Repetitive cycles of high-dose cytarabine are effective for childhood acute myeloid leukemia: Long-term outcome of the children with AML treated on two consecutive trials of Tokyo Children's Cancer Study Group

2007 ◽  
Vol 49 (2) ◽  
pp. 127-132 ◽  
Author(s):  
Daisuke Tomizawa ◽  
Ken Tabuchi ◽  
Akitoshi Kinoshita ◽  
Ryoji Hanada ◽  
Hisato Kigasawa ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
High Dose ◽  
Study Group ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Cancer Study Group ◽  
High Dose Cytarabine ◽  
Childhood Acute Myeloid Leukemia ◽  
Acute Myeloid

Repetitive Cycles of High-Dose Cytarabine Are Effective for Childhood Acute Myeloid Leukemia (AML): Long Term Outcome of the Children with AML Treated on Two Consecutive Trials of Tokyo Children’s Cancer Study Group.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 888-888
Author(s):  
Daisuke Tomizawa ◽  
Ken Tabuchi ◽  
Akitoshi Kinoshita ◽  
Ryoji Hanada ◽  
Hisato Kigasawa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Myeloid Leukemia ◽  
High Dose ◽  
Study Group ◽  
Consolidation Chemotherapy ◽  
Cancer Study Group ◽  
High Dose Cytarabine ◽  
Acute Myeloid

Abstract Intensive chemotherapy has contributed to an improved survival in pediatric acute myeloid leukemia (AML). We here report the long term results of the two consecutive AML trials of Tokyo Children’s Cancer Study Group; TCCSG M91-13 and M96-14. Between August 1991 and September 1998, a total of 216 eligible children with newly diagnosed AML entered either of the two trials. In M91-13 trial, patients received 3-drug induction therapy consisted of cytarabine, mitoxantrone, and etoposide, 4 courses of intensive consolidation chemotherapy including 2 courses with high-dose cytarabine. Subsequently, patients received another 4 courses of high-dose cytarabine containing consolidation chemotherapy, or autologous bone marrow or peripheral blood stem cell transplantation (A-BMT/PBSCT) instead. Allogeneic bone marrow transplantation (allo-BMT) was recommended for patients with HLA-matched family donor. In M96-14 trial, the last two courses of consolidation chemotherapy were omitted from the chemotherapy arm, and patients with FAB M3 were treated with all-trans-retinoic acid containing regimen. The remission induction rate, as a whole, was 81% and probability of 5-year overall survival and event-free survival were 62%±6% (95% confidence interval) and 56%±6% by Kaplan-Meier method, respectively. There were no significant differences in survivals among the three types of post-remission therapy (chemotherapy (n = 126), 64%±8%; allo-BMT (n = 34), 76%±14%; A-BMT/PBSCT (n = 32), 80%±13%). Although the number of consolidation chemotherapy courses were reduced from 8 to 6 in M96-14 trial, overall survival rate of each trial was similar (61%±8% vs. 64%±10%, P = 0.48). The overall survival rates of patients with low risk features, namely, t(8;21), inv(16), t(15;17) or FAB M3, and Down syndrome, were significantly better than that of the other patients (75%±9% vs. 55%±8%, P = 0.002). These results suggest that intensive high-dose cytarabine containing treatment was very effective for childhood AML regardless of types of post-remission therapy. As the chemotherapy courses could be safely reduced in number without compromising the results in the latter study, further optimization of AML therapy is required.

The Long-Term Outcome Of Adult Patients With Acute Myeloid Leukemia NPM+ and FLT3/ITD- Is Not Significantly Improved By The Application Of An Allogeneic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2648-2648
Author(s):  
Tamara Intermesoli ◽  
Marco Frigeni ◽  
Elena Oldani ◽  
Pamela Zanghì ◽  
Orietta Spinelli ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Risk Groups ◽  
High Dose ◽  
Consolidation Therapy ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Acute Myeloid

Abstract Introduction The discovery of the NPM mutation in acute myeloid leukemia (AML) allowed to identify a distinct entity with intermediate-good prognosis particularly when the FLT3/ITD mutation is absent. The most appropriate consolidation treatment of these patients upon the achievement of the first complete remission has not been established yet and the role of allogeneic stem cell transplantation (SCT) is still debated. Aim to assess long-term outcome of adult patients with NPM positive acute myeloid leukemia according to type and intensity of consolidation therapy. Patients and methods Between May 2000 and February 2012, 1155 patients were enrolled into two consecutive, prospective Northern Italy Leukemia Group (NILG) trials (00/01 and 02/06). Six-hundred sixty nine were studied for NPM mutation and 218 (33%) proved positive (by immunohistochemistry or by molecular analysis) (Falini et al, Haematologica. 2007 Apr;92(4):519-32). Median age of NPM+ patients was 50 years (range 16-72) and 134 (61%) were female. Median WBC was 33.3 x 10^9/L (range 0.9-313.9), 71 (33%) had myelomonocytic leukemia (FAB M4), and 211 (96%) had de novo AML. According to the European Leukemia Net (ELN) classification, cytogenetic risk groups were: normal 178 (82%), intermediate 26 (12%), unfavorable 2 (1%) and unknown 12 (5%). Eighty-two (38%) patients had a concurrent FLT3/ITD mutation and 31 (14%) a FLT3/TKD mutation. According to cytogenetics and additional risk factors (late response, WBC count >50x10^9/L, FAB class M0/6/7, hepato/splenomegaly, MDS-related/secondary AML, FLT3/ITD mutation), patients were stratified in standard (SR) and high (HR) risk groups. In both studies the remission induction was based on combination of cytarabine with idarubicin. Post-remission therapy was allogeneic SCT in HR while high-dose cytarabine or busulfan/cyclophosphamide with autologous SCT was given to SR patients. The molecular evaluation of minimal residual disease (MRD) was planned after induction, before the post-remission consolidation and the follow-up. Results Complete remission (CR) was achieved in 196/218 (90%) NPM+ patients. One hundred sixty-eight out of 196 remitters (86%) received post-remission consolidation therapy: allogeneic SCT 72 (37%), high dose Ara-C 74 (38%), autologous SCT 14 (7%), other therapy 8 (4%); 28 patients did not receive consolidation due to early relapse (n=24), CR death (n=3), and loss to follow-up (n=1). With a median follow-up of 1.8 years (range 0.008-12.66), 99 CR patients (50.5%) were alive in 1st CR, 13 (6.5%) died of complications, and 84 (43%) had recurrent AML. In a cumulative analysis, 5-year overall and disease-free survival were 46% (OS) and 43% (DFS), respectively. In univariate analysis FLT3/ITD mutation (n=82) affected negatively 5-year OS (29% vs. 49%, P < .0001) and DFS (27% vs. 46%, P < .0001), whereas FLT3/TDK mutation did not. In patients with FLT3/ITD mutation able to receive consolidation therapy (n=49), the application of allogeneic SCT improved DFS significantly (55% vs. 18%, P = .03) and reduced the cumulative incidence of relapse (CIR) (39% vs. 81%, P = .026). In patients with NPM+ and FLT3/ITD- AML, the risk of relapse after high dose cytarabine or autologous SCT (n=68) was more than doubled compared to that observed after allogeneic SCT (n=42) (50% vs. 23%, P= .08) (Figure). However, DFS (48% vs. 69.5%, p= .17), and OS (60% vs. 72%, p= .80) were not significantly different since allogeneic SCT was associated with higher treatment related mortality, albeit effective in the salvage of some relapsed patients. In multivariate analysis, FLT3/ITD mutation was the most powerful factor that unfavorably affected OS, DFS and CIR, while age > 55 years negatively affected OS and DFS. No other clinical factor was predictive for relapse in FLT3- patients. The relationship between MRD and clinical outcome is currently being studied and will be presented. Conclusions Our data indicate that allogeneic SCT is the most active post-remission treatment for NPM+ AML, but its benefit over chemotherapy may be limited in patients without FLT3/ITD. For this reason the evaluation of MRD could help identify the patients for whom an allogeneic SCT should be preferable. Disclosures: No relevant conflicts of interest to declare.

Core-binding factor acute myeloid leukemia: can we improve on HiDAC consolidation?

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 209-219 ◽  
Author(s):  
Peter Paschka ◽  
Konstanze Döhner
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Genetic Alterations ◽  
High Dose ◽  
Core Binding Factor ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Binding Factor ◽  
High Dose Cytarabine ◽  
Acute Myeloid

Abstract Acute myeloid leukemia (AML) with t(8;21) or inv(16) is commonly referred to as core-binding factor AML (CBF-AML). The incorporation of high-dose cytarabine for postremission therapy has substantially improved the outcome of CBF-AML patients, especially when administered in the setting of repetitive cycles. For many years, high-dose cytarabine was the standard treatment in CBF-AML resulting in favorable long-term outcome in approximately half of the patients. Therefore, CBF-AML patients are generally considered to be a favorable AML group. However, a substantial proportion of patients cannot be cured by the current treatment. Additional genetic alterations discovered in CBF-AML help in our understanding of the process of leukemogenesis and some of them may refine the risk assessment in CBF-AML and, importantly, also serve as targets for novel therapeutic approaches. We discuss the clinical and genetic heterogeneity of CBF-AML, with a particular focus on the role of KIT mutations as a prognosticator, and also discuss recent efforts to target the KIT kinase in the context of existing therapeutic regimens.

scholarly journals Long-term outcome of childhood acute myeloid leukemia: A 10-year retrospective cohort study

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Tran Kiem Hao ◽  
Chau Van Ha ◽  
Nguyen Huu Son ◽  
Pham Nhu Hiep
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
High Rate ◽  
Induction Phase ◽  
Term Outcome ◽  
Middle Income ◽  
Long Term Outcome ◽  
Childhood Acute Myeloid Leukemia ◽  
Serious Disease ◽  
Acute Myeloid

Аcute Myelоid Leukemiа (АML) in children is а serious disease. With a prоper treаtment, а lоng-term survivаl rаte аbоve 50% is typicаl. Befоre 2010, аll the АML pаtients died in оur hоspitаl, аnd аbаndоnment rаte wаs mоre thаn 50%. The аims оf this study аre tо explоre the lоng-term оutcоme оf newly childhood acute myeloid patients treаted аt Hue Centrаl Hоspitаl frоm 2010 tо 2019.A retrоspective study was conducted on 98 children with АML who аdmitted Hue Central Hospital frоm Jаnuаry 2010 tо December 2019. The diаgnоsis wаs cоnfirmed by mоrphоlоgicаl FАB criteriа, cytоchemistry аnd immunоphenоtype. Pаtients were treаted with using mоdified АML 7-3 Regimen. Sоciаl suppоrts were prоvided tо pаtients/fаmilies. А tоtаl оf 98 children with АML were аnаlyzed with meаn аge оf 5.6 yeаrs rаnging frоm 3 mоnths tо 15 yeаrs. The mаle tо femаle rаtiо wаs 1.8:1. The оverаll cоmplete remissiоn rаte after inductiоn were 82.6%. Pаtients аccоunted fоr 46 (46.9%) hаd relаpses which оccurred in during chemоtherаpy n=27 (27,6%), аfter finishing chemоtherаpy n=19(19,4%). Оverаll survivаl аt 3 yeаrs were 23.2%. The event-free survivаl аt 3 yeаrs were 20.2%. Аbаndоnment cаses were 4 (4.1%). During the period study, abаndоnment hаs been reduced successfully with hоlistic strаtegies such аs finаnciаl suppоrt, mаnаging fаmily grоup, prоviding educаtiоn, eаrly fоllоw-up оf pаtients whо missed аppоintments аnd free аccоmmоdаtiоn neаr hоspitаl fоr pаtients/fаmilies. However, with a high rate patient achieved complete remission after induction phase (82.6%), but the overal survival and event-free survival at 3 years were still low in my hospital (23.2 % and 20.2% respectively). It reflected that it was very difficult to treat successfully AML in lowand middle-income countries. We are considering the way how to improve the quality treatment for childhood acute myeloid leukemia in my hospital.

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