bluuebunny/crossref_metadata_2025 huggingface dataset:
Hematopoietic cell transplant comorbidity index (HCT-CI) to assess AML induction risk.
Authors: Schoen Martin W. , Mohammed Kahee A. , Freter Carl , Lionberger Jack M
Published: September 2018

e18519

Background: Induction therapy for acute myeloid leukemia (AML) is intense and methods for risk appraisal of therapy are controversial. Formal comorbidity assessment may allow for improved prognostication in addition to age. The HCT-CI(+/-Age) was developed to inform risk of patients undergoing stem cell transplant, and has found use in predicting early outcomes in AML induction. We applied HCT-CI retrospectively to our experience to analyze the predictive power regarding patient survival during induction. Methods: 140 cases induced with idarubicin and cytarabine (IA) or IA plus cladribine (IAC) between Jan 2008 and Sept 2015. HCT-CI (+/- Age) was derived from information available prior to chemotherapy and NCCN Leukemia Risk were calculated. Death prior to discharge from the initial induction hospitalization was the primary outcome for logistic regression. Results: 107 patients received IAC and 33 IA with mean age of 57 and 66 years respectively (p<0.01). Regimen did not predict death (p=0.27). Median age was 61 (range 20-86) with mean scores of 2.0±0.2 (HCT-CI) and 2.9±0.2 (HCT-CI+Age). In univariate analysis HCT-CI (+/-Age) predicted death during induction. In multivariate analyses, when HCT-CI (+/-Age) was adjusted for (NCCN risk and regimen) or (age and regimen) predictive power was maintained (Table). Conclusions: These data suggest that HCT-CI predicts death during induction of AML and age did not augment prediction, up to age 70. We conclude that HCT-CI(+/-Age) may be a more useful tool than age alone or clinical instinct to help patients and providers make difficult decisions about therapy. [Table: see text]
Phase I study of lurbinectedin (PM11083) in patients with advanced AML and MDS.
Authors: Benton Christopher Brent , Rodriguez Diaz -Pavon Jose , Maiti Abhishek , Daver Naval Guastad , Ravandi Farhad , Jain Nitin , Alvarado Yesid , Jabbour Elias , Pierce Sherry , Kwari Monica , Santos Margarida A , Martinez Sara , Siguero Mariano , Tefferi Ayalew , Cortes Jorge E. , Kantarjian Hagop M. , Pardanani Animesh Dev , Garcia-Manero Guillermo
Published: September 2018

e18521

Background: The FDA-approved drug trabectedin is a DNA minor groove binder (MGB) with activity against translocation-associated sarcomas. Lurbinectedin is a next-generation MGB, with activity against myeloid leukemia cells. A phase I clinical trial was initiated to determine recommended doses in MDS/AML. Further assessment of its safety, tolerability, and pharmacogenetics were studied. Methods: In total, 42 patients with relapsed/refractory MDS/AML received lurbinectedin, using a 3+3 study design. It was administered as a 1-hour IV infusion first at 3.5, 5, 6, and 7mg per dose on days 1 and 8. Subsequently, it was administered on days 1, 2, and 3, using 1, 1.5, 2, or 3mg per dose per patient. Results: Three patients had dose-limiting toxicities (DLTs), which were rhabdomyolysis (up to gr 4), hyperbilirubinemia (gr 3), and oral herpes (gr 3). All DLTs occurred in the 6 and 7mg cohorts. Adverse events included febrile neutropenia/infections (n = 3), GI (n = 6) and pulmonary (n = 2) toxicity, hyperhidrosis (n = 1), and QT prolongation (n = 1). Overall, 33 of 42 patients (79%) had reduction of blasts in peripheral blood (PB) or bone marrow (BM) at nadir, including 23 (55%) with > 50% reduction in PB blasts alone (n = 18) or both BM and PB blasts (n = 5). One patient had PR, 2 patients had morphologic leukemia-free survival, and most (n = 30) were discontinued for progressive disease. Early deaths occurred from disease-related causes, not attributable to lurbinectedin. Thirty-two patients treated at MD Anderson were analyzed for clinical characteristics and responses. Notably, among patients with follow-up bone marrow biopsy, those with a cytogenetic abnormality at chromosome 11q21-23 had significantly greater bone marrow blast reduction than those without such abnormality (change in percentage blasts: -31±14% [n = 4] vs. 8±8% [n = 16], respectively; P= 0.04). Conclusions: Lurbinectedin is generally safe and tolerated at dose levels tested. While no sustained remissions > 3 cycles were observed in these highest-risk patients, single-agent lurbinectedin was transiently leukemia suppressive for some patients, including some with abnormal chr11q or TP53 mutation. Rational combinations and situational uses of lurbinectedin are under consideration. Clinical trial information: NCT01314599.
Quality of life of acute myeloid leukemia patients in a real-world setting.
Authors: Pandya Bhavik J. , Hadfield Anna , Medeiros Bruno C. , Wilson Samuel , Bui Cat N. , Bailey Tom , Flanders Scott , Rider Alex , Horvath Laura E.
Published: September 2018

e18525

Background: There is currently limited data on the quality-of-life (QoL) of patients with acute myeloid leukemia (AML) in the real-world setting. The objective of this analysis was to understand the impact of AML on patients receiving first-line treatment vs those who were relapsed/refractory to first-line treatment and therefore on later lines of therapy. Methods: The Adelphi AML Disease-Specific Programme, a real-world, cross-sectional survey involving 61 US hematologists/hemato-oncologists and their consulting AML patients, was conducted between February–May 2015. Physicians provided details on patient demographics and clinical information. Each patient was asked to complete both the EQ-5D-3L and Functional Assessment of Cancer Therapy Leukemia (FACT-Leu). Scores range from −1.09–1 (EQ-5D-3L) and 0–176 (FACT-Leu), where a higher score indicates a better QoL. Data from physician-completed record forms and corresponding patient self-completion forms on a matched sample of 75 patients were analyzed. Results: Of the patients who took part in the survey, 75% (n = 56) were receiving first-line treatment for AML and 25% (n = 19) were relapsed/refractory to first-line treatment and had progressed to later lines of therapy. The first-line patients had a mean age of 56.6 years and an average of 2.1 symptoms whereas the relapsed/refractory patients had a mean age of 56.9 years and an average of 2.4 symptoms, according to the physician. First-line patients may have a directionally better QoL scores than those on later lines of therapy, according to both the EQ-5D (0.75 and 0.71 respectively, P= .51) and the FACT-Leu (103.7 and 92.5 respectively, P= .098) measures. Results from the FACT-Leu-Physical Well-Being sub-domain show that relapsed/refractory patients were significantly more likely than first-line patients to be affected physically by their AML condition (13.0 and 17.6 respectively, P= .005). Conclusions: AML patients who have relapsed or become refractory to first-line treatment report worse QoL than those still on first-line treatments. These observational data shows a need for effective and tolerable treatments that can maintain or improve patients’ QoL, especially for patients with relapsed or refractory disease.
Systematic literature review and indirect treatment comparisons (ITC) of glasdegib (GLAS) plus low dose ara-c (LDAC) versus a hypomethylating agent (HMA) for previously untreated acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy (NIC).
Authors: Forsythe Anna , Arondekar Bhakti , Tremblay Gabriel , Chan Geoffrey , Su Yun
Published: September 2018

e18526

Background: In a randomized phase 2 study, GLAS, an oral, smoothened inhibitor, combined with LDAC, showed significantly better overall survival (OS) vs LDAC alone in previously untreated AML NIC patients. HMAs azacitidine (AZA) and decitabine (DEC) are considered current standard of care in this population. An ITC was conducted to compare OS for GLAS+LDAC vs. AZA and DEC, respectively. Methods: Embase, MEDLINE, Cochrane database, and conference abstracts (ASCO, ESMO and ASH) were systematically searched through 12/2016 for relevant RCTs of GLAS, AZA and DEC in AML patients ineligible for IC. Classical frequentist ITC using the Bucher method was used to indirectly compare OS hazards ratios with 95% confidence intervals (CI) using LDAC as the common comparator. Results: Four studies met inclusion criteria: AZA Fenaux 2010, N (treatment/ comparator) = 14/20, AZA Dombret 2015, N = 241/158, DEC: Kantarjian 2012, N = 242/243, and GLAS+LDAC: Cortes 2016, N = 88/44. Upon review of baseline characteristics, Fenaux 2010 was excluded based on major population differences (% bone marrow blasts). Three studies contributed data to ITC based on comparable populations: age, cytogenic risk and OS of comparator were similar among studies: age 75/73/76 years old, poor cytogenic risk 34%/37%/39%, OS of the comparator 6.4/5.0/4.3 months in AZA/DEC/GLAS+LDAC, respectively. In the ITC, GLAS+LDAC showed significantly better OS HR vs. AZA and DEC (0.51 and 0.56 respectively) (Table). Conclusions: Using ITC, treatment with GLAS+LDAC yielded significantly better OS HR than AZA and DEC in previously untreated AML patients ineligible for treatment with IC. Limitations include mixed IC & NIC population for the AZA trial, and mixed comparator arm of both LDAC and BSC for the DEC trial. Analyses using patient-level data matching baseline characteristics across studies may enable more robust ITC. [Table: see text]
Stroma-free long-term growth of primary acute myeloid leukemia (AML) cells.
Authors: Chen Jing , Ibanez Sanchez Glorymar , Calder Paul , Frattini Mark G.
Published: September 2018

e18535

Background: To individualize therapy for relapsed/refractory AML patients, optimal in-vitro culture conditions to support primary leukemic cells are essential for drug sensitivity testing. Our lab has validated a high throughput chemosensitivity assay with primary AML cells maintained by growth factors (cytokines); however, growth factors have not been shown to support long-term assays of primary AML cells. Stromal cells of the tumor microenvironment are crucial to maintain normal hematopoiesis and leukemic cells and have been shown to support long term in-vitro expansion of primary AML cells. However, there is little information characterizing these growth conditions. The aim of this study was to compare long-term proliferation and phenotypes of primary AML cells with growth factors or stromal support to best determine their utility as a platform for drug sensitivity testing in functional assays. Methods: Patient-derived AML cells were cultured in 96-well plates in: 1) cell culture medium only 2) Human HS5 or HS27 stromal cells 3) HS5 or HS27 stroma-conditioned media or 4) cytokine cocktail. Viability readout by Guava ViaCount and leukemic cell surface phenotypes by fluorescently-conjugated antibodies were performed weekly over 3 weeks. Results: Primary AML cells cultured with only cytokines maintained proliferation at 3 weeks. In comparison, AML cells cultured in HS5 stroma-conditioned medium also maintained proliferation at a similar rate at 3 weeks, while co-culture with HS5 stromal cells demonstrated significantly higher proliferation. Leukemic immunophenotypes were maintained for all growth conditions over 3 weeks. Conclusions: Contrary to known data, primary AML cells with cytokines continued to expand at 3 weeks, at a similar rate to HS5 stroma-conditioned medium, a finding that has not been reported. Consistent with previous studies, we confirmed that stromal cells such as HS5 can provide long-term in-vitro expansion of primary AML cells, which cannot be substituted by stroma-conditioned medium. The ability to maintain long-term expansion of primary AML cells by both cytokines and stromal cells sets up a platform for a direct comparison of high throughput drug sensitivity testing under these growth conditions.
Influence of acute graft-versus-host disease (aGVHD) during allogeneic hematopoietic stem cell transplantation (HSCT) engraftment admission on hospital length of stay (LOS), charges, and costs.
Authors: Yu Jingbo , Parasuraman Shreekant , Shah Anshul , Narayanan Siva
Published: September 2018

e18544

Background: aGVHD is a common complication of allogeneic HSCT and a significant cause of transplant-related morbidity and mortality. Limited data exist on healthcare resource use and costs of aGVHD during HSCT engraftment admission. This study estimated LOS, charges, and costs of aGVHD during HSCT engraftment admission in the US. Methods: Inpatient discharges between 2009-2013 using the Nationwide In-patient Sample (NIS) database were analyzed. NIS is a representative (20% stratified) sample of all discharges from US community hospitals included in the Healthcare Cost and Utilization Project (HCUP). Discharges for allogeneic HSCT engraftment admissions with aGVHD (ICD-9 279.51) were compared with those without GVHD. Costs were calculated from hospital charges using a standard HCUP Charge-to-Cost Ratio. LOS, charges, and costs were compared using Wilcoxon rank sum test. Correlation between LOS and charges or costs was calculated using Pearsons coefficient. Results: 729 discharges with aGVHD and 5958 discharges without GVHD were analyzed. Demographic characteristics were similar for both groups except age: female (40% vs 42%), Caucasian (67% vs 68%), private insurance (60% vs 63%); mean age was 39 and 45 years for patients with and without aGVHD respectively (p < 0.001). In-hospital mortality rate was 16% for patients with aGVHD vs 5% without GVHD (p < 0.001). Despite younger age of the aGVHD group, mean unadjusted LOS was significantly longer, and mean unadjusted charges and costs were significantly higher with aGVHD vs without GVHD (54.2 days vs 29.8 days, $690,244 vs $366,213, $218,425 vs $122,387, respectively). Charges and costs were directly proportional to LOS (r = 0.711, p < 0.001). Conclusions: Overall, occurrence of aGVHD during HSCT engraftment admission resulted in almost doubling of LOS, charges, and costs. Mitigating aGVHD may reduce LOS and subsequent inpatient resource use for HSCT. [Table: see text]
Long term efficacy of nilotinib as front- and second-line therapy in Bosnia and Herzegovina: Real life experience.
Authors: Kozaric Amina Kurtovic , Islamagic Erna , Beslija Semir , Kurtovic Sabira , Mehinovic Lejla , Hasic Azra
Published: September 2018

e18549

Background: In this study we examined the long-term real life clinical outcomes of patients receiving front- line nilotinib and patients who switched from branded or generic imatinib to nilotinib (second-line therapy) in Bosnia and Herzegovina. Methods: Patients in CML-CP (n = 70) who started their TKI treatment in period from June 2005 to August 2016 were included in this multicentre retrospective cohort study. Patients were categorized as: Group 1 (n = 31) contained patients receiving front-line nilotinib (300 mg twice daily) and Group 2 (n = 39) consisted of patients who started with front-line imatinib (Glivec or generic imatinib) and then were switched to nilotinib (400 mg or 600 mg twice daily). Nilotinib became available as front or second-line therapy in March 2011. Standard patients' variables were collected and disease progression was established as loss of CCyR and MMR. Survival probabilities were estimated with the Kaplan-Meier method and compared using the log-rank test. Results: Seventy patients (median age was 54.5 years; 61% was males) were enrolled in this study. The median follow-up was 39 months (range 3-51 months). Median wait period for therapy was 12 months (range 1-62) from diagnosis. In both studied groups, overall survival was 87% at 39 months. According to ITT principle, achievement of CCyR and MMR at 24 months on nilotinib therapy was higher in Group 1 compared to Group 2 (81% vs 67% and 74% vs 49%, respectively). Rate of death was similar in both studied groups (4/31 vs 5/39). In Group 2, five patients who had suboptimal response on front-line imatinib discontinued therapy (median period of 19.5 months) were switched when nilotinib became available. Interestingly, none of these patients died. Conclusions: Our results suggest that at 3 years, there was no difference in the overall suvival between studied groups. However, achievement of CCyR and MMR at 24 months was higher in patients on front-line nilotinib therapy. Patients who waited for therapy had optimal response regardless the wait period on nilotinib therapy.
Early results of lower-dose dasatinib, 50 mg daily, in newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase.
Authors: Naqvi Kiran , Cortes Jorge E. , Skinner Jeffrey A , Jabbour Elias , Pemmaraju Naveen , Borthakur Gautam , Estrov Zeev , Bose Prithviraj , Thompson Philip A. , Kantarjian Hagop M.
Published: September 2018

e18551

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. The approved dose in chronic phase is 100mg orally daily. Notable side effects include pleural effusions and myelosuppression.We evaluated the efficacy and toxicity profile of dasatinib 50mg orally daily in patients with newly diagnosed CML-CP. Methods: Adults with newly diagnosed CML-CP were eligible. Prior TKI therapy for up to 1 month was allowed. Eligibility criteria were standard. Patients received dasatinib 50mg daily. Responses were defined according to the European LeukemiaNet guidelines (Baccarani et al. Blood 2013 122:872-884). Results: From March 2016 until January 2017, 30 patients were enrolled. Median age was 47 years (22 to 84). Sokal risk was low in 17 patients, intermediate in 10, and high in 3. Response data are shown below. Among 7 patients not in CCyR at 3 months by FISH (% FISH + 3, 3.5, 4.5, 5.5, 7, 9 and 83%), the respective BCR-ABL transcripts (IS) were 0.49, 0.08, 0.1, 0.09, 0.60, 0.69 and 9.2%. Thus, 6/7 patients with FISH + disease at 3 months had BCR-ABL transcripts (IS) < 1%, and 17/18 patients evaluable at 3 months had BCR-ABL transcripts (IS) < 1% (equivalent to CCyR). Significant myelosuppression requiring treatment interruption occurred in only 1 patient. No patients so far had pleural effusions requiring intervention. To date, there have been no dose modifications. Conclusions: Dasatinib 50mg daily is active and well-tolerated in newly diagnosed CML-CP. It should be further explored as a new potential dose-schedule standard-of-care in CML. [Table: see text]
Clinical significance of HFE gene mutations in patients with refractory anemia with ring sideroblasts (RARS).
Authors: Nanah Rama , Patnaik Mrinal , Gangat Naseema , Zblewski Darci , He Rong , Nguyen Phuong L. , Elliott Michelle A. , Hogan William J. , Litzow Mark Robert , Al-Kali Aref
Published: September 2018

e18556

Background: RARS is a subtype of myelodysplastic syndromes (MDS) defined by < 5% blasts and ≥15% ring sideroblasts (WHO 2008). Hereditary hemochromatosis is a disorder characterized by dysregulations in iron absorption, largely associated with C282Y and H63D mutations of the HFE gene. Iron levels are elevated in both disorders and pathophysiologic correlations were suggested. HFE gene mutations were previously found higher in MDS compared to controls (50% vs 36%) ( Nearman et al, Am J Hematol 2007). Methods: A total of 168 RARS patients’ data from 1994 to 2015 at Mayo Clinic were reviewed after appropriate IRB approval was obtained. All cases had their bone marrow slides reviewed at our center. We searched patients’ records retrospectively to Identify those tested for HFE gene (C282Y, H62D, S65C) mutations, done inside or outside our institution. Survival estimates were calculated using Kaplan-Meier curves. Results: Out of the 168 RARS patients, only 17 (10%) were tested for HFE gene mutations. Out of the 17 tested, 11 (65%) were found to have mutations; 2 of which (18%) had homozygous H63D mutation, 1 patient (9%) had double heterozygous H63D and C282Y mutations, 5 (45%) had only one H36D heterozygous mutation vs 3 patients (27%) with only one C282Y heterozygous mutation. Only one patient was tested for the additional S65C mutation and it was not detected. H63D mutation was present in a total of 8 patients (73%) vs C282Y mutation which was present in 4 patients (36%). Bone marrow iron stores were increased in all 17 tested patients, except one who had decreased stores, this patient had one heterozygous C282Y mutation. Median overall survival (mOS) was 117 months in the HFE mutated patients vs 75 months in the non-mutated (p = 0.6). Conclusions: Our study found the HFE gene, when tested, to be mutated in higher frequencies among patients with RARS compared to that reported in the general population (65% vs 36%), with H63D mutation in almost three quarters of all mutated patients. Although it did not reach statistical significance, the longer survival observed among HFE mutated patients compared to the wild-type raises the question whether testing for HFE gene mutations among patients with MDS-RARS should be further explored.
Chronic hepatitis C as an adverse prognostic factor in myelodysplastic syndromes.
Authors: Thibaud Santiago , Kaner Justin D. , Shastri Aditi , Budhathoki Anjali , Sridharan Ashwin , Goel Swati , Mantzaris Ioannis , Janakiram Murali , Kornblum Noah Saul , Braunschweig Ira , Verma Amit
Published: September 2018

e18557

Background: Chronic hepatitis C virus (HCV) infection has been associated with hematologic malignancies such as B-cell non-Hodgkin lymphoma. In contrast, there is very little known about the relationship between HCV and myeloid malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). To determine the effect of HCV on MDS/AML clinical outcomes we conducted a retrospective analysis in a large inner city cohort of patients (pts) Methods: 478 pts with MDS and MDS-transformed AML were identified between 1997 and 2016; 13 pts were HCV-positive (HCV+/MDS) and 465 were HCV-negative (HCV-/MDS). Demographics, hematologic parameters, cytogenetics, IPSS-R scores and molecular profiles were compared for both groups (grp). Survival (surv) analysis was done using the Kaplan-Meier method Results: HCV+/MDS had significantly worse surv than HCV-/MDS pts on univariate analysis (UA) (median surv 16 vs 52 months, HR 2.8, 95% CI 1.4-5.5, p < 0.01). Difference remained strongly significant after exclusion of HIV-coinfected pts (HR 2.7, p = 0.02) and pts w/ AML on presentation (HR 3.1, p < 0.01). Cytopenias were worse in HCV+/MDS (mean Hgb level 8.2 vs 9.4 g/dl, p = 0.04; mean plt count 64 vs 139 103/µL, p = 0.03). Average IPSS-R score was higher in HCV+/MDS pts (5.5 vs 3.8, p = 0.02). IDH1 mutation was more prevalent in HCV+/MDS (25% vs 2%, p < 0.01). Differences in age between HCV+/MDS and HCV-/MDS were non-significant (mean 64 vs 69 respectively, p = 0.2). Male-to-female ratio was higher in HCV+/MDS but difference was non-significant (2.3 vs 0.9, p = 0.2). Interestingly, high HCV viral load and cirrhosis did not correlate with poor surv in the HCV+/MDS grp, suggesting deleterious effect occurs even in early stages of HCV infection. Conclusions: Our analysis suggests that chronic HCV infection strongly correlates with worse surv in UA and is associated with lower blood counts and higher IPSS-R scores at the time of diagnosis of MDS. We observed a high rate of MDS refractory to standard therapies and speculate that HCV may affect biology of the disease. Larger studies are warranted to determine the effect of HCV on surv in this population and to provide a rationale for trials of anti-HCV drugs concomitantly with MDS Tx.
Outcome of patients younger than 50 years old diagnosed with myelodysplastic syndromes (MDS): Single institution experience.
Authors: Al-Kali Aref , He Rong , Patnaik Mrinal , Hanna Karen , Viswanatha David , Greipp Patricia T. , Zblewski Darci , Elliott Michelle A. , Litzow Mark Robert , Nguyen Phuong L.
Published: September 2018

e18560

Background: Myelodysplastic syndromes (MDS) are rare hematological neoplasms typically seen in the elderly. Young MDS (yMDS) patients ( < 50 years old) have been reported to comprise between 3-6% in the Surveillance, Epidemiology and End Results (Ma X et al, Cancer 2007; Rollison R et al, Blood 2008) with a better overall survival (OS). Methods: 1012 MDS patients from 1993 to 2015 were found after IRB approval was obtained. All cases had their bone marrow slides reviewed at our institution. yMDS Patients were included as cohort 1, while the rest as cohort 2. Survival estimates were calculated using Kaplan-Meier curves and univariate and multivariate analyses was based on log-rank testing using JMP software version 10. Results: We found 68 (7%) yMDS patients with a median age of 42 years (range, 18-49). Female gender was more common (43% vs 31%, p = 0.05) while platelets were lower in yMDS (61 vs 102, p < 0.0001). Therapy related MDS (t-MDS) was more frequent (33% vs 17%, p = 0.005), as was transformation to acute myeloid leukemia (AML) in yMDS (28 % vs 11%, p = 0.0004). Allogenic hematopoietic cell transplantation (HCT) was more frequent in yMDS (42% vs 4%, p < 0.0001). Survival outcome: Median OS was longer for cohort 1 vs cohort 2 but did not reach statistical significance (43 vs 21 months, p = 0.1). Median progression free survival (PFS) was shorter for cohort 1 vs cohort 2 but also did not reach statistical significance (8 vs 12 months, p = 0.3). Median OS for cohort 1 based on R-IPSS was 44, 105, 40, 18, and 12 months for very low, low, intermediate, high and very high risk groups, respectively (p = 0.09). Median OS was shorter in t-MDS vs de novo MDS in yMDS (13 vs 47 months, p = 0.04). yMDS patients who transformed to AML had worse median OS (18 vs 93 months, p = 0.001). On multivariate analysis neither t-MDS nor R-IPSS had a statistically significant impact on OS. Conclusions: MDS is rarely diagnosed under the age of 50 with IPSS-R being less powerful in detecting mOS. Among yMDS patients, there was a higher proportion of t-MDS compared to older patients with subsequent higher rates of AML transformation and higher rates of allogeneic HCT. In our study, we did not find an improved OS for yMDS patients compared to older patients.
Correlation between blast percentage in myelofibrosis and outcomes: A single-center experience.
Authors: Masarova Lucia , Bose Prithviraj , Newberry Kate , Abou Zahr Abdallah , Cortes Jorge E. , Kantarjian Hagop M. , Verstovsek Srdan
Published: September 2018

e18562

Background: Patients with accelerated phase (AP) myelofibrosis (MF; >10% blasts [BL] in bone marrow [BM] or peripheral blood [PB]) have shorter overall survival (OS) than those in the chronic phase (<10% BM/PB BL). However, outcomes of patients with “lower” BM/PB BL (1-9%) are not well described. Methods: Clinical characteristics and OS of 1099 patients with MF who presented to MD Anderson Cancer Center between years 1984 – 2013 were retrospectively evaluated. Kaplan-Meier analysis and Cox regression models were used for calculations and comparisons. Results: PB and BM BL were available for 1038 (94%) patients at presentation. Five percent had AP, 10% had 5-9% BM or PB BL; 45% had < 5% BM BL and 1% (n=282), 2% (n=110), 3% (n=47) or 4% (n=27) PB BL; and 40% had < 5% BM BL and 0% PB BL (normal range). OS was similar among patients with 5-9% BM or 4-9% PB BL and those in AP (P>0.05). OS was also similar among patients with BL in the normal range and those with <5% BM and 1-3% PB BL (p>0.05). By grouping patients with similar OS, we have identified 2 groups with distinctive OS of 54 and 27 months, respectively (Table; p<0.001; HR = 1.81 [95%CI 1.5-2.2]). Five-year leukemia free survival was 65% for those in AP, 76% for ≥ 5-9% BM or ≥ 4-9% PB blasts, and 91% for < 4% BM or ≤ 3% PB BL (P<0.001). Clinical characteristics were similar for patients in the AP and with ≥ 5-9% BM or ≥ 4-9% PB blasts. Both groups had significantly higher leukocytes, lower hemoglobin and platelet levels, and were more likely to be transfusion dependent, have systemic symptoms, and unfavorable karyotype than patients with ≤ 4% BM or ≤ 3% PB blasts. There was no significant difference in age, splenomegaly, BM fibrosis grade, or distribution of JAK2, MPL and CALR mutations among these groups. Conclusions: Patients with ≥ 4% PB or ≥ 5% BM BL have OS that appears to be the same as those with >10% BL, suggesting that these patients may require a more aggressive treatment approach. [Table: see text]
Comparing adherence levels of CLL treatment from both the patient and physician perspective in the U.S.
Authors: Schenkel Brad , Hallworth Pam , Rider Alex , Macomson Brian , McRae Jacquelyn
Published: September 2018

e19009

Background: Prior research has shown that there is a lack of congruency between physicians and patients regarding choice of therapy in CLL care. The aim of this study was to look at whether there are any similar differences in regard to perceptions of drug adherence between a group of CLL patients and their corresponding physicians. Methods: From February to May 2016, the Adelphi CLL Disease Specific Programme (DSP) recruited US physicians who are responsible for treatment decision-making in CLL. Patient Record Forms (PRF) and Patient Self-Completion questionnaires (PSC) were completed by physicians and patients, respectively. Means and standard deviations (SD) were calculated for continuous variables, and proportions were calculated for categorical variables. Results: A total of 81 physicians and 326 patients participated in the CLL DSP. The majority of physicians were heme-oncologists (68%), male (79%), and practiced in both a hospital and office-based setting (86%). Physicians reported that 87% of their CLL patients were “always” or “almost always” adherent to their CLL treatment. However, only 42% of patients reported that they were “never” or “hardly ever” non-adherent to CLL treatment. Patients reported that their physicians addressed adherence in the following methods: physicians asked patients about adherence (56%), nurses/other staff assisted patients (23%), physician did not check (15%), pill checking (3%), materials/resources were given (1%), and other (2%). Three-quarters (75%) of physicians reported that they discussed adherence with their CLL patients consistently. Conclusions: In this study, patients’ and physicians’ perceptions of adherence with regard to CLL treatment were not aligned. Although most physicians reported consistent discussions about adherence with their patients, the majority of patients reported subpar adherence to CLL treatment. As more oncology medications, including those approved in CLL, are available in a pill or capsule formulation and thus self-administered, it will be increasingly important to make patients aware of the importance of adhering to their medication and including physicians and caregivers in this dialogue.
A trial-based EuroQol EQ-5D health utility analysis in patients with classical Hodgkin lymphoma.
Authors: Wu Elise , Liao Jane , Balakumaran Arun
Published: September 2018

e19011

Background: Pembrolizumab has shown a high response in patients classic Hodgkin lymphoma (cHL) patients who have experienced disease progression after brentuximab vedotin in KEYNOTE (KN)-087 and the results have been presented. This study aimed to evaluate the health-related quality of life (HRQoL) of the trial patients in KN087. Methods: KN-087 is an ongoing single-arm multi-center, non-randomized Phase II trial evaluating pembrolizumab 200mg Q3W IV in patients with relapsed or refractory cHL. In KN-087, HRQoL data were collected at baseline and every drug administration over the 18 months of follow-up. HRQoL was assessed using both the EQ-5D and EORTC QLQ-C30 instruments. The generic health statuses assessed from both instrument were converted to population-based utility values using published algorithms. More specifically, US-based scoring was applied to US patients, UK-based scoring for UK patients and EU-based scoring for all other patients. HRQoL was reported by status of respond and disease progression. Response was defined based upon IWG criteria. Furthermore, stratified analyses were conducted to examine the health disabilities of the patients who experienced grade 3+ adverse events (AEs), and by ECOG performance and the number of prior therapies. Results: Among 210 trial patients, HRQoL data were collected for 205 patients at baseline and the mean health utility score was 0.759 (95% CI 0.730-0.788). Mean health utility score among responders and non-responders was 0.826 (95% CI 0.811-0.842) and 0.760 (95% CI 0.718-0.801), respectively. The difference is considered clinically significant. Mean utility decreased from 0.820 (95% CI 0.807-0.833) for time spent prior to progression to 0.806 (95% CI 0.780-0.832) post disease progression. Progression-free patients who experienced grade 3+ AEs (N=17) had a mean health utility of 0.736 (95% CI 0.662-0.811), compared with 0.825 (95% CI 0.811-0.838) among those did not. Conclusions: The results showed a substantial HRQoL impact of R/R cHL. Treatment response was associated with significant clinically meaningful improvement in HRQoL. The utility estimates from the study are important for economic evaluations of treatments in R/R cHL patients. Clinical trial information: NCT02453594.
Ibrutinib associated infections: A retrospective study.
Authors: Chaul Barbosa Caroline , DeAngelis Lisa Marie , Grommes Christian
Published: September 2018

e19020

Background: Ibrutinib (IBRU) is a Bruton tyrosine kinase (BTK) inhibitor that has been FDA approved for chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL) and Waldenstrom's Macroglobulinemia (WM). BTK inhibition may contribute to immunosuppression through B- and T-cell inhibition, resulting in an increase in infections. We therefore characterized IBRU-related infections retrospectively. Methods: The study was an IRB approved retrospective review. Patients (pts) treated with IBRU between 4/2014-11/2016 who developed any infection were identified using ICD10 codes in a clinical database. Study population was defined using descriptive statistics. Results: 200 pts were identified: 78 pts had CLL (39%), 30 diffuse large B-cell lymphoma (15%), 28 MCL (14%), 19 WM (9.5%), 15 (7.5%) marginal zone lymphoma, 14 (7%) follicular lymphoma, 7 (3.5%) multiple myeloma, 7 (3.5%) T-cell lymphoma and 2 (1%) primary central nervous system lymphoma (PCNSL). Median age was 68 (range 28-96), 34% were men and median ECOG was 1. The majority of pts received IBRU as second line treatment (172, 86%) with a median of 2 prior lines of treatment; 23 pts (11.5%) were post transplant. Median IBRU dose was 420mg daily (range 140-840mg), administered a median of 316 days (range 3-1780). Single agent IBRU was used in 162 pts (81%). 105 pts (52%) developed an infection, with pneumonia (30%), upper airway infection (26%); skin infection (18%); and sinusitis (13%) being the most common. 10 (9.5%) had neutropenic fever and 1 (1%) cryptococcal pneumonia. Seven (7%) developed fungal infections, with invasive aspergillosis in 5 (5%). 34 (32%) developed ≥3 infections. 46 pts (44%) were hospitalized, 10 (9.5%) interrupted IBRU and 3 pts (2.9%) died due to infections (2 pneumonia; 1 neutropenic fever). The median time to infection after starting IBRU was 70 days (range 2-1261). The highest infection rate was seen in pts with PCNSL (100%, 2/2), MZL (67%, 10/14), followed by CLL (64%, 50/78). Conclusions: We identified infections in half of the pts treated with IBRU. Pts treated with IBRU should be monitored closely for the development of infections, particularly airway infections.
Clinicopathological characteristics compared between primary effusion lymphoma and human herpesvirus 8 (HHV8)-unrelated primary effusion lymphoma-like lymphoma.
Authors: Shin Junghoon , Koh Youngil
Published: September 2018

e19024

Background: Primary effusion lymphoma (PEL) and human herpesvirus 8 (HHV8)-unrelated primary effusion lymphoma-like lymphoma (PEL-LL) are among the most rare subtypes of non-Hodgkin B-cell lymphoma. Although a few number of case reports and small case series have suggested a better outcome of PEL-LL compared to PEL, systematic comparison of prognosis between PEL and PEL-LL has never been conducted owing to their rare incidence. Methods: We consecutively collected PEL and PEL-LL patients diagnosed between 2000 and 2016 in 10 institutions in South Korea. All patients were cytogically confirmed and received systemic evaluation to exclude detectable tumor formation. Clinicopathological characteristics and prognosis were compared. Results: A total of 12 PEL and 4 PEL-LL cases were analyzed. Median age at diagnosis was 68.5 (range, 40-88) and 68.5 (range, 59-77) for PEL and PEL-LL, respectively. Male-to-female ratio was 7:5 and 3:1 in each group. Pleural effusion was the most common presentation in both groups. One patient in PEL-LL group presented with vitreous fluid containing lymphoma cells. Seven and two PEL patients were treated with CHOP and CVP-based chemotherapy, respectively and 3 did not receive chemotherapy due to poor performance. Three PEL-LL patients were treated with R-CHOP and the remaining 1 patient with malignant vitreous fluid received high dose methotrexate. One PEL patient received autologous hematopoietic stem cell transplantation after second remission and lived over 14 years thereafter. With estimated median follow-up duration of 99.6 and 20.7 months for PEL and PEL-LL respectively, 3 and 1 death occurred during the entire period in each group. Median overall survival was 119.6 and 66.5 months in PEL and PEL-LL group respectively without statistically significant difference. Conclusions: In our study, long-term prognosis of PEL and PEL-LL showed no difference. This result might be attributed to 2 remarkably long-lived patients in PEL group (longer than 174 and 123 months, respectively) and low statistical power owing to the small sample size.
Association of FDG PET-CT (PET) avid skeletal lesions (SL) with progression-free survival (PFS) in patients (pts) with previously untreated follicular lymphoma (FL).
Authors: Maly Joseph J. , Wei Lai , Hemminger Jessica , Christian Beth , Maddocks Kami J. , Jones Jeffrey Alan , Wright Chad , Blum Kristie A.
Published: September 2018

e19026

Background: PET scan is frequently utilized in FL. Reduced EFS has been observed in DLBCL pts with SL treated with RCHOP (Held, JCO 31:4115, 2013). Methods: We performed a retrospective single center study to assess outcomes of FL pts with PET avid SL between January 2005 and November 2015. 131 pts with newly diagnosed FL and PET performed within 1 month of diagnosis were included. Results: 32 of these pts had SL (median 4, range 1-11) on initial PET. Median age was 57 (range 43-79), 15 (47%) were female, 30 (94%) had stage IV disease, LDH was elevated in 6 (19%), 6 (19%) had bulky disease > 6 cm, and FLIPI-1 score was low in 5, intermediate in 11, and high 16 pts. 27 pts had grade (gr) 1-2 FL, 2 had gr 3a, and 3 had gr 3 (not classified). All but 1 patient received rituximab (R)-containing therapy (9 received BR, 7 received RCHOP, 5 RCVP, 9 other). 8 pts received maintenance R, and none received radiation. There were no statistically significant differences in median age, tumor gr, LDH, or use of anthracycline containing therapy (28% in SL group vs 16% in non-SL group, p = 0.13) in pts with SL compared to those without SL (n = 99). Pts with SL had higher incidence of bone marrow involvement (27% vs 9%, p = 0.013). With a median follow-up of 35 months, SL pts had 44% rate of transformation to DLBCL compared 12% in non-SL pts (p = 0.004). Median PFS was 45.8 months in SL pts not-reached in non-SL pts (p = 0.003). Median OS was 105.9 months in SL pts and not reached in non-SL pts (p = 0.08). In the multi-variate analysis, SL (p = 0.037), male gender (p = 0.048), higher FLIPI-1 score (p = 0.009), and absence of anthracycline containing therapy (p = 0.005) were significantly associated with decreased PFS using backward selection. Conclusions: The presence of PET identified SL in previously untreated FL is associated with an increased risk of transformation and reduced PFS in this single center retrospective analysis. Larger studies of uniformly treated pts are needed to validate these data. The identification of high-risk PET avid SL in FL pts in future prospective therapeutic trials could be used to select pts for specific induction regimens, maintenance rituximab, or consolidative radiation.
Primary bone lymphoma (PBL) real world experience of a single cancer hospital. results, prognostic factors, treatment and long term follow up of 12 patients.
Authors: Stoumbos Dionisios , Gkekas Christos , Asmanis Evangelos , Christaki Evangelia Eleni , Dadakaridou Magdalini , Lampropoulou Polykseni , Megalakaki Aikaterini , Repousis Panagiotis , Kotsopoulou Maria
Published: September 2018

e19033

Background: PBL is a very rare condition which constitutes less than 1% of all lymphomas. Due to the uncommon entity of this disease there is a lack of concordance in the characteristics, optimal management, treatment strategies and the associated outcome. Methods: Herein, we retrospectively review 12 consecutive patients initially diagnosed with PBL and also treated at our institution from 2001 to present. Results: The median age of the patients was 49 years old. Eight patients were female and 4 male. The histological type of all 12 patients presented was DLBCL. Ten patients (83%) were presented with Ann Arbor Stage I or II disease. While 2 patients (17%) had stage IV disease, none of them showed bone marrow involvement at their initial diagnosis. The median follow-up after achieving CR was 80 months. Our analysis demonstrated that age less than 47 years, lack of B symptoms, normal LDH level, Stage I or II and female gender were found to be favorable prognostic factors for achieving CR and OS. All 12 patients underwent chemotherapy with most of them (10; 83%) receiving 6 to 8 cycles of the RCHOP regimen. The majority (11; 92%) of them received chemotherapy followed by radiotherapy. After front line chemotherapy followed by radiotherapy most patients (9; 75%) achieved CR. Among the remaining three patients, the one patient died before completing first line chemotherapy due to an infection during chemotherapy-induced neutropenia, the other patient is undergoing autologous stem-cell transplantation due to refractory PBL and the third one achieved CR after he underwent high-dose chemotherapy and autologous stem-cell transplantation due to refractory PBL. Both patients that had refractory disease were male and initially diagnosed with stage IV PBL. The median OS was 100 months. Conclusions: The data from our study supports that most PBL patients have had early stage disease (IE-IIE) on diagnosis which also was the most important favorable prognostic factor. Overall, patients with primary lymphoma involving the bone with DLBCL have an excellent prognosis and only a limited number of patients underwent autologous stem-cell transplantation in order to achieve CR.
Age as a potential new prognostic indicator in primary cutaneous B-cell lymphoma (PCBCL).
Authors: Desai Poorvi Kirit , Van den Bergh Magali , Zhang Xiaohui , Zhang Hailing , Schaible Braydon , Ma Zhenjun , Sokol Lubomir
Published: September 2018

e19034

Background: PCBCL is a group of rare lymphoproliferative disorders, with an estimated annual incidence of 2.5 per 1,000,000 persons. Indolent subtypes include Primary Cutaneous Marginal Zone Lymphoma (PCMZL) and Primary Cutaneous Follicular Center Lymphoma (PCFCL). Primary Cutaneous Diffuse Large B-cell Lymphoma (PCDLBCL) is an aggressive subtype with a fatality rate of 50%. The Cutaneous Lymphoma International Prognostic Index (CLIPI) can risk-stratify indolent subtypes, but age is not considered. Here we present our single-institutional analysis of clinicopathologic features and outcomes of patients with PCBCL. Methods: This is a retrospective study of patients evaluated at Moffitt Cancer Center between 01/1990 and 12/2016. Patients were identified using our PCBCL database and diagnosis was verified by independent hematopathologists and dermatopathologists. Staging was determined by ISCL/EORTC criteria. Demographics, subtype, stage, disease course, and CLIPI scores were collected. Continuous and categorical values were tested using Kruskal-Wallis ANOVA method and Fisher’s Exact Test, respectively. Kaplan-Meier curves were produced to determine PFS. Results: We identified 37 patients who met diagnostic criteria for PCBCL (35% PCFCL, 40.5% PCMZL, 13.5% PCDLBCL, and 11% indolent, unspecified). Male:female ratio was 2.4:1. 51% of patients were ≥ 60 years old (yo), and 49% were < 60 yo. 54% had stage T1 disease, 27% T2, and 19% T3. Median PFS for patients <60 was 1.1 years, but was not reached for those ≥60. Mean follow-up time was 2.6 years for all patients. Log-rank test showed a statistically significant difference in PFS between the two age groups (p=0.01). PFS for stage of indolent subtypes showed marginal significance (p <0.06). CLIPI for indolent subtypes did not show a significant difference in PFS. Conclusions: We found that age is a highly statistically significant prognostic parameter in PCBCL, as patients ≥ 60 yo had a longer PFS compared to younger patients, even after adjusting for stage and CLIPI. These results are promising for age as a possible prognostic indicator for PCBCL, but validation is needed with a larger sample size.
External validation of prognostic indices for aggressive adult T-cell leukemia/lymphoma (ATL-PI/JCOG-PI) in Okinawa.
Authors: Tamaki Keita , Morishima Satoko , Nomura Shogo , Tomoyose Takeaki , Nakachi Sawako , Nishi Yukiko , Taira Naoya , Miyagi Takashi , Karimata Kaori , Ohama Masayo , Yamanoha Atsushi , Tamaki Kazumitsu , Hayashi Masaki , Uchihara Jun-nosuke , Ohshiro Kazuiku , Asakura Yoshitaka , Kuba-Miyara Megumi , Karube Kennosuke , Fukushima Takuya , Masuzaki Hiroaki
Published: September 2018

e19036

Background: Aggressive adult T-cell leukemia/lymphoma (aATL) has an extremely poor prognosis (median OS, 8-10 months). Okinawa, Japan’s only subtropical region, is hyperendemic for aATL. Recently, we demonstrated poorer outcomes among aATL patients in Okinawa compared with patients elsewhere in Japan, and a possible association of strongyloidiasis with ATL-related death. Two prognostic indices (PIs)—ATL-PI and JCOG-PI—have been developed using a database of national surveys and clinical trials. However, aATL patients in Okinawa were not included. This study aimed to validate these PIs using an Okinawa database. We also investigated the impact of strongyloidiasis on aATL patient survival. Methods: We constructed a clinical database of aATL patients from 7 institutions in Okinawa diagnosed between January 2002 and December 2011. The study endpoint was OS. Standard survival analysis methods (Kaplan-Meier method, log-rank test, and Cox proportional-hazards model) were used. Results: The study involved 433 evaluable patients (median OS, 6 months). Risks according to the two PIs in each patient were not always consistent (Table), but both PIs stratified aATL patients by risk. Three-year OS rates for ATL-PI were 35.9% (low-risk, n=66), 10.4% (intermediate-risk, n=256), and 1.6% (high-risk, n=111); rates for JCOG-PI were 22.4% (moderate-risk, n=176) and 5.3% (high-risk, n=257). Strongyloidiasis had little impact on OS (HR and 95% CI from univariate Cox analysis, 1.22 and 0.90-1.66, respectively). Multivariable Cox analysis returned almost the same factors as had been screened out in the previous studies to construct the two PIs. Conclusions: ATL-PI and JCOG-PI were well reproducible in Okinawa database. Strongyloidiasis did not affect prognosis in aATL patients. ATL-PI identifies low-risk aATL patients more clearly than JCOG-PI, and both identify high-risk patients with extremely poor prognosis. These will be useful to devise novel treatment strategies based on risk stratification of all Japan/world aATL patients. [Table: see text]