Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease.

Adolescent Adult Aged Child Cytomegalovirus Infections / etiology Female Glucocorticoids / therapeutic use Graft vs Host Disease / drug therapy Humans Immunologic Factors / adverse effects Janus Kinases / antagonists & inhibitors Male Middle Aged Nitriles Photopheresis Pyrazoles / adverse effects Pyrimidines Survival Analysis Thrombocytopenia / chemically induced Treatment Failure Young Adult

Journal

The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562

Informations de publication

Date de publication:
15 07 2021
Historique:
entrez: 14 7 2021
pubmed: 15 7 2021
medline: 23 7 2021
Statut: ppublish

Résumé

Chronic graft-versus-host disease (GVHD), a major complication of allogeneic stem-cell transplantation, becomes glucocorticoid-refractory or glucocorticoid-dependent in approximately 50% of patients. Robust data from phase 3 randomized studies evaluating second-line therapy for chronic GVHD are lacking. In retrospective surveys, ruxolitinib, a Janus kinase (JAK1-JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory or -dependent chronic GVHD. This phase 3 open-label, randomized trial evaluated the efficacy and safety of ruxolitinib at a dose of 10 mg twice daily, as compared with the investigator's choice of therapy from a list of 10 commonly used options considered best available care (control), in patients 12 years of age or older with moderate or severe glucocorticoid-refractory or -dependent chronic GVHD. The primary end point was overall response (complete or partial response) at week 24; key secondary end points were failure-free survival and improved score on the modified Lee Symptom Scale at week 24. A total of 329 patients underwent randomization; 165 patients were assigned to receive ruxolitinib and 164 patients to receive control therapy. Overall response at week 24 was greater in the ruxolitinib group than in the control group (49.7% vs. 25.6%; odds ratio, 2.99; P<0.001). Ruxolitinib led to longer median failure-free survival than control (>18.6 months vs. 5.7 months; hazard ratio, 0.37; P<0.001) and higher symptom response (24.2% vs. 11.0%; odds ratio, 2.62; P = 0.001). The most common (occurring in ≥10% patients) adverse events of grade 3 or higher up to week 24 were thrombocytopenia (15.2% in the ruxolitinib group and 10.1% in the control group) and anemia (12.7% and 7.6%, respectively). The incidence of cytomegalovirus infections and reactivations was similar in the two groups. Among patients with glucocorticoid-refractory or -dependent chronic GVHD, ruxolitinib led to significantly greater overall response, failure-free survival, and symptom response. The incidence of thrombocytopenia and anemia was greater with ruxolitinib. (Funded by Novartis and Incyte; REACH3 ClinicalTrials.gov number, NCT03112603.).

Sections du résumé

BACKGROUND
Chronic graft-versus-host disease (GVHD), a major complication of allogeneic stem-cell transplantation, becomes glucocorticoid-refractory or glucocorticoid-dependent in approximately 50% of patients. Robust data from phase 3 randomized studies evaluating second-line therapy for chronic GVHD are lacking. In retrospective surveys, ruxolitinib, a Janus kinase (JAK1-JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory or -dependent chronic GVHD.
METHODS
This phase 3 open-label, randomized trial evaluated the efficacy and safety of ruxolitinib at a dose of 10 mg twice daily, as compared with the investigator's choice of therapy from a list of 10 commonly used options considered best available care (control), in patients 12 years of age or older with moderate or severe glucocorticoid-refractory or -dependent chronic GVHD. The primary end point was overall response (complete or partial response) at week 24; key secondary end points were failure-free survival and improved score on the modified Lee Symptom Scale at week 24.
RESULTS
A total of 329 patients underwent randomization; 165 patients were assigned to receive ruxolitinib and 164 patients to receive control therapy. Overall response at week 24 was greater in the ruxolitinib group than in the control group (49.7% vs. 25.6%; odds ratio, 2.99; P<0.001). Ruxolitinib led to longer median failure-free survival than control (>18.6 months vs. 5.7 months; hazard ratio, 0.37; P<0.001) and higher symptom response (24.2% vs. 11.0%; odds ratio, 2.62; P = 0.001). The most common (occurring in ≥10% patients) adverse events of grade 3 or higher up to week 24 were thrombocytopenia (15.2% in the ruxolitinib group and 10.1% in the control group) and anemia (12.7% and 7.6%, respectively). The incidence of cytomegalovirus infections and reactivations was similar in the two groups.
CONCLUSIONS
Among patients with glucocorticoid-refractory or -dependent chronic GVHD, ruxolitinib led to significantly greater overall response, failure-free survival, and symptom response. The incidence of thrombocytopenia and anemia was greater with ruxolitinib. (Funded by Novartis and Incyte; REACH3 ClinicalTrials.gov number, NCT03112603.).

Identifiants

DOI: 10.1056/NEJMoa2033122 PMID: 34260836
pubmed: 34260836
doi: 10.1056/NEJMoa2033122
doi:

Substances chimiques

Glucocorticoids 0
Immunologic Factors 0
Nitriles 0
Pyrazoles 0
Pyrimidines 0
ruxolitinib 82S8X8XX8H
Janus Kinases EC 2.7.10.2

Banques de données

ClinicalTrials.gov
['NCT03112603']

Types de publication

Clinical Trial, Phase III Comparative Study Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

228-238

Investigateurs

David Ritchie (D)
Nada Hamad (N)
Johannes Clausen (J)
Margit Mitterbauer (M)
Hildegard Greinix (H)
Hélène Schoemans (H)
Dimitri Breems (D)
Penka Ganeva (P)
Dennis Kim (D)
Brian Leber (B)
Jennifer White (J)
Pavel Zak (P)
Veronika Valkova (V)
Brian Thomas Kornblit (BT)
Ibrahim Yakoub Agha (IY)
Jean-Baptiste Mear (JB)
Marie-Therese Rubio (MT)
Gerard Socié (G)
Anne Laplace (A)
Mohamad Mohty (M)
Anne Huynh (A)
Herrad Baurmann (H)
Guido Kobbe (G)
Tobias Holderried (T)
Jan Moritz Middeke (JM)
Julia Winkler (J)
Klaus Daniel Stachel (KD)
Gesine Bug (G)
Robert Zeiser (R)
Francis Ayuketang Ayuk (FA)
Inken Hilgendorf (I)
Udo Holtick (U)
Georg-Nikolaus Franke (GN)
Eva Wagner (E)
Stefan Klein (S)
Matthias Stelljes (M)
Natalie Schub (N)
Goetz Grigoleit (G)
Achilleas Anagnostopoulos (A)
Panagiotis Tsirigotis (P)
Alexandros Spyridonidis (A)
Dinesh Bhurani (D)
Shashikant Apte (S)
Moshe Yeshurun (M)
Tsila Zuckerman (T)
Ron Ram (R)
Franca Fagioli (F)
Domenico Russo (D)
Maria Caterina Micò (MC)
Francesca Bonifazi (F)
Lucia Prezioso (L)
Francesca Patriarca (F)
Maurizio Musso (M)
Paolo Corradini (P)
Angelo Michele Carella (AM)
Stefania Bramanti (S)
Franco Locatelli (F)
Francesca Gualandi (F)
Fabio Ciceri (F)
Attilio Olivieri (A)
Luisa Giaccone (L)
Takanori Teshima (T)
Masaya Okada (M)
Koichi Miyamura (K)
Masahiro Ashizawa (M)
Takehiko Mori (T)
Takayuki Ishikawa (T)
Tadakazu Kondo (T)
Koji Kato (K)
Yoshinobu Maeda (Y)
Hirohisa Nakamae (H)
Kentaro Fukushima (K)
Takashi Ikeda (T)
Yasushi Onishi (Y)
Kiyoshi Ando (K)
Noriko Doki (N)
Shuichi Taniguchi (S)
Husam AbuJazar (H)
Sung-Soo Yoon (SS)
C J M Halkes (CJM)
J H E Kuball (JHE)
Tobias Gedde-Dahl (T)
Sebastian Giebel (S)
Jan Zaucha (J)
Tomasz Wrobel (T)
Isabelina Ferreira (I)
Elena Parovichnikova (E)
Ivan Moiseev (I)
Shahrukh Hashmi (S)
Sonia Gonzalez Perez (S)
Carlos Vallejo (C)
Isabel Sanchez Ortega (I)
Valle Gómez (V)
Lucia Del Corral (LD)
Maria Del Mar Perera-Alvarez (MDM)
Andres Sanchez Salinas (A)
Jose Antonio Perez Simon (JA)
Krista Vath (K)
Joerg Halter (J)
Antonia Mueller (A)
Ant Uzay (A)
Sinem Civriz Bozdag (S)
Erdal Kurtoglu (E)
Fevzi Altuntas (F)
Hakan Goker (H)
Hugues De Lavallade (H)
Fiona Dignan (F)
David Irvine (D)
Ronjon Chakraverty (R)
Emi Caywood (E)
Murali Kodali (M)
Malgorzata McMasters (M)
Ali Haris (A)
Betty Hamilton (B)
Mitchell Horwitz (M)
Joseph Pidala (J)
John Edwards (J)
Michael Grunwald (M)
Patrick Stiff (P)
Reshma Ramlal (R)
Zachariah DeFilipp (Z)
Amin Alousi (A)
Nirav Shah (N)
Miguel Perales (M)
Anne Renteria (A)
Jennifer Choi (J)
Samantha Jaglowski (S)
Essell James (E)
Mary Flowers (M)
Aric Hall (A)
Salmon Fazal (S)
Leland Metheny (L)
Gary Schiller (G)
Dimitrios Tzachanis (D)
Andrew Artz (A)
Nosha Farhadfar (N)
Damiano Rondelli (D)
Sunil Abhyankar (S)
Jan Cerny (J)
Vijaya Bhatt (V)
William Wood (W)
Carrie Yuen (C)
Mary Ellen Martin (ME)
Annie Im (A)
George Yaghmour (G)
Madhuri Vusirikala (M)
Madan Jagasia (M)
Dianna Howard (D)
Stuart Seropian (S)

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2021 Massachusetts Medical Society.

Auteurs

Robert Zeiser (R)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), and Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Dresden (J.M.M.) - both in Germany; the Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, ASST Spedali Civili di Brescia, University of Brescia, Brescia (N.P.), UOC di Oncoematologia e TMO, Dipartimento Oncologico "la Maddalena," Palermo (M.M.), and Dipartimento di Oncoematologia Pediatrica, IRCCS, Ospedale Pediatrico Bambino Gesu', Sapienza, Università di Roma, Rome (F.L.) - all in Italy; the BMT Unit, Tel Aviv (Sourasky) Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (R.R.); the Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia (S.K.H.); the Department of Medicine, Sheikh Shakhbout Medical City, Mayo Clinic, Abu Dhabi, United Arab Emirates (S.K.H.); UCL Cancer Institute, Institute of Immunity and Transplantation, London (R.C.); the Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland (S.G.); Acibadem University Hospital, Hematology Department, Istanbul, Turkey (A.U.); Incyte, Wilmington, DE (P.L.); Novartis Pharma, Basel, Switzerland (N.H., T.S.); Novartis Pharmaceuticals, East Hanover, NJ (M.G.); the Fred Hutchinson Cancer Research Center, Seattle (S.J.L.); and the Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan (T.T.).

Nicola Polverelli (N)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), and Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Dresden (J.M.M.) - both in Germany; the Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, ASST Spedali Civili di Brescia, University of Brescia, Brescia (N.P.), UOC di Oncoematologia e TMO, Dipartimento Oncologico "la Maddalena," Palermo (M.M.), and Dipartimento di Oncoematologia Pediatrica, IRCCS, Ospedale Pediatrico Bambino Gesu', Sapienza, Università di Roma, Rome (F.L.) - all in Italy; the BMT Unit, Tel Aviv (Sourasky) Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (R.R.); the Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia (S.K.H.); the Department of Medicine, Sheikh Shakhbout Medical City, Mayo Clinic, Abu Dhabi, United Arab Emirates (S.K.H.); UCL Cancer Institute, Institute of Immunity and Transplantation, London (R.C.); the Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland (S.G.); Acibadem University Hospital, Hematology Department, Istanbul, Turkey (A.U.); Incyte, Wilmington, DE (P.L.); Novartis Pharma, Basel, Switzerland (N.H., T.S.); Novartis Pharmaceuticals, East Hanover, NJ (M.G.); the Fred Hutchinson Cancer Research Center, Seattle (S.J.L.); and the Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan (T.T.).

Ron Ram (R)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), and Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Dresden (J.M.M.) - both in Germany; the Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, ASST Spedali Civili di Brescia, University of Brescia, Brescia (N.P.), UOC di Oncoematologia e TMO, Dipartimento Oncologico "la Maddalena," Palermo (M.M.), and Dipartimento di Oncoematologia Pediatrica, IRCCS, Ospedale Pediatrico Bambino Gesu', Sapienza, Università di Roma, Rome (F.L.) - all in Italy; the BMT Unit, Tel Aviv (Sourasky) Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (R.R.); the Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia (S.K.H.); the Department of Medicine, Sheikh Shakhbout Medical City, Mayo Clinic, Abu Dhabi, United Arab Emirates (S.K.H.); UCL Cancer Institute, Institute of Immunity and Transplantation, London (R.C.); the Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland (S.G.); Acibadem University Hospital, Hematology Department, Istanbul, Turkey (A.U.); Incyte, Wilmington, DE (P.L.); Novartis Pharma, Basel, Switzerland (N.H., T.S.); Novartis Pharmaceuticals, East Hanover, NJ (M.G.); the Fred Hutchinson Cancer Research Center, Seattle (S.J.L.); and the Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan (T.T.).

Shahrukh K Hashmi (SK)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), and Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Dresden (J.M.M.) - both in Germany; the Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, ASST Spedali Civili di Brescia, University of Brescia, Brescia (N.P.), UOC di Oncoematologia e TMO, Dipartimento Oncologico "la Maddalena," Palermo (M.M.), and Dipartimento di Oncoematologia Pediatrica, IRCCS, Ospedale Pediatrico Bambino Gesu', Sapienza, Università di Roma, Rome (F.L.) - all in Italy; the BMT Unit, Tel Aviv (Sourasky) Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (R.R.); the Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia (S.K.H.); the Department of Medicine, Sheikh Shakhbout Medical City, Mayo Clinic, Abu Dhabi, United Arab Emirates (S.K.H.); UCL Cancer Institute, Institute of Immunity and Transplantation, London (R.C.); the Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland (S.G.); Acibadem University Hospital, Hematology Department, Istanbul, Turkey (A.U.); Incyte, Wilmington, DE (P.L.); Novartis Pharma, Basel, Switzerland (N.H., T.S.); Novartis Pharmaceuticals, East Hanover, NJ (M.G.); the Fred Hutchinson Cancer Research Center, Seattle (S.J.L.); and the Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan (T.T.).

Ronjon Chakraverty (R)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), and Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Dresden (J.M.M.) - both in Germany; the Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, ASST Spedali Civili di Brescia, University of Brescia, Brescia (N.P.), UOC di Oncoematologia e TMO, Dipartimento Oncologico "la Maddalena," Palermo (M.M.), and Dipartimento di Oncoematologia Pediatrica, IRCCS, Ospedale Pediatrico Bambino Gesu', Sapienza, Università di Roma, Rome (F.L.) - all in Italy; the BMT Unit, Tel Aviv (Sourasky) Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (R.R.); the Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia (S.K.H.); the Department of Medicine, Sheikh Shakhbout Medical City, Mayo Clinic, Abu Dhabi, United Arab Emirates (S.K.H.); UCL Cancer Institute, Institute of Immunity and Transplantation, London (R.C.); the Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland (S.G.); Acibadem University Hospital, Hematology Department, Istanbul, Turkey (A.U.); Incyte, Wilmington, DE (P.L.); Novartis Pharma, Basel, Switzerland (N.H., T.S.); Novartis Pharmaceuticals, East Hanover, NJ (M.G.); the Fred Hutchinson Cancer Research Center, Seattle (S.J.L.); and the Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan (T.T.).

Jan Moritz Middeke (JM)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), and Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Dresden (J.M.M.) - both in Germany; the Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, ASST Spedali Civili di Brescia, University of Brescia, Brescia (N.P.), UOC di Oncoematologia e TMO, Dipartimento Oncologico "la Maddalena," Palermo (M.M.), and Dipartimento di Oncoematologia Pediatrica, IRCCS, Ospedale Pediatrico Bambino Gesu', Sapienza, Università di Roma, Rome (F.L.) - all in Italy; the BMT Unit, Tel Aviv (Sourasky) Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (R.R.); the Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia (S.K.H.); the Department of Medicine, Sheikh Shakhbout Medical City, Mayo Clinic, Abu Dhabi, United Arab Emirates (S.K.H.); UCL Cancer Institute, Institute of Immunity and Transplantation, London (R.C.); the Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland (S.G.); Acibadem University Hospital, Hematology Department, Istanbul, Turkey (A.U.); Incyte, Wilmington, DE (P.L.); Novartis Pharma, Basel, Switzerland (N.H., T.S.); Novartis Pharmaceuticals, East Hanover, NJ (M.G.); the Fred Hutchinson Cancer Research Center, Seattle (S.J.L.); and the Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan (T.T.).

Maurizio Musso (M)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), and Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Dresden (J.M.M.) - both in Germany; the Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, ASST Spedali Civili di Brescia, University of Brescia, Brescia (N.P.), UOC di Oncoematologia e TMO, Dipartimento Oncologico "la Maddalena," Palermo (M.M.), and Dipartimento di Oncoematologia Pediatrica, IRCCS, Ospedale Pediatrico Bambino Gesu', Sapienza, Università di Roma, Rome (F.L.) - all in Italy; the BMT Unit, Tel Aviv (Sourasky) Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (R.R.); the Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia (S.K.H.); the Department of Medicine, Sheikh Shakhbout Medical City, Mayo Clinic, Abu Dhabi, United Arab Emirates (S.K.H.); UCL Cancer Institute, Institute of Immunity and Transplantation, London (R.C.); the Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland (S.G.); Acibadem University Hospital, Hematology Department, Istanbul, Turkey (A.U.); Incyte, Wilmington, DE (P.L.); Novartis Pharma, Basel, Switzerland (N.H., T.S.); Novartis Pharmaceuticals, East Hanover, NJ (M.G.); the Fred Hutchinson Cancer Research Center, Seattle (S.J.L.); and the Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan (T.T.).

Sebastian Giebel (S)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), and Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Dresden (J.M.M.) - both in Germany; the Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, ASST Spedali Civili di Brescia, University of Brescia, Brescia (N.P.), UOC di Oncoematologia e TMO, Dipartimento Oncologico "la Maddalena," Palermo (M.M.), and Dipartimento di Oncoematologia Pediatrica, IRCCS, Ospedale Pediatrico Bambino Gesu', Sapienza, Università di Roma, Rome (F.L.) - all in Italy; the BMT Unit, Tel Aviv (Sourasky) Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (R.R.); the Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia (S.K.H.); the Department of Medicine, Sheikh Shakhbout Medical City, Mayo Clinic, Abu Dhabi, United Arab Emirates (S.K.H.); UCL Cancer Institute, Institute of Immunity and Transplantation, London (R.C.); the Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland (S.G.); Acibadem University Hospital, Hematology Department, Istanbul, Turkey (A.U.); Incyte, Wilmington, DE (P.L.); Novartis Pharma, Basel, Switzerland (N.H., T.S.); Novartis Pharmaceuticals, East Hanover, NJ (M.G.); the Fred Hutchinson Cancer Research Center, Seattle (S.J.L.); and the Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan (T.T.).

Ant Uzay (A)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), and Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Dresden (J.M.M.) - both in Germany; the Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, ASST Spedali Civili di Brescia, University of Brescia, Brescia (N.P.), UOC di Oncoematologia e TMO, Dipartimento Oncologico "la Maddalena," Palermo (M.M.), and Dipartimento di Oncoematologia Pediatrica, IRCCS, Ospedale Pediatrico Bambino Gesu', Sapienza, Università di Roma, Rome (F.L.) - all in Italy; the BMT Unit, Tel Aviv (Sourasky) Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (R.R.); the Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia (S.K.H.); the Department of Medicine, Sheikh Shakhbout Medical City, Mayo Clinic, Abu Dhabi, United Arab Emirates (S.K.H.); UCL Cancer Institute, Institute of Immunity and Transplantation, London (R.C.); the Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland (S.G.); Acibadem University Hospital, Hematology Department, Istanbul, Turkey (A.U.); Incyte, Wilmington, DE (P.L.); Novartis Pharma, Basel, Switzerland (N.H., T.S.); Novartis Pharmaceuticals, East Hanover, NJ (M.G.); the Fred Hutchinson Cancer Research Center, Seattle (S.J.L.); and the Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan (T.T.).

Peter Langmuir (P)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), and Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Dresden (J.M.M.) - both in Germany; the Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, ASST Spedali Civili di Brescia, University of Brescia, Brescia (N.P.), UOC di Oncoematologia e TMO, Dipartimento Oncologico "la Maddalena," Palermo (M.M.), and Dipartimento di Oncoematologia Pediatrica, IRCCS, Ospedale Pediatrico Bambino Gesu', Sapienza, Università di Roma, Rome (F.L.) - all in Italy; the BMT Unit, Tel Aviv (Sourasky) Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (R.R.); the Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia (S.K.H.); the Department of Medicine, Sheikh Shakhbout Medical City, Mayo Clinic, Abu Dhabi, United Arab Emirates (S.K.H.); UCL Cancer Institute, Institute of Immunity and Transplantation, London (R.C.); the Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland (S.G.); Acibadem University Hospital, Hematology Department, Istanbul, Turkey (A.U.); Incyte, Wilmington, DE (P.L.); Novartis Pharma, Basel, Switzerland (N.H., T.S.); Novartis Pharmaceuticals, East Hanover, NJ (M.G.); the Fred Hutchinson Cancer Research Center, Seattle (S.J.L.); and the Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan (T.T.).

Norbert Hollaender (N)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), and Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Dresden (J.M.M.) - both in Germany; the Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, ASST Spedali Civili di Brescia, University of Brescia, Brescia (N.P.), UOC di Oncoematologia e TMO, Dipartimento Oncologico "la Maddalena," Palermo (M.M.), and Dipartimento di Oncoematologia Pediatrica, IRCCS, Ospedale Pediatrico Bambino Gesu', Sapienza, Università di Roma, Rome (F.L.) - all in Italy; the BMT Unit, Tel Aviv (Sourasky) Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (R.R.); the Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia (S.K.H.); the Department of Medicine, Sheikh Shakhbout Medical City, Mayo Clinic, Abu Dhabi, United Arab Emirates (S.K.H.); UCL Cancer Institute, Institute of Immunity and Transplantation, London (R.C.); the Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland (S.G.); Acibadem University Hospital, Hematology Department, Istanbul, Turkey (A.U.); Incyte, Wilmington, DE (P.L.); Novartis Pharma, Basel, Switzerland (N.H., T.S.); Novartis Pharmaceuticals, East Hanover, NJ (M.G.); the Fred Hutchinson Cancer Research Center, Seattle (S.J.L.); and the Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan (T.T.).

Maanasa Gowda (M)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), and Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Dresden (J.M.M.) - both in Germany; the Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, ASST Spedali Civili di Brescia, University of Brescia, Brescia (N.P.), UOC di Oncoematologia e TMO, Dipartimento Oncologico "la Maddalena," Palermo (M.M.), and Dipartimento di Oncoematologia Pediatrica, IRCCS, Ospedale Pediatrico Bambino Gesu', Sapienza, Università di Roma, Rome (F.L.) - all in Italy; the BMT Unit, Tel Aviv (Sourasky) Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (R.R.); the Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia (S.K.H.); the Department of Medicine, Sheikh Shakhbout Medical City, Mayo Clinic, Abu Dhabi, United Arab Emirates (S.K.H.); UCL Cancer Institute, Institute of Immunity and Transplantation, London (R.C.); the Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland (S.G.); Acibadem University Hospital, Hematology Department, Istanbul, Turkey (A.U.); Incyte, Wilmington, DE (P.L.); Novartis Pharma, Basel, Switzerland (N.H., T.S.); Novartis Pharmaceuticals, East Hanover, NJ (M.G.); the Fred Hutchinson Cancer Research Center, Seattle (S.J.L.); and the Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan (T.T.).

Tommaso Stefanelli (T)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), and Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Dresden (J.M.M.) - both in Germany; the Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, ASST Spedali Civili di Brescia, University of Brescia, Brescia (N.P.), UOC di Oncoematologia e TMO, Dipartimento Oncologico "la Maddalena," Palermo (M.M.), and Dipartimento di Oncoematologia Pediatrica, IRCCS, Ospedale Pediatrico Bambino Gesu', Sapienza, Università di Roma, Rome (F.L.) - all in Italy; the BMT Unit, Tel Aviv (Sourasky) Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (R.R.); the Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia (S.K.H.); the Department of Medicine, Sheikh Shakhbout Medical City, Mayo Clinic, Abu Dhabi, United Arab Emirates (S.K.H.); UCL Cancer Institute, Institute of Immunity and Transplantation, London (R.C.); the Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland (S.G.); Acibadem University Hospital, Hematology Department, Istanbul, Turkey (A.U.); Incyte, Wilmington, DE (P.L.); Novartis Pharma, Basel, Switzerland (N.H., T.S.); Novartis Pharmaceuticals, East Hanover, NJ (M.G.); the Fred Hutchinson Cancer Research Center, Seattle (S.J.L.); and the Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan (T.T.).

Stephanie J Lee (SJ)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), and Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Dresden (J.M.M.) - both in Germany; the Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, ASST Spedali Civili di Brescia, University of Brescia, Brescia (N.P.), UOC di Oncoematologia e TMO, Dipartimento Oncologico "la Maddalena," Palermo (M.M.), and Dipartimento di Oncoematologia Pediatrica, IRCCS, Ospedale Pediatrico Bambino Gesu', Sapienza, Università di Roma, Rome (F.L.) - all in Italy; the BMT Unit, Tel Aviv (Sourasky) Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (R.R.); the Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia (S.K.H.); the Department of Medicine, Sheikh Shakhbout Medical City, Mayo Clinic, Abu Dhabi, United Arab Emirates (S.K.H.); UCL Cancer Institute, Institute of Immunity and Transplantation, London (R.C.); the Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland (S.G.); Acibadem University Hospital, Hematology Department, Istanbul, Turkey (A.U.); Incyte, Wilmington, DE (P.L.); Novartis Pharma, Basel, Switzerland (N.H., T.S.); Novartis Pharmaceuticals, East Hanover, NJ (M.G.); the Fred Hutchinson Cancer Research Center, Seattle (S.J.L.); and the Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan (T.T.).

Takanori Teshima (T)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), and Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Dresden (J.M.M.) - both in Germany; the Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, ASST Spedali Civili di Brescia, University of Brescia, Brescia (N.P.), UOC di Oncoematologia e TMO, Dipartimento Oncologico "la Maddalena," Palermo (M.M.), and Dipartimento di Oncoematologia Pediatrica, IRCCS, Ospedale Pediatrico Bambino Gesu', Sapienza, Università di Roma, Rome (F.L.) - all in Italy; the BMT Unit, Tel Aviv (Sourasky) Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (R.R.); the Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia (S.K.H.); the Department of Medicine, Sheikh Shakhbout Medical City, Mayo Clinic, Abu Dhabi, United Arab Emirates (S.K.H.); UCL Cancer Institute, Institute of Immunity and Transplantation, London (R.C.); the Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland (S.G.); Acibadem University Hospital, Hematology Department, Istanbul, Turkey (A.U.); Incyte, Wilmington, DE (P.L.); Novartis Pharma, Basel, Switzerland (N.H., T.S.); Novartis Pharmaceuticals, East Hanover, NJ (M.G.); the Fred Hutchinson Cancer Research Center, Seattle (S.J.L.); and the Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan (T.T.).

Franco Locatelli (F)

From the Department of Medicine I, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg (R.Z.), and Medizinische Klinik und Poliklinik I, Universitätsklinikum Dresden, Dresden (J.M.M.) - both in Germany; the Unit of Blood Diseases and Stem Cell Transplantation, Department of Clinical and Experimental Sciences, ASST Spedali Civili di Brescia, University of Brescia, Brescia (N.P.), UOC di Oncoematologia e TMO, Dipartimento Oncologico "la Maddalena," Palermo (M.M.), and Dipartimento di Oncoematologia Pediatrica, IRCCS, Ospedale Pediatrico Bambino Gesu', Sapienza, Università di Roma, Rome (F.L.) - all in Italy; the BMT Unit, Tel Aviv (Sourasky) Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (R.R.); the Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia (S.K.H.); the Department of Medicine, Sheikh Shakhbout Medical City, Mayo Clinic, Abu Dhabi, United Arab Emirates (S.K.H.); UCL Cancer Institute, Institute of Immunity and Transplantation, London (R.C.); the Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland (S.G.); Acibadem University Hospital, Hematology Department, Istanbul, Turkey (A.U.); Incyte, Wilmington, DE (P.L.); Novartis Pharma, Basel, Switzerland (N.H., T.S.); Novartis Pharmaceuticals, East Hanover, NJ (M.G.); the Fred Hutchinson Cancer Research Center, Seattle (S.J.L.); and the Department of Hematology, Hokkaido University Faculty of Medicine, Sapporo, Japan (T.T.).

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questionsmedicales.fr › Personnes › Tranches d'âge › Adolescent › Ruxolitinib for Glucocorticoid-Refractory...
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