The association between mediastinal germ cell tumors (MGCT) and acute megakaryoblastic (M7) leukemia has been known for many years. We hereby present this review to better characterize the coexistence of these entities as well as the salient features, the treatment options, and the overall prognosis. A search of PUBMED, Medline, and EMBASE databases via OVID engine for primary articles and case reports under keywords "germ cell tumors" and "acute myeloid leukemia" revealed a total of 26 cases in English that reported MGCT and M7 leukemia. The median age at diagnosis of MGCT was 24 (13-36) years. All cases were stage III. All cases of MGCT were of non-seminomatous origin and one case was unclassified. MGCT occurred prior to the diagnosis of leukemia in 46% of cases and concomitantly in 31% of cases. M7 leukemia was never reported prior to the appearance of MGCT. Complex cytogenetics and hyperdiploidy were the most commonly reported cytogenetic abnormalities. In the 23 cases where the treatment regimen was available, platinum-based chemotherapy directed towards management of the germ cell tumors was used initially in 21 cases and leukemia-directed treatment was used initially in 2 cases only. The median time from diagnosis of MGCT to development of M7 leukemia was 5 (2.25-39) months. Median time to death from the initial diagnosis of MGCT was 6 (0.5-60) months. Patients with a history of MGCT are at higher risk of developing M7 leukemia. They need long-term follow-up with a particular attention to the development of hematological malignancies. The overall prognosis remains poor.

Venous thromboembolism (VTE) is a leading cause of death among outpatient chemotherapy patients. However the VTE preventive measures for outpatients are not widely advocated. We did a meta-analysis to evaluate the outpatient VTE prevention's effectiveness and safety. We searched electronic databases until the end of December 2012 and reviewed the abstracts and manuscripts following the PRISMA guidelines. Occurrence of first VTE event was the efficacy outcome. The safety end point was major bleeding. We calculated Q statistic and a homogeneity formal test. The odds ratio (OR) estimates were pooled by using the Mantel–Haenszel fixed-effects method in the absence of heterogeneity. Data were analyzed using the R META package). We identified 1,485 articles and reviewed 37 articles based on initial screening. The number of patients included in 11 selected trials was 7,805. The odds of VTE was lower in the prophylaxis group (OR 0.56; 95 % CI 0.45–0.71) and improved when heparin-based prevention was analyzed (OR 0.53; 95 % CI 0.41–0.70). We found strong prevention among patients with lung cancer (OR 0.46; 95 % CI 0.29–0.74) and pancreatic cancer (OR 0.33; 95 % CI 0.16–0.67). Major bleeding events were frequent in the intervention group (OR 1.65; 95 % CI 1.12–2.44). Thromboprophylaxis reduced VTE episodes. The VTE events were reduced by 47 % in heparin-based prophylaxis trials compared to placebo. The patients receiving heparin-based prophylaxis had a 60 % increase in bleeding events. Improving risk stratification tools to personalize prevention strategies may enhance the VTE prevention applicability in cancer patients.

Background and Aim: The association of mediastinal germ cell tumors and acute megakaryoblastic leukemia has been known for many years. Characterization of this association is not well reported systematically in the literature. We hereby present this systematic review to describe the salient features of this association, treatment options and overall prognosis. Material and Methods: A systematic review of PUBMED, Medline and EMBASE databases via OVID engine was conducted to search for primary articles and case reports under keywords “germ cell tumors” and “acute myeloid leukemia”. Search was extensive from 1946 to 2014; all the cases that were written in English language in pediatric and adult patients were included. The search yielded 679 results and was individually examined by two authors. All the studies that described acute lymphoblastic leukemia or other malignancies aside from AML were excluded. A total of 25 studies reported mediastinal germ cell tumors (MGCT) and acute megakaryoblastic leukemia (M7). We also included in this analysis, one additional case with mediastinal germ cell tumor with subsequent development of acute megakaryoblastic leukemia that was recently diagnosed and treated at our institution. Results: After our extensive review of the literature a total of 25 previous patients with MGCT + M7 were found from 1946-2014. With the inclusion of our case we report a total of 26 cases from 1946-2014.Twenty of the included patients were males and in 6 cases there was no mention of the gender. Median age at diagnosis of MGCT was 23 years (range - 15 to 36 y). In 92 % of cases the germ cell tumor was of non-seminomatous origin with 27% cases reporting teratoma and 40.7 % of cases reporting embryonal carcinoma. All the reported cases were stage III and had elevated tumor markers with significant elevation in serum AFP compared to beta-HCG. MGCT occurred prior to appearance of leukemia in 46% of cases and concomitantly in 30% of cases. The rest of the cases did not describe the sequence of disease occurrence. M7 leukemia was never reported prior to the appearance of GCT. All the patients were treated with platinum based chemotherapy which was primarily directed towards management of the germ cell tumors. The time from diagnosis of MGCT to development of M7 leukemia ranged from 9 weeks to 39 months with the median time being 4 months. Median time to death from the initial diagnosis of NSGCT was 6 months (range - 3 to 39 months). Only one reported case with MGCT+M7 combination was successfully treated with an allogenic stem cell transplant for the M7 leukemia with surgical resection of the mediastinal mass. Among the cases that reported cytogenetic abnormalities, trisomy 8 and complex cytogenetics were reported in 18.6 % cases each and hyperdiploidy was reported in 22 % cases. Surprisingly, Klinefelters syndrome (47, XXY) that is historically associated in 20 % of cases of mediastinal germ cell tumors was only reported in one case in this review. The i(12p) abnormality was reported only in 14.8 % of cases. Conclusion: Patients with history of mediastinal germ cell tumors are at higher risk of developing acute leukemia especially the megakaryoblastic subtype. This warrants long term follow up of such patients with regular monitoring of blood counts and a high degree of suspicion for hematological malignancies. In selected cases, allogeneic stem cell transplant may be considered in those who achieve leukemia remission after optimal surgical resection. In spite of the advances in chemotherapeutic options, the overall outcome in patients with mediastinal germ cell tumors who have acute megakaryoblastic leukemia remains poor. Disclosures No relevant conflicts of interest to declare.

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1157 Background: Venous thromboembolism [VTE] is the second highest cause of mortality among patients with cancer. However, pharmacological thromboprophylaxis for patients with solid tumor is only recommended during hospitalization. Primary outpatient thromboprophylaxis is not a widely accepted practice. Objective: Determine safety and efficacy of outpatient primary VTE prophylaxis in patients with solid tumors. Data sources: A systematic review was conducted using MEDLINE and EMBASE up to June 2012. Key search words included venous thromboembolism, malignancy, anticoagulants, and chemotherapy. Studies were considered for our meta-analysis if they included outpatient primary pharmacological thromboprophylaxis in adult patients with active solid cancer. All the information was independently reviewed by 2 of the authors [MP, SJ] and a third reviewer resolved discrepancies. The measure of association was calculated with R (R: A Language and Environment for Statistical, R Development Core Team, www.R-project.org), R META package (Version 0.8–2, Author: Guido Schwarzer). The Q statistic was calculated and a formal test of homogeneity was conducted. Random-effects model was preferred in case of heterogeneity. Results: A total of 1371 abstracts were reviewed and 29 manuscripts were fully abstracted. Eight randomized controlled trials including 6706 patients were analyzed. There were less VTE events with outpatient prophylaxis: odds ratio [OR] of 0.53 (95% CI, 0.40–0.70). Six studies used low or ultra-low molecular weight heparin and two studies used warfarin. In the subgroup analysis of heparin based primary prophylaxis, there was a significant reduction in VTE events [OR 0.47, 95% CI, 0.34–0.64], no significant heterogeneity [FIG 1]. In addition, there was no difference in major bleeding events between groups [OR 1.48, 95% CI, 0.89–2.46]. Five studies reported mortality data; there was significant heterogeneity between studies. Conclusions: Heparin based outpatient VTE prophylaxis in patients with solid tumors reduced by half the risk of VTE with no significant differences in major bleeding events. The current publications do not allow a meaningful grouped analysis of survival data, improved patient selection is necessary in order to adequately target VTE prevention strategies. Disclosures: No relevant conflicts of interest to declare.

e17010 Background: Myelodysplasia (MDS) is a myeloid clonal disorder characterized by dysplastic and ineffective hematopoiesis. Hypoplastic MDS is a rare variant found in <15 % of MDS patients.Severe aplastic anemia (SAA) is defined as <10% marrow cellularity associated with pancytopenia. Paroxysmal nocturnal hemoglobinuria (PNH) an acquired clonal hematopoietic disorder presenting as chronic intravascular hemolysis, venous thrombosis, deficient hematopoiesis and can be found in both SAA and MDS. PNH can be diagnosed by measuring the surface markers for phosphatidylinositolglycan (PIG),CD59, CD55 and CD14. In clinical practice, these three diagnoses have significant overlap with unclear thresholds for the level of clone for which therapy should be directed. Methods: We present a 69 year old patient who was found to have hypoplastic MDS/SAA by bone marrow biopsy and flow cytometry with no chromosomal abnormalities.Treatment with Anti-thymocyte globulin (ATG) and cyclosporine (CSA) was initiated. He achieved transfusion independence and was in complete remission for 6 months. He developed recurrent thrombocytopenia and was retreated with ATG & CSA with minimal improvement. He remained transfusion dependent.Repeat BM biopsy showed persistent hypoplastic MDS/SAA. PNH evaluation showed a small clone of PIG deficient cells quantified as 0 % red cell, 2% granulocytes and 0.9% monocytes which was negative at initial diagnosis. Eculizumab was instituted weekly for the last 18 months.Transfusion independence was obtained within 2 months with significant improvement in all cell lineages. BM biopsy performed 4 months after therapy showed hypercellular marrow. Patient continues to be treated with eculizumab and has maintained a complete remission for over 18 months. Results: The diagnosis hypoplastic MDS/aplastic anemia is usually highly sensitive to therapy with ATG and CSA. Although our patient initially responded to ATG, retreatment was not successful. Eculizumab has documented a significant and sustained response in this patient’s treatment. . Conclusions: We report a patient with less than 1% PNH clone that achieved complete transfusion independence with eculizumab and full resolution of hypoplastic MDS/SAA by marrow histology.

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4380 Myelodysplasia (MDS) is a myeloid clonal disorder with a relatively heterogeneous spectrum of presentation characterized by dysplastic and ineffective hematopoiesis. Hypocellular or hypoplastic MDS is a rare variant of MDS and is found in <15 % of patients at the time of diagnosis. Severe aplastic anemia (SAA) is defined as less than 10% marrow cellularity associated with anemia, thrombocytopenia and neutropenia and global marrow failure. Paroxysmal nocturnal hemoglobinuria (PNH), an acquired clonal hematopoietic disorder which presents as chronic intravascular hemolysis, venous thrombosis, deficient hematopoiesis and can be found in both severe aplastic anemia and MDS. The diagnosis of PNH can be made by measuring the direct expression of the phosphatidylinositolglycan (PIG) anchored surface molecules. Surface markers for CD59 (all lineages), CD55 (neutrophils, monocytes, lymphoid cells) and CD14 (monocytes) are analyzed for deficiency. In clinical practice, these three diagnoses often have significant overlap, with no clear thresholds for the level of clone for which therapy should be directed. Although treatment of PNH and aplastic anemia has been well defined, treatment of small clones that are PIG deficient in MDS and aplastic anemia patients is not clear. Here we present a case of a 69-year-old patient who was found to have macrocytic anemia leading to a diagnosis of hypoplastic MDS/aplastic anemia by bone marrow biopsy and flow cytometry. Bone marrow biopsy showed hypocellular marrow with granulocytic and megakaryocytic hypoplasia and had 1% myeloblasts, mild myelodysplastic features and no chromosomal abnormalities. Standard treatment with Anti-thymocyte globulin (ATG) and cyclosporine (CSA) was initiated at diagnosis 2 years ago. Patient achieved transfusion independence, and went into a complete remission that lasted 6 months. As shown in attached graph, patient developed recurrent thrombocytopenia, and was retreated with ATG & CSA with minimal improvement. Our patient has remained transfusion dependent of both platelets and red cells. Bone marrow biopsy was repeated which showed persistent aplastic anemia/hypoplastic MDS. PNH evaluation was performed showing a small clone of PIG deficient cells quantified as 0 % red cell, 2% granulocytes and 0.9% monocytes cells. Of note, PNH evaluation at the initiation of therapy showed no PNH clone. Eculizumab was instituted after failure of second dosing of ATG, dosed weekly for the last 18 months. Transfusion independence was obtained within 2 months, and as seen in the attached graph, the platelet counts improved significantly after therapy with Eculizumab. Similar response was reflected in other cell lineages. Bone marrow biopsy performed 4 months after therapy showed hypercellular marrow with mild dysplastic changes, cytogenetic analysis remains normal. Patient continues to be treated with eculizumab and has maintained a complete remission for over 18 months. As noted in a study done by Kaiafa et al, up to 15.5% of of MDS patients may exhibit a PNH clone, defined in the study by deficiency of CD55 and CD59 on granulocytes. The diagnosis Hypoplastic MDS/aplastic anemia is usually highly sensitive to therapy with ATG and CSA. Although our patient initially responded to ATG, retreatment at relapse was not successful. Eculizumab has documented a significant and sustained response in this patient’s treatment. We report a patient with a less than 1% clone that achieved complete transfusion independence with eculizumab and full resolution of hypoplastic MDS/severe aplastic anemia by marrow histology. Disclosures: No relevant conflicts of interest to declare.