Cost-effectiveness of postremission intensive therapy in patients with acute leukemia

Article (PDF Available)inAnnals of Oncology 18(3):529-34 · April 2007with26 Reads
DOI: 10.1093/annonc/mdl420 · Source: PubMed
Abstract
We assessed the cost-effectiveness of high-dose arabinoside (HiDAC)-based and allogeneic stem-cell transplantation (alloSCT)-based therapy in patients with acute leukemia. We analyzed the outcome, cost and cost-effectiveness of 106 patients treated from January 1994 to January 2002 [94 acute myelogenous leukemia (AML)/12 acute lymphoblastic leukemia (ALL)]. Forty-two young patients at either intermediate or unknown cytogenetic risk received postremission intensive therapy (24 HiDAC-based/18 alloSCT-based therapy). After a median follow-up of 50 months, the estimated 7-year overall survival for the HiDAC-based group showed a tendency to be higher than the alloSCT-based group (48% versus 28%, P = 0.1452). The HiDAC-based group spent a significantly lower total cost ($US51,857 versus 75,474, P = 0.004) than the alloSCT-based group. Cost-effectiveness analysis showed that the mean cost per year of life saved for the HiDAC-based group is considerably less expensive than the alloSCT-based group ($US11,224 versus 21,564). The reduced total cost for the HiDAC-based group originated from lower cost in room fees, medication, laboratory and procedure, but not in blood transfusion and professional manpower fees. For the postremission therapy in young AML patients at either intermediate or unknown cytogenetic risk, cost-effectiveness of HiDAC-based therapy compares favorably with that of alloSCT-based therapy, which deserves further clinical trials.
Annals of Oncology 18: 529–534, 2007
doi:10.1093/annonc/mdl420
Published online 12 December 2006
original article
Cost-effectiveness of postremission intensive therapy
in patients with acute leukemia
Y.-B. Yu
1,2
, J.-P. Gau
1,2
, J.-Y. You
1,2
, H.-H. Chern
3
, W.-K. Chau
1,2
, C.-H. Tzeng
2,4
,
C.-H. Ho
1,2
& H.-C. Hsu
1,2,5
*
1
Division of Hematology and Oncology, Department of Medicine, Taipei-Veterans General Hospital;
2
Department of Medicine, School of Medicine,
National Yang-Ming University;
3
Information Service Center, Taipei-Veterans General Hospital;
4
Division of Transfusion Medicine, Department of Medicine,
Taipei-Veterans General Hospital;
5
Institute of Physiology, School of Medicine, National Yang-Ming University; Taipei, Taiwan, Rep ublic of China
Received 10 July 2006; revised 16 September 2006; accepted 12 October 2006
Background: We assessed the cost-effectiveness of high-dose arabinoside (HiDAC)-based and allogeneic stem-cell
transplantation (alloSCT)-based therapy in patients with acute leukemia.
Patients and methods: We analyzed the outcome, cost and cost-effectiveness of 106 patients treated from
January 1994 to January 2002 [94 acute myelogenous leukemia (AML)/12 acute lymphoblastic leukemia (ALL)].
Forty-two young patients at either intermediate or unknown cytogenetic risk received postremission intensive
therapy (24 HiDAC-based/18 alloSCT-based therapy).
Results: After a median follow-up of 50 months, the estimated 7-year overall survival for the HiDAC-based group
showed a tendency to be higher than the alloSCT-based group (48% versus 28%, P = 0.1452). The HiDAC-based
group spent a significantly lower total cost ($US51 857 versus 75 474, P = 0.004) than the alloSCT-based group.
Cost-effectiveness analysis showed that the mean cost per year of life saved for the HiDAC-based group is
considerably less expensive than the alloSCT-based group ($US11 224 versus 21 564). The reduced total cost for
the HiDAC-based group originated from lower cost in room fees, medication, laboratory and procedure, but not in
blood transfusion and professional manpower fees.
Conclusion: For the postremission therapy in young AML patients at either intermediate or unknown cytogenetic
risk, cost-effectiveness of HiDAC-based therapy compares favorably with that of alloSCT-based therapy, which
deserves further clinical trials.
Key words: acute myelogenous leukemia, allogeneic stem-cell transplantation, cost-effectiveness, high-dose
arabinoside, postremission therapy
introduction
Postremission intensive therapy is definitely required for the
treatment of acute myelogenous leukemia (AML) in order to
achieve long-term, disease-free survival; the possible approaches
include high-dose arabinoside (HiDAC), autologous stem-cell
transplantation (ASCT) and allogeneic stem-cell transplantation
(alloSCT) [1]. AlloSCT has been established as a potentially
curative treatment of patients with AML, but its role remains
controversial because a definitive survival advantage has not
been shown in a number of controlled studies [2–5]. This may
be the result of a combination of high transplantation-related
mortality during alloSCT treatment and continuous
improvements in non-alloSCT strategies. Numerous studies
have identified the impact of cytogenetic risk on the patients’
outcome and this further stratifies AML patients into favorable,
intermediate and unfavorable groups [5–8]. In the last decade,
the standard approach to the young AML patient has been
adjusted towards risk-adapted postremission therapy, that is
HiDAC-based therapy for those at favorable risk and alloSCT
for those with unfavorable cytogenetics [1, 9–11]. The best
postremission therapy, however, for AML patients with
either intermediate or unknown cytogenetic risk is still a
controversial issue.
AML is an expensive disease to treat, which is due to
prolonged hospital care, high-level technological medical
intervention and the provision of specialized facilities. In 1989,
Welch and Larson [12] first reported that the total costs for
American AML patients for a period of 5 years was greater for
alloSCT treatment than that for chemotherapy (193 000 versus
136 000, in 1989 USD), but that the former was more cost-
effective than the latter. In 1992, Dufoir et al. [13] also reported
the ‘estimated’ total costs of alloSCT, ASCT and HiDAC
therapies as $US78 144; 92 986 and 56 091, respectively,
(converted from 1990 French Francs) for French AML
patients after the first complete remission (CR), and that
original
article
*Correspondence to: Dr H.-C. Hsu, Division of Hematology and Oncology,
Department of Medicine, Taipei-Veterans General Hospital, Shih-Pai Road,
Taipei, Taiwan 11217, Republic of China. Tel: +886-2-2871-2121 ext. 3865;
Fax: +886-2-6610-9119; E-mail: hchsu@vghtpe.gov.tw
ª 2006 European Society for Medical Oncology
by guest on June 7, 2013http://annonc.oxfordjournals.org/Downloaded from
alloSCT was as cost-effective as HiDAC and preferable to ASCT.
Previous studies have also demonstrated the learning curve
effects in the decrease of cost over time in the ASCT for patients
with lymphoma due to the development of new technologies,
organizational changes and the more cost-effective use of
laboratory tests and pharmaceuticals [14, 15]. The best cost-
effective approach, however, to postremission intensive
treatment in acute leukemia has been rarely studied both over
the last decade and in developing countries. We conducted
this study to analyze the outcome and cost of acute leukemic
patients treated with AML-type postremission intensive therapy
in our single institute over the last decade. Our special objective
is to analyze the cost-effectiveness of HiDAC-based therapy
and alloSCT-based therapy especially among patients at either
intermediate or unknown cytogenetic risk.
patients and methods
From January 1994 to January 2002, 106 patients with acute leukemia were
admitted to our hematological ward for treatment (Table 1). All AML
patients received conventional remission induction chemotherapy with
arabinoside and daunorubine (or idarubicin) [16]. Patients with acute
promyelocytic leukemia received all-trans-retinoic acid and idarubicin as
remission induction treatment. The acute lymphoblastic leukemia (ALL)
patients received standard remission induction regimens. After achieving
CR, 54 young patients (<60 years old) received postremission intensive
therapy, including HiDAC, ASCT and alloSCT or a combination of these
according to the in charge physician’s decision. The HiDAC regimen
includes arabinoside (3 g/m
2
) every 12 h for 3–4 days, in combination with
either mitoxantrone or idarubicin for 3 days [17]. All patients treated with
either ASCT or alloSCT, except one patient, received stem cells harvested
from the peripheral blood. The conditioning regimen for ASCT and alloSCT
was a standard busufan–cyclophosphamide regimen for the AML patients,
and total body irradiation and cyclophosphamide regimen for the ALL
patients. Cyclosporine and methotrexate were used for graft-versus-host
disease prophylaxis. All patients received granulocyte colony-stimulating
factor (G-CSF) after chemotherapy or stem-cell transplantation (SCT).
No maintenance therapy was given after intensive therapy in all patients.
Conventional consolidation or supportive care was given to older patients
(>60 years old) or those with a poor performance after their first CR.
cytogenetic studies
Bone marrow cells were harvested after 3 days of unstimulated culture.
Metaphase chromosomes were banded by the conventional trypsin–Giemsa
banding technique. Cytogenetic abnormalities were grouped according to
published criteria adopted by the Southwest Oncology Group [7].
total cost analysis
All patients were admitted for chemotherapy, SCT and supportive care,
including control of graft-versus-host disease or infection, blood transfusion
and terminal care, over the whole treatment period. All patients except one
received postremission intensive therapy in a regular single bedroom
without a laminar airflow device. Payments of all 512 hospitalizations were
retrieved from the administrative database. Outpatient direct medical costs,
patient time costs, productivity costs and direct nonmedical costs were not
included, but are expected to be low compared with direct medical inpatient
costs [18]. All costs have been converted to 2003 $US (1 $US = 33.5 New
Taiwan Dollars).
cost-effectiveness
To calculate cost-effectiveness, we divided the mean total cost of
each treatment group by the number of saved life-years calculated by the
Kaplan–Meier method, and thus cost-effectiveness was expressed in $US per
additional year of life (‘life-year’) [12].
statistical analysis
All analyses were carried out using the SPSS statistical package software.
Actuarial probability of survival was calculated by the method of Kaplan and
Meier [19]. Comparisons of the use of resources and costs were carried out
by the Mann–Whitney test and Fisher’s exact test. A value of P <0.05 was
considered statistically significant.
results
treatment outcome and cost in all patients with
acute leukemia
A total of 106 patients with acute leukemia were included in this
study, including 94 patients with AML and 12 patients with
ALL. The mean age of our patients was 45.5 ± 18.5 years, and 30
patients were >60 years old. Ten patients were in poor general
condition and did not receive any chemotherapy. A total of 111
courses of remission induction chemotherapy were carried out
during the study period, including 15 patients who underwent
a second induction course after relapse. Among these patients,
70 entered CR (63.1%), 20 patients had refractory disease (18%)
and 21 patients had treatment-related mortality (<30 days,
18.9%). After the first CR, 54 patients received intensive therapy
and 14 patients received conventional consolidation. After
a median follow-up of 14 months (range 0.5–142 months), 25
patients remained alive and the estimated 5-year overall survival
(OS) rate was 24%. Further analysis showed that younger age
(<60 years versus >60 years, P < 0.0001), cytogenetic risk
(favorable versus intermediate versus unfavorable; P = 0.0437)
and intensive therapy (P < 0.0001, Figure 1) were associated
with higher OS. Sex and disease type (AML versus ALL),
however, had no effect on the survival rate.
Table 1. Intensive versus conservative treatment in patients with
acute leukemia
Conservative
treatment
Intensive
treatment
P value
No. 52 54
Age 57.5 6 17.3 34.0 6 10.9 <0.0001
AML/ALL 45/7 49/5 0.707
Karyotype, favorable/
intermediate/unfavorable
2/12/4 6/12/5 0.566
Survival days
a
Median 124 1308 <0.0001
Range 14–2074 96–4270
Total cost
a
(USD)
Mean 6 SD 25 776 6 26 794 60 406 6 28 660 <0.0001
Range 1494–143 014 23 205–172 332
Hospital days
a
Mean 6 SD 80.0 6 69.9 153.9 6 70.5 <0.0001
Range 4–297 56–377
a
Calculated from diagnosis to the end of therapy, either cure or mortality.
ALL, acute lymphoblastic leukemia; AML, acute myelogenous leukemia;
SD, standard deviation.
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The 54 patients who received intensive therapy had
a significantly higher 5-year OS than those who did not (43%
versus 2.5%, P < 0.0001, Figure 1) and they were associated with
a significantly younger age (34.0 ± 10.9 years versus 57.5 ± 17.3
years; P < 0.0001; Table 1), but without any difference for
disease type and karyotype. Ninety-six courses of intensive
therapy were carried out, in which treatment-related mortalities
(<30 days after the start of treatment) for HiDAC, ASCT and
alloSCT were 7.7%, 0% and 15.1%, respectively (Table 2).
From diagnosis to the end of the treatment, either cure or
mortality, all patients need a median of 4.0 hospitalizations
(range 1–15) and a median total of 117 days (4–377 days) of in-
hospital care. The median cost for the entire treatment across
the 106 patients was $US43 418 (range $US1494–172 332).
The costs for drugs, room fee, blood transfusion, laboratory,
procedure, professional manpower fee and private cost were
35%, 21%, 13%, 11%, 14%, 4% and 2% of the total cost,
respectively. Patients receiving intensive treatment needed
47.3% more hospital-care days and showed a 57.3% higher total
cost than those without intensive treatment (Table 1). Among
the intensive therapies, alloSCT resulted in a higher cost than
HiDAC or ASCT (P < 0.05 and P < 0.05, respectively), and also
needed more hospital-care days (Table 2). The cost of HiDAC
treatment was higher than ASCT; however, the cost of
peripheral blood stem-cell mobilization and processing was
included in the cost of the HiDAC treatment.
HiDAC-based versus alloSCT-based intensive
therapy in patients regardless of their cytogenetic
risk group
We further divided the 54 patients who underwent intensive
therapy into HiDAC-based and alloSCT-based groups for
further analysis (Table 3). There were 33 patients who
underwent HiDAC-based therapy, of whom nine patients
received additional ASCT immediately after HiDAC and three
patients received alloSCT after relapse from the previous
HiDAC therapy. All patients received alloSCT-based treatment
during their first CR. After a median follow-up of 44 months
(range 3–142 months), the estimated 5-year OS for the HiDAC-
based group showed a tendency to be higher than the alloSCT-
based group (48% versus 28%, P = 0.1452). Further analysis
showed that alloSCT-based group included significantly more
patients with an unfavorable karyotype (P = 0.047) and ALL
type (P = 0.009). We further analyzed the role of ASCT after
HiDAC in nine patients, but there was no associated survival
benefit detected compared with the 21 HiDAC-only treatment
patients (P = 0.649). Similarly, HiDAC therapy before alloSCT
therapy (nine patients) in the alloSCT-based group was not
associated with a survival benefit compared with those receiving
only alloSCT therapy (12 patients, P = 0.488).
HiDAC-based versus alloSCT-based therapy in
patients at either intermediate or unknown
cytogenetic risk
We further determined the impact of the intensive treatment
modality on the outcome and cost for the 16 patients at
intermediate risk and the 26 patients without cytogenetic data
(Table 4). After a median follow-up of 50 months (range, 5–142
months), the estimated 7-year OS in the HiDAC-based group
showed a tendency to be higher than that in the alloSCT-based
group (54% versus 34%, P = 0.1563, Figure 2). Table 4 shows
Figure 1. Overall survival (Kaplan–Meier) of acute myelogenous
leukemia patients after conservative treatment (N = 52) or intensive
therapy (N = 54). Time 0 indicated the time of diagnosis.
Table 2. Cost analysis of the different stages of treatment of patients with acute leukemia
Treatment RI Postremission therapy Supportive care Terminal care
C/T HiDAC AlloSCT ASCT
Courses (No.) 113 41 52 33 11 219 45
In-hospital days
a
Median 38 22 27.5 48 28 7 26
Range 4–115 3–60 3–81 22–141 19–65 1–113 1–110
Treatment cost
a
($US)
Mean 6 SD 15 085 6 9316 7607 6 5865 13 668* 6 6048 29 208 + 20 901 10 037** 6 7291 3013 6 4586 15 726 6 17 083
Range 698–52 955 546–23 115 1538–29 180 9100–106 212 4709–28 995 120–25 581 500–96 923
a
Cost for single period of therapy.
*Versus alloSCT, P <0.05; **versus alloSCT, P <0.05 by Kruskal–Wallis test.
AlloSCT, allogeneic stem-cell transplantation; ASCT, autologous stem-cell transplantation; C/T, conventional chemotherapy; HiDAC, high-dose
arabinoside; RI, remission induction; SD, standard deviation.
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that across the 24 patients who received HiDAC-based
therapy, less was spent in terms of total cost (P = 0.004),
out-of-pocket money (P = 0.004) and hospital days (P = 0.067).
The reduced total cost for the HiDAC-based group originated
from a lower total room fee (P = 0.003), medication (P = 0.003),
laboratory tests cost (P = 0.001) and procedure costs (P =
0.031), but not from blood transfusion costs (P = 0.741) and
professional manpower fees (P = 0.195).
The cost-effectiveness analysis showed that the estimated
length of survival of patients at 7 years was 4.62 years for the
HiDAC-based group and 3.5 years for the alloSCT-based group
(Figure 2). Thus, at 7 years, the mean cost per year of life saved
was $US11 224 for the HiDAC-based group, but was much
higher at $US21 564 for the alloSCT-based group.
We also analyzed the effect of treatment period (1994–1997
versus 1998–2002) on the total cost. In the latter period, the total
cost decreased 0.1% in patients with HiDAC-based therapy, but
increased 9.3% in those with alloSCT-based group. The percent
contributions of the seven cost-drivers, however, remained similar
between the two treatment periods in both treatment modalities.
discussion
Taiwan is a developing country with a population of about
24 million, in which the majority of people (96%) are covered
by the National Health Insurance. Our study demonstrates
that the total cost of treating young AML patients with intensive
therapy in Taiwan is far less expensive than that in the
Table 3. HiDAC-based versus alloSCT-based intensive therapy for patients regardless of their cytogenetic risk group
HiDAC based AlloSCT based P value
a
No. 33 21
Treatment (No.) HiDAC only (21) AlloSCT (12)
HiDAC / ASCT (9)
HiDAC / alloSCT
b
(3) HiDAC / alloSCT
c
(9)
Age 36.0 6 10.6 30.9 6 10.7 0.097
AML/ALL 33/0 16/5 0.009
Karyotype, favorable/intermediate/unfavorable 6/9/2 0/7/3 0.047
Median survival days (range) 1590 (96–4053) 702 (150–4270) 0.214
Total cost
d
, mean 6 SD ($US) 51 690 6 23 540 76 423 6 31 033 0.001
Out-of-pocket
d
, mean 6 SD ($US) 6550 6 3874 10 301 6 3717 0.001
Hospital days (median) 116 (69–377) 169 (56–323) 0.021
Daily cost, mean 6 SD ($US) 380 6 74 460 6 170 0.090
a
Mann–Whitney rank sum test.
b
Carried out after relapse from HiDAC.
c
Carried out during first complete remission.
d
Calculated from diagnosis to the end of therapy, either cure or mortality.
AlloSCT, allogeneic stem-cell transplantation; ALL, acute lymphoblastic leukemia; AML, acute myelogenous leukemia; ASCT, autologous stem-cell
transplantation; HiDAC, high-dose arabinoside; SD, standard deviation.
Table 4. HiDAC-based versus alloSCT-based therapy for patients at either intermediate or unknown cytogenetic risk
HiDAC-based Tx AlloSCT-based Tx P value
a
No. 24 18
Treatment (No.) HiDAC only (14) AlloSCT (9)
HiDAC / ASCT (7)
HiDAC / alloSCT
b
(3) HiDAC / alloSCT
c
(9)
Age 38.0 6 9.1 31.9 6 9.9 0.045
AML/ALL 24/0 15/3
Median survival days (range) 2292 (240–4053) 905 (150–4270) 0.208
Total cost
d
, mean 6 SD ($US) 51 857 6 23 762 75 474 6 32 397 0.004
Out-of-pocket
d
, mean 6 SD ($US) 6548 + 3892 10 034 + 3279 0.004
Hospital days
d
(median) 118 (69–377) 175 (56–323) 0.067
Cost-effectiveness ($US/year) 11 224 21 564
a
Mann–Whitney rank sum test.
b
Carried out after relapse from HiDAC.
c
Carried out during first complete remission.
d
Calculated from diagnosis to the end of therapy, either cure or mortality.
AlloSCT, allogeneic stem-cell transplantation; ALL, acute lymphoblastic leukemia; AML, acute myelogenous leukemia; ASCT, autologous stem-cell
transplantation; HiDAC, high-dose arabinoside; SD, standard deviation; Tx, treatment.
original article
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United States and European countries [12, 13]. Expressed on
the basis of the corresponding national Annual Average Income
of Household (AAIH), the total cost of treating a young AML
patient with either alloSCT-based or HiDAC-based postCR
therapy was 2.4 times and 1.6 times the AAIH in Taiwan (2001),
respectively, but was 4.6 times and 3.2 times for the United
States (USA Census Bureau, 1986–1988), respectively [12].
Similarly, the mean cost of alloSCT procedure alone in our
study ($US29 208, between 1996 and 2001) is much lower
than that among the Western countries (France: 76 237,
between 1998 and 2000 [20]; United States: $US105 300,
between 1994 and 1997 [21]), which can be represented as
0.9 times relative to the Taiwanese AAIH (2001) and 2.5 times
relative to the United States AAIH (1997) [21]. Besides
undercompensated by our National Health Insurance compared
with Western countries, the lower treatment cost of our AML
patients mainly originated from the marked decrease in the
room fee. The latter occupied 22% of the total cost in our study,
but occupied 56%–81% of total cost in the Western countries
[22, 23]. Our patients under SCT or HiDAC therapy were
treated in a regular single bedroom, with the average daily
room fee of $US73. The average daily cost of the special
High Efficiency Particulate Air filtered bone marrow
transplantation (BMT) facilities, however, was $US1196 and
1089 in the American and French hospitals, respectively [13,
21]. Different from the previous study [14], the reduced total
cost in our study is unlikely due to learning curve effect because
the recently developed medications and technology such as
G-CSF and peripheral blood SCT had been applied from the
beginning of this study and no major organizational change
during the whole study period.
The central finding in our study is that HiDAC-based therapy
is a more cost-effective approach than alloSCT-based therapy in
the AML patients at either intermediate or unknown cytogenetic
risk. In AML patients with all-risk cytogenetic risk groups, two
studies, carried out two decades ago, reported alloSCT to be as
cost-effective as HiDAC and preferable to conventional
consolidation during postremission treatment [12, 13]. The
superior cost-effectiveness of HiDAC-based therapy in our
study was derived from both a higher survival rate (54% versus
34% at 7 years) and a lower total cost ($US51 857 versus
$US75 474), when compared with the alloSCT-based therapy.
Our results are consistent with previous studies that there was
a marginal advantage in terms of OS for HiDAC compared with
alloSCT during postremission therapy for AML patients [5, 7].
The Medical Research Council AML-10 trial showed that
alloSCT was associated with better survival than the
intermediate dose arabinoside therapy among AML patients in
the intermediate risk group [6]. Compared with patients
undergoing alloSCT-based therapy, the reduced total cost in our
HiDAC-based group was derived mostly from, first, less total
hospital-care days (median 118 days versus 175 days) due to the
shorter duration of the HiDAC therapy (median 27.5 days
versus 48 days in alloSCT) and less terminal care (45% versus
67% in the alloSCT-based group) and, secondly, less cost for
medication, laboratory tests and procedures. It is unlikely that
the cost for alloSCT-based group is relatively high in our study
because the median duration of the in-hospital care days for
alloSCT in our study (48 days) was comparable to that in
Western countries (39–62 days) and most patients received
alloSCT without a laminar airflow device, which also reduces
the cost of alloSCT [13, 21].
Our results only enrolled a limited number of patients,
although this number is similar to that analyzed in the previous
two cost-effectiveness studies [12, 13]. Cytogenetic data were
available for only 50% of patients in our study because of
technical failure and because it is not reimbursed by our
insurance system, which was higher than many large cooperative
clinical studies for AML patients in Western countries
(17%–23%) [6–8]. Our analysis therefore targeted the data
from patients without cytogenetic data and at intermediate risk,
grouping these patients for specific study because optimal
postCR intensive therapy for these patients is still not clear for
either group. The better survival outcome of the HiDAC-based
group in our study is unlikely to be due to the enrollment of
more patients with a favorable risk profile because the latter only
constitutes less than one fourth of all AML patients [6–8]. In
spite of these limiting factors in our study, our data represent
the most up-to-date cost-effective analysis in the treatment of
AML. There is also strength in our single-institute experience
because the same medical team was in charge of the patients
during all stages of treatment using the same equipment,
facilities and charging system for all patients. This makes
both treatment groups comparable and without institutional
bias effects, which can easily occur with multicenter trials.
Our data will encourage more prospective clinical trials to
enroll larger number of patients and address more fully the
cost-effectiveness issue.
It is not clear whether our results can be extrapolated to either
Western countries or to multicenter clinical trials. Several
controversial issues still exist relative to the postremission
treatment of AML, such as the optimal number of cycles of
HiDAC and nonmyeloablative SCT. A previous study conducted
by the Cancer and Leukemia Group B in AML patients with
a normal karyotype demonstrated that fewer cycles of HiDAC
gave a similar survival to either four cycles of HiDAC or one cycle
of HiDAC followed by ASCT [24]. This was because of positive
salvage SCT in relapse patients with less cycles of HiDAC [24].
Figure 2. Disease-free survival (Kaplan–Meier) of 42 acute myelogenous
leukemia patients at either intermediate or unknown cytogenetic risk, who
received either high-dose arabinoside (HiDAC)-based (N = 24) or
allogeneic stem-cell transplantation (alloSCT)-based therapy (N = 18)
after the first complete remission. Time 0 indicated the time of diagnosis.
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From this standpoint, more cycles of HiDAC therapy will
further increase total treatment cost, but without a definite
improvement insurvival. Recently, studies have also demonstrated
that there is no difference in cost between myeloablative
and nonmyeloablative SCT in AML patients, and between
allogeneic BMT and allogeneic peripheral blood SCT [23, 25].
Matched unrelated BMT further increases treatment cost
compared with matched sibling BMT (151 754 versus
98 334), although the cost can be reduced by T-cell depletion
(from $US155 000 to $US113 000) [25, 26]. It is unlikely that
the cost of alloSCT will decrease in the near future, except for
a selected group of patients who can benefit from the substantial
cost savings of an outpatient-based BMT program [27].
Recently, many somatic mutations have been detected in
AML patients with a normal karyotype such as FMS-like
tyrosine kinase 3 (FLT3), mixed lineage leukaemia (MLL), Brain
and Acute Leukemia (BAALC), CCAAT/enhancer-binding
protein a (CEBPA) and nucleophosmin and these have been
associated with different prognostic effects [28]. Unfortunately,
molecular information is not available at most hospitals that
lack a research laboratory. It is likely that patients with certain
molecular abnormalities may benefit from specific
postremission treatments, although the specific nature of these
is currently unknown. We conclude that, for the postremission
therapy in the young AML patients at either intermediate or
unknown cytogenetic risk, cost-effectiveness of the HiDAC-
based therapy compares favorably with that of alloSCT-based
therapy, which deserves further prospective clinical trials.
acknowledgements
We thank Pui-Ching Lee and Muh-Hwa Yang for their help
with the statistical analysis. This study was supported by grant
NSC 94-2314-B-010-13 and a grant from the Taipei-Veterans
General Hospital.
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original article
Annals of Oncology
534 | Yu et al. Volume 18 | No. 3 | March 2007
by guest on June 7, 2013http://annonc.oxfordjournals.org/Downloaded from
    • "There are various ways to analyze costs, including cost identification, cost-effectiveness, cost-utility, and cost-benefit analyses (Table 1). The method used depends on the purpose of the research and the data available78910111213141516. Various issues must be considered when reviewing economic studies of HCT. "
    [Show abstract] [Hide abstract] ABSTRACT: Interest is growing in economic and comparative effectiveness analyses, with increasing emphasis on optimizing healthcare resources and costs. Limited information is available on the economic aspects of hematopoietic cell transplantation (HCT). We review contemporary literature on the costs and cost-effectiveness of HCT in the United States and worldwide. Published studies confirm the high costs associated with HCT, although the reported costs are highly variable, related to the differing methodologies used across studies. We examine the challenges in reviewing costs and cost-effectiveness across studies specific to HCT and highlight factors identified as associated with higher costs of HCT. We also discuss opportunities for future research in this area.
    Full-text · Article · Apr 2012
    • "USD; moreover, the minimum to the end of therapy, either cure or mortality [17]. Drug and hospital costs are far less expensive in China compared to developed countries and that accounts for some of the difference [18, 26]. Despite the fact that the overall cost is less in developing countries, the expense represents a larger proportion of income. "
    [Show abstract] [Hide abstract] ABSTRACT: High-dose arabinoside (HiDAC) and daunorubicin (DNR)-based chemotherapy are the primary consolidation treatment options for older adults (50-60 years old) with acute myeloid leukemia in China. We analyzed the event-free survival (EFS) and hospital treatment charges of older adult patients with different cytogenetic risk profiles. In patients with a better/intermediate risk profile, the average total treatment cost of HiDAC was similar to that of DNR (P = 0.11). A 5-year follow-up of patients with better/intermediate cytogenetic risk profiles revealed that the median EFS of patients who received HiDAC was significantly longer than for patients who received the DNR-based regimen (27 vs. 20 months, P = 0.03). Average cost per year of life saved was 18,746.84 USD for HiDAC, compared to 32,733.37 USD for DNR. In contrast, for patients with a poor cytogenetic risk profile, the average total treatment cost for HiDAC was higher than for DNR (P < 0.005). In addition, the median EFS in the HiDAC protocol group was significantly lower than in the DNR group (11 vs. 20 months, P = 0.003). Meanwhile, in this risk group, the average cost per year of life saved was 103,237.70 USD compared to 32,277.93 USD, respectively, in the HiDAC and DNR regimens. We conclude that HiDAC is a more efficacious and cost-effective consolidation treatment regimen in the better/intermediate risk group, while the DNR-based regimen is more cost-effective in the poor risk group.
    Full-text · Article · Mar 2011
  • [Show abstract] [Hide abstract] ABSTRACT: Allogeneic transplantation in patients with acute lymphoblastic leukaemia in first remission (ALL-CR1) has been studied in several clinical trials. However, no pooled survival analysis has yet been done. We conducted a survival meta-analysis to compare allogeneic transplantation vs chemotherapy or autologous transplantation using an intention-to-treat approach. Our study included the controlled clinical trials, wherein allocation to allogeneic transplant was based on donor availability. The event-free individual survival data were reconstructed on the basis of published information and Kaplan-Meier graphs. We then generated the meta-analytic event-free survival curves for the two treatments. The mean survival gain per patient was estimated and a simplified cost-effectiveness assessment was carried out. In the allogeneic transplantation group, 293 patients were examined and 479 as controls (four trials). The event-free survival difference was statistically significant (P=0.011). The relative risk for event occurrence was 0.79 for the experimental group vs the controls (95% CI: 0.66-0.96; P=0.017). The mean survival gain was 1 year per patient. The cost per life-year gained was less than the conventional threshold of 50,000 euros. Allogeneic transplantation in ALL-CR1 improves event-free survival as compared to chemotherapy or autologous transplantation. Its cost-effectiveness profile is acceptable.
    Full-text · Article · Nov 2007
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