ALBERT

Beschreibung: BACKGROUND: Anthracycline based treatment for acute myeloid leukemia (AML) can be associated with significant morbidity and mortality amongst older patients or those with significant co-morbidities. Furthermore, for patients with previous anthracycline exposure or preexisting cardiac disease anthracyclines pose an increased risk of cardiotoxicity. For such patients intensive treatment options are limited. The FLAG (fludarabine, cytarabine and filgrastim) regimen is a non-anthracycline based chemotherapy useful for relapsed/refractory AML and as initial therapy for “fit” eligible patients. We present our experience using FLAG as first line therapy in a cohort of newly diagnosed AML patients with advanced age, significant co-morbidities or preexisting cardiac disease. METHODS: A single institution retrospective chart review was undertaken of patients treated with FLAG as frontline therapy from 2004 – 2013 with follow-up until June 2014. All patients were considered ineligible for standard ‘3+7’ treatment by the attending physician. RESULTS: Over the study period 56 patients received FLAG. Due to patient refusal or induction complications bone marrow assessments to ascertain remission status were not performed in 10 patients – to minimize bias these patients were evaluated for toxicity and overall survival (OS) but excluded from complete remission (CR) and relapse free survival (RFS) analysis. Of the 56 patients, 68% were males. The median age was 69 (21 – 80) with 79% aged ≥ 60 and 43% aged ≥ 70. Fifty-five percent (31) of the patients had primary AML and cytogenetics were favorable in 5% (3), intermediate in 66% (37), poor-risk in 21% (12) and failed in 7% (4). Forty-six percent (26) were treated with FLAG due to preexisting cardiac disease and others due to advanced age (20%), poor performance status (16%), co-morbidities (16%) or previous anthracycline exposure (2%). The ages of patients treated with FLAG due to cardiac disease or other reasons was similar (63.5 years vs. 66.9 years, p=0.27). Amongst patients with cardiac disease a pre-chemotherapy cardiac evaluation revealed wall motion abnormalities in 39% and an ejection fraction (EF) ranging from 33% - 81% with a borderline (≤ 50-51%) EF in 46%. Febrile neutropenia was observed in 82% (46) of patients, 27% (15) required intensive care support and the induction mortality was 16% (9). Amongst patients evaluated for a CR (46/56), 48% (22/46) obtained a CR. Although a CR was seen in 100% (3/3), 46% (15/33) and 37% (3/8) of patients with favorable, intermediate and poor-risk cytogenetics respectively there was no statistically significant difference (p=0.22) between groups. A CR was obtained in two additional patients following a second course of FLAG for an overall CR rate of 52% (24/46). Of these 24 patients, 8 (33.3%) received no additional treatment while 16 (66.7%) received consolidative chemotherapy. Of 10 eligible patients, 4 proceeded to an allogeneic stem cell transplant (allo-SCT) including two with preexisting cardiac disease. Of patients not transplanted 50% (10/20) eventually relapsed. There was no difference in relapse rates for those receiving FLAG for age/co-morbidities vs. cardiac disease (60% vs. 40%, p= 0.66) or for patients age

Beschreibung: Background: The diagnosis of acute myeloid leukemia (AML), response to treatment and disease recurrence are most commonly assessed with bone marrow studies. Recommendations from leading experts (Bain, 2001) and guidelines of the European LeukemiaNET (Dohner, 2010) and the National Comprehensive Cancer network (O’Donnell, 2012) suggest that only the bone marrow aspirate (BMA) is necessary to assess residual disease while the trephine biopsy (TB) is necessary only when an aparticulate BMA is obtained. In contrast, guidelines of the International Council for Standardization in Hematology (Lee, 2008) suggest that BMA and the TB should be routinely performed together as they provide complementary information. Due to these conflicting recommendations we sought to determine whether the TB provides additional sensitivity for the detection of residual leukemia following intensive chemotherapy for AML. Methods: A single centre retrospective chart review was conducted of bone marrow studies of all AML patients who had received intensive chemotherapy from 2004 – 2013. Those lacking a TB were excluded. Residual disease was assessed by morphological examination of the BMA and TB +/- immunostaining but minimal residual disease (MRD) analysis was not performed. Results: 598 bone marrow studies from 227 patients were evaluated. The median age of the patients was 54.6 (range 18 -77) with 70% age 〈 60. Forty-four percent were female. Cytogenetics were favorable in 30 (13%), intermediate in 146 (64%), high-risk in 44 (19%) and failed in 7 (3%) of the patients. Of the 598 bone marrow samples 198 (33%) were interim marrows performed 14 days following initiation of induction or re-induction chemotherapy (D14 marrow), 251(42%) were recovery marrows following induction/re-induction chemotherapy (EOI marrow) and 149 (25%) were during follow-up. The BMA was considered to be acellular/hypocellular in 31%, hemodilute in 16.4% and aparticulate/pauciparticulate in 27.3% of samples. As per guidelines 〉 200 cells were counted in 99.8% of the aspirate samples to ascertain remission status. The median length of the TB segments was 1.85 cm (0.2 – 7.0 cm) and it was considered inadequate in 12.7%, of good or excellent quality in 24.9% and adequate for residual disease assessment in the remainder of cases. Approximately 19 % of TB samples had mild to significant hemorrhagic artifact. The bone marrow cellularity could not be assessed in 1.2% of samples but was patchy in 0.5%, aplastic in 2.8%, hypocellular in 36%, normocellular in 23.6%, hypercellular in 23.2%, packed in 6% and was not described in 6.7% of the cases. Residual leukemia was identified in 33.1% of BMA and in 33.3% of TB samples. The BMA and the TB findings were concordant in 562 of 598 (94%) of cases. In 3.5% (21) of cases residual leukemia was seen in the TB but not the BMA whereas in 2.5% (15) of cases the BMA detected residual disease but the TB failed to do so. The TB led to a change in diagnosis from ‘No Leukemia’ to ‘Residual Disease’ in 5.1% of D14 marrows, 3.6% of EOI marrows and in 1.3% of follow-up marrows with no statistically significant difference between the groups (p=0.178). There was no relationship between a change in diagnosis and whether patients received an anthracycline or a non-anthracycline based chemotherapy regimen (4.4% vs. 3.2%, p=1.0). The TB, however, led to a change in diagnosis more commonly in patients with favorable risk karyotype relative to those with intermediate risk karyotype (20% vs. 6.2%, p= 0.02) but not relative to those with unfavorable risk karyotype (20% vs. 13.6%, p=0.53). Hemodilute bone marrow samples were more likely to have a TB related change in diagnosis relative to undilute samples (8.2% versus 2.6%, p=0.01) as were aparticulate/pauciparticulate samples relative to particulate samples (8% vs. 1.9%, p=0.00046). However, in multivariate analysis, only an aparticulate/pauciparticulate sample was associated with TB related change in diagnosis (p=0.015, OR = 3.6). Conclusions: Our data demonstrate that, following intensive chemotherapy, the BMA alone may fail to identify residual leukemia particularly when the BMA is aparticulate/pauciparticulate. In these situations the TB provides additional sensitivity for the detection of residual disease. Further studies are required to evaluate the need for the TB in particulate samples when combined with MRD analysis. Disclosures No relevant conflicts of interest to declare.

Beschreibung: BACKGROUND: The study of rare diseases is limited by the uncommon nature of the conditions as well as the widely dispersed patient populations. Current rare disease registries such as the National Organization of Rare Diseases utilize centralized platforms for data collection; however because of their broad nature, these do not always capture unique, disease specific elements. Hairy Cell Leukemia (HCL) is a rare leukemia globally with approximately 900 new cases diagnosed in the US each year. The HCL Foundation undertook creation of a Patient Data Registry that collects data from multiple HCL Centers of Excellence (COE) around the globe to better understand the complications, treatment outcomes, disease subtypes, comorbid conditions, epidemiology, and quality of life of patients with HCL. METHODS: Investigators at The Ohio State University Department of Biomedical Informatics and Division of Hematology in collaboration with the HCL Foundation developed a Patient Data Registry (PDR) for the longitudinal capture of high quality research data. This system differs from other registries in that it uses a federated( rather than centralized) architecture, wherein data is queried and integrated in an on-demand manner from local registry databases at each participating site. Further, the data collected for use in the registry combines both automated exports from existing electronic health records (EHRs) as well as additional data entered via a set of web-based forms. All manually entered data comes from source documents, and data provenance spanning electronic and manually entered data is maintained via multiple technical measures. Patients may be enrolled at HCL COE, or, if they do not have access to a COE they may enroll via a web-based portal (www.hairycellleukemia.org). At this time due to regulatory requirements the web-based portal is available to US patients only. All data are de-identified (see Figure 1: De-Identification Workflow) which reduces regulatory burden and increases opportunities for data access and re-use. End users have access to data via a project-specific query portal. RESULTS: The Patient Data Registry has been deployed at The Ohio State University, Royal Marsden Hospital, and MD Anderson Cancer Center, and is undergoing deployment at the University of Rochester. Up to 25 international HCL COE may participate. In addition, US patients are actively entering the registry via the web-based portal. To date, 227 patients have been consented to the registry with 119 of these being via the web-based entry point. CONCLUSION: We created an international and web-based patient data registry which will enable researchers to study outcomes in HCL in ways not previously possible given the rarity of the disease. This work was made possible by research funding from the Hairy Cell Leukemia Foundation. Figure De-Identification Workflow Figure. De-Identification Workflow Disclosures Andritsos: Hairy Cell Leukemia Foundation: Research Funding. Anghelina:Hairy Cell Leukemia Foundation: Research Funding. Lele:Hairy Cell Leukemia Foundation: Research Funding. Burger:Pharmacyclics: Research Funding. Delgado:Gilead: Consultancy, Honoraria; Novartis/GSK: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Infinity: Research Funding. Jones:AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lozanski:Beckman Coulter: Research Funding; Genentech: Research Funding; Stemline Therapeutics Inc.: Research Funding; Boehringer Ingelheim: Research Funding. Montserrat:Morphosys: Other: Expert Testimony; Vivia Biotech: Equity Ownership; Gilead: Consultancy, Other: Expert Testimony; Pharmacyclics: Consultancy; Janssen: Honoraria, Other: travel, accommodations, expenses. Parikh:Pharmacyclics: Honoraria, Research Funding. Park:Genentech/Roche: Research Funding; Amgen: Consultancy; Juno Therapeutics: Consultancy, Research Funding. Robak:Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Tam:janssen: Honoraria, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees. Heckler:Hairy Cell Leukemia Foundation: Research Funding. Payne:Hairy Cell Leukemia Foundation: Research Funding.

Beschreibung: Hairy cell leukemia is an uncommon hematologic malignancy characterized by pancytopenia and marked susceptibility to infection. Tremendous progress in the management of patients with this disease has resulted in high response rates and improved survival, yet relapse and an appropriate approach to re-treatment present continuing areas for research. The disease and its effective treatment are associated with immunosuppression. Because more patients are being treated with alternative programs, comparison of results will require general agreement on definitions of response, relapse, and methods of determining minimal residual disease. The development of internationally accepted, reproducible criteria is of paramount importance in evaluating and comparing clinical trials to provide optimal care. Despite the success achieved in managing these patients, continued participation in available clinical trials in the first-line and particularly in the relapse setting is highly recommended. The Hairy Cell Leukemia Foundation convened an international conference to provide common definitions and structure to guide current management. There is substantial opportunity for continued research in this disease. In addition to the importance of optimizing the prevention and management of the serious risk of infection, organized evaluations of minimal residual disease and treatment at relapse offer ample opportunities for clinical research. Finally, a scholarly evaluation of quality of life in the increasing number of survivors of this now manageable chronic illness merits further study. The development of consensus guidelines for this disease offers a framework for continued enhancement of the outcome for patients.