Indian Journal of Cancer
Home  ICS  Feedback Subscribe Top cited articles Login 
Users Online :227
Small font sizeDefault font sizeIncrease font size
Navigate here
  Search
 
  Ahead of print
  
Resource links
    Search Pubmed for
 
    -  Sazawal S
    -  Singh K
    -  Chhikara S
    -  Chaubey R
    -  Mishra P
    -  Seth T
    -  Saxena R

 
  In this article
   References
   Article Figures

 Article Access Statistics
    Viewed59    
    PDF Downloaded4    

Recommend this journal

 

Previous Article  Table of Contents  Next Article
LETTER TO THE EDITOR
Ahead of print publication
 

Pediatric chronic myeloid leukemia with myeloid blast crisis and complex karyotype at presentation


 Department of Hematology, All India Institute of Medical Sciences, New Delhi, India

Date of Submission22-Apr-2017
Date of Decision11-Jun-2020
Date of Acceptance12-Jun-2020
Date of Web Publication20-Jul-2020

Correspondence Address:
Renu Saxena,
Department of Hematology, All India Institute of Medical Sciences, New Delhi
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijc.IJC_208_17




How to cite this URL:
Sazawal S, Singh K, Chhikara S, Chaubey R, Mishra P, Seth T, Saxena R. Pediatric chronic myeloid leukemia with myeloid blast crisis and complex karyotype at presentation. Indian J Cancer [Epub ahead of print] [cited 2020 Aug 9]. Available from: http://www.indianjcancer.com/preprintarticle.asp?id=290270




In pediatric age group, chronic myeloid leukemia blast crisis (CML-BC) is a rare hematological disorder. Approximately 95% of children present in chronic phase CML (CML-CP) and the remainder present in the accelerated phase CML or in CML-BC.[1] The progression from CML-CP to CML-BC in the pretyrosine kinase era is well described, but CML-BC at presentation in children is very rare. In children, CML presents in two types: (i) two-third are adult form of CML seen in adolescents (ii) one-third are juvenile form of CML seen in children below 2 years of age. The more common acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) should always be excluded in childhood CML-BC.

Here, we present a 4-year-old child who was referred to All India Institute of Medical Sciences (AIIMS), New Delhi, as a case of acute leukemia (on treatment). This case was finally diagnosed as CML-BC with complex karyotype (trisomy 8, t(9:22) and isochromosome 17q). This case reports the importance of molecular techniques in the diagnosis and risk stratification which helped in the targeted therapy to improve the prognosis.

A 4-year-old boy presented to a government hospital in New Delhi, in March 2016, with chief complaints of pain abdomen, on and off fever, and loss of appetite for 2 weeks duration. Complete hemogram revealed Hb - 7.1 g/dL (range,12.5 ±1.5mg/dL), total leukocyte count (TLC) - 119210/μL (range, 10000±5000/μL), and platelet count - 138 000/μL (range, 2,00,000-490,000/μL). Differential leukocyte count (DLC) showed blast count of 38% with predominance of myeloid precursors and basophilia (09%). Ultrasonography showed hepatomegaly and splenomegaly. Immunophenotyping (IPT) revealed CD34, CD117, and HLA-DR positivity with negative T- and B-cell lineage markers. Bone marrow aspirate showed 36% blasts, myelocytes 12%, metamyelocytes 12%, and basophils 6%. Diagnosis of acute leukemia was made, and the patient was started on chemotherapy along with antibiotics, antiemetics, analgesics, and antacids. Repeat marrow aspirate after 1 month showed blasts 65% with basophils 2%. The condition of the patient was deteriorating, and the patient was then referred to AIIMS, New Delhi.

At AIIMS, general physical examination showed hepatomegaly and significant splenomegaly. Complete hemogram revealed Hb - 8.8 g/dL, TLC - 18,900/μL, and platelet count - 142 000/μL with DLC of 32% blasts, myelocytes and metamyelocytes 15%, and basophils 3%. Considering the possibility of acute leukemia vis-a-vis CML-BC, the parents were advised bone marrow aspirate and biopsy, IPT, cytogenetics, reverse transcription-polymerase chain reaction (RT-PCR) (Breakpoint cluster region - Abelson gene (BCR-ABL1) transcript).

Bone marrow aspirate revealed cellular marrow with predominance of myeloid series with differential count of blast count - 30%, myelocytes and metamyelocytes - 33%, eosinophils - 10%, and basophils - 2%. Bone marrow biopsy showed hypercellularity with scattered blasts, raised myeloid precursors, and increase in megakaryocytes with clustering at places. Reticulin stain revealed Grade 1–2 fibrosis. Based on the above findings, impression of CML-BC was made.

IPT showed significant positivity for CD34, HLA-DR, MPO, and negative T- and B-cell lineage markers [Figure 1]a, [Figure 1]b, [Figure 1]c, [Figure 1]d. Karyotyping revealed complex karyotype: trisomy 8, t(9:22), and isochromosome 17q. RT-PCR for BCR-ABL showed positivity for p210 fusion transcript (b3a2/e14a2 junction) and was negative for p190. Real-time PCR (RQ-PCR) revealed BCR-ABL fusion transcript ratio 94.09%. RT-PCR for t(8:21), t(15:17), inversion 16, and FLT-3 was negative. Final diagnosis of CML in myeloid BC with complex karyotype was made, and the patient was started on imatinib mesylate. The patient is on regular follow-up and attained hematological response after 5 months of treatment and doing well till date.
Figure 1: (a-d) Immunophenotyping showing CD13, CD33, HLA-DR & CD117 positivity

Click here to view


The child was diagnosed as CML in myeloid BC rather than de novo ALL or AML based on >20% blasts, predominance of metamyelocytes, and myelocytes and basophilia in bone marrow. The presence of hepatosplenomegaly, IPT findings, karyotyping, and RT-PCR for the presence of p210 BCR-ABL transcript further augmented the diagnosis. The following features make this case unusual: firstly, it was a childhood CML at presentation; secondly, it presented with myeloid BC; and thirdly, it had a complex karyotype. As per revised WHO classification 2016, new entity “AML with BCR-ABL1” should always be considered in differential diagnosis.[2] The presence of splenomegaly, basophilia, and abnormal cytogenetics points more toward diagnosis of “CML-BC” rather than “AML with BCR-ABL 1.”

BC is the final phase in the evolution of CML and behaves like an acute leukemia, with rapid progression and short survival.[3] This type of presentation accounts for 10% of cases of CML and may mimic acute leukemia morphologically in pediatric cases. These findings are in line with our case. Blast transformation of CML is lymphoid in 30% and myeloid in 70% of cases.[4],[5] About 80%–85% of CML-BC cases undergo karyotypic evolution with most common karyotypic changes being +8, +Ph, i (17q), and +19.[6],[7] Our case had complex karyotype of trisomy 8, t(9:22), and isochromosome 17q. Pediatric CML is an unique disease that requires a different approach. Because of the low incidence of CML in children and lack of robust clinical data, the management of pediatric CML is not as established as for adult patients.[8] Even in children, CML-BC may be the initial presentation and should always be differentiated from “AML with BCR-ABL1.”

Acknowledgments

The authors wish to acknowledge Mr. Rajender and Mr. R. Jaiswal for technical assistance.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Millot F, Traore P, Guilhot J, Nelken B, Leblanc T, Leverger G, et al. Clinical and biological features at diagnosis in 40 children with chronic myeloid leukemia. Pediatrics 2005;116:140-3.  Back to cited text no. 1
    
2.
Arber DA, AttilloOrazi, Hasserjian R, Thiele J, Michael J, Borowitz, et al. The 2016 revision to the WHO classification of myeloid neoplasms and acute leukemia. Blood 2016;127:2391-405.  Back to cited text no. 2
    
3.
Tefferi A. Classification, diagnosis and management of myeloproliferative disorders in the JAK2V617F era. Hematology Am Soc Hematol Educ Program 2006:240-5.  Back to cited text no. 3
    
4.
Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002;100:2292-302.  Back to cited text no. 4
    
5.
Andolina JR, Neudorf SM, Corey SJ. How I treat childhood CML. Blood 2012;119:1821-30.  Back to cited text no. 5
    
6.
Johansson B, Fioretos T, Mitelman F. Cytogenetic and molecular genetic evolution of chronic myeloid leukemia. Acta Haematol 2002;107:76-94.  Back to cited text no. 6
    
7.
Faderl S, Talpaz M, Estrov Z, Kantarjian HM. Chronic myelogenous leukemia: Biology and therapy. Ann Intern Med 1999;131:207-19.  Back to cited text no. 7
    
8.
Hijiya N, Millot F, Suttorp M. Chronic myeloid leukemia in children: Clinical findings, management, and unanswered questions. Pediatr Clin North Am 2015;62:107-19.  Back to cited text no. 8
    


    Figures

  [Figure 1]



 

Top
Previous Article  Next Article

    

  Site Map | What's new | Copyright and Disclaimer
  Online since 1st April '07
  2007 - Indian Journal of Cancer | Published by Wolters Kluwer - Medknow