Simon Mantha
Memorial Sloan Kettering Cancer Center
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Publication
Featured researches published by Simon Mantha.
Journal of Thrombosis and Thrombolysis | 2017
Simon Mantha; Eva Simona Laube; Yimei Miao; Debra Sarasohn; Rekha Parameswaran; Samantha Stefanik; Gagandeep Brar; Patrick Samedy; Jonathan Wills; Stephen Harnicar; Gerald A. Soff
Low-molecular weight heparin (LMWH) has been the standard of care for treatment of venous thromboembolism (VTE) in patients with cancer. Rivaroxaban was approved in 2012 for the treatment of pulmonary embolism (PE) and deep vein thrombosis (DVT), but no prior studies have been reported specifically evaluating the efficacy and safety of rivaroxaban for cancer-associated thrombosis (CAT). Under a Quality Assessment Initiative (QAI), we established a Clinical Pathway to guide rivaroxaban use for CAT and now report a validation analysis of our first 200 patients. A 200 patient cohort with CAT (PE or symptomatic, proximal DVT), whose full course of anticoagulation was with rivaroxaban, were accrued. In competing risk analysis, primary endpoints at 6 months included new or recurrent PE or symptomatic proximal lower extremity DVT, major bleeding, clinically-relevant non-major bleeding leading to discontinuation of rivaroxaban, or death. In competing risk analysis, the 6 months cumulative incidence of new or recurrent VTE was 4.4 % (95 % CI = 1.4–7.4 %), major bleeding was 2.2 % (95 % CI = 0−4.2 %) and all-cause mortality 17.6 % (95 % CI = 11.7–23.0 %). In this cohort of 200 patients with active cancer and CAT the rates of new or recurrent VTE and major bleeding were comparable to the cancer subgroup analysis from the EINSTEIN studies. The results of our Clinical Pathway provide guidance on Rivaroxaban use for treatment of CAT, and suggest that safety and efficacy is preserved, compared with past-published experience with LMWH.
Journal of Thrombosis and Haemostasis | 2013
Simon Mantha; Stephan Moll; Patrick Hilden; Sean M. Devlin; Adam J. Rose
Summary. Background: Anticoagulation control is often summarized using the percentage of time spent in a therapeutic range (TTR). This method does not describe the timing and severity of fluctuations in the International Normalised Ratio (INR).Objective: To evaluate whether the TTR method can be improved by considering the patterns of INR over time.Methods: The cohort included adults aged 40+ years with atrial fibrillation (AF) and laboratory records of INR as recorded in the UK Clinical Practice Research Datalink. Statistical clustering techniques based on simple INR measures were used to describe the patterns of INR. Nested case–control studies calculated the odds ratios (ORs) for the risk of stroke, bleeding and mortality with TTR and different INR patterns. It was also evaluated whether cluster analyses improved the prediction of outcomes over TTR.Results: A number of 27 381 patients were studied with a mean age of 73 years. The OR for mortality was 3.76 (95% confidence interval [CI] 3.03–4.68) in patients with < 30% TTR compared with patients with 100% TTR. INR patterns were found to be best described by six different clusters. The cluster with the most unstable pattern was associated with the largest risk of mortality (OR 10.7, 95% CI 8.27–13.85) and stroke (OR 3.42, 95% CI 2.08–5.63). INR measures that predicted death independent of the TTR‐included absolute difference between two subsequent INR measurements and change relative to the mean over time.Conclusion: Cluster analysis of INR patterns improved the prediction of clinical outcomes over TTR and may help to identify warfarin users who need additional anticoagulation monitoring.
Journal of Thrombosis and Thrombolysis | 2014
Jennifer L. Aron; Robert C. Gosselin; Stephan Moll; Charles F. Arkin; Simon Mantha
The direct thrombin inhibitor dabigatran has been approved for clinical use in many countries for the prevention of stroke and systemic embolism in patients with atrial fibrillation. However, there is no known reversal agent or proven management strategy, and the best laboratory marker of hemostatic impairment to use in guiding treatment is unknown. We report the case of a patient on dabigatran for atrial fibrillation presenting with spontaneous intracranial hemorrhage (ICH). Recombinant activated factor VII (rFVIIa) was administered, with thrombin generation (TG) and thromboelastography (TEG) testing performed before and after injection. A 76-year-old man presented to the emergency department with a 1 h history of increasing and marked confusion, headache, tinnitus, aphasia and difficulty with comprehension. The last dose of dabigatran 150 mg was taken 4 h before the onset of symptoms. Medications included dabigatran (started 4 months earlier) at 150 mg twice daily and aspirin 81 mg daily for coronary artery disease. An emergent CT study of the head showed a left temporoparietal hemorrhage, measuring 8.0 9 3.5 cm, with intraventricular extension and mild rightward midline shift, but without evidence of acute hydrocephalus or underlying lesion. Initial laboratory studies showed a stable creatinine at 1.7 mg/dL (calculated clearance = 39 mL/min), a dabigatran level of 430 ng/mL as measured with the Aniara Hemoclot TT-based test, an activated partial thromboplastin time (aPTT) of 53 s (normal range 31.0‐40.0 s), a prothrombin time (PT) of 18.7 s (normal range\14.8 s) and a thrombin time (TT) greater than 60 s (normal range 10.0‐18.0 s); see Table 1 for results of those tests. Citrated plasma was saved and used later to perform TG [Siemens
Blood | 2017
Simon Mantha; Debra A. Goldman; Sean M. Devlin; Ju Whei Lee; Diana Zannino; Marnie Collins; Dan Douer; Harry Iland; Mark R. Litzow; Eytan M. Stein; Frederick R. Appelbaum; Richard A. Larson; Richard Stone; Bayard L. Powell; Susan Geyer; Kristina Laumann; Jacob M. Rowe; Harry P. Erba; Steven Coutre; Megan Othus; Jae H. Park; Peter H. Wiernik; Martin S. Tallman
Acute promyelocytic leukemia (APL) is commonly complicated by a complex coagulopathy. Uncertainty remains as to which markers of bleeding risk are independent predictors. Drawing from 5 large clinical trials that included all-trans retinoic acid (ATRA) as part of induction, we assessed known determinants of bleeding at baseline and evaluated them as potential predictors of hemorrhagic death (HD) in the first 30 days of treatment. The studies included were ALLG APML3 (single arm of ATRA + idarubicin ± prednisone), ALLG APML4 (single arm of ATRA + idarubicin + arsenic trioxide + prednisone), CALGB C9710 (single arm of ATRA + cytarabine + daunorubicin), Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) E2491 (intergroup I0129, consisting of daunorubicin + cytarabine vs ATRA), and SWOG S0521 (single-arm induction of ATRA + cytarabine + daunorubicin). A total of 1009 patients were included in the original trials, of which 995 had sufficient data to be included in our multivariate analysis. In this final cohort, there were 37 HD cases during the first 30 days following induction, for an estimated cumulative incidence of 3.7% (95% confidence interval [CI], 2.6% to 5.0%). Using multivariate Cox proportional hazards regression, the hazard ratio of HD in the first 30 days was 2.17 (95% CI, 0.84-5.62) for an ECOG performance status of 3-4 vs 0-2 and 5.20 (95% CI, 2.70-10.02) for a white blood cell count of ≥20 000/μL vs <20 000/μL. In this large cohort of APL patients, high white blood cell count emerged as an independent predictor of early HD.
Current Opinion in Hematology | 2016
Simon Mantha; Martin S. Tallman; Gerald A. Soff
Purpose of reviewAcute promyelocytic leukemia (APL) is associated with a complex coagulopathy. In spite of substantial recent improvements in treatment regimens, hemorrhagic death remains the main cause of induction failure. In this review, we delineate recent understanding of the pathophysiology and management of the hemorrhagic diathesis of APL. Recent findingsLaboratory and clinical data suggest that the malignant leukocytes mediate the hemorrhagic diathesis associated with APL through multiple mechanisms which lead to a combination of consumptive coagulopathy and primary hyperfibrinolysis. Exposure of tissue factor and Annexin II by the leukemic blasts is the main determinants of these processes. Promyelocyte-derived microparticles have recently been implicated in the coagulopathy as well. Total white cell count and platelet count have emerged as good general predictors of hemorrhagic death, along with the different routine hemostatic parameters. Prompt treatment with all-trans retinoic acid, with or without arsenic trioxide, is the most important step in preventing bleeding complications. Repletion of coagulation factors and platelets with blood products remains the mainstay of supportive treatment, whereas the role of recombinant soluble thrombomodulin is currently being investigated. SummaryThe coagulopathy of APL is multifactorial, with both disseminated intravascular coagulation and primary hyperfibrinolysis mediated largely by the malignant leukocytes.
Journal of Thrombosis and Thrombolysis | 2017
Simon Mantha; Yimei Miao; Jonathan Wills; Rekha Parameswaran; Gerald A. Soff
The development of thrombocytopenia in the setting of therapeutic anticoagulation for venous thromboembolic disease (VTE) is common in cancer patients, but guidelines for management are based on limited past data and have not been validated. In 2011, Memorial Sloan Kettering Cancer Center (MSKCC) implemented the following guidelines in this setting: administer full dose enoxaparin for a platelet count > 50,000/mcL, half-dose enoxaparin for a platelet count of 25,000–50,000/mcL, and hold anticoagulation for a platelet count < 25,000/mcL. We now report validation of safety and efficacy of these guidelines. As a Quality Assessment Initiative, we evaluated our guidelines for adult cancer patients at MSKCC who were on therapeutic-dose enoxaparin for VTE during the years 2011 through 2013 and experienced at least one 7-day period of thrombocytopenia (platelet count ≤ 50,000/mcL). We assessed adherence to the enoxaparin dose modification guidelines, major bleeding, clinically relevant non-major bleeding, recurrent VTE, and mortality during the thrombocytopenic episodes. We identified 99 patients with 140 episodes of thrombocytopenia of 7 or more days. The median duration of these thrombocytopenic episodes was 12 days. The enoxaparin dose was modified in 133 of the 140 episodes (95%), reflecting satisfactory adherence to our institutional guidelines. There were no recurrent VTE events or major bleeding episodes when the anticoagulant dose was reduced or held. In this cohort, there was only one major bleeding episode, a trauma-associated retroperitoneal hemorrhage that occurred on the third day of a thrombocytopenic episode, prior to enoxaparin dose modification. There were 13 clinically relevant non-major bleeding episodes. Lastly, 10 patients died of cancer-related causes during an episode of thrombocytopenia. This Quality Assessment Initiative supports the safety and efficacy of our guidelines for therapeutic enoxaparin dose modification.
American Journal of Hematology | 2017
Eva Simona Laube; Simon Mantha; Patrick Samedy; Jonathan Wills; Stephen Harnicar; Gerald A. Soff
patients treated with conventional ABO identical, leukoreduced, irradiated transfusions. Long-term mortality in recipients of washed transfusions (20–40%) was half to two-thirds of that in the comparable historical comparison group and the current literature (60%) (Supporting Information Table 5). A limitation of these data, in addition to the lack of randomization, is that we did not collect detailed information on treatment regimens (e.g., choice and dose of anthracycline in AML). The striking differences we observed in long-term survival are unlikely solely due to progress in treatment regimens or supportive care. Identical differences were observed when we restricted the comparison to the years 2003–2005 and 2006–2008. For lower risk patients (favorable or intermediate cytogenetics; <46 years of age or younger) in New York State treated between 2006 and 2011 long-term mortality rate was 2.5-fold higher (50% versus 20%) in conventionally treated patients compared with recipients of washed transfusions. This approach has the potential to substantially improve outcomes for many patients with AML. This may be limited, at present, to younger patients with favorable or intermediate cytogenetics. Larger randomized trials will be required to determine whether our promising results are generalizable and reproducible, and whether they might be applicable to older patients (who often receive less intensive therapy), and to patients with other hematologic malignancies or solid tumors.
American Journal of Obstetrics and Gynecology | 2015
Simon Mantha; Debra Sarasohn; Weining Ma; Sean M. Devlin; Dennis S. Chi; Kara Long Roche; Rudy S. Suidan; Kaitlin M. Woo; Gerald A. Soff
OBJECTIVE Ovarian vein thrombosis is associated with pregnancy and pelvic surgery. Postpartum ovarian vein thrombosis is associated with infection and a high morbidity rate and is treated with anticoagulant and intravenous antibiotic therapy. The natural history of such thrombotic events after debulking surgery for ovarian cancer has not been well described. Our objective was to characterize the presentation and outcomes for patients with this condition at our institution. STUDY DESIGN We conducted a retrospective study of patients who underwent surgical debulking for ovarian cancer at Memorial Sloan Kettering Cancer Center between the years 2001 and 2010. Patients were included if contrast computed tomography scans of both the abdomen and pelvis were performed within 12 weeks before and 12 weeks after the surgery. The images were reviewed to assess for the presence and extent of a new postoperative ovarian vein thrombosis. When available, subsequent studies were assessed for thrombus progression. Medical records were reviewed to determine whether anticoagulation was used for treatment of the thrombotic episode and to record the occurrence of any new significant venous thromboembolic event in the next year. RESULTS One hundred fifty-nine patients had satisfactory imaging. New ovarian vein thrombosis was a common complication of debulking surgery, as found in 41 of patients (25.8%). Only 5 women with ovarian vein thrombosis were started on anticoagulation, of which 2 individuals had an independent venous thromboembolic event as indication for treatment. Only 2 of the ovarian vein thromboses (4.9%) progressed to the inferior vena cava or left renal vein on subsequent scan. The estimated cumulative incidence of venous thromboembolism 1 year after the first postoperative scan was 17.1% for patients in the new ovarian vein thrombosis group vs 15.3% of individuals for the group without a postoperative ovarian vein thrombosis (P = .78). CONCLUSION Ovarian vein thrombosis is commonly encountered after debulking surgery for ovarian cancer. Anticoagulation is usually not indicated, and clinically meaningful thrombus progression rarely occurs.
Journal of Clinical Oncology | 2016
Gerald A. Soff; Rekha Parameswaran; Simon Mantha; Yimei Miao; Jodi Victoria Mones
10134Background: Chemotherapy-induced thrombocytopenia (CIT) is a common toxicity of cancer therapy, often leading to delay or reduction in chemotherapy. We conducted a randomized open-label phase ...
Journal of Thrombosis and Thrombolysis | 2013
Simon Mantha
Dabigatran, rivaroxaban, apixaban and edoxaban administered in fixed doses and without routine laboratory monitoring have been compared to warfarin for the prevention of stoke in patients with nonvalvular atrial fibrillation (AF). Phase III data is currently available for dabigatran, rivaroxaban and apixaban. It is derived from three randomized controlled trials: RE-LY, ROCKET AF and ARISTOTLE. Dabigatran and apixaban appeared to be superior to warfarin for the primary endpoint of stroke or systemic embolism, while rivaroxaban was deemed non-inferior. The risk of major bleeding was modestly decreased overall with the new agents, while the risk of intracranial hemorrhage was substantially reduced. The results of ENGAGE AF-TIMI 48 comparing edoxaban to warfarin are still pending. Large, well designed clinical trials support the use of three new target-specific oral anticoagulants for the prevention of stroke in individuals with nonvalvular AF.