Hematopoietic stem cell mobilization with the reversible CXCR4 receptor inhibitor plerixafor (AMD3100)—Polish compassionate use experience

Recent developments in the field of targeted therapy have led to the discovery of a new drug, plerixafor, that is a specific inhibitor of the CXCR4 receptor. Plerixafor acts in concert with granulocyte colony-stimulating factor (G-CSF) to increase the number of stem cells circulating in the peripheral blood (PB). Therefore, it has been applied in the field of hematopoietic stem cell mobilization. We analyzed retrospectively data regarding stem cell mobilization with plerixafor in a cohort of 61 patients suffering from multiple myeloma (N = 23), non-Hodgkin’s lymphoma (N = 20), or Hodgkin’s lymphoma (N = 18). At least one previous mobilization attempt had failed in 83.6% of these patients, whereas 16.4% were predicted to be poor mobilizers. The median number of CD34+ cells in the PB after the first administration of plerixafor was 22/μL (range of 0–121). In total, 85.2% of the patients proceeded to cell collection, and a median of two (range of 0–4) aphereses were performed. A minimum of 2.0 × 106 CD34+ cells per kilogram of the patient’s body weight (cells/kg b.w.) was collected from 65.6% of patients, and the median number of cells collected was 2.67 × 106 CD34+ cells/kg b.w. (0–8.0). Of the patients, 55.7% had already undergone autologous stem cell transplantation, and the median time to neutrophil and platelet reconstitution was 12 and 14 days, respectively. Cases of late graft failure were not observed. We identified the diagnosis of non-Hodgkin’s lymphoma and previous radiotherapy as independent factors that contributed to failure of mobilization. The current report demonstrates the satisfactory efficacy of plerixafor plus G-CSF for stem cell mobilization in heavily pre-treated poor or predicted poor mobilizers

Sinusitis in patients undergoing allogeneic bone marrow transplantation – a review

Abstract Introduction Sinusitis is a common morbidity in general population, however little is known about its occurrence in severely immunocompromised patients undergoing allogeneic hematopoietic stem cell transplantation. Objective The aim of the study was to analyze the literature concerning sinusitis in patients undergoing allogeneic bone marrow transplantation. Methods An electronic database search was performed with the objective of identifying all original trials examining sinusitis in allogeneic hematopoietic stem cell transplant recipients. The search was limited to English-language publications. Results Twenty five studies, published between 1985 and 2015 were identified, none of them being a randomized clinical trial. They reported on 31–955 patients, discussing different issues i.e. value of pretransplant sinonasal evaluation and its impact on post-transplant morbidity and mortality, treatment, risk factors analysis. Conclusion Results from analyzed studies yielded inconsistent results. Nevertheless, some recommendations for good practice could be made. First, it seems advisable to screen all patients undergoing allogeneic hematopoietic stem cell transplantation with Computed Tomography (CT) prior to procedure. Second, patients with symptoms of sinusitis should be treated before hematopoietic stem cell transplantation (HSCT), preferably with conservative medical approach. Third, patients who have undergone hematopoietic stem cell transplantation should be monitored closely for sinusitis, especially in the early period after transplantation

The Emerging Link Between the Complement Cascade and Purinergic Signaling in Stress Hematopoiesis

Innate immunity plays an important role in orchestrating the immune response, and the complement cascade (ComC) is a major component of this ancient defense system, which is activated by the classical-, alternative-, or mannan-binding lectin (MBL) pathways. However, the MBL-dependent ComC-activation pathway has been somewhat underappreciated for many years; recent evidence indicates that it plays a crucial role in regulating the trafficking of hematopoietic stem/progenitor cells (HSPCs) by promoting their egress from bone marrow (BM) into peripheral blood (PB). This process is initiated by the release of danger-associated molecular patterns (DAMPs) from BM cells, including the most abundant member of this family, adenosine triphosphate (ATP). This nucleotide is well known as a ubiquitous intracellular molecular energy source, but when secreted becomes an important extracellular nucleotide signaling molecule and mediator of purinergic signaling. What is important for the topic of this review, ATP released from BM cells is recognized as a DAMP by MBL, and the MBL-dependent pathway of ComC activation induces a state of “sterile inflammation” in the BM microenvironment. This activation of the ComC by MBL leads to the release of several potent mediators, including the anaphylatoxins C5a and desArgC5a, which are crucial for egress of HSPCs into the circulation. In parallel, as a ligand for purinergic receptors, ATP affects mobilization of HSPCs by activating other pro-mobilizing pathways. This emerging link between the release of ATP, which on the one hand is an activator of the MBL pathway of the ComC and on the other hand is a purinergic signaling molecule, will be discussed in this review. This mechanism plays an important role in triggering defense mechanisms in response to tissue/organ injury but may also have a negative impact by triggering autoimmune disorders, aging of HSPCs, induction of myelodysplasia, and graft-versus-host disease after transplantation of histoincompatible hematopoietic cells

Deferasirox Decreases Liver Iron Concentration in Iron-Overloaded Patients with Myelodysplastic Syndromes, Aplastic Anemia and Other Rare Anemias

Iron overload in transfusion-dependent patients with rare anemias can be managed with chelation therapy. This study evaluated deferasirox efficacy and safety in patients with myelodysplastic syndromes (MDS), aplastic anemia (AA) or other rare anemias. A 1-year, open-label, multicenter, single-arm, phase II trial was performed with deferasirox (10-40 mg/kg/day, based on transfusion frequency and therapeutic goals), including an optional 1-year extension. The primary end point was a change in liver iron concentration (LIC) after 1 year. Secondary end points included changes in efficacy and safety parameters (including ophthalmologic assessments) overall as well as in a Japanese subpopulation. Overall, 102 patients (42 with MDS, 29 with AA and 31 with other rare anemias) were enrolled; 57 continued into the extension. Mean absolute change in LIC was -10.9 mg Fe/g dry weight (d.w.) after 1 year (baseline: 24.5 mg Fe/g d.w.) and -13.5 mg Fe/g d.w. after 2 years. The most common drug-related adverse event was increased serum creatinine (23.5%), predominantly in MDS patients. Four patients had suspected drug-related ophthalmologic abnormalities. Outcomes in Japanese patients were generally consistent with the overall population. Results confirm deferasirox efficacy in patients with rare anemias, including a Japanese subpopulation. The safety profile was consistent with previous studies and ophthalmologic parameters generally agreed with baseline values (EUDRACT 2006-003337-32). (C) 2015 S. Karger AG, Base

Romiplostim in Thrombocytopenic Patients (Pts) with Low-Risk or Intermediate-1 (Int-1)-Risk Myelodysplastic Syndrome (MDS) Results in Reduced Bleeding without Impacting Leukemic Progression: Updated Follow-up Results from a Randomized, Double-Blind, Placebo (PBO)-Controlled Study

Abstract Background: Thrombocytopenia occurs in ~50% of pts with low/int-1 MDS and is associated with reduced survival; few therapies are available for thrombocytopenic MDS pts. In a PBO-controlled study, 250 pts with MDS were randomized 2:1 to receive weekly romiplostim or PBO. In the original June 2011 analysis, romiplostim reduced clinically significant bleeding events (HR romiplostim vs PBO 0.83, 95% CI: 0.66-1.05, P =0.13) and platelet transfusions (RR 0.77, 95% CI: 0.66-0.88, P 10% were more frequent with romiplostim (25/167, 15%) than PBO (3/83, 3.7%) and resolved after discontinuation in most cases. In February 2011, the data monitoring committee recommended that treatment with study drug be discontinued over safety concerns that the potential benefit seen in the reduction of bleeding did not outweigh the potential risk for disease progression to AML, and that transient increases in blast cell counts might put pts at risk for diagnosis of and treatment for AML. Pts were then moved into the long-term follow-up (LTFU) portion of the study. Previously reported (Giagounidis et al, Cancer 2014) 58-week incidence of AML was 6.0% (n=10) for romiplostim and 4.9% for PBO (n=4); HR 1.20 (95% CI: 0.38-3.84). This report provides additional data on LTFU of these pts through January 2015, with emphasis on AML incidence. Methods: Eligible pts had IPSS low/int-1 MDS and platelets 1) ≤20 × 109/L or 2) ≤50 × 109/L with a history of bleeding and were receiving only supportive care. Disease progression to AML was defined as 1) ≥20% blasts in bone marrow or peripheral blood after 4 weeks following discontinuation of romiplostim; 2) pathology consistent with leukemia, including chloroma or leukemia cutis; or 3) antileukemic treatment initiation. Results are presented by treatment group. Results: Of 250 pts in the study, 210 entered LTFU and 71 of these pts remained on study as of January 2015; median (Q1, Q3) follow-up was 27.5 (10.8, 50.2) months. Reasons for discontinuation (death, lost to follow-up, and consent withdrawal) during LTFU were similar in the romiplostim and PBO groups. During the active study period or during LTFU, death was reported in 89 (53.3%) pts in the romiplostim group and 44 (53.0%) pts in the PBO group (HR romiplostim vs PBO 1.01, 95% CI: 0.70-1.45) (Figure 1A); mortality rates were greater in those with int-1 vs low IPSS status for both groups (Table 1). AML was reported in 19 (11.3%) pts in the romiplostim group and 9 (11.0%) pts in the PBO group (HR 1.02, 95% CI: 0.46-2.27). The proportions of pts who either died or developed AML were 54.5% (n=91) in the romiplostim group and 54.2% (n=45) in the PBO group (HR for AML-free survival 1.03, 95% CI: 0.72-1.47) (Figure 1B). One half (n=14, 50%) of the 28 AML cases occurred in pts who were RAEB-1 at screening (none were RAEB-2), and 5 cases were diagnosed because of anti-AML treatment use alone (Table 2). In LTFU, pt-reported use of MDS therapy (eg, azacitidine or cyclosporine) in the romiplostim group was 42.8% (n=59, 95% CI: 34.4%-51.5%) and 28.2% (n=20, 95% CI: 18.1%-40.1%) in the PBO group. AML therapy (eg, chemotherapy) was used in 13 (9.5%) patients in the romiplostim group and 7 (9.9%) patients in the PBO group. Conclusions: Following the decision in 2011 to stop study drug, LTFU results have been updated with more observational time on study. Specifically, the 2015 HRs (romiplostim vs PBO) for death or progression to AML, respectively, are 1.01 (95% CI: 0.70-1.45) and 1.02 (95% CI: 0.46-2.27), compared with 2014 HRs of 1.04 (95% CI: 0.71-1.52) and 1.21 (95% CI: 0.53-2.76). Risks of disease progression to AML continue to be investigated. A final data analysis will be completed next year. Table 1. Mortality by Baseline IPSS n (%) Romiplostimn=167 PBOn=83 Low 17/46 (37.0) 6/23 (26.1) 95% CI (%) 23.2-52.5 10.2-48.4 Int-1 72/121 (59.5) 38/60 (63.3) 95% CI (%) 50.2-68.3 49.9-75.4 Table 2. Progression to AML to Date Study-Defined AML, n (%) Romiplostimn=19* PBOn=9 TotalN=28 Baseline WHO classification RAEB-1 11 (58) 3 (33) 14 (50) Non-RAEB 8† (42) 6 (67) 14 (50) AML diagnosis by Bone marrow/peripheral blast >20% 16 (84) 6 (67) 22 (79) Anti-AML therapy alone 3 (16) 3 (33) 6 (21) *Does not include 1 pt with AML who died. †Included 7 with RCMD and 1 with MDS-U classification. Figure 1. Figure 1. Disclosures Off Label Use: Romiplostim is indicated for use in adults with chronic immune thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. The use of romiplostim in MDS is investigational.. Mufti:GlaxoSmithKline: Consultancy, 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, Research Funding, Speakers Bureau; Amgen: 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, Speakers Bureau. Fenaux:Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Sekeres:TetraLogic: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees. Szer:Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: 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, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion Australia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: 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, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Platzbecker:Novartis: Honoraria; Celgene: Honoraria; Amgen, Inc.: Honoraria; GlaxoSmithKline: Honoraria, Research Funding. Gaidano:Amgen: Honoraria, Other: Advisory boards; Novartis: Honoraria, Other: Advisory boards; GlaxoSmithKline: Honoraria, Other: Advisory boards; Celgene: Research Funding; Morphosys: Honoraria, Other: Advisory boards; Roche: Honoraria, Other: Advisory boards; Janssen: Honoraria, Other: Advisory boards; Karyopharm: Honoraria, Other: Advisory boards. Wiktor-Jedrzejczak:Roche: Other: Advisory Board, Research Funding; Onconova: Other: Advisory Board; Pfizer: Other: Advisory Board; Amgen, Inc.: Research Funding; Novartis: Research Funding; Jansen: Other: Advisory Board; Celgene: Other: Advisory Board. Franklin:Amgen, Inc.: Employment, Other: shareholder

Romiplostim in Thrombocytopenic Patients with Low- or Int-1- Risk MDS Results in Reduced Bleeding without Impacting Leukemic Progression: Final Follow-up Results from a Randomized, Double-Blind, Placebo-Controlled Study

Abstract Background: Thrombocytopenia occurs in ~50% of patients with low/int-1 risk myelodysplastic syndrome (MDS) and is associated with reduced survival. In a placebo (PBO)-controlled study, 250 patients with MDS were randomized 2:1 to receive weekly romiplostim or PBO. In the original June 2011 analysis, romiplostim reduced clinically significant bleeding events [hazard ratio (HR) romiplostim vs PBO 0.83, 95% CI: 0.66−1.05, P = 0.13] and platelet transfusions (relative risk 0.77, 95% CI: 0.66−0.88, P10% were more frequent with romiplostim (25/167, 15%) than PBO (3/83, 3.6%) and resolved after discontinuation in most cases. In February 2011, the DMC recommended that treatment with study drug be discontinued as the potential benefit seen in the reduction of bleeding did not outweigh the potential risk for disease progression to AML, and that transient increases in blast cell counts might put patients at risk for diagnosis of and treatment for AML. Patients were moved into long-term follow-up (LTFU). Previously reported (Giagounidis et al, Cancer 2014) 58-week incidence of AML was 6.0% (N = 10) for romiplostim and 4.9% for PBO (N = 4); HR 1.20 (95% CI: 0.38−3.84). This report provides final 5-year LTFU data. Methods: Eligible patients were receiving only supportive care and had IPSS low/int-1 risk MDS and platelets 1) ≤20 × 109/L or 2) ≤50 × 109/L with a history of bleeding. Disease progression to AML was defined as 1) ≥20% blasts in bone marrow or peripheral blood after 4 weeks following discontinuation of romiplostim; 2) pathology consistent with leukemia; or 3) antileukemic treatment. Results are presented by treatment group. Results: At baseline, median (Q1, Q3) age was 70 (61, 77) years, the majority (59%) of patients were male; 27.6% were IPSS low risk and 72.4% were int-1 risk. WHO classifications were RCMD: 67.6%, RAEB-1: 13.2%, MDS-U: 11.2%, RA: 4.4%, RCMD-RS: 2.4%, RARS: 0.8%, and RAEB-2: 0.4%. Of 250 patients in the study, 210 entered LTFU and 66 completed the 5 years of LTFU; median (Q1, Q3) follow-up was 27.5 (10.8, 58.7) months. Reasons for discontinuation (death, lost to follow-up, and consent withdrawal) during LTFU were similar in both groups. During the active study period and LTFU, death was reported in 93 (55.7%) patients in the romiplostim group and 45 (54.2%) patients in the PBO group (HR romiplostim vs PBO 1.03, 95% CI: 0.72−1.47) (Figure); mortality rates were greater in those with IPSS int-1 vs low risk for both groups (Table). AML was reported in 20 (11.9%) patients in the romiplostim group and 9 (11.0%) patients in the PBO group (HR 1.06, 95% CI: 0.48−2.33). The proportions of patients who either died or developed AML were 56.9% (N = 95) in the romiplostim group and 55.4% (N = 46) in the PBO group (HR for AML-free survival 1.04, 95% CI: 0.73−1.48) (Figure). Nearly half (N = 14, 48%) of the 29 AML cases occurred in patients who were RAEB-1 at screening (none RAEB-2), and 6 cases were diagnosed because of anti-AML treatment use alone (Table). In LTFU, patient-reported use of MDS therapy (eg, azacitidine or cyclosporine) was 42.8% (N = 59, 95% CI: 34.4%−51.5%) in the romiplostim group and 31.4% (N = 22, 95% CI: 20.9%−43.6%) in the PBO group. AML therapy (eg, chemotherapy) was used in 14 (10.2%) patients in the romiplostim group and 7 (10.0%) patients in the PBO group. Conclusions: Following the decision in 2011 to stop study drug secondary to increased AML rates at that time and transient blasts increases, final 5-year LTFU HRs (romiplostim vs placebo) for death or progression to AML, respectively, are 1.03 (95% CI: 0.72−1.47) and 1.06 (95% CI: 0.48−2.33). In conclusion, romiplostim reduced bleeding events and platelet transfusions, with no increase in AML incidence or impact on survival. Disclosures Kantarjian: Amgen Inc.: Research Funding. Fenaux:Amgen Inc.: Research Funding. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen Inc.: Membership on an entity's Board of Directors or advisory committees; Millenium/Takeda: Membership on an entity's Board of Directors or advisory committees. Szer:Alexion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion Australia: Consultancy, Honoraria; Amgen Inc.: 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, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Platzbecker:Celgene Corporation: Honoraria, Research Funding; TEVA Pharmaceutical Industries: Honoraria, Research Funding; Janssen-Cilag: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Kuendgen:Celgene: Research Funding. Gaidano:Morphosys: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Wiktor-Jedrzejczak:Angelini: Consultancy; Novartis: Consultancy, Research Funding; Celgene: Consultancy; Janssen-Cilag: Consultancy; Novartis: Consultancy, Research Funding; BMS: Research Funding; Sandoz: Consultancy; Amgen Inc.: Research Funding. Carpenter:Amgen Inc.: Employment, Equity Ownership. Mehta:Amgen Inc.: Employment, Equity Ownership. Franklin:Amgen Inc.: Employment, Equity Ownership. Giagounidis:Amgen Inc.: Consultancy, Honoraria

Treatment with Romiplostim, a Thrombopoietin-Receptor Agonist, in Thrombocytopenic Patients (Pts) with Low or Intermediate-1 (Int-1) Risk Myelodysplastic Syndrome (MDS): Updated Follow-up Results for Acute Myeloid Leukemia (AML) and Survival from a Randomized, Double-Blind, Placebo (PBO)-Controlled Study

Abstract Background: Thrombocytopenia in MDS occurs in ~50% of pts with low/int-1 MDS and is associated with reduced survival; few therapies are available for these thrombocytopenic MDS pts. In a randomized PBO-controlled study, 250 pts with MDS were randomized 2:1 to receive weekly romiplostim or PBO. In the original June 2011 analysis, romiplostim reduced clinically significant bleeding events (HR romiplostim vs. PBO 0.83, 95% CI: 0.66, 1.05, P = 0.13) and platelet transfusions (RR 0.77, 95% CI: 0.66, 0.88, P 10% were more frequent with romiplostim (25/167, 15%) than PBO (3/83, 3.7%), and in most cases resolved after discontinuation. Due to concerns of the safety data monitoring committee that the potential benefit seen in the reduction of bleeding did not outweigh the potential risk for disease progression to AML and that transient increases in blast cell counts might put pts at risk for diagnosis of and treatment for AML, treatment with study drug was discontinued in February 2011. Pts were then moved into the long-term follow-up (LTFU) portion of the study. Previously reported (Giagounidis et al, Cancer 2014) 58-week incidence of AML was romiplostim: 6.0% (10 pts), PBO: 4.9% (4 pts), HR 1.20 (95% CI: 0.38, 3.84). This report provides additional data on LTFU of these pts up to March 2014, with a particular emphasis on AML incidence. Methods: Eligible pts had IPSS low/int-1 MDS and platelets 1) ≤20x109/L or 2) ≤50x109/L with a history of bleeding, and were receiving only supportive care. Disease progression to AML was defined as 1) ≥20% blasts in the bone marrow or peripheral blood after 4 weeks following discontinuation of romiplostim, 2) pathology consistent with leukemia including chloroma or leukemia cutis, or 3) anti-leukemic treatment initiation. Results are presented by treatment group. Results: Of 250 pts in the study, 210 entered LTFU, and 83 of these pts remained on study as of March 2014; the median (Q1, Q3) follow-up was 27.5 (10.8, 41.2) months. Reasons for discontinuation during LTFU were similar in the romiplostim and PBO groups and included death, lost to follow-up, and withdrawal of consent. During the active study period or during LTFU, death was reported in 50.9% (N = 85) of pts in the romiplostim group and 48.2% (N = 40) of pts in the PBO group (HR romiplostim vs. PBO 1.04, 95% CI: 0.71, 1.52) (Figure); mortality rates were greater in those with int-1 vs. low IPSS status for both the PBO and romiplostim groups (Table 1). AML was reported in 11.9% (N = 20) of pts in the romiplostim group and 9.8% (N = 8) of pts in the PBO group (HR 1.21, 95% CI: 0.53, 2.76). The proportions of pts who either died or developed AML were 52.7% (N = 88) in the romiplostim group and 48.2% (N = 40) in the PBO group (HR 1.10, 95% CI: 0.75, 1.60) (Figure). Fourteen of the 28 AML cases occurred in pts who were RAEB-1 at screening (none were RAEB-2) and 5 cases were diagnosed due to anti-AML treatment use alone (Table 2). In LTFU, the rate of pt-reported use of MDS therapy (e.g., azacitidine or cyclosporine) in the romiplostim group was 42.8% (N = 59, 95% CI: 34.4%, 51.5%) and 28.2% (N = 20, 95% CI: 18.1%, 40.1%) in the PBO group. Reported use of AML therapy (e.g., chemotherapy) occurred at a rate of 10.2% (N = 14) in the romiplostim group and 8.5% (N = 6) in the PBO group. Conclusion:Following the 2011 decision to stop study drug, results have been updated with more observational time on study. Specifically, the HRs for death or progression to AML (romiplostim vs. PBO) are 1.04 (95% CI: 0.71, 1.52) and 1.21 (95% CI: 0.53, 2.76), respectively, compared with 2013 HRs of 1.04 (95% CI: 0.70, 1.54) and 1.14 (95% CI: 0.49, 2.62), respectively. As LTFU continues, additional data will be evaluated. Safety concerns regarding risk of disease progression to AML are still being investigated. Table 1: Survival by Baseline IPSS n (%) RomiplostimN = 167 PBON = 83 Low 14/46 (30.4%) 3/23 (13.0%) 95% CI (%) 17.7, 45.8 2.8, 33.6 Int-1 71/121 (58.7%) 37/60 (61.7%) 95% CI (%) 49.4, 67.6 48.2, 73.9 Table 2: Progression to AML to Date Study-defined AML, n (%) RomiplostimN = 20 PBON = 8 TotalN = 28 Baseline WHO classification RAEB-1/2 11 (55%) 3 (37.5%) 14 (50%) Non-RAEB 9 (45%) 5 (62.5%) 14 (50%) AML diagnosis by Bone marrow/peripheral blast >20% 17 (85%) 6 (75%) 23 (82.1%) Anti-AML therapy alone 3 (15%) 2 (25%) 5 (17.9%) Figure Figure 1 Figure 1. Disclosures Kantarjian: Amgen Inc.: Research Funding. Off Label Use: Romiplostim is indicated for the treatment of thrombocytopenia in patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. The use of romiplostim in myelodysplastic syndromes is under investigation.. Mufti:Amgen Inc.: 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, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Fenaux:Amgen Inc.: Research Funding. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen Inc.: Membership on an entity's Board of Directors or advisory committees. Szer:Sandoz: 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, Speakers Bureau; Alexion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Platzbecker:Amgen Inc.: Honoraria. Kuendgen:Celgene: Research Funding. Gaidano:Amgen Inc.: Consultancy, Honoraria. Wiktor-Jedrzejczak:Amgen Inc.: Research Funding. Orejudos:Amgen Inc.: Consultancy. Lopez:Amgen Inc.: Employment, Equity Ownership. Giagounidis:Amgen Inc.: Consultancy, Honoraria