bluuebunny/crossref_metadata_2025_split huggingface dataset:
Granulocyte transfusions in patients with skin and soft tissues infections and leukemia: Are they useful?
Authors: Michelen Yamil , Kantarjian Hagop M. , Ravandi Farhad , Pemmaraju Naveen , Kadia Tapan M. , Konopleva Marina , Verstovsek Srdan , Daver Naval Guastad , Garcia-Manero Guillermo , Krause Heidi , Dinardo Courtney Denton , Burger Jan Andreas , Ferrajoli Alessandra , Wierda William G. , Cortes Jorge E. , Aung Fleur M. 
Published: March 2020

7022 Background: Granulocyte transfusions (GTX) have been proposed to improve clinical outcome of neutropenic patients (pts) with serious infections. We evaluated the impact of unirradiated GTX in pts with skin and soft tissue infections (SSTI) and leukemia. Methods: We did a retrospective analysis of pts with leukemia and SSTI that received GTX from 2014 to 2018. We analyzed infection outcome and changes in ANC after GTX. Donors were mobilized using G-CSF plus oral dexamethasone 12 hours prior to apheresis. Results: Twenty-seven pts received 141 GTX for 33 SSTI. Transfusions were unirradiated, except for 10 (7%) radiated units administered due to availability. Twenty pts were male (74%); median age was 59 yrs (20–83 yrs). Hematologic diagnoses included AML (23, 70%), MDS (3, 9%), ALL (3, 9%), CLL (2, 6%), CML (1, 3%), and MF (1, 3%). In 24 (73%) SSTI, pts had a baseline ANC<0.5 x109/L, 3 (9%) had ANC between 0.51x109L to 0.99 x 109L, and 6 (18%) with ANC >1 x109/L. After GTX, ANC increased in 99 (70%) cases by a median of 0.7 x 109/L (0.02 to 10.03) with a median peak time of 9 hrs (4 to114 hrs), with a median time from GTX to first drop of 34 hrs (10 to 136 hrs). ANC decreased in 27 (19%) (by a median -0.5 x 109/L,-0.02 to -2.41). There was no change of ANC in 15 (11%). Improvement was determined by reduction in fever and inflammation, or resolution of SSTI 7 days after first GTX. Twenty-seven (82%) episodes improved. In those improved, ANC remained <1.5x109/L in 15 (56%) episodes after last GTX and after improvement. Main adverse reactions were fever in 21% (29), and respiratory complications in 6% (9) (pulmonary effusion, respiratory distress and acute hypoxemia). One pt (3%) required intubation. There was no transfusion-related GVHD. Cumulative survival from first GTX on each SSTI by Kaplan-Meier Survival was 82% (8) at 30 days, 49% (17) at 90 days, 41% (17) at 180 days, and 24% (12) at 360 days. Eight of this pts died of infections, 4 of which were SSTI described on this paper. Conclusions: GTX have a beneficial effect on clinical improvement in patients with SSTI and underlying hematological malignancies and severe neutropenia. It can be safely administered without GVHD. Further prospective studies are warranted.
Association of the GATA3 rs3824662A allele with clinical outcomes in adult patients with adult B-ALL.
Authors: Koller Paul B. , Kantarjian Hagop M. , Jabbour Elias , Pierce Sherry A. , Roberts Kathryn , Zhang Hui , Yang Wenjian , Mullighan Charles Grenfell , Yang Jun J. , Konopleva Marina , Jain Nitin 
Published: March 2020

7023 Background: Inherited GATA3 variants (rs3824662) have been described in higher frequency in both adults and children with Ph-like acute lymphoblastic leukemia (Ph-like ALL) (Perez-Andreu, Nat Genetics 2013; Jain, ASH 2017). The clinical outcomes of Ph-like ALL are well known, and as we have previously described, it as a high-risk subtype of ALL in both children and adults (Roberts, NEJM 2014; Roberts, JCO 2017; Jain, Blood 2017). However, the clinical outcomes of ALL patients with different germline variants of GATA3 that are commonly seen in Ph-like ALL is unknown. Methods: Of the newly diagnosed patients treated at MD Anderson Cancer Center (MDACC) with B-ALL, we performed analyses for the GATA3 rs3824662 variant in 85 patients (42 Ph-like ALL, 43 non-Ph-like ALL). Testing for Ph-like ALL, CRLF2 rearrangement, and GATA3 genotypes was performed as previously described (Jain, ASH 2017). Results: Of the 85 patients, the rs3824662 AA genotype was identified in 22 patients, the AC genotype in 33 patients, and the CC genotype in 29 patients. There was a trend towards increased frequency of Hispanic heritage in the AA genotype (86%) vs AC genotype (61%), vs the CC genotype (31%). Additionally, amongst patients with the AA genotype, 91% had the Ph-like ALL vs 45% of the AC genotype vs 10% of the CC genotype. The median white blood count at diagnosis was 52.1 x 109/L in the AA genotype group, 20 x 109/L in the AC genotype group, and 5.9 x 109/L in the CC genotype group. The 5 year event-free-survival (EFS) of the CC group was 55% vs 36% of the AC group vs 14% of the AA group. The EFS between the 3 genotypic groups was statistically significant with a p value of 0.018. The 5 year overall survival (OS) of the CC group was 64% vs 42% of the AC group vs 14% of the AA group. Conclusions: We observed significant differences in the EFS between patients with 0, 1, 2 copies of this genetic polymorphism in the GATA3 gene. The role of genomic AA GATA3 variant on the biology of ALL and understanding of the downstream mechanisms needs to be determined. [Table: see text]
Does intensity of induction chemotherapy affect the impact of measurable residual disease (MRD) on prognosis in acute myeloid leukemia (AML)?
Authors: Hochman Michael Jamie , Othus Megan , Shaw Carole , Gardner Kelda , Percival Mary-Elizabeth M. , Hendrie Paul C. , Estey Elihu 
Published: March 2020

7031 Background: Absence of MRD in first complete remission (CR1) of AML decreases the probability of subsequent relapse both in patients given more (e.g. 7+3 or FLAG) or less (e.g. azacitidine) intense induction. Although high-intensity induction seems to increase the chance of CR without MRD, it is unknown whether induction intensity affects outcomes beyond eradication of MRD. Methods: We retrospectively studied adults with newly diagnosed AML or MDS with 10-20% blasts who received induction at the University of Washington from 2008 through 2015. Induction was classified as high or low intensity, CR defined by standard criteria, and marrow MRD by presence of blasts on multiparameter flow cytometry within 1-2 weeks of CR. Post-remission therapy in 10 patients included allogeneic hematopoietic cell transplant (HCT). Multivariate regression analysis examined the independent effects of age, initial cytogenetics (favorable, intermediate, adverse), performance status, de novo vs secondary AML, induction intensity, and MRD on post-CR outcomes. Results: 217 patients received high- and 38 low-intensity induction. 75% of the former vs. 42% of the latter achieved CR without MRD. Although high-intensity therapy was associated with longer overall survival (OS), this difference disappeared after accounting for the above covariates (HR 0.94, 95% CI 0.58  1.52, P = 0.8) and OS was poor regardless of chemotherapy intensity if MRD was present. Multivariate analysis found no interaction between the presence or absence of MRD and induction intensity (HR 0.95, 95% CI 0.4  2.29, P = 0.9). Conclusions: Receiving high-intensity induction chemotherapy does not appear to confer a separate advantage in long-term outcomes once CR without MRD is achieved, at least in patients mostly not receiving HCT. We are currently including more such patients who received HCT. Our results suggest that any effect of high-intensity induction largely reflects its association with a higher probability of achieving an MRD-negative CR.
Results from ongoing phase 1/2 clinical trial of tagraxofusp (SL-401) in patients with intermediate or high risk relapsed/refractory myelofibrosis.
Authors: Pemmaraju Naveen , Ali Haris , Gupta Vikas , Schiller Gary J. , Lee Sangmin , Yacoub Abdulraheem , Talpaz Moshe , Wysowskyj Halyna , Shemesh Shay , Chen Janice , Brooks Christopher , Poradosu Enrique , Rupprecht Nicole , Pardanani Animesh Dev , Tefferi Ayalew , Wang Eunice S. , Taparia Minakshi , Verstovsek Srdan , Khoury Joseph , Patnaik Mrinal Mahesh 
Published: March 2020

7058 Background: Patients with myelofibrosis (MF) who fail or are intolerant to JAK inhibitors (JAKi) have no standard treatment options. CD123 is expressed on a variety of malignancies, including MF. CD123+ plasmacytoid dendritic cells (pDCs), in the MPN microenvironment, including chronic myelomonocytic leukemia and MF, may be tumor-promoting. Monocytosis in MF associated with rapid disease progression and short survival, suggesting an accelerated disease phase. Notably, monocytes share a common precursor with CD123+ pDCs. Tagraxofusp, a novel CD123 targeted therapy, demonstrated high activity in patients with BPDCN, an aggressive hematologic malignancy derived from CD123+ pDCs, and is FDA approved in BPDCN. As such, tagraxofusp may offer a novel therapeutic approach in MF. Methods: Multicenter, 2-stage Ph 1/2 trial enrolling patients (pts) with MF relapsed, refractory, or intolerant to JAKi. Objectives: determine optimal dose, evaluate safety and efficacy. Stage 1 dose escalation: IV tagraxofusp (7, 9, and 12 mcg/kg/day) dosed daily days 1-3 every 21 days (C1-4), 28 days (C5-7), and 42 days (C8+). Stage 2 (ongoing): pts receive optimal S1 dose (12 mcg/kg/day; no MTD). Results: 23 r/r pts treated. Median age 69 (55-81); 57% female. DIPSS Plus: 4% INT-1, 55% INT-2, 41% high. Baseline platelets: median 59 K/uL (15-579); 70% (16/23) <100 K/uL, 8 pts <50 K/uL. 87% (20/23) baseline splenomegaly (palpable ≥5 cm below left costal margin by physical exam). Most common TRAEs: headache (22%), hypoalbuminaemia (22%), ALT incr. (17%) and thrombocytopenia (17%). Most common ≥Gr3 TRAE thrombocytopenia (2%). Capillary leak syndrome in 1 pt (4%; Gr3). 57% (8/14) of pts with baseline spleen ≥5cm BCM spleen responses: 43% (6/14) had ≥29% and 21% (3/14) had ≥45% reduction. 100% of pts with baseline spleen ≥5cm and monocytosis splenomegaly reductions: 80% (4/5) had ≥29% and 40% (2/5) had ≥45%. 6 pts (3 monocytosis pts and 5 pts platelets <100 K/uL) had 6 mos+ duration, 9 pts ongoing. Conclusions: Tagraxofusp demonstrated single agent activity (reduction in splenomegaly) and manageable safety in R/R MF, including pts with monocytosis, an unmet medical need. Given the presence of CD123+ pDCs, tagraxofusp may offer a novel targeted approach in MF. Updated data to be presented. Registrational designs are being evaluated. Clinical trial information: NCT02268253.
Acalabrutinib with obinutuzumab (Ob) in treatment-naive (TN) and relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): Three-year follow-up.
Authors: Woyach Jennifer Ann , Rogers Kerry Anne , Bhat Seema Ali , Blachly James Stewart , Jianfar Mojgan , Frigault Melanie M. , Hamdy Ahmed M. , Izumi Raquel , Munugalavadla Veerendra , Quah Cheng Seok , Wang Min Hui , Byrd John C. 
Published: March 2020

7500 Background: Acalabrutinib is a highly selective, potent, covalent Bruton tyrosine kinase inhibitor. This Phase 1b/2 trial evaluated acalabrutinib with the CD20 antibody Ob in TN and R/R CLL. Methods: Patient (pts) with TN and R/R (≥1 prior therapy) CLL were eligible. In 28-day cycles, acalabrutinib was given at 100 mg BID or 200 mg QD PO (n=15; all switched to 100 mg BID) until progressive disease (PD); Ob was given in standard fashion for 6 cycles starting with Cycle 2. The primary endpoints were overall response rate (ORR) and safety. Minimal residual disease (MRD) was assessed using flow cytometry (sensitivity 10-4). Results: 19 TN and 26 R/R pts were treated; median age of all pts was 61 y (range 42-76). Pt characteristics, disposition, efficacy and MRD are in the Table. Common adverse events (AEs; any grade) were upper respiratory tract infection (71%), increased weight (71%), maculopapular rash (67%), cough (64%), diarrhea (62%), headache (56%), nausea (53%), arthralgia (51%) and dizziness (47%). Common Gr 3/4 AEs were decreased neutrophil count (24%), syncope (11%), decreased platelet count, increased weight and cellulitis (9% each). There were 2 (4%) Gr 3 bleeding events (hematuria, muscle hemorrhage) and 1 (2%) Gr 3 atrial fibrillation event. Conclusions: Acalabrutinib plus Ob was well tolerated and yielded high response rates that were durable and deepened over time in TN and R/R CLL patients. Clinical trial information: NCT02296918. [Table: see text]
Polatuzumab vedotin (Pola) + obinutuzumab (G) and lenalidomide (Len) in patients (pts) with relapsed/refractory (R/R) follicular lymphoma (FL): Interim analysis of a phase Ib/II trial.
Authors: Diefenbach Catherine , Kahl Brad , Banerjee Lalita , McMillan Andrew , Ramchandren Radhakrishnan , Miall Fiona , Briones Javier , Cordoba Raul , González Barca Eva , Panizo Carlos , Hirata Jamie , Chang Naomi , Musick Lisa , Abrisqueta Costa Pau 
Published: March 2020

7505 Background: Pola-G-Len may enhance anti-tumor immune response in R/R FL. We report a pre-planned interim analysis of the safety/efficacy of induction and maintenance with Pola-G-Len in pts with R/R FL in a phase Ib/II study. Methods: Pts received induction treatment with 6x 28-D cycles of: G 1000mg IV (C1: D1, D8, D15; C2–6: D1); Pola 1.4mg/kg or 1.8mg/kg (dose escalation [DE]) or RP2D (expansion) IV (D1); and Len 10–20mg (DE) or RP2D (expansion) PO (D1–21). Pts with CR/PR/SD at the end of induction (EOI) received G 1000mg (D1 every 2mo, for 24mo), and Len (10mg, D1–21 monthly, 12mo). Primary endpoints: C1 DLTs, safety/tolerability, CR rate at EOI (modified Lugano criteria). Results: At the interim data cut-off (7/6/2018), 52 pts were enrolled: 9 discontinued the study (adverse events [AE], n=3; death due to PD, n=4; pt withdrawal, n=1; other, n=1). Median pt age was 62 (range 32–87) years; 58% FLIPI 3–5; 79% ≥2 prior therapy lines; 50% refractory to last treatment. Grade ≥3 AEs were experienced by 75% of pts: neutropenia (46%), thrombocytopenia (17%), anemia (12%) and infections (12%) were most common. AEs leading to Len dose reduction/interruption occurred in 31%/52% of pts. One Grade 5 AE was reported (septic shock after PD in pt receiving subsequent therapy). RP2D: Pola 1.4mg/kg + Len 20mg. Preliminary efficacy data suggest high activity (Table). Median PFS not reached (median follow-up duration 8.95mo; efficacy-evaluable population [EEP]). Conclusions: The safety profile of Pola-G-Len is consistent with known profiles of the individual drugs. Response rates at EOI with Pola-G-Len are promising, with high CR compared with available R/R FL treatments. Responses at EOI (EEP; RP2D; N=18). Clinical trial information: NCT02600897. [Table: see text]
Final analysis from RESONATE: Six-year follow-up in patients (pts) with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) on ibrutinib.
Authors: Barr Paul M. , Munir Talha , Brown Jennifer R. , O'Brien Susan Mary , Barrientos Jacqueline Claudia , Reddy Nishitha M. , Coutre Steven , Tam Constantine Si Lun , Mulligan Stephen P. , Jäger Ulrich , Kipps Thomas J. , Moreno Carol , Montillo Marco , Burger Jan Andreas , Byrd John C. , Hillmen Peter , Dai Sandra , Szoke Anita , Dean James P. , Woyach Jennifer Ann 
Published: March 2020

7510 Background: Ibrutinib (ibr), a first-in-class, once-daily Bruton’s tyrosine kinase inhibitor, has redefined treatment paradigms for CLL/SLL. We report final analysis with up to 6 years of follow-up on ibr from the phase 3 RESONATE study of single-agent ibr vs ofatumumab (ofa) in pts with relapsed/refractory (R/R) CLL/SLL. Methods: Pts were randomized to receive oral ibr 420 mg daily until PD or intravenous ofa for up to 24 weeks. Long-term efficacy endpoints were investigator-assessed. Results: Among 391 pts randomized to receive ibr (n=195) or ofa (n=196), 86% and 79%, respectively, were in the genomic high-risk population (del(17p), del(11q), TP53 mutation, and/or unmutated IGHV). At final analysis, median follow-up was 64 mo (range, 0.3-72) on ibr. Of pts randomized to ofa, 68% crossed over to receive ibr. Significant sustained PFS benefit was observed with ibr vs ofa, with median PFS 44.1 vs 8.1 mo (HR 0.15; 95% CI 0.11-0.20; P˂0.0001) and was consistent across baseline subgroups. Median PFS in genomic high-risk population was 44.1 vs 8.0 mo on ibr vs ofa (HR 0.11; 95% CI 0.08-0.15). ORR with ibr was 88% (CR/CRi in 11%). Initial ibr treatment conferred better OS than ofa when censored for crossover (HR 0.64; 95% CI 0.42-0.98). Median duration of ibr was 41 mo (range 0.2-71); 41% of pts received ibr >4 yrs. AE profile with ibr remained consistent with prior reports. Cumulatively during long-term ibr therapy, all-grade (grade ≥3) hypertension and atrial fibrillation occurred in 21% (9%) and 12% (6%) of pts, respectively; major hemorrhage occurred in 10%. Most common reasons for ibr discontinuation (DC) prior to study closure were PD (37%) and AEs (16%); DC due to AEs occurred in 6%, 3%, 4%, 4%, 6% and 4% of pts during yrs 0-1, 1-2, 2-3, 3-4, 4-5 and 5-6, respectively. Conclusions: With up to 6 years of follow-up, extended ibr treatment showed sustained efficacy in pts with R/R CLL, including in pts with high-risk genomic features. Safety remained acceptable with low rates of DC due to AEs, and with no new safety signals over long-term therapy. These results establish long-term benefit and tolerability for continuous ibr treatment in pts with R/R CLL. Clinical trial information: NCT01578707.
Hematopoietic recovery and immune reconstitution after axi-cel CAR T-cell therapy in patients with relapsed/refractory large B-cell lymphoma.
Authors: Strati Paolo , Adkins Sherry , Nastoupil Loretta J. , Westin Jason , Hagemeister Fredrick B. , Fowler Nathan Hale , Lee Hun Ju , Fayad Luis , Samaniego Felipe , Ahmed Sairah , Varma Ankur , Arafat Sara , Johncy Swapna , Kebriaei Partow , Mulanovich Victor , Ariza-Heredia Ella , Neelapu Sattva Swarup 
Published: March 2020

7545 Background: Cytopenia lasting beyond 30 days has been observed after CAR T cell therapy. Here, we describe the hematopoietic recovery and immune reconstitution following axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory large B-cell lymphoma. Methods: Patients with available complete blood counts 30 days after axi-cel infusion were eligible for the analysis. Results: Of 31 patients treated on ZUMA-1 (=24) and ZUMA-9 (=7) trials at our institution, grade ≥3 cytopenias were observed in 15 (48%) patients at day 30 (d30), represented by neutropenia in 9 (29%), anemia in 5 (16%), and thrombocytopenia in 13 (42%). Baseline (d-5) characteristics associated with d30 grade ≥3 cytopenia on univariate analysis were ECOG performance status >0 (60% vs 19%, p=0.03) and >3 prior therapies (67% vs 25%, p=0.03). While on study, patients with d30 grade ≥3 cytopenia had a significantly higher need for intravenous immunoglobulins (Ig) (67% vs 25%, p=0.03) and platelet transfusion (73% vs 25%, p=0.01). No significant association was observed between d30 grade ≥3 cytopenia and subsequent grade ≥3 infections (27% vs 31%, p=1), need for growth factor support (both 100%), red blood cell transfusions or diagnosis of myelodysplastic syndromes. At a median follow-up of 2.7 years, a trend for a higher 3-year PFS was observed for patients with d30 grade ≥3 cytopenia (63% vs 35%, p=0.18). Among patients with ongoing response at most recent follow-up, resolution of grade ≥3 cytopenia was observed in 75% of patients at 1 year and 86% at 2 years; recovery in CD4, CD8, CD56, CD19, and IgG was observed in 63%, 100%, 100%, 29%, and 58% of patients at 1 year, and 86%, 100%, 100%, 25% and 50% of patients at 2 years. Among patients with d30 cytopenia, a significant correlation was observed between platelet count and CD56 count (r=+0.64, p<0.001). Conclusions: Grade > 3 cytopenias are common after axi-cel therapy, but resolve in most patients by 1 year. Recovery of CD4 T cells appears to be delayed beyond 1 year in 1/3 of the patients, highlighting the need for prolonged prophylaxis for opportunistic infections.
E3A06: Randomized phase III trial of lenalidomide versus observation alone in patients with asymptomatic high-risk smoldering multiple myeloma.
Authors: Lonial Sagar , Jacobus Susanna J. , Weiss Matthias , Kumar Shaji , Orlowski Robert Z. , Kaufman Jonathan L. , Yacoub Abdulraheem , Buadi Francis , O'Brien Timothy E. , Matous Jeffrey , Anderson Daniel M. , Emmons Robert , Dhodapkar Madhav V. , Wagner Lynne I. , Rajkumar S. Vincent 
Published: March 2020

8001 Background: Smoldering multiple myeloma (SMM) is a precursor to myeloma, wherein current standard of care is observation (obs). Data from a randomized Spanish trial (Mateos et al, NEJM 2015) suggest that lenalidomide(len)/dexamethasone improves time to developing myeloma (TTP) and overall survival (OS) for patients (pts) with high risk (HR) SMM over obs. However, pts were not screened with advanced imaging techniques, used a HR definition that is not routinely available, and combination therapy limited the ability to isolate the effect of len, and thus has not become standard of care. Methods: E3A06 is a randomized phase III intergroup trial, testing the effect of single agent len compared with obs for pts with intermediate or high risk SMM. In an initial phase II run in all pts received len to demonstrate safety. Eligibility required ≥10% PCs and abnormal serum FLC ratio (<0.26 or >1.65). The primary endpoint was progression PFS was estimated by the Kaplan-Meier method and compared using the one-sided stratified log-rank test. Results: PII enrolled 44 pts and PIII randomized 182 pts to either len (n=90) or obs (n=92) [stratified on time since SMM diagnosis ≤1y vs >1y]. Baseline characteristics were similar between the arms. 80% (PII) and 51% (PIII) are off len, primarily due to adverse events (AE) or pt withdrawal. Among the len treated pts, G3/4 non-hematologic AE occurred in 28% of PIII pts with fatigue being most common (n=5). G4 hematologic AE rate was 5.7%, primarily neutropenia (n=4). 3-year cumulative incidence of invasive SPMs was 5.2% (len) and 3.5% (obs). Overall response rate was 47.7% for the phase II study, and in phase III, 48.9% for the len arm, and 0% for the obs arm. Median follow up was 71 months (PII), and 28 months (PIII). 3-year PFS was 87% for the PII cohort. One, 2 and 3-year PFS was 98%, 93%, and 91% for len, and 89%, 76%, and 66% for the obs arm (HR 0.28, p=0.0005) favoring the len arm. No difference in QOL score was noted between arms. Conclusions: Overall, this trial represents the largest randomized trial in SMM to date. In conjunction with the Spanish data, this trial may support a change in clinical practice. Clinical trial information: NCT01169337. [Table: see text]