Analysis of relapse childhood acute lymphoblastic leukemia at hue central hospital in vietnam

Hue Central Hospital
Journal of Clinical Medicine - No. 51/2018 19
ANALYSIS OF RELAPSE CHILDHOOD ACUTE LYMPHOBLASTIC 
LEUKEMIA AT HUE CENTRAL HOSPITAL IN VIETNAM
Nguyen Thi Kim Hoa1, Tran Kiem Hao1, Chau Van Ha1, Kazuyo Watanabe1 
ABSTRACT
Background: Treatment outcome of acute lymphoblastic leukemia (ALL) in children has shown an 
improvement. However, relapse of disease is still a big protslen in developing countries. This study aimed 
to analyze the percentage and survival rate of relapsed in patients with childhood acute lymphoblastic 
leukemia treated at Hue Central Hospital, Vietnam, during the period of January 2012 - April 2018.
Methods: It was a retrospective and prospective descriptive study. Data were analyzed according to 
age, gender, relapse type, relapse time.
Results: There were 156 new patients with ALL admitted hospital, in which, there were 26 relapsed 
cases, accounted for 16.67%. Of 26 relapsed cases, the ratio of male to female was 2.71:1. High risk 
group was 1.6 times higher than standard group (61.5% vs 38.5%). 85.5% of patients achieved remission 
after induction phase. The mean time from diagnosis to relapse was 29.3 ± 18.2 months, in which the 
rate of early, intermediate and late relapse were 38.5%, 26.9% and 34.6% respectively. Based on relapse 
abandonment. Based on relapse type, bone marrow relapse accounted 38.5%, followed by isolated CNS, 
bone marrow combined CNS relapse (23.1% and 23.1% for respectively), while the rest had a relapse in 
testes, combination of testis and bone marrow, and testis combined CNS. The median time from relapse to 
death were 7.5 ± 8.3 months. Until April 2018, 73.1% of relapsed cases passed away and 26.9% of cases 
were are alive.
Conclusions:
marrow and CNS were the main sites of relapse. 
Key words: Childhood acute lymphoblastic leukemia, relapse.
I. INTRODUCTION
Acute lymphoblastic leukemia (ALL) is the most 
common malignant disease in children. It accounts 
for one-fourth of all childhood cancers and 72% of 
all cases of childhood leukemia. The incidence is 
about 2 to 5 per 100.000 children. The peak incidence 
of ALL occours between 2 to 5 year of age. With 
advances in chemotherapy, hematopoietic stem 
cell transplantation and supportive care, long-term 
survival in childhood acute lymphoblastic leukemia 
is now 85-90%. Despite increasing, concerns 
regarding treatment related mortality and second 
1. Hue Central Hospital
2. ACCL, Japan
- Received: 24/7/2018; Revised: 16/8/2018 
- Accepted: 27/8/2018
- Corresponding author: Nguyen Thi Kim Hoa 
- Email: kimhoa.fmi@gmail.com.
T20 Journal of Clinical Medicine - No. 51/2018
malignancies, the main reason for treatment failure 
is still relapse. The prognostic factors most important 
for determining survival post-relapse include: site 
of relapse (bone marrow vs. isolated extramedullary 
vs. combined), timing of relapse (early vs. late), 
phenotype of the original and recurrent disease, 
prognostic features characterizing the primary 
diagnosis and depth of response [2], [3], [4]..
Hue Central Hospital plays an important role to 
treat childhood acute lymphoblastic leukemia in the 
central zone of Vietnam which covers geographically 
wide areas. Since 2008, ALL patients have treated 
by CCG 1882 & 1881 protocol. In order 
to improve the treatment outcome, we carry out 
this research to analyze the incidence and survival 
rate of relapse in patients with childhood acute 
lymphoblastic leukemia treated at Hue Central 
Hospital, Vietnam, during the period of January 
2012 - April 2018.
II. PATIENTS AND METHODS
2.1. Patients
We reviewed the medical records of pediatric 
patients treated for acute lymphoblastic leukemia 
between the ages 1 months and 16 years old, 
registered at Hue Pediatric Center- Hue Central 
Hospital, between 1st January 2012 to 30th April 
2018. Medical records of the patients who were 
diagnosed relapse during this period were further 
analyzed for the purpose of this study.
2.2. Methods
A describe retrospective and prospective study: 
We collected the data of 156 new patients diagnosed 
acute lymphoblastic leukemia at Hue Pediatric 
Center, then we analysed and followed up 26 cases 
with relapse ALL.
Diagnosis of ALL at presentation was made on 
bone marrow morphology showed more than 25% 
leukemic blasts. 
CCG 1882 & 1881 protocol. 
diagnosis (early: <18 months; intermediate: 18-36 
Data were analyzed according to age, gender, 
relapse type, relapse time.
Statistical analysis: Data were analyzed using 
Medcalc program.
III. RESULTS
3.1. The percentage of relapse rate
Table 1: The incidence of relapse rate
Characteristic n %
Relapsed patients 26 16.67
Non-relapsed patients 130 83.33
Total 156 100
Of 156 patients, relapsed cases accounted for 16.67%.
3.2. Characteristics of relapsed patients
Table 2: The characteristics of relapsed patients
Characteristics n %
Gender
Male 19 73.1
Female 7 26.9
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Journal of Clinical Medicine - No. 51/2018 21
Standard 10 38.5
High 16 61.5
Yes 23 88.5
No 3 11.5
Total 26 100
standard group (61.5% vs 38.5%). 88.5% of patients achieved remission after induction phase.
Table 3: Time of relapse
n %
Early relapse 10 38.5
Intermediate relapse 7 26.9
Late relapse 9 34.6
29.3 ± 18.2 
Maintenance phase 14 53.8
Finishing treatment 6 23.1
4 15.4
Consolidation 2 7.7
Total 26 100
Of 26 relapsed cases: 14 (53.8%) occurred in maintenance phase, 4 (15.4%) occurred in delay 
Table 4: Site of relapse
n %
10 38.5
CNS 6 23.1
6 23.1
Testis 2 7.6
1 3.85
Testis + CNS 1 3.85
Total 26 100
by CNS and BM + CNS (23.1% and 23.1% respectively).
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3.5. Time from relapse to death
Table 5: Time from relapse to death
Status of patient until April 2018 n %
Alive 7 26.9
dead 19 73.1
Total 26 100
Median time, month range 7.5 ± 8.3
Comment: Until April, 2018, there was only 7 (26.9%) alive patients, 19 (73.1%) patients passed away. 
The median time from relapse to death was 7.5 ± 8.3 months
3.6. Relation between relapse events and survival after relapse
Figure 1: The relation between relapse events and the survival after relapse
Intermediate relapse had better survival time than early relapse
Survival after relapse 
0 5 10 15 20 25 30 35
0 
20 
40 
60 
80 
100 
Relapse events 
< 18 months 
 36 months 
Time (months) 
18-36 months 
IV. DISCUSSION
4.1. The incidence of relapse rate:
Table 1 showed the relapse rate for ALL was 
16.67%. Similarly, Locatelli and Oskarsson showed 
relapse occurred in 15-20% patients [4], [8]. 
According to Mulatsih and Nguyen, the rate were 
higher: 24.5% and 20.5 % respectively [5], [6]. 
4.2. Characteristics of relapse patients
Table 2 showed the ratio of male to female 
was 2.7:1. Some researches also showed that the 
incidence of ALL was higher among boys than girls, 
and male has a distinctly poor prognosis factor, girls 
has a better prognosis than boys [9], [10].
High risk group was 1.6 times higher than 
Hue Central Hospital
Journal of Clinical Medicine - No. 51/2018 23
standard group (61.5% vs 38.5%) in our study. 
[9]. According to Nguyen, 5 - year survival rates for 
NCI SR: 50.4 ± 2.4% vs NCI HR: 22.6 ± 2.1% [6]. 
3 patients (11.5%) didn’t achieve remission. This 
induction therapy has prognositc value [8].
The median time from diagnosis to relapse 
±
34.6% respectively. Based on relapse timing, 53.8% 
relapsed during maintenance phase, 23.1% relaspe 
patient relapsed during maintenance phase [5]. 
respectively). The last percentage (15.3%) belonged 
According to Mulatsih, the highest site for relapse 
result (19.05% and 13.55% respectively) [5]. Philip 
testicular relapse (2-3%) [9]. The reason for relapse 
testes had long been considered a sanctuary site in 
the blood-testes barrier can be overcome. And our 
protocol couldn’t be strong enough to eradicate 
ALL cell in testis [7].
researches. It can be the seasson of our protocol. 
some tests, such as MRD to evaluate the response. 
±
± 2.1%) or concurrent BM (39.4% ± 5.0%) relapses 
[6].
resonable. Time to relapse remains the strongest 
predictor of survival. According to Nguyen, 
estimates of 5 year survival rates for isolated 
± 1.9, 18.4 ± 3.1 
and 43.5 ± 5.2% respectively. The relative risk of 
35% respectively [11].
Most relapse cases occurred at maintenance 
these facts, modifying the protocol to use escalated 
therapies such as stem cell transplantation need to 
be applied. With the support from Asian Children 
T24 Journal of Clinical Medicine - No. 51/2018
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transplantation, we hope in the near future, we can do stem cell transplantation to save relapse children.