 50%, respectively. The most common post-therapy complication was pneumonitis, which occurred in 62% of patients. Three (5%) patients developed second malignancies. On univariate analysis, gender, stage at diagnosis, stage at relapse, presence of B symptoms at relapse, and the interval to first relapse did not significantly affect OS or DFS. Conclusions: Our results confirm that HDT followed by ASCT offers an excellent chance for long-term DFS and OS in patients with relapsed or refractory HD, with a low risk of treatment-related mortality. No significant financial relationships to disclose.
Identification of specific immune responses in monoclonal gammopathy of undetermined significance with therapeutic implications
Authors: Blotta S. , Mitsiades C. , Tassone P. , Negri J. , Tai Y. , Prabhala R. , Franco B. , Venuta S. , Anderson K. , Munshi N. 
Published: March 2020

8103 Background: Monoclonal gammopathy of undetermined significance (MGUS) is a benign condition with only 30% patients developing symptomatic multiple myeloma (MM). The events leading to the transformation from MGUS to MM remain unclear, however several evidences have supported the idea that immune surveillance play a role in preventing progression. Therefore, identification of antigenic targets with immune response in MGUS may provide insight into disease biology and immune-based therapeutic applications. Methods: Using the Serological identification of antigen by Recombinant Expression cloning (SEREX) technique, we have screened a MM cDNA library with 3 MGUS patients sera. Results: We have identified 11 gene products with an antibody response in MGUS. The response appeared to be directed against intracellular proteins involved in apoptosis (SON, Hip1), DNA and RNA binding proteins (KIAA0530, GPATC4), signal transduction regulators (AKAP11), developmental proteins (OFD1), transcriptional co-repressors (IRF2BP2), protein of the ubiquitin-proteosome pathways (PSMC1). We have further analyzed frequency of antibody response against these antigens in additional 26 MGUS sera, 10 newly diagnosed, 11 post-transplant remission and 12 relapsed MM patients and 25 normal donors. Whereas an antibody response was observed against OFD1 (20.6%), KIAA0530 (10.3%), AKAP11 (10.3%) and GPATC4 (6.8%) in MGUS patients, no responses were observed in normal donors or MM patients except against OFD1 in 3 post transplant patients. We have further focused our studies on OFD1, a developmentally expressed Hedgehog (Hh)-pathway-related protein with most frequent antibody response. We have previously showed that Hh-pathway genes are involved in development of MGUS. Our microarray analysis showed that OFD1 and other Hh pathway-related genes (Sonic, Smothened, Patched, Gli-1 and Gli-3) are selectively expressed in MM cell lines and primary cells. We have further evaluated a specific inhibitor of Hh- pathway, Cyclopamine, in MM and observed an inhibition of the proliferation in 5 MM cell lines with an IC50 between 13 - 20 μM. Conclusion: We have confirmed a specific immune response in MGUS and have identified a novel therapeutic target for treatment of MM. No significant financial relationships to disclose.
Determining familial risk of multiple myeloma
Authors: Coleman E. A. , Lynch H. , Enderlin C. , Stewart C. B. , Kennedy R. , Barlogie B. 
Published: March 2020

8111 Background: The etiology of multiple myeloma (MM) remains unknown although genetic and environmental factors have been implicated. Familial MM has been reported; however, whether this familial tendency is due to genetic factors or environmental exposures or both is not known. Analysis of SEER data showed that Iowa, an agricultural state, had the highest incidence of MM; however, once we adjusted for race, sex, age, and year of diagnosis, the effect of geographic area was small and the main effect was race. This project aims to build a Familial MM Registry of families and investigate the families’ pedigrees and environmental factors to determine the familial risk of MM. The long term goal is to identify myeloma susceptibility loci which ultimately could lead to finding myeloma prone germline mutations. Methods: Patients (n = 67) from the Myeloma Institute for Research and Therapy at the University of Arkansas for Medical Sciences and their family members with MM or a related malignancy (amyloidoses, lymphoma, chronic lymphocytic leukemia, chronic myelogenous leukemia, Waldenstrom's macroglobulinemia, Hairy cell leukemia, acute myelogenous leukemia, acute lymphocytic leukemia, Hodgkin's disease) were interviewed for environmental factors associated with MM and for family history data to complete pedigrees. Pedigrees were analyzed to determine the patterns of inheritance. Results: Data show that 26 patients (39%) have family members with MM (one having five family members with MM) and 34 patients (51%) have family members with related malignancies. Eighteen families (27%) have a putative autosomal dominant mode of genetic transmission of MM. Pancreatic cancer, malignant melanoma, breast cancer and lymphoma may be part of a myeloma syndrome. Pesticide/insecticide exposure, raising cattle or growing cotton were the most prevalent environmental risk factors. Conclusions: The pedigrees suggest the existence of genetic traits affecting MM susceptibility. This work will be part of the efforts to create an international consortium to study familial MM. Research in the area of molecular epidemiology is needed to discover the genetic and environmental determinants of this disease and the reasons for the racial and gender differences. No significant financial relationships to disclose.
Cytogenetic analysis using multiple myeloma targets in POEMS syndrome
Authors: Bryce A. H. , Ketterling R. P. , Gertz M. A. , Kyle R. A. , Lust J. A. , Fonseca R. , Lacy M. , Greipp P. R. , Witzig T. A. , Rajkumar S. , Dispenzieri A. 
Published: March 2020

8116 Background: POEMS syndrome, or osteosclerotic myeloma, is an uncommon plasma cell disorder associated with Peripheral neuropathy, Organomegaly, Endocrinopathy, M protein, and Skin changes, as well as bone lesions, Castlemans disease, and edema. The pathogenesis of POEMS is poorly understood, and its clinical course is distinct from Multiple Myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). While various cytogenetic abnormalities have been well described in MM and MGUS, we provide the first report of testing for these abnormalities in POEMS syndrome. Methods: Using a prospectively held dysproteinemia database, we reviewed all cases of POEMS seen at our institution, identifying 36 with metaphase cytogenetic testing results, and 9 with fluorescence in situ hybridization (FISH) testing results. Combined cytoplasmic immunoglobulin/FISH testing (cIg- FISH) was performed with fluorescent-tagged antibodies to kappa/lambda immunoglobulin and FISH probes corresponding to the following anomalies: trisomies 3, 7, 9, 11, 15 and 17; del13/del13q; 14q32 split/del14; and t(11;14). Results: Five patients had insufficient plasma cells for cIg-FISH, and 9 were adequate for testing. Monosomy 13 was seen in 5 of the 9 cIg-FISH samples of which 2 of these cases also had apparent monosomy 14. cIg-FISH in one patient revealed trisomy 3 and 7. No abnormalities were seen at 11q13 (CCND1), 17p13 (p53) or translocations involving 14q32 (IGH). Thrity-eight total karyotypes analyses were attempted, though two showed an insufficient number of suitable metaphases. Of the 36 karyotype analyses, 31 were normal, 2 displayed characteristic plasma cell anomalies (hyperdiploid with structural anomalies), 2 treated patients displayed del20q anomalies and 1 patient had a constitutional 13;14 translocation. Conclusion: We are the first to report del13 as a possibly common abnormality in POEMS syndrome, detected by cIg-FISH in 5 of 9 (55%) samples with sufficient plasma cells, similar to the rate observed in MM and MGUS. The lack of abnormalities at 14q32 (IgH locus) is in contrast to MM and MGUS. Abnormal karyotypes, consistent with dividing plasma cells, are rare in POEMS, observed in only 2 of 36 (5.5%) cases. These observations could possibly lend insight into all three disorders. No significant financial relationships to disclose.
Impact of intensive stem cell mobilization therapy on outcomes following autologous stem cell transplantation (ASCT) for non- Hodgkin lymphoma (NHL)
Authors: Damon L. E. , Damon L. , Kaplan L. , Martin T. , Linker C. A. 
Published: March 2020

8119 Background: We retrospectively evaluated the impact of intense [I] stem cell mobilization therapy on event-free survival [EFS] and overall survival [OS] following ASCT for NHL. Methods: 80 patients (pt) were studied (2 Burkitt, 3 primary CNS, 3 follicular, 2 intravascular, 43 large cell, 12 mantle cell, 9 transformed, and 6 peripheral T-cell). Patients with very-high risk features (LDH > 500 IU/L, first remissions < 1 year, 2 or more extra-nodal sites, and/or primary CNS/intravascular/mantle cell/peripheral T-cell histology) were prospectively allocated to I stem cell mobilization (requiring hospitalization) with either cyclophosphamide [C] (6 g/m2) + etoposide [E] (2g/m2) + filgrastim [G-CSF] (±rituximab [R]) (n=5) or with cytarabine [A] (2 g/m2 bid for 8 doses) + E (40 mg/kg) + G- CSF (±R) (n=45). 30 pt were mobilized (outpatient) with C 4g/m2 + G-CSF ±R (non-intense [NI] mobilization). 76 pt received ASCT conditioning with carmustine [B] + E and C (CBV) and 2 with B + E + A and melphalan (BEAM); 2 pt did not undergo ASCT. Results: The median age was 54 (21–69 years [yr]) and 57% had an elevated LDH at presentation. 39 pt (49%) were primary induction failures (PIF). At NHL presentation, 38% were IPI high-intermediate or high risk. There were 3 non-relapse mortalities (4%): (2) B pneumonitis and (1) multi-organ failure (all following ASCT). With a median follow-up of 1.8 yr (0.1–6.4), the overall median EFS is 3 yr (48% [34–62] at 4 yr) and the median OS is 4.7 yr (59% [43–72] at 4 yr). Patients receiving I mobilization were similar to those receiving NI mobilization in terms of the # of prior therapies (median 2, each), the presenting IPI risk score, and the percent PIF (57% vs 41%; p=0.17). There were trends favoring I mobilization for both 4 yr EFS (58% [41–75] vs 35% [13–57]) and OS (66% [48–84] vs 52% [32–72]), neither statistically significant. In the sub-group of large B-cell NHL, 4 yr EFS was the same in pt receiving I mobilization (81% [63–98] vs 73% [50–96]; p=0.33) but OS was better (91% [79–100] vs 58% [35–82]; p=0.02). Conclusions: I stem cell mobilization therapy, compared to NI mobilization therapy, may improve outcomes for NHL pt with very-high risk features and may overcome the anticipated poor prognosis of these pt. No significant financial relationships to disclose.
Phase I trial of escalating doses of total marrow irradiation (TMI) with helical tomotherapy and peripheral blood progenitor cell rescue (PBPC) following high-dose melphalan and PBPC as part of tandem high-dose therapy (THDT) for patients with multiple myeloma (MM)
Authors: Wong J. Y. , Somlo G. , Spielberger R. , Forman S. , Poppelwell L. , Schultheiss T. , Frankel P. , Krishnan A. , Sahebi F. , Parker P. 
Published: March 2020

8121 Background: Attempts to combine total body irradiation (TBI) with high-dose melphalan (Mel) resulted in substantial organ toxicities and precluded optimal dosing of Mel. Helical tomotherapy may allow delivery of total marrow irradiation (TMI), while avoiding collateral toxicities. Methods: We designed a phase I/II study for patients (pts) with responding or stable stage I-III MM. Following PBPC mobilization, pts receive THDT first with Mel 200 mg/m2 and PBPC, and, ≥ 6 weeks later, escalating doses of TMI (starting dose: 200 cGy daily × 5 [1,000 cGy], up to 200 cGy twice daily × 5 days [2,000 cGy]) and PBPC. Maintenance consists of dexamethasone 40 mg/day × 4 days every 28 days and thalidomide 50–200 mg/day. Results: The median number of prior chemotherapy regimens is 2 (1- 4). The median duration from diagnosis to the HDT is 8 mos (4–13). Median age of pts is 53 (35–66). Sixteen pts with stages II (6) and III (10) MM have received Mel; 15 of 16 pts (8F/8M) have received treatment at dose levels 1–5 of TMI (1,000 cGy through 1,800 cGy); 1 pt is about to start TMI at 1,800 cGy. The median time between the first and second THCT cycles is 74 days (47–125). Hematopoietic toxicities were independent of TMI dose levels: granulocyte recovery to >1,000/microliter following Mel required 12 days (11–38) versus a median of 10 days after TMI (range; 9–12). Platelet (excluding 6 pts not needing plt transfusion) independence was seen by day 10 (8–13) versus 8 (6–11) following TMI. In the first 15 pts the estimated median radiation dose to normal organs was 15–60% of the targeted bone marrow dose. Reversible grade 3 non-hematologic toxicities by TMI dose levels included fatigue and febrile neutropenia (FN) (level 1: 1 pt each), FN (level 2: 1 pt); none (level 3); fatigue (level 4: 2 pts); anorexia and stomatitis (level 5: 1pt; anorexia: 1 pt). The median follow-up is 8 mos (3–21); 1 pt progressed at 8 mos. Final data on toxicities including patients already in screening for treatment at TMI 2,000 cGy, tolerability of maintenance, and response rate will be presented. Conclusion: TMI is feasible and could potentially be useful as part of THDT for patients with MM. No significant financial relationships to disclose.
Interferon alfa-induced autoimmunity and serum S100 levels as predictive and prognostic biomarkers in high-risk melanoma in the ECOG-intergroup phase II trial E2696
Authors: Stuckert J. J. , Tarhini A. A. , Lee S. , Sander C. , Kirkwood J. M. 
Published: March 2020

8506 Background: Uncontrolled evidence demonstrates that adjuvant high-dose interferon alfa-2b (HDI) benefit in high-risk melanoma patients is predicted by autoimmunity induction, and the prognosis of melanoma has been correlated with levels of S-100 protein. We have evaluated these two serological markers in the context of a completed phase II study E2696. Methods: Patients with resectable AJCC stage IIB, III, and IV melanoma were randomly assigned to receive GM2-KLH/QS-1 (GMK vaccine) plus concurrent HDI (Arm A) or GMK plus sequential HDI (Arm B), or GMK without HDI (Arm C). Sera from 103 patients were banked at baseline and 3 additional time points, and have been tested for serum protein S100, and anti-nuclear, anti-thyroid peroxidase, anti-thyroglobulin, anti-mitochondrial, and total anti-cardiolipin autoantibodies (AA) using ELISA. Results: At a median follow-up of 96.5 mo (range: 17–109), the median relapse-free survival (RFS) was 28.3 mo, 95% CI (18.4, 43.6) (64 /103 patients relapsed). Median survival has not been reached (54/103 alive). AA were induced in 17 subjects (25%; n=69) receiving HDI and GMK versus 2 (6%; n=34) receiving GMK alone (2p-value=0.031). In HDI arms induced AA were detected = 12 weeks after therapy initiation. RFS was improved among HDI recipients with AA, but with the limited numbers in this phase II trial this trend does not achieve significance. In the multivariate (Cox regression model) analysis, adjusting for treatment (HDI vs. no HDI) and baseline S-100 value for later time points, S-100 level ≥0.08 microg/l was an independent prognostic factor for RFS at baseline (HR=1.96; p=0.0273), week 4–6 (HR=1.72; p=0.073), wk 12–14 (HR=1.81; p=0.048) and wk 52 (HR=4.3; p<0.001). The hazard ratio (HR) for OS was 1.86 at wk 12–14 (p=0.061), and 5.7 at wk 52 (p<.001). In the model using wk 52 S-100 value (at completion of HDI), the HR adjusted for treatment was 7.1 p=0.009. Conclusions: Autoimmunity is a predictive biomarker of RFS with HDI in the E2696 trial compared to GMK. Serum protein S-100 level ≥0.08 microg/l is an independent prognostic marker for RFS and OS most significant at baseline and 1 year of followup. Current studies will evaluate these markers in the larger phase III trial E1694 with 880 subjects. [Table: see text]