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ORIGINAL ARTICLE: HEMATOLYMPHOID MALIGNANCIES
Year : 2019  |  Volume : 8  |  Issue : 4  |  Page : 241-243

Clinico-epidemiological features and response in childhood acute lymphoblastic leukemia at regional cancer center of Northeast India


1 Department of Medical Oncology, Dr. B Borooah Cancer Institute, Guwahati, Assam, India
2 Department of Pathology, Dr. B Borooah Cancer Institute, Guwahati, Assam, India

Date of Web Publication22-Oct-2019

Correspondence Address:
Prof. Bhargab Jyoti Saikia
Department of Medical Oncology, Dr. B Borooah Cancer Institute, Guwahati, Assam
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sajc.sajc_249_19

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  Abstract 

Introduction: Acute lymphoblastic leukemia (ALL) comprises 19.3% of all childhood cancers in Northeast India. Methods: We analyzed clinicoepidemiological features and early response to the treatment of all the cases of childhood ALL (age <15 years) diagnosed and treated at Dr. B Borooah Cancer Institute over 1 year. Results: Of 52 eligible cases, 69% were male (male:female ratio of 2.2:1) and the mean age was 7.1 years. Thirty-three children (63%) had baseline white blood cell count ≥20 × 109/L. Precursor B-cell was most the common subtype seen in 61% of children. Seven cases (14%) had high-risk (HR) cytogenetics, with t (9,22) being the most common one. Male sex and HR cytogenetics were significantly associated with poor early responses. Conclusion: ALL is a common childhood malignancy with high cure rates. However, poor socioeconomic status and the presence of higher proportions of disease-related factors lead to poor outcome in this part of the country.

Keywords: Cytogenetics, early response, minimum residual disease, risk stratification


How to cite this article:
Saikia BJ, Roy PS, Kumar G, Mishra RK, Sarma A. Clinico-epidemiological features and response in childhood acute lymphoblastic leukemia at regional cancer center of Northeast India. South Asian J Cancer 2019;8:241-3

How to cite this URL:
Saikia BJ, Roy PS, Kumar G, Mishra RK, Sarma A. Clinico-epidemiological features and response in childhood acute lymphoblastic leukemia at regional cancer center of Northeast India. South Asian J Cancer [serial online] 2019 [cited 2019 Nov 12];8:241-3. Available from: http://journal.sajc.org/text.asp?2019/8/4/241/269696


  Introduction Top


Leukemia constitutes about 30%–50% of all childhood cancers globally.[1],[2],[3],[4] In India, the proportion of children with acute leukemia ranged from 26.7% to 52.3% of all childhood cancers.[5],[6],[7] However, in Northeast India, acute leukemia constitutes around 27% of all childhood cancers with acute lymphoblastic leukemia (ALL) being the most common, comprising 19.3% of all childhood cancers.[8]

We sought to provide a comprehensive assessment of clinicoepidemiological features and early response to the treatment of childhood ALL diagnosed and treated at our institute over a period of 1 year.


  Methods Top


In this retrospective study, we analyzed all the cases of childhood ALL diagnosed and treated at Dr. B Borooah Cancer Institute, Guwahati, from January 1, 2018, to December 31, 2018. The study received the Institutional Ethics Committee approval.

All newly diagnosed children aged <15 years with flow cytometry-based diagnosed cases of ALL were included in the study. Children with relapsed ALL at presentation, referred patients from other centers for continuing part of their treatment, patients not received any treatment after confirmation of the diagnosis, and patients who failed to undergo complete diagnostic workup were excluded from the study. Clinicoepidemiological and treatment-related data were collected from patient case file and health records available in the hospital database.

Patients were risk stratified into standard risk (SR), intermediate risk (IR), and high risk (HR) (“SR:” defined as prednisolone good response [PGR], age 1 year to younger than 6 years, initial white blood cell [WBC] <20 × 109/L and M1 [<5% blasts] or M2 [≥5% to <25% blasts] marrow on day-15, and M1 marrow on day-33 [all criteria must be fulfilled]; “IR:” defined as PGR, age younger than 1 year or age 6 years or older and/or WBC ≥20 × 109/L and M1 or M2 marrow on day-15 and M1 marrow on day-33, or SR criteria but M3 [≥25% blasts] marrow on day-15 and M1 marrow on day-33; and “HR:” defined as at least one of the following – prednisolone poor response, IR and M3 marrow on day-15, M2 or M3 marrow on day-33, t(9;22) [BCR-ABL], or t(4;11) [MLL-AF4]).[9] All patients received initial treatment as per “SR” BFM 2002 protocol irrespective of the presence of baseline risk factors.

Day-8 hemogram after steroid use was used to evaluate early response (“Good response” was defined as absolute blast count <1000/mm 3 in peripheral blood).[9] After the completion of induction Phase I therapy, day-33 bone marrow blast percentage was used to define “minimum residual disease” (MRD) status (negative MRD defined as blast percentage <0.01% in bone marrow aspiration specimen by flow cytometry).[9] Early response to treatment includes both day-8 response and day-33 MRD. Treatment is intensified to “HR” protocol in patients who have not achieved negative MRD even after completion of both the induction phases of therapy. Early death was defined as death within 30 days of starting the treatment.


  Results Top


A total of 73 patients of childhood ALL were registered at our institute during the study period. Of the 73 cases, 52 children were found to be eligible for inclusion in this study.

Patient profile

These included 36 (69%) boys and 16 (31%) girls, with male-to-female ratio was 2.2:1. The mean age for the entire cohort was 7.1 years (standard deviation [SD] ±4.7; percentile [1–3]–[3.1–11]).

Disease profile

Of the 52 patients of childhood ALL, precursor B-cell ALL was the most common subtype accounting for 32 (61%), B-cell type 11 (21%), and T-cell 9 (18%) of all cases [Table 1]. The most common presenting symptom was fever followed by bleeding and generalized weakness, which were present in 77%, 38%, and 26% of all patients, respectively.
Table 1: Baseline demographic profile

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Regarding baseline hemogram, mean hemoglobin level was 6.9 g/dl (SD ±2.6; percentile [1-3]–[5–8.8]), mean WBC count was 110 × 109/L (SD ± 150 × 109/L; percentile [1–3]–[6022–161,500))and mean platelet count was 52.8 × 109/L (SD ± 36.5 × 109/L; percentile [1–3]– [19,250–68,750))

Of the 52 patients, cytogenetic profile was available for 49 patients. Normal cytogenetics was seen in 39 (80%) patients. Seven (14%) patients had HR cytogenetics (t [9,22)in 3 [43%]; t [4,11] in 2 [29%]; and t [1,19] and hypoploidy in 1 case [14%] each). Three (6%) patients had good risk cytogenetics (hyperploidy in two patients and t (12,21) in one patient). Cytogenetics report could not be retrieved for three patients [Table 1]. Baseline cerebrospinal fluid (CSF) cytology was performed in 49 of 52 children and was negative in all cases. CSF cytology was not done in three patients at baseline (low platelet count <10 × 109/L).

Treatment response

Early deaths were seen in 11 (21%) of 52 children. The most common cause was bleeding which accounts for early death in 7 cases (64%) and tumor lysis syndrome and febrile neutropenia in 2 cases (18%) each. Mean number of days from start of treatment to early deaths was 5.5 days (range 3–13 days).

Early response to treatment was assessed with day-8 peripheral blood blast count in 45 of 52 patients (seven children died before completing day-8 steroid) and day-33 MRD assessed in 41 of 52 patient (11 children died before completing Phase I of induction chemotherapy). Of 45 children, 8 (18%) children did not achieve “good response” to steroid and 11 (27%) children had positive MRD after completing Phase I induction therapy [Table 2].
Table 2: Factors associated with poor early responses

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On further analysis, it was found that male sex had poor early responses (poor day-8 response in 8 patients [26%] [P = 0.04; confidence interval (CI) 95%] and positive day-33 MRD in 11 [39%] patients [P = 0.007; CI 95%]) [Table 2]. The presence of HR cytogenetics was also found to be associated with poor day-8 response in 4 (57%) patients (P = 0.01; CI 95%) and positive day-33 MRD in 4 (66%) patients (P = 0.04; CI 95%). Contrary to this, age <1 and >5 years and higher baseline WBC counts ≥20 × 109/L were not seen to be significantly associated with poor early responses. Regarding subtypes of ALL, although precursor B-cell and T-cell ALL were found to have better day-8 response as compared to B-cell type; however, the association was not found to be statistically significant (P = 0.07; CI 95%).


  Discussion Top


In this study, we found the mean age of children with ALL to be 7.1 years with male preponderance. The proportion of children with baseline WBC count ≥20 × 109/L was 33 (63%). Precursor B-cell was the most common subtype and children with T-cell subtype were 7 (18%) of all cases. Seven (14%) of 49 cases had HR cytogenetics, of which t(9,22) was most commonly present in 3 (43%) of seven children. The number of early deaths was 11 (21%), of which bleeding was the most common cause. Regarding early response to treatment, 8 (18%) of all evaluable children had poor day-8 response to steroids and 11 (27%) children had positive day-33 MRD. Male sex and HR cytogenetics were significantly associated with poor early responses. B-cell subtype was associated with poor early responses as compared to precursor B-cell and T-cell subtype, but the difference was not statistically significant.

Age at presentation and male sex predominance in our study were found to be similar when we compared the results with other Indian studies.[10],[11],[12] The proportion of T-cell subtype was lower (18% in our study) than average of 30%–50% in different Indian studies.[10],[13] More children presented with higher baseline WBC count (65% in our study) than average of 30%–40% in other studies.[10],[14],[15] We found higher proportions of BCR-ABL positivity (43% vs. 8.3% from a South Indian study).[16] We did not found any CNS-positive disease at baseline, as compared to 3%–6% positivity reported in various Indian studies.[12],[17],[18] We also found higher early deaths in our study (21% vs. 10%–12%) compared to other studies from India.[17],[18] Regarding early treatment response rates, we found negative day-33 MRD as 73% when compared with morphological complete response (CR) of 83%–94% reported by different studies from India.[10],[17],[18],[19] It is inappropriate to compare day-33 MRD with morphologic CR, as bone marrow assessment for MRD was not done in majority of those studies which were conducted before the year 2010. Reason for poor early response seen in our study is due to higher proportion of children with HR factors.

Poor outcomes of treatment in middle- to low-income countries are mainly attributed to frequent treatment abandonment, more early toxic deaths, and higher relapse rates as compared to high income countries.[8],[20]


  Conclusion Top


ALL is a common childhood malignancy with high cure rates. However, poor socioeconomic status in addition to the presence of higher proportions of disease-related risk factors in children with ALL leads to poor outcome in this part of the country.

Acknowledgment

Authors are grateful to the Hospital-Based Cancer Registry (HBCR) of Dr. B Borooah Cancer Institute, Guwahati, Assam, for providing the data.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Magrath I, Steliarova-Foucher E, Epelman S, Ribeiro RC, Harif M, Li CK, et al. Paediatric cancer in low-income and middle-income countries. Lancet Oncol 2013;14:e104-16.  Back to cited text no. 1
    
2.
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010;127:2893-917.  Back to cited text no. 2
    
3.
Dinand V, Arya LS. Epidemiology of childhood Hodgkins disease: Is it different in developing countries? Indian Pediatr 2006;43:141-7.  Back to cited text no. 3
    
4.
Yaris N, Mandiracioglu A, Buyukpamukcu M. Childhood cancer in developing countries. Pediatr Hematol Oncol 2014;21:237-53.  Back to cited text no. 4
    
5.
Arora RS, Eden TO, Kapoor G. Epidemiology of childhood cancer in India. Indian J Cancer 2009;46:264-73.  Back to cited text no. 5
[PUBMED]  [Full text]  
6.
National Cancer Registry Programme 2013. Consolidated Report of Hospital Based Cancer Registries: 2007-2011. Cancer in Childhood. Bangalore: National Centre for Disease Informatics and Research-Indian Council of Medical Research; 2013.  Back to cited text no. 6
    
7.
Asthana S, Labani S, Mehrana S, Bakhshi S. Incidence of childhood leukemia and lymphoma in India. Pediatr Hematol Oncol J 2018;3:115-20.  Back to cited text no. 7
    
8.
Hazarika M, Krishnatreya M, Bhuyan C, Saikia BJ, Kataki AC, Roy PS, et al. Overview of childhood cancers at a regional cancer centre in North-East India. Asian Pac J Cancer Prev 2014;15:7817-9.  Back to cited text no. 8
    
9.
Stary J, Zimmermann M, Campbell M, Castillo L, Dibar E, Donska S, et al. Intensive chemotherapy for childhood acute lymphoblastic leukemia: Results of the randomized intercontinental trial ALL IC-BFM 2002. J Clin Oncol 2013;48:6522.  Back to cited text no. 9
    
10.
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. 10
    
11.
Kulkarni KP, Arora RS, Marwaha RK. Survival outcome of childhood acute lymphoblastic leukemia in India: A resource-limited perspective of more than 40 years. J Pediatr Hematol Oncol 2011;33:475-9.  Back to cited text no. 11
    
12.
Bajel A, George B, Mathews V, Viswabandya A, Kavitha ML, Srivastava A, et al. Treatment of children with acute lymphoblastic leukemia in India using a BFM protocol. Pediatr Blood Cancer 2008;51:621-5.  Back to cited text no. 12
    
13.
Mukhopadhyay A, Gangopadhyay S, Dasgupta S, Paul S, Mukhopadhyay S, Ray UK. Surveillance and expected outcome of acute lymphoblastic leukemia in children and adolescents: An experience from Eastern India. Indian J Med Paediatr Oncol 2013;34:280-2.  Back to cited text no. 13
[PUBMED]  [Full text]  
14.
Gupta A, Kapoor G, Jain S, Bajpai R. Absolute lymphocyte count recovery independently predicts outcome in childhood acute lymphoblastic leukemia: Experience from a tertiary care cancer center of a developing country. J Pediatr Hematol Oncol 2015;37:e143-9.  Back to cited text no. 14
    
15.
Radhakrishnan V, Gupta S, Ganesan P, Rajendranath R, Ganesan TS, Rajalekshmy KR, et al. Acute lymphoblastic leukemia: A single center experience with Berlin, Frankfurt, and Munster-95 protocol. Indian J Med Paediatr Oncol 2015;36:261-4.  Back to cited text no. 15
[PUBMED]  [Full text]  
16.
Sugapriya D, Preethi S, Shanthi P, Chandra N, Jeyaraman G, Sachdanandam P, et al. BCR-ABL translocation in pediatric acute lymphoblastic leukemia in Southern India. Indian J Hematol Blood Transfus 2012;28:37-41.  Back to cited text no. 16
    
17.
Arya LS, Kotikanyadanam SP, Bhargava M, Saxena R, Sazawal S, Bakhshi S, et al. Pattern of relapse in childhood ALL: Challenges and lessons from a uniform treatment protocol. J Pediatr Hematol Oncol 2010;32:370-5.  Back to cited text no. 17
    
18.
Kulkarni KP, Marwaha RK, Trehan A, Bansal D. Survival outcome in childhood ALL: Experience from a tertiary care centre in North India. Pediatr Blood Cancer 2009;53:168-73.  Back to cited text no. 18
    
19.
Varghese B, Joobomary AA, Savida P. Five-year survival rate and the factors for risk-directed therapy in acute lymphoblastic leukemia. J Med Paediatr Oncol 2018;39:301-6.  Back to cited text no. 19
    
20.
Pui CH, Yang JJ, Hunger SP, Pieters R, Schrappe M, Biondi A, et al. Childhood acute lymphoblastic leukemia: Progress through collaboration. J Clin Oncol 2015;33:2938-48.  Back to cited text no. 20
    



 
 
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