Successful induction therapy with decitabine in refractory childhood acute lymphoblastic leukemia

Introduction: ETV6-RUNX1 is the most common genetic aberration in childhood acute lymphoblastic leukemia (ALL), occurring in approximately 25% of cases with a precursor-B phenotype. The presence of ETV6-RUNX1 has been associated with a relatively low rate of relapse in multiple studies. Relapses tend to occur late and have a better salvage rate than other ALL subtypes. Moreover, conflicting data in literature regarding the prognostic significance of ETV6-RUNX1 after accounting for age, initial count and treatment intensity. We sought to study the clinical features, therapy response in newly diagnosed ETV6-RUNX1-positive treated at King Hussein Cancer Center. Methods: Patients were treated per modified St Jude Total (XV) study, risk stratification was further refined by including minimal residual disease (MRD)measurements on day 15 and day 46 of remission induction therapy. Patients with the ETV6- RUNX1 fusion or hyperdiploidy without CNS or testicular disease and a satisfactory early MRD decline (<1% on day 15 and <0.01% on day 46) were classified as being low-risk for relapse and were treated on lower -risk arm regardless of age and leukocyte count. Results: Seventy patients (n=70) with ETV6-RUNX1-positive treated at our institution between May 2006 to October 2017. The median age at diagnosis, 5.8 years (range, 1.5-10.8). ETV6-RUNX1 was associated with favorable age between 1- and 6-years in 55 patients (79%), male gender in 41 patients (59%), initial leukocyte count <10 in 39 patients (56%), CNS status 1 in 100% of patients. The majority, n= 58 (83%) of patients had NCI standard risk (SR) and n=12 (17%) had NCI high risk (HR). Sixty-six patients (94%) had MRD <1% at day 15 and all patients achieved remission with MRD<0.01% at day 46 of remission induction. All patients were treated as LR ALL per modified St Jude total XV protocol. At median follow up of (36 months; range, 26 to 154), in the subgroups of ETV6-RUNX1-positive patients classified as NCI standard risk (SR)and NCI high risk (HR) the 5-year EFS estimates were 94.1% ± 3.2 and 82%±1(P=.13), 5-year OS estimates were 100% and 92% ± 8 (p=0.31) respectively. Conclusion: MRD treatment schema in ETV6/RUNX1 -positive patients have excellent outcomes if they achieved favorable response at day 15 and end of remission induction regardless of the age and Initial leukocyte count. Treatment reduction is feasible and declared safe for children with NCI-HR who are predicted to have a low risk of relapse on the basis of rapid clearance of MRD post remission induction therapy. Disclosures No relevant conflicts of interest to declare.

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Central Nervous System Involvement in Childhood Acute Lymphoblastic Leukemia: An Analysis of Day-One Versus Day-Eight Lumbar Punctures in Remission Induction Therapy

Cureus ◽

10.7759/cureus.12464 ◽

2021 ◽

Author(s):

Uzma Arshad ◽

Naeem Jabbar ◽

Neelum Mansoor ◽

Maryam Haider ◽

Zainab Butt ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Acute Lymphoblastic Leukemia ◽

Induction Therapy ◽

Lymphoblastic Leukemia ◽

Central Nervous System Involvement ◽

Childhood Acute Lymphoblastic Leukemia ◽

Remission Induction ◽

System Involvement

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Infections During Induction Therapy of Protocol CCLG-2008 in Childhood Acute Lymphoblastic Leukemia

Chinese Medical Journal ◽

10.4103/0366-6999.151085 ◽

2015 ◽

Vol 128 (4) ◽

pp. 472-476 ◽

Cited By ~ 3

Author(s):

Si-Dan Li ◽

Yong-Bing Chen ◽

Zhi-Gang Li ◽

Run-Hui Wu ◽

Mao-Quan Qin ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Induction Therapy ◽

Lymphoblastic Leukemia ◽

Childhood Acute Lymphoblastic Leukemia

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MRD at the end of induction therapy in childhood acute lymphoblastic leukemia: outcome prediction strongly depends on the therapeutic regimen

Leukemia ◽

10.1038/sj.leu.2402019 ◽

2001 ◽

Vol 15 (2) ◽

pp. 283-285 ◽

Cited By ~ 25

Author(s):

U zur Stadt ◽

DO Harms ◽

S Schlüter ◽

M Schrappe ◽

U Goebel ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Induction Therapy ◽

Outcome Prediction ◽

Lymphoblastic Leukemia ◽

Childhood Acute Lymphoblastic Leukemia ◽

Therapeutic Regimen

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Long non-coding RNA MEG3 as a candidate prognostic factor for induction therapy response and survival profile in childhood acute lymphoblastic leukemia patients

Scandinavian Journal of Clinical and Laboratory Investigation ◽

10.1080/00365513.2021.1881998 ◽

2021 ◽

pp. 1-11

Author(s):

Wenjin Gao

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Prognostic Factor ◽

Induction Therapy ◽

Lymphoblastic Leukemia ◽

Therapy Response ◽

Childhood Acute Lymphoblastic Leukemia ◽

Non Coding Rna ◽

Long Non Coding Rna

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Reduced intensity of induction does not increase the risk of relapse in childhood acute lymphoblastic leukemia - A multi-centric clinical study of GD-2008-ALL protocol

10.21203/rs.3.rs-25689/v1 ◽

2020 ◽

Author(s):

Xin-Yu Li ◽

Jia-Qiang Li ◽

Xue-Qun Luo ◽

Xue-Dong Wu ◽

Xin Sun ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Induction Therapy ◽

Lymphoblastic Leukemia ◽

Childhood Acute Lymphoblastic Leukemia ◽

Event Free Survival ◽

Childhood All ◽

Free Survival ◽

Reduced Intensity ◽

Treatment Related Mortality ◽

Related Mortality

Abstract Background The prognosis of childhood acute lymphoblastic leukemia (ALL) is optimistic with a 5-year event-free survival (EFS) rate of 70%-85%. However, the major causes of mortality are chemotherapy toxicity, infection and relapse. The Guangdong(GD)-2008-ALL collaborative protocol was carried out to study the effect of reduced intensity in terms of duration in ALL chemotherapy on chemotherapy related mortality. The study was designed to elucidate weather the reduced intensity of induction is effective and safe for children with ALL, compared with Berlin-Frankfurt-Münster (BFM) backbone treatment. Methods The clinical data was obtained from February 28, 2008 to June 30, 2016. A total of 1,765 childhood ALL cases from 9 medical centers were collected and data was retrospectively analyzed. Bone marrow morphology, prednisone response, age, genotype, and karyotype information was evaluated for the stratification of chemotherapy intensity. Patients were stratified into 3 groups: standard risk (SR), intermediate risk (IR) and high risk (HR). The dose of cyclophosphamide (CTX), Cytarabine (Ara-c) and 6-mercaptopurine (6-MP) during induction for the SR group was half that of the BFM backbone treatment. Results The 5-year and 8-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 83.5±0.9% and 83.1±1.0%, 71.9±1.1% and 70.9±1.2%, and 19.5±1.0% and 20.5±1.1%, respectively. The 2-year treatment-related mortality (TRM) was 5.2±0.5%. The 5-year and 8-year OS were 90.7±1.4% and 89.6±1.6% in the SR group, while the 5-year and 8-year EFS were 81.5±1.8% and 80.0±2.0%. In the SR group, 74 (15.2 %) patients measured minimal residual disease (MRD) on Day 15 and Day 33 of induction therapy. Among them, 7 patients (9.46%) were MRD positive (≥ 0.01%) on Day 33. The incidence of relapse in the MRD Day33 positive group (n=7) was 28.6%, while the incidence of relapse in the MRD Day33 negative group (n=67) was 7.5% (p=0.129).Conclusions The results of GD-2008-ALL protocol are outstanding for reducing treatment related mortality in childhood ALL in China with excellent long term EFS. This protocol provided the evidence for further reducing intensity of induction therapy in the SR group according to the risk stratification. MRD levels on Day 15 and Day 33 are appropriate indexes for stratification.

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