bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment response monitoring in chronic phase CML (CP-CML) patients receiving tyrosine kinase inhibitor (TKI) therapy in US Oncology network.
Authors: Kolibaba Kathryn S. , Chung Hsing-wen , Dhanda Rahul , Rembert Debra , Lustgarten Stephanie , Marantz Jing L. , Huang Hui 
Published: March 2020

7065 Background: To identify pts with TKI resistance in a timely manner, the National Comprehensive Cancer Network (NCCN) guidelines recommend monitoring pts at specific time points. We evaluated the relationship between NCCN guidelines and current treatment response monitoring patterns and outcomes of CP-CML pts in community practice. Methods: A retrospective longitudinal cohort study was conducted on newly diagnosed CP-CML pts initiating TKI therapy from Jan 1, 2008 to Dec 31, 2010. Data was extracted from the MSH/USON iKnowMed electronic health record database and chart reviews through Jul 31, 2012. Pts were stratified by presence of any cytogenetic monitoring by 12 mos or any molecular monitoring by 18 mos. Results: Of the 410 pts identified, 91% received imatinib and 9% received dasatinib/nilotinib. Median follow-up was 28 mos. Cytogenetic and molecular monitoring did not occur in 69% and 27% of pts, respectively. BCR-ABL mutation testing occurred in 10% of pts who were monitored for response. Pts ≥65 yrs old (vs <65 yrs, p<0.01), with public insurance (vs private insurance, p<0.001), or with Karnofsky Score ≤80 (vs >80, p<0.05) were less likely to have cytogenetic monitoring. Similar differences for age (p<0.05) and insurance (p<0.001) were seen for molecular monitoring. For pts with available monitoring results, 36% had complete cytogenetic response by 12 mos, and 59% had major molecular response by 18 mos. 4-yr overall survival (OS) rates were higher in pts with cytogenetic (98% vs. 89%, P=0.0003) or molecular (95% vs. 82%, P≤0.0001) monitoring vs. those with no monitoring. Conclusions: In these CP-CML pts, 69% did not receive any cytogenetic monitoring by 12 mos and 27% did not receive any molecular monitoring by 18 mos. Obstacles related to monitoring may include age, payer status, and performance status. Pts that were monitored for cytogenetic and molecular responses had significantly higher OS rates at 4 yrs. Increasing the proportion of pts that are monitored according to NCCN guidelines in the community setting could improve patient outcomes.
Do quality of life and physical function at diagnosis predict short-term outcomes during intensive chemotherapy in acute myeloid leukemia patients?
Authors: Timilshina Narhari , Breunis Henriette , Brandwein Joseph , Minden Mark D. , Gupta Vikas , Li Madeline , Tomlinson George A. , Buckstein Rena , Alibhai Shabbir M.H. 
Published: March 2020

7067 Background: Intensive chemotherapy (IC) used to treat acute myeloid leukemia (AML) is associated with multiple short-term toxicities including mortality, particularly in older adults. Emerging data suggest that baseline quality of life (QOL) assessment and/or objective physical function tests may predict outcomes in oncology, although there are no data in AML patients. We investigated the association between baseline QOL and physical function with short-term treatment outcomes in adult and elderly AML patients. Methods: We conducted a prospective, longitudinal study of adult (age 18+) AML patients undergoing IC. Prior to starting IC, patients completed the EORTC QLQ-C30 and FACT-Fatigue in addition to physical function tests (grip strength, timed chair stands, and 2-minute walk test). Outcomes included 60-day mortality, intensive care unit (ICU) admission, and achievement of complete remission (CR). Univariate and multivariable logistic regression were performed to evaluate each outcome. Results: Of the 243 patients (median age 57.5 y), 56.7% were male and median Charlson comorbidity score was 0. 60-day mortality, ICU admission, and CR occurred in 9 (3.4%), 15 (6.2%), and 171 (70.4%), respectively. In univariate regressions, neither QOL nor physical function tests were predictive of 60-day mortality (all P>0.05), whereas cytogenetic risk group (P=0.04), ICU admission (P=<0.001), and remission status at 30 days (P=0.006) were. Fatigue was a significant predictor of ICU admission (p=0.02) whereas QOL and baseline physical function were not significant predictors. In univariate analyses, higher Charlson score was found to be a significant predictor of both ICU admission (P=0.01) and remission status at 30 days (P=0.002). Cytogenetic risk group was correlated with achievement of CR whereas neither QOL nor physical function were predictive (all P>0.05). Findings were similar when the subset of 96 elderly patients (age 60+) were examined. Conclusions: Baseline QOL and physical function tests in this prospective study were not associated with short-term mortality, ICU admission, or achievement of CR after the 1st cycle of chemotherapy.
Result of APL treatment associated with more experience of centers and more treatment as consolidation.
Authors: Ghavamzadeh Ardeshir , Alimoghaddam Kamran , Jalili Mahdi , Rostami Shahrbano , Ghaffari Seyed Hamidolah , Jahani Mohammad , Mousavi Seyed Asadollah , Bahar Babak , Vaezi Mohammad , Esfandbod Mohsen 
Published: March 2020

7069 Background: The first line therapy strategy remains controversial in acute promyelocytic leukemia (APL) patients. Arsenic trioxide (AS2O3) approved in relapsed or resistance patients and recently studies reveals benefits of AS2O3in first line therapy. Regardless of these, important challenges are early mortality during remission induction and post treatment relapse. Methods: Between 2000 and 2012, patients suffered APL whose was new case and confirmed by t(15;17) translocation with RT-PCR, enrolled in study. Until 2007, patients received 28 days AS2O3(0.15 mg/kg iv) as induction and after 28 days rest, treatment continued for 2 courses of consolidation therapy with the same dose and after 2007, two additional consolidation courses, one and two year after start treatment, was added for prevent post treatment relapse. At beginning of 2nd and 3th consolidation, consider CSF cytology and RT-PCR for detection of APL cells and weekly CNS prophylaxis by MTX and cytarabine, IT chemotherapy start if needed. Patients received no other treatment. Results: Totally 271 patients enrolled in study. Ninety six patients received 3 dose and 175 patients received 5 dose of AS2O3. Fifty four (20%) patients died during remission induction before achieve remission. In recent years, early mortality rate reduced below 10% compared with more than 24% in the early years. With median follow-up of 30 months, 170 (78.4%) patients among 217 patients (whose survived after successful induction therapy) were alive (mortality rate: 21.6%) and 2.5-year overall survival and leukemia free survival was 85% and 73% respectively. The cumulative incidence of relapse in group which received three courses of AS2O3 and group which received five courses of AS2O3was 41.5% and 12.6%, respectively (95%CI: 2.5-9.6, P-value=0.0001). Conclusions: Currently according recent studies, AS2O3 has been considered as first line therapy in APL patients but either early mortality or post treatment relapse remain challengeable factors which affect treatment result. Expedite the referral of patients and improvement of emergencies care can reduce early mortality. The next step might be in order to achieve best treatment strategy for reduce post treatment relapse.
Preliminary safety and efficacy of IPI-145, a potent inhibitor of phosphoinositide-3-kinase-δ,γ, in patients with relapsed/refractory CLL.
Authors: Patel Manish R. , Kahl Brad S. , Horwitz Steven M. , Younes Anas , Foss Francine M. , Oki Yasuhiro , Sweeney Jennifer , Allen Kerstin , Faia Kerrie , Kelly Patrick Francis , Flinn Ian 
Published: March 2020

7070 Background: Phosphoinositide-3-kinases (PI3Ks) are pivotal in cell signaling and regulate a variety of cellular functions relevant to oncogenesis. IPI-145, a potent oral inhibitor of the PI3KEδ and PI3K-γ isoforms, is in clinical development for patients (pts) with hematologic malignancies. Early results in pts with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) from an ongoing Phase I study are reported here. Methods: This dose-escalation study evaluates the safety, maximum tolerated dose (MTD), clinical activity, and pharmacokinetics (PK) of IPI-145. Expansion cohorts (EC) < MTD are allowed. IPI-145 is given orally twice daily (BID) in 28-day cycles. Tumor response is based on modified IWCLL guidelines criteria. Results: 55 pts have been dosed with IPI-145. PK, available through 50 mg BID, are linear with continuous 24 hr inhibition of pAKT (Ser473) in primary pt CLL cells after a single dose of 25 mg. In the 16 pts with CLL (5 pts in dose escalation < 25 mg BID and 11 pts in a 25 mg BID EC), the median [range] number of cycles was 2.7 [1–14] and 81% remain on study. Treatment-related adverse events (TRAEs) occurred in 10 (63%) pts with CLL, a similar incidence as seen in the total study population (56%). The most common > Grade 3 TRAE in pts with CLL was neutropenia (25%). No > Grade 3 ALT elevations occurred in pts with CLL. Among evaluable pts with CLL (n=11), 82% (n=9) had a PR or nodal response after 2 cycles of IPI-145, with a best response to date of 6 PR, 4 SD (all nodal responses), and 1 PD. Conclusions: IPI-145 appeared well tolerated and has shown clinical activity at the doses examined in pts with relapsed/refractory advanced CLL. The single agent MTD has not been determined and dose escalation continues. Updated safety and efficacy data from pts with CLL enrolled in dose escalation and ECs evaluating 25 mg BID and a higher dose (<MTD) of IPIE145 will be presented. Clinical trial information: NCT01476657.
Phase I study of NRC-an-019, a tyrosine kinase inhibitor, in imatinib-resistant chronic myeloid leukemia (CML) in an Indian tertiary care hospital.
Authors: Digumarti Raghunadharao , Myneni Praveen Chowdary , Gogula Venkata Ramana , Uppalapati Srihari , Jiwatani Sangeeta Premchand 
Published: March 2020

7080 Background: NRC-AN-019 is an orally administered tyrosine kinase inhibitor (TKI) of the Bcr-Abl protein-tyrosine kinase. The drug was given to patients as a ready-to-use liquid formulation. Methods: The primary objectives of the Phase-I study were to estimate the Dose Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD) of NRC-AN-019 and also to establish the safe dose for Phase II clinical trial. The secondary objectives were to study the pharmacokinetic properties and antileukemic activity of NRC-AN-019. Philadelphia positive CML patients in all phases, in the age group of 18-65 years were eligible. They had to be resistant or intolerant to Imatinib, with ECOG ≤ 2. Dosing was initiated at 50 mg/day and dose escalation was done in increments of 50 mg per each additional cohort. The maximum dose administered was 450 mg/day. The protocol-specific study duration was 30 days; patients continued to receive the study drug subsequently based on Investigator’s decision. Results: A total of 30 patients were enrolled (3 at 50 mg, 4 at 100 mg, 3 at 150 mg, 3 at 200 mg, 4 at 250 mg, 4 at 300 mg, 3 at 350 mg, 3 at 400 mg, and 3 at 450 mg). DLT was not observed and MTD was not reached. The recommended Phase II-A dose is 300 mg/day, with a scope for escalation up to 450 mg/day. The maximum plasma concentration of NRC-AN-019 was 9,342 ng/mL and AUC was 1,262,191 ng.hr/mL. Common adverse events were skin rash, nausea, and vomiting. Hematological response was observed in 11 patients, cytogenetic response in 7 patients and molecular response in 5 patients. The maximum duration a patient has been on NRC-AN-019 is 863 days. Conclusions: Based on the Phase-I data, NRC-AN-019 showed considerable safety and response; it could be a potential treatment option for imatinib-resistant CML. Clinical trial information: CTRI/2009/091/000204.
Clinical features and outcome of T-cell acute lymphoblastic leukemia in patients older than 9 years: A single center experience of 110 patients from AIIMS, New Delhi, India.
Authors: Cyriac Sunu Lazar , Biswas Bivas , Bakhshi Sameer , Sharma Atul , Gupta Ritu , Kumar Lalit , Kumar Rajive , Raina Vinod 
Published: March 2020

7081 Background: It is known that T cell acute lymphoblastic leukemias (ALL) have poorer outcomes than their B cell counterparts. Data on T-ALL in the age group of >9 years from India is minimal. Methods: This is a single institutional analysis of patients of above 9 years who were treated from January 2000 to December 2010. All patients who completed at least 4 weeks of induction therapy were analysed for various outcomes. Results: T-ALL formed 30% of all ALL in this age group. Of the 110 newly registered patients of T-ALL, the median age was 17 years (Range 10-50 years) with an M:F ratio of 5.9:1. Of this 62%, 30% and 18% patients belonged to 10-18, 19-30 and > 31 years age group respectively. Eighteen (19%) and 2 (2%) and 33 (30%) had CSF, testicular and other extramedullary sites involvement respectively. Twenty eight per cent had a total leucocyte count (TLC) of above 100x109/L. Patients available for survival analysis were 104(94.5%). Complete remission (CR)rate was 68.2% and induction mortality was 14.4%. At a median follow up of 56.4 months 5 year leukemia free survival was 52.3% (median not attained). Twenty seven (38%) patients relapsed (median relapse time of 15.2 months, range 0.7 to 47.3 months), 55% during maintenance phase. The 5 year overall survival (OS) was 46.9% (median OS of 35.4 months). The 5 year OS of 10-18, 19-30 and > 31 years age groups were 42.8%, 71% and 16.6% respectively (p value not significant). Not attaining CR in 1st induction, spontaneous tumor lysis syndrome and peripheral blood blast count of > 80% were significant poor prognostic factors for survival. Conclusions: This is one of the largest study of T-ALL outcomes in patients above 9 years from a single center from India. Attainment of CR in 1st induction was the most important risk factor for survival. 5 year OS was 47%.
Prognostic impact of trisomy 8 cytogenetic abnormality in acute myelogenous leukemia: Analysis of a large cohort (N=2187) of newly diagnosed patients.
Authors: Borthakur Gautam , Arana Yi Cecilia Ysabel , Cortes Jorge E. , Qiao Wei , Kadia Tapan M. , Ravandi Farhad , Faderl Stefan , Garcia-Manero Guillermo , Brandt Mark , Kantarjian Hagop M. 
Published: March 2020

7089 Background: Trisomy 8 is grouped as intermediate risk in cytogenetic (CG) classifications of acute myelogenous leukemia (AML). In a multi-variate analysis of MRC data, trisomy 8 was associated with worse overall survival (OS). Methods: Between years 1993-2012, 2,187 patients (pts) with newly diagnosed AML presented at MD Anderson Cancer Center and 21 (10%) were with a trisomy 8 CG abnormality. The median age of trisomy 8 pts was 63 years (range, 17-89 years) and 59% were males. Sixty four (30%) had isolated trisomy 8, 45 (21%) had trisomy 8 +≤2 additional cytogenetic abnormalities and 102 (49%) had trisomy 8 + ≥3 additional abnormalities. Thirty three percent of pts with trisomy 8+≤2 additional abnormalities, had secondary AML compared to 21% of diploid CG (p=.007). Mutations in the FLT3 gene was seen in 9% and N or KRAS gene in 8%. Results: The overall remission rate (RR) was 47%, 53% and 43% among pts with trisomy 8 alone, trisomy 8+≤2 and trisomy 8+≥3 abnormalities respectively. Among pts <60 years of age and with trisomy 8 + ≤2 abnormalities, RR was 71% and the same was 77% for pts with diploid CG. For pts ≥ 60 years, the RRs were 26% and 57% respectively. Among pts ≥ 60 years and trisomy 8 with complex CG (≥3 additional abnormalities) the RR was 38% and that for patients with complex (non-trisomy 8) CG was 41%. Patients with trisomy 8 either alone or ≤2 additional abnormalities had a shorter OS (p= .04 and .05 respectively, median 10.8 and 8.6 months vs 16.5 months) compared to those with diploid CG. Event free survival was also shorter among patient with isolated trisomy 8 versus those with diploid CG (p=.008, median 2.9 versus 7.5 months). On the other hand, patients with trisomy 8+≥3 abnormalities had outcomes comparable to non-trisomy 8 CG group. Conclusions: Non-complex CG trisomy 8 is associated with worse clinical outcome in patients with AML than those with diploid CG and its inclusion in intermediate risk group may need reconsideration. The most adverse impact appears to be from lower RR among patients with trisomy 8+≤2 additional abnormalities and ≥60 years of age.
Incidence and outcomes of chronic myeloid leukemia (CML) patients (pts) treated with second-generation tyrosine kinase inhibitors (TKI) who develop other chromosomal abnormalities (OCA).
Authors: Pemmaraju Naveen , Kantarjian Hagop M. , Jabbour Elias , Quintas-Cardama Alfonso , Borthakur Gautam , Burton Elizabeth M , Dellasala Sara , Pierce Sherry , Kornblau Steven Mitchell , Verstovsek Srdan , O'Brien Susan Mary , Cortes Jorge E. 
Published: March 2020

7090 Background: Development of OCA has been reported among pts receiving imatinib as initial therapy for CML. Little is known about OCA development in CML pts treated with frontline 2nd generation TKI (dasatinib, nilotinib). Methods: OCA is defined as cytogenetic abnormality in non-Philadelphia chromosome positive clones as pts respond to TKI. Among pts treated with frontline dasatinib (n=99) or nilotinib (n=117), on parallel prospective single-arm phase II protocols at MDACC, 30 OCA ptswere identified, chronic (n=25) or accelerated phase (AP) (n=5). Results: 11 (11%) pts treated with dasatinib and 19 (16%) with nilotinib developed OCA; median follow-up 30 mo (range 0-71). Difference in OCA incidence with dasatinib and nilotinib was not statistically significant. At start of therapy, median age (years) of OCA pts was 53 (41-71) with dasatinib and 52 (37-82) with nilotinib, compared to those pts without OCA: 48 (18-83) with dasatinib and 49 (17-87) with nilotinib. Most common OCA was abnormality of chromosome 7 with 6 occurrences in 5 pts (1 pt with both inv(7) and +7) (inversion (n=1), 2 different translocations (n=2), deletions (n=2), and additions (n=1)). No pts developed trisomy 8 (historically most common OCA in imatinib-treated pts). Median time to first OCA: 9 mo (range 3-58) for all pts (12 mo (range 3-58) for dasatinib group and 9 mo (3-48) for nilotinib group). OCA disappeared spontaneously in 25 pts during follow-up. Outcomes for OCA versus non-OCA group (Table). For AP pts: 3/6 (50%) in dasatinib group and 2/17 (12%) in nilotinib group developed OCA. None of the OCA pts has developed AML or MDS. Conclusions: OCA is observed in 10-15% of pts receiving initial therapy with 2nd generation TKI. At median follow-up of 30 mo, occurrence of OCA confers no adverse impact on outcomes when compared to non-OCA pts treated with 2nd generation TKI and has not resulted in other hematologic disorders. [Table: see text]
Phase I/II study of the combination of inotuzumab ozogamicin (CMC-544) with low-intensity chemotherapy in patients (pts) with acute lymphoblastic leukemia (ALL).
Authors: Jain Nitin , O'Brien Susan Mary , Thomas Deborah A. , Jabbour Elias , Faderl Stefan , York Sergernne , Kantarjian Hagop M. 
Published: March 2020

7092 Background: Older pts with ALL have a significantly worse outcome. This is primarily due to poor tolerance of intensive chemotherapy which results in ineffective delivery of induction-consolidation-maintenance chemotherapy. Addition of targeted non-myelosuppressive therapy to effective low-intensity chemotherapy might improve outcome. CD22 expression occurs in >90% of pts with ALL. Inotuzumab ozogamicin (IO) is a CD22 monoclonal antibody bound to a toxin, calecheamicin, and has shown single-agent activity in relapsed/refractory ALL (Kantarjian, Lancet Oncology 2012). Methods: Pts ≥60 years (yrs) with newly-diagnosed B-cell ALL were eligible. The chemotherapy was low-intensity hyper-CVAD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, ara-C at 0.5 g/m2 x 4 doses). Rituximab and intrathecal chemotherapy were given for first 4 courses. IO was given on day 3 of each of the first 4 courses. First 6 pts received 1.3 mg/m2 for cycle 1 followed by 0.8 mg/m2 for subsequent cycles; pts 7 onwards received 1.8 mg/m2 for cycle 1 followed by 1.3 mg/m2 for subsequent cycles. Results: Eleven pts (7 men, 4 women) have been treated so far. Median age is 70 yrs (range 60-79). Median follow-up is 8.2 months (mos). Grade 3-4 non-hematological toxicity included 2 pts with grade 3 LFT elevation. Seven pts had one or more infections. No dose-limiting toxicity was observed. Ten of 11 pts (91%) achieved complete remission (CR). All pts achieving CR have also achieved flow-cytometric MRD negative status and continue to be on study in CR anywhere from 1.0 to 12.4 mos. There have been no relapses. One patient did not achieve CR and died 2 mos later after receiving a salvage regimen. This is the only death on the study. Six-month disease-free and overall survival are 90% and 90%, respectively. Conclusions: Combination of IO with low-intensity chemotherapy is safe and shows very encouraging results (91% CR) in the frontline setting in elderly pts with ALL. These results appear to be better than those achieved with chemotherapy only approach and may become the new standard of care for frontline treatment of elderly pts with ALL. Clinical trial information: NCT01371630.
Body mass index impact on acute myeloid leukemia (AML) outcomes.
Authors: Elkhanany Ahmed , Keane Niamh , Hashmi Sharukh , Begna Kebede , Pruthi Rajiv , Hogan William J. , Liu Shujun , Litzow Mark Robert , Al-Kali Aref 
Published: March 2020

7094 Background: Obesity is associated with comorbidities that could cause negative outcome upon delivering intensive care. In pediatric AML patients (pts), obesity was associated with more toxicity and worse prognosis. Here, we study Body-Mass Index (BMI) impact on clinical outcome of adult AML pts. Methods: A total of 180 adult pts with AML between 2003-2011 were enrolled. Retrospective data included demographics, labs, cytogenetics and outcome. LeukemiaNET Standardization (LNS), complete remission (CR), overall survival (OS) and relapse free survival (RFS) were obtained (Dohner E, Blood 2010). BMI of 25-30 was defined as overweight, while >30 as obesity. Fischer’s and Wilcoxon tests were used for comparatives between groups, cox proportional hazards and logistic regression for associations for OS/RFS and CR, Kaplan-Meier test for OS and RFS estimates via JMP software V9.0. IRB approval was obtained according to Helsinki declaration. Results: The median age was 63 years, with 115 (64%) were men. Of 159 pts, karyotype was favorable, Intermediate I, II and adverse in 21 (13%), 76 (48%), 23 (%14) and 39 (25%) pts respectively. Median BMI was 28.2 (range 16.8-47.8). 48 (26%) had normal BMI, 62 (34%) were overweight, and 70 (38%) were obese. At diagnosis, BMI classes were not associated with age, sex, glucose, white blood count (WBC), platelets, blasts, ECOG status, LNS, FLT3/NPM1 status; nor treatment toxicities, CR rates, or relapse after CR. BMI classes were associated with presence of concomitant comorbidities (p=0.047) and glucose levels (p=0.044). In univariate analysis, overweight (OR=1.8, p=0.16) and obesity (OR=1.9, p=0.13) did not affect CR rates. On adjusting for age, sex, LNS, WBC and blast count at diagnosis, only overweight pts had a significant higher CR (76% vs 63%) rates (OR=2.99, p=0.043). OS and RFS were not associated with BMI in univariate (p=0.51) and multivariate (p=0.32) models. Median OS and RFS were not different across BMI subgroups (p=0.52 and 0.59). Conclusions: BMI subgroups showed no correlation with treatment toxicity, LNS, relapse rates, OS or RFS. This should encourage giving therapy to pts regardless of their BMI status. Overweight was associated with better CR rates despite increased concomitant morbidities.