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Article: Clofarabine, cytarabine, and mitoxantrone in refractory/relapsed acute myeloid leukemia: High response rates and effective bridge to allogeneic hematopoietic stem cell transplantation

TitleClofarabine, cytarabine, and mitoxantrone in refractory/relapsed acute myeloid leukemia: High response rates and effective bridge to allogeneic hematopoietic stem cell transplantation
Authors
Keywordsacute myeloid leukemia
adult
clofarabine
cytarabine
mitoxantrone
Issue Date2020
PublisherWiley Open Access. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2045-7634
Citation
Cancer Medicine, 2020, Epub 2020-03-18 How to Cite?
AbstractClofarabine is active in refractory/relapsed acute myeloid leukemia (AML). In this phase 2 study, we treated 18‐ to 65‐year‐old AML patients refractory to first‐line 3 + 7 daunorubicin/cytarabine induction or relapsing after 3 + 7 induction and high‐dose cytarabine consolidation, with clofarabine (30 mg/m2/d, Days 1‐5), cytarabine (750 mg/m2/d, Days 1‐5), and mitoxantrone (12 mg/m2/d, Days 3‐5) (CLAM). Patients achieving remission received up to two consolidation cycles of 50% CLAM, with eligible cases bridged to allogeneic hematopoietic stem cell transplantation (allo‐HSCT). The mutational profile of a 69‐gene panel was evaluated. Twenty‐six men and 26 women at a median age of 46 (22‐65) years were treated. The overall response rate after the first cycle of CLAM was 90.4% (complete remission, CR: 69.2%; CR with incomplete hematologic recovery, CRi: 21.2%). Twenty‐two CR/CRi patients underwent allo‐HSCT. The 2‐year overall survival (OS), relapse‐free survival (RFS), and event‐free survival (EFS) were 65.8%, 45.7%, and 40.2%, respectively. Multivariate analyses showed that superior OS was associated with CR after CLAM (P = .005) and allo‐HSCT (P = .005), and superior RFS and EFS were associated with allo‐HSCT (P < .001). Remarkably, CR after CLAM and allo‐HSCT resulted in 2‐year OS of 84.3% and 90%, respectively. Karyotypic aberrations and genetic mutations did not influence responses or survivals. Grade 3/4 neutropenia/thrombocytopenia and grade 3 febrile neutropenia occurred in all cases. Other nonhematologic toxicities were mild and uncommon. There was no treatment‐related mortality and the performance of allo‐HSCT was not compromised. Clofarabine, cytarabine, and mitoxantrone was highly effective and safe in refractory/relapsed AML. This study was registered at ClinicalTrials.gov (NCT02686593).
Persistent Identifierhttp://hdl.handle.net/10722/281838
ISSN
2019 Impact Factor: 3.491
2015 SCImago Journal Rankings: 1.811
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSingh, G-
dc.contributor.authorYim, R-
dc.contributor.authorPang, HH-
dc.contributor.authorLee, P-
dc.contributor.authorChan, TSY-
dc.contributor.authorHwang, Y-Y-
dc.contributor.authorLeung, GMK-
dc.contributor.authorIp, H-W-
dc.contributor.authorLeung, RYY-
dc.contributor.authorYip, S-F-
dc.contributor.authorKho, B-
dc.contributor.authorLee, HKK-
dc.contributor.authorMak, V-
dc.contributor.authorChan, C-C-
dc.contributor.authorLau, JSM-
dc.contributor.authorLau, C-K-
dc.contributor.authorLin, S-Y-
dc.contributor.authorWong, RSM-
dc.contributor.authorLi, W-
dc.contributor.authorMa, ESK-
dc.contributor.authorLi, J-
dc.contributor.authorPanagiotou, G-
dc.contributor.authorSim, JPY-
dc.contributor.authorLie, AKW-
dc.contributor.authorKwong, Y-L-
dc.date.accessioned2020-04-03T07:22:31Z-
dc.date.available2020-04-03T07:22:31Z-
dc.date.issued2020-
dc.identifier.citationCancer Medicine, 2020, Epub 2020-03-18-
dc.identifier.issn2045-7634-
dc.identifier.urihttp://hdl.handle.net/10722/281838-
dc.description.abstractClofarabine is active in refractory/relapsed acute myeloid leukemia (AML). In this phase 2 study, we treated 18‐ to 65‐year‐old AML patients refractory to first‐line 3 + 7 daunorubicin/cytarabine induction or relapsing after 3 + 7 induction and high‐dose cytarabine consolidation, with clofarabine (30 mg/m2/d, Days 1‐5), cytarabine (750 mg/m2/d, Days 1‐5), and mitoxantrone (12 mg/m2/d, Days 3‐5) (CLAM). Patients achieving remission received up to two consolidation cycles of 50% CLAM, with eligible cases bridged to allogeneic hematopoietic stem cell transplantation (allo‐HSCT). The mutational profile of a 69‐gene panel was evaluated. Twenty‐six men and 26 women at a median age of 46 (22‐65) years were treated. The overall response rate after the first cycle of CLAM was 90.4% (complete remission, CR: 69.2%; CR with incomplete hematologic recovery, CRi: 21.2%). Twenty‐two CR/CRi patients underwent allo‐HSCT. The 2‐year overall survival (OS), relapse‐free survival (RFS), and event‐free survival (EFS) were 65.8%, 45.7%, and 40.2%, respectively. Multivariate analyses showed that superior OS was associated with CR after CLAM (P = .005) and allo‐HSCT (P = .005), and superior RFS and EFS were associated with allo‐HSCT (P < .001). Remarkably, CR after CLAM and allo‐HSCT resulted in 2‐year OS of 84.3% and 90%, respectively. Karyotypic aberrations and genetic mutations did not influence responses or survivals. Grade 3/4 neutropenia/thrombocytopenia and grade 3 febrile neutropenia occurred in all cases. Other nonhematologic toxicities were mild and uncommon. There was no treatment‐related mortality and the performance of allo‐HSCT was not compromised. Clofarabine, cytarabine, and mitoxantrone was highly effective and safe in refractory/relapsed AML. This study was registered at ClinicalTrials.gov (NCT02686593).-
dc.languageeng-
dc.publisherWiley Open Access. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2045-7634-
dc.relation.ispartofCancer Medicine-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectacute myeloid leukemia-
dc.subjectadult-
dc.subjectclofarabine-
dc.subjectcytarabine-
dc.subjectmitoxantrone-
dc.titleClofarabine, cytarabine, and mitoxantrone in refractory/relapsed acute myeloid leukemia: High response rates and effective bridge to allogeneic hematopoietic stem cell transplantation-
dc.typeArticle-
dc.identifier.emailSingh, G: gillhsh@hku.hk-
dc.identifier.emailYim, R: ritayim@hku.hk-
dc.identifier.emailPang, HH: herbpang@hku.hk-
dc.identifier.emailLee, P: pl85@hku.hk-
dc.identifier.emailChan, TSY: drtchan@hku.hk-
dc.identifier.emailHwang, Y-Y: yyhwang@hku.hk-
dc.identifier.emailIp, H-W: iphowan@hku.hk-
dc.identifier.emailLeung, RYY: leungyyr@hku.hk-
dc.identifier.emailPanagiotou, G: gipa@hku.hk-
dc.identifier.emailSim, JPY: jpysim@hku.hk-
dc.identifier.emailLie, AKW: akwlie@hkucc.hku.hk-
dc.identifier.emailKwong, Y-L: ylkwong@hkucc.hku.hk-
dc.identifier.authoritySingh, G=rp01914-
dc.identifier.authorityPang, HH=rp01857-
dc.identifier.authorityPanagiotou, G=rp01725-
dc.identifier.authorityKwong, Y-L=rp00358-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1002/cam4.2865-
dc.identifier.hkuros309608-
dc.identifier.volumeEpub 2020-03-18-
dc.identifier.isiWOS:000520259600001-
dc.publisher.placeUnited Kingdom-

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