Role of ancillary techniques in diagnosis, therapy and prognosis of a case of precursor B-cell acute lymphoblastic leukemia in an elderly patient

The chromosomal abnormality of Philadelphia chromosome is mostly seen in Chronic Myeloid Leukemia (CML). But it is observed that the Philadelphia chromosome (Ph), t(9,22), is the most common cytogenetic abnormality in adult patients with acute lymphoblastic leukemia (ALL), occurring in about 20% to 30 % of all cases. Patients with Ph-positive ALL have breaks in the minor breakpoint region, m?BCR (exons 1?2) lead to a short fusion proteins (p190) and is most frequently associated with Ph chromosome- positive ALL. They have an increased risk for central nervous system (CNS) involvement, an aggressive clinical course and poor prognosis. Historically, they had an inferior outcome when compared with their Ph-negative counterparts. Adult Ph+ patients achieve Complete Remission rates comparable to Ph? ALL patients with standard chemotherapy, but the remissions are short and survival poor. The addition of tyrosine kinase inhibitors (TKIs) including imatinib has dramatically improved outcomes. We are presenting this case report of t(9;22), p190 BCR-ABL1 positive ALL in an elderly female patient of south Gujarat.

Philadelphia Chromosome Positive Chronic Myelogenous Leukemia In Childhood: A Rare Case Report

CML is a clonal hematopoietic stem cell disorder. As per WHO classification, CML is included in Myeloproliferative disorder. Adult type - CML is rare in childhood constituting about 3% of childhood leukaemia. We have reported such a case in a 7yr old male child. Peripheral blood smear and bone marrow revealed features of chronic myeloproliferative disorder and cytogenetic analysis has proved Ph chromosome positivity. We report one such case of Philadelphia positive CML in a 7 year old male patient with chief complaints of fever on & off since 4-5 months and sense of abdominal fullness since 1 month, on examination pallor was found with mild hepatomegaly and moderate splenomegaly. The clinical differential diagnosis was malaria, storage disorder or tropical splenomegaly. Though biological behaviour and prognosis are identical to that of adult type, we are reporting this case because of its extremely uncommon incidence.

Ponatinib: a miracle or a disaster in chronic myeloid leukemia.

Chronic myeloid leukemia (CML), the most common myeloproliferative disorder, occurring due to balanced reciprocal translocation between chromosome 9 and 22 and resulting in a chimeric oncogene called breakpoint cluster region-abelson (BCR-ABL) whose protein product has tyrosine kinase activity, causes uncontrolled proliferation of the myeloid cells. Although, imatinib, the first-generation tyrosine kinase inhibitor (TKI) achieved an extremely high response rate, some patients developed resistance to it. Thus, second-generation TKIs such as nilotinib, dasatinib, bosutinib were developed which proved very useful, till the emergence of T315I point mutation which occurs in the BCR-ABL gene and renders CML resistant to previous TKIs. Ponatinib, a third generation TKI approved by the United States Food and Drug Administration (FDA), showed great promise as it was effective even against T315I point mutation. However, a recent increase in the incidence of blood clots observed in patients taking ponatinib has resulted in FDA temporarily suspending all trials, marketing and distribution of the drug. Hence, whether ponatinib evolves as a miracle or disaster for the patients of CML is yet to be answered.