bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of allograft rejection with reduction of immunosuppression for post-transplant lymphoproliferative disorder: Analysis of a 20-year single-institutional experience.
Authors: Franke Aaron J , Bishnoi Rohit , Bajwa Ravneet , Skelton William Paul , Patel Niraj , Slayton William Birdsall , Dang Nam H. 
Published: September 2018

e19047 Background: Post transplant lymphoproliferative disorder (PTLD) is a rare, but potentially fatal complication of transplantation and therapeutic immunosuppression (IS). The cornerstone of PTLD management is reduction of IS, which carries the risk of allograft rejection. Methods: Retrospective analysis of patients diagnosed with PTLD after solid organ (SOT) or allogeneic stem cell transplant (HSCT) at the University of Florida were identified through a review of individual EMR charts. This analysis focused on rates of allograft rejection and graft failure with RI. Results: Of 138 patients diagnosed with PTLD between 1994 and 2016, 15% (n = 20) experienced allograft rejection during PTLD treatment. The primary organ of transplant and rejection included liver (35%), lung (25%), heart (10%), HSCT (15%) and kidney (15%). Median age at PTLD diagnosis was 14.5 years (range 2-59), males (50%) and median time from transplant to PTLD diagnosis was 25 months (range 0-173). RI was a documented as a component of initial PTLD treatment in 19/20 (95%) patients, with 2/20 (10%) undergoing complete withdrawal of immunosuppression, 13/20 (65%) partial RI (withdraw of one or more drugs) and 3/20 (10%) dose reductions of their established IS regimen. One lung recipient (5%) was transitioned to an alternative agent, and one patient had no documented records of IS adjustment. Treatment for acute rejection included observation 2/20 (10%), pulse steroids 11/29 (55%) or IS increase 12/20 (60%). 7/20 (35%) received combination steroids and increased IS. Allograft failure developed in 5/20 (25%) (1 kidney, 1 lung, 1 heart, 1 liver, 1 BMT). Allograft failure was not shown to correlate with RPI score at diagnosis, organ transplanted, induction therapy at transplant or 3-year OS. Of note 5/5 (100%) of patients received Rituximab as part of initial treatment, versus 5/15 patients whose grafts survived. Conclusions: RI for PTLD is associated with moderate rates of response, however acute graft rejection is common and is associated with high rates of graft failure. PTLD may still have favorable outcomes when combining partial RI with chemotherapy and Rituximab.
Paraprotein levels in assessing effectiveness of polychemotherapy plus selective plasma exchange for multiple myeloma patients.
Authors: Lysenko Irina B. , Guskova Nailya , Kit Oleg Ivanovich , Ushakova Natalya Dmitrievna , Golomeeva Nadezhda , Zuderman Natalia , Guskova Ekaterina , Nozdricheva Anastasia , Abakumova Svetlana V. , Donskaya Aliya K. , Gusareva Marina A. , Avanesova Kristina , Torpudzhyan Izabella , Tselishcheva Irina V. , Zakharchenko Viktoria , Belgova Svetlana V. , Gornostaeva Ekaterina 
Published: September 2018

e19511 Background: Our purpose was to analyze levels and types of paraprotein in polychemotherapy combined with selective plasma exchange in patients with multiple myeloma. Methods: Blood levels of paraprotein (PP) were studied by capillary electrophoresis (Helena Bioscience V8), and content of plasma cells was determined in the bone marrow of 16 patients (main group) with multiple myeloma (MM) during polychemotherapy (PCT) plus selective plasma exchange (SPE). 14 patients receiving standard PCT were the controls. Results: MM patients in both groups were characterized with the presence of PP in the blood serum with the M-peak in the gamma-globulin zone. Only heavy IgG chains were found, bound to lambda (λ) light chains in 48% and to cappa (κ) light chains in 57.15%. The initial PP level in MM-IgGλ was 91.01±0.79 g/L and was 2.4 times higher than in MM-IgGκ (38.3±0.34 g/L). Significant differences in were found in PP reduction rate and intensity depending on the treatment. PP in the main group reduced by 42.4% after course1, by 41.4% after course 2, by 52.2% after course 3 and by 24% after course 4; in the control group – by 17.2%, 19.3%, 27.9% and 47.3%, respectively. PP levels decreased by 87.4% and 74.6% by the end of the treatment, respectively. The data were confirmed by a decrease in plasma cell content in the bone marrow of patients: up to 1.2% in the main group and 6.2% in the controls. Response to treatment in the main group was registered at the early stages of therapy, and at the late stages in the control group. Treatment effect was associated with the type of secreted PP. In MM-IgGκ, PP levels in the main group decreased by 59.7% after course 1, by 40.6% more after course 2 and by 51.9% after course 3; in MM-IgGλ – by 25.1%, 42.1% and 52.5%, respectively. Treatment effect was noted earlier and PP reduction was more intensive in MM-IgGκ than in MM-IgGλ. PP levels decreased by the end of the treatment by 85.4% in MM-IgGκ and by 73% in MM-IgGλ. Similar changes were observed in the control group. Conclusions: Increased rates and intensiveness of paraprotein reduction reflect effectiveness of polychemotherapy plus selective plasma exchange for multiple myeloma. Patients with MM-IgGκ are more sensitive to the therapy.
A single-center retrospective cohort analysis of venetoclax in post-transplant, relapsed/refractory multiple myeloma.
Authors: Galligan Derek , Shah Nina , Wolf Jeffrey Lee , Wong Sandy Wai Kuan , Abramovitz Linda , Donnelly Brenn , Narayan Rupa , Mannis Gabriel N. , Arora Shagun D. , Martin Thomas G. 
Published: September 2018

e19514 Background: Despite recent advances, treatment of relapsed multiple myeloma (MM) remains a challenge. Pre-clinical studies suggest that bcl-2 inhibition can lead to MM cell death and may synergize with bortezomib. Methods: We performed a single-center, retrospective chart review of patients with relapsed MM following autologous stem cell transplantation (auto-HCT) who were treated with venetoclax, a bcl-2 inhibitor, with bortezomib. Results: 11 patients were identified. Median number of lines of prior therapy was 9 (range 5-13). 1 patient had documented high risk cytogenetics, defined as the presence of a 17p deletion, t(14;16), or t(14;20). In the 8 patients with cytogenetics/FISH available, no patients had t(11,14). 9/11 patients were refractory to bortezomib. 11/11 patients had progressed after carfilzomib, 9/11 after pomalidomide, and 11/11 after anti-CD38 antibody therapy. In all cases, patients were treated with venetoclax in combination with bortezomib. Patients were started at 400 mg daily for 7 days then increased to the median dose of 800mg daily. Overall patients received a median of 14.24 weeks of treatment (range 3-25.5). IMWG criteria were utilized to assess responses, including: 0/11 CR, 1/11 VGPR and 3/11 PR for an overall response rate of 36% (4/11). 1/11 had a minor response (light chain decrease by greater than 25% but less than 50%), 1/11 achieved stable disease, 5/11 had progressive disease. Median time to best response was 35 days (range 21-37) and median duration of response was 45 days (with several patients remaining on drug). All patients who responded had bortezomib-refractory disease. With median follow-up of 57 days, 4/11 patients have not progressed and 9/11 remain alive. The most common adverse effect was GI upset (bloating, nausea, vomiting, diarrhea) in 4/11 patients with no patients discontinuing due to side effects. There was no evidence of tumor lysis and there were no treatment-related deaths. Conclusions: Venetoclax is an active agent in relapsed multiple myeloma. Further efforts to study this therapy include prospective phase II trials and combination therapy with proteasome inhibitors and steroids.
Characteristics of adult multiple myeloma patients receiving carfilzomib in a U.S. community oncology setting.
Authors: Rifkin Robert M. , Medhekar Rohan , Mezzi Khalid , Aguilar Kathleen , Wilson Thomas , Amirian E. Susan , Panjabi Sumeet 
Published: September 2018

e19517 Background: Carfilzomib (K) is indicated for treatment of relapsed or refractory multiple myeloma (MM). We studied the characteristics of patients receiving K in the US Oncology Network’s (USON) EHR database. Methods: Patients ≥18 years who received a K-containing regimen between 11/01/2013-02/29/2016, were not in a clinical trial, and had ≥2 visits at a USON clinic were eligible. Baseline characteristics were compared between patients who received a K-based doublet, triplet or other regimen (monotherapy or >3 treatments). Results: Of the 718 patients who received a K-based regimen during the study period, 219 (30.5%) had doublet regimens, 287 (40.0%) received triplet regimens and 212 (29.5%) received other regimens; 494 (68.8%) received regimens with ≥3 therapies. Mean age was 69.7 and 64.7 years among patients on doublets and triplets, respectively. A higher proportion of female patients received doublets (53.0%) (Table). There were no differences in ISS stage or number of comorbidities across patients receiving doublets, triplets, or other regimens. Conclusions: In this real-world analysis of K-regimens, a majority of patients received triplet regimens. Older patients received doublet regimens more frequently. The influence of regimen on outcomes controlling for patient characteristics and prior treatments among MM patients receiving K-based regimens should be studied. [Table: see text]
Effect of lenalidomide use as part of induction chemotherapy on the risk of peri-transplant venous thromboembolic events (VTE) in patients undergoing autologous stem cell transplant for multiple myeloma.
Authors: Bumma Naresh , Peravali Monica , Jeyakumar Ghayathri , Kim Seongho , Alavi Asif , Bhutani Divaya , Ayash Lois Jeanne , Ratanatharathorn Voravit , Uberti Joseph P. , Deol Abhinav 
Published: September 2018

e19524 Background: Lenalidomide (len) is approved for treatment in Multiple Myeloma (MM) Use of len has been associated with an increase in venous thrombotic events (VTE) and aspirin prophylaxis is recommended for pts who are on active treatment with len. Autologous stem cell transplant (ASCT) is used during the treatmentof MM after initial induction therapy. The use of intravenous catheters and hospitalization increase the risk of VTE in peri-transplant period. We evaluated the incidence of VTE in peri-transplant period to determine if len use increased the risk of VTE. Methods: We performed a retrospective chart review of pts with MM who underwent first ASCT at our institution between 1/2011-1/2015.Data was collected on pt. demographics, len use, VTE prophylaxis, VTE incidence and VTE treatment. Chemical anticoagulation during the peri-transplant period was based on physician preference and chemical anticoagulation was stopped once platelet counts dropped below 50,000/ uL. All pts were encouraged to ambulate daily for mechanical prophylaxis. Associations with incidence of VTE were conducted by univariable and multivariable logistic regression analyses. Results: A total of 303 pts met the study criteria. 204 pts received Len as part of induction treatment while 99 did not. There was no significant difference in demographics of the 2 groups. 87% pts in the Len group and 81% in the non-Len group did not receive any chemical prophylaxis, respectively during hospitalization. 15 pts developed DVT within 100 days of transplant: 10 in len group and 5 in non-len group (p > 0.99). 14 of the 15 were catheter associated. Median time to DVT was 10.5 days post-transplant. Caucasians had a higher risk of DVT; adjusted OR 0.315 (95%CI 0.03-0.99; p = 0.046). Incidence of VTE was not affected by prophylaxis, or response to induction. Conclusions: Despite the fact that during the peri-transplant period most of the patients were not on prophylactic chemical anticoagulation due to chemotherapy associated thrombocytopenia len use during the induction treatment did not increase the risk of peri-transplant VTE.
Overuse of organ biopsies in immunoglobulin light chain (AL) amyloidosis: The consequence of failure of early recognition.
Authors: Muchtar Eli , Dispenzieri Angela , Lacy Martha , Buadi Francis , Kapoor Prashant , Hayman Suzanne R. , Gonsalves Wilson I. , Kourelis Taxiarchis , Chakraborty Rajshekhar , Russell Stephen J. , Lust John A. , Lin Yi , Go Ronald S. , Zeldenrust Steven R. , Rajkumar S.Vincent , Dingli David , Leung Nelson , Kyle Robert A. , Kumar Shaji , Gertz Morie A. 
Published: September 2018

e19532 Background: The diagnosis of amyloidosis requires histological confirmation of Congo-red (CR) deposits. The tissue source is preferably fat and/or bone marrow biopsy, but at times organ biopsy is required. Methods: We studied 612 patients with systemic light chain amyloidosis to characterize the tissues used to establish the diagnosis Results: The median number of tissue samples biopsied for CR staining was 3. Ninety-five percent of bone marrow (BM) biopsies were stained for CR, while 79% of patients had fat aspiration performed for CR staining. Overall, 76% of patients underwent both procedures. CR stain sensitivity was 69% in BM samples, 75% in fat aspiration and in 89% for both sources combined. CR stain sensitivity was 97-100% for heart, renal and liver biopsies. 42% of patients with renal involvement, 21% of patients with liver involvement and 13% of patients with heart involvement underwent organ biopsy, when a less invasive safer biopsy would have established the diagnosis. Predictors of need for organ biopsy were male sex, limited organ involvement and lack of fat aspiration (Table). Conclusions: Fat aspiration is underutilized for histologic confirmation of amyloidosis. Organ biopsies (particularly renal biopsies) were performed at a high rate, which represents a failure to recognize the disease (i.e. failure to screen with a light chain assay etc.). Early awareness of amyloidosis in the differential diagnosis of patients with organ dysfunction may lead to fewer unnecessary organ biopsies [Table: see text]
Characterizing the amyloidogenic protein in patients with light chain amyloidosis using mass spectrometry.
Authors: Kourelis Taxiarchis , Kohlhagen Mindy C. , Mills John , Barnidge David R. , Dasari Surendra , Dispenzieri Angela , Murray David L 
Published: September 2018

e19534 Background: Our group has developed a mass spectrometry (MS) method that can identify circulating monoclonal proteins, based on their unique molecular mass signatures. Given the propensity for patients with AL amyloidosis to have MS patterns consistent with post-translational modifications (PTMs), we posed the question whether these changes might be present long before the diagnosis of AL and potentially serve as a predictor for AL in patients with an asymptomatic plasma cell dyscrasia (aPCD). Methods: We included 64 patients with AL who had a preceding aPCD and who had stored serum samples at both time-points. The mass/charge (m/z) of monoclonal LC peaks (P) was noted for each sample. Presence of a PTM was defined as the presence of ≥1 “heavy” Ps at a particular charge state. A P was considered heavy if its m/z exceeded the right sided 95% C.I. of the m/z distribution of the respective normal LC. We used 9 patients with relapsed multiple myeloma (MM) without AL as controls. Results: Prior aPCDs were MGUS (N = 33), smoldering myeloma (n = 9) and MM (N = 1). In 21 patients aPCD was not further classified with a bone marrow biopsy. The median interval between aPCD and AL diagnosis was 77 months. At aPCD diagnosis, 42 patients had a single, typical P and 21 patients (33%) had PTMS: 13 patients had a single heavy P; 5 patients had 2 P (only one of which was heavy); and 3 patients had 2 heavy peaks. No PTMs were noted in our MM controls. The m/z of all typical and heavy P observed at aPCD remained unchanged for 63 patients as they transitioned to AL, which suggests no new PTMs occurred with the exception of one patient, who had a single PTM at aPCD diagnosis, but developed 2 additional heavy P appearing at +1232 and +1392 Dalton at AL diagnosis, suggestive of new PTMs. In all but 3 aPCD, the typical P was more abundant relative to heavy P. Heavy P abundance increased in 6 patients as they transitioned from the aPCD to the AL state and exceeded that of the typical P in 3 patients, suggestive of increasing abundance of existing PTMs in these cases. Conclusions: Pre-existing PTMs are present in 1/3 of AL patients and not in MM and can be used to identify patients at risk for AL. New PTMs are uncommon, but the relative abundance can change over time.
Thermal ablation for treatment of hepatic metastasis from thymic epithelial tumors (TETs).
Authors: Chen Angela , Abi-Jaoudeh Nadine , Lee Min-Jung , Trepel Jane B , Guha Udayan , Levy Elliot B , Krishnasamy Venkatesh P , Wood Bradford J. , Rajan Arun 
Published: September 2018

e20000 Background: Thermal ablation [radiofrequency ablation (RFA), cryoablation, microwave ablation (MWA)] has been used effectively for control of hepatic metastases from various solid tumors. However, these interventions have not been systematically evaluated in patients (pts) with TETs. We present our experience of the safety and clinical efficacy of thermal ablation in pts with advanced TETs and limited sites of disease progression. Methods: Pts with metastatic TETs followed at the National Cancer Institute were considered for thermal ablation if extrathoracic disease progression was limited to 3 or fewer anatomic sites amenable to percutaneous thermal ablative techniques. Appropriate imaging studies were used to evaluate for recurrence, and recurrence-free survival (RFS) was calculated. Biopsies were performed prior to ablation to study mutational and signaling events that may predispose to benefit. Results: From November 2012 to June 2016, 11 metastases (9 liver, 2 chest wall) in 4 pts (3 male, 1 female; median age 59.5 (range, 59-67); 3 thymic carcinoma, 1 WHO B2 thymoma; all Masaoka stage IVB) were treated with thermal ablation (6 MWA, 3 RFA, 2 cryoablation). Median size of metastasis was 1.5 cm (range, 1-4 cm). Local recurrence occurred at 2 (18%) of 11 treated sites, 11.5 months and 10 months after thermal ablation. All pts experienced distant recurrence (1 mesenteric/pelvic mass, 1 lung, 1 malignant pleural effusion, 1 liver) with a median RFS of 7 months (range, 2.5-14). Treatment was well tolerated with no serious adverse events. One pt died due to disease progression 9 months after thermal ablation; 3 pts are alive at the time of reporting (23.5, 37.5 and 38 months after treatment). Conclusions: Thermal ablation is well tolerated and largely successful in achieving local control in pts with advanced, unresectable TETs. Further studies are needed to assess the clinical benefit of thermal ablation compared with systemic therapy and surgery in specific pts with recurrent, oligometastatic TETs. The exact role of thermal ablation tools remains to be defined in this population. The potential for local thermally-induced cell death to induce or augment immunogenic tumor cell death will be assessed and reported.
Surgical resection of large anterior mediastinal masses: Results of median sternotomy approach.
Authors: Mohan Raj 
Published: September 2018

e20005 Background: Anterior mediastinal masses are a diverse group of tumors generally presenting as compressive symptoms. Larger masses require open surgical approaches including median sternotomy or sterno-thoracotomy. In this study we analyzed the surgical and pathological outcomes of large anterior mediastinal masses resected through sternotomy approach. Methods: Data of 16 patients with anterior mediastinal masses ( > 10 cms) treated surgically was analyzed retrospectively. All the patients were evaluated preoperatively with MRI, CT guided biopsy and pulmonary function test followed by exploration through median sternotomy approach with/without cardiac bypass (through femoral access). Adjuvant chemo-radiation was used according to histopathological features. Results: A total of 10 male and 6 females with median age 42 years (range: 6-62) underwent resection. Three patients received neoadjuvant chemotherapy and the mean tumor size was 12.2 cms. Histopathologies included mature teratomas/dermoids (4), thymic carcinoma (3), nerve sheath tumors (3), malignant germ cell tumors (3), synovial sarcoma (1) primary mediastinal goiter (1) and inflammatory pseudo tumor (1). There was no postoperative mortality and two patients required cardiac bypass. Bovine pericardium was used in two patients for the loss of large are of pericardium. One patient required biograft for replacement of resected superior vena cava. Major morbidities included prolonged ventilation and intrathoracic collection in two patients. All the patients were disease free after a median follow up of 14 months. Conclusions: Large anterior mediastinal masses are challenging surgically. An aggressive surgical approach through median sternotomy in association with cardiac bypass helps in complete resection and may lead to optimal results.
Prognostic factors and combined histologies in 205 resected small cell lung cancer (SCLC) patients.
Authors: Zhao Xiao-Liang , McCutcheon Justine N , Kallakury Bhaskar , Chahine Joeffrey J , Raffeld Mark , Pratt Drew , Chen Yu-Long , Zhang Bin , Zhang Hua , Zhang Yu-Wen , Wang Chang-li , Giaccone Giuseppe 
Published: September 2018

e20009 Background: SCLC accounts for 15%-20% of all lung cancer, 2%-5% of them are combined SCLC. The objectives of this study were to evaluate the prognostic factors in a large series of resected SCLC patients, and to perform genetic analysis of combined forms. Methods: 205 SCLC cases were resected at Tianjin Cancer Hospital between 1/2005 and 12/2015. We analyzed: gender, age, type of resection, cigarette index (CI), tumor markers (CEA, SCC, NSE, Cyfra21-1), R resection type, number of resected lymph nodes (LNs), ratio of metastatic LNs, and pathological stage. All combined SCLC cases were identified by H&E staining and confirmed by immunohistochemistry. The different components were microdissected using an automated dissection system (MillisectTM, Roche Diagnostics) and DNA was extracted and subjected to targeted exome sequencing. Results: The median follow-up time was 24 (2-121) months. Median survival time of all the patients was 24 months; 5-year survival rates were 51.4% overall, and 69.5%, 66.5%, 34.4%, and 0% for pathological stage I, II, III, and IV, respectively. Multivariate analysis indicated age, CI, complete resection, number of resected LNs and the ratio of metastatic LNs as independent prognostic factors. Twelve cases of combined SCLC were identified out of 170 with adequate histological material: 6/12 were combined with squamous cell carcinoma. 1-, 3-, 5-year survival rates were 73.3%, 0% and 0%. There were no significant differences between combined SCLC and pure SCLC with respect to gender, age, pathological stage, LN status and tumor markers. Three cases were successfully sequenced. Around 50% gene mutations were present in both components (10/24; 14/27; 4/5 respectively). TP53 mutations were present in all three cases. One case displayed amplification of 2 genes in both components. Interestingly, there were also gene mutations and amplifications that are unique to one of the components. Conclusions: In this large resected SCLC series we identified CI, complete resection, resected number of LNs and ratio of metastatic LNs to be prognostic. Combined SCLC had worse survival than pure SCLC. The histologically different components had a significant number of common as well as unique genetic alterations.