Pediatric Hematology and Oncology, 28:269278, 2011

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C Informa Healthcare USA, Inc.

ISSN: 0888-0018 print / 1521-0669 online
DOI: 10.3109/08880018.2010.533249

ORIGINAL ARTICLE
Malignant Hematology - Acute Myeloid Leukemia

Improved Survival Outcome of Childhood Acute

Myeloid Leukemia with Intensified Chemotherapy
in Chinese Children

Xiao Wen Zhai, PhD,1 Frankie Wai Tsoi Cheng, MD,2 Vincent Lee, MRCP,2
Wing Kwan Leung, MRCPCH,2 Margaret Heung Ling Ng, MD,3 Kam Sze
Tsang, PhD,3 Ming Kong Shing, FRCP,2 and Chi Kong Li, MD2
1
Department of Pediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong,
Shatin, New Territories, Hong Kong; and Department of Pediatrics, Childrens Hospital of
Fudan University, Shanghai, China; 2 Department of Pediatrics, Prince of Wales Hospital,
Shatin, New Territories, The Chinese University of Hong Kong, Hong Kong; 3 Department of
Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Shatin,
New Territories, Hong Kong

With the use of intensive chemotherapy and hematopoietic stem cell transplantation (HSCT), the
prognosis of childhood acute myeloid leukemia (AML) improved over the last 2 decades. Survival
data of Chinese pediatric patients were seldom reported. The authors adopted modied UK Med-
ical Research Council (MRC) AML protocols for treatment of childhood AML since 1994. From 1994
to 2008, the outcomes of Chinese AML patients were studied. Sixty-eight patients were studied.
The median age at diagnosis was 9.9 years. Twenty-ve patients (36.8%) had favorable cytoge-
netic karyotypes, including t(15;17), t(8;21) and inv(16). Complete remission (CR) rate was 91.2%.
The relapse rate was 29.4%. For non-M3 patients, the 5-year overall survival (pOS) was 64%
7% and event-free survival (pEFS) was 53% 7%. For those nongood-risk patients who achieved
CR, there were no signicant dierences in outcomes between patients who received HSCT
in CR1 and those received chemotherapy alone (5-year pOS 80% 13% and 69% 9%,
P = .52), 5-year pEFS 69% 15% and 55% 10%, P = .40). The pOS of the 20 relapsed
patients was 29% 11%. Sixteen patients with t(8;21) and inv(16) had similar outcome with
those without favorable cytogenetics (pOS 66% 12% versus 65% 7%, P = .39; pEFS
60% 11% versus 54% 8%, P = .45). Patients who achieved CR after 2 or more courses of
chemotherapy and presenting white blood cell count (WBC) 100 109 /L had poorer outcome
(pOS 40% versus 80%P < .01; 43% versus 70%, P = .02, respectively). Intensied chemotherapy
improved outcome of Chinese AML children. CR after rst course of chemotherapy and WBC at
diagnosis were important prognostic factors.
Keywords AML, chemotherapy, children

Acute leukemia is the most common childhood malignancy. Acute myeloid

leukemia (AML) accounts for 20% of childhood acute leukemia [1]. With the use of in-
tensive chemotherapy and hematopoietic stem cell transplantation (HSCT), the prog-

Received 2 June 2010; accepted 15 October 2010.

Address correspondence to Dr. Chi Kong Li, Consultant Pediatrician, Department of Pediatrics,
Room G15, G/F, Lady Pao Childrens Cancer Center, Prince of Wales Hospital, Shatin, New
Territories, Hong Kong. E-mail: ckli@cuhk.edu.hk

 X. W. Zhai et al.

nosis of childhood AML improves significantly. About 90% of patients can achieve
complete remission (CR). The 5-year overall survival rate (pOS) and event-free sur-
vival rate (pEFS) are 50% to 60% and 40% to 50%, respectively. Relapse is still the main
cause of treatment failure [25]. HSCT can improve outcome in selected patients with
AML, but carries significant risk of transplant-related morbidity and mortality.
The Medical Research Council (MRC) of United Kingdom (UK) has conducted se-
ries of AML trials, including UK MRC AML 8, 10, and 12, for childhood AML. MRC
AML 10 consisted of 4 blocks of intensive chemotherapy (ADE [daunorubicin + Ara-
C + etopside] 3 + 10 + 5, ADE 3 + 8 + 5, MACE [amasacrine + Ara C + etoposide],
and MidAC [mitoxantrone + Ara C]). HSCT was recommended for all children with
a matched sibling donor (MSD). Children without MSD were randomized to receive
autologous HSCT in first CR following 4 blocks of intensive chemotherapy, or to re-
ceive no further treatment. In the MRC AML 12 trial, allogeneic HSCT was restricted
to standard and poor-risk patients in whom relapse remained the main cause of treat-
ment failure. In the absence of benefit in overall survival with substantial morbidity
in children receiving autologous HSCT, it was omitted from the MRC AML 12 trial.
The survival of children with AML on these trials has improved dramatically over the
past 2 decades. The 5-year pOS and pEFS were 66% and 56%, respectively. Intensive
chemotherapy and advanced supportive care have improved the treatment outcome.
Risk-group stratification based on karyotype and response to the first induction course
were identified in UK MRC AML 10 and subsequently adopted as stratification criteria
in subsequent trials [2].
Data from our local study showed that 3-year disease-free survival was only 26.6%
in the 1980s [6]. Since 1994, our center adopted modified UK MRC AML protocols for
treatment of childhood AML. From 1994 to 1996, we treated patients with a modified
UK MRC AML 10 protocol. The modified UK MRC AML 12 protocol was adopted after
1996. Data on survival of Chinese children treated with intensive chemotherapy proto-
cols were scarce. We retrospectively reviewed the treatment outcome of Chinese AML
patients based on modified UK MRC AML protocols.

METHODS
Eligibility
The inclusion criteria included (1) de novo AML and (2) less than 18 years old. Pa-
tients with the following conditions were excluded: (1) previously received cytotoxic
chemotherapy; (2) blastic transformation of chronic myeloid leukemia; (3) secondary
malignancy; and (4) Down syndrome. Informed consents were obtained from patients
and/or parents.

Diagnosis
The diagnosis of AML was established by morphological examination of bone mar-
row according to the French-American-British (FAB) and World Health Organization
(WHO) classifications [7]. Central nervous system (CNS) involvement was diagnosed if
more than 5 leucocytes per microliter in the cerebrospinal fluid (CSF) and/or presence
of identifiable blasts, with or without presence of neurological signs and symptoms.
Cytogenetic analysis was performed in our cytogenetics laboratory, whose quality
control was monitored by an external quality assurance scheme. Karyotypes were re-
viewed and described in accordance with the International System for Human Cyto-
genetic Nomenclature. Quality performance was reflected in the 2 proficiency testing
schemes separately organized by College of American Pathologists and Australasian
Society of Cytogeneticists.

Pediatric Hematology and Oncology

 Improved Outcome of AML in Chinese Children

TABLE 1 Treatment Schema of Modified MRC AML Protocol

Course 1 induction
Course 2 induction
Course 3 consolidation
Course 4 consolidation
Course 5 consolidation
Note. i.v. = intravenous; s.c. = subcutaneous.
ADE 10 + 3 + 5
Daunorubicin 50 mg/m2 daily by 6 hours infusion on days 1, 3,
and 5
Cytarabine 100 mg/m2 q12h i.v. bolus on days 110
Etoposide 100 mg/m2 daily by 4 hours infusion on days 15
ADE 8 + 3 + 5
Daunorubicin 50 mg/m2 daily by 6 hours i.v. on days 1, 3, and 5
Cytarabine 100 mg/m2 q12h by i.v. bolus on days 18
Etoposide 100 mg/m2 daily by 4 hours infusion on days 15
MACE
Amsacrine 100 mg/m2 daily by 1 hour i.v. (in 5% dextrose) on days
15
Cytarabine 200 mg/m2 daily by continuous i.v. on days 15
Etoposide 100 mg/m2 daily by 4 hours i.v. on days 15
MidAC
Mitoxantrone 10 mg/m2 by 6 hours i.v. on days 15
Cytarabine 1.0 g/m2 q12h by 2 hours i.v. on days 13
CLASP
Cytarabine 3 g/m2 q12h by 3 hours i.v. on days 1, 2, 8, and 9
Asparaginase 6000 units/m2 s.c. on days 2 and 9 (on 3 hours after
completion of 4th and 8th doses of cytarabine)

Favorable cytogenetics were defined as presence of t(15;17), t(8;21) or

inv(16)/t(16;16). Adverse cytogenetics were defined as 5, 7, del(5q), abn(3q),
and complex karyotypes. Complex karyotype was defined as presence of more than
3 chromosomal aberrations, including at least 1 structural aberration. Standard risk
was defined as presence of neither favorable nor adverse genetic abnormalities.

Treatment
Prior to 1996, 6 patients were treated according to the modified MRC AML 10 protocol
and followed the ADE arm. We adopted the modified MRC AML 12 protocol after 1996
[2]. The first 3 patients followed the mitoxantrone arm, and afterwards all the other
patients switched to the daunorubicin arm due to apparently greater toxicity after re-
ceived mitoxantrone. Risk-group assignment, induction chemotherapy, consolidation
chemotherapy, HSCT, and CNS-directed therapy followed MRC AML approaches [2,
8]. The protocol is shown in Table 1.

Denitions and Statistics

Complete remission (CR), nonresponse, and resistant disease (RD) were defined by
the criteria as described in the MRC trial reports [2, 8].

Statistical Analysis
SPSS Analysis System Version 11.5 software was used for the statistical analysis. pOS
was calculated from the date of diagnosis to death of any cause or to last follow-up.
pEFS was calculated from the date of diagnosis to last follow-up or first event (fail-
ure to achieve remission, relapse, secondary malignancy, or death of any cause). Pa-
tients who did not attain CR were considered failures at time 0. The probabilities of
pOS and pEFS were calculated using the Kaplan-Meier method and the different sub-
groups were compared using log-rank test and Breslow test.

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 X. W. Zhai et al.

TABLE 2 Baseline Characteristics

N %
Number eligible patients 68
Gender (male) 38 55.9
Age (years)
<10 34 50.0
10 34 50.0
WBC ( 109 /L)
<100 61 89.7
100 7 10.3
CNS leukemia 8 11.8
FAB subtypes
M0 2 2.9
M1 9 13.2
M2 17 25.0
M3 12 17.7
M4 8 11.8
M5 9 13.2
M6 1 1.5
M7 9 13.2
Others 1 1.5
Karyotypes
t(8;21) 10 14.7
Inv(16) 6 8.8
t(15;17) 9 13.2
t(9;11) 3 4.4
t(10;11) 2 2.9
Normal 18 26.5
Others 16 23.6
ND 4 5.9
Note. WBC = white blood cell count; CNS = central nervous system; ND = not done.

RESULTS
Patient Characteristics
From August 1994 to December 2008, 68 AML patients with 56 (non-M3) patients were
enrolled. The clinical characteristics are presented in Table 2. The male to female ratio
was 1.3:1. The median age at presentation was 9.9 years. Of 68 patients, 50% were 10
years old at diagnosis. An 11.8% had CNS involvement at diagnosis. The median white
blood cell count (WBC) at diagnosis was 27 109 /L and 10.3% of the children had
WBC 100 109 /L. Data of FAB subtypes and karyotypes are also shown in Table 2.

Response to Induction Treatment and Early-Death Rate

Sixty patients received DAE (daunorubicin + Ara-C + etopside) induction course,
and 3 patients received MAE (mitoxantrone + Ara-C + etopside). Two patients re-
ceived IA (idarubicin + Ara-C) course. Three children died in the first induction course
due to pneumonia, septicemia, and hyperviscosity syndrome. Of 68 children, CR was
achieved in 62 children and CR rate was 91.2%. The induction death rate was 4.4%. The
relapse rate was 29.4%.

Postremission Therapy and Outcome

Allogeneic HSCT in CR1 was performed in 11 patients (16.2%), including 6 patients
with matched sibling donor (MSD), 4 with 1 antigen-mismatched related donor
(MRD), and 1 with matched unrelated donor transplantation (MUD). Autologous
HSCT was performed in 2 patients who were analyzed in the chemotherapy group.

Pediatric Hematology and Oncology

 Improved Outcome of AML in Chinese Children

Among 11 patients with allogeneic HSCT, 3 died of post-HSCT relapses, 8 patients were
alive without disease. The other 51 patients continued with chemotherapy, 17 patients
had relapses and 13 patients died. There were no significant differences in 5-year pOS
and pEFS between patients receiving HSCT in CR1 compared to chemotherapy alone
(pOS 82% 12% versus 70% 7%, P = .55; pEFS 72% 14% versus 60% 7%, P =
.45). The relapse rates between the 2 groups were also similar (27% versus 33%, P =
.70). For 52 patients achieved CR1 after first induction chemotherapy, 10 patients with
HSCT in CR1 had 5-year pOS 80% 13% and pEFS 69% 15%, and 42 patients with
chemotherapy had pOS 68% 8% and pEFS 54% 8%. The treatment outcomes did
not differ significantly between the 2 groups (pOS, P = .56; pEFS, P = .40). Regard-
ing postremission treatment, in 36 nongood-risk patients who achieved CR1, 10 pa-
tients received HSCT and 26 patients received postremission chemotherapy only; both
groups had good outcomes, with 5-year pOS 80% 13% and 69% 9% (P = .52) and
pEFS 69% 15% and 55% 10% (P = .40), respectively.

Deaths in Remission
Three deaths occurred in CR1 within 6 months from diagnosis. One patient died of
infection after HSCT and the other 2 patients in the chemotherapy group died of fungal
septicemia and bacterial septicemia. The cumulative incidence of death in continuous
CR was 4.4% and 3.9% for the whole group and the chemotherapy group, respectively.

Relapses
Twenty patients relapsed (29.4%) after achieving remission. Three relapses occurred
in the HSCT group (total 11 patients), and 17 relapses occurred in the chemotherapy
group. Eighteen patients had isolated bone marrow (BM) relapse, 1 had BM and CNS
relapses, and 1 had CNS and extramedullary relapses. The 5-year pOS of these relapsed
patients was 29% 11%. Thirteen of 20 relapsed patients (65%) achieved CR2. HSCT
in CR2 was performed in 11 patients: 2 patients with MSD, 1 with MRD, 2 with MUD,
and 6 with unrelated cord blood transplantation (UCBT). Four of 11 were alive and
the others died of second relapse or treatment-related toxicity. HSCT was performed
in 2 relapsed patients with active leukemia; both achieved CR2 but subsequently had
further relapses and died. Five did not achieve CR2 without HSCT and all died.

Survival Outcome
The treatment outcomes are shown in Table 3. The 5-year overall survival (pOS) was
64% 7% and event-free survival (pEFS) was 53% 7% in non-M3 AML patients. The

TABLE 3 Results of 68 Patients

N %
Number of patients 68 100
Early deatha 6 8.8
Nonrespondent and resistant disease 0 0
CR achieved 62 91.2
CR after the first induction course 52 76.5
Death in CCR (cumulative incidence) 3 4.4
Relapse (cumulative incidence) 20 29.4
Lost follow-up in CCR 2 2.9
Allogeneic SCT in first CR 11 16.2
Note. CR = complete remission; CCR = continuous complete remission.
a
Early deaths are defined as death before day 42.

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 X. W. Zhai et al.

a b
1.0
1.0
.9
.9
.8
.8
OS (exclude M3) 647% n=56 Event=18 .7
.7
EFS (exclude M3) 537% n=56 Event=25

Probability
.6 .6
Probability

.5 .5

.4 .4

.3 .3

.2 .2
.1 .1
0.0 0.0
0 2 4 6 8 10 12 14 16 0 2 4 6 8 10 12 14 16
Years from diagnosis Year from diagnosis

FIGURE 1 (a) Overall survival (OS) and (b) event-free survival (EFS) in patients with AML (exclude
M3).

median follow-up time of all patients was 5.8 years (014.4 years), and was 9.6 years
(1.114.4) for survivors.

Prognostic Factors
Response to First Course of Induction Chemotherapy
Fifty-two (80%) patients achieved complete remission after the first induction course.
They had better outcome compared to 10 patients who achieved CR after 2 or more
courses (pOS 80% 6% versus 40% 15%, P < .01; and pEFS 66% 7% versus 40%
15%, P = .04) (Figure 1a and b).

White Blood Cell Count (WBC) at Diagnosis

Sixty-one patients with WBC < 100 109 /L at diagnosis had a better pOS (70% 6%
versus 43% 19%, P = .02) and a better pEFS (61% 7% versus 14% 13%, P <.01)
compared to 7 patients with WBC 100 109 /L at diagnosis. Among 62 patients who
achieved CR1, patients with WBC < 100 109 /L at diagnosis also had better outcome
(pEFS 66% 7% versus 20% 18%, P <.01). Patients with WBC 100 109 /L at di-
agnosis had higher relapse rates (72% versus 28%, P = .02).

Age at Diagnosis
Of 68 children, older patients (10 years of age, n = 34) had similar prognosis as
younger children (n = 34, pOS 56% 10% versus 76% 7%, P = .19; pEFS 49%
9% versus 63% 9%, P = .31). The relapse rates did not differ between younger and
older children (P = .28).

Gender
The pOS and pEFS were similar in 38 boys and 30 girls (pOS 65% 8% versus 69%
9%, P = .93; pEFS 59% 8% versus 54% 10%, P = .89). The relapse rates were similar
between boys and girls (P = .93).

CNS Leukemia
Eight patients (11.8%) had CNS involvement at diagnosis. The pOS and pEFS were not
different between patients with or without CNS involvement (pOS 53% 20% versus
70% 6%, P = .90; pEFS 53% 20% versus 56% 7%, P = .73). Relapse rates were
similar between the 2 groups (P = .83).

Pediatric Hematology and Oncology

 Improved Outcome of AML in Chinese Children

a Survival b pEFS
1.0 1.0

.9 .9
CR after the first course pOS 806% n=52 Event=9
.8 .8
CR after the first course pEFS 667% n=52 Event=16
.7 .7
Probability

Probability
.6 .6

.5 .5
CR after more than one course pOS 4015%?coursecr
n=10 Event=7 ?coursecr
CR after more than one course pEFS 4015% n=10 Event=7
.4 .4

.3
p<0.01 .3 p=0.02

.2 .2
.1 .1
0 2 4 6 8 10 12 14 16 0 2 4 6 8 10 12 14 16
Years from diagnosis Years from diagnosis

FIGURE 2 (a) Overall survival (pOS) and (b) event-free survival (pEFS) in patients with CR achieved
with 1 or more courses of chemotherapy.

Cytogenetics
Karyotypic analysis was performed in 64/68 (94.1%) of subjects. Clonal aberrations
were found in 67.6% patients (Table 2). Sixteen patients had favorable cytogenet-
ics (28.6%); they had similar outcome as compared to patients without favorable
cytogenetics (pOS 66% 12% versus 65% 7%, P = .39; pEFS 60% 11% versus 54%
8%, P = .45). Ten patients with t(8;21) had EFS 60% 15%and 6 patients with inv(16)
had EFS 50% 20%. Separate analysis was done for the favorable cytogenetic group
and compared with the nonfavorable cytogenetic group, there was no statistical sig-
nificant difference. For children with 11q23/MLL rearrangement, 3 children had t(9;
11) and 2 children had t(10; 11). These 5 children had outcome similar to children with-
out 11q23/MLL rearrangement (pOS 80% 18% versus 65% 6%, P = .55; pEFS 53%
25% versus 56% 7%, P = .75).

Hematopoietic Stem Cell Transplantation (HSCT)

HSCT was performed in 24 patients (35.3%). Eleven children had HSCT in CR1, 11 and
2 children were transplanted in CR2 and active leukemic state, respectively. Two chil-
dren with HSCT in active leukemia both died of second relapses. Eight of 11 patients
with HSCT in CR1 survived with remission, 2 had relapses. Four of 11 patients with
HSCT in CR2 survived in remission, 4 had relapses, and 3 died of treatment-related
complications. Eleven patients with HSCT in CR2 had worse outcome compared to
those with HSCT in CR1 (pOS 30% 14% versus 82% 12%, P = .05). The details are
shown in Figure 2.

DISCUSSION
From 1988 to 2002, 758 children with acute myeloid leukemia (AML) were treated with
Medical Research Council (MRC) AML 10 and AML 12 protocols. MRC AML 10 eval-
uated the role of HSCT following 4 blocks of intensive chemotherapy. Both allogeneic
and autologous HSCT significantly reduced the relapse risk but did not translate into
significant improvement in overall survival (pOS). This was due to significant risk of
transplant-related mortality. Risk-group stratification based on cytogenetics and re-
sponse to the first course of chemotherapy derived from MRC AML 10 was used to
deliver risk-directed therapy in the MRC AML 12 trial [2].
Since 1994, we adopted similar approach of UK MRC AML protocols to treatment
childhood AML. The treatment outcomes of 5-year overall survival (pOS) was 64%

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 X. W. Zhai et al.

7% and event-free survival (pEFS) was 53% 7% in non-M3 AML patients, which are
comparable to those reported by European and American trials [25].
The CR rate of 91.2% is also similar to those reported by MRC AML 10 and NOPHO-
AML 93 [2, 3, 8]. A 76.5% of patients can achieve CR after 1 course of induction
chemotherapy. Death rate in continuous complete remission (CCR) of 4.4% is also
similar to other published data [25]. There is no nonresponder in our cohort and
this suggests that DAE may be effective in childhood AML. Complications such as
CNS bleeding, hyperviscosity syndrome, and other treatment-related complications
should be handled carefully to avoid early death. With intensive treatment approach,
we do not observe an increase in treatment-related mortality in Chinese children.
The benefit of HSCT must be balanced with the risk of transplant-related mortality
and presence of long-term complications [9]. Most studies reported HSCT with MSD
had better survival. Nowadays, human leukocyte antigen (HLA)-compatible siblings
can only be found in 25% of patients; unrelated donor HSCT in CR1 remains a contro-
versial issue in childhood AML. Most investigators agree that low-risk AML subgroup
such as AML patients with Down syndrome and patients with favorable cytogenetics
should not undergo HSCT in CR1, whereas there are differences in the view for other
patients [10, 11]. According to UK MRC AML protocol, HSCT in CR1 is recommended
in nongood-risk group when HLA-matched sibling donor is available. For postrem-
ission treatment, our data show that 52 non-M3 patients achieved CR1, 10 patients
received HSCT in CR1 and 42 patients continued postremission chemotherapy. They
had similar outcomes, with 5-year pOS 80% 13% and 68% 8% and pEFS 69%
15% and 54% 8%, respectively. In addition, our data also show that there was no dif-
ference in relapse rate between the 2 groups. So we should restrict the indications for
HSCT in CR1 to avoid unnecessary transplant-related mortality (TRM) and late com-
plications of HSCT.
Relapse is the main cause of treatment failure in AML. Recent data from European
and American studies show that a cumulative incidence of relapse varied from 26%
to 47%. Bone marrow is the most common site of relapse (about 80% of all relapses),
and CNS relapse is less common (10% to 15% of all relapses). Most studies show that
patients with relapsed AML are seldom cured with chemotherapy alone and the sur-
vival rate is usually less than 30% [1215]. To improve the treatment outcome of these
patients, allogeneic HSCT is always recommended. The pOS of patients with HSCT in
CR2 have been reported to be 33% to 36% [14, 16]. The incidence of TRM for AML pa-
tients with HSCT in CR2 ranged from 10% to 50%. Posttransplant relapse occurs in 30%
to 60% of patients [13, 17]. In our cohort of HSCT in CR2, 36.4% had relapse and died,
and the TRM was 27.2%. Thus 5-year pOS was 30% 14%, which is similar to other
published reports [13, 14]. For those relapsed AML patients who cannot achieve CR2,
HSCT may not be a good option. Two patients with refractory leukemia underwent
HSCT and both died of early second relapse.
Cytogenetics is one of the best predictors of outcome in AML. t(8;21), inv(16), and
t(15;17) are associated with favorable outcome, whereas 5, del(5q), and 7 usually
predict poor outcome [18]. In the CCG2891 study, patients with favorable cytogenetics
achieved pEFS at 5 years of 45% compared with pEFS of 30% for patients with normal
and other cytogenetics [12]. Our study showed that 25 patients with favorable cytoge-
netics had similar pOS, pEFS, and relapse rate to nongood-risk patients. This unex-
pected finding might be due to relatively small sample size of our study. We observed
a higher relapse rate and HSCT did not achieve salvage successfully. For 10 t(8;21) pa-
tients achieved CR, 4 patients (40%) relapsed and underwent HSCT. But 3 of these pa-
tients died of relapse or septicemia, and only 1 patient survived. Thus the 5-year pEFS
was only 60% 15%. Of 6 patients with inv(16), CR rate was also 100%, but 3 patients
(50%) relapsed. After relapse, 1 patient survived with chemotherapy alone, 1 patient

Pediatric Hematology and Oncology

 Improved Outcome of AML in Chinese Children

was alive with HSCT, and 1 patient died of septicemia after MUD HSCT in CR2. Of
these 6 patients with inv(16), the pEFS was only 50% 20%.
Other important cytogenetic abnormalities include rearrangements of the mixed-
lineage leukemia (MLL) gene, which occurs in about 15% to 20% of AML patients. In
AML, the most common 11q23 rearrangements are t(9;11) (in approximately 50% of
cases), t(11;19), t(6;11), and t(10;11) [19]. Balgobind et al evaluated the data of 756
children with 11q23- or MLL-rearranged AML from 11 collaborative groups [21]. The
5-year pEFS of all patients was 44% 5%, and they identified large differences in out-
come between subgroups. Patients with t(1;11) had an excellent outcome, with pEFS
of 92% 5%, whereas patients with t(10;11) and t(6;11) had a poor prognosis, with
pEFS 17% 11% and 11% 5%, respectively; the pEFS of t(9;11) was 50% 3% [20].
Racial difference may be an important outcome predictor of AML [21]. Li et al eval-
uated the outcomes of childhood AML treated with the AML-XH-99 protocol. The CR
rate was 84.1%, with 5-year pEFS 46.1% 9.1% and disease-free survival (pDFS) was
54.3% 10.3% [22]. However, our result did not support any difference in treatment
outcome in Chinese children as compared to Caucasians.
Our data showed that important prognostic factors were (i) response to induction
chemotherapy: patients achieved CR1 after first induction course had better outcome
than those who achieved CR after 2 or more induction courses; and (ii) patients with
WBC 100 109 /L at diagnosis had inferior pEFS due to higher relapse rate.

CONCLUSION
Chinese children with AML achieved an improved outcome by using intensified
chemotherapy protocols. Despite the intensified treatment, treatment-related mortal-
ity remained low. WBC at diagnosis and CR after the first induction course were shown
to be important prognostic factors. HSCT in CR1 should be limited to high-risk pa-
tients to avoid unnecessary treatment-related toxicity and long-term complications.

Declaration of Interest
The authors report no conflicts of interest. The authors alone are responsible for the
content and writing of the paper.

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