Baseline clinical profile of children and adolescents (n=51) with chronic myelogenous leukemia

The physical signs at diagnosis are reported in [Table 1]. Splenomegaly was the predominant abnormality detected in 90.2% of patients with a median spleen size of 12 cm (range: 1?28 cm) below the costal margin, of these 67.4% of patients had massive splenomegaly (spleen size >8 cm below the costal margin). The presence of a splenomegaly was significantly more frequent in symptomatic (Fischer's exact test,?P?< 0>

A white blood cell (WBC) count >10 ? 109/L was observed in all of our patients [Table 2]. A higher presenting WBC count was associated with symptoms at diagnosis (Kruskal?Wallis test,?P?< 0 class="i" xss=removed>P?= 0.01). Nearly, 27.4% of our patients presented with thrombocytosis. There was no influence of age or gender on the WBC count, the hemoglobin level, or the platelet count.

Baseline laboratory parameters of children and adolescents (n=51) with chronic myelogenous leukemia

About 27.5% and 25.5% of our patients were categorized as low risk as per Sokal and Hasford scoring system, respectively, and 60.7?ll in the low risk category as per EUTOS score at baseline [Table 3].

Prognostic scores of children and adolescents (n=51) with chronic myelogenous leukemia

Molecular analysis of BCR-ABL mutation was done using reverse transcription and the RT-PCR in our patients [Table 4]. Majority of the patients (50) were positive for p210 and 1 patient was positive for p230. None of the patients were positive for p190. BCR-ABL p210 transcripts had been analyzed in 25 patients. These patients were studied for the type of chimeric BCR-ABL mRNA, of which b3a2 was positive in 17 and b2a2 was positive in 8 patients. The most common transcript was b3a2 in our patients.

Distribution of molecular subtype transcript of BCR-ABL p210

Discussion

Till date, the major focus of studies on reported clinical and biological data has been in adults with CML with pediatric CML as an incidental part; similarly, at our center, adult CML data of 20 years was published in 2013.[4]

However, the numbers of children in most of these reports were small and were published between 1990?2010.[5],[6],[7],[8],[9] Earlier studies before 2002 may have included patients with juvenile myelomonocytic leukemia as there was a diagnostic dilemma between these two entities.[5],[6],[10] The earlier studies from AIIMS have presented data up to 2010 but without the molecular transcript data.[4] We, in our study, have retrieved data from the last 9 years and correlated it along with the molecular transcript data available.

Our data show male preponderance; this has been reported both in pediatric cases by the French group and in our adult series.[8] CML remains extremely rare in very young children; more than 90% of children in our study were older than 10 years at diagnosis, as previously reported; this can be ascribed to the fact that the incidence of CML rises with increasing age. Similar trend of rising incidence with age in the pediatric patients has been seen in the SEER data and Asian studies including Indian and Japanese group.[1],[2],[11],[12] The Japanese group found that CML represented 0.2% of leukemias between 1 and 4 years of age, 2.2?tween 5 and 9 years, 3.7?tween 10 and 14 years, and 8.3?tween 15 and 19 years.[12] The Asian group diagnosed CML in 0.3% in age group 0?4 years, 1.2% in 5?9 years, 2.7% in 10?14 years, 5.1% in 15?19 years.[11] Only the French multicenter study has shown more patients in the younger age group which may be due to a separate adult CML clinic.[8] However, in the present study, the majority of our pediatric and adolescent population with CML were diagnosed in the age group >10 years. Out of these 43 were diagnosed in chronic phase and 4 in accelerated phase and 4 in blast crisis. The rate of detection of CML in aggressive phase is higher than reported by earlier studies, which may be ascribed to the delay in initiating therapy or confirming diagnosis.

Generalized weakness, fever, distress caused by splenomegaly, and bleeding were the most common presenting symptoms, which was different from previous pediatric studies by the French group and Raut et al., where bleeding manifestations were seen in rare cases.[8],[9] Children with symptoms at diagnosis had higher leukocyte counts and lower hemoglobin levels than those without symptoms, as reported in adults in data published by our institution.[4]

Hepatomegaly was more common in our patients in comparison with a previous pediatric study by Raut (35% vs. 14%).[9] Hepatomegaly may be related to adverse prognosis as previously reported by some older studies, and these patients will require greater follow-up to monitor response to therapy before a definitive conclusion can be drawn. Mild hemorrhage was common in our patients, as in adult patients of our institution.[4] This was not associated with thrombocytopenia and may have been attributable to platelet dysfunction.[13]

The type of BCR-ABL transcript was investigated in 25 of the children in our study: two-thirds of these had b3a2 transcript of p210, as compared to adults where b2a2 transcripts are more common as reported in a recent study and data published from our center in the past.[14] This may explain the presence of higher leukocyte count at presentation in pediatric CML.[15],[16]

The main difference in CML at presentation between the children in our study and adults with CML was the higher leukocyte count in the children (median: 170 ? 109/L) than reported in several adult studies, which can be explained by two-thirds of patients having b3a2 transcripts [15],[16] [Table 5]. Despite the high median leukocyte count in our study, leukostasis was evident in only a few of our patients which has also been seen in the French group study; this finding is in contrast to older reviews in which leukostasis was more common in children.[17] Bleeding manifestations were also more common in our study than previously published series. Hepatomegaly was also present in many of our patients which are in contrast to published data by the French group.[8] The most common BCR-ABL transcript was b3a2 in our study which is higher (41%) than as reported in a recent study in this part of the world.[15]

Comparison between adult[4] and pediatric chronic myelogenous leukemia patients

Conclusions

This retrospective study represents the largest series of children and adolescents in which the clinical signs and biology of CML have been reported from South Asian part of the subcontinent. The main differences that we have identified between the children and adolescents in this study are the higher leukocyte count at diagnosis, presence of hepatomegaly, bleeding manifestations at presentation, presence of b3a3 transcript of p210 breakpoint of BCR-ABL being more common in our patients. A prospective analysis of a larger cohort is needed to determine the clinical significance of these observations and also to identify if these factors affect response to tyrosine kinase inhibitor therapy or have any prognostic significance.

Conflict of Interest

There are no conflicts of interest.

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Publication History

Article published online:
23 June 2021

? 2018. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

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