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Table of Contents
Year : 2020  |  Volume : 3  |  Issue : 3  |  Page : 642-643

Acute leukemia treatment in low- and middle-income countries: Is it time for tailored therapy?

Department of Pediatrics, University Hospital Southampton, UK

Date of Submission10-Jul-2020
Date of Decision15-Jul-2020
Date of Acceptance16-Jul-2020
Date of Web Publication19-Sep-2020

Correspondence Address:
Sneha Tandon
MD Anderson Physicians Network, Houston, Texas
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/CRST.CRST_238_20

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How to cite this article:
Tandon S. Acute leukemia treatment in low- and middle-income countries: Is it time for tailored therapy?. Cancer Res Stat Treat 2020;3:642-3

How to cite this URL:
Tandon S. Acute leukemia treatment in low- and middle-income countries: Is it time for tailored therapy?. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Oct 21];3:642-3. Available from: https://www.crstonline.com/text.asp?2020/3/3/642/295493

The outcomes for acute leukemia are inferior in the low- and middle-income countries compared to those in the developed ones, because of a multitude of factors, the most important being the lack of availability of resources not only to the patients but also to the healthcare professionals. This could translate into delayed diagnosis and/or adverse clinical outcomes. This is ironic as the majority of the patients with cancer live in the developing countries. A risk-directed and good systemic chemotherapy backbone has led to a cure rate of >90% for acute lymphoblastic leukemia (ALL) across most centers in the developed countries.[1] However, the outcomes are not comparable in resource-limited nations; the cure rates range from 40% to 70% based on where the patient is treated.[2],[3],[4] The disease biology, socioeconomic factors, higher infection rate, and malnutrition also contribute to the inferior survival observed in these settings.[3],[5] In the study by Pandey et al., a significant proportion of the cohort presented with higher white blood cell counts and extramedullary disease.[7] The high frequency of toxic deaths, especially during induction, is an important factor contributing to the inferior outcomes in the developing countries compared to the developed ones. In Pandey et al.'s study, the frequency of toxic deaths was 19%, which is similar to that reported by other centers.[7]

The use of intensive chemotherapy protocols from the resource-intense settings requires increased supportive care and can therefore be counterproductive in the resource-limited settings, leading to higher toxic deaths, treatment costs, and therapy abandonment. In a study from India, higher toxic deaths, increased treatment delays, and higher relapse rates were observed when patients were treated with the Berlin–Frankfurt–Munster protocol compared to the less-intense protocols such as MCP-841.[8] Indigenous protocols that are adapted to the population and require less supportive care can not only drastically reduce the cost of therapy but also increase the uptake and reduce therapy abandonment. Pandey et al. in their single-center retrospective study of 130 adult and pediatric patients with ALL have reported the outcomes using an indigenously developed MCP-841 protocol. The advantage of this protocol is that it is less draining on the resources because it has a decreased requirement for supportive care and can be administered in the outpatient setting.[3],[7] The authors have reported a 2-year overall survival of 60% with the use of MCP-841 protocol, which is comparable to the outcomes reported by many Indian centers.[3],[5],[7] However, this could be due to the better outcomes in general for children and may not be truly reflective of the benefits of this protocol in young adults. Moreover, using a blanket therapy for all patients and not using a risk-based approach may not be justifiable in the current times, as this could lead to additional late effects of therapy, especially in the standard-risk patients who may not require such intensive therapy.

Minimal residual disease (MRD) has emerged as the strongest prognostic factor in the treatment of ALL, and it guides post-induction therapy.[9] MRD was evaluated in 78% of the patients in this study; however, therapy was not altered as per the post-induction MRD.[7] In the current era, efforts should be directed at delivering risk-adapted therapy as far as possible.

The therapy abandonment rate of 18% reported in this study is very high for a highly curable disease such as ALL and warrants the development of infrastructure and a patient support system in collaboration with non-governmental organizations or other charitable institutions.[7] The “TREAT” model was successfully implemented in a center in India which translated into a dramatic reduction in therapy abandonment.[11]

Acute myeloid leukemia (AML) is very heterogeneous, and the current survival rate is in the range of 60%–70%, with improved survival attributable to better supportive care. Intensive cytarabine- and anthracycline-based therapy is the standard of care; however, unlike in the developed world, this therapy may not be available to all the patients in the resource-limited settings. Oral metronomic chemotherapy is the chronic administration of chemotherapy at low, minimally toxic doses without prolonged treatment-free intervals.[12] It is a cost-effective, outpatient therapy with a manageable toxicity profile. The data from its use in older patients with AML appear encouraging.[13],[14] At the Tata Memorial Center, an indigenous protocol containing 6-thioguanine, etoposide, and prednisolone was developed for use in adults with AML as a bridge to standard therapy, because it often takes time to make resources available for the latter. There are promising data from its use, both in pediatric and older patients with AML.[15],[16],[17],[18] Studies have shown that these drugs affect not only the proliferating tumor cells but also the tumor microenvironment. These drugs exert antimetabolite and antiangiogenic effects.[19] Recently, Pandey et al. in their single-center retrospective study have shown an improved complete remission rate of 46% and 1-year survival rate of 45% with the use of the prednisolone, etoposide, and mercaptopurine (PREM) regimen as definitive therapy.[10] However, the use of this regimen in young patients may only prolong the interval to receive standard of care chemotherapy, thereby increasing the interval morbidity. However, larger prospective studies are needed to justify the use of the PREM regimen in older age groups or in patients who are too frail to undergo intensive therapy.

I would like to congratulate the author for single-handedly developing and running the cancer unit, and despite the constraints, being able to produce outcomes comparable to those from most other centers in the country. With further infrastructure development, cancer awareness, public–private partnership, and collaboration with other regional and national centers, these outcomes could improve in the future. Acute leukemia, especially ALL, is an extremely curable disease, and this inequity in care between the developed and developing nations can be addressed with national as well as global alliances, to ensure that no child succumbs to cancer in these modern times.[20] Improving outcomes by reducing the frequency of toxic deaths, therapy abandonment, and relapse rates should be the mantra.

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Conflicts of interest

There are no conflicts of interest.

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Magrath IT, Foucher ES, Epelman S, Ribeiro RC, Harif M, Li CK et al. Pediatric cancer in low-income and middle-income countries. Lancet Oncol. 2013;14: e104-e116. doi:10.1016/S1470-2045.  Back to cited text no. 2
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