Search

Your search keyword '"Stone, R.M."' showing total 42 results
Start Over Author "Stone, R.M."
42 results on '"Stone, R.M."'

1. Molecular landscape and prognostic impact of FLT3-ITD insertion site in acute myeloid leukemia: RATIFY study results

Author

Rücker, F.G., Du, L., Luck, T.J., Benner, A., Krzykalla, J., Gathmann, I., Voso, M.T., Amadori, S., Prior, T.W., Brandwein, J.M., Appelbaum, F.R., Medeiros, B.C., Tallman, M.S., Savoie, L., Sierra, J., Pallaud, C., Sanz, Mariano, Jansen, J.H., Niederwieser, D., Fischer, T., Ehninger, G., Heuser, M., Ganser, A., Bullinger, L., Larson, R.A., Bloomfield, C.D., Stone, R.M., Döhner, H., Thiede, C., Döhner, K., Rücker, F.G., Du, L., Luck, T.J., Benner, A., Krzykalla, J., Gathmann, I., Voso, M.T., Amadori, S., Prior, T.W., Brandwein, J.M., Appelbaum, F.R., Medeiros, B.C., Tallman, M.S., Savoie, L., Sierra, J., Pallaud, C., Sanz, Mariano, Jansen, J.H., Niederwieser, D., Fischer, T., Ehninger, G., Heuser, M., Ganser, A., Bullinger, L., Larson, R.A., Bloomfield, C.D., Stone, R.M., Döhner, H., Thiede, C., and Döhner, K.

Abstract

Item does not contain fulltext

Published
2021

2. Midostaurin reduces relapse in FLT3-mutant acute myeloid leukemia: the Alliance CALGB 10603/RATIFY trial

Author

Larson, R.A., Mandrekar, S.J., Huebner, L.J., Sanford, B.L., Laumann, K., Geyer, S., Bloomfield, C.D., Thiede, C., Prior, T.W., Döhner, K., Marcucci, G., Voso, M.T., Klisovic, R.B., Galinsky, I., Wei, A.H., Sierra, J., Sanz, Mariano, Brandwein, J.M., Witte, T.J. de, Niederwieser, D., Appelbaum, F.R., Medeiros, B.C., Tallman, M.S., Krauter, J., Schlenk, R.F., Ganser, A., Serve, H., Ehninger, G., Amadori, S., Gathmann, I., Döhner, H., Stone, R.M., Larson, R.A., Mandrekar, S.J., Huebner, L.J., Sanford, B.L., Laumann, K., Geyer, S., Bloomfield, C.D., Thiede, C., Prior, T.W., Döhner, K., Marcucci, G., Voso, M.T., Klisovic, R.B., Galinsky, I., Wei, A.H., Sierra, J., Sanz, Mariano, Brandwein, J.M., Witte, T.J. de, Niederwieser, D., Appelbaum, F.R., Medeiros, B.C., Tallman, M.S., Krauter, J., Schlenk, R.F., Ganser, A., Serve, H., Ehninger, G., Amadori, S., Gathmann, I., Döhner, H., and Stone, R.M.

Abstract

Item does not contain fulltext, The prospective randomized, placebo-controlled CALGB 10603/RATIFY trial (Alliance) demonstrated a statistically significant overall survival benefit from the addition of midostaurin to standard frontline chemotherapy in a genotypically-defined subgroup of 717 patients with FLT3-mutant acute myeloid leukemia (AML). The risk of death was reduced by 22% on the midostaurin-containing arm. In this post hoc analysis, we analyzed the cumulative incidence of relapse (CIR) on this study and also evaluated the impact of 12 4-week cycles of maintenance therapy. CIR analyses treated relapses and AML deaths as events, deaths from other causes as competing risks, and survivors in remission were censored. CIR was improved on the midostaurin arm (HR = 0.71 (95% CI, 0.54-0.93); p = 0.01), both overall and within European LeukemiaNet 2017 risk classification subsets when post-transplant events were considered in the analysis as events. However, when transplantation was considered as a competing risk, there was overall no significant difference between the risks of relapse on the two randomized arms. Patients still in remission after consolidation with high-dose cytarabine entered the maintenance phase, continuing with either midostaurin or placebo. Analyses were inconclusive in quantifying the impact of the maintenance phase on the overall outcome. In summary, midostaurin reduces the CIR.

Published
2021

3. Impact of NPM1/FLT3-ITD genotypes defined by the 2017 European LeukemiaNet in patients with acute myeloid leukemia

Author

Dohner, K., Thiede, C., Jahn, N., Panina, E., Gambietz, A., Larson, R.A., Prior, T.W., Marcucci, G., Jones, Dan, Krauter, J., Heuser, M., Voso, M.T., Ottone, T., Nomdedeu, J.F., Mandrekar, S.J., Klisovic, R.B., Wei, A.H., Sierra, J., Sanz, Mariano, Brandwein, J.M., Witte, T.J. de, Jansen, J.H., Niederwieser, D., Appelbaum, F.R., Medeiros, B.C., Tallman, M.S., Schlenk, R.F., Ganser, A., Serve, H., Ehninger, G., Amadori, S., Gathmann, I., Benner, A., Pallaud, C., Stone, R.M., Dohner, H., Bloomfield, C.D., Dohner, K., Thiede, C., Jahn, N., Panina, E., Gambietz, A., Larson, R.A., Prior, T.W., Marcucci, G., Jones, Dan, Krauter, J., Heuser, M., Voso, M.T., Ottone, T., Nomdedeu, J.F., Mandrekar, S.J., Klisovic, R.B., Wei, A.H., Sierra, J., Sanz, Mariano, Brandwein, J.M., Witte, T.J. de, Jansen, J.H., Niederwieser, D., Appelbaum, F.R., Medeiros, B.C., Tallman, M.S., Schlenk, R.F., Ganser, A., Serve, H., Ehninger, G., Amadori, S., Gathmann, I., Benner, A., Pallaud, C., Stone, R.M., Dohner, H., and Bloomfield, C.D.

Abstract

Contains fulltext : 218279.pdf (Publisher’s version ) (Open Access), Patients with acute myeloid leukemia (AML) harboring FLT3 internal tandem duplications (ITDs) have poor outcomes, in particular AML with a high (>/=0.5) mutant/wild-type allelic ratio (AR). The 2017 European LeukemiaNet (ELN) recommendations defined 4 distinct FLT3-ITD genotypes based on the ITD AR and the NPM1 mutational status. In this retrospective exploratory study, we investigated the prognostic and predictive impact of the NPM1/FLT3-ITD genotypes categorized according to the 2017 ELN risk groups in patients randomized within the RATIFY trial, which evaluated the addition of midostaurin to standard chemotherapy. The 4 NPM1/FLT3-ITD genotypes differed significantly with regard to clinical and concurrent genetic features. Complete ELN risk categorization could be done in 318 of 549 trial patients with FLT3-ITD AML. Significant factors for response after 1 or 2 induction cycles were ELN risk group and white blood cell (WBC) counts; treatment with midostaurin had no influence. Overall survival (OS) differed significantly among ELN risk groups, with estimated 5-year OS probabilities of 0.63, 0.43, and 0.33 for favorable-, intermediate-, and adverse-risk groups, respectively (P < .001). A multivariate Cox model for OS using allogeneic hematopoietic cell transplantation (HCT) in first complete remission as a time-dependent variable revealed treatment with midostaurin, allogeneic HCT, ELN favorable-risk group, and lower WBC counts as significant favorable factors. In this model, there was a consistent beneficial effect of midostaurin across ELN risk groups.

Published
2020

4. PF256 RATIFY: PROGNOSTIC IMPACT OF FLT3 TYROSINE KINASE DOMAIN (TKD) AND NPM1 MUTATION STATUS IN PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA (AML) TREATED WITH MIDOSTAURIN + STANDARD CHEMOTHERAPY

Author

Voso, M.T., primary, Larson, R.A., additional, Prior, T., additional, Marcucci, G., additional, Jones, D., additional, Krauter, J., additional, Heuser, M., additional, Lavorgna, S., additional, Nomdedeu, J., additional, Geyer, S.M., additional, Klisovic, R., additional, Wei, A.H., additional, Sierra, J., additional, Sanz, M.A., additional, Brandwein, J.M., additional, de Witte, T.M., additional, Jansen, J.H., additional, Niederweiser, D., additional, Appelbaum, F.R., additional, Medeiros, B.C., additional, Tallman, M.S., additional, Schlenk, R.F., additional, Ganser, A., additional, Amadori, S., additional, Cheng, Y., additional, Chen, Y., additional, Tiecke, E., additional, Du, L., additional, Ehninger, G., additional, Thiede, C., additional, Döhner, K., additional, Döhner, H., additional, Stone, R.M., additional, Bloomfield, C.D., additional, and Lo-Coco, F., additional

Published
2019
Full Text
View/download PDF

5. PS1337 IVOSIDENIB (AG-120) INDUCES DURABLE REMISSIONS AND TRANSFUSION INDEPENDENCE IN PATIENTS WITH IDH1-MUTANT RELAPSED/REFRACTORY MYELODYSPLASTIC SYNDROME IN A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY

Author

Foran, J.M., primary, DiNardo, C.D., additional, Watts, J.M., additional, Stein, E.M., additional, de Botton, S., additional, Fathi, A.T., additional, Prince, G.T., additional, Stein, A.S., additional, Stone, R.M., additional, Patel, P.A., additional, Tallman, M.S., additional, Choe, S., additional, Wang, H., additional, Zhang, V., additional, Dai, D., additional, Fan, B., additional, Yen, K.E., additional, Kapsalis, S.M., additional, Hickman, D., additional, Agresta, S.V., additional, Liu, H., additional, Wu, B., additional, Attar, E.C., additional, and Kantarjian, H.M., additional

Published
2019
Full Text
View/download PDF

6. PS1025 IVOSIDENIB (AG-120) INDUCES DURABLE REMISSIONS AND TRANSFUSION INDEPENDENCE IN PATIENTS WITH IDH1-MUTANT NEWLY-DIAGNOSED AML: UPDATED RESULTS FROM A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY

Author

Roboz, G.J., primary, DiNardo, C.D., additional, Stein, E.M., additional, Botton, S. de, additional, Mims, A.S., additional, Prince, G.T., additional, Altman, J.K., additional, Arellano, M.L., additional, Donnellan, W., additional, Erba, H.P., additional, Mannis, G.N., additional, Pollyea, D.A., additional, Stein, A.S., additional, Uy, G.L., additional, Watts, J.M., additional, Fathi, A.T., additional, Kantarjian, H.M., additional, Tallman, M.S., additional, Choe, S., additional, Dai, D., additional, Fan, B., additional, Wang, H., additional, Zhang, V., additional, Yen, K.E., additional, Kapsalis, S.M., additional, Hickman, D., additional, Liu, H., additional, Agresta, S., additional, Wu, B., additional, Attar, E.C., additional, and Stone, R.M., additional

Published
2019
Full Text
View/download PDF

7. PS1023 MUTANT IDH1 INHIBITOR IVOSIDENIB (AG-120) IN COMBINATION WITH AZACITIDINE FOR NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA

Author

DiNardo, C.D., primary, Stein, A.S., additional, Stein, E.M., additional, Fathi, A.T., additional, Frankfurt, O., additional, Schuh, A.C., additional, Döhner, H., additional, Martinelli, G., additional, Patel, P.A., additional, Raffoux, E., additional, Tan, P., additional, Zeidan, A., additional, Botton, S. de, additional, Kantarjian, H.M., additional, Stone, R.M., additional, Lam, D., additional, Wang, X., additional, Gong, J., additional, Kapsalis, S.M., additional, Hickman, D., additional, Zhang, V., additional, Winkler, T., additional, Wu, B., additional, and Vyas, P., additional

Published
2019
Full Text
View/download PDF

8. PS968 GENETIC LANDSCAPE OF FLT3-MUTATED ACUTE MYELOID LEUKEMIA (AML) PATIENTS TREATED WITHIN THE RATIFY TRIAL: CALGB 10603 (ALLIANCE)

Author

Jahn, N., primary, Panina, E., additional, Bullinger, L., additional, Dolnik, A., additional, Herzig, J., additional, Blätte, T.J., additional, Benner, A., additional, Gambietz, A., additional, Krzykalla, J., additional, Gathmann, I., additional, Larson, R.A., additional, Lo-Coco, F., additional, Amadori, S., additional, Prior, T.W., additional, Brandwein, J.M., additional, Appelbaum, F.R., additional, Medeiros, B.C., additional, Tallman, M.S., additional, Tiecke, E., additional, Pallaud, C., additional, Ehninger, G., additional, Heuser, M., additional, Ganser, A., additional, Stone, R.M., additional, Thiede, C., additional, Döhner, H., additional, Bloomfield, C.D., additional, and Döhner, K., additional

Published
2019
Full Text
View/download PDF

10. PF260 PROGNOSTIC AND PREDICTIVE IMPACT OF NPM1/FLT3-ITD GENOTYPES AS DEFINED BY 2017 EUROPEAN LEUKEMIANET RISK CATEGORIZATION FROM AML PATIENTS TREATED WITHIN THE INTERNATIONAL RATIFY STUDY

Author

Döhner, K., primary, Thiede, C., additional, Jahn, N., additional, Ekaterina, P., additional, Gambietz, A., additional, Prior, T.W., additional, Marcucci, G., additional, Jones, D., additional, Krauter, J., additional, Michael, H., additional, Lo-Coco, F., additional, Ottone, T., additional, Nomdedeu, J., additional, Mandrekar, S.J., additional, Huebner, L., additional, Laumann, K.M., additional, Geyer, S.M., additional, Klisovic, R.B., additional, Wei, A., additional, Sierra, J., additional, Sanz, M.A., additional, Brandwein, J.M., additional, de Witte, T.M., additional, Jansen, J.H., additional, Niederwieser, D., additional, Appelbaum, F.R., additional, Medeiros, B.C., additional, Tallman, M.S., additional, Schlenk, R.F., additional, Ganser, A., additional, Serve, H., additional, Ehninger, G., additional, Amadori, S., additional, Gathmann, I., additional, Axel, B., additional, Pallaud, C., additional, Larson, R.A., additional, Stone, R.M., additional, Döhner, H., additional, and Bloomfield, C.D., additional

Published
2019
Full Text
View/download PDF

11. Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation

Author

Stone, R.M., Mandrekar, S.J., Sanford, B.L., Laumann, K., Geyer, S., Bloomfield, C.D., Thiede, C., Prior, T.W., Dohner, K., Marcucci, G., Lo-Coco, F., Klisovic, R.B., Wei, A., Sierra, J., Sanz, M.A., Brandwein, J.M., Witte, T.J. de, Niederwieser, D., Appelbaum, F.R., Medeiros, B.C., Tallman, M.S., Krauter, J., Schlenk, R.F., Ganser, A., Serve, H., Ehninger, G., Amadori, S., Larson, R.A., Dohner, H., Stone, R.M., Mandrekar, S.J., Sanford, B.L., Laumann, K., Geyer, S., Bloomfield, C.D., Thiede, C., Prior, T.W., Dohner, K., Marcucci, G., Lo-Coco, F., Klisovic, R.B., Wei, A., Sierra, J., Sanz, M.A., Brandwein, J.M., Witte, T.J. de, Niederwieser, D., Appelbaum, F.R., Medeiros, B.C., Tallman, M.S., Krauter, J., Schlenk, R.F., Ganser, A., Serve, H., Ehninger, G., Amadori, S., Larson, R.A., and Dohner, H.

Abstract

Item does not contain fulltext, BACKGROUND: Patients with acute myeloid leukemia (AML) and a FLT3 mutation have poor outcomes. We conducted a phase 3 trial to determine whether the addition of midostaurin - an oral multitargeted kinase inhibitor that is active in patients with a FLT3 mutation - to standard chemotherapy would prolong overall survival in this population. METHODS: We screened 3277 patients, 18 to 59 years of age, who had newly diagnosed AML for FLT3 mutations. Patients were randomly assigned to receive standard chemotherapy (induction therapy with daunorubicin and cytarabine and consolidation therapy with high-dose cytarabine) plus either midostaurin or placebo; those who were in remission after consolidation therapy entered a maintenance phase in which they received either midostaurin or placebo. Randomization was stratified according to subtype of FLT3 mutation: point mutation in the tyrosine kinase domain (TKD) or internal tandem duplication (ITD) mutation with either a high ratio (>0.7) or a low ratio (0.05 to 0.7) of mutant to wild-type alleles (ITD [high] and ITD [low], respectively). Allogeneic transplantation was allowed. The primary end point was overall survival. RESULTS: A total of 717 patients underwent randomization; 360 were assigned to the midostaurin group, and 357 to the placebo group. The FLT3 subtype was ITD (high) in 214 patients, ITD (low) in 341 patients, and TKD in 162 patients. The treatment groups were well balanced with respect to age, race, FLT3 subtype, cytogenetic risk, and blood counts but not with respect to sex (51.7% in the midostaurin group vs. 59.4% in the placebo group were women, P=0.04). Overall survival was significantly longer in the midostaurin group than in the placebo group (hazard ratio for death, 0.78; one-sided P=0.009), as was event-free survival (hazard ratio for event or death, 0.78; one-sided P=0.002). In both the primary analysis and an analysis in which data for patients who underwent transplantation were censored, the benefit of mi

Published
2017

12. Azacitidine Versus Conventional Care Regimens (CCR) in Elderly Patients (≥75 Years) with Acute Myeloid Leukemia (AML) in the AZA-AML-001 Study

Author

Seymour, J.F., primary, Buckstein, R., additional, Santini, V., additional, Döhner, H., additional, Stone, R.M., additional, Minden, M.D., additional, Kuo, C.Y., additional, Ben-Yehuda, D., additional, Bargay, J., additional, Songer, S., additional, Weaver, J., additional, Beach, C.L., additional, and Dombret, H., additional

Published
2017
Full Text
View/download PDF

14. Enasidenib (AG-221), A Selective Oral Inhibitor of Mutant Isocitrate Dehydrogenase 2 (IDH2) Enzyme, In Patients with Myelodysplastic Syndromes (MDS)

Author

Stein, E.M., primary, Fathi, A.T., additional, DiNardo, C.D., additional, Pollyea, D.A., additional, Swords, R.T., additional, Roboz, G.J., additional, Collins, R., additional, Sekeres, M.A., additional, Stone, R.M., additional, Attar, E.C., additional, Tosolini, A., additional, Xu, Q., additional, Amatangelo, M., additional, Gupta, I., additional, Knight, R.D., additional, de Botton, S., additional, Tallman, M.S., additional, and Kantarjian, H.M., additional

Published
2017
Full Text
View/download PDF

15. Azacitidine Prolongs Overall Survival in Older Patients with Acute Myeloid Leukemia (AML) with Poor Prognostic Karyotypes

Author

Döhner, H., primary, Vyas, P., additional, Seymour, J.F., additional, Santini, V., additional, Stone, R.M., additional, Minden, M.D., additional, Al-Ali, H.K., additional, del Castillo, T. Bernal, additional, Morrill, J., additional, Songer, S., additional, Weaver, J., additional, Skikne, B.S., additional, Beach, C.L., additional, and Dombret, H., additional

Published
2017
Full Text
View/download PDF

16. The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

Author

Townsend, E.C. (Elizabeth), Murakami, M.A. (Mark), Christodoulou, A. (Alexandra), Christie, A.L. (Amanda), Köster, J. (Johannes), DeSouza, T.A. (Tiffany), Morgan, E.A. (Elizabeth), Kallgren, S.P. (Scott), Liu, H. (Huiyun), Wu, S.-C. (Shuo-Chieh), Plana, O. (Olivia), Montero, J. (Joan), Stevenson, K.E. (Kristen), Rao, P. (Prakash), Vadhi, R. (Raga), Andreeff, M. (Michael), Armand, P. (Philippe), Ballen, K.K. (Karen), Barzaghi-Rinaudo, P. (Patrizia), Cahill, S. (Sarah), Clark, R.A. (Rachael), Cooke, V.G. (Vesselina), Davids, M.S. (Matthew), DeAngelo, D.J. (Daniel), Dorfman, D.M., Eaton, H. (Hilary), Ebert, B.L. (Benjamin), Etchin, J. (Julia), Firestone, B. (Brant), Fisher, D.C. (David), Freedman, A.S. (Arnold), Galinsky, (), I.A. (Ilene), Gao, H. (Hui), Garcia, (), J.S. (Jacqueline), Gamache-Ottou, F. (Francine), Graubert, T.A. (Timothy), Gutierrez, A. (Alejandro), Halilovic, E. (Ensar), Harris, M.H. (Marian), Herbert, Z.T. (Zachary), Horwitz, S.M. (Steven), Inghirami, G. (Giorgio), Intlekofer, A.M. (Andrew), Ito, M. (Moriko), Izraeli, S. (Shai), Jacobsen, E.D. (Eric), Jacobson, C.A. (Caron), Jeay, S. (Sébastien), Jeremias, I. (Irmela), Kelliher, M.A. (Michelle), Koch, R. (Raphael), Konopleva, M. (Marina), Kopp, N. (Nadja), Kornblau, S.M. (Steven), Kung, A.L. (Andrew), Kupper, T.S. (Thomas), LeBoeuf, N.R. (Nicole), LaCasce, A.S. (Ann), Lees, E. (Emma), Li, L.S. (Loretta), Look, A.T. (Thomas), Murakami, M. (Masato), Muschen, M. (Markus), Neuberg, D. (Donna), Ng, S.Y. (Samuel), Odejde, O.O. (Oreofe), Orkin, S.H. (Stuart), Paquette, R.R. (Rachel), Place, A.A. (Andrew), Roderick, J.E. (Justine), Ryan, J.A. (Jeremy), Sallan, S.E. (Stephen), Shoji, B. (Brent), Silverman, L.B. (Lewis), Soiffer, R.J. (Robert), Steensma, D.P. (David), Stegmaier, K. (Kimberley), Stone, R.M. (Richard), Tamburini, J. (Jerome), Thorner, A.R. (Aaron), Hummelen, P. (Paul) van, Wadleigh, M. (Martha), Wiesmann, M. (Marion), Weng, A.P. (Andrew), Wuerthner, J.U. (Jens), Williams, D.A. (David), Wollison, B.M. (Bruce), Lane, A.A. (Andrew), Letai, A. (Anthony), Bertagnolli, M.M. (Monica), Ritz, J. (Jerome), Brown, M. (Myles), Long, H. (Henry), Aster, J.C. (Jon), Shipp, M.A. (Margaret), Griffin, J.D. (James), Weinstock, D.M. (David), Townsend, E.C. (Elizabeth), Murakami, M.A. (Mark), Christodoulou, A. (Alexandra), Christie, A.L. (Amanda), Köster, J. (Johannes), DeSouza, T.A. (Tiffany), Morgan, E.A. (Elizabeth), Kallgren, S.P. (Scott), Liu, H. (Huiyun), Wu, S.-C. (Shuo-Chieh), Plana, O. (Olivia), Montero, J. (Joan), Stevenson, K.E. (Kristen), Rao, P. (Prakash), Vadhi, R. (Raga), Andreeff, M. (Michael), Armand, P. (Philippe), Ballen, K.K. (Karen), Barzaghi-Rinaudo, P. (Patrizia), Cahill, S. (Sarah), Clark, R.A. (Rachael), Cooke, V.G. (Vesselina), Davids, M.S. (Matthew), DeAngelo, D.J. (Daniel), Dorfman, D.M., Eaton, H. (Hilary), Ebert, B.L. (Benjamin), Etchin, J. (Julia), Firestone, B. (Brant), Fisher, D.C. (David), Freedman, A.S. (Arnold), Galinsky, (), I.A. (Ilene), Gao, H. (Hui), Garcia, (), J.S. (Jacqueline), Gamache-Ottou, F. (Francine), Graubert, T.A. (Timothy), Gutierrez, A. (Alejandro), Halilovic, E. (Ensar), Harris, M.H. (Marian), Herbert, Z.T. (Zachary), Horwitz, S.M. (Steven), Inghirami, G. (Giorgio), Intlekofer, A.M. (Andrew), Ito, M. (Moriko), Izraeli, S. (Shai), Jacobsen, E.D. (Eric), Jacobson, C.A. (Caron), Jeay, S. (Sébastien), Jeremias, I. (Irmela), Kelliher, M.A. (Michelle), Koch, R. (Raphael), Konopleva, M. (Marina), Kopp, N. (Nadja), Kornblau, S.M. (Steven), Kung, A.L. (Andrew), Kupper, T.S. (Thomas), LeBoeuf, N.R. (Nicole), LaCasce, A.S. (Ann), Lees, E. (Emma), Li, L.S. (Loretta), Look, A.T. (Thomas), Murakami, M. (Masato), Muschen, M. (Markus), Neuberg, D. (Donna), Ng, S.Y. (Samuel), Odejde, O.O. (Oreofe), Orkin, S.H. (Stuart), Paquette, R.R. (Rachel), Place, A.A. (Andrew), Roderick, J.E. (Justine), Ryan, J.A. (Jeremy), Sallan, S.E. (Stephen), Shoji, B. (Brent), Silverman, L.B. (Lewis), Soiffer, R.J. (Robert), Steensma, D.P. (David), Stegmaier, K. (Kimberley), Stone, R.M. (Richard), Tamburini, J. (Jerome), Thorner, A.R. (Aaron), Hummelen, P. (Paul) van, Wadleigh, M. (Martha), Wiesmann, M. (Marion), Weng, A.P. (Andrew), Wuerthner, J.U. (Jens), Williams, D.A. (David), Wollison, B.M. (Bruce), Lane, A.A. (Andrew), Letai, A. (Anthony), Bertagnolli, M.M. (Monica), Ritz, J. (Jerome), Brown, M. (Myles), Long, H. (Henry), Aster, J.C. (Jon), Shipp, M.A. (Margaret), Griffin, J.D. (James), and Weinstock, D.M. (David)

Abstract

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease.

Published
2016
Full Text
View/download PDF

17. 124 AZACITIDINE VERSUS CONVENTIONAL CARE REGIMENS (CCR) IN OLDER PATIENTS WITH NEWLY DIAGNOSED AML (>30% MARROW BLASTS) WITH MYELODYSPLASIA-RELATED CHANGES: SUBGROUP ANALYSIS OF THE AZA-AML-001 STUDY

Author

Seymour, J.F., primary, Döhner, H., additional, Butrym, A., additional, Wierzbowska, A., additional, Selleslag, D., additional, Jang, J.H., additional, Cavenagh, J.D., additional, Kumar, R., additional, Schuh, A.C., additional, Candoni, A., additional, Récher, C., additional, Sandhu, I., additional, del Castillo, T. Bernal, additional, Al-Ali, H.K., additional, Martinelli, G., additional, Falantes, J., additional, Nopenney, R., additional, Stone, R.M., additional, Minden, M.D., additional, McIntyre, H., additional, Songer, S., additional, Lucy, L.M., additional, Beach, C.L., additional, and Dombret, H., additional

Published
2015
Full Text
View/download PDF

18. 96 OVERALL SURVIVAL IN OLDER PATIENTS WITH NEWLY DIAGNOSED AML WITH >30% BONE MARROW BLASTS AND POOR-RISK CYTOGENETICS TREATED WITH AZACITIDINE: SUBANALYSIS OF THE AZA-AML-001 STUDY

Author

Döhner, H., primary, Seymour, J.F., additional, Butrym, A., additional, Wierzbowska, A., additional, Selleslag, D., additional, Jang, J.H., additional, Cavenagh, J.D., additional, Kumar, R., additional, Schuh, A.C., additional, Candoni, A., additional, Récher, C., additional, Sandhu, I., additional, del Castillo, T. Bernal, additional, Al-Ali, H.K., additional, Martinelli, G., additional, Falantes, J., additional, Nopenney, R., additional, Stone, R.M., additional, Minden, M.D., additional, McIntyre, H., additional, Songer, S., additional, Lucy, L.M., additional, Beach, C.L., additional, and Dombret, H., additional

Published
2015
Full Text
View/download PDF

24. 1LBA Clinical safety and activity in a phase I trial of AG-120, a first in class, selective, potent inhibitor of the IDH1-mutant protein, in patients with IDH1 mutant positive advanced hematologic malignancies

Author

Pollyea, D.A., primary, de Botton, S., additional, Fathi, A.T., additional, Stein, E.M., additional, Tallman, M.S., additional, Agresta, S., additional, Bowden, C., additional, Fan, B., additional, Prah, M., additional, Yang, H., additional, Yen, K., additional, and Stone, R.M., additional

Published
2014
Full Text
View/download PDF

25. A 2-gene classifier for predicting response to the farnesyltransferase inhibitor tipifarnib in acute myeloid leukemia

Author

Raponi, M. (Mitch), Lancet, J.E. (Jeffrey), Fan, H. (Hongtao), Dossey, L. (Lesley), Lee, G. (Grace), Gojo, I. (Ivana), Feldman, E.J. (Eric), Gotlib, J. (Jason), Morris, L.E. (Lawrence), Greenberg, P.L. (Peter), Wright, J.J. (John), Harousseau, J-L. (Jean-Luc), Löwenberg, B. (Bob), Stone, R.M. (Richard), Porre, P. (Peter) de, Wang, Y. (Ying), Karp, J.E. (Judith), Raponi, M. (Mitch), Lancet, J.E. (Jeffrey), Fan, H. (Hongtao), Dossey, L. (Lesley), Lee, G. (Grace), Gojo, I. (Ivana), Feldman, E.J. (Eric), Gotlib, J. (Jason), Morris, L.E. (Lawrence), Greenberg, P.L. (Peter), Wright, J.J. (John), Harousseau, J-L. (Jean-Luc), Löwenberg, B. (Bob), Stone, R.M. (Richard), Porre, P. (Peter) de, Wang, Y. (Ying), and Karp, J.E. (Judith)

Abstract

At present, there is no method available to predict response to farnesyltrans- ferase inhibitors (FTIs). We analyzed gene expression profiles from the bone marrow of patients from a phase 2 study of the FTI tipifarnib in older adults with previously untreated acute myeloid leukemia (AML). The RASGRP1/APTX gene expression ratio was found to predict response to tipifarnib with the greatest accuracy using a "leave one out" cross validation (LOOCV; 96%). RASGRP1 is a guanine nucleotide exchange factor that activates RAS, while APTX (aprataxin) is involved in DNA excision repair. The utility of this classifier for predicting response to tipifarnib was validated in an independent set of 58 samples from relapsed or refractory AML, with a negative predictive value (NPV) and positive predictive value (PPV) of 92% and 28%, respectively (odds ratio of 4.4). The classifier also predicted for improved overall survival (154 vs 56 days; P < .001), which was independent of other covariates, including a previously described prognostic gene expression classifier. Therefore, these data indicate that a 2-gene expression assay may have utility in categorizing a population of patients with AML who are more likely to respond to tipifarnib.

Published
2008
Full Text
View/download PDF

26. O-024 Next-generation sequencing of 213 MDS patient samples identifies mutation profiles associated with response to hypomethylating agents and overall survival

Author

Bejar, R., primary, Stevenson, K., additional, Stojanov, P., additional, Zaneveld, J.E., additional, Bar-Natan, M., additional, Caughey, B., additional, Wang, H., additional, Garcia-Manero, G., additional, Kantarjian, H., additional, Cibulskis, K., additional, Getz, G., additional, Steensma, D.P., additional, Stone, R.M., additional, Chen, R., additional, Neuberg, D., additional, and Ebert, B.L., additional

Published
2013
Full Text
View/download PDF

27. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia.

Author

Cheson, B.D., Greenberg, P.L., Bennett, J.M., Lowenberg, B., Wijermans, P.W., Nimer, S.D., Pinto, A., Beran, M., Witte, T.J.M. de, Stone, R.M., Mittelman, M., Sanz, G.F., Gore, S., Schiffer, C.A., Kantarjian, H., Cheson, B.D., Greenberg, P.L., Bennett, J.M., Lowenberg, B., Wijermans, P.W., Nimer, S.D., Pinto, A., Beran, M., Witte, T.J.M. de, Stone, R.M., Mittelman, M., Sanz, G.F., Gore, S., Schiffer, C.A., and Kantarjian, H.

Abstract

Contains fulltext : 50832.pdf (publisher's version ) (Closed access), The myelodysplastic syndromes (MDSs) are heterogeneous with respect to clinical characteristics, pathologic features, and cytogenetic abnormalities. This heterogeneity is a challenge for evaluating response to treatment. Therapeutic trials in MDS have used various criteria to assess results, making cross-study comparisons problematic. In 2000, an International Working Group (IWG) proposed standardized response criteria for evaluating clinically significant responses in MDS. These criteria included measures of alteration in the natural history of disease, hematologic improvement, cytogenetic response, and improvement in health-related quality of life. The relevance of the response criteria has now been validated prospectively in MDS clinical trials, and they have gained acceptance in research studies and in clinical practice. Because limitations of the IWG criteria have surfaced, based on practical and reported experience, some modifications were warranted. In this report, we present recommendations for revisions of some of the initial criteria.

Published
2006

31. Case 17-1992

Author

Cabot, Richard C., primary, Scully, Robert E., additional, Mark, Eugene J., additional, McNeely, William F., additional, McNeely, Betty U., additional, Stone, R.M., additional, and Quintanilla, L., additional

Published
1992
Full Text
View/download PDF

32. Further report of a prospective randomized trial comparing distal splenorenal shunt with end-to-side portacaval shunt

Author

Langer, B., Taylor, B.R., Mackenzie, D.R., Gilas, T., Stone, R.M., and Blendis, L.

Abstract

We electively compared the distal splenorenal (“selective”) shunt with the end-to-side portacaval shunt in 80 prospectively randomized patients with variceal bleeding. Selective shunts required more operative time (3.9 vs. 2.8 h) and blood replacement (4.6 vs. 2.5 U) and postoperative mortality was slightly higher (5 of 38 selective vs. 0 of 40 portacaval). Postoperative complication rates were similar. After 65-mo mean follow-up, both shunts have protected well against late gastrointestinal bleeding (5 selective, 4 portacaval episodes). However, after selective shunts, spontaneous encephalopathy occurred less often (23% vs. 40% of patients), was severe in fewer patients (12% vs. 33%), and precipitated fewer hospital admissions (6 admissions in 4 selective patients vs. 26 admissions in 13 portacaval patients). Furthermore, selective shunt patients remained longer without functional disability (83% vs. 70% of postoperative patient months). Long-term survival was not significantly different in the two groups (5-yr survival: selective 51%, portacaval 56%).

Published
1985
Full Text
View/download PDF

36. A Modified Sugiura Procedure

Author

Ginsberg, R.J., primary, Waters, P.F., additional, Zeldin, R.A., additional, Spratt, E.H., additional, Shandling, B., additional, Stone, R.M., additional, and Strasberg, S., additional

Published
1982
Full Text
View/download PDF

39. Bile duct injury

Author

Stone, R.M., primary, Cohen, Z., additional, Taylor, B.R., additional, Langer, B., additional, and Tovee, E.B., additional

Published
1973
Full Text
View/download PDF

42. Targeting mutant BRAF in relapsed or refractory hairy-cell leukemia

Author

Martin S. Tallman, L. De Carolis, Sasinya N. Scott, Enrico Tiacci, Maria Paola Martelli, Alessandro Pulsoni, Antonella Anastasia, Monia Capponi, A. M. Carella, Robert Foa, Alessandro Broccoli, S. A. Pileri, Brunangelo Falini, Pietro Leoni, Franca Falzetti, Marzia Varettoni, Michael R. Grever, Davide Rossi, Kanti R. Rai, Vincenzo Fraticelli, Giovanna Motta, Jae H. Park, Achille Ambrosetti, M.F. Berger, Alan Saven, Young Rock Chung, Omar Abdel-Wahab, Ross L. Levine, Christopher Y. Park, Stefano Ascani, Neal Rosen, Pier Luigi Zinzani, Mario E. Lacouture, Alessandro Rambaldi, Francesco Zaja, Eunhee Kim, Michele Cimminiello, Stephen S. Chung, Jessica K. Altman, Sean M. Devlin, Richard Stone, Tiacci, E, Park, J.H., De Carolis, L., Chung, S.S., Broccoli, A., Scott, S., Zaja, F., Devlin, S., Pulsoni, A., Chung, Y.R., Cimminiello, M., Kim, E., Rossi, D., Stone, R.M., Motta, G., Saven, A., Varettoni, M., Altman, J.K., Anastasia, A., Grever, M.R., Ambrosetti, A., Rai, K.R., Fraticelli, V., Lacouture, M.E., Carella, A.M., Levine, R.L., Leoni, P., Rambaldi, A., Falzetti, F., Ascani, S., Capponi, M., Martelli, M.P., Park, C.Y., Pileri, S.A., Rosen, N., Foà, R., Berger, M.F., Zinzani, P.L., Abdel-Wahab, O., Falini, B., Tallman, M.S., Park, J. H., Chung, S. S., Zaja, Francesco, Chung, Y. R., Stone, R. M., Altman, J. K., Grever, M. R., Rai, K. R., Lacouture, M. E., Carella, A. M., Levine, R. L., Martelli, M. P., Park, C. Y., Pileri, S. A., Berger, M. F., Zinzani, P. L., Abdel Wahab, O., and Tallman, M. S.

Subjects
Oncology, Male, Indoles, Hairy Cell, Drug Resistance, Administration, Oral, Drug resistance, Antineoplastic Agent, Moxetumomab pasudotox, Bone Marrow, Recurrence, 80 and over, Vemurafenib, Aged, 80 and over, Leukemia, Hairy Cell, Proto-Oncogene Protein, Sulfonamides, Leukemia, Medicine (all), Remission Induction, General Medicine, Middle Aged, HCL, Arthralgia, Administration, Biological Markers, Female, Adult, Aged, Antineoplastic Agents, Biomarkers, Disease-Free Survival, Drug Resistance, Neoplasm, Exanthema, Humans, Mutation, Proto-Oncogene Proteins, Proto-Oncogene Proteins B-raf, ras Proteins, medicine.drug, Human, Oral, medicine.medical_specialty, Purine analogue, BRAF, leukemia, hairy cell, cladribine, Sulfonamide, Article, Proto-Oncogene Proteins p21(ras), Refractory, Internal medicine, medicine, business.industry, Biomarker, medicine.disease, ras Protein, Surgery, Clinical trial, Indole, Neoplasm, business, V600E
Abstract

BRAF V600E is the genetic lesion underlying hairy-cell leukemia. We assessed the safety and activity of the oral BRAF inhibitor vemurafenib in patients with hairy-cell leukemia that had relapsed after treatment with a purine analogue or who had disease that was refractory to purine analogues.We conducted two phase 2, single-group, multicenter studies of vemurafenib (at a dose of 960 mg twice daily)--one in Italy and one in the United States. The therapy was administered for a median of 16 weeks in the Italian study and 18 weeks in the U.S. study. Primary end points were the complete response rate (in the Italian trial) and the overall response rate (in the U.S. trial). Enrollment was completed (28 patients) in the Italian trial in April 2013 and is still open (26 of 36 planned patients) in the U.S. trial.The overall response rates were 96% (25 of 26 patients who could be evaluated) after a median of 8 weeks in the Italian study and 100% (24 of 24) after a median of 12 weeks in the U.S. study. The rates of complete response were 35% (9 of 26 patients) and 42% (10 of 24) in the two trials, respectively. In the Italian trial, after a median follow-up of 23 months, the median relapse-free survival was 19 months among patients with a complete response and 6 months among those with a partial response; the median treatment-free survival was 25 months and 18 months, respectively. In the U.S. trial, at 1 year, the progression-free survival rate was 73% and the overall survival rate was 91%. Drug-related adverse events were usually of grade 1 or 2, and the events most frequently leading to dose reductions were rash and arthralgia or arthritis. Secondary cutaneous tumors (treated with simple excision) developed in 7 of 50 patients. The frequent persistence of phosphorylated ERK-positive leukemic cells in bone marrow at the end of treatment suggests bypass reactivation of MEK and ERK as a resistance mechanism.A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia. (Funded by the Associazione Italiana per la Ricerca sul Cancro and others; EudraCT number, 2011-005487-13; ClinicalTrials.gov number NCT01711632.).

Published
2015

Catalog

Books, media, physical & digital resources
See catalog results