• Users Online: 287
  • Print this page
  • Email this page


 
 
Table of Contents
LETTER TO EDITOR
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
UK
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_238_20

Get Permissions


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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Rodriguez-Galindo C, Friedrich P, Alcasabas P, Antillon F, Banavali S, Castillo L, et al. Toward the cure of all children with cancer through collaborative efforts: Pediatric oncology as a global challenge. J Clin Oncol 2015;33:3065-73.  Back to cited text no. 1
    
2.
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
    
3.
Magrath I, Shanta V, Advani S, Adde M, Arya LS, Banavali S, et al. Treatment of acute lymphoblastic leukaemia in countries with limited resources; lessons from use of a single protocol in India over a twenty year period [corrected]. Eur J Cancer 2005;41:1570-83.  Back to cited text no. 3
    
4.
Friedrich P, Lam CG, Itriago E, Perez R, Ribeiro RC, Arora RS. Magnitude of treatment abandonment in childhood cancer. PLoS One 2015;10:e0135230.  Back to cited text no. 4
    
5.
Radhakrishnan V, Gupta S, Ganesan P, Rajendranath R, Raghavan K, Rajalekshmy, et al. Acute lymphoblastic leukemia: A single centre experience with Berlin, Frankfurt, and Munster-95 protocol. Indian J Med Paediatr Oncol 2015;36:261-4.  Back to cited text no. 5
[PUBMED]  [Full text]  
6.
Tandon S, Moulik NR, Kumar A, Mahdi AA, Kumar A. Effect of pre-treatment nutritional status, folate and vitamin B12 levels on induction chemotherapy in children with acute lymphoblastic leukemia. Indian Pediatr 2015;52:385-9.  Back to cited text no. 6
    
7.
Pandey A, Ahlawat S, Singh A, Singh S, Krishna M, Aryan R. Outcomes and impact of minimal residual disease in pediatric, adolescent, and young adults with acute lymphoblastic leukemia treated with modified MCP 841 protocol. Cancer Res Stat Treat 2020;3:183-91.  Back to cited text no. 7
  [Full text]  
8.
Ganesan P, Sagar TG, Kannan K, Radhakrishnan V, Dhanushkodi M, Swaminathan R, et al. Acute lymphoblastic leukemia in young adults treated with intensive “Paediatric” type protocol. Indian J Hematol Blood Transfus 2018;34:422-9.  Back to cited text no. 8
    
9.
Berry DA, Zhou S, Higley H, Mukundan L, Fu S, Reaman GH, et al. Association of minimal residual disease with clinical outcome in pediatric and adult acute lymphoblastic leukemia: A meta-analysis. JAMA Oncol 2017;3:e170580.  Back to cited text no. 9
    
10.
Pandey A, Deshpande P, Singh A, Singh S, Murari K, Aryan R. Oral prednisolone, etoposide, 6-mercaptopurine (PREM) metronomic chemotherapy in treatment naïve and partially treated acute myeloid leukemia in a resource constrained setting. Cancer Res Stat Treat 2020;3:172-82.  Back to cited text no. 10
  [Full text]  
11.
Jatia S, Prasad M, Paradkar A, Bhatia A, Narula G, Chinnaswamy G, et al. Holistic support coupled with prospective tracking reduces abandonment in childhood cancers: A report from India. Pediatr Blood Cancer 2019;66:e27716.  Back to cited text no. 11
    
12.
Amegan-Aho KH. Surviving on less. Cancer Res Stat Treat 2020;3:87-8.  Back to cited text no. 12
  [Full text]  
13.
Tandon N, Banavali S, Menon H, Gujral S, Kadam PA, Bakshi A. Is there a role for metronomic induction (and maintenance) therapy in elderly patients with acute myeloid leukaemia? A literature review. Indian J Cancer 2013; 50:154-8.  Back to cited text no. 13
  [Full text]  
14.
Mukhopadhyay S, Chitalkar P, Gupta P, Roy U, Mukhopadhyay A. Oral chemotherapeutic agents in elderly acute myeloid leukaemia patients, a study from a developing country. J Clin Oncol 2007;25:18S-Abs 7057.  Back to cited text no. 14
    
15.
André N, Banavali S, Shiur Y, Pasquier E. Time for metronomics in developing countries? Lancet Oncol 2013;14: E239-48.  Back to cited text no. 15
    
16.
Banavali SD, Biswas G, Nair CN, Kurkure PA. PrET: An effective oral protocol for out-patient therapy in patients with acute myeloid leukaemia. Ped Blood Cancer 2004;43:355.  Back to cited text no. 16
    
17.
Banavali SD, Goyal L, Padhye B, Khadwal A, Nair CN, Gujral S, et al. A Novel Therapeutic Approach Yields Excellent Results in Minimally Differentiated Acute Myeloid Leukemia (AML-M0): Time to Think out of the box. Blood 2005;106:4615.  Back to cited text no. 17
    
18.
Sengar M, Nair R, Banavali SD, Menon H. Metronomic approach for treatment of acute myeloid leukaemia (AML): Dose intensity does not always matter. Haematologica 2009;94:551.  Back to cited text no. 18
    
19.
Presta M, Belleri M, Vacca A, Ribatti D. Anti-angiogenic activity of the purine analog 6-thioguanine. Leukemia 2002;16:1490-9.  Back to cited text no. 19
    
20.
Nayak L. Optimizing acute leukemia treatment in resource-constrained settings. Cancer Res Stat Treat 2020;3:287-9.  Back to cited text no. 20
  [Full text]  




 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
References

 Article Access Statistics
    Viewed46    
    Printed2    
    Emailed0    
    PDF Downloaded16    
    Comments [Add]    

Recommend this journal