bluuebunny/crossref_metadata_2025_split huggingface dataset:
A retrospective review of pegylated liposomal doxorubicin (PLD), bortezomib, and dexamethasone (DVD) for relapsed or refractory (R/R) multiple myeloma (MM)
Authors: Waterman G. N. , Yellin O. , Swift R. A. , Hilger J. , Berenson J. R. 
Published: August 2020

e19523 Background: Preclinical data show that PLD and bortezomib demonstrate synergistic anti-MM effects. Clinical trials have demonstrated the efficacy of this combination for MM patients (pts) as well as its superiority to bortezomib alone. In vivo studies have shown that more frequent administration of low-dose PLD produces enhanced anti-MM effects with better tolerability compared to weekly standard doses of PLD. Thus, a low dose PLD dosing schedule was evaluated in combination with bortezomib and dexamethasone for pts with R/R MM. Methods: This retrospective analysis sought to evaluate the DVD regimen for pts with R/R MM. Twenty pts who had received and failed at least one prior treatment for MM were studied. Treatment consisted of intravenous administration of 40 mg dexamethasone, 1.0 mg/m2 bortezomib and 5.0 mg/m2 PLD on days 1, 4, 8 and 11 of a 28-day cycle. Pts ranged in age from 43–81 years (median 65), and had received between 1–14 prior therapies (median 5). Baseline disease stage was: 6 (I), 7 (II), and 7 (III). Elevated serum creatinine levels at baseline were found in 30% of patients. Results: The objective response rate (ORR) was 50%, which included 1 complete response (5%), 1 very good partial response (5%), 4 partial responses (20%), and 4 minimal responses (20%). Sixteen pts had previously received bortezomib-containing regimens and 6 (38%) responded. Among the entire cohort, the duration of response was 2+-19+ months (mo) (median 7 mo). Six pts had stable disease (30%) lasting between 5–9 mo (median 9 mo). Progression-free survival was 1+-19+ mo (median 8 mo). The regimen was well tolerated with a single mild case of transient hand and foot syndrome and 10 pts developed grade 1 or 2 peripheral neuropathy. One pt discontinued the regimen due to an adverse event (AE; 5%). The median overall survival was 17 mo (range 1+-33+ mo). Conclusions: Patients treated with the DVD regimen in this study who had failed many prior regimens (median 5) with progressive disease demonstrated a high response rate (50%). In addition, there were few significant or drug-related AEs. Because of these encouraging results, we are now evaluating this regimen in a phase 2 clinical trial in the frontline setting. [Table: see text]
Elevated troponin and abnormalities of cardiac structure and function in AL cardiac amyloidosis
Authors: Apridonidze T. , Steingart R. , Comenzo R. L. , Hoffman J. E. , Goldsmith Y. , Liu J. 
Published: August 2020

e19524 Background: Patients with systemic amyloidosis involving the heart have generally a poor prognosis. Elevated cardiac troponin (cTn) has been shown to predict poor survival in patients with AL cardiac amyloidosis (CA). However, cardiac structure and function associated with an elevated cTn in patients with CA remains uncertain. Methods: Eighty patients with CA who had an echocardiogram and cTnI measured at the time of diagnosis between March 1997 May 2008 were included in the study. The patients were divided into 2 groups: normal cTnI ( <0.06 ng/ml, n = 28) or elevated cTnI (≥0.06 ng/ml; n = 52). Results: The elevated cTnI group was slightly older with higher brain natriuretic peptide (BNP) level and creatinine clearance than the normal cTnI group. There was a trend towards higher prevalence of congestive heart failure (CHF) in the elevated cTnI group than the normal group at time of diagnosis. The elevated cTnIgroup had thicker interventricular septum and higher left atrial (LA) volume than the normal group. LV ejection fraction, left atrial systolic force (LASF) and stroke volume were lower in the elevated cTnI group than the normal group. Mean survival was significantly shorter in the elevated cTnI group than the normal group (10 vs. 47 months). Conclusions: Elevated troponin in patients with AL cardiac amyloidosis is associated with worse left atrial and ventricular structure and function. The raised troponin level reflects myocardial injury due to the amyloid deposition and correlates with more abnormal alteration of cardiac structure and function. Routine measurement of troponin is useful in identifying high risk patients with CA. [Table: see text] No significant financial relationships to disclose.
SEER analysis of subcutaneous panniculitis-like T-cell lymphoma (SPTL)
Authors: Martin M. G. , Cashen A. F. 
Published: August 2020

e19527 Background: The uncommon nature of SPTL has hampered its clinical characterization. The EORTC described 83 cases of SPTL across 8 centers and suggested a difference in prognosis between patients with alpha/beta (AB) SPTL, who were predominantly younger (median age 36 y) and those with gamma/delta (GD) SPTL, who had a median age of 59 years (1–Blood 2008; 111: 838–45). But regional differences in the frequency of SPLT have also been suggested, with its frequency >2x higher in North America than Europe (2–J Clin Oncol 2008 26: 4121–30). We hypothesized that there may be differences in the presentation between SPTL in Europe and North America. Methods: Analysis of the SEER 17 Nov 2007 (1973–2005) database was conducted with SEER Stat version 6.4.4 and GraphPad Prism 5. Cases of SPTL were defined by the ICD-O-3 code 9708. We also analyzed outcomes for patients < and ≥ 50y at diagnosis. Results: 64 patients were identified with SPTL. The median age was 53y (range 2–83); 28 were <50y and 36 were ≥50y. 19 (30%) patients were male, 45 were female; 44 (69%) patients were white, 13 were black and 7 were Asian. Stage was available on 27 patients: 16 (59%) were Stage I/II and 11 were stage III/IV. There was no difference in gender, ethnicity or stage distribution between those < 50 and ≥ 50. Information on B symptoms was available on 20 patients, 11 (55%) of whom had B symptoms. 5-year lymphoma specific survival was 51%; 5-year OS was 41%. Median OS for patients < 50 was 60 months compared to 12 months for patients ≥50 (G-B-W p=0.0183). Lymphoma specific survival was also significantly longer in the younger patients (G-B-W p=0.0015). Conclusions: In the SEER database, outcome of SPTL is strongly correlated with age. This result suggests a different biology between younger and older patients with SPTCL, possibly because the AB- subtype is more prevalent in younger patients, as reported by the EORTC. As well as differences in the overall frequency of SPTL (2), there may be geographic differences in the distribution of subtypes. [Table: see text] No significant financial relationships to disclose.
Systematic assessment of potential cardiac effects of the novel histone deacetylase (HDAC) inhibitor romidepsin
Authors: Cabell C. , Bates S. , Piekarz R. , Whittaker S. , Kim Y. , Godfrey C. , Schoonmaker C. , McCulloch W. , Nichols J. , Burris H. A. 
Published: August 2020

e19533 Background: Romidepsin is a novel pan-HDAC inhibitor with single-agent activity in T-cell lymphoma. HDAC inhibitors reportedly have cardiovascular effects, in particular, QTc prolongation. To systematically and rigorously evaluate the potential cardiac effects of romidepsin, a cardiac safety monitoring plan was developed after discussions with the FDA. Methods: The effect of romidepsin on the change from baseline QTcF (Fridericia's correction) at key pharmacokinetic and pharmacodynamic (PD) time points was investigated. ECGs from 110 pts with advanced malignancies in 3 open-label, clinical studies of romidepsin 14 mg/m2 administered on days 1, 8 and 15 of a 28 day cycle were evaluated by blinded, independent assessors. Results: A mean 2.7 msec increase (90% confidence interval [CI]: 0.2, 5.3) in QTcF interval from a baseline post-antiemetic administration to after infusion of romidepsin was measured. A subanalysis of 74 patients (pts) evaluated QTcF from pre-antiemetic to post-romidepsin showed a mean change in QTcF of 5.0 msec (90% CI: 2.3, 7.7). Thus, antiemetic comedications likely accounts for a portion of the clinically apparent QTc effect. The QTc returned to baseline within 48 hrs. No absolute QTc values >480 msec and no QTc changes >60 msec were observed. No relationship was observed in an analysis of romidepsin plasma concentration versus QT changes. Mean heart rate (HR) increased 10.1±9.0 bpm after romidepsin administration, with a return to baseline by 24 hrs. Several treatment-emergent morphological changes in ECGs (including T wave and ST-segment) were reported. Many of the ECG morphologic abnormalities (determined by automated machine reading) were also observed at baseline. These ECG changes were transient and were not associated with functional cardiovascular changes or with symptoms. Conclusions: Romidepsin has a slight effect on the QT interval but rigorous ECG evaluation found this effect to be mild, below the threshold of regulatory and clinical concern, and not associated with any observed clinical cardiovascular events. Concentration response modeling found no PD relationship between romidepsin concentration and changes in QTcF, but did suggest a relationship between romidepsin concentration and HR. [Table: see text]
Relationship between efficacy of denileukin diftitox (Dd) and antibody development in cutaneous T-cell lymphoma (CTCL): An analysis of two phase III studies
Authors: Acosta M. , Duvic M. , Lopez-Anaya A. 
Published: August 2020

e19534 Background: Dd is a novel IL-2 receptor-targeted recombinant fusion protein approved for persistent/recurrent CTCL expressing CD25. The effect of antibody titers on efficacy in CTCL was assessed in 2 phase III studies (11 & 14). Methods: Dd doses were 9 or 18 mcg/kg daily for 5 days, repeating every 21 days, up to 8 courses. Serum samples were collected prior to Dd infusion on day 1 of courses 1, 3, 5, and 7. Immune response to Dd was assessed using 2 enzyme-linked immunoassays: 1 for anti-IL-2 antibody (Ab) and the other for anti-Dd Ab. Immunogenicity data reflect percentage of subjects whose test results were considered positive for antibody to the intact Dd fusion protein. Results: In Study 11, 66% of subjects tested positive for anti-Dd Ab at baseline, possibly due to prior exposure to diphtheria toxin or its vaccine. In both studies, and for both doses, rapid increases in Ab titers were observed in nearly 100% of subjects from courses 1 to 3 (∼650-fold, 11; >=625-fold, 14). After 3 treatment courses, mean Ab levels stabilized and did not change appreciably with time. Pharmacokinetic (PK) parameters (Cmax and AUC) decreased substantially during the same period, but no relationship between Ab formation and clearance was identified. Low Spearman Correlation coefficient values indicated lack of a significant association (i) between the pre-treatment or treatment-related Ab levels and (ii) between PK changes for subjects who responded and subjects who did not respond. Of subjects positive for Ab at baseline, 43% (27/63) and 38% (13/34) responded to treatment, as compared to 50% (16/32) and 54% (7/13) for subjects who had no detectable Ab at baseline in Studies 11 and 14 respectively. There appeared to be higher incidences of response in subjects with lower initial Ab titers. Conclusions: In the studies analyzed, antibody formation in response to Dd exposure did not appear to compromise efficacy for treatment of CTCL. [Table: see text]
Unexpected toxicity (UT) and opportunistic infections (OI) after rituximab-containing therapy for non-Hodgkin's lymphoma (NHL)
Authors: Hentrich M. , Gerl A. , Lutz L. , Karthaus M. , Schiel X. 
Published: August 2020

e19546 Background: Rituximab (R) is increasingly used for the treatment of B-NHL. Most adverse events are mild to moderate. In rare cases, however, R may be associated with severe UT and OI. Methods: The records of consecutive pts treated at 2 institutions from 01/06 to 12/08 with R-containing chemotherapy or R-maintenance therapy (R-M) for NHL were analyzed for severe UT and OI. UT was considered as related to R if it could not be explained otherwise. Results: 99 pts were included in the cohort study. Pts received a median of 6 cycles (range 1 - 18) of R. A total of 517 cycles of R were evaluable for OI or UT. 7 of 99 pts (7%) (2 females, 5 males) with a median age of 69.5 yrs (range 41–76) experienced UT (n=4) or OI (n=3). UT consisted of interstitial pneumonitis (IP) in 2 pts after 8 and 6 cycles of R-CHOP for diffuse large cell lymphoma (DLCL), a case of congestive heart failure (NYHA III°) after 6x R-CHOP + 2x R-M for follicular lymphoma (FL) and a case of grade 4 pancytopenia lasting for 22 days following 2x R-FC for chronic lymphocytic leukemia. IP completely resolved after initiation of prednisone (n=1) or under empiric antimicrobial therapy (n=1). Congestive heart failure improved under appropriate therapy and the pt received 2 more cycles of R-M. Pancytopenia slowly recovered under therapy with G-CSF, R was terminated. OI consisted of pneumocystis jirovecii pneumonia after 5x R-CHOP-14 for DLCL, Epstein-Barr-virus (EBV)-associated hepatitis after 5x R-CHOP-21 for relapsed FL and generalized herpes zoster following 6x R-bendamustine (RB) + 1x R-M for recurrent BALT-lymphoma. R was restarted in the latter 2 pts. Infections resolved under antimicrobial therapy. EBV-hepatitis improved spontaneously. Moreover, 2 pts were transferred to us for therapy of enterovirus-induced encephalitis after 6x R-CHOP-21 + 2x R-M for FL (n=1) and cerebral toxoplasmosis in a pt heavily pretreated with R-containing therapy for relapsed mantle cell lymphoma (n=1). Conclusions: Severe UT and OI are rare but potentially fatal complications. Awareness of UT/OI, rapid diagnostic proceedings and, whenever possible, initiation of therapy are essential. In selected cases reexposure of R may be feasible. No significant financial relationships to disclose.
The usefulness of interphase fluorescence in situ hybridization at diagnosis of myeloma in addition to metaphase cytogenetics
Authors: Park S. , Kim C. , Kim H. , Hong D. , Lee S. , Won J. , Park H. , Bae S. , Lee Y. , Kim E. , Jung Y. 
Published: August 2020

e19558 Background: Multiple myeloma is characterized by the accumulation of malignant plasma cells within the bone marrow and regarded as incurable, but remissions may be induced with steroids, chemotherapy, thalidomide and stem cell transplants. The clinical heterogeneity of myeloma is dictated by the cytogenetic aberrations present in the clonal plasma cells. Fluorescence in situ hybridization (FISH) overcomes the limitations of standard cytogenetics and allows for the detection of numerical and structural chromosomal abnormalities in both metaphase spreads and interphase nuclei. Methods: We evaluated the chromosome abnormalities in 34 MM patients using conventional cytogenetics and interphase FISH with 6 probes such as IGH/CCND1, IGH/FGFR3, IGH/MAF, DS13S319/LAMP1, IGH/BAP, and p53/CEP17. Results: Cytogenetic abnormalities were found in 24 (70.6%) of the 28 MM patients. 10 (35.7%) patients had abnormal metaphases by conventional cytogenetics. Interphase FISH results were abnormal in 21 (61.8%) patients and 11 (52.3%) patients had abnormal interphase FISH but normal metaphases. The evidence of the loss of D13S319 with or without loss of LAMP1 was found in 6 (21.4%) patients, and loss of p53±CEP17 for 2 patients, IGH-BAP for 9 (26.5%) patients, IGH/FGFR3 for 2 patients, and IGH/CCND1 for 7 (20.6%) patients, respectively. However, there were none positive for IGH/MAF. Chromosome 13 abnormalities and IGH rearrangement is correlated with poor clinical outcome. Conclusions: Interphase FISH can provide useful information to evaluate the presence of prognostic chromosome abnormalities in addition to metaphase cytogenetics. And it should be used in the routine evaluation of multiple myeloma. No significant financial relationships to disclose.
Regression of follicular lymphoma with alternative therapy using Devil's Claw (DC); Coincidence or causation?
Authors: Wilson K. S. 
Published: August 2020

e19560 Background: Alternative therapies are used by c 30% of cancer pts (Ernst and Cassileth, Cancer 2000). Two follicular lymphoma (FL) pts who had objective tumor regression after taking the herb DC without cytotoxic therapy are reported here. Methods: This was a retrospective chart review. In January 2000, pt #1 presented with co-existent IgG plasma cell dyscrasia and stage 3A grade 2 FL with 5 cm cervical and R/P nodes. CT scan 10 months later showing partial regression of adenopathy. On enquiry, he was taking DC and Essiac. He developed overt myeloma in Aug 2001, when he stopped DC/Essiac and received HDCT/ASCT following which there has been no clinical progression of lymphoma. In November 2003, pt #2 presented with stage 3A grade 1 FL. CT scan showed widespread adenopathy (2.5 cm max.). He learned of pt #1 through the local Lymphoma Patient Support Group and started DC alone. CT scan 11 months later showed decreased adenopathy and splenomegaly which has been sustained. Results: CT images at baseline and follow-up confirm objective regression. Conclusions: DC (Harpagophytum procumbens) tuberous root contains Harpagoside and Beta sitosterol and has anti-inflammatory properties probably by suppressing COX-2 and iNOS expression (Jang et al, J Pharmacol Sci, 2003). There is good evidence for its use in osteoarthritis ( http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-devilsclaw.html ) but it has not been reported to have anticancer activity. COX-2 inhibition has an accepted role in cancer prevention (Steinbach et al, NEJM 2000), has been implicated in lymphomagenesis (Wun et al, Leuk Res 2004) and associated with both stage of lymphoma and response to standard treatment (Hazar et al, Leuk Lymphoma 2004). However, spontaneous regression in low grade lymphoma has been reported in 7 of 44 pts on observation only (Krikorian et al, 1980); none were on herbal medications or COX-2 inhibitors. The key issue in both these patients is whether or not the disease regression was “spontaneous” or causally related to DC therapy, but the timing of response suggests a potential therapeutic benefit. Considering the role of COX-2 inhibitors and the relation between components of DC and COX-2, further investigation is warranted, preferably with a COX-2 inhibitor of known purity. No significant financial relationships to disclose.
The signet ring cell melanoma-rare morphologic variant of melanoma: Case report
Authors: Maksimovic S. , Jakovljevic B. 
Published: August 2020

e20020 Background: Melanoma is a malignant tumor of melanocytes of skin. The histopathological variants of malignant melanoma include the common type (lentigo maligna (5%), superficial spreading melanoma (65%), nodular melanoma (15%), acrolentiginous melanoma (5%). The signet ring cell melanoma is a rare form melanoma, being seen in some 0.5% of melanomas. Aim of work: That showed young women with signet ring cell melanoma is a rare form melanoma. Methods: We describe a 39-year-old patient with a primary signet-ring cell melanoma of the skin located on the left upper quadrant of abdominal wall. Results: Diagnosis the tumour of skin was in department of surgery and histhopatology in General hospital in Bijeljini in December of the 2007. We performed clinical and histhopatologic examination. Physical examination revealed a well circumscribed and firm mass measuring 150x 100x 80 mm of the skin located on the upper quadrant of abdominal wall and solid mass in pelvis. Because of high suspect melanoma in patient performed surgical excision of skin tumor. Pathohysthology diagnosis was: Melanoma nodularis achromaticum. Immunohistochemistry showed positive reaction of the tumor cells for S-100, HMB-45 protein and vimentin, confirming their melanocytic differentiation. Tumor cells were negative for cytokeratins, epithelial membrane antigen (EMA), and carcinoembryonic antigen (CEA). After immunohistochemistry analysis definitive pathohystology was: Signet ring cell melanoma. The signet-ring cell melanoma disclosed an invasion to Clark Level V and tumor thickness Breslow level III. Tumor from pelvis was appertain uterus and histopathologic diagnosis is a leomyoma. Conclusions: Signet-ring cell melanoma is a rare morphologic variant of melanoma. Its recognition is important for differentiation from other tumors featuring signet ring cells. No significant financial relationships to disclose.
The impact of telemedicine in cancer care
Authors: Yunus F. , Gray S. , Fox K. C. , Allen J. W. , Sachdev J. , Merkel M. , Chambley B. , Yunus R. , Waters T. M. 
Published: August 2020

e20508 Background: The Technology Exchange for Cancer Health Network is a collaborative, multi-state effort using Telemedicine and integrated electronic health records to provide rural cancer care management. Methods: The purpose of the study was to compare quality, safety, and cost outcomes for patients receiving rural Telehealth care versus “routine” urban care. Patients with a cancer diagnosis requiring treatment for at least 1 year were eligible for the study. Telehealth patients saw their oncologist in person at rural sites for initial care and via telemedicine for about half of subsequent visits, allowing clinicians in-person clinical assessments while still taking advantage of time savings associated with telemedicine. Results: 217 patients (134 rural, 83 urban) were enrolled from 05/25/05 to 09/30/08. Patient satisfaction was high; 95 % of patients indicated their telemedicine visit was as good as or better than an in-person visit. Telemedicine patients also reported significant time and travel cost savings. Cost analysis comparing cost savings (physician travel time) with telemedicine costs (equipment, high speed lines) indicated that cost-benefit is driven by distance to rural facility and number of physician trips avoided. Telemedicine must save at least 5 hours of physician travel time per month to break even. Telemedicine was also associated with improvements in access to care. Using patient self-reported health care visit data (verified with local providers), we identified a significant decline in disparities between urban and rural patients (see Table ). Conclusions: Telemedicine offers a promising method for increasing access to oncology care that is convenient for and well-accepted by patients at reasonable costs. Our results also suggest that telemedicine facilitates access to more than just oncology care. The regular follow-up care provided through telemedicine visits may identify unmet need that might otherwise go untreated, yielding improvements in patient outcomes. [Table: see text] No significant financial relationships to disclose.