ALBERT

Description: Background: Next-generation sequencing (NGS) technologies have led to the discovery of recurrently-mutated genes in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). These mutations have proven useful in diagnosis, prognostication, and prediction of treatment response when used in conjunction with cytogenetics and other clinical characteristics known to influence patient outcome. NGS platforms that test for the presence of genetic mutations associated with myeloid malignancies are now widely available in clinical practice and are often utilized during initial diagnostic evaluation. However, there is considerable variability among hematologists in the use of such data, and it is still unclear whether physicians are using molecular data to properly prognosticate or make treatment decisions for their patients. Thus, the purpose of this study is to assess real-world practices of physicians caring for patients with AML or MDS at a large National Comprehensive Cancer Network (NCCN) Member Institution and to determine the degree to which molecular data is being utilized to prognosticate or alter clinical management. Methods: Patients presenting to the University of Wisconsin-Madison Hospital and Clinics with newly-diagnosed AML or MDS from 1/1/2014 through 12/31/2018 were included in the study. Data was collected retrospectively, including patient demographics, clinical characteristics, cytogenetic and mutational data, and treatment. The medical record was scrutinized for documentation regarding impact of molecular data on physician prognostication and decision-making. Results and Discussion: 102 patients were included in the analysis, including 54 patients with AML and 48 patients with MDS. For AML patients, 36% were classified as adverse risk, 34% as intermediate risk, and 30% as favorable risk based on ELN criteria. For MDS patients, 50% were classified as very high or high risk, 27% as intermediate risk, and 23% as low or very low risk by IPSS-R criteria. The proportion of AML and MDS patients having normal cytogenetics were comparable (37% versus 29% respectively, p=0.40). The type and frequency of molecular data utilized differed significantly according to diagnosis (p

Description: Background: Asparaginase may improve outcomes in chemotherapy resistant malignancy, especially of lymphoid origin. L-asparaginase (L-ASP) was introduced in 1992 and hence has been incorporated in multiple regimens. An effective regimen including steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) was developed by the NK-Cell Tumor Study Group as a unique chemotherapeutic regimen to combat chemo-resistant NK-cell neoplasms (Yamaguchi et al. 2008) and later shown to have efficacy in relapsed and refractory lymphoblastic lymphoma (Chang et al. 2014). The pegylated-asparaginase (PEG-ASP) is the only readily available commercial product as the other forms either have limited availability due to shortages (Erwinia asparaginase) or are no longer available in the United States (E-coli asparaginase). We present retrospective data incorporating PEG-ASP into a modified SMILE (mSMILE) regimen. To our knowledge, no prior comparison between the PEG-ASP and L-ASP based SMILE regimen is available in the literature. Methods: All adult patients treated with mSMILE for either extranodal NK/T-cell leukemia and lymphoma (ENKTL), T-cell acute lymphoblastic leukemia (T-ALL), T-cell lymphoblastic lymphoma (T-LBL), adult T-cell leukemia/lymphoma (ATLL), or peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) from 12/1/2009-6/30/2019 at Moffitt Cancer Center were included. PEG-ASP replaced L-ASP in SMILE regimen at a dose of 2500 units/m2/dose IV on Day 8 only (maximum dose of 3750 units). Cycles were repeated every 28 days until disease progression, excessive toxicity, or consolidation with hematopoietic cell transplantion (HCT). Patients received appropriate supportive care with peg-filgrastim or filgrastim (until absolute neutrophil count 〉 1000/ul x 3Days or 〉3,000/ul) as well as antimicrobial prophylaxis with acyclovir, ciprofloxacin, and fluconazole once methotrexate cleared and post-chemotherapy. Toxicity assessment was analyzed retrospectively and graded based upon Common Terminology Criteria for Adverse Events (CTCAE) version 5. Toxicity profiles of PEG-ASP-based mSMILE in present study were compared to profiles of L-ASP-based SMILE in the recently published literature (Pokrovsky & Vinnikov Expert Rev Anticancer Ther, 2019). Results: A total of 13 patients were treated with mSMILE during the 10-year period (Table 1). Of these patients, the median age was 46 years (range, 19-69), caucasians (46%) and males (70%). Most of the patients were treated for ENKTL (46%). mSMILE was the first line therapy in 3 patients, while the median number of prior therapies was 1 (range 0-3). Toxicity assessment for mSMILE focused on PEG-ASP-induced toxicity as no patients had any hemorrhagic cystitis, neurotoxicity, or renal dysfunction that could be associated with ifosfamide, methotrexate, or etoposide. mSMILE was comparatively associated with more hematologic toxicity, likely related to inclusion of patients with lymphoblastic leukemia (table 2). Grade 3/4 hepatotoxicity rates are low, possibly owing to inclusion of carnitine prophylaxis (Schulte et al. 2018). Thrombosis was not observed. Hypertriglyceridemia was observed in 15% with no cases of pancreatitis. Hypersensitivity and neurotoxicity were not observed. Of the two patients who discontinued therapy due to toxicity, one was related to grade 3 hypofibrinogenemia and the other grade 4 bleeding. Mortality was attributable to disease progression in all cases, with 0% treatment related mortality. Efficacy is comparable, with ORR 54% (7/13), including 30% (4/13) successfully bridged to HCT. Conclusion: In a non-Asian population, modified SMILE regimen with PEG-ASP is a safe alternative to L-ASP-based SMILE regimen. There is increased hematological toxicity, which did not seem to affect chemotherapy delivery. Disclosures Chavez: Genentech: Speakers Bureau; Janssen Pharmaceuticals, Inc.: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees; Kite Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees. Bello:Celgene: Speakers Bureau. Pinilla Ibarz:Sanofi: Speakers Bureau; Bayer: Speakers Bureau; TG Therapeutics: Consultancy; Teva: Consultancy; Janssen: Consultancy, Speakers Bureau; Novartis: Consultancy; Bristol-Myers Squibb: Consultancy; Takeda: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau. Sokol:EUSA: Consultancy. Shah:AstraZeneca: Honoraria; Spectrum/Astrotech: Honoraria; Novartis: Honoraria; Celgene/Juno: Honoraria; Kite/Gilead: Honoraria; Incyte: Research Funding; Jazz Pharmaceuticals: Research Funding; Pharmacyclics: Honoraria; Adaptive Biotechnologies: Honoraria.

Description: Background: Only a small subset of Lower risk (LR) MDS patients benefit from treatment with rhu-Erythropoietin (Epo). We previously reported that lenalidomide (LEN) restores sensitivity to Epo in MDS progenitors by inducing the formation of lipid rafts that are enriched for signaling competent, JAK2/Epo-receptor complexes (McGraw K, et. al. PLoS One 2014; Basiorka A, et. al. Cancer Res 2016). In the MDS-002 and MDS-005 trials, treatment with LEN monotherapy gave rise to RBC transfusion-independence (TI) in 26% of azanucleoside-naïve, transfusion-dependent (TD) LR, non-del(5q) MDS patients for a median of 10.2 and 7.75 months, respectively. In a pilot study of Epo-refractory LR-MDS patients, the addition of epoetin alfa (EA) to LEN treatment yielded erythroid responses in 28% of patients who were unresponsive to LEN alone, suggesting that LEN may overcome clinical resistance to augment response to rhEpo (Komrokji R, et. al. Blood 2012). To test this hypothesis, we performed a randomized phase III trial comparing treatment with LEN to LEN+EA in LR non-del(5q) MDS patients who were refractory to, or not candidates for treatment with rhEpo. Methods: Patients with Low or Intermediate-1 IPSS risk MDS with hemoglobin 2 units/month) with serum Epo 〉500mU/mL were eligible. Patients were stratified by serum Epo level and prior rhEpo (EA vs. darbepoetin vs. none) then randomized to treatment with LEN 10 mg/d x21d q4wk (Arm A) or LEN + EA 60,000U SC/wk (Arm B). The primary endpoint was major erythroid response (MER) at week 16 which was defined according to transfusion status at baseline: (1) achievement of RBC-TI for ≥ 8 consecutive weeks AND a sustained ≥1 g/dL hemoglobin rise compared to mean pre-transfusion baseline value in TD patients; and (2) a 〉2 g/dL rise in hemoglobin without transfusion for ≥ 8 consecutive weeks in non-TD patients (Grade 3, non-hematologic adverse events between treatment arms. Two patients progressed to AML while on study (Arm A), and no thromboembolic events were reported. Conclusions: LEN restores sensitivity to rhEpo in otherwise refractory, LR-non-del(5q) MDS patients to yield a significantly higher frequency of durable major erythroid responses compared to LEN alone. The addition of LEN to EA treatment is an effective strategy for the management of Epo-refractory patients with a potential duration of benefit extending to years. Disclosures List: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Verma:Janssen: Research Funding; BMS: Research Funding; Stelexis: Equity Ownership, Honoraria; Acceleron: Honoraria; Celgene: Honoraria. Maciejewski:Novartis: Consultancy; Alexion: Consultancy. Komrokji:JAZZ: Speakers Bureau; Novartis: Speakers Bureau; JAZZ: Consultancy; Agios: Consultancy; Incyte: Consultancy; DSI: Consultancy; celgene: Consultancy; pfizer: Consultancy. Luger:Onconova: Research Funding; Pfizer: Honoraria; Seattle Genetics: Research Funding; Cyslacel: Research Funding; Biosight: Research Funding; Ariad: Research Funding; Agios: Honoraria; Genetech: Research Funding; Jazz: Honoraria; Daichi Sankyo: Honoraria; Kura: Research Funding; Celgene: Research Funding. Mattison:Pfizer: Membership on an entity's Board of Directors or advisory committees. Altman:Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Theradex: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Glycomimetics: Consultancy, Honoraria, Other: Data Safety and Monitoring Committee; Agios: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; France Foundation: Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; prIME Oncology: Speakers Bureau; PeerView: Speakers Bureau; Cancer Expert Now: Consultancy; Novartis: Consultancy; Biosight: Other: US Lead. Claxton:Astellas Pharma: Other: Pharma support of clinical studies; Merck Sharp & Dohme Corp.: Other: Pharma support of clinical studies; Cyclacel Pharmaceuticals, Inc.: Other: Pharma support of clinical studies; Medimmune Inc.: Other: Pharma support of clinical studies; Novartis Pharmaceuticals: Other: Pharma support of clinical studies; Celgene Corporation: Other: Pharma support of clinical studies; Incyte Corporation: Other: Cyclacel Pharmaceuticals, Inc; Daiichi Sankyo Co. and Ambit Biosciences Corp: Other: Pharma support of clinical studies. Artz:Miltenyi: Research Funding. Tallman:Daiichi-Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Research Funding; Oncolyze: Consultancy, Membership on an entity's Board of Directors or advisory committees; Tetraphase: Consultancy, Membership on an entity's Board of Directors or advisory committees; UpToDate: Patents & Royalties; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cellerant: Research Funding; Rigel: Consultancy, Membership on an entity's Board of Directors or advisory committees; KAHR: Consultancy, Membership on an entity's Board of Directors or advisory committees; Biosight: Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Nohla: Consultancy, Membership on an entity's Board of Directors or advisory committees; Orsenix: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Delta Fly Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; BioLineRx: Consultancy, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Lenalidomide used for treatment non-del 5q myelodysplastic syndromes.

Description: Post-transplant lymphoproliferative disorders (PTLDs) are classified as early PTLDs (E-PTLD), polymorphic PTLDs (P-PTLD), monomorphic PTLDs (M-PTLD) and classical Hodgkin's Lymphoma PTLD (HL). These entities are felt to represent a disease continuum, with a precursor-product relationship, though they are morphologically and clinically distinct. However, this process remains poorly understood, and limited evidence exists to support this hypothesis. We report a series of nine cases extracted from a PTLD database, including both pediatric and adult solid organ transplant recipients, with recurrent disease episodes that evince an apparent evolution in their morphologic categorization between episodes. All patients identified were high risk for PTLD, with multiple identifiable predisposing factors. Presentations varied from isolated lymphadenopathy, to gastrointestinal involvement to pulmonary involvement. Four of the patients were deceased at the time of acquisition, though only one directly from PTLD. Eight of the nine identified patients developed E or P-PTLD lesions that preceded a subsequent M-PTLD or HL lesion at a similar tissue site. Two of the cases had metachronous P and M-PTLD lesions. The six M-PTLD subtypes were variable, including DLBCL, Burkitt, T-cell, and extramedullary plasmacytoma, in addition to the three cases of classical Hodgkin's lymphoma. These cases suggest that E and P-PTLD may act as common precursor lesions to the development of both the M-PTLD variants and HL type lesions, and that the PTLD classification schema represents different stages of a common underlying pathology. Disclosures Owen: Lundbeck: Honoraria; Gilead: Honoraria; Janssen: Honoraria; Roche: Honoraria.

Description: Experiments were conducted to investigate the effects of intravenous immunoglobulin (IVIG) in a rat model of immune thrombocytopenia (ITP). Rats were pretreated with 0 to 2 g/kg IVIG and then challenged with an antiplatelet antibody (7E3, 8 mg/kg). IVIG effects on 7E3-induced thrombocytopenia and on 7E3 pharmacokinetics were determined. IVIG pretreatment led to significant changes in the degree and time-course of 7E3-induced thrombocytopenia (P = .031). Nadir percent platelet counts were 121% to 279% greater in animals treated with IVIG (0.4-2 g/kg) than in animals receiving 7E3 alone. IVIG treatment also led to dose-dependent increases in 7E3 clearance (P 

Description: Bone marrow biopsy (BMB) examination is an essential part of diagnosis for hematologic disorders. BMB length guidelines exist but are inconsistently followed; recommendations have included 〉 20mm for lymphoma (Cheson et al. JCO2014), 15 mm for myeloproliferative disease (Thiele et al. Haematologica 2005), 16 mm for malignant neoplasms in general (Bishop et al, J. Clin. Pathol. 1992). Poor BMB quality hinders pathology interpretation, may impact diagnosis, accurate lymphoma staging and may necessitate repeat procedure with associated patient anxiety and therapy delay. We had observed significant variation in BMB quality at our institution. We therefore undertook a quality improvement (QI) project to identify factors associated with suboptimal BMB and to implement strategies to improve overall BMB quality. Aim: To evaluate the proportion of our biopsies that meet above criteria and identify factors that contribute to suboptimal sampling. The ultimate goal is to improve the quality and length of BMB at our institution for better diagnostic accuracy. Methods: We collected data prospectively on 212 consecutive BMBs performed on adult patients at our institution for baseline evaluation. As BM performers knew about the project, we also collected retrospective data on BMB length to assess for a Hawthorne effect. We recorded the following BMB performance data: patient age, body mass index (BMI), clinic or inpatient setting, sedated or non-sedated procedure, needle gauge, use of trap, performing clinician and disease category. BMB performers included faculty, fellows and nurse practitioners. The BMB length, amount of marrow space, degree of crush and aspiration artifact and disease involvement were assessed in each case. We analyzed which BMB performance factors were associated with differences in BMB length and quality. QI intervention : We performed an email survey on perceived BMB adequacy criteria, discussed overall results and coded individual performance data at a meeting of all providers. We also presented the guidelines about recommended BM length. Individual data were revealed confidentially to each performer. Follow up : Data on BM length and performer were collected on 122 BMB following the intervention. Two-tailed Student t tests under the normality assumption were used to determine significance of differences in BM lengths between pre and post intervention biopsies. Results: Baseline BMB: 210 BMB samples from 24 performers were evaluated. Results were compared to 104 historical marrows to rule out observation bias (Hawthorne effect). No difference was seen in biopsy lengths before or after initiation of study. Median biopsy length was 12 mm (range 1-35 mm). There were no statistically significant differences in BM length depending on patient BMI, location (inpatient vs outpatient), sedation, diagnosis and needle gauge. However there was significant variation in biopsy lengths between performers varying from a mean of 8 to 23 mm (p

Description: Introduction The host immune status is central to both the pathogenesis and treatment of Post-Transplant Lymphoproliferative Disorders. (PTLD) The most commonly used prognostic model for PTLD, the International Prognostic Index (IPI), currently does not account for the effect of immune status on patient outcomes. We hypothesize that CD3 positive T-cell infiltrate density in the tumor microenvironment, thought to be a surrogate of the potency of the host versus tumor immune response, may be prognostic of overall survival in PTLD. Methods A database consisting of 131 biopsy confirmed PTLD cases occurring in pediatric and adult solid organ transplant recipients after the year 2000 in Alberta, Canada was analyzed for clinical prognostic variables and overall survival. CD3 infiltrate was determined by a blinded pathologist (JZ) using a standardized integer scoring system (0 - 3) to quantify CD3-positive cells in archived, formalin-fixed paraffin embedded tissue stained by immunohistochemistry. Tissue was available and assessed on a total of 72 patients. Survival analysis was done by Cox regression, with between group differences tested by a Pearson's chi-square test, with p 〈 0.05 being taken as significant. Results Median age at diagnosis was 40.2 years. Histology subtypes included early (n = 7), polymorphic (n = 17), monomorphic, (n = 100) Hodgkin, (n = 8) and unavailable. (n = 2) Immune suppression regimens at diagnosis included tacrolimus + mycophenolate (n = 29), tacrolimus + azathioprine (n = 11), cyclosporine + mycophenolate (n = 14), cyclosporine + azathioprine (n = 4), single agent tacrolimus (n = 11), single agent cyclosporine (n = 2), and other immunosuppressive regimens. (n = 4) A denser CD3 T-cell infiltrate, defined as a CD3 score of 2-3, had a statistically significant protective effect by univariate Cox regression with respect to overall survival. (HR 0.352, p = 0.008) A CD3 score of 2-3 was negatively associated with a monomorphic histology (p 〈 0.001), but was not statistically associated with lymphocyte count, early PTLD, EBV status or bone marrow involvement. In the diffuse large B-cell type PTLD subgroup (n = 61) the association of a dense CD3 T-cell infiltrate with an improved OS was preserved. (HR 0.276, p = 0.041) Clinical factors identified as significant by univariate Cox regression with respect to overall survival included age 〈 18 (HR = 0.380, p = 0.010), monomorphic histology (HR = 2.287, p = 0.02), IPI 3-5 (HR = 3.697, p 〈 0.001), BM involvement (HR 2.437, p = 0.008), and lymphocyte count 〈 1.0. (HR 2.449, p = 0.001) Clinical factors deemed to not be significant with respect to overall survival by univariate Cox regression included CD20 (p = 0.730), thoracic transplant organ (p = 0.314), PTLD onset within 1 year of transplant (p = 0.763), allograft involvement (p = 0.253), albumin of 〈 30 (p = 0.062) and tumor EBV status. (p = 0.278) Multivariate Cox regression with respect to overall survival, including monomorphic histology, IPI 3-5, lymphocyte count 〈 1.0 and CD3 score of 2-3 again showed a statistically significant protective effect of a higher CD3 score. (HR 0.307, p = 0.022) No other clinical variables reached significance in the multivariate analysis. Conclusions A dense CD3 T-cell infiltrate in the tumor microenvironment at diagnosis is protective with regards to overall survival in PTLD by both univariate and multivariate Cox regression, versus traditional clinical prognostic markers. This is reflective of the prognostic importance of the host immune response, which can be altered by changes in exogenous immunosuppression. In the future, validated histologic measures of immune status such as the CD3 score may be integrated into existing models, such as the IPI, to provide additional prognostic power in PTLD. Table 1 Baseline Patient Characteristics - A database with 131 pediatric and adult solid organ transplant recipients with PTLD were analyzed for clinical prognostic factors and available formalin fixed paraffin embedded tissue stained for CD3 by immunohistochemistry. Table 1. Baseline Patient Characteristics - A database with 131 pediatric and adult solid organ transplant recipients with PTLD were analyzed for clinical prognostic factors and available formalin fixed paraffin embedded tissue stained for CD3 by immunohistochemistry. Table 2 CD3 Score by Univariate Analysis - A univariate Cox regression was carried out for a CD3 score of 2-3 versus 0-1 for all analyzed samples. (n = 72) * denotes the reference variable. Table 2. CD3 Score by Univariate Analysis - A univariate Cox regression was carried out for a CD3 score of 2-3 versus 0-1 for all analyzed samples. (n = 72) * denotes the reference variable. Table 3 CD3 score by Multivariate Analysis versus Clinical Factors - A multivariate Cox regression was performed for a CD3 score of 2-3, versus selected clinical factors identified by univariate Cox regression. Table 3. CD3 score by Multivariate Analysis versus Clinical Factors - A multivariate Cox regression was performed for a CD3 score of 2-3, versus selected clinical factors identified by univariate Cox regression. Disclosures Owen: Janssen: Honoraria; Gilead: Honoraria, Research Funding; Pharmacyclics: Research Funding; Celgene: Honoraria, Research Funding; Abbvie: Honoraria; Lundbeck: Honoraria, Research Funding; Novartis: Honoraria; Roche: Honoraria, Research Funding.

Description: Introduction: Asparaginase (ASP) has demonstrated a survival benefit in pediatric patients (pts) with acute lymphoblastic leukemia (ALL) and is now part of standard-of-care frontline treatment. As a result, asparaginase preparations have been incorporated into the treatment of adult ALL to improve outcomes. Pegaspargase (PEG-ASP), a modified version of asparaginase with prolonged asparagine depletion, appears to be safe in adults up to age 40 (Stock, et al., Blood, 2019), but is associated with a unique spectrum of toxicities, the risks of which appear to increase with age. Therefore, the safety of PEG-ASP remains a significant concern in older adults w/ ALL. Methods: We conducted a single center retrospective chart review of pts age ≥40 years who received PEG-ASP as part of frontline induction/consolidation or reinduction, between March 2008 and June 2018 at Memorial Sloan Kettering Cancer Center. The primary objective was to evaluate the tolerability and toxicity of PEG-ASP based on the incidence and severity of ASP-related toxicities (hypersensitivity reactions, hypertriglyceridemia, hyperbilirubinemia, transaminitis, pancreatitis, hypofibrinogenemia, etc) according to the Common Terminology Criteria for Adverse Events, version 4.03. Laboratory values recorded were either the peak or the nadir, the more appropriate for toxicity assessment, within a 4-week period following PEG-ASP administration. Secondary objectives were to determine the total number of doses of PEG-ASP administered in comparison to the number of doses intended, and to characterize the rationale for PEG-ASP discontinuation when applicable. Fisher's exact test was used to compare the incidence of PEG-ASP toxicities with respect to pt and treatment characteristics (regimen, age, BMI, gender, Philadelphia chromosome positive (Ph+) vs. Ph-, presence of extramedullary disease, PEG-ASP dose). P values were not adjusted for multiple comparisons. Results: We identified 60 pts with ALL (40 B-ALL and 20 T-ALL) who received at least one dose of PEG-ASP. Nine pts were Ph+. The median pt age at initiation of the treatment was 53, (range, 40 to 80), and 19 pts had a BMI ≥30 kg/m2. Forty-four pts received treatment for newly diagnosed ALL, and 16 pts for relapsed disease. Table 1 lists pt baseline characteristics. Among the 44 pts with newly diagnosed ALL, 27 pts received PEG-ASP as part of pediatric or pediatric-inspired regimens at doses of 2000 - 2500 units/m2, and 1 pt received a modified dose of 1000 units/m2 due to age. The remaining 16 pts received PEG-ASP at doses of 1000 - 2000 units/m2 for consolidation, per established adult regimens (ALL-2 and L-20; Lamanna, et al., Cancer, 2013). Grade 3/4 ASP-related toxicities with a 〉10% incidence included: hyperbilirubinemia, transaminitis, hypoalbuminemia, hyperglycemia, hypofibrinogenemia, and hypertriglyceridemia. Frontline treatment regimens in which PEG-ASP was used in consolidation cycles only (ALL-2, L-20) were associated w/ a lower incidence of hyperbilirubinemia (p=0.009) and hypertriglyceridemia (p

Description: Background The inflammatory and immune response in tumor microenvironment plays a critical role in cancer progression. Neutrophil-to-lymphocyte ratio (NLR) has been reported as a prognostic factor in solid and lymphoid malignancies. We explored the association of NLR with response to chemotherapy and overall survival (OS) in patients with relapsed/refractory acute myeloid leukemia (RR-AML). Methods A single-center retrospective study was conducted, including 63 adult RR-AML patients who underwent salvage therapy at the University of Wisconsin from 2009 to 2018. Demographic, clinical and pathologic factors were ascertained at the time of RR-AML diagnosis. Refractory AML was defined as failure to achieve remission and

Description: Introduction Acute myeloid leukemia (AML) in older adults is a challenging clinical problem with a poor prognosis. Hypomethylating agents, such as azacitidine, improve survival in this population. (Oran B, Haematologica 2012) These treatments can be challenging to deliver, particularly in patients far from tertiary care centres. We examined whether residence outside of a major metropolitan area impacted referral patterns, treatments, and outcomes in a population-based cohort of AML patients over age 60 in British Columbia (BC), Canada. Methods Patients with ICD-10 diagnoses of AML were identified from the population based BC Cancer registry and BC Cancer pharmacy database. Diagnoses between 2010 and 2016 were included. Exclusion criteria included diagnosis age less than 60 years, any treatment outside BC, or APL. The diagnosis of AML was verified by chart review. Azacitidine was available at our institution in 2010, and is used primarily for patients with bone marrow blast counts below 30%. Patients were defined as having a hematologist/oncologist assessment if a provider with these credentials was listed in notes or pathology reports. Patients were defined as having received a treatment if it was dispensed at least once, with a date after AML diagnosis. Patients were defined as urban if they had a mailing address in a center of 〉/= 100,000 people, per the Statistics Canada definition, and rural if they had a mailing address elsewhere. Urban residences included greater Vancouver, Victoria and Kelowna, which comprise 71.5% of the population. (Statistics Canada, 2016 census) Between group differences were assessed by 2-tailed t-test or chi-square tests. Overall survival (OS) was assessed by Kaplan-Meier, with a log-rank test, and Cox regression. A p 〈 0.05 was significant. Results A total of 879 patients over age 60 with AML, excluding APL, were identified. Of these, 525 (60%) resided in urban areas vs 354 (40%) residing in rural areas. These groups were similar for median age at diagnosis (urban 75.9 years, rural 74.3 years, p = 0.067), adverse cytogenetic profile (urban 56%, rural 44%, p = 0.356), NPM1 positivity (urban 69%, rural 31%, p = 0.101) and FLT3 positivity (urban 76%, rural 24%, p = 0.052). Rural residents were less likely to have a documented hematologist/oncologist assessment (urban 84%, rural 65%, p 〈 0.001). Few patients overall received induction chemotherapy (151, 17%), with no difference between rural and urban residency (p = 0.524). Similarly, few patients underwent hematopoietic stem cell transplantation (38, 4%), with no difference with place of residence (p = 1.000). Median OS for patients treated with induction chemotherapy was 11.0 months (95% CI 9.0 - 13.1 mo). Median OS for patients treated with subcutaneous (SC) azacitidine was 7.1 months (95% CI 4.8 - 9.5 mo) vs 4.7 months (95% CI 3.3 - 6.1 mo) with SC cytarabine. With best supportive care, the median OS was 1.7 months (95% CI 1.5 - 1.9 mo). Median follow-up was 43.7 months (95% CI 39.2 - 48.2 mo), with 706 (97%) of patients deceased at last follow-up. Amongst the 728 patients who did not receive induction chemotherapy, 82 (11%) received SC cytarabine and 127 (17%) received SC azacitidine. Place of residence did not impact whether patients received SC cytarabine (urban 10%, rural 13%, p = 0.285). Rural residents were, however, less likely to receive SC azacitidine (urban 21%, rural 12%, p = 0.002). In patients not undergoing induction, rural residents had a worse OS by Kaplan-Meier analysis (p = 0.021), with a hazard ratio of 1.2 (95% CI 1.026 - 1.387, p = 0.022) on univariate Cox regression. Conclusions Older adults with a diagnosis of AML who reside in rural areas of BC are less likely to have a documented hematologist/oncologist assessment, and are less likely to receive SC azacitidine. This group also has a worsened OS, though the effect size is modest. There was no difference in rates of treatment with potentially curative regimens, although this approach applied to a minority of patients. We hypothesize that this difference may be partially due to the travel burdens placed on rural patients who receive SC azacitidine, which must be administered in a healthcare facility, unlike SC cytarabine. Less access to supportive care in rural areas is also likely a contributing factor. Policymakers should direct additional resources for rural oncologic healthcare delivery, and the importance of low burden drug formulations is AML should be emphasized. Disclosures No relevant conflicts of interest to declare.