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Table of Contents
LETTER TO EDITOR
Year : 2020  |  Volume : 3  |  Issue : 3  |  Page : 648-649

Author's reply to Saikia, Jayakar, Tandon, and Jain et al.


Department of Medical Oncology, State Cancer Institute, Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India

Date of Submission25-Jul-2020
Date of Decision29-Jul-2020
Date of Acceptance30-Jul-2020
Date of Web Publication19-Sep-2020

Correspondence Address:
Avinash Pandey
Room Number 83, 84, Department of Medical Oncology, State Cancer Institute, Indira Gandhi Institute of Medical Sciences, Patna, Bihar
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_253_20

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How to cite this article:
Pandey A. Author's reply to Saikia, Jayakar, Tandon, and Jain et al. Cancer Res Stat Treat 2020;3:648-9

How to cite this URL:
Pandey A. Author's reply to Saikia, Jayakar, Tandon, and Jain et al. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Oct 26];3:648-9. Available from: https://www.crstonline.com/text.asp?2020/3/3/648/295500



We read with interest the comments, appraisal, and critique[1],[2],[3],[4] for our original articles[5],[6] published in the last issue of this journal. We concur with Dr. Saikia[1] that a few of our patients, especially those residing in the far-off districts from where it takes more than a few hours to reach our center, were admitted to the local district hospitals under the care of the concerned physician in the event of sepsis, febrile neutropenia, or invasive fungal infection. However, all such patients were closely monitored by our team centrally from our center. The patients also received antimicrobials, antifungals, and blood product support as per standard recommendations in our institute or outside. The cost of the above-mentioned medications along with the supportive care was not factored into our analysis. Nevertheless, because of the less intensive oral therapy that required admission for a median duration of 7 days (range, 4–14 days) per admission, our costs appear to be less compared to the expense incurred with standard therapy at another apex center mentioned in our article.[5] However, as suggested, a thorough cost–benefit analysis is warranted to compare both the approaches. We agree that prednisolone, even at low doses, can increase the risk of invasive fungal infection, but our protocol already had dose interruption and reduction to half, in the event of such an episode. Moreover, only two of the nine patients required the above dose reduction.

As per our eligibility criteria, patients with a poor performance status (PS) or life-threatening infections were excluded from the study and were not treated with the prednisolone, mercaptopurine, and etoposide (PREM) regimen. Patients who were young and had an Eastern Cooperative Oncology Group PS of 0–2 but could not afford the standard 3 + 7 induction and high-dose cytarabine consolidation were offered oral PREM therapy. However, during the same study period, a considerable number of financially sound patients also received standard induction and consolidation; this was not mentioned in our publication as it was beyond the scope of the article. We reported the outcomes on all the 11 patients who initiated oral PREM therapy and continued it for at least 1 month. As suggested by Dr. Jayakar, we also do not propose oral metronomic therapy as the standard of care in view of the small sample size, selection bias, retrospective nature of our study, and the lack of a comparator arm.[3]

We believed that patients who could not complete at least two courses of consolidation cytarabine after “3 + 7” induction were at a higher risk for relapse. Hence, we used PREM maintenance for 2 years in patients who could not complete the standard therapy due to prior life-threatening toxicity (Group B). We agree that routine maintenance after the completion of standard therapy is still exploratory as suggested in the editorial accompanying our article.[7] As requested by Jain and Mirgh[4] the rationale behind the use of oral PREM is well summarized by Dr. Tandon along with its use in older and pediatric populations.[2] Our intent was to use this regimen in adult patients with acute myeloid leukemia, who could not afford the “standard 3 + 7 induction” but were otherwise fit and for whom best supportive care was the only option. We did not perform baseline karyotyping or fluorescence in situ hybridization, as no public or private laboratory in our state performs these tests and outsourcing to a private lab was exorbitant. Moreover, neither midostaurin nor allogeneic stem cell transplant was conceivable in our cohort as it comprised patients who could not even afford standard induction.

We concede with Dr. Saikia, that it is time to move beyond the MCP 841 protocol for acute lymphoblastic leukemia (ALL). We also agree that high-dose cytarabine escalates cost and toxicity, as shown in our work too.[1],[6] However, we do consider it appropriate to first augment the background resources, laboratory support, and skilled workforce before shifting to more refined and intensive protocols. Ours is a single-faculty department with neither a cytogenetic/molecular laboratory nor a serum methotrexate monitoring facility available in the entire state. Moreover, we have very limited number of inpatient beds that cater to a gamut of solid/hematological and adult/pediatric patients with cancer.

We concur with Dr. Tandon and are adopting the newer risk-adapted protocols that reduce the higher treatment to standard risk, especially after a minimal residual disease-negative status post induction, and augment treatment for high-risk patients with ALL, but within the confines of the resources made available to us.[2] In addition, our abandonment rates are high as we included “all comers” irrespective of the distance they traveled to reach our center and their commitment to pursue treatment.[1] We accept that further collaboration with charitable organizations and use of the TREAT model may reduce the limitations too. For Jain and Mirgh, the rationale for using the total leukocyte count >15,000/μL for BCR-ABL (breakpoint cluster region-Abelson murine leukemia 1 gene) testing and the method used, along with the definition of overall survival, are mentioned in the original manuscript.[4],[6] However, we do accept that using the above “cutoff” is not ideal, and we may have missed a few patients with Philadelphia chromosome positivity among those presenting with a lower total leukocyte count.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Saikia T. Challenges in managing acute leukemia in India. Cancer Res Stat Treat 2020;3:645-6.  Back to cited text no. 1
  [Full text]  
2.
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.  Back to cited text no. 2
    
3.
Jayakar V. Navigating the financial impasse in AML: PREM metronomic chemotherapy. Cancer Res Stat Treat 2020:3;644-5.  Back to cited text no. 3
    
4.
Jain A, Mirgh S. Navigating the financial impasse in acute myeloid leukemia: Prednisolone, etoposide, and 6-mercaptopurine metronomic chemotherapy. Cancer Res Stat Treat 2020:3;647-8.  Back to cited text no. 4
    
5.
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.  Back to cited text no. 5
    
6.
Pandey A, Ahlawat S, Singh A, Singh S, Murari K, Aryan R. Outcomes and impact of minimal residual disease (MRD) in pediatric, adolescent and young adults (AYA) with acute lymphoblastic leukemia treated with modified MCP 841 protocol. Cancer Res Stat Treat 2020;3:183.  Back to cited text no. 6
  [Full text]  
7.
Nayak L. Optimizing acute leukemia treatment in resource-constrained settings. Cancer Res Stat Treat 2020;3:287.  Back to cited text no. 7
  [Full text]  




 

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