bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of blast phase chronic myeloid leukemia (BP-CML) in the tyrosine kinase inhibitor (TKI) era.
Authors: Talati Chetasi , Isenalumhe Leidy Lismeri , Shams Samantha Reiter , Kuykendall Andrew Tucker , Chavez Julio C. , Shah Bijal D. , Sweet Kendra Lynn , Pinilla-Ibarz Javier
Published: September 2018

e18546

Background: Primary goal in management of chronic myeloid leukemia (CML) is to prevent progression to BP-CML. Even with the use of induction chemotherapy with a TKI, outcome remains dismal in BP-CML. We describe our experience with the management of BP-CML. Methods: Retrospective chart review was performed on CML patients treated between 2001 and 2016. Out of 585 CML cases, 58 (10%) had a diagnosis of BP-CML. Kaplan-Meier method with log-rank test was utilized for survival calculations. All p-values calculated were two sided. Results: The overall survival (OS) of BP-CML cohort was 31.9 months (mo) from diagnosis. In the patients diagnosed in chronic or accelerated phase, median time to progression to BP-CML was 19.1 mo. The median OS from the BP-CML diagnosis was not different when progressed from an earlier phase compared toBP-CML (10.8 vs 11.0, p 0.62). Trend toward worse OS was noted in myeloid BP-CML compared to lymphoid BP-CML (9.2 vs 17.5 mo, p 0.32). The median OS in the single agent TKI cohort (n=21) was 12.8 mo vs 10.9 mo (p 0.72) in the combination cohort (n = 36). Treatment with a single agent TKI vs combination therapy did not significantly impact OS in either myeloid (9.2 vs 9.1 mo, p 0.32) or lymphoid (14.5 vs 18.3 mo, p 0.24) BP-CML. Out of 26 patients (44.8%) who received allogeneic stem cell transplant, 26% (n=6) received a single agent TKI prior to transplant and 76.9% (n=20) received combination therapy. A trend toward improved OS was noted in the single agent TKI cohort (128.5 vs 24.0 mo, p 0.23). When stratified by the presence of standard Philadelphia chromosome or with additional cytogenetic aberrations, no difference in OS was noted (10.9 vs 12.1 mo, p 0.51). Monosomy 7 was present in greater frequency in lymphoid BP-CML than myeloid BP-CML (35.7% vs 6.3%, p 0.02). Conclusions: Our data suggest no survival difference when BP-CML is treated with a single agent TKI compared to a combination therapy, regardless of histology type. Therefore, single agent TKIs should be considered as an effective frontline therapy option for BP-CML, which may prevent the potential toxicity associated with chemotherapy. These findings need further validation in a larger prospective cohort.
Patients with myeloproliferative neoplasms (MPN) who later develop ph+ chronic myelogenous leukemia (CML): A case series.
Authors: Patel Shahina , Kim Seo-Hyun , Shammo Jamile M. , Radich Jerald P. , Terebelo Howard R.
Published: September 2018

e18563

Background: Myeloproliferative Neoplasms are divided by the presence or absence of the Philadelphia Chromosome. Ph- MPN, typically possess driver mutations of JAK-2, MPL and CALR. CALR is involved with apoptosis and cell proliferation . MPL leads to TPO receptor stimulation and mutations are reported as a known cause of AA. JAK-2 mutations render hematopoietic stem cells more sensitive to growth. Though the true incidence is unknown, there are infrequent reports of pts with ET who later develop CML. CALR, MPL and JAK-2 mutations may have some further role in determining whether these are two separate events or clonally derived. We report three pts with MPN who later developed CML. Methods: Chart Review Results: Pt 1 had ET, diagnosed 21 yrs earlier treated with hydroxyurea. He then developed a rising WBC and platelets which necessitated a marrow which detected Ph+ CML. He was CALR positive. NGS was negative for nondriver mutations. Platelets initially declined from 3 million to 975K with TKI and he achieved a MMR. However, the inability to control his thrombocytosis required the addition of ruxolitinib. Pt 2 was diagnosed with ET and was treated with P32. Nine yrs later CML was diagnosed and TKI administration achieved a MMR. Subsequently, a profound anemia evaluation diagnosed PNH requiring eculizumab without benefit and repeat marrow with NGS revealed a MPLmutation and post-ET myelofibrosis. Pt 3 presented with a JAK-2 positive mutation and Polycythemia Vera. After four yrs of hydroxyurea extreme leukocytosis led to a marrow revealing a diagnosis of Ph+ CML. Dasatinib achieved a prompt MMR. NGS revealed KIT D618 V , coinciding with a diagnosis of systemic mastoytosis (SM). Conclusions: The rare observation of patients with both ET and CML have been reported by others with some recent implications of CALR as a common clone with double-mutant properties of CML. Our patients had a lead time of 21, 9, and 4 yrs, all having different mutations. Pts with MPN who develop unexplained leuko or thrombocytosis should be evaluated for CML.We plan to retrieve archival tissue to perform serial genetic analyses. Further work is required to determine whether these events are stochastic or represents clonal evolution.
Life expactation and intensity of cancer in brief: Family histories of the patients with myeloproliferative neoplasms.
Authors: Bolaman Ali Zahit , Unubol Mustafa , Kadikoylu Gurhan , Yavasoglu Irfan
Published: September 2018

e18564

Background: Thrombosis and bleeding are the most important prognostic factors in myeloproliferative neoplasm (MPN). But there is not a prognostic factor for predicting survival at diagnosis. The determination of the intensity of the cancer incidence in brief- and family histories of patients may help to make a comment on the nature of the MPN. We investigated the effects of the concomitant diseases on survival and cancer intensity in brief- and family histories of the patients with MPN. Methods: Thirty-five (19 female, mean age 59 ±11 years) patients with MPN were enrolled to the study. The diagnosis of the patients were essential thrombocythemia in 19, polycythemia vera in six and primary myelofibrosis in six, and chronic myelocytic leukemia in four. By using Charlson’s concomitant disease index, concomitant disease weight incidence, concomitant state-age relationship, and probability of 10 years survey were investigated. Results: In brief history of the patients, only one (3%) patient had skin cancer. However there were some cancers in family history of 9 patients (26%). These were hematological malignancies in four patients (2 acute myelocytic leukemia and 2 non-Hodgkin’s lymphoma) and solid tumors in five patients (2 breast, 2 colon cancer, one skin and lung cancers). Mean Charlson’s concomitant disease weight index was 1.4±1.5 (0-6), concomitant state-age relationship was 3.2±2 (0-8), and probability of 10 years survey was 63±35% (0-98%). Conclusions: Although our study group is small, Charlson’s concomitant disease index may be used for the determining of life expectancy in MPN. Moreover cancer cluster in family history of these patients was notable.
Blastic transformation in Mexican population with chronic myelomonocytic leukemia treated in a tertiary referral center.
Authors: Rivera Duarte Alfonso Alfredo , Armengol Alonso Alejandra , Tuna-Aguilar Elena
Published: September 2018

e18566

Background: Chronic myelomonocytic leukemia (CMML) is the most aggressive of chronic leukemias, with a short overall survival and a high transformation rate to acute leukemia. We investigated factors related to blastic transformation in Mexican population treated in a tertiary referral center Methods: Records of patients diagnosed with CMML between 2000-2015 were reviewed; patients with incomplete data were excluded. IBM SPSS Statics 21.0 software was used to perform statistical analysis. Results: 54 patients were included, with a median age of 71 years and an overall survival of 16 months. The rate of blastic transformation found was 33% (18 patients), with a time to progression of 9 (0-87) months. Comparing patients who didn’t underwent blastic transformation to those who did, those who progress to acute leukemia tend to be younger (58 vs. 71 years, p = 0.001), have a higher peripheral blood blast count (2% vs. 0%, p = 0.003), where more likely to have immature myeloid precursors circulating in peripheral blood (94% vs. 64%, p = 0.02). In multivariate analysis, age continued to be statistically significant (HR 0.97, 95% IC = 0.929-0.987). There where no statistical difference in the two groups regarding hemoglobin levels (8.2g/dL vs. 10.1g/dL) platelets count (115 X 109 vs. 93 X 109), absolute neutrophil count (5.83 X 109 vs. 5.18 X 109), absolute monocyte count (3.09 X 109 vs. 2.680 X 109), and bone marrow blast count (0 vs. 2%). Cytogenetic considered as high risk was not predictor of blastic progression. Intensive chemotherapy was offered to 7(38.9%) patients, with a complete response rate of 0%, the overall survival was 1.4 months (0-9). Conclusions: Contrary to other reported series;Mexican patients with CMML that progresses to overt acute leukemia were considerably younger, with a higher tumor burden and a very short overall survival. In this population, it is important to consider more aggressive treatments at diagnosis, focusing in high dose chemotherapy and hematopoietic stem cell transplantation in a short term ratter than watching and waiting or using agents that do not impact in disease natural history.
Safety and efficacy of autologous stem cell transplantation in lymphoma patients in their 70s.
Authors: Sun Lova , Li Shuli , Armand Phillippe , Chen Yi-Bin Albert , DeFilipp Zachariah
Published: September 2018

e19003

Background: High-dose chemotherapy and autologous stem cell transplantation (ASCT) can offer durable remission in many patients with relapsed or high-risk lymphoma. Elderly patients, who make up an increasing proportion of lymphoma patients, are often not considered candidates due to concern for excess toxicity and mortality. However, preliminary reports suggest that ASCT in carefully selected elderly patients can be feasible, safe, and effective. Methods: We identified patients ≥70 years of age with Hodgkin or non-Hodgkin lymphoma who underwent ASCT between 2000 and 2016 at two partner institutions. We recorded clinical characteristics, lymphoma diagnosis, conditioning regimen; and outcomes regarding engraftment, treatment toxicities, and relapse. Kaplan-Meier survival analysis for overall and relapse-free survival was performed. Results: 119 elderly patients with lymphoma who were treated with ASCT were identified. Median age at transplant was 72 (range, 70-79). The most common lymphoma subtype was diffuse large B-cell (n=75, 63%); others were T-cell (n=19), mantle cell (n=12), follicular (n=7), and Hodgkin (n=6). Conditioning regimens included BEAM (BCNU, etoposide, Ara-C, melphalan), CBV (cyclophosphamide, BCNU, etoposide), and Bu/Cy (busulfan/cyclophosphamide). Median time to neutrophil recovery (ANC>500) and platelet recovery (>20,000) were 10 and 12 days, respectively. Three patients had early mortality (within 100 days) from rapid disease progression (n=1) or treatment toxicity (n=2). Median follow up for survivors was 23 months (range, 0-157). Two-year progression-free survival and overall survival were 58% (95%CI, 48-67%) and 66% (95%CI, 55-74%), respectively. The leading cause of treatment failure was disease relapse, which occurred in 33% of patients (n=39). Two-year estimate for non-relapse mortality was 7% (95%CI, 3-14%). Conclusions: ASCT is safe and feasible in selected elderly lymphoma patients, although relapse and non-relapse mortality may be higher than in younger patients. Eligibility for ASCT should be an individualized decision, and age should not be an absolute barrier to ASCT referral in healthy elderly patients with lymphoma.
An in-depth interview study of oncology nurses and infusion pharmacists of bendamustine product attributes that drive relative product preferences.
Authors: Gabriel Susan , Welstead Jennifer , Shockley Shannon , Barr Peri
Published: September 2018

e19007

Background: Two bendamustine products, Treanda and Bendeka, are currently in the market. This study sought to better understand which attributes are meaningful in driving product preferences between these products as determined by a sample of front-line oncology nurses and infusion pharmacists. Methods: Two target panels of 10-15 oncology nurses and infusion pharmacists/pharmacy technicians who practice at different settings across the US were identified. Each study-eligible respondent was required to complete a pre-interview survey designed to collect background information on their practice site and their relative preferences for the two bendamustine products. All interviews were conducted between October and December 2016 by a trained nurse facilitator, and were taped and later transcribed. The survey results were analyzed using descriptive statistics, while content analysis was used to analyze the interview transcripts. Results: A total of 11 nurses and 10 pharmacists completed the pre-interview survey and participated in the in-depth interviews. The majority of nurse respondents were female (90.1%), resided in the South (72.7%), and practiced primarily in ambulatory care clinics (60%). The pharmacist respondents were also mostly female (60%), resided in the Mid-West (40%), and practiced primarily in comprehensive cancer care centers (40%). Both nurse and pharmacist responders reported that product attributes that address better safety, cost savings, productivity improvements, and improved workflow efficiency were most meaningful to them and drove their preferences for either Treanda or Bendeka. The majority of respondents reported a stronger preference for Bendeka over Treanda based on their respective product attributes that addressed these domains. Conclusions: Nurses and pharmacists involved in compounding, dispensing, and administering Bendeka or Treanda revealed that specific product attributes that impact safety, cost, productivity, and workflow efficiency drive usage of Bendeka.
Outcomes of de novo CD5+ diffuse large b-cell lymphoma (DLBCL) in the rituximab (R) era.
Authors: Hu Bei , Loghavi Sanam , Fayad Luis , Noorani Mansoor , Fowler Nathan Hale , Hagemeister Fredrick B. , Lee Hun Ju , Nastoupil Loretta J. , Neelapu Sattva Swarup , Fanale Michelle A. , Samaniego Felipe , Turturro Francesco , Wang Michael , Davis Richard Eric , Westin Jason R. , Medeiros L Jeffrey , Oki Yasuhiro
Published: September 2018

e19019

Background: De novo CD5+ DLBCL is associated with poor prognosis. Methods: We retrospectively reviewed the MD Anderson Lymphoma Outcome Database and identified 104 patients (pts) with de novo CD5+ DLBCL diagnosed between 2001-2016. We excluded primary CNS lymphoma and Richter’s transformation. Results: Median age was 62 (range 29-96); 55% were male. Most (71%) pts had advanced stage at diagnosis, with 55% being Stage IV. Eighty percent (n = 79) had extranodal disease at presentation with bone/bone marrow being the most common site (40%); central nervous involvement was seen in 5%. Two-thirds had elevated LDH; 37% had B symptoms on presentation. ECOG PS was ≥2 in 26% of pts; beta-2 microglobulin was elevated in 68%. Of the 77 pts with IPI score, 21% (n = 16), 23% (n = 18), 26% (n = 20), and 30% (n = 23) were considered low, low-intermediate, high-intermediate, and high risk, respectively. In the diagnostic specimen, median Ki67 was 85%. Majority were non-GCB by Han’s criteria (n = 47 of 77). Two pts were double-hit lymphoma. All received R-containing regimens for primary therapy, including RCHOP (n = 64), dose-adjusted R-EPOCH (n = 24), R-HyperCVAD (n = 6), and other (n = 10). Prophylactic intrathecal chemotherapy use was 35%. Sixty-eight (65%) pts achieved complete response (CR) with primary therapy. Two pts underwent frontline autologous stem cell transplant. Median PFS duration was 28 months (mo) (95% CI: 10-27). Median OS duration was 112 mo (95% CI: 10-214). Pts with primary refractory disease had the worst OS duration of 14 mo. Pts with relapse within 1 year of achieving CR fared no better with median OS of 22 mo. PFS and OS were not significantly different by choice of primary therapy. By multivariate analysis using Cox proportional hazard model, male gender (HR = 3.0, 95% CI: 1.1-8.1, p = 0.029) and high IPI (HR = 2.5, 95% CI: 1.4-4.3, p = 0.001) were associated with shorter PFS. Only IPI score was significantly associated with worse OS (HR = 3.0, 95% CI: 1.6-5.7, p = 0.001). Conclusions: De novo CD5+ DLBCL is frequently associated with extranodal presentation and poor outcome with R-containing intensive chemotherapy. IPI remains the most significant prognostic factor for worse PFS and OS. There is clearly an unmet need for novel treatment for this disease.
Hypereosinophilic syndrome (HES) during rituximab treatment.
Authors: Basu Chinmay
Published: September 2018

e19021

Background: Hypereosinophilic syndrome (HES) is a rare disease defined by organ damage directly attributable to hypereosinophilia of any type. The most commonly involved organ is the lung, followed by the skin. Methods: We report a single-center cohort of patients with NHL (DLBCL). Of these patients, nine had been treated with RCHOP on standard reatment protocol (6 cycle chemotherapy). In a retrospective analysis, data on treatment response, frequency of relapses, adverse events reconstitution were evaluated. Heamotology and biochemistry tests abs analysis were performed after every cycle. Results: All patients had high disease activity before RTX treatment. We found 3 patients who developed severe drug-induced hypereosinophilia with gastrointestinal involvement as a consequence of RCHOP infusion. For the case 1 Full blood count revealed a new mild eosinophilia with eosinophil count of 1 9 109 /l. After the third infusion, the eosinophil count had risen to 7.0 9 109 /L. In case 2, after the 6th infusion, the eosinophil count had risen to 6.4 9 109/L. In case 3 also it occurred in follow up period after 6th infusion and 6.8 9 109 /L. However the finding was not associated with any severe toxicity or other malignancy. No alarming feature was also notice alongside this abnormality Conclusions: Preemptive retreatment with RTX, combined with CHOP, resulted in a sustained treatment response. Hence clinical significant is not clear this stage. Strict post marketing vigilance for evaluating the use of RCHOP was warranted.
Effect of adding immunotherapy (IT) to treatment regimen of mantle cell lymphoma (MCL): Analysis of the National Cancer Data Base (NCDB).
Authors: Altahan Alaa , Vick Eric , Giri Upama , Wiedower Eric , Martin Michael Gary
Published: September 2018

e19022

Background: There has been some improvement in overall survival (OS) for patients with MCL over the past years [Gordon 2014]. However, side effects of treatment remain a major concern. With introduction of novel therapies like IT, it is imperative to optimize treatment regimens to improve survival while minimizing toxicity. Methods: MCL patients (pts) who were diagnosed in 2013 or later with information available about chemotherapy (CT) and IT and did not receive transplant were extracted from NCDB. Pts were assigned to age categories and were sorted into six groups based on different combinations of CT (none, single agent (SA), and multi-agent (MA)) with or without IT. Cox regression analysis was used to perform multivariate analysis that included age category, sex, race, clinical stage, Charlson/Deyo score, CT, radiation, and IT for each group. Multivariate p values (p) were used to analyze statistical significance. Kaplan Meier method was utilized to analyze OS. T-test was used to compare means (t-p). Results: 1438 total pts were identified with a mean age of 70 (range 24-90); 71% male; 93% white, 4% black, 3% others; 42% with stage III/IV disease. 667 pts did not receive CT or IT, and 40 received IT alone and both of these groups were excluded from further analysis. 52 pts received SA- (without) IT, 206 received SA+(with) IT and 260 pts received MA-IT and 213 MA+IT. Mean age was 72 and 66 for SA and MA groups, respectively (t-p<0.01). Mean OS for SA+IT was 27 months (m) vs SA-IT 16 m (p < 0.01). MA+IT v MA-IT showed no difference in mean OS (25 vs 26 m, respectively, p =0.49). Although there was a significant difference in OS between SA and MA groups without IT (16 vs 25 months, p < 0.01). SA + IT group showed comparable mean OS time to MA + IT (27 vs 26 m, p =0.145). Conclusions: For MCL pts, MA has superior OS to SA group. However, adding IT significantly improves OS for SA group and makes it comparable to MA. Adding IT to MA did not provide significant difference in OS. These results highlight the possibility of achieving same OS with less toxic regimens. Hence further evaluation in a prospective study to optimize treatment while reducing toxicity is warranted.
Cost burden of first-line antineoplastic treatment failure in patients with chronic lymphocytic leukemia.
Authors: Senbetta Mekre , Lafeuille Marie-Helene , Lefebvre Patrick , Romdhani Hela , Emond Bruno , Wang Song
Published: September 2018

e19037

Background: Treatment failure (TF) is associated with significant cost burden in patients with non-Hodgkin’s lymphoma (NHL) in the US. This study assessed treatment patterns and healthcare cost burden of first-line (FL) TF in patients with chronic lymphocytic leukemia (CLL), a subtype of NHL, overall, and for the top 5 FL regimens. Methods: A retrospective study of a large national claims database identified adult patients with CLL who initiated an antineoplastic agent (AA) after their first CLL diagnosis (index date) from 01/2011- 07/2016. Patients included had ≥12 and ≥6 months of observation pre- and post-index, respectively, and were treatment-naïve with no solid or selected blood malignancies in the pre-index period. FL therapy included AA administered within the first 30 days post-index. TF occurred at the earliest of: initiation of a new AA, resumption of initial treatment following a gap of ≥3 months, radiotherapy, stem cell transplant, or hospice care. The total cost difference between patients with and without FL TF was estimated using ordinary least squares regressions adjusted for baseline characteristics. Non-parametric bootstrap was used to estimate confidence intervals (CI) and p-values. Results: Among the 2,226 patients included (mean age: 68 years; female: 41%), 46% experienced FL TF. Overall, the average adjusted total cost difference between patients with and without FL TF was $3,011 per patient per month (PPPM) (95% CI: 2,400, 3,583; P < 0.001). Among the 5 most common FL regimens, fludarabine / cyclophosphamide / rituximab (FCR) regimen was associated with the highest PPPM cost of TF (N = 281; $4,758; 95% CI: 2,652, 7,346), followed by other cyclophosphamide-based regimens (N = 142; $4,579; 95% CI: 2,474, 6,311), chlorambucil-based regimens (N = 223; $3,761; 95% CI: 2,029, 5,602), bendamustine / rituximab (BR) regimen (N = 592; $3,163; 95% CI: 2,206, 4,148), and other rituximab-based regimens (N = 474; $3,030; 95% CI: 2,164, 3,956) (P < 0.001 for all). Conclusions: The most common FL regimens used in patients with CLL were associated with 46% treatment failure. Clinicians should consider the cost of treatment failure when selecting the initial therapy in these patients.
Primary non-Hodgkin’s lymphoma of the thoracic spine: A case report with a review of the literature.
Authors: Man Muran , Liu Qinghua
Published: September 2018

e19039

Background: Primary non-Hodgkin lymphomas of thoracic vertebra are rare, hard to confirm the diagnosis and with unfavorable prognosis. It is characterized by pain, asthenia, numbness, motor disturbances, etc. However, these symptoms don’t have their specificity. Biopsies are needed to confirm the diagnosis. Methods: A 37-year- old man presented with 3 months lumbar region pains and 4 days motor disturbances before he was admitted. The lumbar spine MRI showed lumbar disc herniation with no spinal compression. The thoracic spine MRI revealed altered vertebra signal and compressed marrow in the T10 vertebra. After the posterior tumor reduction and decompression and internal fixation of T10, the histopathology and immunohistochemistry was consistent with diffuse large B cell lymphoma. After surgery, treatment of chemotherapy (ECHOP, RCHOP) in combination with radiotherapy (T8-T12, L5-S1, 45Gy/25F) were followed. Results: Six-year follow-up MRI showed no relapses, metastasis and instability. The patient currently has the self-care ability which could deal with the everyday activities. Conclusions: Primary non-Hodgkin lymphoma originated in the thoracic vertebra is rare, easily to be misdiagnosed. To learn more about the diagnoses and to do the needle biopsy as early as possible would be beneficial to improve the survival rate and the quality of patients’ lives. Key words: Non-Hodgkin Lymphoma, Thoracic Vertebra, Case Report
Venetoclax (VEN) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL).
Authors: Davids Matthew Steven , Roberts Andrew Warwick , Seymour John Francis , Wierda William G. , Puvvada Soham D. , Gressick Lori A. , Alter Debbie , Zhou Lang , Kim Su Young , Verdugo Maria , Gerecitano John F.
Published: September 2018

e19041

Background: VEN is a selective orally bioavailable BCL-2 inhibitor. The dose-escalation Phase 1 study of VEN in 106 patients (pts) with relapsed/refractory NHL reported an ORR of 44%. Most pts had diffuse large B-cell/follicular lymphoma; we report on updated results in pts with less common NHL subtypes. Methods: VEN was administered and continued until progressive disease (PD)/unacceptable toxicity, in dose cohorts ranging from 300–1200 mg. Adverse events (AEs) were assessed by NCI-CTCAE v4.0 and response by 2007 Cheson IWG response criteria, utilizing CT scans beginning at wk 6. Results: 35 of 106 pts had mantle cell lymphoma (MCL, n=28), marginal zone lymphoma (MZL, n=3) or Waldenström macroglobulinemia (WM, n=4). Most common all grade treatment emergent AEs were nausea (51%), diarrhea (49%) and fatigue (34%); grade 3/4 AEs in >10% of pts were neutropenia and anemia (17% each). Laboratory TLS was reported in a single pt (bulky MCL). MCL pts (median age: 72 years) had received a median of 3 (1–7) prior treatments (tx). Median time from start of prior tx to start of VEN was 13 mo (2–148) and time on VEN was 11 mo (0.2–42). ORR was 75%, 6 pts (21%) achieved CR and remain on study (DORs: 25–40 mo). One pt with a PR proceeded to elective allogeneic stem cell transplant and remained disease free at last protocol defined follow-up (24 mo after coming off study). Median PFS was 11 mo and DOR was 15 mo. MZL pts (median age: 63 years) had received a median of 4 (2–6) prior tx. Time from start of prior tx to start of VEN was 8, 14, 73 mo and time on VEN was 5, 1, 35 mo. One pt (6 prior tx) received VEN for <1 mo due to progressive cytopenias; 1 pt (4 prior tx) achieved a PR with VEN at wk 6 but had PD at wk 16; 1 pt (2 prior tx) achieved PR at wk 6 and is the only pt to remain on study (DOR:32 mo). WM pts (median age: 67 years) had a median of 4 (3–5) prior tx. Time from start of prior tx to start of VEN was 5, 18, 33, 67 mo and time on VEN was 42, 17, 54, 20 mo. All pts achieved PR (at wks 6 [n=2], 16 and 36), with DORs of 11, 12, 38 and 50+ mo (latter is ongoing and remains on study). Conclusions: VEN monotherapy has a tolerable safety profile in MCL, MZL and WM pts. ORR were high and most responses durable; median PFS and DOR suggest significant activity in MCL pts. Further investigation of VEN in each disease is indicated. Clinical trial information: NCT01328626.
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.