BACKGROUND: The preferred salvage treatment for children with relapsed/refractory acute myeloid leukemia (R/R-AML) remains unclear. The combination of cladribine/Ara-C/granulocyte-colony stimulating factor and mitoxantrone (CLAG-M) shown promising results in adult R/R-AML. We aim to investigate the efficacy and safety of CLAG-M versus mitoxantrone/etoposide/cytarabine (MEC) or idarubicin/etoposide/cytarabine (IEC) in R/R-AML children. METHODS: Fifty-five R/R-AML children were analyzed. The overall response rate (ORR), overall survival (OS), and progression-free survival (PFS) at 3-year were documented. Karyotype or mutations status were summarized as different risk groups. RESULTS: The ORR was achieved in 80% (16/20) and 51% (18/35) of patients after one-cycle of CLAG-M and MEC/IEC treatment (p < 0.001). The CLAG-M group's OS (66.8% ± 16.2% vs. 40.4% ± 10.9%, p = 0.019) and PFS (52.6% ± 13.7% vs. 34.9% ± 9.1%, p = 0.036) at 3-year was significantly higher than the MEC/IEC group. In high-risk patients, 33.3% experienced progression of disease (PD) and 22.2% dead in CLAG-M group, while 50% experienced PD and 43.8% dead in MEC/IEC. When it comes to low-risk group, none of them in CLAG-M experienced PD or death, while up to 50% of patients received MEC/IEC suffered PD, and all of them died eventually. Similar results were also found in the intermediate-risk group. Surprisingly, the presence of FLT3-ITD was associated with poor outcome in both groups. The most common adverse events were hematologic toxicities, and the incidence was similar in both group. CONCLUSIONS: CLAG-M group demonstrated effective palliation along with acceptable toxicity in R/R-AML patients. However, patients with FLT3-ITD may benefit less from CLAG-M, owing to higher PD rate and all-cause mortality than other patients.
BACKGROUND: The preferred salvage treatment for children with relapsed/refractory acute myeloid leukemia (R/R-AML) remains unclear. The combination of cladribine/Ara-C/granulocyte-colony stimulating factor and mitoxantrone (CLAG-M) shown promising results in adult R/R-AML. We aim to investigate the efficacy and safety of CLAG-M versus mitoxantrone/etoposide/cytarabine (MEC) or idarubicin/etoposide/cytarabine (IEC) in R/R-AMLchildren. METHODS: Fifty-five R/R-AMLchildren were analyzed. The overall response rate (ORR), overall survival (OS), and progression-free survival (PFS) at 3-year were documented. Karyotype or mutations status were summarized as different risk groups. RESULTS: The ORR was achieved in 80% (16/20) and 51% (18/35) of patients after one-cycle of CLAG-M and MEC/IEC treatment (p < 0.001). The CLAG-M group's OS (66.8% ± 16.2% vs. 40.4% ± 10.9%, p = 0.019) and PFS (52.6% ± 13.7% vs. 34.9% ± 9.1%, p = 0.036) at 3-year was significantly higher than the MEC/IEC group. In high-risk patients, 33.3% experienced progression of disease (PD) and 22.2% dead in CLAG-M group, while 50% experienced PD and 43.8% dead in MEC/IEC. When it comes to low-risk group, none of them in CLAG-M experienced PD or death, while up to 50% of patients received MEC/IEC suffered PD, and all of them died eventually. Similar results were also found in the intermediate-risk group. Surprisingly, the presence of FLT3-ITD was associated with poor outcome in both groups. The most common adverse events were hematologic toxicities, and the incidence was similar in both group. CONCLUSIONS:CLAG-M group demonstrated effective palliation along with acceptable toxicity in R/R-AMLpatients. However, patients with FLT3-ITD may benefit less from CLAG-M, owing to higher PD rate and all-cause mortality than other patients.
Authors: Hartmut Döhner; Elihu Estey; David Grimwade; Sergio Amadori; Frederick R Appelbaum; Thomas Büchner; Hervé Dombret; Benjamin L Ebert; Pierre Fenaux; Richard A Larson; Ross L Levine; Francesco Lo-Coco; Tomoki Naoe; Dietger Niederwieser; Gert J Ossenkoppele; Miguel Sanz; Jorge Sierra; Martin S Tallman; Hwei-Fang Tien; Andrew H Wei; Bob Löwenberg; Clara D Bloomfield Journal: Blood Date: 2016-11-28 Impact factor: 22.113
Authors: Ursula Creutzig; Marry M van den Heuvel-Eibrink; Brenda Gibson; Michael N Dworzak; Souichi Adachi; Eveline de Bont; Jochen Harbott; Henrik Hasle; Donna Johnston; Akitoshi Kinoshita; Thomas Lehrnbecher; Guy Leverger; Ester Mejstrikova; Soheil Meshinchi; Andrea Pession; Susana C Raimondi; Lillian Sung; Jan Stary; Christian M Zwaan; Gertjan J L Kaspers; Dirk Reinhardt Journal: Blood Date: 2012-08-09 Impact factor: 22.113
Authors: Andrea Pession; Riccardo Masetti; Carmelo Rizzari; Maria Caterina Putti; Fiorina Casale; Franca Fagioli; Matteo Luciani; Luca Lo Nigro; Giuseppe Menna; Concetta Micalizzi; Nicola Santoro; Anna Maria Testi; Marco Zecca; Andrea Biondi; Martina Pigazzi; Sergio Rutella; Roberto Rondelli; Giuseppe Basso; Franco Locatelli Journal: Blood Date: 2013-05-14 Impact factor: 22.113
Authors: C Michel Zwaan; Edward A Kolb; Dirk Reinhardt; Jonas Abrahamsson; Souichi Adachi; Richard Aplenc; Eveline S J M De Bont; Barbara De Moerloose; Michael Dworzak; Brenda E S Gibson; Henrik Hasle; Guy Leverger; Franco Locatelli; Christine Ragu; Raul C Ribeiro; Carmelo Rizzari; Jeffrey E Rubnitz; Owen P Smith; Lillian Sung; Daisuke Tomizawa; Marry M van den Heuvel-Eibrink; Ursula Creutzig; Gertjan J L Kaspers Journal: J Clin Oncol Date: 2015-08-24 Impact factor: 44.544