ALBERT

Description: Background: Treatment of chronic myeloid leukemia (CML) with a tyrosine kinase inhibitor (TKI) offers significant improvements over previous treatments in terms of survival and toxicity yet has been associated with reduced health-related quality of life and very high cost. Discontinuing TKIs with regular monitoring is safe, but little is known about the impact of discontinuation on patient-reported outcomes (PROs). In the largest U.S. study to date, we evaluated molecular recurrence of CML and PROs after TKI discontinuation. Methods: The Life After Stopping TKIs (LAST) study was a prospective single-group longitudinal study. Key inclusion criteria were age 〉 18 years, patient on TKI therapy (imatinib, dasatinib, nilotinib, or bosutinib) for 〉 3 years with documented BCR-ABL 〈 0.01% by PCR for 〉 2 years, and no previous TKI resistance. We monitored disease outcome (PCRs by central lab) and PROs (PROMIS computerized adaptive tests via REDCap) monthly for the first 6 months, every 2 months until 24 months, then every 3 months until 36 months. Molecular recurrence was defined as 〉 0.1% BCR-ABL IS by central lab (loss of major molecular response [MMR]). We considered 3 points to be clinically meaningful and hypothesized that by 6 months after TKI discontinuation, fatigue, depression, sleep disturbance, and diarrhea would improve by at least 3 points each, corresponding to a standardized effect size of 0.3. Given reports of a withdrawal syndrome of musculoskeletal pain in some patients after discontinuation, pain was an additional outcome of particular interest. For each PRO domain, we estimated a polynomial piecewise linear mixed effects model that specified one nonlinear trajectory after TKI discontinuation and, for those with molecular recurrence, another trajectory after TKI restart. The models included patient-level random effects for the intercepts and linear slopes. Results: From 12/2014 to 12/2016, 172 patients enrolled from 14 U.S. sites. Median age was 60 years (range 21-86) and 89 (52%) were female. The median time on TKI prior to enrollment was 81 months (IQR 54-123). With a minimum follow-up of 24 months, 107 (62%) patients remained in a treatment free remission (TFR). Reasons for restarting therapy were: loss of MMR by central (n=56) or local (n=2) lab, patient decision (n=4), and withdrawal syndrome (n=3). Missing PRO data was minimal (〈 5%) with 〉 2000 assessments completed. For patients in TFR at 6 months, the average estimated improvement in fatigue was 2.6 points (95% CI 2.5-2.7), depression was 1.9 points (95% CI 1.8-1.9), sleep disturbance was 0.9 points (95% CI 0.8-1.0), and diarrhea was 2.7 points (95% CI 2.6-2.7). The average estimated worsening in pain interference (i.e., the extent to which pain affects daily life) was 0.4 points (95% CI 0.3-0.5). The figure shows the distribution of estimated change for each domain at 6 months. All patients showed improvements in depression, diarrhea, and fatigue. About 1 in 6 patients (17%) experienced a clinically meaningful (i.e., at least 3 points) improvement in fatigue and/or diarrhea at 6 months. Conclusion: The LAST study is the largest US TKI discontinuation study to date, and the first to include comprehensive PRO measurement. For patients in TFR at 6 months, TKI discontinuation conferred modest benefits in fatigue and diarrhea on average, with a negligible increase in pain interference. Some patients experienced more notable improvements in fatigue and diarrhea. Planned secondary analyses will include change over time up to 3 years and evaluation of additional PRO domains, including anxiety, physical function, social function, and sexual function. Our results provide important new evidence to support shared patient-provider clinical decision making regarding TKI discontinuation for patients with CML. Figure. Disclosures Radich: Novartis: Other: RNA Sequencing; TwinStrand Biosciences: Research Funding. Mauro:Pfizer: Consultancy; Takeda: Consultancy; Novartis Oncology: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy. Pinilla Ibarz:Sanofi: Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Teva: Consultancy; Janssen: Consultancy, Speakers Bureau; Novartis: Consultancy; Takeda: Consultancy, Speakers Bureau; Bayer: Speakers Bureau; TG Therapeutics: Consultancy; Bristol-Myers Squibb: Consultancy. Larson:Celgene: Consultancy; Novartis: Honoraria, Other: Contracts for clinical trials; Agios: Consultancy. Oehler:Blueprint Medicines: Consultancy; NCCN: Consultancy; Pfizer Inc.: Research Funding. Deininger:Humana: Honoraria; Incyte: Honoraria; Blueprint: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Research Funding; Ascentage Pharma: Consultancy, Honoraria; TRM: Consultancy; Sangoma: Consultancy; Fusion Pharma: Consultancy; Adelphi: Consultancy; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Sangamo: Consultancy. Shah:Bristol-Myers Squibb: Research Funding. Ritchie:Tolero: Other: Advisory board; Celgene: Other: Advisory board; Celgene, Novartis: Other: travel support; Jazz Pharmaceuticals: Research Funding; Celgene, Incyte, Novartis, Pfizer: Consultancy; AStella, Bristol-Myers Squibb, Novartis, NS Pharma, Pfizer: Research Funding; Ariad, Celgene, Incyte, Novartis: Speakers Bureau; Genentech: Other: Advisory board; Pfizer: Other: Advisory board, travel support; agios: Other: Advisory board. Silver:PharmEssentia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Cortes:Sun Pharma: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Forma Therapeutics: Consultancy, Honoraria, Research Funding; BiolineRx: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Biopath Holdings: Consultancy, Honoraria; Immunogen: Consultancy, Honoraria, Research Funding; Merus: Consultancy, Honoraria, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding. Atallah:Jazz: Consultancy; Helsinn: Consultancy; Pfizer: Consultancy; Takeda: Consultancy, Research Funding; Jazz: Consultancy; Helsinn: Consultancy; Novartis: Consultancy.

Description: Background: There have been significant advances in the management of acute myeloid leukemia (AML) in the past decade. However, management of AML in the pregnant patient has been challenging and as most interventions are contraindicated in pregnancy. Medical termination of pregnancy is advocated over chemotherapy in the first trimester as delaying chemotherapy could often be fatal. Chemotherapy during second and third trimesters may be provided with close surveillance of fetal abnormalities. There have been reports of worse outcomes in women with AML compared to non-pregnant age-matched female patients with AML. The outcomes in these patients have not been systematically studied and have been limited to case reports and case series in medical literature. Methods: Patients hospitalized with a diagnosis of AML were identified using the International Classification of Disease (ICD-9) codes in the National Inpatient Sample database. This database is maintained by the Agency of Healthcare Research Quality under the United States Department of Health and Human Services. It represents 20% of all hospitalizations occurring in the United States every year. Amongst these AML patients, all patients who were pregnant were identified and their demographic information was extracted. Other details related to their hospitalization, hospital size, location, region and teaching status were also determined. The association of outcomes with common medical comorbidities such as hypertension, hyperlipidemia, chronic kidney disease and diabetes were studied. Pregnancy related outcomes, mode of delivery and mortality rates were calculated for the 15 year time period. Results: During the time period of 2000 to 2014, 678942 hospitalizations involved AML patients of which 5076 were noted to be from pregnant women. The hospitalization trend gradually increased over these years and was noted to be the highest in the age group of 18-34 years. The highest hospitalization rates were noted in African American and Native American patient populations. There was no difference in rate of hospitalizations between different hospital sizes (small vs. medium vs. large) and geographical location (Northeast vs. Midwest vs. South vs. West). Hypertension, hyperlipidemia, chronic kidney disease and smoking were noted to be more prevalent in pregnant women with AML. A majority of these patients had a Charlson's comorbidity index of 1-3. 3.5% of patients underwent medical termination of pregnancy, 16.25% suffered from pregnancy related complications, 0.6% suffered from puerperal infection, 4% of patients had normal vaginal delivery, 2.8% of patients had cesarian section and 5.7% of patient died. The rate of mortality was the highest in Native Americans followed by Caucasians. Mortality in these patients was also not related to hospital size or geographical location. Multiple regression showed that odds of mortality have decreased from 2000 to 2015 and that a higher Charlson's comorbidity score was an independent predictor of mortality. Conclusions: This is the first nationwide study to document the outcomes of pregnancy in hospitalized AML patients. AML in pregnancy is rare and this study shows that the mortality has been improving over the past 15 years. Notably, vaginal delivery has been more common than cesarian section in pregnant AML patients. Native Americans have high prevalence and high mortality rates, a likely result of healthcare disparity. Pregnant AML patients with high Charlson's comorbidity score may benefit from aggressive management of their comorbidities. Further studies are required to better characterize outcomes in pregnant women with AML. Disclosures Kota: Pfizer: Honoraria; BMS: Honoraria; Incyte: Honoraria; Xcenda: Honoraria; Novartis: Honoraria.

Description: Background: The Early T-cell precursor (ETP) variant of acute lymphoblastic lymphoma/leukemia (ALL) is a recognized high risk variant, recognized by the absence of CD1a, with aberrant myeloid antigen expression (CD13, CD33, CD117, and CD34), and frequent absence of CD4 or CD8. Treatment intensification may improve outcome in this subset. We undertook a multi-center retrospective analysis to explore clinical features, treatment exposure, and outcomes in ETP ALL as compared to non-ETP variants. Methods Adult T-ALL/T-LBL cases were compiled from 3 high volume cancer centers between the years 2003-2015. Data collected included patient demographics, tumor characteristics (white count at diagnosis, flow cytometry, FISH, cytogenetics, bone marrow involvement), treatment regimens and patient outcomes. ETP cases were defined as definite (CD1a-/CD8-/myeloid+) or probable (CD1a unk/CD8-/myeloid+, or CD1a-/myeloid+ with CD4+ and/or CD8+). All other cases were defined as non-ETP. Demographic data were compared using independent t-test assuming non-equal variance. OS and PFS were calculated from diagnosis and compared by Kaplan Meier and log-rank testing. Results Among 95 cases, 33 met criteria for definite/probable ETP (35%). OS and PFS data were indistinguishable between these groups (p=0.24, p=0.34), and were subsequently analyzed as a single group. Within the ETP group, no factors were associated with OS, including histology (CD1a+ vs unk, CD3cyt vs CD3sur, CD5dim vs CD5+, CD1a+/13+ vs CD1a+/13-, or CD13, CD33, CD117, CD34, & TdT status), marrow blast burden, peripheral blast burden, white blood cell count (wbc), hemoglobin (hgb), platelet count (plt), cytogenetics/FISH status, chemotherapy choice, or allogeneic transplant (in CR1 or at any time). With regards to PFS, only the inclusion of asparaginase with induction was associated with outcome (p=0.009), while all other covariates failed to show any significance. The ETP group was compared with the non-ETP subset (table 1). ETP were more likely to abuse marijuana, possibly reflecting unrecognized pesticide exposure, and were more likely to abnormalities of chrom 5 & 7. ETP trended towards lower response and higher rate of relapse, with lower PFS. Comparison of OS was not significant, likely related to small numbers (5y OS 37% vs 22%, figure 1). Non-ETP failed to show PFS benefit with frontline asparaginase, otherwise no treatment differences were apparent. Conclusions In this muti-center cohort we were able to identify and characterize ETP cases, confirming poor outcomes. Improvement in PFS among ETP patients treated with frontline asparaginase warrants attention and prospective confirmation. Unfortunately, OS remains poor independent of treatment or receipt of allogeneic transplant, suggesting a critical need remains for development and study novel therapies. Table 1. ETP Non-ETP p-value Median Age 37.45 34.74 0.42 Male 82% 66% 0.89 FamilyHx of Lymph/Leuk 21% 8% 0.112 FamilyHx of Ca 42% 25% 0.09 THC 24% 5% 0.021 P blasts 40% 28% 0.158 〉25% M blasts 30% 55% 0.0571 WBC 78.45 76.55 0.948 wbc〉100 24% 24% 0.995 Hgb 10.72 11.78 0.148 hgb

Description: Introduction: Bosutinib is approved for newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML) and CML resistant or intolerant to prior therapy. Efficacy and safety of first-line bosutinib and imatinib were assessed in older vs younger patients in the ongoing phase 3 BFORE trial (NCT02130557). Methods: In all, 536 patients were randomized 1:1 to receive bosutinib or imatinib (400 mg once daily). We compared outcomes in patients aged ≥65 years (older group) vs

Description: Background: APL is a highly curable malignancy with reported survival above 90% in many large co-operative group studies. A recent study with use of ATRA/Arsenic versus ATRA/chemotherapy in low and intermediate risk patients showed an expected survival of 99% and 91% respectively. These spectacular results are not evident in the general population. A recent study from US SEER data showed that the 1 and 5 year relative survival in APL patients is 71% and 65%. Studies from Swedish Cancer Registry and Brazil showed that the early deaths (ED) can be approximately 30%. This is in contrast to observation in clinical trials where the early mortality is around 5%. The common causes of death are hemorrhagic complications (HC), infection, differentiation syndrome (DS) and multi-organ failure. It is now agreed that decreasing early deaths is a high priority at all leukemia treatment centers and will improve population wide survival. We report results of our prospective trial using a set of streamlined treatment guidelines along expert support that has been highly effective in reducing ED. Methods: The high ED rate in APL prompted us to develop a single page treatment algorithm with emphasis on quick diagnosis, prompt initiation of therapy and proactive and aggressive management of all the major causes of death during induction. More importantly we made our treatment protocol available to smaller outlying treatment centers and guided the treating oncologist/hematologist during induction. We were awarded a grant by the Leukemia Lymphoma Society (LLS) to implement this protocol in the states of Georgia and South Carolina to cover 15 million people over a 3 year period. We partnered with 3 other large leukemia treating centers and the study was approved by the respective institutional review boards. Aggressive outreach effort were made by visiting most of the leukemia treatment centers in both states to publicize the concept and educate the treating physicians about ED. Physicians called one of the leukemia treating physicians at the larger centers when a diagnosis of APL was suspected or confirmed and all patients were co-managed till the end of induction. Patients were consented using a telephone consent approved by the IRB for obtaining treatment information. There were no exclusion criteria but 3 patients were excluded for refusing transfusion support for religious reasons. Results: From 11/2010 to 06/2015, we treated a total of 106 patients. 40 patients were managed at large leukemia treatment centers and 66 were managed in the community at 18 practices spread across Georgia, South Carolina and neighboring states. Median age was 52 years (range 21-87 years) and 53% were males. Out of a total of 106 patients, there were 7 deaths (6.6%) with cause of death being bleeding due to DIC (n=3), multi organ failure and differentiation syndrome (n=3) and infection (n=1). 5/7 deaths were in patients older than 60 years with 3 being in patients above 70 years. Deaths occurred in both academic (2/40, 5%) and community centers (5/66, 7%). 3 patients died after induction from non APL causes which were metastatic colon cancer, infection not related to the APL treatments and another 87 year old patient who refused treatments and opted for hospice care. Conclusions: Our experience clearly shows that a streamlined treatment algorithm along with help from experts will result in better outcomes in this most curable hematological malignancy. A similar approach pioneered by investigators in Brazil (IC-APL consortium) confirmed this to be an effective intervention to decrease early deaths in APL. We believe our experience warrants large scale implementation of our protocol and is presently approved as an ECOG/ACRIN trial. Figure 1. Survival in APL patients treated using the algorithm and network of treatment centers. Figure 1. Survival in APL patients treated using the algorithm and network of treatment centers. Disclosures Jillella: Leukemia Lymphoma Society: Research Funding. Stuart:Novartis: Research Funding. Galipeau:Emory University: Patents & Royalties. Kota:Pfizer: Membership on an entity's Board of Directors or advisory committees; Leukemia Lymphoma Society: Research Funding.

Description: Background: T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) in adults is an aggressive bone marrow malignancy that historically has a poor prognosis. Hyper-CVAD/methotrexate-cytarabine (hyper CVAD) regimen is a commonly used induction regimen following the protocol developed at MD Anderson Cancer center. Recent reports from Swedish Cancer Registry showed that relapse rates were much higher than expected with this regimen. We report our retrospective experiences across three different centers, Winship Cancer Institute of Emory University (Atlanta), University of Alabama Cancer Center (Birmingham) and Moffitt Cancer Center, (Tampa), with the use of this regimen for management of T-ALL/LBL. Methods: We conducted a retrospective chart review of all adult T-ALL/T-LBL cases at three large cancer centers between the years 2005-2015, treated at the physician's discretion. Data collected included patient demographics, tumor characteristics (white count at diagnosis, flow cytometry, FISH, cytogenetics, bone marrow involvement), treatment regimens and patient outcomes. Since hyper CVAD is a commonly used regimen outside of clinical trials, we focused our analysis on outcomes with this regimen. This regimen consisted of 4 courses of hyper-CVAD (fractionated cyclophosphamide, vincristine [VCR], doxorubicin, dexamethasone; the odd courses 1, 3, 5, 7); and 4 courses of MTX-Ara-C (methotrexate-cytarabine; the even courses 2, 4, 6, 8). CNS prophylaxis was given to all patients as per standard of care recommendations. All patients eligible for maintenance received 2 years of POMP (6 mercaptopurine, methotrexate, vincristine and prednisone) maintenance. Relapse-free survival (RFS) and overall survival (OS) were examined looking at medians and interquartile ranges of times to events. Kaplan Meier curves provided a graphical representation of the survival probability. Results: The final analysis included 95 adult patients with 64/95 (67%) patients receiving hyper-CVAD induction. Among the hyper-CVAD patients the median age at diagnosis was 30 (range 17-74). 71% of patients were male. Median white cell count (WBC) was 13.6/mm3 (1.7-500). Cytogenetic analysis revealed diploid in 36, complex (1 or more abnormalities in 16) and was not available in 12. WBC count was 〉 100,000/mm3 in 9 patients. 14 patients had mediastinal disease while 7 had CNS disease at diagnosis. Hyper-CVAD was the primary induction regimen in 56/64. Other patients either started on non-hyper CVAD induction prior to switching (n=3) or had asparaginase added to induction (n=5). The median number of cycles given as 7 (range 2-10) with 27(45%) patients receiving the planned 8 cycles. 37 patients did not complete 8 cycles due to stem cell transplant in remission (n=12), progressive disease (n=10) and unclear reasons (n=15). After induction therapy, remission status was unknown in 3 patients while 43/61 patients (70%) achieved remission. Maintenance with POMP was started in 21 patients that were in remission while 12 patients were taken to transplant without starting on maintenance. At the time of analysis, 23/64 (35%) patients are alive. The median relapse free survival was 387 days (12.9 months) and the median overall survival was 536 days (17.6 months). Excluding one patient lost to follow up, 44/63 (69.8%) relapsed. There was no difference in relapse versus non relapse patients in terms of median age (30 vs 33 years), median WBC at diagnosis (13.2 vs 13.6 mm3). Relapse rate was lower in patients with diploid karyotype (22/36, 61%) as compared to those with complex karyotype (14/16). Median survival in patients post relapse was 150 days. Only 9 patients were able to go for transplant after relapse with post transplant survival also being low (6 deaths). For the entire group, the two year survival was 35%. Conclusion: Our multi-institutional retrospective review shows that outcomes are poor across various centers in patients outside of clinical trials. This is the largest reported series of patients with adult T-ALL/T-LBL treated with hyper-CVAD outside of clinical trials. This data warrants investigation with newer agents to improve outcomes in this disease. Figure 1. Relapse free survival and overall survival in patients treated with hyper-CVAD (n=64) Figure 1. Relapse free survival and overall survival in patients treated with hyper-CVAD (n=64) Disclosures Kota: Leukemia Lymphoma Society: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees. Hathaway:OnQ Health: Research Funding. Shah:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Acetylon: Membership on an entity's Board of Directors or advisory committees; PLexus Communications: Honoraria; Pharmacyclics: Speakers Bureau; Spectrum: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Honoraria; Rosetta Genomics: Research Funding; Seattle Genetics: Research Funding. Jillella:Seattle Genetics, Inc.: Research Funding. Borate:Genoptix: Consultancy; Seattle Genetics: Research Funding; Gilead: Speakers Bureau; Alexion: Speakers Bureau; Novartis: Speakers Bureau; Amgen: Speakers Bureau.

Description: Introduction Myelodysplastic syndromes (MDS) are a group of hematological disorders leading to ineffective hematopoiesis and excess blast formation. We aimed to establish the incidence rates and median survival periods in MDS by gender, race and geographic location in a large population cohort. Methods We performed a retrospective analysis of the United States (US) SEER database for MDS cases diagnosed between 2001 and 2010 using ICD-0-3 histology codes 9980/3, 9982/3, 9983/3, 9984/3 and 9986/3. Incidence rates were calculated using the 2000 US standard population. Five-year relative survival rates were measured using the Kaplan-Meier method after excluding cases diagnosed by death certificate and autopsy. Results 14,920 cases were identified of which 87.2 % (n = 13,009) were present in age group sixty years and above. Age-adjusted incidence rates (per 100,000) for males were 14.8, 10.0, and 12.7 for white, black and other races respectively. The rates for females were 7.7, 7.1, and 7.0. On US county wise MDS case analysis, 11296 (86.8%) of cases were diagnosed in metropolitan counties and 1694 (13%) cases in nonmetropolitan counties. Median relative survival for white, black and other males were 27 months, 36 months and 24 months respectively ; 35 months, 38 months and 37 months for females. Five-year relative survival for white, black, and other males were 32.5% (95% CI 30.7- 34.3), 36.1% (95% CI 28.3 - 43.9) and 30% (95% CI 24.2 - 36.0) vs. 36.2% (95%CI 34.1 - 38.3), 41.1% (95% CI 34.4 - 47.8) and 37.3% (95% CI 30.2 - 44.5) for females. Median relative survival for cases from metropolitan and non-metropolitan counties were 31 months and 31 months respectively. Five-year relative survivals were 35.1% (95% CI 33.7-36.5) and 32.6% (95% CI 29.1-36.0) for metropolitan and non-metropolitan counties MDS cases respectively. Conclusion The incidence of MDS was higher in males compared to females with the highest rate in white males. Survival rates were similar in both sexes. No significant difference in survival rates were seen among the racial groups. No significant difference in the median survival and five-year relative survival rates were noticed between metropolitan and non-metropolitan groups. Disclosures: No relevant conflicts of interest to declare.

Description: Background APL is a highly curable malignancy with cure rates of greater than 90% in most co-operative group trials. Population-based studies show that the survival is only about 65-70% with up to 30% early deaths. The most common reasons of early deaths are bleeding, differentiation syndrome (DS) and infection. Differentiation syndrome is very peculiar to this disease and potentially fatal unless recognized early. The wide variety of clinical presentations associated with DS might lead to delay in diagnosis in some patients which may lead to poorer outcomes. European Leukemia Net recommendations suggest that congestive heart failure (CHF) is one of the presenting features of DS and most of the reports on cardiac abnormalities focus on pericardial effusion. Cardiac stunning is only briefly reported in the literature. Cardiac stunning might be a result of cytokine storm attributable to tumor lysis in addition to being part of the DS. Here we report the incidence of CHF in patients undergoing induction for APL. Methods We performed a retrospective chart review on patients diagnosed with APL who received induction between December 1, 2004 and July 31, 2013 at Georgia Regents University and also patients who were referred to us from surrounding treatment centers with whom we co-manage these patients. Baseline and follow up ejection fractions (EF) were recorded by echocardiogram or nuclear medicine scan. We evaluated patients who had a drop in EF during the induction period. Results 41 consecutive patients with APL with normal ejection fraction at diagnosis were evaluated. 1 patient refused treatment and was excluded. 38/40 patients received idarubicin and ATRA remission induction and 2 patients received Arsenic and ATRA. There were seven deaths during induction phase of treatment In the surviving patients, 10 patients had a repeat ECHO during the first 30 days of induction phase for suspected cardiomyopathy. 5 patients (15.1% of surviving patients) demonstrated a decrease in EF and all five were in the anthracycline group. The age range of patients with drop in EF was 30-75 years. Absolute drop in EF was between 10- 35%. Only one patient had mild elevation in troponins while others had no elevation. 3 out of the 5 patients had significant DS. Of the surviving patients, 4 out of 5 patients recovered their EF completely with one patient recovering partially to 45-50% (from 20-25%). Conclusions Anthracyclines, along with ATRA, are still the mainstay of treatment for this curable malignancy. Although the incidence of cardiac abnormalities is described with repeated courses of anthracyclines, a single dose of anthracyclines can also play a role in cardiac injury. The highly inflammatory state present during the early treatment of APL might also play a role in cardiac injury resulting in higher number of patients with decreased EFs. DS clinical presentation most commonly involves dyspnea and edema, which are also symptoms of heart failure. Prompt cardiac evaluation should be undertaken to rule out congestive heart failure as an early start to therapy will lead to improved outcomes. Disclosures: Awan: Lymphoma Research Foundation: Research Funding; Spectrum Pharmaceuticals Inc.: Speakers Bureau. Jillella:Lymphoma Leukemia society: Research Funding. Kota:Teva: Speakers Bureau; Ariad: Advisory board, Advisory board Other.

Description: The second-generation TKIs (2G-TKIs) Dasatinib (DAS) and Nilotinib (NIL) yield faster responses in newly diagnosed chronic phase (CP) CML as compared to Imatinib (IM) however, long-term safety of these agents is a growing concern. We identified 10 patients with CP CML diagnosed between 08/2013 and 06/2015 who initiated 2G-TKIs and were then switched after optimal response at 3 months to IM. DAS was administered to 8 patients at 100 mg/d and NIL in two patients at 300 mg twice a day. Response to TKI was assessed by quantitative reverse transcriptase polymerase chain reaction (qPCR) for BCR-ABL1. Response to 2G-TKIs after 3 months was as follows: CHR (n=10), 1 log (

Description: Background Acute Promyelocytic Leukemia is a highly curable malignancy with cure rates of greater than 90% in most co-operative group trials.  However, population based studies indicate that the survival is much lower with up to 30% early deaths.  The most common causes of early deaths are bleeding, differentiation syndrome and infection. Early identification and management of these three complications is essential if the outcomes are to be improved further. Bleeding in APL is secondary to disseminated intravascular coagulation (DIC) a peculiar complication of the disease and coagulation panel including d-dimer, fibrinogen levels, prothrombin time, activated partial thromboplastin time are commonly used as markers of DIC. There are presently no available tests to identify DS or infection early and are entirely clinical diagnoses. Here we report the importance of d-dimer levels as probable markers of DS or infection during induction treatment for APL. Methods We performed a retrospective chart review on forty one patients diagnosed with Acute Promyelocytic Leukemia and treated with ATRA from September 2005 – June 2013 from Georgia Regents University and those referred here from surrounding treatment centers.  Data obtained included D-Dimer levels at diagnosis, daily d-dimer levels when available, dates of differentiation syndrome from start of treatment and dates of infectious complications when available which was obtained from progress notes and microbiology lab and radiology reports. Results 41 consecutive APL patients were evaluated for this study. One patient refused treatment and 15 patients did not have coagulation labs (specifically d-dimer) done throughout the course of induction treatment and had to be excluded. Age range of all the patients treated was 21-75 years. There were seven deaths overall and 21 patients had some evidence of DS. The diagnosis of DS was made clinically as per standard guidelines. We included 25 patients in whom there were d-dimer levels done throughout the hospitalization in this study. In these 25 patients, all had an increase in d-dimer levels after an initial drop as the DIC is corrected. 6 patients did not have any complications. In 4 patients the rise in d-dimer was followed by infectious complications. In the other 15 patients, their hospitalization was complicated by DS. In these 15 patients,  6 had elevation in d-dimer prior (0-5 days) to development of DS. In 3 patients the DS developed followed shortly by an elevation in d-dimer. The correlation between d-dimer elevation and DS could not be clearly ascertained from the available documentation in the other 6 patients. Conclusions APL is a curable malignancy but early deaths leads to poor outcomes outside of clinical trials. Early identification of the complications of the disease and treatment will allow us to further improve the outcomes in the community. D-dimer is an acute phase reactant and is elevated in any inflammatory state. From our data, the elevation in d-dimers following an initial decrease after correction of coagulopathy secondary to DIC might be marker of differentiation syndrome and or infection. These two conditions are pro-inflammatory states and might explain the increase in d-dimers observed. A larger scale validation is essential to confirm this observation which then might lead to more prompt identification of the complications and ultimately improved outcomes. Disclosures: No relevant conflicts of interest to declare.