Cost analysis for treatment of adult patients with acute leukemia in Thailand

Parichat Thanawut ( )* Dr. Kanchana Chansung (. )**

Dr. Chulaporn Limwattananon (. )***

ABSTRACT
This was a retrospective descriptive study. The aim of this study was to explore cost of treatment of adult
acute leukemia currently used in Thailand by phases of treatment. Cost was assessed during 1 July 2003 and 30 June
2005. Health resource utilization was collected from reviewing the medical records of acute leukemia patients
diagnosed at 10 tertiary care hospitals.
Of 778 adult acute leukemia patients, 601 (77%) patients were acute myeloid leukemia (AML), and 175
(23%) patients were acute lymphoblastic leukemia (ALL). For AML treatment, the most common chemotherapy
regimen in induction phase included idarubicin and cytarabine (IDA+Ara-c) 26%, followed by regimen of
doxorubicin and cytarabine (ADM+Ara-c) 20%. For ALL treatment, the most common chemotherapy regimen in
induction phase included the combined regimen of doxorubicin, vincristine, prednisolone and L-asparaginase
(AOP+L-asp) 31%, followed by regimen of doxorubicin, vincristine, prednisolone (AOP) 22%. The direct medical
costs of acute leukemia treatments across treatment phases were different. The lowest cost of treatment was found in
palliative phase for both AML (median 42,717 Baht) and ALL (median 57,928 Baht). Median cost of bone marrow
transplant was 775,706 Baht and 738,041 Baht for AML and ALL, respectively. For AML treatment, the most
expensive regimen of induction phase was IDR+Ara-c regimen, and followed by ADM+Ara-c regimen (median cost,
231,997 Baht and 185,195 Baht, respectively). For post remission phase, HIDAC regimen was more costly regimen
than ADM+Ara-c regimens (median cost, 421,120 Baht and 70,271 Baht, respectively). For ALL treatment, the
highest costly regimen was AOP+L-asparaginase regimen (median cost, 174,312 Baht per patient), followed by AOP
regimen (median cost, 87,925 Baht per patient). The median cost of treatment during intensification and consolidation
phase and maintenance phase were 104,075 Baht and 26,603 Baht, respectively.
The cost of standard treatment for adult acute leukemia patients was high; however, the outcomes were
favorable. Subsidy payment for treatment by government might lead to more accessible to receive the standard
therapy among all acute leukemia patients. In the future, cost-effectiveness of various treatment regimens should be
studied to define the most effective regimens for adult patients with acute leukemia in Thailand.

Key Words: Acute leukemia, Cost of treatment

:
* Graduate student, Faculty of Pharmaceutical Science, Khon Kaen University
** Assistant Professor, Faculty of Medicine, Khon Kaen University
*** Associate Professor, Faculty of Pharmaceutical Science, Khon Kaen University



10 1
2546 30 2548 788
(AML) 601 ( 77) (ALL) 175 ( 23)
AML ( 31) induction
idarubicin cytarabine (IDR+Ara-c) 26 doxorubicin cytarabine (ADM+Ara-
c) 20 ALL doxorubicin
vincristine prednisolone L-asparaginase (AOP+L-asp) 31 doxorubicin
vincristine prednisolone (AOP) 22 20

AML ALL
42,717 / 57,928 /
775,706 / 738,041 / AML induction
idarubicin (231,997 /) doxorubicin (185,195 /)
HIDAC (421,120 /)
ADM+Ara-C (70,271 /) ALL induction AOP+L-asp
174,312 / AOP 87,925 / consolidation maintenance
104,075 / 26,603 /


-

Background using advanced and more effective drugs, improved

Acute leukemia is a serious disease with a
high mortality rate. However, several studies have
provided evidence of improvement in clinical outcomes
in acute leukemia patients in the last few decade years
(Jabbour EJ, Estey E, Kantarjian HM, 2006; Gokbuget,
Hoelzer, 2006). Improvements in survival of patients
treated for acute leukemia have resulted primarily from
the development of more intensive treatment,
innovative therapeutic intervention and diagnostics,
supportive care, and bone marrow transplantation.
In Thailand, The Adult Hematologic
Malignancy Registry was conducted by Thai Society
of Hematology since 2003. Approximate 700 patients
of these were diagnosed with acute leukemia. Based
on this data, there are variations of treatment.
Standard treatment, according to international
guidelines, seems to be limited to some patients
because of budget constraint. Analyses of the cost of
treatment in adult acute leukemia are limited.
Because the cost of resource consumption can be
related to survival time and quality of life for leukemia
patients, such information is essential for setting
treatment priorities in an era of cost constraints and for
developing suitable treatment guidelines of acute
leukemia in this country.
The aim of this study was to explore cost of
treatment of adult acute leukemia currently used in
Thailand by phases of treatments.
Methods
Study design
This study was a retrospective descriptive
study by reviewing medical charts.
The ten tertiary care hospitals as the study
sites included Chulalongkorn, Ramathibodi, Siriraj,
Phramongkutklao, Prince of Songklanagarind,
Srinagarind, Maharaj Nakorn Chiang Mai, Khon Kaen,
Rajavithi, and Sappasitthiprasong Hospitals.
Study sample
All adult acute leukemia patients who enrolled
in the Adult Hematologic Malignancy Registry project
were included in this study if patients met the following
criteria: (1) age 15 years or older; and (2) patients had
received treatments for acute leukemia in 10
participating hospitals between 1 July 2003 and 30 June
2005.
For clinical outcome analysis, this study
excluded patients whose treatment results and vital
status were unknown. In addition, patients who died
within the first week of diagnosis were also excluded.
For direct medical costs, patients were
excluded if at least 80% of their medical records were
not available since each patient had multiple outpatient
visits and several times of hospitalization.
Data sources
This study used clinical data from The Adult
Hematologic Malignancy Registry. The health
resource utilization was abstracted from all in-patient
and out-patient medical charts during 1 July 2003 to
30 June 2005. Unit prices of laboratory, procedure,
and room and board were mainly based on the data
from Srinagarind Hospital in year 2006, and National
Official Prices directly set by the MOPH in year
2004. Cost of drugs was mainly based on prices from
Srinagarind Hospital in year 2006.
Determination of costs association with treatment
This study was restricted to direct medical
costs incurred by the treatments and its consequences
and was conducted from health providers
perspective. The costs of treatment were sub-grouped
by treatment phases and were collected by a bottom
up method that divided into two parts including
quantification and valuation. For quantification,
health resource utilization was collected from
reviewing retrospectively the medical records. For
valuation, charges or unit prices of each health
resource were estimated.
Health resource utilization composed of
seven components including Diagnostic laboratory,
Investigation laboratory, Chemotherapy, Antibiotics,
Blood products, Room and board, and Medical
procedure components
Data analysis
All analyses were conducted using STATA
version 8.0. Descriptive statistics were used.
Distributions of cost data were positively by skewed
distribution thus non-parametric tests were performed.
 This study was approved by the Ethical
Review Committee for Research in Human Subjects,
Khon Kaen University.
Results
1. Acute myeloid leukemia
1.1 Induction regimens
For the induction therapy of 581 patients, 117
patients (20.14%) received doxorubicin 45-50
mg/m2/day for 2-3 days plus cytarabine 100-200
mg/m2/day for 5-7 days, referred as to ADM+Ara-c
regimen; 153 (26.33%) received idarubicin 10-13
mg/m2/day for 2-3 days plus cytarabine 100-200
mg/m2/day for 5-7 days, referred as to IDR+Ara-c
regimen; 58 patients (9.98%) received other regimens
for AML patient except AML subtype M3 such as
mitoxanthrone plus cytarabine, thioguanine plus
cytarabine or mercaptopurine plus cytarabine regimens;
and 70 patients (12.05%) received a chemotherapy
regimen for the treatment of AML subtype M3, called
M3-Rx regimen. One hundred and eighty-three
patients (31.50%) did not receive the induction therapy.
These patients were treated with supportive therapy
(No-Rx) such as hydroxyurea, antibiotics, and blood
components.
1.2 Costs of treatments by phases of treatment
Costs of AML treatments are presented in
Table 2. The overall median cost of AML treatments
was 146,134 Baht/patient. Costs of AML treatments
were different by phases of therapy. For patients who
received palliative treatment with low dose
chemotherapy or supportive care only, the median cost
was 42,717 Baht/patient. The cost associated with bone
marrow transplant (BMT) was highest (median costs,
775,706 Baht/patient). Costs of induction and post
induction therapy varied greatly depending on
chemotherapy regimens.
The costs of induction therapy were
different across regimens. The highest cost was
IDR+Ara-c regimen (median 231,997 Baht/patient)
followed by ADM+Ara-c regimen (median 185,195
Baht/patient). The costs of all-trans retinoic acid
regimen were higher than arsenic trioxide regimen for
specific treatment in AML subtype M3 patients.
Patients who did not respond to the standard induction
regimen or relapsed, they might receive salvage
therapy. The median cost of salvage therapy was
247,552 Baht/patient.
For post remission therapy, the cost of high dose
cytarabine (HIDAC) regimen was higher than that of
ADM+Ara-c and other regimens.
1.3 Clinical outcome
Median overall survival in all patients of
this study was 4.16 months. The overall survivals at 6
months, 12 months and 24 months were 43.68%,
26.66% and 12.71%. In addition, there were
differences in the survival across induction regimen,
which the median survivals were 3.52, 5.07, 7.09, and
8.76 months for other, ADM+Ara-c, M3-Rx, and
IDR+Ara-c regimens, respectively. For No-Rx group
the median survival was 1.27 months, and overall
survivals at 6 months, 12 months and 24 months were
24.00%, 5.26%, and 2.49%, respectively.
Overall Survival by Induction Treatment (age 50 adjusted)
1.00
0.75
0.50
0.25
0.00
0 180 360
days
540 720
drug = No Rx drug = ADR+Ara
drug = IDR+Ara drug = Others
drug = M3-Rx
Figure1 Overall survivals of induction regimens
in AML patients adjusted for age 50
Table 1 Induction regimens for AML patients by hospitals
Hospital, N (%)
Treatment
1 2 3 4 5 6 7 8 9 10 Total
Not received 39 15 15 2 10 9 15 53 13 12 183
chemotherapy (35.78) (26.32) (23.81) (12.50) (52.63) (34.62) (10.60) (54.08) (40.63) (60.00) (31.50)
4 3 26 7 7 5 34 23 8 0 117
ADM+Ara-c
(3.67) (5.26) (41.24) (43.75) (36.84) (19.23) (24.10) (23.47) (25.00) (0.00) (20.14)
59 26 0 3 1 10 48 2 2 2 153
IDR+Ara-c
(54.13) (45.61) (0.00) (18.75) (5.26) (38.46) (34.04) (2.04) (6.25) (10.00) (26.33)
Other 0 5 12 2 0 0 15 18 6 0 58
regimens (0.00) (8.77) (19.05) (12.50) (0.00) (0.00) (10.60) (18.37) (18.75) (0.00) (9.98)
7 8 10 2 1 2 29 2 3 6 70
M3-Rx
(6.42) (14.04) (15.87) (12.50) (5.26) (7.69) (20.50) (2.04) (9.38) (30.00) (12.05)

Total 109 57 63 16 19 26 141 98 32 20 581

ADM+Ara-c; doxorubicin plus cytarabine regimen, IDR+Ara-c; idarubicin plus cytarabine regimen, M3-Rx;
chemotherapy regimen for the treatment of AML subtype M3

Table2 Costs of AML treatments by phases of treatment

Cost of treatment (Baht / patient)
Phase of treatment No. of patients
Median Interquartile range
Supportive care before
288 19,100 9,966 38,121
chemotherapy
Induction phase 286 192,122 107,836 331,707
ADM+Ara-c 90 185,195 84,057 328,944
IDR+Ara-c 133 231,997 148,806 376,889
Other regimens 17 120,529 74,046 195,754
ATRA 15 184,085 146,134 269,847
Arsenic 6 138,744 46,766 179,230
Post remission 101 146,474 62,202 -295,416
HIDAC 11 421,120 206,110 476,419
ADM+Ara-c 22 70,271 31,355 236,210
Other regimens 4 46,451 30,662 253,302
No-Rx 64 143,311 78,498 267,210
Palliative care 110 42,717 13,969 110,213
Salvage 34 247,552 136,658 493,605
BMT* 12 775,706 628,119 965,947
Total 509 146,134 42,548 351,994

*Not included cost of donors investigation for bone marrow transplant

ADM+Ara-c; doxorubicin plus cytarabine regimen, IDR+Ara-c; idarubicin plus cytarabine regimen, ATRA; all-trans
retinoic acid regimen, Arsenic; arsenic trioxide regimen, HIDAC; high dose cytarabine regimen, No-Rx; supportive
therapy only, BMT; bone marrow transplant
2. Acute lymphoblastic leukemia Baht/patient), intensification and consolidation phases
2.1 Induction regimen (median 104,075 Baht/patient), and induction phase
Proportions of treatments with induction
(median 142,710 Baht/patient). For patients who did
regimens for ALL patients were summarized in Table 4.
not respond to standard induction regimen or relapsed
For induction therapy of 172 patients, 53 patients
and received salvage therapy, the cost range for
(30.81%) received a 4-drug regimen including
salvage therapy was 159,928 to 848,843 Baht/patient
doxorubicin, vincristine, prednisolone and L-
(median 442,406 Baht/patient). The cost associated
asparaginase, referred as to AOP+L-asp regimen; 37
with BMT was highest (median 738,041
patients (21.51%) received a 3-drug regimen including
Baht/patient).
doxorubicin, vincristine and prednisolone, referred as to
The costs of induction therapy were
AOP regimen; 5 patients (2.91%) received a 2-drug
different across chemotherapy regimens. The highest
regimen including vincristine and prednisolone, referred
cost of induction therapy was the other regimens
as to OP regimen; 10 patients (5.81%) received a oral
(median 190,686 Baht/patient), followed by AOP+L-
regimen including mercaptopurine, prednisolone or
asp (median 174,312 Baht/patient), AOP (median
cyclophosphamide, referred as to Oral regimen; and
87,925 Baht/patient), OP (median 43,644
32 patients (18.60%) received other regimens such as
Baht/patient), and oral regimens (median 38,296
GMALL and Hyper-CVAD regimens. Thirty-five
Baht/patient).
patients (20.35%) did not receive induction therapy
2.3 Clinical outcome
(No-Rx). These patients were treated with supportive
The median overall survival in all patients
therapy such as hydroxyurea, antibiotics, and blood
of this study was 4.60 months. The 6-month, 12-
products
month, and 24-month overall survivals were 46.80%,
2.2 Costs of treatments by phases of treatment
32.40%, and 15.20%, respectively. In addition, there
Costs of ALL treatments are presented in
were differences in the overall survival across
Table 5. This study found that overall median cost of
regimens, which the median overall survivals were
ALL treatment was 142,710 Baht/patient. The costs
10.51, 7.68, 5.49, and 2.37 months for AOP+L-asp,
range for ALL treatments was 50,029 to 333,635
oral, AOP, other regimens, respectively. For patients
Baht/patient.
who did not receive chemotherapy or patients who
The costs of ALL treatment were different by
received OP regimen, median survivals were 1.32 and
phases of treatment. The lowest cost was supportive
1.45 months, respectively.
before induction phase (median 21,130 Baht/patient),
followed by maintenance phase (median 26,603
Baht/patient), palliative care phase (median 57,928
Table 3 Induction regimens for ALL patients by hospitals
Hospital, N (%)
Treatment
1 2 3 4 5 6 7 8 9 10 Total
No 6 0 9 1 1 0 2 10 3 3 35
chemotherapy (17.65) (0.00) (47.37) (20.00) (20.00) (0.00) (3.92) (47.62) (33.33) (37.50) (20.35)
AOP + L-asp 0 13 6 1 0 4 24 0 3 2 53
(0.00) (92.86) (31.58) (20.00) (0.00) (66.67) (47.06) (0.00) (33.33) (25.00) (30.81)
AOP 1 0 0 3 3 1 18 7 1 3 37
(2.94) (0.00) (0.00) (60.00) (60.00) (16.67) (35.29) (33.33) (11.11) (37.50) (21.51)
OP 1 0 2 0 0 0 1 0 1 0 5
(2.94) (0.00) (10.53) (0.00) (0.00) (0.00) (1.96) (0.00) (11.11) (0.00) (2.91)
Oral 1 0 2 0 1 0 2 3 1 0 10
(2.94) (0.00) (10.53) (0.00) (20.00) (0.00) (3.92)) (14.29) (11.11) (0.00) (5.81)
Other 25 1 0 0 0 1 4 1 0 0 32
regimens (73.53) (7.14) (0.00) (0.00) (0.00) (16.67) (7.84) (4.76) (0.00) (0.00) (18.60)

Total 34 14 19 5 5 6 51 21 9 8 172

AOP+L-asp; 4-drug regimen including doxorubicin, vincristine, prednisolone and L-asparaginase, AOP; 3-drug
regimen including doxorubicin, vincristine and prednisolone, OP; 2-drug regimen including vincristine and
prednisolone, Oral; oral regimen including mercaptopurine, prednisolone or cyclophosphamide

Table 4 Costs of ALL treatments by phases of treatment

Cost of treatment (Baht / patient)
Treatment phase No. of patients
Median Interquartile range
Supportive care before induction 75 21,130 11,188 - 34,365
Induction 125 142,710 59,528 - 321,892
No Rx 3 52,065 9,810 - 231,338
AOP + L-asp 51 174,312 79,608 - 397,047
AOP 34 87,925 31,332 - 258,952
OP 4 43,644 38,425 - 55,108
Oral 2 38,296 16,268 - 60,323
Other regimens 31 190,686 97,366 - 381,473
Intensification/ consolidation 42 104,075 47,824 - 175,502
Maintenance 14 26,603 16,368 - 65,371
Palliative care 18 57,928 15,670 - 117,632
Salvage 4 442,406 159,928 - 848,843
BMT* 3 738,041 219,612 - 1,142,389
Total cost 163 142,710 50,029 - 333,635

*Not included cost of donors investigation

AOP+L-asp; 4-drug regimen including doxorubicin, vincristine, prednisolone and L-asparaginase, AOP; 3-drug
regimen including doxorubicin, vincristine and prednisolone, OP; 2-drug regimen including vincristine and
prednisolone, Oral; oral regimen including mercaptopurine, prednisolone or cyclophosphamide, No-Rx; supportive
therapy only, BMT; bone marrow transplant
 Overall Survival by Induction Treatment (age 50 adjusted) received chemotherapy when expenditure increased.
1.00

However, this increased cost was necessary for

achieving the longer survival times in patients who
0.75

received chemotherapy. This finding was consistent

0.50

with the study of Menzin et al. (2002) which reported

0.25

that cost of chemotherapy treatment in elderly patients

0.00

0 180 360 540 720

with AML was nearly three times higher than those of
other patients (average cost, $77,769 +/- 1989 versus
days

drug = No Rx drug = AOP

drug = AOP+L-asp
drug = Oral
drug = OP
drug = Other $26,287 +/- 636). Furthermore, the study found that
AML patients who received chemotherapy lived
Figure 2 Overall survivals of induction regimens in longer than patients who received only palliative
ALL patients adjusted for age 50 treatment (median survival, 7 versus 1 month).
Although the resource consumption in acute
Discussion
leukemia patients may be related to survival time and
This study found that the total cost of
quality of life, this study could not clearly identify
treatment in AML patients who received ADM+Ara-c
how much of the increased cost could be attributed
chemotherapy regimen was higher than patients who
the effective of treatment. In addition, this study could
received only palliative treatment. For ALL patients,
not identify which regimen was the most effective for
total cost of treatment in patients who received AOP+L-
acute leukemia patients. This study did not estimate
asp or AOP regimen was higher than patients who
the average cost per life-year gain or cost
received palliative treatment. This may be caused by
effectiveness of each regimen of treatment. However,
that patients who received palliative treatment had the
the cost of treatment in this study would be regarded
shortest median survival and had the lower use of health
that chemotherapy treatments and bone marrow
care resources compared with patients receiving
transplant in adult acute leukemia patients were
curative chemotherapy. The supportive care and
expensive treatment in Thailand. These treatment
palliative treatment did not contribute to achieve a
costs were approximately 2 to 7 times of The Thai
complete remission in patients with acute leukemia.
gross domestic product (GDP) per capita (110,000
Nevertheless, using an appropriate regimen of induction
Baht per year in the fiscal year 2005). This finding
and post-remission chemotherapy can improve
was consistent with the study of Songnuy T. (1999)
remission rate and survival rate. The effects of
which reported that cost of treatment in childhood
chemotherapy regimen to survival were showed in
ALL was nearly three times of GDP (average cost,
figure 1 and 2. These figures showed the Kaplan-Meier
264,998 Baht/patient). Although, the cost of treatment
survival curves for the AML and ALL patients who did
for adult acute leukemia is high, the outcome is
not receive chemotherapy or received induction
favorable. The improvements of survival outcome are
chemotherapy regimens. The area between the curves
achieved at a significant cost in terms of
showed the increased survival time in patients who
hospitalization. Supporting payment for treatment by
government may lead to increasing accessibility to
standard treatment for all acute leukemia patients in
Thailand.
Conclusion
The cost of chemotherapy treatment for adult
acute leukemia patient was high; however, the
outcomes were favorable. The improvements of
survival are achieved at a cost in terms of
hospitalization.
Acknowledgements
We would like to thank all key informants and
contact individuals at the study sites. In particular, this
study was supported in part by the National Research
Council of Thailand, the Graduate School Grant
49211126, and the Faculty of Pharmaceutical Sciences,
Khon Kaen University.
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