DISCUSSION;
Lymphoma is the third most common childhood malignancy accounting for
10-12% of childhood cancers. NHL account for 7% of cancers in children
<20 yrs of age2 . T-LBL is the most common
paediatric T cell Lymphoma. They develop in lymphoid tissues such as
lymph nodes and spleen or outside of lymphoid tissues like
gastrointestinal tract, liver, nasal cavity, skin etc. CML is rare in
children & constitutes 2% of all leukemias in children younger than 15
years and 9% of all leukemias in adolescents between 15 and 19 years3About 90-95 percent of children with CML have a
genetic alteration called the Philadelphia chromosome.
Atypical chronic myeloid leukemia, BCR-ABL1 negative (aCML) is a
rare myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) in
children. Currently, the diagnosis of aCML is reached primarily on
morphology-based criteria. The main feature characterizing aCML is the
presence of neutrophilic leucocytosis and marked dysgranulopoiesis.
Moreover, to fulfil the diagnostic criteria, WBC should be ≥ 13 ×
109/L with ≥ 10% of immature granulocytes, and ≤ 20%
blasts in the blood and the BM 4,5. To
rule out other myeloproliferative
disorders, BCR-ABL1 rearrangement should be excluded in all cases6.
There has been case report of secondary malignancies in
CML7 . Fu X et al9 reported
simultaneous diagnosis of T-LBL and BCR-ABL positive CML in two adult
patients reported which were treated with imatinib and HYPER-CVAD.
Chemotherapy. Simultaneous AML and lymphoma has been reported in
literature and is more frequent than simultaneous CML and lymphoma9. Melikian AL etal reported 20 adult patients with
synchronous and metachronous tumors10.
Our index patient fulfilled the criteria of both T-NHL based on
immunohistochemistry and typical morphology on lymph node biopsy and
BCR-ABL negative CML on Bone marrow. This association, till to date, has
not been previously described in literature both in adults and children.
Due to rarity of this co existence, little is known about pathogenesis
and optimal treatment plan.
T-NHL is an aggressive malignancy but with the development of
intensified T-ALL–focused protocols has resulted in significant
improvements in outcome in children 11. No standard of
care is currently available for aCML management. Drugs called tyrosine
kinase inhibitors (TKIs) are the first line of treatment for BCR ABL
positive CML. However, the only curative treatment for atypical CML
remains HSCT 12, an option available for the younger
patients only. Participation on clinical trials should be considered in
all cases. Different treatment options like hypomethylating agents
(azacytidine or decitabine)13, Hydroxy urea.
Interferon alpha, AML like therapy or targeted therapies (JAK inhibitor
ruxolitinib, the SRC kinase inhibitor dasatinib, and the MEK inhibitor
trametinib) have been used with variable results in patients not
suitable for BMT 14,15. The prognosis of the
concurrent bi-lineage malignancies is generally poorly understood and
chemotherapy is necessary. More cases are required to optimize
management for such children.