bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimum tolerable interval of 90yttrium ibritumomab-tiuxetan to autologous stem cell transplantation after high-dose chemotherapy with carmustin, etoposide, cytarabine, and melphalan for relapsed or refractory aggressive B-cell non-Hodgkin lymphoma.
Authors: Hasenkamp Justin , Hess Georg , Hertenstein Bernd , Dreger Peter , Uharek Lutz , Gramatzki Martin , Schubert Jörg , Wulf Gerald , Truemper Lorenz , Schmitz Norbert , Glass Bertram ,   DSHNHL
Published: March 2020

6543 Background: High-dose therapy and autologous stem cell transplantation (ASCT) in patients (pts) with aggressive B-NHL failing from immunochemotherapy including rituximab show poor outcome with 3y PFS of 39% (Gisselbrecht et al. JCO 2010). Combining BEAM with 90yttrium ibritumomab tiuxetan is a promising option to enhance the efficacy of the high-dose regimen. Methods: Pts without disease progression during salvage therapy of relapsed or refractory CD20+ aggressive B-NHL were included in this prospective, multicenter, phase I/II trial. Primary endpoint was the maximum tolerated dose of 90Yttrium ibritumomab tiuxetan given as close as possible to ASCT defined as <2 pts with dose limiting toxicity in a 6+6 pts cohort. First, we reduced the time interval of 90yttrium ibritumomab tiuxetan (0.4 mCi/kg body weight) to ASCT from 14 to 12 and then 10 days. Subsequently it was planned to increase the 90yttrium ibritumomab tiuxetan dose. Results: From 2006 to 2009 26 pts, median age 58y (34-66) were enrolled. Histology included 14 DLBCL, 6 FL III°, 5 transformed FL and 1 aggressive B-NHL without further subtyping. 11/26 pts had relapse/progression within 1y after diagnosis. Secondary IPI was >1 in 14 pts. Response to salvage therapy was CR in 6/26 pts and PR in 12/26 pts. 20/26 pts achieved CR after ASCT. Engraftment showed no significant differences in pts of different cohorts with median recovery of leukocytes (>1/nl) and platelets (>25/nl) at d +10 and +13. Two early deaths (d +7, +18) occurred due to infections. 90Yttrium ibritumomab tiuxetan (0.4 mCi/kg body weight) at d -10 of ASCT was determined as minimum tolerated interval of radioimmunotherapy to ASCT after BEAM. Median follow-up of the survivors is 3.3 y. 3y PFS and OS is 67% (95% CI, 49%-85%) and 75% (95% CI, 58%-92%), respectively. Main cause of death was relapse/progression with 27% (95% CI, 6%-38%) at 3y. Conclusions: Z-BEAM followed by ASCT was safe and feasible and results in a high response rate with durable remissions in rituximab pretreated patients with aggressive B-NHL. Extended studies at the maximum tolerated dose and confirmation of superiority compared to conventional ASCT are warranted.
Prevalence of autoimmune manifestations in patients with large granular lymphocytic leukemia: Exploratory analysis of a series of consecutive patients.
Authors: Bockorny Bruno , Grabska Joanna , Codreanu Ion , Mewawalla Prerna , Silver Joel , Dasanu Constantin 
Published: March 2020

6555 Background: Review of literature suggests certain autoimmune abnormalities to accompany LGL leukemia. The present study was set to identify the prevalence of autoimmune phenomena in LGL leukemia patients and compare it with same in general population. Methods: We conducted both retrospective and prospective analyses in a series of consecutive patients (n=11) with LGL leukemia that had been followed in outpatient setting. Median age was 71 years ( ± 14 years). The presence of associated autoimmune disorders in our cohort was compared to the published prevalence of these conditions in general population. Statistical analysis: The obtained values were tested for statistical significance using Fisher’s exact test for small number of observations (95% confidence); a p value < 0.05 was considered significant. Results: A total of 45% patients in our study were diagnosed with autoimmune conditions. Identified autoimmune disorders included rheumatoid arthritis [RA] (n=3), Hashimoto thyroiditis (n=3), Felty syndrome (n=1), aplastic anemia (n=1), pernicious anemia (n=1), and leukocytoclastic vasculitis (n=1). Statistical analysis showed the following significance: Hashimoto thyroiditis (p=0.044), RA (p=0.003), Felty syndrome (p<0.001), aplastic anemia (p<0.001), pernicious anemia (p<0.001), and leukocytoclastic vasculitis (p<0.001). Statistical difference was also noted for autoimmune serologic abnormalities, with ANA positivity present in 63.6% of the cases (p< 0.001) and RF present in 50% of the patients (p=0.005). Conclusions: Nearly half of LGL leukemia patients in our cohort had autoimmune conditions, thus significantly exceeding the overall prevalence in general population. Statistically significant differences were recorded for RA, Hashimoto thyroiditis, Felty syndrome, aplastic anemia, pernicious anemia, leukocytoclastic vasculitis, ANA and RF positive serologies. The prevalence of Hashimoto thyroiditis and ANA positivity in our patient cohort was significantly higher than the one in existing literature. Given the relatively small size of the analyzed cohort, larger studies are expected to confirm our findings.
Predicting outcome based on minimal residual disease (MRD) using multiparameter flow cytometry (FC) in acute myeloid leukemia (AML) patients (Pts).
Authors: Sardesai Sagar D , Tan Wei , Ford Laurie Ann , Deeb George , Block Anne Marie W. , Sait Sheila N.J. , McCarthy Philip L. , Vigil Carlos E , Griffiths Elizabeth A. , Thompson James E , Wang Eunice S. , Wallace Paul K , Wetzler Meir 
Published: March 2020

6565 Background: Most AML pts will experience relapse caused by persistent leukemic cells during complete remission (CR). The aim of our study was to predict outcome in AML pts in CR by assessing their MRD using standard 4-colour FC panels available at our institute. Methods: We queried our AML database between 1/2004 to 10/2010 for newly diagnosed untreated AML pts >18 years of age who achieved CR after one induction regimen. Treatment included 7+3 or similar intensive approaches. The gating strategy used a series of Boolean regions that best defined the diagnostic abnormal population based on its expression patterns using three 4-colour FC panels (F7-CD38,CD10,CD19,CD34; F9-C11b,CD33,CD13,CD34; F38-CD15,CD56,CD7,CD34). The same regions were applied to post-induction samples, and the number of residual events was determined. Results: 140 AML patients with a median age of 64 (range 24-93) years, including 74 females (52.8%) were analyzed; 67 (47.8%) patients relapsed. Eighty-eight (62.8%) pts were CD34-positive (CD34+) at diagnosis. Normal karyotype was detected in 27 (30.7%): FLT-3 ITD was detected in 4/23 (17.4%) and NPM-1 mutation was detected in 1/15 (0.07%) samples. Median follow-up for CD34+ pts was 17.9 months. Forty-two (30%) pts underwent stem cell transplantation (SCT) in first CR: 31 (22.1 %) were allogeneic and 11 (7.9%) autologous. In multivariate analysis, a detectable MRD in any of the 3 panels at or beyond week 16 among CD34+ AML pts in CR was significantly associated with inferior relapse free survival (F7: P=0.035 , F9: P=0.027, F38: P=0.042). In addition, MRD ≥ week 16 using panel F9 was also significantly associated with inferior overall survival (P=0.0224). In pair-wise comparison, those who were MRD-negative ≥ week 16 did not benefit from SCT compared to the non-SCT group. Similar analyses among CD34– AML pts did not achieve statistical significance. Conclusions: MRD+ by FC in CD34+ AML is an independent prognostic factor and can identify pts who may benefit from SCT/more intensive therapy to maintain remission. However, the value of studying MRD in CD34– AML requires further consideration. More effort is needed to identify stem cells in CD34– AML.
Analysis of outcomes of patients (pts) with blastic plasmacytoid dendritic cell neoplasm (BPDCN).
Authors: Pemmaraju Naveen , Thomas Deborah A. , Kantarjian Hagop , O'Brien Susan Mary , Daver Naval Guastad , Nazha Aziz , Pierce Sherry , Garcia-Manero Guillermo , Cortes Jorge E. , Faderl Stefan 
Published: March 2020

6578 Background: BPDCN, formerly known as CD4 + CD56 + hematodermic tumor or blastic NK cell lymphoma, is a rare and aggressive hematologic malignancy. Little is known about outcomes of pts with BPDCN. Methods: We conducted a retrospective review of pts meeting following criteria: pathological diagnosis of BPDCN confirmed by an experienced hematopathologist and age ≥ 18. Results: 13 pts, diagnosed October 1998-July 2011, were identified. Median (med) age: 62 years (range 20-86 years), 12 (92%) were male. Bone marrow (BM) involved in 9 (69%), skin 8 (62%), lymph nodes 5 (38%), brain 1 and uterine/ovarian 1 pt. Immunophenotype by flow cytometry: CD4+ (11/11 pts), CD56+ (10/11 pts), TCL-1+ (4/4 pts). Karyotype (8 pts): del(12) (1pt), complex (2), and diploid (5). Med CBC: WBC 5.8 x 109/L (1.7-76.5), Hb 12.3 g/dL (8.3-17.0), platelet 107 x 109/L (44-255). Med BM blasts: 22% (0-77). 10 pts received first-line therapy with Hyper-CVAD alternating with high-dose methotrexate(MTX) and cytarabine (HCVAD) (in 1 pt following one cycle of CHOP), CHOP (2), oral MTX (1). Med follow-up time: 9 months (mo) (2-14 mo). Med number chemotherapy regimens: 1 (1-5). Complete remission (CR) in 10 pts. Med CR1: 19 mo (4-39 mo). Med overall survival (OS) 29 mo (1-44 mo). 9 pts have died, unknown cause (3), multi-organ failure (6). 10 pts received HCVAD as part of first line therapy: med OS: 29 mo (1-44 mo), med CR1: 21 mo (4-39 mo), 9/10 (90%) pts achieved CR1; 1 pt did not achieve CR1 (died, pneumonia, day 15). 9 pts (69%) had BM involvement (7 with other organs involved besides BM). 4 (31%) pts had no BM involvement; all 4 of these pts had skin involvement only. Med OS, med CR1 of pts with BM involvement: 23 mo (1-44mo), 22 mo (4-39mo), respectively. Med OS, med CR1 of skin only pts: 29 mo (2-31 mo), 7 mo (6-19 mo), respectively, p=not significant. 4 pts received stem cell transplant (SCT) (2 allogeneic ,2 autologous). Med OS for pts receiving SCT (n=4) was 31 mo(8-31 mo) versus med OS for non-SCT group (n=9) of 29 mo (1-44), p=not significant. Conclusions: Despite intensive multi-agent chemotherapy and SCT, response rates are low and survival is short. Better understanding of the biologic basis of this disease and novel treatment approaches for treatment of BPCDN are crucial.
FLT3 mutations in myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML).
Authors: Bhamidipati Pavan Kumar , Daver Naval Guastad , Kantarjian Hagop , Pierce Sherry , Daver Roshni , Cortes Jorge E. , Ravandi Farhad , Mathisen Michael , Pemmaraju Naveen , Nazha Aziz , Kadia Tapan M. , Jabbour Elias , Borthakur Gautam , Faderl Stefan , Garcia-Manero Guillermo 
Published: March 2020

6597 Background: FLT3 mutations occur in one third of acute myeloid leukemia (AML) patients (pts) and predict poor outcome. The incidence and impact of FLT3 in MDS/ CMML is unknown. Methods: We conducted a retrospective review at MDACC to identify FAB MDS/ CMML pts with FLT3 mutations at diagnosis. Results: From 1996 to 2010; 2052 MDS/ CMML pts had mutation analysis. 45 (2.2%) had FLT3 mutations (internal tandem duplication-ITD or D835) at diagnosis. 29 pts had MDS and 16 had CMML. Median (Med) age was 64 years (21 to 83) and 69% were males. FAB groups: 3 pts with refractory anemia (RA), 11 pts with refractory anemia-excess blasts (RAEB), 18 pts with refractory anemia-excess blasts in transformation (RAEB-T) and 13 pts with CMML. IPSS: 3 in Low (7%), 16 in Int-1 (36%), 11 in Int-2 (24%), and 15 in High (33%). Med white count, hemoglobin, platelet count and marrow blast percent at diagnosis were 5.2 x 109/l (1.2 to 211), 10.0 g/l (6.8 to 14.9), 78 x 109/l (8 to 429), and 14% (1 to 28), respectively. FLT3 ITD and FLT3 D835 mutations were present in 32 (71%) and 13 pts (29%), respectively. Karyotype was diploid in 30 (66%); -5/-7 in 5 (11%), 11q in 1 (2%), and others in 9 pts (19%). All 5 pts with -5/ -7 had the ITD mutation. Concurrent mutations were identified in RAS, NPM1 and C-Kit in 6 (13%), 3 (7%) and 1 (2%) pt, respectively. Med overall survival (OS) for FLT3 pts was 15 months compared to 17 months for non FLT3 pts (P=0.9). 18 pts had RAEB-T: 13 (72%) received AraC-based therapy and 3 (17%) received hypomethylating therapy (HMT) with complete remission (CR) in 14 pts (78%). 14 pts had RA/ RAEB: 5 (36%) received AraC-based therapy and 7 (50%) received HMT with CR in 5 (37%) and hematological improvement (HI) in 4 (28%). 13 pts had CMML: 4 (31%) received AraC-based therapy and 6 (46%) received HMT with CR in 3 (23%) and HI in 3 (23%). Repeat FLT3 was available on 16 pts achieving any response and was absent/ decreased in 14 (88%), stable in 1 (6%) and increased in 1 (6%). Notably, the 14 pts with absent/ decreased FLT3 had med OS of 27 months versus 12 months for remaining group (P=0.004). Conclusions: FLT3 occurs in MDS/ CMML at a lower frequency than AML and does not predict poor outcome. Pts who achieve absent/ decreased FLT3 seem to have significantly improved overall survival.
A comparison of CR versus CRi response following CPX-351 treatment of newly diagnosed AML in elderly patients (pts).
Authors: Lancet Jeffrey E. , Cortes Jorge E. , Kovacsovics Tibor , Hogge Donna , Kolitz Jonathan E. , Tallman Martin S. , Chiarella Michael , Louie Arthur Chin , Feldman Eric Jay 
Published: March 2020

6601 Background: A Phase 2b study randomized untreated elderly AML pts to CPX-351 or 7+3. CPX-351 improved leukemia clearance (88% v 71%, <5% marrow blasts), CR+CRi rate (67% v 51%), and was particularly effective in pts with adverse karyotype and antecedent hematologic disorders (sAML). Survival following CRi is usually inferior compared to CR. CPX-351 markedly prolongs plasma drug levels and maintains the 5:1 molar ratio for optimal leukemic cell killing potentially delaying hematologic recovery among CRi patients. Consequently, we compared the characteristics and outcomes of pts achieving CR v CRi. Methods: Untreated AML pts, aged 60-75, PS= 0-2, SCr < 2.0 mg/dL, total bilirubin <2.0 mg/dL, ALT/AST <3 x ULN, and LVEF ≥50% were eligible. Pts were randomized 2:1 to receive up to 2 inductions and 2 consolidations with CPX-351 (100 u/m2; D 1, 3, 5; 90 min infusion) or 7+3 (cytarabine=100 mg/m2 and daunorubicin=60 mg/m2). Consolidation with stem cell transplantation (SCT) was permitted. The 1o endpoint was CR+CRi rate. The 7+3 control arm had only a single CRi among 21 responders. The CPX-351 arm had 15 CRi (27%) and 41 CR (73%) allowing a CR v CRi comparison to be made. Results: CR and CRi pts were balanced by age, race, and PS. The CRi group had more males (87% v 51%), more baseline WBC>20K (27% v 15%), and more adverse karyotype (40% v 27%) and sAML (47% v 29%). A smaller proportion of CRi pts received post-remission chemotherapy (47% v 73%) but had similar rates of SCT (13% v 20%). Most CRi pts had delayed platelet recovery (80%). By 1-year more CRi pts had relapsed (54% v 39%) and more had died (54% v 34%). Contributing causes included: relapsed AML (7 CRi v 10 CR pts), complications post SCT (1 CRi v 1 CR pt), chemotherapy complications (0 CRi v 2 CR pts) and unknown causes (0 CRi v 1 CR pt). The survival curves were not significantly different (p=0.39). Conclusions: More CRi patients had adverse karyotype and sAML and most (53%) received no post remission chemotherapy. Survival was not significantly different compared to CR patients but was markedly better than that of non-responders. These data suggest that CRi following CPX-351 provides clinically meaningful benefit, a finding that needs to be confirmed in a larger randomized study.
Impact of immunoglobulin heavy chain variable region mutational status on the outcome of patients with chronic lymphocytic leukemia harboring isolated 13q deletion.
Authors: Domingo Gelenis C. , Dalia Samir , Chavez Julio C. , Carballido Estrella M. , Aguayo-Hiraldo Paibel I. , Sweet Kendra Lynn , Crescentini Robert M. , Sokol Lubomir , Cultrera Jennifer L. , Shah Bijal D. , Lancet Jeffrey E. , Sotomayor Eduardo M. , Komrokji Rami S. , Pinilla-Ibarz Javier 
Published: March 2020

6608 Background: Several prognostic factors can predict the course of chronic lymphocytic leukemia (CLL). Among them, the IGVH mutational status and the presence of cytogenetic abnormalities are the strongest predictors of outcome. Mutated IGVH and deletion 13q independently confer a survival advantage. CLL patients with mutated IGVH in combination with deletion 13q have a better prognosis when compared to their unmutated IGVH counterparts. However, there is limited data on the outcome of patients harboring favorable deletion 13q and the unfavorable unmutated IGVH. This study aimed at identifying patients with these two indicators in order to obtain important prognostic information. Methods: We used the Moffitt Cancer Center Total Cancer Care (TCC) database to find patients with a diagnosis of CLL between January 1993 and December 2009. Individual charts were reviewed for demographic data and CLL cytogenetics, including IGVH mutation status and presence of deletion 13q. We analyzed the impact of having deletion 13q in combination with an unmutated IGVH on the overall survival (OS) for this subset of CLL patients using Kaplan Meier curves with SPSS statistical software. Results: 546 patients were identified during the aforementioned time period with a diagnosis of CLL. Median age was 62.5 years. 144 (26.4%) of these patients had IGVH and cytogenetic analysis available. 53 patients had 13q deletion as their sole genetic abnormality. Patients with unmutated IGVH and positive for deletion 13q were 19/53 (35.8%). Patients with mutated IGVH and positive for deletion 13q were 34/53 (64.2%). Patients with mutated IGVH and positive for deletion 13q had an OS of 17 years. While patients with unmutated IGVH and positive deletion 13q had a lower median OS of 12 years (91.2% vs 78.9%, p=0.05). Hazard ratio for patients with IGVH mutated and positive deletion 13q was 0.4, p=0.05. Conclusions: Mutated IGVH appears to be associated with improved OS in patients with isolated 13q deletion when compared to patients with unmutated IGVH and isolated 13q deletion. Further research is needed to assess these mutations in relation to other cytogenetic abnormalities in CLL.
Novel risk factors for osteonecrosis of the jaw in multiple myeloma: A RADAR report.
Authors: Holbrook Jaimee S , Trifilio Steven M , Mckoy June M. , Singhal Seema , Rademaker Alfred , Mehta Jayesh , Belknap Steven M , Tica Stefani , Clark Sarah Victoria , Godinez-Puig Victoria , Nardone Beatrice , Gradishar William John , West Dennis P. , Edwards Beatrice J. 
Published: March 2020

6623 Background: Osteonecrosis of the jaw (ONJ) was identified in 2001 and is commonly seen in multiple myeloma (MM). The objective of this study is to evaluate novel risk factors in MM cases from a retrospective database. We hypothesized that ONJ may be related to stem cell transplant, chronic kidney disease and active smoking. Methods: We conducted a retrospective case-control study of 231 MM cases (from January 1, 1998 to September 30, 2010) identified from the electronic data warehouse (EDW) at Northwestern University (NU). The EDW is cross-institutional and integrates clinical data across NU. It comprises more than 2.3TB of data on roughly 2 million patients. The search terms used were: bisphosphonates, pamidronate, zoledronic acid, multiple myeloma, plasma cell disorders, osteonecrosis of the jaw, jaw abscess, dental abscess, among other terms described in literature. Data was abstracted onto a standardized form by 2 trained abstractors and validated by a clinician reviewer (BJE). Known and hypothesized new risk factors were abstracted, including duration of myeloma, treatment used, duration of bisphosphonate use, renal function indices, chemotherapy (vincristine, doxorubicin (A), dexamethasone (D) , thalidomide (T), cisplatin (P), cyclophosphamide (C), etoposide (E), novel agents [bevacizumab, sorafenib, angiostatin]) GCSF, smoking, and MM clinical stage. Analyses included T test, Wilcoxon, and log rank analysis. Results: ONJ occurring after MM diagnosis was identified in 33 cases out of a total of 233 cases of MM. ZOL, VAD, DT-PACE, and diabetes were more common in ONJ cases. Log rank analysis identified 2 risk factors for ONJ, the use of DT-PACE (p= 0.003), and complete and partial remission (p=0.007). Stem cell transplant and chronic kidney disease were not associated with ONJ. Conclusions: We identified novel risk factors for ONJ in MM, mainly partial or complete remission and use of DT-PACE. These results should prompt clinicians to heightened awareness and increased surveillance for the symptoms of ONJ for patients treated with DT-PACE.
Adverse events (AEs) and the return of myelofibrosis (MF)-related symptoms after interruption or discontinuation of ruxolitinib (RUX) therapy.
Authors: Verstovsek Srdan , Mesa Ruben A. , Gotlib Jason R. , Gupta Vikas , DiPersio John F. , Catalano John V. , Deininger Michael W.N. , Miller Carole Brennan , Silver Richard T. , Talpaz Moshe , Winton Elliott F. , Harvey Jimmie Huling , Arcasoy Murat O. , Hexner Elizabeth O. , Lyons Roger M. , Paquette Ronald , Raza Azra , Sun William , Kantarjian Hagop ,   for the COMFORT-I Investigators
Published: March 2020

6624 Background: RUX is a JAK1/JAK2 inhibitor that demonstrated significant clinical benefit in patients (pts) with MF in COMFORT-I (NCT00952289), a phase 3, randomized (1:1), double-blind, placebo (PBO)-controlled study (N=309). Methods: Pts assessed MF-related symptoms daily using the modified Myelofibrosis Symptom Assessment Form v2.0; Total Symptom Score (TSS) was calculated from individual scores for abdominal discomfort, pain under left ribs, early satiety, night sweats, itching, and bone/muscle pain. Therapy was interrupted if platelet or absolute neutrophil count fell below 50,000/µL or 500/µL, respectively. AEs were evaluated during treatment interruption or discontinuation. The protocol suggested an optional tapering strategy and possible addition of steroids if RUX therapy was discontinued for reasons other than thrombocytopenia. Results: In RUX-treated patients with treatment interruption, TSS gradually returned to baseline levels over approximately 1 week. The most common AE leading to treatment interruption or discontinuation in each group was thrombocytopenia (n=11, RUX) and abdominal pain (n=4, PBO). Of these, only 1 RUX pt discontinued for thrombocytopenia. A summary of new onset/worsening AE data after treatment interruption or discontinuation is presented (Table). Of 58 pts who discontinued study treatment, 23 (n=10, RUX; n=13, PBO) experienced a total of 43 SAEs (19, RUX; 24, PBO) that showed no specific pattern or difference between treatment groups. Four of 21 RUX-treated pts had dose tapering following study drug discontinuation. Conclusions: Apart from the expected return of MF-related symptoms, there was no pattern of AEs to suggest that RUX interruption or discontinuation is associated with a specific withdrawal syndrome. [Table: see text]