US Intergroup Study of Chemotherapy Plus Dasatinib and Allogeneic Stem Cell Transplant in Philadelphia Chromosome Positive ALL.

Autor:	Ravandi F; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX., Othus M; SWOG Statistical Center, Seattle, WA., O'Brien SM; University of California - Irvine, Orange, CA., Forman SJ; City of Hope National Medical Center, Duarte, CA., Ha CS; University of Texas Health Science Center, San Antonio, TX., Wong JYC; City of Hope National Medical Center, Duarte, CA., Tallman MS; Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY., Paietta E; Cancer Center, Montefiore Medical Center, Bronx, NY.; Albert Einstein College of Medicine, New York, NY., Racevskis J; Cancer Center, Montefiore Medical Center, Bronx, NY.; Albert Einstein College of Medicine, New York, NY., Uy GL; Division of Oncology, Washington University School of Medicine, St. Louis, MO., Horowitz M; Medical College of Wisconsin, Milwaukee, WI., Takebe N; Cancer Therapy Evaluation Program, Investigational Drug Branch, Bethesda, MD., Little R; Cancer Therapy Evaluation Program, Investigational Drug Branch, Bethesda, MD., Borate U; University of Alabama at Birmingham, Birmingham, AL., Kebriaei P; Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX., Kingsbury L; SWOG Statistical Center, Seattle, WA., Kantarjian HM; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX., Radich JP; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA., Erba HP; University of Alabama at Birmingham and UAB Comprehensive Cancer Center, Birmingham, AL., Appelbaum FR; Fred Hutchinson Cancer Research Center, Seattle, WA.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2016 Dec 27; Vol. 1 (3), pp. 250-259.
DOI:	10.1182/bloodadvances.2016001495
Abstrakt:	This multicenter trial was conducted to determine whether the addition of dasatinib to chemotherapy followed by an allogeneic hematopoietic cell transplant (HCT) in patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) was feasible. Patients ≥ 18 and ≤ 60 years of age with newly diagnosed Ph+ ALL received up to 8 cycles of alternating hyperCVAD and high dose cytarabine and methotrexate with dasatinib. Patients with an available matched sibling or unrelated donor underwent an allogeneic HCT in first complete remission (CR1) followed by daily dasatinib starting from day 100. Others received maintenance therapy with vincristine and prednisone for 2 years and dasatinib indefinitely. 97 patients (94 evaluable) with median age of 44 years (range, 20 - 60) and median WBC at presentation of 10 × 10 9 /L (range, 1 - 410 × 10 9 /L) were accrued. 83 (88%) patients achieved CR or CR with incomplete count recovery (CRi) and 41 underwent ASCT in CR1. Median follow-up is 36 months (range, 9 - 63). For the overall population, overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS) at 3 years were 69%, 55%, and 62%, respectively. The 12-month RFS and OS after transplant were 71% and 87%, respectively. Landmark analysis at 175 days from the time of CR/CRi (longest time to HCT), showed statistically superior advantages for RFS and OS (p=0.038 and 0.037, respectively) for the transplanted patients. Addition of dasatinib to chemotherapy and HCT for younger patients with Ph+ ALL is feasible and warrants further testing. Competing Interests: CONFLICT OF INTEREST DISCLOSURES No COI information to disclose: Partow Kebriaei, Laura Kinsbury, Richard Little, Janis Racevskis, Naoko Takebe, Honoraria: Uma Borate, self, Alexion, Novartis, Amgen; Elisabeth Paietta, self, Amgen; Susan O’Brien, self, Gilead, Pharmacyclics, Janssen; Jerald Radich, self, Novartis, BMS, Ariad; Farhad Ravandi, self, BMS, Ariad; Martin Tall, self, St. Vincent’s Hospital, Hartford Hospital, Lundbeck Canada; Jeffrey Wong, self, Accuray, Inc. Consulting or Advisory Role: Fred Appelbaum, self, Igenica, Amgen, Pfizer, Neumedicine, Celator; Uma Borate, self, Alexion, Novartis, Suneisis; Harry Erba, self, Novartis, Incyte, Celgene, Amgen, Ariad, Seattle Genetics, Sunesis, Pfizer, Janssen, Daiichi Sankyo; Megan Othus, self, Glycomemetics, Celgene (DSMB both); Elisabeth Paietta, self, Amgen; Susan O’Brien, self, Amgen, Celgene, CLL Global Research Foundation, GSK; Jerald Radich, self, Novartis, BMS, Ariad; Farhad Ravandi, self, Ariad; Martin Tallman, self, Bioline, Biosight, Agios; Travel, Accommodations, Expenses: Uma Borate, self, Novartis, Alexion, Amgen and Jazz (as part of speakers’ bureau); Elisabeth Paietta, self, Amgen; Susan O’Brien, self (company pending); Mary Horowitz, self, Novartis; Jerald Radich, self, Novartis, BMS; Jeffrey Wong, self, Accuray, Inc. Research Funding: Harry Erba, institution, Celator, Millennium/Takeda, Seattle Genetics, Astellas, Amgen, Agio, Juno, Janssen; Mary Horowitz, self, Sobi Pharmaceuticals; Hagop Kantarjian, institution, Ariad, BMS, Pfizer, Amgen, Novartis; Jerald Radich, self, Novartis; Susan O’Brien, self/institution, Acerta, TG Therapeutics, Regeneron, Gilead, Pharmacyclics, ProNAi; Farhad Ravandi, self/institution, BMS; Martin Tallman, self, Bioline, Epizyme, Arog; Jeffrey Wong, institution, Accuray, Inc. Speakers’ Bureau: Uma Borate, self, Novartis, Alexion, Amgen and Jazz; Harry Erba, self, Novartis, Incyte, Celgene; Stock or Other Ownership: Fred Appelbaum, self, Adaptive Biotechnology; Patents, Royalties, Other Intellectual Property: Chul Ha, self, has patents but no royalty arrangements (patents held by Dr. Chul and his institution) Other Relationship: Harry Erba, self, Gyclomemetics Inc., (DSMB Chair)
Databáze:	MEDLINE
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