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Koreth, John

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Koreth

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Koreth, John

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2012 - 20183

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Author's Publications: search.filters.isAuthorOfPublication.ec0f3d70-b8de-49b4-afc0-3479e02bede2

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    Venous thromboembolism is associated with graft-versus-host disease and increased non-relapse mortality after allogeneic hematopoietic stem cell transplantation
    (Ferrata Storti Foundation, 2017) Kekre, Natasha; Kim, Haesook; Ho, Vincent; Cutler, Corey; Armand, Philippe; NIkiforow, Sarah; Alyea, Edwin P.; Soiffer, Robert; Antin, Joseph; Connors, Jean; Koreth, John
    Although venous thromboembolism rates and risk factors are well described in patients with cancer, there are limited data on the incidence, risk factors and outcomes of thrombosis after allogeneic stem cell transplantation, a curative therapy for patients with hematologic malignancies. We aimed to determine the incidence and risks associated with venous thrombosis in allogeneic stem cell transplants. We studied 2276 recipients of first transplant between 2002–2013 at our institution with a median follow up of 50 months (range 4–146). Using pharmacy records and subsequent chart reviews, 190 patients who received systemic anticoagulation for venous thrombosis were identified. The 1-and 2-year cumulative incidence of all venous thrombotic events were 5.5% (95% confidence interval (CI) 4.6–6.5%) and 7.1% (95% CI 6.1–8.2%), respectively. There was no difference in age, sex, body mass index, diagnosis, disease risk index, conditioning intensity, donor type or graft source between transplant recipients with and without subsequent thrombosis. In multivariable models, both acute and chronic graft-versus-host disease were independently associated with thrombosis occurrence (Hazard ratio (HR)=2.05, 95% CI 1.52–2.76; HR=1.71, 95% CI 1.19–2.46, respectively). Upper extremity thrombosis differed from all other thromboses in terms of timing, risk factors and clinical impact, and was not associated with non-relapse mortality (HR=1.15; 95% CI 0.69–1.90), unlike all other thromboses which did increase non-relapse mortality (HR=1.71; 95% CI 1.17–2.49). In subgroup analysis evaluating conventional thrombosis predictors by comparing patients with and without thrombosis, a history of prior venous thrombosis was the only significant predictor. Venous thromboembolism has a high incidence after allogeneic stem cell transplant and is associated with graft-versus-host disease and non-relapse mortality.
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    Long-Term Follow-up of Reduced Intensity Allogeneic Stem Cell Transplantation for Chronic Lymphocytic Leukemia: Prognostic Model to Predict Outcome
    (2012) Brown, Jennifer; Kim, Haesook T.; Armand, Philippe; Cutler, Corey; Fisher, David; Ho, Vincent; Koreth, John; Ritz, Jerome; Wu, Catherine; Antin, Joseph; Soiffer, Robert; Gribben, John G.; Alyea, Edwin P.
    CLL remains incurable with chemoimmunotherapy, and allogeneic hematopoietic stem cell transplantation (HSCT) offers potential for cure. We assessed the outcomes of 108 CLL patients undergoing first allogeneic HSCTs, 76 with reduced intensity (RIC) and 32 with myeloablative (MAC) conditioning between 1998 and 2009 at Dana-Farber Cancer Institute. With median follow-up 5.9 years in surviving patients, the 5 year OS for the entire cohort is 63% for RIC regimens and 49% for MAC regimens (p=0.18). The risk of death declined significantly starting in 2004 and we found that 5 year OS for HSCT between 2004–2009 was 83% for RIC regimens compared to 47% for MAC regimens (p=0.003). For RIC transplantation, we developed a prognostic model based on predictors of PFS, specifically remission status, LDH, comorbidity score and lymphocyte count, and found 5-year PFS 83% for score 0, 63% for score 1, 24% for score 2, and 6% for score >= 3 (p<0.0001). We conclude that RIC HSCT for CLL in the current era is associated with excellent long-term PFS and OS, and, as potentially curative therapy, should be considered early in the disease course of relapsed high-risk CLL patients.
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    Bortezomib-based immunosuppression after reduced-intensity conditioning hematopoietic stem cell transplantation: randomized phase II results
    (Ferrata Storti Foundation, 2018) Koreth, John; Kim, Haesook; Lange, Paulina B.; Poryanda, Samuel J.; Reynolds, Carol G.; Rai, Sharmila Chamling; Armand, Philippe; Cutler, Corey; Ho, Vincent; Glotzbecker, Brett; Yusuf, Rushdia; NIkiforow, Sarah; Chen, Yi-Bin; Dey, Bimalangshu; McMasters, Malgorzata; Ritz, Jerome; Blazar, Bruce R.; Soiffer, Robert; Antin, Joseph; Alyea, Edwin P.
    Aprior phase I/II trial of bortezomib/tacrolimus/methotrexate prophylaxis after human leukocyte antigen (HLA)-mismatched reduced intensity conditioning allogeneic hematopoietic stem cell transplantation documented low acute graft-versus-host disease incidence, with promising overall and progression-free survival. We performed an open-label three-arm 1:1:1 phase II randomized controlled trial comparing grade II–IV acute graft-versus-host disease between conventional tacrolimus/methotrexate (A) versus bortezomib/tacrolimus/methotrexate (B), and versus bortezomib/sirolimus/tacrolimus (C), in reduced intensity conditioning allogeneic transplantation recipients lacking HLA-matched related donors. The primary endpoint was grade II–IV acute graft-versus-host disease incidence rate by day +180. One hundred and thirty-eight patients (A 46, B 45, C 47) with a median age of 64 years (range: 24–75), varying malignant diagnoses and disease risk (low 14, intermediate 96, high/very high 28) received 7–8/8 HLA-mismatched (40) or matched unrelated donor (98) grafts. Median follow up in survivors was 30 months (range: 14–46). Despite early immune reconstitution differences, day +180 grade II-IV acute graft-versus-host disease rates were similar (A 32.6%, B 31.1%, C 21%; P=0.53 for A vs. B, P=0.16 for A vs. C). The 2-year non-relapse mortality incidence was similar (A 14%, B 16%, C 6.4%; P=0.62), as were relapse (A 32%, B 32%, C 38%; P=0.74), chronic graft-versus-host disease (A 59%, B 60% C 55%; P=0.66), progression-free survival (A 54%, B 52%, C 55%; P=0.95), and overall survival (A 61%, B 62%, C 62%; P=0.98). Overall, the bortezomib-based regimens evaluated did not improve outcomes compared with tacrolimus/methotrexate therapy. clinicaltrials.gov Identifier: 01754389