|LETTER TO THE EDITOR
|Ahead of print
Pediatric chronic myeloid leukemia with myeloid blast crisis and complex karyotype at presentation
Sudha Sazawal, Kanwaljeet Singh, Sunita Chhikara, Rekha Chaubey, Pravas Mishra, Tulika Seth, Renu Saxena
Department of Hematology, All India Institute of Medical Sciences, New Delhi, India
|Date of Submission||22-Apr-2017|
|Date of Decision||11-Jun-2020|
|Date of Acceptance||12-Jun-2020|
|Date of Web Publication||20-Jul-2020|
Department of Hematology, All India Institute of Medical Sciences, New Delhi
Source of Support: None, Conflict of Interest: None
|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. 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|
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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. 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. 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., About 80%–85% of CML-BC cases undergo karyotypic evolution with most common karyotypic changes being +8, +Ph, i (17q), and +19., 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. Even in children, CML-BC may be the initial presentation and should always be differentiated from “AML with BCR-ABL1.”
The authors wish to acknowledge Mr. Rajender and Mr. R. Jaiswal for technical assistance.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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