Abstract

Subsequent to the development and global availability of BCR/ABL–targeted tyrosine kinase inhibitors (TKIs), the prognosis of patients with chronic myeloid leukemia (CML), at least those in the chronic phase, has markedly improved, and in the developed world, the average lifespan of these patients is now close to that of age- and sex-matched subjects without the disease. However, the situation in low- and middle-income countries (LMICs) may not be so rosy. Many important differences in hematological cancers, including CML, have been highlighted in various publications in LMICs vs developed countries. These include differences in incidence and prevalence rates, age and stage of disease at diagnosis, response rates, and survival. Some of the possible reasons proposed for these are varying socioeconomic milieu (impacting availability of effective drugs and essential monitoring), environmental factors (mainly exposure to viral infections and pesticides), nutritional factors with interplay of malnutrition and diet on drug absorption and blood levels, and possible unknown genetic factors. Although generic first-generation TKIs (imatinib) are available in many parts of the world, several challenges remain in providing optimal treatment to patients with CML in resource-poor countries. Some of these include availability of optimal and high-quality BCR/ABL testing, availability and expense related to use of second- and third-generation TKIs (nilotinib, dasatinib, bosutinib, and ponatinib) and hematopoietic stem cell transplantation, issues with compliance and toxicities of drugs, and ensuring a minimal standard-of-care treatment and monitoring for every patient diagnosed with CML. For the purpose of this article, the more objective country label—LMIC—coined by the World Bank will be used (gross national income per capita between $1026 and $3995; World Bank, June 2019). Some of these issues will be discussed in this article in greater detail by experts in the field in 3 different but interconnected sections.

References

References
1.
Gunnarsson
N
,
Sandin
F
,
Höglund
M
, et al
.
Population-based assessment of chronic myeloid leukemia in Sweden: striking increase in survival and prevalence
.
Eur J Haematol
.
2016
;
97
(
4
):
387
-
392
.
2.
Björkholm
M
,
Ohm
L
,
Eloranta
S
, et al
.
Success story of targeted therapy in chronic myeloid leukemia: a population-based study of patients diagnosed in Sweden from 1973 to 2008
.
J Clin Oncol
.
2011
;
29
(
18
):
2514
-
2520
.
3.
Bower
H
,
Björkholm
M
,
Dickman
PW
,
Höglund
M
,
Lambert
PC
,
Andersson
TM
.
Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population
.
J Clin Oncol
.
2016
;
34
(
24
):
2851
-
2857
.
4.
Ganesan
P
,
Ganesan
TS
,
Radhakrishnan
V
, et al
.
Chronic myeloid leukemia: long-term outcome data in the imatinib era
.
Indian J Hematol Blood Transfus
.
2019
;
35
(
1
):
37
-
42
.
5.
Ganesan
P
,
Kumar
L
.
Chronic myeloid leukemia in India
.
J Glob Oncol
.
2016
;
3
(
1
):
64
-
71
.
6.
Malhotra
H
,
Sharma
R
,
Singh
Y
, et al
.
Report of chronic myeloid leukemia SMS Medical College Hospital, Jaipur
.
Ind J Med Paed Oncol.
2013
;
34
(
3
):
177
-
179
.
7.
Goldman
JM
.
Chronic myeloid leukemia in India
.
Indian J Med Paediatr Oncol
.
2013
;
34
(
3
):
147
-
148
.
8.
Tapela
N
,
Nzayisenga
I
,
Sethi
R
, et al
.
Treatment of chronic myeloid leukemia in rural Rwanda: promising early outcomes
.
J Glob Oncol
.
2016
;
2
(
3
):
129
-
137
.
9.
Kayastha
GK
,
Ranjitkar
N
,
Gurung
R
, et al
.
Treating Philadelphia chromosome/BCR-ABL1 positive patients with Glivec (Imatinib mesylate): 10 years’ experience at Patan Hospital, Nepal
.
Br J Haematol
.
2017
;
177
(
6
):
991
-
999
.
10.
Au
WY
,
Caguioa
PB
,
Chuah
C
, et al
.
Chronic myeloid leukemia in Asia
.
Int J Hematol
.
2009
;
89
(
1
):
14
-
23
.
11.
Unnikrishnan
R
,
Veeraiah
S
,
Mani
S
, et al
.
Comprehensive evaluation of adherence to therapy, its associations, and its implications in patients with chronic myeloid leukemia receiving imatinib
.
Clin Lymphoma Myeloma Leuk
.
2016
;
16
(
6
):
366
-
371.e3
.
12.
Menon
H
.
Non-adherence to CML therapy and its clinical implications in India
.
Natl Med J India
.
2017
;
30
(
3
):
142
-
147
.
13.
Yanamandra
U
,
Malhotra
P
,
Sahu
KK
, et al
.
Variation in adherence measures to imatinib therapy
.
J Glob Oncol
.
2018
;
4
:
1
-
10
.
14.
Cantú-Rodríguez
OG
,
Sánchez-Cárdenas
M
,
Gutiérrez-Aguirre
CH
, et al
.
Cultural factors related to adherence to imatinib in CML: a Mexican perspective
.
Hematology
.
2015
;
20
(
2
):
72
-
76
.
15.
Sokal
JE
,
Cox
EB
,
Baccarani
M
, et al
.
Prognostic discrimination in “good-risk” chronic granulocytic leukemia
.
Blood
.
1984
;
63
(
4
):
789
-
799
.
16.
Hoffmann
VS
,
Baccarani
M
,
Lindoerfer
D
, et al
.
The EUTOS prognostic score: review and validation in 1288 patients with CML treated frontline with imatinib
.
Leukemia
.
2013
;
27
(
10
):
2016
-
2022
.
17.
Deb
P
,
Nath
U
,
Aich
R
, et al
.
EUTOS score predicts long-term outcome in chronic myeloid leukemia patients transitioning from pre-imatinib era to imatinib upon availability
.
Blood
.
2015
;
126
(
23
):
4023
.
18.
Ali
MD
,
Badi
AI
,
Al-Zebari
SS
,
Al-Allawi
NA
.
Response to tyrosine kinase inhibitors in chronic myeloid leukemia: experience from a west Asian developing country
.
Int J Hematol
.
2014
;
100
(
3
):
274
-
280
.
19.
WHO. WHO essential drug list 2017. https://www.who.int/medicines/publications/essentialmedicines/20th_EML2017.pdf. Accessed 8 August 2019.
20.
Experts in Chronic Myeloid Leukemia
.
The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: from the perspective of a large group of CML experts
.
Blood
.
2013
;
121
(
22
):
4439
-
4442
.
21.
Madhav
D
.
Generic imatinib in chronic myeloid leukemia: survival of the cheapest
.
Blood
.
2016
;
128
:
630
.
22.
Mathews
V
.
Generic imatinib: the real-deal or just a deal?
Leuk Lymphoma
.
2014
;
55
(
12
):
2678
-
2680
.
23.
Malhotra
H
,
Sharma
P
,
Bhargava
S
,
Rathore
OS
,
Malhotra
B
,
Kumar
M
.
Correlation of plasma trough levels of imatinib with molecular response in patients with chronic myeloid leukemia
.
Leuk Lymphoma
.
2014
;
55
(
11
):
2614
-
2619
.
24.
Natarajan
H
,
Kumar
L
,
Bakhshi
S
, et al
.
Imatinib trough levels: a potential biomarker to predict cytogenetic and molecular response in newly diagnosed patients with chronic myeloid leukemia
.
Leuk Lymphoma
.
2019
;
60
(
2
):
418
-
425
.
25.
Rousselot
P
,
Prost
S
,
Guilhot
J
, et al
;
French CML Group
.
Pioglitazone together with imatinib in chronic myeloid leukemia: a proof of concept study
.
Cancer
.
2017
;
123
(
10
):
1791
-
1799
.
26.
Malhotra
H
,
Malhotra
B
,
Yadav
A
, et al
.
358P - PPAR GAMMA Agonist in combination with BCR/ABL TKI in patients of CML-CP with suboptimal molecular response
.
Ann Oncol.
2016
;
27
(
suppl 9
):
ix104
-
ix111
.
27.
Bhargava
S
,
Malhotra
H
,
Rathore
OS
, et al
.
Anti-leukemic activities of alcoholic extracts of two traditional Indian medicinal plants
.
Leuk Lymphoma
.
2015
;
56
(
11
):
3168
-
3182
.
28.
Yeung
DT
,
Osborn
MP
,
White
DL
, et al
;
Australasian Leukaemia and Lymphoma Group
.
TIDEL-II: first-line use of imatinib in CML with early switch to nilotinib for failure to achieve time-dependent molecular targets
.
Blood
.
2015
;
125
(
6
):
915
-
923
.
29.
Elias
F
,
Gebran
A
,
Said
C
,
Beker
RV
,
Ammar
W
.
Budget impact of treatment-free remission in treating chronic-phase Philadelphia-positive CML in Lebanon
.
J Glob Oncol
.
2019
;
5
:
1
-
7
.
30.
Winn-Deen
ES
,
Helton
B
,
Van Atta
R
, et al
.
Development of an integrated assay for detection of BCR-ABL RNA
.
Clin Chem
.
2007
;
53
(
9
):
1593
-
1600
.
31.
CDC
.
Availability of an assay for detecting mycobacterium tuberculosis, including rifampin-resistantstrains, and considerations for its use
.
MMWR Morb Mortal Wkly Rep.
2013
;
62
(
41
):
821
-
824
.
32.
Sala Torra
O
,
Beppu
L
,
Smith
JL
, et al
.
Paper or plastic? BCR-ABL1 quantitation and mutation detection from dried blood spots
.
Blood
.
2016
;
127
(
22
):
2773
-
2774
.
33.
Drain
PK
,
Hyle
EP
,
Noubary
F
, et al
.
Diagnostic point-of-care tests in resource-limited settings
.
Lancet Infect Dis
.
2014
;
14
(
3
):
239
-
249
.
34.
Stevens
WS
,
Scott
LE
,
Crowe
SM
.
Quantifying HIV for monitoring antiretroviral therapy in resource-poor settings
.
J Infect Dis
.
2010
;
201
(
suppl 1
):
S16
-
S26
.
35.
Petti
CA
,
Polage
CR
,
Quinn
TC
,
Ronald
AR
,
Sande
MA
.
Laboratory medicine in Africa: a barrier to effective health care
.
Clin Infect Dis
.
2006
;
42
(
3
):
377
-
382
.
36.
Postel
A
,
Letzel
T
,
Frischmann
S
,
Grund
C
,
Beer
M
,
Harder
T
.
Evaluation of two commercial loop-mediated isothermal amplification assays for detection of avian influenza H5 and H7 hemagglutinin genes
.
J Vet Diagn Invest
.
2010
;
22
(
1
):
61
-
66
.
37.
Sooknanan
R
,
Malek
L
,
Wang
XH
,
Siebert
T
,
Keating
A
.
Detection and direct sequence identification of BCR-ABL mRNA in Ph+ chronic myeloid leukemia
.
Exp Hematol
.
1993
;
21
(
13
):
1719
-
1724
.
38.
Dugan
LC
,
Hall
S
,
Kohlgruber
A
,
Urbin
S
,
Torres
C
,
Wilson
P
.
Detection of BCR-ABL Fusion mRNA Using Reverse Transcriptase Loop-mediated Isothermal Amplification.
Livermore, CA
:
Lawrence Livermore National Lab
;
2011
.
Report no. LLNL-TR-520096
.
39.
Hashimoto
Y
,
Hatayama
Y
,
Kojima
N
, et al
.
Development of reverse transcription loop-mediated isothermal amplification for simple and rapid detection of promyelocytic leukemia-retinoic acid receptor α mRNA
.
Yonago Acta Med
.
2016
;
59
(
4
):
262
-
269
.
40.
World Health Organization. Global Health Observatory, 2018. who.int/gho/database/en/. Accessed 8 August 2019.
41.
Kanavos
P
,
Vandoros
S
,
Garcia-Gonzalez
P
.
Benefits of global partnerships to facilitate access to medicines in developing countries: a multi-country analysis of patients and patient outcomes in GIPAP
.
Global Health
.
2009
;
5
(
1
):
19
.
42.
Garcia-Gonzalez
P
,
Boultbee
P
,
Epstein
D
.
Novel humanitarian aid program: the Glivec International Patient Assistance Program—lessons learned from providing access to breakthrough targeted oncology treatment in low-and middle-income countries
.
J Glob Oncol
.
2015
;
1
(
1
):
37
-
45
.
43.
The Max Foundation
.
The Max Foundation. www.themaxfoundation.org. Accessed May 15, 2019
.
44.
American Cancer Society
.
American Cancer Society statistics
. .
45.
Mendizabal
AM
,
Garcia-Gonzalez
P
,
Levine
PH
.
Regional variations in age at diagnosis and overall survival among patients with chronic myeloid leukemia from low and middle income countries
.
Cancer Epidemiol
.
2013
;
37
(
3
):
247
-
254
.
You do not currently have access to this content.