bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of a novel disease risk model for patients with AML receiving allogeneic hematopoietic cell transplantation.
Authors: Kongtim Piyanuch , Hasan Omar , Ramos Perez Jorge Miguel , Varma Ankur , Chen Julianne , Rondon Gabriela , Srour Samer , Bashir Qaiser , Qazilbash Muzaffar H. , Mehta Rohtesh , Shpall Elizabeth J. , Alousi Amin Majid , Khouri Issa F. , Kebriaei Partow , Popat Uday R. , Champlin Richard E. , Ciurea Stefan O. 
Published: March 2020

7016 Background: Molecular data and minimal residual disease (MRD) have been shown to influence outcomes in AML patients undergoing allogeneic hematopoietic cell transplantation (AHCT). Here we developed and validated a novel AML-specific Disease Risk Group (AML-DRG) and revise our previously developed Hematopoietic Cell Transplant - Composite Risk (HCT-CR) model by incorporating molecular data and MRD status before transplant to predict post-transplant outcomes of patients with AML. Methods: The study included 1414 consecutively treated adult AML patients, who received first AHCT between 1/2005-8/2018 at our institution. Patients were randomly assigned into a training (N = 944) and validation set (N = 470). To develop the AML-DRG model, the coefficient of all significant AML-related variables in multivariable Cox’s regression analysis (MVA) in a training dataset was converted into scores.The AML-DRG was the sum of scores from all significant covariates, while the AML-HCT-CR was the sum of disease-related factors assessed by the AML-DRG model with the addition of weighted scores from patient-related factors. Results: Based on results of MVA, the following scores were assigned to each AML-related variable; 1 point to secondary AML; 1 point to the 2017 ELN adverse risk; 2 points to CR with MRD positive/unknown; and 4 points to active disease at transplant. These were used to generate the AML-DRG (low-risk score 0-2; intermediate-risk score 3-4; and high-risk score > 4) with significantly different OS with HR of 2.02 (P < 0.001), and 3.85 (P < 0.001) for intermediate and high risk group compared with low risk group. By adding 1 point for patients > / = 60 years or HCT-CI > 3 to the AML-DRG, we created 4 risk groups of AML-HCT-CR (low-risk: score 0-2; intermediate-risk: score 3; high-risk: score 4 and very high-risk: score ≥5) with distinct survival outcomes. The AML-DRG and AML-HCT-CR model had C-index of 0.672 and 0.715, respectively which were better compared with DRI, ELN2017 and cytogenetic risk model. Conclusions: Prognostic models incorporating molecular data and MRD status before transplant allow better stratification and improved survival estimates of AML patients post-transplant.
Adult Langerhans cell histiocytosis: A contemporary single-institution series of 186 patients.
Authors: Goyal Gaurav , Hu Marie , Young Jason R , Vassallo Robert , Ryu Jay H , Bennani Nabila Nora , Shah Mithun Vinod , Rech Karen , Go Ronald S. ,   Mayo Clinic Histiocytosis Working Group
Published: March 2020

7018 Background: Langerhans cell histiocytosis (LCH) is a rare histiocytic neoplasm driven by MAPK-ERK mutations in majority of patients. Contemporary data on treatments and outcomes in adult LCH are lacking. Hence, we undertook this study to analyze a large cohort of adult LCH patients. Methods: This was a retrospective study of adult (≥18 years) LCH patients seen at our institution between 1998 and 2018. Results: We included 186 patients with adult LCH (median age 43; 19-88), and 54% were females. 70% of patients were diagnosed after 2007. Common presenting symptoms were cough/dyspnea (30%), rash (17%), pain/swelling in head (17%), and diabetes insipidus (10%). 70 (38%) patients had multisystem LCH, 62 (33%) had isolated pulmonary LCH, and 35 (19%) had unifocal LCH. Common sites of involvement included lung (59%), bone (37%), skin (21%), and nervous system (16%). 121 (65%) were smokers; 48% of these had lung disease, while 52% had multisystem disease. 18 of 31 tested (58%) patients had BRAF-V600E mutation. Most common first-line treatment was smoking cessation in 24 patients, and led to an overall response rate (ORR) of 83% in pulmonary lesions. Radiation therapy was used in 11 patients, and led to an ORR 82%. Surgical resection of lesion was done in 23 patients, with relapses in 24%. Systemic therapies were used in 78 (42%) patients (Table). Most common first-line systemic therapy was cladribine with ORR of 78%. Vemurafenib was used in 3 patients with BRAF-V600E, leading to an ORR of 67% . After a median follow-up of 23 months (0-261), 21 patients had died. Of these, 10 died of progressive LCH. Median OS was not reached, and mean OS was 196 months. Conclusions: This is the largest contemporary series of adult LCH. It shows that diverse clinical spectrum, ranging from benign course to a progressive multisystem disease. Although smoking cessation was an effective treatment for pulmonary LCH, a large subset required systemic chemotherapy. [Table: see text]
Inotuzumab ozogamicin (InO) treatment in patients with relapsed/refractory acute lymphoblastic leukemia (R/R ALL): Outcomes of patients treated in salvage one with a long duration of first remission.
Authors: Kantarjian Hagop M. , Stelljes Matthias , Advani Anjali S. , DeAngelo Daniel J. , Marks David I. , Stock Wendy , O'Brien Susan Mary , Cassaday Ryan Daniel , Wang Tao , Neuhof Alexander , Vandendries Erik , Jabbour Elias 
Published: March 2020

7029 Background: In R/R ALL, data are limited supporting targeted therapies like InO as first salvage in patients (pts) who had a long first complete remission (CR1). InO, a calicheamicin-conjugated antibody, targets CD22 on ALL blasts. Here we report outcomes in pts with ALL in first salvage (S1) who had a long CR1 before receiving InO vs standard of care chemotherapy (SC). Methods: Adults with CD22+ R/R ALL, stratified by salvage and length of remission (CR1 ≥ or < 12 mos), were randomized to receive InO (n = 164) or SC (n = 162). Methods were previously described (Kantarjian et al, NEJM 2016), with data shown up to the last patient last visit (January 4, 2017). Outcomes including complete remission (CR)/CR with incomplete hematologic recovery (CRi) and overall survival (OS) were determined for S1 pts who achieved CR1 ≥ 12 mos and CR1 ≥ 18 mos. Results: For S1 pts with CR1 ≥ 12 mos or CR1 ≥ 18 mos, InO and SC arms had generally comparable baseline characteristics. For S1 pts with CR1 ≥ 12 mos and CR1 ≥ 18 mos, fewer pts had received a prior stem cell transplant in the InO vs SC arm (10.4% vs 25.0% and 9.7% vs 21.4%). For S1 pts with CR1 ≥ 12 mos and CR1 ≥ 18 mos respectively, InO vs SC treatment led to a higher CR/CRi rate (85.4% vs 27.5% [ P< 0.0001] and 83.9% vs 32.1% [ P< 0.0001]) and improved OS (HR = 0.547 [ P= 0.0086] and 0.504 [ P= 0.0163]), with veno-occlusive liver disease reported in 12.5% and 12.9% of InO pts Clinical trial information: NCT01564784. Conclusions: Improved outcomes were seen with InO vs SC among S1 pts who had a long first complete remission (CR1 ≥ 12 mos or CR1 ≥ 18 mos), supporting the benefit of InO vs SC in this population.[Table: see text]
A video decision aid to improve acute myeloid leukemia patients’ illness understanding: Results of a pilot trial.
Authors: LeBlanc Thomas William , Locke Susan C. , Herring Kris , Davis Debra M. , Troy Jesse D , Steinhauser Karen E. , Pollak Kathryn I. , Ubel Peter A. 
Published: March 2020

7040 Background: Many acute myeloid leukemia (AML) patients harbor misunderstandings about their illness, overestimating both their likelihood of cure and risks of intensive therapies. Decision aids (DA) can improve illness understanding and reduce decisional conflict, but are not routinely used in AML. Methods: We developed an AML DA with input from patients, caregivers, clinicians, and laypersons, via the International Patient Decision Aids Standards (IPDAS) process. It includes 10 short animated videos with voiceovers, covering AML basics, etiology, outcomes, treatment paradigms, and risks/benefits of various treatment approaches. We enrolled 20 patients in a pilot feasibility and efficacy trial, with pre/post survey assessments of AML knowledge via an 18-item questionnaire, decisional conflict (Decisional Conflict Scale; DCS), anxiety (State Trait Anxiety Inventory, Short Form; STAI-6), and measures of DA usability and satisfaction. Results: Participants were a mean of 62.4 years old, 12 (60%) were male, 17 (85%) white, and 15 (75%) had newly-diagnosed disease. Mean time since AML diagnosis was 145 days (median 31; range 2-1092). 16 (80%) exhibited high-school-level understanding of medical terms per the REALM-SF, and participants on average exhibited moderate numeracy (mean score of 4.1 on the Subjective Numeracy Scale). All participants completed the study, exceeding our pre-determined feasibility threshold. AML knowledge scores generally improved, from a mean of 11.8 correct items on pre-test, to 15.2 on post-test assessment (p < 0.0001), with 80% of participants achieving improved scores. Struggles remained regarding patients’ understanding of the role that genetic tests play in AML care. There was no increase in anxiety after watching the videos, but decisional conflict was significantly reduced, from a mean of 28.5 at baseline to 22 in the post-test (p = .019). Participants reported high satisfaction and usability scores for the DA. Conclusions: Our AML decision aid exhibits favorable performance characteristics, with high satisfaction and usability, a marked increase in patient knowledge, and reduced decisional conflict. Further testing is warranted in a randomized trial. Clinical trial information: NCT03442452.
The Transplant Optimization Program (TOP): Implementing a geriatric assessment (GA)-guided interdisciplinary clinic (IDC) prior to allogeneic hematopoietic cell transplantation (HCT) in older adults.
Authors: Derman Benjamin Avi , Kordas Keriann , Ridgeway Jean , Chow Selina Lai-ming , Dale William , Hsiao Yung-Hsuan , Paloma Marc , Pisano Jennifer , Rosinski Thomas , Bishop Michael Russell , Artz Andrew S. 
Published: March 2020

7045 Background: Limitations found on GA correlate with worse outcomes after HCT, but no data exists on prospectively utilizing GA prior to HCT. We established the TOP IDC in March 2013 to implement a cancer-specific GA and an IDC to risk-stratify HCT candidacy and create an individualized care plan for allograft candidates 60+ yrs. Methods: The IDC consisted of a HCT physician, advanced practice provider, dietician, PT/OT, social worker, ID physician, and a geriatric oncologist to devise a pt specific optimization strategy. We compared consecutive HCT pts ≥ 60 years undergoing GA prior to TOP implementation (pre-TOP) from 2005-2012 (n=75) to TOP pts from 2013-2018 (n=86). Results: 3/89 HCT pts 60+ yrs who did not attend TOP were excluded; all 3 died before 1 year post-HCT. Compared with controls, the TOP group was older (median age 67 vs. 64 yrs, p<0.001) but was similar in HCT-CI ≥ 3 (37% vs. 48%, p=0.2), use of myeloablative regimens (20% vs. 19%, p=0.8), and advanced ASBMT risk disease (46% for both). Relative to the pre-TOP group, TOP pts at baseline had fewer impairments in independent activities of daily living (30% vs. 48%, p=0.02) and fewer frail 4-meter walk tests (7% vs. 31%, p<0.001). Pts undergoing optimization in TOP fared better versus pre-TOP (Table). 1-yr non-relapse mortality (NRM) and 1-yr overall survival (OS) continued to improve including 11% NRM and 89% OS in 2017. Conclusions: A GA-guided interdisciplinary optimization clinic for allograft recipients age 60+ reduced transplant associated morbidity and mortality, with marked improvements in NRM and OS over time. A GA-based IDC can facilitate selection and optimization of older pts considering HCT.[Table: see text]
Allogeneic stem cell transplantation (AlloSCT) for patients (pts) with acute leukemia following venetoclax-based therapy.
Authors: Mukherjee Akash , Milton Denai R. , Jabbour Elias , Konopleva Marina , Dinardo Courtney Denton , Gulbis Alison , Ravandi Farhad , Daver Naval Guastad , Kadia Tapan M. , Oran Betul , Popat Uday R. , Ciurea Stefan O. , Im Jin , Kebriaei Partow , Mehta Rohtesh S. , Kantarjian Hagop M. , Champlin Richard E. , Khouri Issa F. 
Published: March 2020

7047 Background: BCL-2 inhibitor Ven has shown a promising benefit in pts with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). There is paucity of information about the safety and efficacy of alloSCT post Ven. Methods: We conducted a retrospective analysis of 35 AML/ALL pts who received alloSCT following Ven-based therapies between 2013-2018 at MDA. Results: Median age at alloSCT was 60 years and 15 (43%) pts had an age-adjusted HCT-CI score ≥ 4. Disease diagnosis – AML (n = 31; 89%), ALL (n = 4; 11%). Disease status at transplant was CR1 (n = 17; 49%), CR2/CR3 (n = 9; 26%) or refractory (n = 9; 26%). 20/26 (77%) CR pts were MRD-negative. Median # of prior therapies was 2 (range 1-7) and 4 (11%) pts had failed a prior alloSCT. AML pts were classified by ELN 2017 criteria to have favorable, intermediate and adverse risks in 16%, 23% and 61% respectively. Ven was provided in combination of hypomethylating agents (HMA) or other chemotherapies in 26 (74%) and 9 (26%) pts, respectively. Among pts treated with Ven + HMA, some also received IDH1/2 inhibitors (n = 7, 20%), FLT3 inhibitors (n = 4; 11%) or anti-PD1 (n = 3, 9%). Median duration of Ven-based treatment was 2 months (range 0.5- 4.6). Ven was discontinued in 6 (17%) pts due to adverse events (n = 4) or progression (n = 2); the remaining pts (83%) continued their Ven-therapy as a bridge to alloSCT. The median time from last Ven dose and transplant was 26 days. Conditioning regimens were melphalan-based reduced intensity (n = 26, 74%), or busulfan-based myeloablative regimens (n = 9; 26%). Donor source was matched -unrelated (n = 14, 40%), -related (n = 9; 26%) or haplo- (n = 12; 34%). GVHD prophylaxis consisted of tacrolimus with either PT-Cy in 25 (71%) pts or methotrexate in 10 (29%) pts. All pts engrafted (median day 30 donor cells = 100%). Median days to ANC > 500 and platelets > 20K was 15.5 and 22.5, respectively. With a median follow up of 5.7 months (range 0.7-15.4), the 1-year rates of OS, PFS, and NRM were 71%, 63% and 3% respectively. CI of acute grade 2-4 and 3-4 GVHD were 26% and 3% respectively. Four pts died: 3 because of disease relapse and 1 of infection. Conclusions: AlloSCT is a safe and feasible consolidation treatment option in acute leukemia pts who were pre- treated with Ven, without excessive risk of NRM or acute GVHD. Larger prospective studies are required to validate our observations.
Update on lower-dose dasatinib 50 mg daily as frontline therapy in newly diagnosed chronic phase chronic myeloid leukemia (CML-CP).
Authors: Naqvi Kiran , Jabbour Elias , Skinner Jeffrey A , Anderson Kristin N , Yilmaz Musa , Jain Nitin , Ferrajoli Alessandra , Bose Prithviraj , Thompson Philip A. , Alvarado Yesid , Takahashi Koichi , Burger Jan Andreas , Borthakur Gautam , Estrov Zeev , Pemmaraju Naveen , Paul Shilpa , Dellasala Sara , Cortes Jorge E. , Kantarjian Hagop M. 
Published: March 2020

7052 Background: Dasatinib, a potent BCR-ABL tyrosine kinase inhibitor (TKI), is approved for the treatment of chronic phase CML (CML-CP) in the frontline and salvage settings. Notable side effects include pleural effusions and myelosuppression. We previously reported dasatinib 50 mg daily to be active and better tolerated than the approved 100 mg daily dose (CANCER. 2018 Jul 1;124(13):2740-2747). We present an update on the efficacy and toxicity profile of lower dose dasatinib 50 mg orally daily in patients with early CML-CP. Methods: All patients presenting to our institution in early CML-CP were eligible to participate. Prior TKI therapy for up to 1 month was allowed. Responses were assessed according to the European LeukemiaNet guidelines (Baccarani et al. Blood 2013 122.872:884). Results: From March 2016 to March 2018, 81 patients have been enrolled. Median age is 47 years (20-84). Patients categorized by Sokal risk are: low 53; intermediate 22 and high 6. Median follow-up is 18 months (9-31). Cumulative response rates over time are shown below: At 3 months, 96% patients achieved early molecular response ( BCR-ABL PCR ≤10%). Median time to CCyR was 4.6 months, MMR 6.0 months, MR4.0 11.4 months and MR4.5 12.2 months. Eighteen patients had treatment interruption: pleural effusion 4 (possibly related 3, unrelated 1 due to pneumonia); gastrointestinal bleed 2; thrombocytopenia 3; transaminitis 2; renal dysfunction 1; asthma exacerbation 1; pneumonitis 1; lower extremity edema 1; myalgias 1, and pregnancy 2. Four patients had dose reductions: pleural effusion 3; myalgias 1. Four patients had dasatinib dose increased to 100mg: lack of CCyR at 6 months, 3; lack of MMR at 12 months, 1. Four patients are off study: no response 2, pneumonitis 1, and insurance 1. None of the patients have transformed or died. Conclusions: These updated results continue to support dasatinib 50 mg daily as an effective and safe dose for early CML-CP. Clinical trial information: NCT02689440. [Table: see text]
Discrepancy of blast percentage between the bone marrow aspirate and biopsy and its impact on survival outcomes in patients with myelodysplastic syndromes excess blast (MDS-EB).
Authors: Yogarajah Meera , Nguyen Phuong L. , He Rong , Alkhateeb Hassan , Shah Mithun Vinod , Patnaik Mrinal Mahesh , Gangat Naseema , Hogan William J. , Tefferi Ayalew , Litzow Mark Robert , Al-Kali Aref 
Published: March 2020

7053 Background: The revised International Prognostic Scoring System (IPSS-R) aids in prognosticating MDS. The percentage (%) of blasts in the bone marrow is one of the major determinants of the scoring system. The aspirate blast % is utilized as the standard of care, but there could be discrepancies in the blast % reported by the aspirate and the biopsy. We aim to study the possible use of bone marrow biopsy blasts in MDS-EB in calculating IPSS-R. Methods: The MDS database was reviewed for cases of MDS-EB after due IRB approval. We calculated IPSS-R scores based on the aspirate blast % (IPSS-RAsp) and biopsy blast % (IPSS-RBx). The biopsy blast % was reported morphologically or by the CD34 stain. Whenever a range was reported the highest value was utilized as the blast %. Suboptimal aspirates were excluded from the study. The overall survival (OS) was determined by IPSS-RAsp, IPSS-RBx and IPSS-R highest blast (IPSS-RHi). OS estimates were calculated by Kaplan-Meier curves and log-rank testing using JMP v.13. Uno’s concordance statistic was used to compare all 3 risk scoring systems. Results: Of 1322 patients, 431 (33%) cases were identified with MDS-EB; out of which 173 cases had both blasts reported in the biopsy and the aspirate. Out of 173 cases, 35 (20%) had MDS-EB1, and 61 (35%) had MDS EB-2 based on both biopsy and aspirate (concordant cases). Seventy seven (45%) patients changed from EB-1 to EB2 or vice versa based on the biopsy blast (44/77 (57%) cases were upstaged). The OS outcomes based on the IPSS-RBx biopsy showed a clear and meaningful separation with median OS decreasing with increased risk but IPSS-RAsp and IPSS-RHi did not (Table). We compared the 3 models for observed OS differences using the Uno model and there was no statistically significant difference. Conclusions: IPSS-RBx (but not IPSS-RAsp and IPSS-RHi) identified prognostic groups for OS with median OS decreasing with increased risk. The small sample size may have led to an insignificant effect on model power by Uno model. This finding needs to be validated by other centers. [Table: see text]
Proposal of an endpoint for a phase III clinical study of essential thrombocythemia: Balancing between short term effects and long term benefits.
Authors: Mesa Ruben A. , Zimmerman Craig , Kang Lih Lisa , Qin Albert , Lee Chungwei , Shih Weichung (Joe) , Zagrijtschuk Oleh , Komatsu Norio , Xiao Zhi-Jian , Hou Hsin-An , Chen Chih-Cheng , Verstovsek Srdan 
Published: March 2020

7055 Background: Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN), covering broad spectrum of clinical scenarios, from asymptomatic patients with only isolated high platelets to highly morbid patients in late stage disease. Due to heterogenous patient population, designing clinical studies in ET is difficult, and after anagrelide there was no new drug approval to treat ET during the past 15 years, thus, high unmet medical to treat patients with ET remains. Interferons alpha (IFNa) are known to have beneficial effects in MPN (Kiladjian et al, 2016). P1101 is a next generation monopegylated IFNa, developed specifically to treat MPNs, including ET. Methods: External published clinical data in ET were analyzed to design optimal clinical study. Proposed endpoints are meant to cover all relevant clinical aspects of ET, and suffice for a regulatory relevant pivotal clinical study. Results: Composite primary endpoint scale is based on modified ELN criteria. Short term study endpoints should have clinical meaningfulness at time of measurement but also predict the later outcomes. The scale consists of: normalization of platelets (<400 G/L) and leukocytes (<9.5 G/L); normalization in size or non-progression of palpable spleen; lack of major cardiovascular event during the observation period; and improvement of Myeloproliferative Neoplasm Symptom Assessment Form total symptom score (MPN-SAF TSS). MPN-SAF TSS is a 10 items questionnaire, allowing concise, valid, and accurate assessment of MPN symptom burden over time (Emanuel et al, 2012). For TSS-10 score, to qualify for response, following rules were elaborated: 10 points or higher reduction for patients with baseline score of ≥20, for patients with baseline score 15-19 – 5 points reduction, baseline scores 10-14 – reduction below 10 points, and for TSS baseline score <10 – stay <10. Bone marrow analysis is not to be a mandatory test for assessment of overall benefit of therapy. Extensive genetic workup is planned to document any change in observed genetic and chromosomal abnormalities, including level of circulating mutant CALR. This would allow for objective evaluation of IFNa’s ability to modify the disease. Long term observation, going beyond the 12 month of initial observation, is planned. Conclusions: Authors conclude that proposed endpoint scale covers well all clinically relevant aspects of ET, in order to make clinically relevant conclusions on durable benefits and risks of P1101 therapy.