ALBERT

Beschreibung: Key Points Infiltrating FLT3-ITD neutrophils identified in skin confirms terminal differentiation of FLT3-ITD blasts after FLT3 inhibitor therapy. Neutrophilic dermatosis after FLT3 inhibition may be a manifestation of a differentiation syndrome associated with this treatment.

Beschreibung: Key Points AE induces hematopoietic self-renewal through a COX/prostaglandin E2/β-catenin signaling pathway. Clinically available COX inhibitors may target AML stem cells and suppress AML of various karyotypes.

Beschreibung: Acute myeloid leukemia with chromosomal alterations impacting the core binding factor transcription complex (CBF-AML), specifically t(8;21) and inv(16), are associated with a greater responsiveness to cytarabine-based chemotherapies and a more favorable prognosis. The latter has been primarily gleaned from outcomes of large clinical trials of AML. However, to date, there is limited population-based outcomes data on CBF-AML. We therefore performed an epidemiologic retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database to assess survival trends for CBF-AML at the population level between 2000 and 2010. Patients and Methods Patients with a diagnosis of CBF-AML between 2000 and 2010 were identified using the SEER 18 registries database. We included patients with a diagnosis code of inv(16)/t(16;16) AML (Code 9871) or t(8;21) AML (Code 9896) diagnosed between January 2000 and December 2010. Patients were divided into cohorts based on age at diagnosis: 15-44 years old, 45-64 years old, 65-74 years old, and 75-84 years old. Disease incidence was calculated, as were early mortality rates, defined as death within 1 month. Overall survival (OS) was estimated using the method of Kaplan and Meier. Cox regression was performed to estimate predictors of survival by specific CBF-AML type, age cohorts, race/ethnicity, gender, year of diagnosis, number of primary malignancies, and residence. Results We identified 777 patients with a new diagnosis of CBF-AML between 2000 and 2010. The incidence of CBF-AML increased with advancing age (ages 15-44, 0.06 per 100,000 people; ages 45-64, 0.13; ages 65-74, 0.25; ages 75-84, 0.28). Median OS for all patients was 22 months, and the combined 3-year OS was 44.3% (Fig. 1). Median OS increased from 16 months during the period encompassing 2000 and 2002 to 25 months during the period from 2006 to 2008 (p=0.002) (Fig. 2). The rate of early death was 13%, which increased with age (15-44 5%, 45-64 10%, 65-74 20%, 75-84 33%; P

Beschreibung: Abstract 1484 Introduction: Acute Myeloid Leukemia (AML) is more common among patients over the age of 60, who also historically have a poorer prognosis. It is unclear which patients will benefit most from intensive chemotherapy; prognostic factors have been identified to risk-stratify these patients, but tend to consider characteristics specific to the disease such as cytogenetics [Lancet 2010; 376: 2000–08], and may not account for patient comorbidities that preceded the diagnosis of AML. Increased body mass index (BMI) has been associated with an increased incidence of various malignancies, including AML [The Oncologist 2010; 15: 1083–1101], and is increasingly prevalent among the general population. We sought to determine whether patient BMI at time of AML diagnosis is related to overall survival among patients older than age 60. Methods: We performed a retrospective chart review of all patients diagnosed at Massachusetts General Hospital with records available in the electronic medical record between January 1, 1992 and May 1, 2011. Patients were identified using billing codes and pathology records and underwent chart review to confirm a diagnosis of AML. Patients were included in this review if they had a pathologically-confirmed new diagnosis of AML, were older than age 60 at the time of diagnosis, and were given cytarabine-based induction chemotherapy. We collected past medical history, presenting labs, patient cytopathology, weight, and height at diagnosis. Overall survival (OS) was estimated using the Kaplan-Meier method, with 95% confidence intervals calculated using Greenwood's formula. We then performed a stepwise multivariable Cox regression analysis, pre-specifying that a variable had to be significant at the 0.3 level before it could be entered into the model, while a variable in the model had to be significant at the 0.05 level for it to remain in the model. Results: We identified 152 patients with AML diagnosed after the age of 60. The median age was 68 years (range 60–87); 54% of patients were male, and 86% were white. Patient disease was identified as de novo in 50%, and secondary in 50%. Cytogenetics, when available (86.2% of patients), were most commonly normal (37.5%) or poor risk (34.2%); only 1.3% of patients were good risk. The median OS for all patients was 269 days (95% CI 217–323). The 60 day OS for all patients was 83% (95% CI 77–89%). Using the log-rank test to perform a univariate analysis, worsened OS was associated with increased age (P=0.024); body mass index (BMI) 〈 27, the median BMI in our cohort, (P=0.011); presence of coronary artery disease (CAD) (P=0.042); and with cytogenetics (P=0.013). The multivariable analysis of the Cox proportional-hazards model found that the hazard rate for death was increased with older age (HR 1.53, P=0.027, 95% CI 1.05–2.24), lower BMI 〈 27 (HR 1.93, P=0.002, 95% CI 1.28–2.92) and cytogenetics (P

Beschreibung: Abstract 1041 Introduction Granulocytic Sarcoma (GS), also known as chloroma or myeloblastoma, is a rare neoplasm composed of immature myeloid cells occurring in any extramedullary organ, most commonly in the lymph node and soft tissue. It can occur as an isolated lesion, or in conjunction with a diagnosis of acute myeloid leukemia (AML), myeloproliferative disorder (MPD) or myelodysplastic syndrome (MDS). GS has been generally associated with more aggressive disease and a poor prognosis. Although it has been described in the literature in small case series, the clinical characteristics and prognosis of patients with GS associated with AML, MDS, MPD or as an isolated lesion have not been thoroughly described. We therefore studied our institutional experience of granulocytic sarcoma to gain further insight into the clinical features and associations of this disease. Methods We conducted a retrospective medical record review of patients who presented with GS to Massachusetts General Hospital from 1994 through 2011. In total, 35 patients with GS were identified. Kaplan Meier method was used to estimate overall survival (OS). OS was defined as the duration from the time of diagnosis of GS to date of death; patients still alive at the time of analysis were censored. Patients were categorized into three groups for analysis depending on the presence of bone marrow disease: primary (isolated) GS, GS associated with AML, and GS associated with MDS or MPD. Result Of 35 patients with GS, 20 (57%) were associated with a diagnosis of AML, 10 (29%) presented with either MDS or MPD, and 5 (14%) presented with primary GS. Of the AML-associated GS, 13 occurred concurrently with AML at diagnosis and 7 presented as AML relapse. Of the 10 cases of GS with either MDS or MPD, one patient presented with MDS and 9 with MPD. The median age of all patients was 57 years old; 19 of 35 patients were female. Median white blood count (WBC) was 4.6 (th/cmm) (IQR 3.5–8.8) for patients with AML-associated GS and 20.2 (th/cmm) (IQR 9.7–61) for those with MDS/MPD-associated GS. One year survival was 10% (95% CI 0.5 – 35.8%) in MDS/MPD associated GS, 49.5% (95% CI 26.5 – 68.9%) in AML associated GS, and 60% (95% CI 12.6 to 88.2%) in primary GS. The most common area of involvement in patients with AML-associated GS was the nervous system (22%). In contrast, among patients with MPD/MDS-associated GS, the most commonly involved site was bone (45%) (Table 1). 63% of all patients had one site of involvement with GS at presentation. The most common presenting symptom was pain either caused by a mass or lymphadenopathy. Cytogenetics were normal for the majority of patients. Interestingly, however, one AML patient and one patient with primary GS presented with a 9;22 translocation, two AML presented with other cytogenetic abnormalities involving chromosome 9 (t(9;11)(p22;q23) & add(9)(q34)), and three others, including one with primary GS, displayed abnormalities at chromosome 11, specifically 11q23 (Table 2). Conclusions With this study, we provide a single institution experience of granulocytic sarcoma, a rare manifestation of myeloid neoplasms. Interestingly, we found variable presentation with different patterns of site involvement and white blood counts in patients with GS associated with AML and in those with GS associated with MPD/MDS. Additionally, certain karyotypic abnormalities were over-represented in patients with GS, including t(9;22) and translocations involving chromosome 11q23. Finally, in our small series, patients with a diagnosis of GS associated with MPD/MDS had worsened outcomes compared to those with AML-associated GS or primary GS. Larger, prospective studies are needed to better and more fully assess outcomes in these patients. Disclosures: No relevant conflicts of interest to declare.

Beschreibung: Background The diagnosis of acute myeloid leukemia (AML) is associated with a poor prognosis, particularly for patients older than age 65 and those with relapsed or refractory disease. Little is known about the specific location where AML patients die and how disease status, therapeutic management, and symptoms influence the place of death. Methods We conducted a retrospective descriptive analysis of consecutive patients with AML who died at our institution between January 2007 and December 2012. In addition to place of death, the variables of interest included: disease status at death, previous transplant, prior chemotherapy, presence of a dedicated caregiver, gender, and age at diagnosis. Disease status was classified as: new diagnosis, active disease, relapsed, or in remission. A new diagnosis was defined as a diagnosis within the prior 30 days. Active disease was defined as disease beyond 30 days and without prior remission. Medical records were reviewed to identify whether palliative care service was consulted, and the range of symptoms reported during the last two weeks of life. Categorical variables were compared among groups using chi-square and continuous variables with the Kruskal Wallis test. Results We identified 166 patients with AML. The majority of study patients were white (90%) and male (55%) with a median age of 69 years (range 21-94 years). Disease was characterized as de novo AML (49%), therapy related (14%), secondary to antecedent myelodysplasia (29%) or other hematologic disease (8%). The median time from diagnosis to death was 5.5 months (range 0.7-50.4). The majority (82%) had active AML at time of death. Other causes of death included transplant related complications (8%), sepsis (4%), bleeding (2%), or other (4%) causes. Palliative care consultation occurred in 35% of the cases. The consults typically were late in the course of illness with the median time from initial consult to time of death of 8 days (range 0-122 days). Information on the location of death was available for 154 patients, of whom, 23 (15%) died in inpatient hospice, 41 (27%) at home, 48 (31%) died while hospitalized in a non-ICU bed and 42 (27%) died in either the Intensive Care Unit or Emergency Department (ED). Location of death was significantly associated with disease status at death (p〈 0.0001, Figure 1), prior anthracycline/cytarabine based induction therapy (p=0.01), social support/dedicated caregiver (p=0.05), and age at diagnosis (p

Beschreibung: Point mutations in isocitrate dehydrogenase (IDH) define distinct subsets of acute myelogenous leukemia (AML). IDH is a metabolic enzyme that interconverts isocitrate and α-ketoglutarate (α-KG), but cancer-associated point mutations in IDH1 and IDH2 confer a neomorphic activity that allows reduction of α-KG to the oncometabolite R-2-hydroxyglutarate (2-HG). High levels of 2-HG have been shown to inhibit α-KG-dependent dioxygenases including histone and DNA demethylases, which play a key role in regulating the epigenetic state of cells, but the relationship between 2-HG and oncogenesis is not completely understood. Consistent with 2-HG promoting cancer via an effect on chromatin structure, patients harboring IDH mutations display a CpG island methylator phenotype (CIMP) and several studies have shown that overexpression of IDH mutant enzymes can induce histone and DNA hypermethylation as well as block cellular differentiation. In addition, mice engineered to express IDH1-R132H in hematopoietic tissue have increased early hematopoietic progenitors, splenomegaly, anemia, hypermethylated histones and altered DNA methylation patterns similar to those found in AML patients harboring IDH1/2 mutations.[i] Taken together, these data suggest that cancer-associated IDH mutations may induce a block in cellular differentiation to promote tumorigenesis. To investigate whether selective pharmacological inhibition of the mutant IDH1 enzyme could provide an effective way to lower intracellular 2-HG levels and restore normal differentiation, we treated TF-1 cells or primary human AML patient samples expressing mutant IDH1 with AG-120, an oral, selective, first-in-class, potent IDH1 mutant inhibitor currently in phase I clinical trials. Treatment with AG-120 decreased intracellular 2-HG levels, inhibited growth factor independent proliferation and restored erythropoietin (EPO)-induced differentiation in TF-1 IDH1-R132H cells. Similarly, pharmacological inhibition of mutant IDH1 enzyme with AG-120 in primary human blast cells cultured ex vivo provided an effective way to lower intracellular 2-HG levels and induced myeloid differentiation. Taken together, these data demonstrate that AG-120 is effective at lowering 2-HG levels and restoring cellular differentiation, and support further clinical development of this compound. Figure 1: Diagnosis and karyotypes of primary AML patient samples used in ex vivo studies Figure 1:. Diagnosis and karyotypes of primary AML patient samples used in ex vivo studies PB = peripheral blood, BM = bone marrow Figure 2: Percent 2-HG remaining relative to DMSO control after 6-day treatment with AG-120 in IDH1 R132H or IDH1 R132C patient samples Figure 2:. Percent 2-HG remaining relative to DMSO control after 6-day treatment with AG-120 in IDH1 R132H or IDH1 R132C patient samples or following 6 days of treatment with control (DMSO) or AG-120 (0.5, 1.0, and 5.0 μM) Figure 3: Relative proportion of cell types in human AML bone marrow samples untreated Figure 3:. Relative proportion of cell types in human AML bone marrow samples untreated [i] M. Sasaki et al., IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics. Nature 488(7413):656-9, 2012. Disclosures Hansen: Agios Pharmaceuticals: Employment, Stockholder Other. Quivoron:Institut National de la Santé Et de la Recherche Médicale (INSERM): Grant Other; Association Laurette Fugain: Grant, Grant Other; Institut National du Cancer (INCa): Grant, Grant Other; Association pour la recherche contre le Cancer (ARC): Grant, Grant Other; AGIOS: Grant Other. Straley:Agios Pharmaceuticals: Employment, Stockholder Other. Lemieux:Agios Pharmaceuticals: Employment, Stockholder Other, US20130190249 (pending) Patents & Royalties. Popovici-Muller:Agios Pharmaceuticals: Employment, Stockholder Other. Fathi:Agios Pharmaceuticals: Advisory board participation Other. Gliser:Agios Pharmaceuticals: Employment, Stockholder Other. David:Institut National de la Santé Et de la Recherche Médicale (INSERM): Grant Other; Institut National du Cancer (INCa): Grant, Grant Other; Association pour la Recherche contre le Cancer (ARC): Grant, Grant Other; Association Laurette Fugain: Grant, Grant Other; AGIOS: Grant Other. Bernard:Institut National de la Santé Et de la Recherche Médicale (INSERM): Grant Other; Association Laurette Fugain: Grant, Grant Other; Institut National du Cancer (INCa): Grant, Grant Other; Ligue Nationale contre le cancer (LNCC): Grant, Grant Other; AGIOS: Grant Other. Dorsch:Agios Pharmaceuticals: Employment, Stockholder Other. Yang:Agios Pharmaceuticals: Employment, Stockholder Other. Su:Agios Pharmaceuticals: Employment, Stockholder Other. Agresta:Agios Pharmaceuticals: Employment, Stockholder Other. de Botton:AGIOS: Grant Other. Penard-Lacronique:Institut National de la Santé Et de la Recherche Médicale (INSERM): Grant Other; Association Laurette Fugain: Grant, Grant Other; Institut National du Cancer (INCa): Grant, Grant Other; Association pour la recherche contre le Cancer (ARC): Grant, Grant Other; AGIOS: Grant Other. Yen:Agios Pharmaceuticals: Employment, Stockholder Other.

Beschreibung: Background: Primary cardiac lymphoma (PCL) is rare extranodal subtype of non-Hodgkin's lymphoma (NHL) .It is extremely rare in immunocompetent patients. PCL usually occurs in adults mean age of 62.1 years with male predominance. Primary cardiac Burkitts lymphoma (PCBL) is small subgroup of the PCL. Characteristics, presentation and the optimal management guideline of BL have not been clearly defined. Method: We performed PubMed searches using the particular terms including but not limited to primary, cardiac, burrkit's , lymphoma to identify reported adult cases of PCBL.Different Variables including demographic, immune status, clinical presentation, radiographic and other clinical variables were analyzed. Result: This is the largest study of PCBL up to now.We analyzed 10 cases of adult PCBL including 9 reported cases in literature and one case who presented to our facility.Majority of patients were older than 65 (7/10), which is consistent with other studies of Burrkit's lymphoma in immunocompetent patients particularly in sporadic type. This can be secondary to similarity of pathogenesis and oncogenesis of PCBL to sporadic type. Although age at presentation ranged from 30 to 85 years old, only (2/10) were younger than 40. .All reported PCBL in our analysis including the one who presented to our facility were HIV negative and immunocompetent state. Thus we propose that PCBL can be categorized as a subtype of sporadic BL (SBL) but interestingly PCBL was more common in older patients in contrast with SBL as is more common in younger individuals, with a peak incidence at age 30 in adults. Most of patients (7/10) were male, which is also consistent with other studies of majority of NHL subgroups including cardiac lymphoma. As expected all patients except one presented with cardiac symptoms. Dyspnea was the most prominent presenting symptom comparing to palpitation, syncope or chest pain. It is most likely secondary to large pericardial effusion, which was present in all patients, rather than the mass effect. Interestingly one case had no cardiac mass identified and PCBL was diagnosed with pericardial analysis. These demonstrate the importance of evaluation for and analysis of possible pericardial effusion in patients, who present with dyspnea As noted, our analysis showed that all patient except the one who presented to our facility, presented with cardiac mass (9/10). Similar to other studies of cardiac lymphoma, right heart particularly right atrium was the most common location of the cardiac mass. Cardiac lymphoma should be highly considered in patient with right atrial mass. Interestingly, Outcomes and chemotherapy response were variable; 3/10 cases reported favorable response to chemotherapy , however two cases with variable burrkit type and other chromosomal abnormalities had poorer prognosis. Due to rarity and low number of the cases ,outcome analysis adjusted with treatment regimen was not performed in our study. Conclusion: There is no comprehensive treatment analysis study for burrkit lymphoma . Due to complexity of pathogenesis and different behavior of this type of lymphoma, an efficient and optimal diagnostic, treatment and management guidelines for Burrkit lymphoma and its subtypes need to be developed. Table 1. Age Gender(Male : M, Female : F) Presenting Symptom Mass Location pericardial effusion Diagnosed by Chromosomal abnormalities HIV status Reference 79 F Dyspnea Left Ventricle (LV) Positive (pos) Pericardial analysis variant type-(8,22)(q24,q11), no c-myc negative (neg) J. Kuroda et al. elderly M Not available (NA) positive mass location NA NA NA NA neg S. Fatimi et al 61 F Dyspnea Right atrium (RA) +Right ventricle (RV) pos Excisional biopsy variant type- 49, XX, +X, t(8;14)(q24;q32), −14, +der(14)(3;8;14) (q27;q24;q32), +18, +20 neg Piero Maria Stefani et al. 33 M Dyspnea RA pos Excisional biopsy NA neg Chang-Fu Peng et al. 44 F Abdominal Discomfort RA pos Pericardial analysis t(8;14) neg Dimitrios et al. 77 M Dyspnea large mass , location NA pos Autopsy of mass t(8;14) neg Takai K. et al. 70 M Dyspnea RA pos Excisional biopsy t(8;14) neg M.De Filippo et al. 74 M Dyspnea RA pos Pericardial analysis NA neg Sylvie et al. 67 M syncope bi-atrial + LV pos Excisional biopsy t(8;14) neg Francesco Santini et al. 84 M Dyspnea No mass pos Pericardial analysis t(8;14) neg Presented to our facility Disclosures No relevant conflicts of interest to declare.

Beschreibung: Mutations in genes encoding the isocitrate dehydrogenase 1/2 (IDH 1/2) enzymes increase production of the oncometabolite 2-hydroxyglutarate (2HG), resulting in elevated 2HG in patients with IDH-mutant AML. This may allow for non-invasive diagnostic and predictive markers of disease; however, the optimal threshold of 2HG levels to predict IDH mutation status, or whether 2-HG measurements in different compartments are equally predictive, is unknown. We measured 2-HG levels in serum, urine, bone marrow aspirate, and bone marrow cell pellet to determine the optimal predictive value of 2HG levels for IDH mutations at AML diagnosis. Patients with newly diagnosed AML had prospective measurements of 2HG levels at diagnosis by liquid chromatography-tandem mass spectrometry in serum, urine, marrow aspirate, and marrow pellet samples. Patients analyzed had IDH1 R132 and IDH2 R140 and R172 testing. Hotspot mutational profiling was performed for AKT1, APC, BRAF, CTNNB1, EGFR, ERBB2, KIT, KRAS, MAP2K1, NOTCH1, NRAS, PIK3CA, P53, and PTEN; patients were also tested for FLT3, NPM1, and CEBPA mutations. IDH1/2 mutant patients were compared to wildtype (WT) patients using a Wilcoxon rank sum, Fisher's exact, or Kruskal Wallis test, as appropriate. Performance characteristics of 2HG to predict the presence of IDH1/2 mutations were done using a recursive partitioning algorithm in R version 3.2.1, with the rpart package. 228 patients with newly diagnosed AML had 2HG levels in serum, urine, marrow aspirate, and marrow pellet samples. All patients had testing for IDH1 R132 and IDH2 R140 and R172 mutations. The patients were 56% male; 13 patients had APL, none with IDH mutations. IDH mutations were identified in 23% (n=52) of the cohort: IDH1 R132C (n=12), IDH2 R172 (n=9), and IDH2 R140Q (n=29), and 2 additional patients had mutations in both IDH1 R132 and IDH2 R140 (Table 1). The optimal test cut-off of 2HG to predict IDH status was 534.5 ng/mL in the serum (n=221), 16650 ng/mL in the urine (n=213), 2210 ng/mL in the marrow aspirate (n=190), and 1146 ng/2*10^6 cells in the pellet (n=159). Serum and pellet values had the greatest specificity for the presence of an IDH1/2 mutation (0.9882 and 1.000, respectively; Table 2). The positive predictive value of an elevated serum or pellet 2HG level at these cut-offs was 95.4% and 100%, given a 23% IDH mutation prevalence in this study population. The marrow aspirate had the greatest sensitivity (0.8837) and negative predictive value (96.6%). Urine 2HG levels were less sensitive than serum 2HG levels, although above the urine cut-off the specificity for IDH mutations was similar (Figure 1). 2HG levels in the serum, urine, and marrow can be used to identify IDH mutations in AML. Serum 2HG testing is an effective non-invasive mechanism to predict IDH1/2 mutation status. A serum cut-off of 534.5 ng/mL has a specificity of 0.9882 and, with an IDH mutation prevalence of 23%, was associated with a PPV of 0.9535.Table 1.Patient CharacteristicsNo IDH mutationIDH mutationTotalp-valueMale sex101 (57%)26 (50%)127 (56%)0.43Cytogenetics0.0002Favorable26 (15%)026 (12%)Intermediate95 (54%)41 (82%)136 (61%)Adverse52 (30%)9 (18%)61 (27%)Age (median, range)66 (20, 87)66.5 (41, 86)66 (20, 87)0.27WBC (median, range)5.35 (0.60, 315.4)3.65 (0.20, 333.2)5.25 (0.20, 333.2)0.33No IDH mutationIDH mutationNumber assessedp-valueNRAS27 (17%)9 (19%)2100.83KRAS16 (10%)0 (0%)2100.03TP5315 (9%)1 (2%)2100.13KIT2 (1%)1 (2%)2100.54FLT3ITD34 (20%)4 (8%)2180.06FLT3TKD10 (6%)2(4%)2180.74NPM129 (17%)15 (30%)2190.07CEBPA13 (13%)3 (10%)1021.002HG MeasurementsNo IDH mutationIDH mutationTotalSerum (ng/mL)79.5 [52,123] n=1701420 [675,2735] n=51101 [58,101] n=221Urine (ng/mL)3590 [2230,6220] n=16318300 [7260,59500] n=504330 [2450,8580] n=213Marrow aspirate (ng/mL)BQL [BQL,BQL] n=14718400 [4270,43100] n=43BQL [BQL,1430] n=190Pellet (1000 ng/2*10^6 cells)64 [BQL,169] n=1271420 [675,2735] N=32107 [BQL,500] n=159 Table 2. Test characteristics based on optimal 2HG cut-off, by compartment. Compartment 2HG cut-off Sensitivity Specificity 23% prevalence PPV NPV Serum 534.5 ng/mL 0.8039 0.9882 0.9535 0.9438 Urine 16650 ng/mL 0.5600 0.9877 0.9333 0.8798 Marrow Aspirate 2210 ng/mL 0.8837 0.9660 0.8837 0.9660 Marrow Pellet 1146 ng/2*10^6 cells 0.7813 1.000 1.000 0.9478 Figure 1. Relative frequencies of 2-HG levels according to cut-off values in serum (top) urine (bottom). Figure 1. Relative frequencies of 2-HG levels according to cut-off values in serum (top) urine (bottom). Figure 2. Figure 2. Disclosures Chen: Bayer: Consultancy, Research Funding. Stone:Agios: Consultancy; Celator: Consultancy; Pfizer: Consultancy; Merck: Consultancy; AROG: Consultancy; Abbvie: Consultancy; Celgene: Consultancy; Roche/Genetech: Consultancy; Karyopharm: Consultancy; Amgen: Consultancy; Sunesis: Consultancy, Other: DSMB for clinical trial; Juno: Consultancy; Novartis: Research Funding. Fathi:Exelexis: Research Funding; Agios: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees; Ariad: Consultancy; Takeda Pharmaceuticals International Co.: Research Funding.

Beschreibung: Abstract 3772 Introduction: Clinical outcomes for patients with chronic myeloid leukemia (CML) have dramatically improved over the course of the past ten years, following the advent of tyrosine kinase inhibitors (TKIs) that target BCR/ABL. Nonetheless, survival differences persist between age groups. Prior analyses suggested that this difference occurs in part due to treatment variation; in Sweden, patients older than age 79 had poorer relative survival, and more typically were treated with hydroxyurea rather than a TKI [Bjorkholm, J Clin Oncol 29:2514]. Other studies have noted gains made in relative survival up to the year 2004 [Brenner, Haematologica93:1544], but longer-term overall survival following the widespread use of TKI therapy is less well described among older patients in the U.S. We performed an epidemiologic study of patients registered in the Surveillance, Epidemiology, and End Results (SEER) database to estimate the 5 year overall survival (OS) of patients treated for CML in the era of TKI therapy to assess for differences in survival outcomes among patients within different age groups. Methods: Patients with a diagnosis of CML were identified using the SEER 19 registries database [www.seer.cancer.gov, 1973–2009, November 2011 submission]. We included patients with a diagnosis code of CML NOS (Code 9863) and BCR/ABL+ CML (Code 9875) diagnosed between January 2000 and December 2005. This interval brackets the FDA approval of imatinibin 2001, and its incorporation into NCCN guidelines in 2003. To reflect the evolution of CML treatment during this interval, we trended 5-year overall survival by the year of initial diagnosis. To evaluate the effect of age on survival, patients were divided into cohorts based on age at diagnosis: 15–44 years old, 45–64 years old, 65–74 years old, and 75–84 years old. Overall survival was estimated using the method of Kaplan and Meier. Cox proportional hazards regression was used to model OS to estimate the effects of year of diagnosis within each age group. All analyses were performed using SAS statistical software. Results: We identified 5,138 patients registered in the SEER database with a new diagnosis of CML between January 2000 and December 2005. The patients were 57.6% male; this was the first recorded primary malignancy for 88.4% of the cohort. The 5-year OS improved among patients in every age group between the years 2000 and 2005 (Table 1, Figure 1). Compared to patients diagnosed in the year 2000, patients between the ages of 15 and 44 years had the greatest improvement in 5 year OS (Figure 1; hazard ratio (HR) for dying 0.427, 95% CI: [0.278;0.655], P