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The goal of therapy for patients with essential thrombocythemia (ET) and polycythemia vera (PV) is to reduce thrombotic events by normalizing blood counts. Hydroxyurea (HU) and interferon-α (IFN-α) are the most frequently used cytoreductive options for patients with ET and PV at high risk for vascular complications. Myeloproliferative Disorders Research Consortium 112 was an investigator-initiated, phase 3 trial comparing HU to pegylated IFN-α (PEG) in treatment-naïve, high-risk patients with ET/PV. The primary endpoint was complete response (CR) rate at 12 months. A total of 168 patients were treated for a median of 81.0 weeks. CR for HU was 37% and 35% for PEG (P = .80) at 12 months. At 24 to 36 months, CR was 20% to 17% for HU and 29% to 33% for PEG. PEG led to a greater reduction in JAK2V617F at 24 months, but histopathologic responses were more frequent with HU. Thrombotic events and disease progression were infrequent in both arms, whereas grade 3/4 adverse events were more frequent with PEG (46% vs 28%). At 12 months of treatment, there was no significant difference in CR rates between HU and PEG. This study indicates that PEG and HU are both effective treatments for PV and ET. With longer treatment, PEG was more effective in normalizing blood counts and reducing driver mutation burden, whereas HU produced more histopathologic responses. Despite these differences, both agents did not differ in limiting thrombotic events and disease progression in high-risk patients with ET/PV. This trial was registered at www.clinicaltrials.gov as #NCT01259856.

Advanced systemic mastocytosis (AdvSM) is a rare hematologic neoplasm driven by the KITD816V mutation and associated with poor survival. This phase 1 study (NCT02561988) evaluated avapritinib (BLU-285), a selective KIT D816V inhibitor, in patients with AdvSM. The primary endpoints were the maximum tolerated dose, recommended phase 2 dose and safety of avapritinib. Secondary endpoints included overall response rate and changes in measures of mast cell burden. Avapritinib was evaluated at doses of 30–400 mg once daily in 86 patients, 69 with centrally confirmed AdvSM. Maximum tolerated dose was not reached, and 200 mg and 300 mg daily were studied in dose-expansion cohorts. The most frequent adverse events observed were periorbital edema (69%), anemia (55%), diarrhea (45%), thrombocytopenia (44%) and nausea (44%). Intracranial bleeding occurred in 13% overall, but in only 1% of patients without severe thrombocytopenia (platelets <50 × 109/l). In 53 response-evaluable patients, the overall response rate was 75%. The complete remission rate was 36%. Avapritinib elicited ≥50% reductions in marrow mast cells and serum tryptase in 92% and 99% of patients, respectively. Avapritinib induced deep and durable responses, including molecular remission of KITD816V in patients with AdvSM, and was well tolerated at the recommended phase 2 dose of 200 mg daily.

The Janus kinase (JAK) inhibitor ruxolitinib is the only approved therapy for patients with symptomatic myelofibrosis. After ruxolitinib failure, however, there are few therapeutic options. We assessed the efficacy and safety of momelotinib, a JAK 1 and JAK 2 inhibitor, versus best available therapy (BAT) in patients with myelofibrosis who had suboptimal responses or haematological toxic effects with ruxolitinib.

Gotlib: Blueprint Medicines Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Chair of the Response Adjudication Committee and Research Funding, Research Funding; Deciphera: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: co-chair of the Study Steering Committee and Research Funding. Radia:Blueprint Medicines Corporation: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Education events. George:Blueprint Medicines Corporation: Consultancy, Other: I have received no funding for this research. ARUP Laboratories, owned by the University of Utah, has received funding; Allakos: Consultancy; Deciphera: Other: consultancy, but has received no financial compensation for the past 12 months; Celgene: Consultancy. Robinson:Blueprint Medicines Corporation: Research Funding. Drummond:Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Blueprint Medicine Corporation: Research Funding. Bose:Incyte Corporation: Consultancy, Honoraria, Research Funding, Speakers Bureau; Kartos Therapeutics: Honoraria, Research Funding; Astellas Pharmaceuticals: Research Funding; NS Pharma: Research Funding; Pfizer, Inc.: Research Funding; Promedior, Inc.: Research Funding; Constellation Pharmaceuticals: Research Funding; Celgene Corporation: Honoraria, Research Funding; CTI BioPharma: Honoraria, Research Funding; Blueprint Medicines Corporation: Honoraria, Research Funding. Hexner:Samus Therapeutics: Research Funding; Novartis: Research Funding; American Board of Internal Medicine: Other: member of the hematology exam committee; Blueprint Medicines Corporation: Other: serves on a data safety monitoring committee, Research Funding. Winton:Blueprint Medicines Corporation: Research Funding; Samus Therapeutics: Research Funding; Incyte Corporation: Research Funding. Horny:Novartis: Consultancy; Blueprint Medicines Corporation: Consultancy. Tugnait:Blueprint Medicines Corporation: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Schmidt-Kittler:Blueprint Medicines Corporation: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Evans:Blueprint Medicines Corporation: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Lin:Blueprint Medicines Corporation: Current Employment, Current equity holder in publicly-traded company. Mar:Blueprint Medicines Corporation: Current Employment, Current equity holder in publicly-traded company. Deininger:Leukemia & Lymphoma Society: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Other, Research Funding; Ariad: Consultancy, Honoraria, Other; Incyte: Consultancy, Honoraria, Other, Research Funding; Novartis: Consultancy, Other, Research Funding; Medscape: Consultancy; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Fusion Pharma: Consultancy; Blueprint Medicines Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: part of a study management committee, Research Funding; DisperSol: Consultancy; Galena: Consultancy, Honoraria, Other; Celgene: Research Funding; Gilead Sciences: Research Funding; SPARC: Research Funding; Sangamo: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Other, Research Funding. DeAngelo:Incyte Corporation: Consultancy; Glycomimetics: Research Funding; Forty-Seven: Consultancy; Amgen: Consultancy; Novartis: Consultancy, Research Funding; Pfizer: Consultancy; Abbvie: Research Funding; Jazz: Consultancy; Autolos: Consultancy; Shire: Consultancy; Takeda: Consultancy; Blueprint Medicines Corporation: Consultancy, Research Funding; Agios: Consultancy.

Introduction:Advanced systemic mastocytosis (AdvSM) comprises a heterogeneous group of clonal mast cell neoplasms, primarily driven by KITD816V. Measures of AdvSM response, including the International Working-Group for Myeloproliferative Neoplasms Research and Treatment and European Competence Network on Mastocytosis (IWG-MRT-ECNM) criteria, are based on improvements in mast cell-related organ damage (C-findings), and further sub-classified by the extent of reduction in measures of mast cell disease (e.g. serum tryptase level, bone marrow mast cell burden). However, assessment of some C-findings lacks precision (such as splenomegaly and its resolution). Normalization of C-findings may not be an adequate surrogate for important clinical outcomes such as overall survival (OS). We evaluated whether pure pathologic response (PPR) criteria based on changes in bone marrow mast cells, serum tryptase, and complete blood count was more closely correlated with OS compared to the modified IWG-MRT-ECNM (mIWG-MRT-ECNM) criteria.

The goal of therapy for essential thrombocythemia (ET) and polycythemia vera (PV) patients is to reduce thrombotic events by normalizing blood counts. Hydroxyurea (HU) and interferon-α (IFN-α) are the most frequently used cytoreductive options for ET and PV patients at high-risk for vascular complications. Myeloproliferative Disorders Research Consortium 112 was an investigator-initiated, phase 3 trial comparing HU to pegylated IFN-α (PEG) in treatment naïve, high-risk ET/PV patients. The primary endpoint was complete response (CR) rate at 12 months. A total of 168 patients were treated for a median of 81.0 weeks. CR for HU was 37% and 35% for PEG (p=0.80) at 12 months. At 24/36 months, CR was 20%/17% for HU and 29%/33% for PEG. PEG led to a greater reduction in JAK2V617F at 24 months, but histopathologic responses were more frequent with HU. Thrombotic events and disease progression were infrequent in both arms, while grade 3/4 adverse events were more frequent with PEG (46% vs. 28%). At 12 months of treatment there was no significant difference in CR rates between HU and PEG. This study indicates that PEG and HU are both effective treatments for PV and ET. With longer treatment PEG was more effective in normalizing blood counts and reducing driver mutation burden, while HU produced more histopathologic responses. Despite these differences, both agents did not differ in limiting thrombotic events and disease progression in high-risk ET/PV patients. (Funded by the National Cancer Institute, 5P01CA108671-09; clinicaltrials.gov number (NCT01259856)

From 1979 to 1988, 82 allogeneic and 2 syngeneic bone marrow transplants (BMT) were performed in 78 patients (age range 13-49 years) with the following diagnoses: acute myelogenous leukemia (AML) (21 patients); acute lymphoblastic leukemia (ALL) (15 patients); chronic myelocytic leukemia in chronic, accelerated, or blastic phase (CMLCP, AP or BC) (25 patients); myelodysplastic syndrome (MDS) (1 patient); multiple myeloma (MM) (1 patient); Hodgkin's disease (HD) (1 patient); diffuse poorly differentiated lymphoma (DPDL) (1 patient); aplastic anemia (AA) (13 patients). Univariant analyses were carried out to determine factors of importance in predicting outcome. AML patients receiving transplants in remission had 12/19 (63%) survivors. Only one of seven ALL patients receiving transplants in remission survives free of disease, and none of eight patients receiving transplants in relapse survived. Six ALL patients relapsed. In CML, 6 of 16 (40%) patients receiving transplants in CP survive; two of nine patients (22%) in AP or BC survive. Of the 13 aplastic anemias, 8 (62%) survive. Graft-vs.-host disease (GVHD) was evaluated in 75 patients, 24 of 33 (73%) who developed GVHD died, compared to 24 of 44 (55%) who did not develop GVHD. Of the 30 patients given the combination of methotrexate (MTX) plus cyclosporine (CSP), only 23% developed GVHD, compared to 58% of those not given the combination. Interstitial pneumonia (IP) occurred in 16 patients and was fatal in 15. The introduction of daily acyclovir and weekly intravenous gamma globulin in 1985 was associated with little reduction in the survival increased from 21% to 47%. Younger patients had significantly better survival than older patients (<20 years, 63% alive; 20-39 years, 31% alive; >39 years, 14% alive; p <.05). These data suggest that age, diagnosis, patient selection (disease status), the use of the combination of MTX/CSP and acyclovir and intravenous gamma globulin favorably affect survival in allogeneic BMT.

The Southeastern Cancer Study Group conducted a post-remission induction randomized trial in adult acute myelogenous leukemia to assess the efficacy of alternate drug therapy during consolidation and of immunotherapy during maintenance. Of 508 evaluable patients entered into the study, 335 (66%) achieved a complete remission treated with a 7-day infusion of cytosine arabinoside at a dose of 100 mg/sq m/day and 3 days of daunorubicin at a dose of 45 mg/sq m/day. Those in remission were randomized to receive 3 courses of 1 of 3 consolidation regimens: (A) a continuous infusion of 5-azacytidine, 150 mg/sq m/day for 5 days; (B) 5-azacytidine plus β-deoxythioguanosine, 300 mg/sq m/day for 5 days; or (C) cytosine arabinoside, 100 mg/sq m/day intravenously, and thioguanine, 100 mg/sq m orally every 12 hr, plus daunorubicin, 10 mg/sq m every 24 hr daily for 5 days. There was no difference in relapse rate among the 3 arms. Those completing consolidation and remaining in remission were randomized to 1 of 3 maintenance regimens: (D) chemotherapy, 5-day infusion of cytosine arabinoside and 2 days of daunorubicin (same doses as induction) given every 13 wk for 1 yr; (E) BCG given twice weekly for 1 mo and then monthly for 1 yr; or (F) the combination of regimens D and E. The median duration of remission was significantly better on regimen D (17.4 versus 9.4 and 9.5 mo), and median survival was 29 mo compared to 21 mo for the other regimens. Those given different drugs during consolidation than used for induction (regimens A and B) and subsequent chemotherapy for maintenance (regimen D) had the longest remission durations and survival. Immunotherpay was not as good as intensive chemotherapy for maintenance.

The ontogeny of a 57-Kd cationic antimicrobial protein (CAP57) that has substantial similarities to bactericidal permeability increasing protein (BPI) has been determined immunocytochemically. CAP57 was detected in the granules of mature peripheral blood neutrophils. However, it was absent from other cells of the peripheral blood: eosinophils, red blood cells (RBCs), and mononuclear cells. In human bone marrow, CAP57 was confined to the neutrophilic series. The earliest stage of development of the myeloid cells at which CAP57 was demonstrated was the promyelocyte. Double immunofluorescent labeling showed that CAP57 was detected in cells positive for myeloperoxidase. The absence of lactoferrin in certain cells (promyelocytes) containing CAP57 indicated that CAP57 was synthesized and packaged in a population of granules prior to the development of granules that contain lactoferrin. CAP57 could not be demonstrated in HL60 cells either by enzyme-linked immunosorbent assay (ELISA) or by immunocytochemistry. However, the presence of another granule-associated cationic antimicrobial protein of molecular weight 37 Kd (CAP37) was readily detected in undifferentiated HL60 cells. Amino acid sequence analysis showed that CAP57 and BPI were identical. Further indication of the identity between CAP57 and BPI was that monoclonal anti-CAP57 antibodies cross reacted with BPI. Sucrose density-gradient centrifugations showed CAP57 was confined to a granule population that exhibited a buoyant density intermediate of the previously described light and heavy azurophil granules. Further resolution of the individual azurophil granule populations by Percoll density-gradient centrifugation revealed that CAP57 was most concentrated in the density range of 1.093 to 1.100 g/cc. These results strongly suggest the unique finding that CAP57 may be associated with a heretofore unreported granule type.

Alkyl-lysophospholipids (ALP) are analogues of 2-lysophos-phatidylcholine that have been reported to have selective antitumor activity. These compounds could potentially be useful in purging bone marrow of leukemic cells in autologous marrow transplantation in acute leukemia. To determine the efficacy of pharmacological purging by ALP, we have designed a human assay system to mimic the conditions expected in the clinical setting of autotransplantation using remission marrow. A simulated remission marrow (SRM) was prepared by mixing normal marrow cells and HL60 cells in a ratio of 1,000:1. The effect of cryopreserva-tion on ALP-treated normal, HL60, and SRM cells was examined. In separate experiments, ALP significantly reduced the number of clonogenic HL60 cells with no effect on normal marrow progenitors. The effect of ALP was more apparent after cryopreservation. Incubation of HL60 cells with 50 μ/mL ALP for four hours followed by cryopreservation resulted approximately in a 3 log reduction of clonogenic HL60 cells. ALP also selectively purged the small number of leukemic cells from SRM. In SRM, the data suggested that ALP had indirect cytotoxic activity on leukemic cells by enhancing the cytotoxic activity of monocytes in addition to its direct effect. We found no evidence that clonogenic HL60 cells decreased because of induction of differentiation by ALP. These data indicated that treatment of marrow cells with ALP offers an efficient means to eliminate leukemic cells from the graft.

Two major types of lymphocytosis of large granular lymphocytes (LGLs) were observed. The proliferating LGLs in each type had distinct immunophenotypes, functional characteristics, and probably belonged to different cell lineages. The more common form (Type A) consisted of cells derived from the T cell lineage and had the T suppressor/cytotoxic phenotype (T11+, T3+, T8+). The expression of the Leu 7 and HLA-DR antigen was variable. These cells did not have natural killer (NK) function but showed a variable degree of antibody-dependent cell-mediated cytotoxic (ADCC) activity. Neutropenia was invariably present and rheumatoid arthritis and autoantibodies were frequent associations. These lymphocytes had many similarities to the major type of LGLs present in normal adult bone marrow. The other type of LGL lymphocytosis (Type B) consisted of cells lacking the antigens T3 and T8 but expressing M1 and NKH1. These cells possessed strong NK and ADCC activity but their cell lineage was not clear. Neutropenia and autoimmune phenomena were not detected. The cytochemical characteristics of the LGL granules from both types of patients were similar but differences in ultrastructure were observed. LGLs from Type B patients proliferated in the presence of Interleukin 2 (IL-2) and 12-O-tetradecanoyl-phorbol-13 acetate (TPA). Significant changes in their basic T11+, T3–, T8– phenotype were not observed. IL-2 and TPA, however, had profound influence on the NK function of the cells with enhancement in the case of IL-2 and marked suppression when stimulated by TPA.

We have studied the effect of recombinant human hematopoietic growth factors (interleukin-3 [rhlL-3], granulocytemacrophage colony-stimulating factor [rhGM-CSF], and granulocyte CSF [rhG-CSF]) on the clonal growth of human colon adenocarcinoma cell lines HTB-38, CCL 187, and WiDr (CCL 218). The factors stimulated clonal growth of HTB-38 and CCL 187 in a capillary modification of the human tumor clonogenic assay in agar up to twofold. There were dose-response correlations over a range of 1 to 10,000 U/mL for rhlL-3, rhGM-CSF, and rhG-CSF. Incubation with neutralizing monoclonal antibodies abolished the stimulation of clonal growth by rhGM-CSF. The WiDr cell line was nonresponsive to rhlL-3 and rhGM-CSF. These results represent the first evidence that a variety of hematopoietic growth factors can stimulate the growth of clonogenic cells of some nonhematopoietic malignant cell lines in vitro. © 1989 by Grune & Stratton, Inc.

A 43-year-old male with a phenotypically homogeneous, expanded subset of T cells presented in 1981 with anemia and neutropenia. The surface antigen phenotype of 99% of the peripheral blood lymphocytes was T3+, T8+, T4-, and they were morphologically large granular lymphocytes (LGL). The same cells comprised 37% of the marrow nucleated cells. Eight months after he presented, the peripheral blood T8+, LGL diminished spontaneously, and the anemia and neutropenia completely resolved. The patient remains hematologically normal as of October 1984. To determine if the T8+, LGL represented a clonal expansion, DNA from peripheral blood lymphocytes collected and cryopreserved when the patient was neutropenic and anemic, and when he was hematologically normal, was analyzed for clonal T-cell antigen receptor gene rearrangements. Using Southern blot analysis, a clonal DNA rearrangement was demonstrated, and this clone diminished but was still demonstrable in peripheral blood lymphocytes collected in 1984. The above observations implicate the expanded T8+, LGL in the pathogenesis of the neutropenia and anemia, yet the exact mechanism remains to be elucidated.

T-γ lymphoproliferative disease (T-γ LPD) is a chronic disorder of mature T cells that is associated with neutropenia and autoimmune phenomena. Although the progression of the lymphoproliferation is indolent, it is often associated with a monoclonal proliferation of T-cell-type large granular lymphocytes (LGL) that manifest multiple in vitro suppressor and cytotoxic activities. We considered the possibility that the granulocytopenia or anemia might represent an autoimmune disorder mediated by the monoclonal LGL via T-cell receptor (TCR) recognition of an antigen involved in hematopoiesis. Therefore, in an effort to characterize the usage of the TCR α-and β-chain genes in patients with T-7 LPD, we cloned and sequenced TCR α-and β-chain mRNAs derived from the T-cell type LGL of five patients. The five patients studied did not use a common Vαnor a common Jαsegment. However, an unusual finding was observed in one of the patients where the occurrence of a single variable-diversity-junctional (VDJ) rearrangement of the βchain confirmed the monoclonal origin of the LGL proliferation. In accord with this evidence for monoclonality, many of the cells studied used a common Vα(Vα19.1). In contrast to this common Vαusage, there was a marked diversity of the Jαsegments and N-region addition that were associated with the Vα19.1 segment. This pattern of common Vαusage associated with different N and Jαsegments suggests an immune-mediated selection process affecting the TCR αchain occurring after the transformation event that established the clone. We suggest that the T-cell-type LGL malignant clone might have developed autoreac-tivity conferred by the selected TCR αchain and that this autoreactivity might be implicated in this patient’s anemia. This is a US government work. There are no restrictions on its use.

Human lactoferrin (LF) has been reported to inhibit in vitro granulopoiesis by means of decreasing colony-stimulating activity production by monocytes. We performed a series of experiments to determine if the reported experimental results could be replicated using highly purified murine LF and murine target cells. Three different types of experiments were performed. (1) Medium was conditioned by lung, femoral shaft, and adherent peritoneal cells in the presence and absence of LF, and the granulopoietic stimulating activity in the conditioned media was assayed by means of a 7-day agar colony assay and a 3-day liquid slide chamber assay, which quantitates 3H-TdR incorporation into DNA. (2) In cultures stimulated by an underlayer of adherent peritoneal cells, marrow cell colony formation in agar was determined after 7 days of culture in the presence or absence of LF. (3) LF was added to 3-day liquid marrow cell cultures that had been stimulated by lung or femoral shaft conditioned media. In all experimental situations, highly purified, iron-saturated LF in concentrations up to 107Mhad no effect on in vitro granulopoiesis. These results do not support LF’s reputed regulatory role in granulopoiesis.

An unusual case of an aggressive leukemia of natural killer (NK) cells occurred in a 65-year-old male. Clinical characteristics of this case included hepatosplenomegaly, ascites, marrow infiltrate with leukemic cells, and a WBC up to 82.8 × 109before therapy. One year before his presentation he had been noted to have a WBC of 12.1 × 109with 78% lymphocytes, and 6 months before had noted intermittent fever and weight loss. He and his brother had well documented hereditary cold urticaria. The patient was treated with a modification of ProMACE CYTABOM regimen and had prompt regression of the leukemia with associated acute tumor lysis. Renal, hepatic, and marrow failure predominated during a terminal course that ended 22 days after therapy was commenced, and at autopsy there was no evidence for leukemic cell infiltrate in the liver, spleen or marrow. The leukemic cells were large granular lymphocytes by light and electron microscopic criteria, and had the following immunophenotype: CD2 +, DR +, Leu7 +, NKH1 +, CD11+, CD3-, CD5-, CD4-, CD8-, CD16-. The cells displayed high antibody-dependent cell-mediated cytotoxicity (ADCC) and NK activity, and had a high rate of spontaneous proliferation in vitro that was not augmented by phytohemagglutinin (PHA), concanavalin A (Con A), or pokeweed mitogen (PWM). Southern analysis of DNA from leukemic cells revealed normal germline arrangements for the βand γchains of the T cell antigen receptor and immunoglobulin heavy chain genes. The majority of metaphases were clonally abnormal revealing consistent rearrangements involving extra material attached to the long arms of chromosomes 5 and 11.

The status of the T cell receptor β and  γ genes in natural killer (NK) cells was investigated in two patients with a marked expansion of CD2 +, CD3- NK cells. Both genes were found to be in the germline state. The Tαand complete Tβgene transcripts were not detected, but a 1.0-kilobase Tβgene transcript could be demonstrated at low levels in freshly isolated cells and at a much higher level in interleukin-2 (IL-2)-cultured cells. The transcript coding for the δ chain of the CD3 complex was also absent. These cells were cultured in IL-2 with or without the addition of the differentiation-inducing agents: retinoic acid, N,N-hexamethylene bisacetamide, and sodium butyrate. The cultured cells retained their NK activity except in culture with sodium butyrate at ≥1 mmol/L. Expression of CD3 or other T cell surface markers by the NK cells was not observed in these cultures. Either CD2 +, CD3- NK cells are derived from a non-T lineage, or they have diverged from the T cell lineage earlier than the stage of Tγ gene rearrangement and CD3 δ chain expression; they are refractory to many induction signals in undergoing further T cell differentiation.

A liquid culture system employing slide chambers was developed to facilitate the study of proliferation and differentiation of mouse neutrophilic granulocytes and cells of the monocyte-macrophage series. Cultures were initiated with 1-2.5 × 104light density marrow cells which had been fractionated on Ficoll-Hypaque. In the presence of colony-stimulating activity (CSAHU), two types of clusters were observed. One was tight, spheroidal, and composed of neutrophilic granulocytes, while the other was a loose grouping of flattened cells of the monocyte-macrophage series. The slide chamber culture is adaptable to microscopic assay techniques (e.g., cluster size, autoradiography, immunofluorescence) as well as quantitative biochemical methods (e.g., rate of 3H-thymidine incorporation, DNA quantitation). We have demonstrated both a shortening of the generation time of granulocytes in tight clusters and increasing rates of 3H-thymidine incorporation into DNA, with a corresponding increase in total culture DNA as a function of CSAHUconcentration. Granulocytic differentiation in the tight spheroidal clusters has been demonstrated by histochemical stains and immunofluorescence of an antibody to a marker protein specific for the secondary granule of the neutrophil (lactoferrin).

A randomized trial was conducted comparing ketoconazole and nystatin in the prevention of oral candidiasis and appearance of invasive fungal infections in 51 neutropenic leukemic patients undergoing induction chemotherapy. Ketoconazole was administered in a 200 mg dose twice daily. Nystatin oral suspension was given in doses of 500,000 units four times daily. Surveillance cultures of the throat and urine were obtained prior to treatment and conducted weekly. Patients were enrolled in the study if the absolute granulocyte count was less than 1500μl, if physical examination revealed no evidence of oral candidiasis, no evidence of urinary tract infection, and there was no pulmonary infiltrate on chest x-ray. Patients were continued on study until the absolute granulocyte count reached 1500μl, evidence of oral candidiasis appeared, or presumed or proven invasive fungal infections appeared. Of the 46 evaluable patients, 22 received ketoconazole, 3 (14) developed oral candidiasis, and 5 developed suspected systemic fungal infections (23). Of 24 patients who received nystatin, 4 (17) developed oral candidiasis and 8 (33) developed systemic fungal infections, 4 proven and 4 suspected. Significantly more patients on the nystatin arm progressed to invasive fungal infections. Ketoconazole was not superior to nystatin in reducing the frequency of oral candidiasis but possibly reduced the frequency of invasive fungal infections.

A review of research on the relation of heart disease to soft water during the past decade uncovers sufficient correlation to suggest that more definitive studies need be undertaken to resolve the question.

In normal human peripheral blood, there is a population of large lymphocytes with slightly eccentric nuclei and abundant pale-blue cytoplasm containing many azurophilic granules. These lymphocytes have been termed large granular lymphocytes (LGLs). It is now clear that almost all natural-killer and antibody-dependent cell-mediated cytotoxic activity resides in this population of cells.1,2 Despite their morphologic similarity, immunologic analysis has shown striking heterogeneity in their surface antigens.3,4 Almost all of these cells bear surface receptors for the Fc fragment of IgG, but some express antigens generally found on T-lymphocytes. Others show surface antigens carried by myelomonocytic cells. This may indicate the presence of multiple distinct subpopulations of cells or a single population of cells expressing different surface antigens at different stages of maturation or functional activity.5 Whether LGLs are derived from the T cell or the myelomonocytic lineage is still not clear.There have been an increasing number

IN the presence of colony stimulating activity (CSA)1–5, both normal and neoplastic cells of the neutrophilic granulocyte (neutrophil) and monocyte–macrophage cell series proliferate and differentiate in semi-solid and liquid cultures6–9. However, as conventionally performed, the clonal assay for CSA depends on cellular proliferation, and does not provide quantitative information on the role of CSA in differentiation. Lactoferrin (LF) is a specific protein marker for the neutrophil cell series10–12, and among bone marrow cells is found exclusively in the specific granules of the maturing neutrophil13,14. These granules first appear at the myelocyte stage of cytodifferentiation15. Thus, synthesis of LF is a biochemical event which may be used to quantify a specific state of neutrophil differentiation. We previously reported the purification of murine LF16, and its quantification by radioimmunoassay17, and also the development of a slide chamber method for culturing bone marrow cells in liquid medium18. We now report that in similar cultures, the net synthesis of LF is correlated in a dose-dependent manner with CSA concentration. To our knowledge, this is the first demonstration of a quantitative relationship at both the biochemical and cellular levels between CSA and a specific marker of neutrophilic granulocyte differentiation19.

Yacoub: Hylapharm: Equity Ownership; Agios: Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; Ardelyx: Equity Ownership; Cara: Equity Ownership; Dynavax: Equity Ownership. Mascarenhas:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Roche: Consultancy, Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Pharmaessentia: Consultancy, Membership on an entity's Board of Directors or advisory committees; CTI Biopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; Promedior: Research Funding; Merus: Research Funding. Mesa:AbbVie: Research Funding; Samus: Research Funding; Incyte: Research Funding; Sierra Onc: Consultancy; Genotech: Research Funding; Promedior: Research Funding; Novartis: Consultancy; Celgene: Research Funding; CTI Biopharma: Research Funding; La Jolla Pharma: Consultancy. Rampal:Agios, Apexx, Blueprint Medicines, Celgene, Constellation, and Jazz: Consultancy; Constellation, Incyte, and Stemline Therapeutics: Research Funding. Silver:PharmEssentia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. McMullin:Daiko Sanyo: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Speakers Bureau; Italopharma: Membership on an entity's Board of Directors or advisory committees. Ewing:Novartis: Honoraria, Other: Meeting attendance sponsorship ; Bristol Myers-Squibb: Other: Meeting attendance sponsorship . O'Connell:Astex: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Shionogi: Membership on an entity's Board of Directors or advisory committees. Mead:Bristol Myers-Squibb: Consultancy; Novartis: Consultancy, Honoraria, Other: Travel/accommodation expenses, Research Funding, Speakers Bureau; CTI: Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Pfizer: Consultancy. De Stefano:Alexion: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. Baer:Astellas: Research Funding; Al Therapeutics: Research Funding; Abbvie: Research Funding; Incyte: Research Funding; Forma: Research Funding; Kite: Research Funding; Takeda: Research Funding. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Italfarmaco: Membership on an entity's Board of Directors or advisory committees; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kremyanskaya:La Jolla: Consultancy; Incyte, Celgene, Constellation, Protagonist.: Research Funding. Hexner:novartis: Research Funding. Rambaldi:Amgen: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Italfarmaco: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Omeros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Other: travel support, Research Funding, Speakers Bureau; Jazz: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, travel support. Ritchie:Genentech: Other: Advisory board; Tolero: Other: Advisory board; agios: Other: Advisory board; Pfizer: Other: Advisory board, travel support; Celgene: Other: Advisory board; Jazz Pharmaceuticals: Research Funding; Celgene, Novartis: Other: travel support; AStella, Bristol-Myers Squibb, Novartis, NS Pharma, Pfizer: Research Funding; Ariad, Celgene, Incyte, Novartis: Speakers Bureau; Celgene, Incyte, Novartis, Pfizer: Consultancy. Kiladjian:Novartis: Honoraria, Research Funding; AOP Orphan: Honoraria, Research Funding; Celgene: Consultancy. Harrison:Promedior: Honoraria; Incyte: Speakers Bureau; Sierra Oncology: Honoraria; Celgene: Honoraria, Speakers Bureau; Janssen: Speakers Bureau; CTI: Speakers Bureau; AOP: Honoraria; Shire: Speakers Bureau; Roche: Honoraria; Gilead: Speakers Bureau; Novartis: Honoraria, Research Funding, Speakers Bureau. Hoffman:Merus: Research Funding.Pegylated Interferon Alfa-2a for in Patients with Polycythemia Vera or Essential Thrombocythemia

Background

Dao: Incyte: Consultancy. Collins:Arog Pharmaceuticals: Research Funding; Bristol Myers Squibb: Research Funding; Celgene Corporation: Research Funding; Agios: Research Funding. Cortes:novartis: Research Funding. Deininger:Blueprint: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Druker:Henry Stewart Talks: Patents & Royalties; Third Coast Therapeutics: Membership on an entity's Board of Directors or advisory committees; ARIAD: Research Funding; Novartis Pharmaceuticals: Research Funding; McGraw Hill: Patents & Royalties; Bristol-Meyers Squibb: Research Funding; Fred Hutchinson Cancer Research Center: Research Funding; MolecularMD: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Consultancy, Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; GRAIL: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cepheid: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oregon Health & Science University: Patents & Royalties; ALLCRON: Consultancy, Membership on an entity's Board of Directors or advisory committees; Aptose Therapeutics: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Vivid Biosciences: Membership on an entity's Board of Directors or advisory committees; Aileron Therapeutics: Consultancy; Monojul: Consultancy; Beta Cat: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Patient True Talk: Consultancy; Leukemia & Lymphoma Society: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Millipore: Patents & Royalties. Gotlib:Incyte: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Research Funding; Kartos: Consultancy; Deciphera: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Blueprint Medicines: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Promedior: Research Funding. Oh:Gilead: Research Funding; CTI Biopharma: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; Janssen: Research Funding. Tyner:Vivid Biosciences: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Array: Research Funding; AstraZeneca: Research Funding; Incyte: Research Funding; Aptose: Research Funding; Genentech: Research Funding; Takeda: Research Funding; Constellation: Research Funding; Gilead: Research Funding.

Background: Patients (pts) with polycythemia vera (PV) and essential thrombocythemia (ET) suffer from difficult MPN associated symptoms which impact quality of life (QoL). The impact of initial cytoreduction on ET/PV symptoms, resulting toxicity and QoL have not been prospectively studied.

Mascarenhas: Novartis: Research Funding; Promedior: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Merck: Research Funding; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding. Rambaldi:Amgen Inc.: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Italfarmaco: Consultancy; Omeros: Consultancy; Roche: Consultancy; Celgene: Consultancy. Harrison:Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; CTI BioPharma: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Gilead: Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau. Kiladjian:AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Mead:Bristol-Myers Squibb: Consultancy; Elstar: Research Funding; Celgene: Research Funding; ARIAD: Consultancy; Evotek: Research Funding; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Cell Therapeutics: Consultancy. Kessler:Genentech: Research Funding; Sangamo: Research Funding; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Biomarin: Research Funding; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; DSMB: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Honoraria, Research Funding; Dimension Advisory boards: Membership on an entity's Board of Directors or advisory committees. Kremyanskaya:Incyte: Research Funding. Rampal:Stemline: Research Funding; Incyte: Honoraria, Research Funding; Constellation: Research Funding; Jazz: Consultancy, Honoraria; Celgene: Honoraria. Mesa:CTI Biopharma: Research Funding; Novartis: Consultancy; Genentech: Research Funding; Promedior: Research Funding; UT Health San Antonio - Mays Cancer Center: Employment; Pfizer: Research Funding; Celgene: Research Funding; Incyte Corporation: Research Funding; Gilead: Research Funding; NS Pharma: Research Funding. Dueck:Pfizer: Honoraria; Bayer: Employment; Phytogine: Employment. Hoffman:Incyte: Research Funding; Formation Biologics: Research Funding; Merus: Research Funding; Janssen: Research Funding; Summer Road: Research Funding.

Introduction

Background

Mesa: Incyte Corporation: Research Funding; CTI Biopharma: Research Funding; Gilead: Research Funding; NS Pharma: Research Funding; Promedior: Research Funding; Novartis: Consultancy; Celgene: Research Funding; UT Health San Antonio - Mays Cancer Center: Employment; Genentech: Research Funding; Pfizer: Research Funding. Mascarenhas:Merck: Research Funding; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Roche: Research Funding; Promedior: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Janssen: Research Funding. Rambaldi:Omeros: Consultancy; Roche: Consultancy; Celgene: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; Italfarmaco: Consultancy; Amgen Inc.: Consultancy. Yacoub:Novartis: Honoraria, Speakers Bureau; Cara Therapeutics: Equity Ownership; Ardelyx, INC.: Equity Ownership; Inycte: Honoraria, Speakers Bureau; Seattle Genetics: Honoraria, Speakers Bureau; Dynavax: Equity Ownership. Harrison:Gilead: Honoraria, Speakers Bureau; CTI BioPharma: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau. Kiladjian:AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees. Mead:Elstar: Research Funding; Celgene: Research Funding; ARIAD: Consultancy; Cell Therapeutics: Consultancy; Evotek: Research Funding; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy. Kessler:Sangamo: Research Funding; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Honoraria, Research Funding; Dimension Advisory boards: Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; DSMB: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Biomarin: Research Funding. Kremyanskaya:Incyte: Research Funding. Rampal:Incyte: Honoraria, Research Funding; Constellation: Research Funding; Jazz: Consultancy, Honoraria; Stemline: Research Funding; Celgene: Honoraria. Hoffman:Incyte: Research Funding; Janssen: Research Funding; Merus: Research Funding; Formation Biologics: Research Funding; Summer Road: Research Funding. Dueck:Pfizer: Honoraria; Bayer: Employment; Phytogine: Employment.

Introduction: A change in TKIs is needed in 30-50% of CP-CML patients due to adverse events or suboptimal response/treatment failure. With 5 TKIs Currently available: imatinib (IM), dasatinib (DAS), nilotinib (NIL), bosutinib (BOS), and ponatinib (PON) we sought to evaluate outcomes of CP CML following sequential TKI treatment.

Background:Resistance or intolerance to hydroxyurea (HU) in highrisk essential thrombocythemia (ET) or polycythemia vera (PV) leaves clinicians with few treatment options other than anagrelide (ET) or ruxolitinib (PV). Historical data on pegylated interferon alpha 2a (PEG) has been favorable in ET and PV, but reports of its use in HU-resistant and -intolerant patients have been anecdotal. We initiated a large phase II trial to better characterize the impact of second-line PEG therapy in these patients and focus on impact on symptom burden and quality of life (QOL).

Background: APL is the most curable leukemia with survival >90% in large co-operative group studies. These excellent outcomes are not seen in elderly patients where early deaths (ED) in trials are 10-18%. Population based registry data shows that ED rate in elderly patients is even higher at 24-50%. The one year relative survival was 37% in patients >60 years in Swedish population data. We report the outcome of patients >60 years from our experience.

Introduction: Tyrosine kinase inhibitors (TKIs) made great success in chronic myeloid leukemia (CML) treatment. However, TKIs often need to be changed due to not only adverse events but also suboptimal response or treatment failure. Currently, 5 TKIs, imatinib (IM), dasatinib (DAS), nilotinib (NIL), bosutinib (BOS), and ponatinib (PON) are approved for CML, and the sequential TKI treatment outcomes has not been well studied. Thus, we sought to evaluate outcomes of CP CML in an era where several TKIs are available.

Background:

Mascarenhas: CTI Biopharma: Research Funding; Janssen: Research Funding; Promedior: Research Funding; Roche: Research Funding; Novartis: Other: DSMB , Research Funding; Incyte: Other: Clinical Trial Steereing Committee, Research Funding. Mesa:Celgene: Research Funding; Promedior: Research Funding; CTI: Research Funding; Gilead: Research Funding; Incyte: Research Funding; Galena: Consultancy; Ariad: Consultancy; Novartis: Consultancy. Yacoub:Alexion: Honoraria; Seattle Genetics: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau. Harrison:Baxaltra: Consultancy, Honoraria, Speakers Bureau; Incyte Corporation: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Shire: Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau. McMullin:Novartis: Honoraria, Speakers Bureau. Vannucchi:Novartis: Honoraria, Speakers Bureau. Kiladjian:Novartis: Honoraria, Research Funding; AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding. Mead:Novartis: Honoraria, Research Funding, Speakers Bureau. Kessler:Incyte: Honoraria. Ritchie:Celgene: Consultancy, Other: Travel, Accomodations, Expenses, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Novartis: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; Ariad: Speakers Bureau; Pfizer: Consultancy, Research Funding; Astellas Pharma: Research Funding; Bristol-Meyers Squibb: Research Funding; NS Pharma: Research Funding. Schlenk:Amgen: Research Funding; Pfizer: Honoraria, Research Funding.

Heffner: Pharmacyclics: Research Funding; AbbVie: Research Funding; Millennium: Research Funding; Celgene: Research Funding. Jillella:Leukemia Lymphoma Society: Research Funding. Kota:Ariad Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Leukemia Lymphoma Society: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees.

Kota: Leukemia Lymphoma Society: Research Funding; Ariad Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Heffner:Millennium: Research Funding; AbbVie: Research Funding; Pharmacyclics: Research Funding; Celgene: Research Funding. Stuart:Bayer: Research Funding; Celator: Research Funding; Incyte: Research Funding; Agios: Research Funding; Sunesis: Consultancy, Honoraria, Other: Travel, Accomodations, Expenses, Research Funding; Astellas: Research Funding. Gerber:Spectrum: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Alexion: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Grunwald:Forma Therapeutics: Research Funding; Medtronic: Equity Ownership; Ariad: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Alexion: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Jillella:Leukemia Lymphoma Society: Research Funding.

Jillella: Leukemia Lymphoma Society: Research Funding. Heffner:AbbVie: Research Funding; Pharmacyclics: Research Funding; Celgene: Research Funding; Millennium: Research Funding. Stuart:Astellas: Research Funding; Celator: Research Funding; Sunesis: Consultancy, Honoraria, Other: Travel, Accomodations, Expenses, Research Funding; Agios: Research Funding; Bayer: Research Funding; Incyte: Research Funding. Gerber:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Spectrum: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding. Grunwald:Medtronic: Equity Ownership; Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Alexion: Membership on an entity's Board of Directors or advisory committees; Ariad: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Research Funding; Amgen: Research Funding; Janssen: Research Funding. Kota:Pfizer: Membership on an entity's Board of Directors or advisory committees; Ariad Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Leukemia Lymphoma Society: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees.

Kvasnicka: Novartis: Consultancy, Honoraria; Incyte Corporation: Consultancy, Honoraria; AOP Pharma: Consultancy, Honoraria. Thiele:Novartis: Consultancy, Honoraria; Incyte Corporation: Consultancy, Honoraria. Sun:Incyte Corporation: Employment, Equity Ownership. Naim:Incyte Corporation: Employment, Equity Ownership. Svaraman:Incyte Corporation: Employment, Equity Ownership. Gao:Incyte Corporation: Employment, Equity Ownership. Gotlib:Incyte Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Gupta:Incyte Corporation: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Dao:Incyte Corporation: Research Funding. Talpaz:Incyte Corporation: Other: Travel expense reimbursement, Research Funding; Novartis: Research Funding; Ariad: Other: Expense reimbursement, travel accomodation expenses, Research Funding; Pfizer: Consultancy, Other: travel accomodation expenses, Research Funding. Winton:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding. Verstovsek:AstraZeneca: Research Funding; Roche: Research Funding; Celgene: Research Funding; Lilly Oncology: Research Funding; Galena BioPharma: Research Funding; NS Pharma: Research Funding; Promedior: Research Funding; CTI BioPharma Corp: Research Funding; Geron: Research Funding; Gilead: Research Funding; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Research Funding; Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Genentech: Research Funding.

Mesa: CTI: Research Funding; Celgene: Research Funding; Promedior: Research Funding; Gilead: Research Funding; Incyte: Research Funding; Galena: Consultancy; Ariad: Consultancy; Novartis: Consultancy. Harrison:Incyte Corporation: Honoraria, Speakers Bureau; Baxaltra: Consultancy, Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Shire: Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau. McMullin:Novartis: Honoraria, Speakers Bureau. Yacoub:Alexion: Honoraria; Seattle Genetics: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau. Kiladjian:Novartis: Honoraria, Research Funding; AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding. Mead:Novartis: Honoraria, Research Funding, Speakers Bureau. Kessler:Pfizer: Consultancy; Octapharma: Consultancy, Research Funding; Novo Nordisk: Consultancy, Research Funding; Grifols: Consultancy; Genentech: Consultancy, Research Funding; Biogen: Consultancy; Bayer: Consultancy, Research Funding; Baxalta: Consultancy, Research Funding; LFB: Other: Member of DSMB. Ritchie:Pfizer: Honoraria; Novartis: Honoraria; Arian: Speakers Bureau; Celgene: Speakers Bureau; Incyte: Speakers Bureau. Schlenk:Pfizer: Honoraria, Research Funding; Amgen: Research Funding. Mascarenhas:Promedior: Research Funding; Janssen: Research Funding; CTI Biopharma: Research Funding; Novartis: Other: DSMB , Research Funding; Roche: Research Funding; Incyte: Other: Clinical Trial Steereing Committee, Research Funding.

Background:MF is a life-shortening complication of myeloproliferative neoplasms associated with ineffective hematopoiesis, splenomegaly, cytopenias, debilitating symptoms, and progressive BM fibrosis The 2 phase 3 COMFORT studies have shown that RUX, an oral Janus kinase (JAK) 1/JAK2 inhibitor, improves splenomegaly, constitutional symptoms, and overall survival in patients with MF. Accumulating evidence suggests that RUX may also modulate the BM microenvironment.

Background:

Background: APL is the most curable leukemia with reported survival above 90% in many large co-operative group studies. These excellent outcomes are not seen in elderly patients where early deaths in trials are 10-18%. Population based registry data shows that ED rate in elderly APL patients is even higher with reported incidence of 24-50%. We conducted a prospective trial using a set of simplified treatment guidelines along with support from a dedicated team of APL experts. Herein, we report outcomes of patients >60 years treated within the prospective trial. We compared these to our institutional experience prior to implementation of the trial.

Background:Patients (pts) with polycythemia vera (PV) and essential thrombocythemia (ET) suffer from disease related events linked to risk of vascular events, splenomegaly, progression to myelofibrosis/acute leukemia, and disease related symptoms arising from both elevated cytokines and issues of vascular flow. Impact of front line therapy on ET/PV symptoms has not been reported in a systematic fashion.

Background: APL is a highly curable malignancy with reported survival above 90% in many co-operative group studies. However these spectacular results are not evident in the general population. US SEER data and other population based studies from Swedish Cancer Registry and Brazil showed that early deaths (ED) can be as high as 30%, leading to a considerably lower survival compared to clinical trials where ED is around 5-10%. Decreasing ED remains a global challenge and the highest priority at all leukemia treatment centers and will result in population wide survival in this most curable leukemia. We report results of our prospective trial using a set of simplified treatment guidelines along with expert support designed to decrease ED.

Jillella: Seattle Genetics, Inc.: Research Funding.

Jillella: Seattle Genetics, Inc.: Research Funding. Kota:Leukemia Lymphoma Society: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees.