Infantile acute megakaryoblastic leukaemia with T(1:22) in a non-down syndrome child.

Megakaryoblastic leukaemia is the commonest form of leukaemia occuring in Down syndrome infants. However, it’s subtype with translocation t(1;22)(p13;q13)is uncommon comprising <1% of all cases and reported to exclusively occur in infant without Down syndrome. It has a female predominance and carries apoor prognosis. We described this rare form of leukaemia in a 9-month-old girl who presented with bruises, massive hepatosplenomegaly and multiple cervical and inguinal lymphadenopathy. The blood film showed severe anaemia with ovalostomatocytosis, thrombocytopenia and mild leucocytosis. The bone marrow aspirate showed numerous blasts showing high nuclear-cytoplasmic ratio and agranular cytoplasm with cytoplasmic blebs. Peroxidase staining was negative. The immunophenotyping of the blasts showed positive expression of CD117, CD13, CD33 and CD61 which confirmed the diagnosis of acute megakaryoblastic leukaemia. Interestingly, the cytogenetic finding of translocation t(1;22) which is most common in acute megaloblastic leukaemia in infants without Down syndrome was found in this case. She received the AML trial 15 ADE protocol chemotherapy regime and developed severe neutropenic sepsis and respiratory distress requiring ventilatory support and granulocyte colony stimulating factor (G-CSF). She recovered wellmafter the first course of chemotherapy and was discharged. Unfortunately, she was not brought in for follow-up chemotherapy and presented a few months later with relapsed AML. She was re-started on ADE protocol and currently is on oral thioguanine for maintenance therapy

The Msi2 protein expression positive correlation with favorable cytogenetics findings in AML

Acute myeloid leukaemia (AML) is the most common subtype of acute leukaemias with a poor outcome. Msi2 protein is a newly discovered prognostic marker and it has been considered as a new target for therapy in AML. The study of Msi2 protein expression in AML cases has not been performed in Malaysia, to date. The main aim of the present study was to observe the expression of Msi2 protein in AML patients by immunohistochemistry (IHC) and to correlate its expression with the well-established prognostic and clinical parameters in AML as well as the overall survival (OS). Sixty four bone marrow trephine biopsy sections were immunostained for Msi2 protein. The percentage of blasts with positive reaction and the intensity of the cytoplasmic and nuclear staining were evaluated. The expression of Msi2 protein was found in 95.3% cases with Msi2 pattern varying between the cases. In 71.9% of cases, the blasts showed total cellular positivity and 23.4% cases showed only cytoplasmic positivity. Majority showed high expression of Msi2 for cytoplasmic staining. Interestingly, there was significant correlation between total cellular staining and the intermediate cytogenetic subgroup (P= 0.04). In conclusion, the results showed that the majority of the patients had high expression of Msi2 but this did not correlate to OS. However, the Msi2 expression correlated to the cytogenetic findings. The results suggest future extensive research to be conducted in order to ascertain the exact role of Msi2 positive blast cells in AML in our population and their association with prognosis and outcome

Idiopathic hypereosinophilic syndrome with unusual presentation : two case reports and review of literature

Idiopathic hypereosinophilic syndrome (HES) is an uncommon disorder which usually presents with prolonged and significant primary eosinophilia with end-organ dysfunction. Damaging proteins released by the eosinophilic granules are responsible for the tissues and organ system damage. Here we report two cases of idiopathic HES. Both the patients were young lady presented with high grade fever and concomitant symptoms. Laboratory findings showed leucocytosis with predominant neutrophilia and marked eosinophilia. A diagnosis of idiopathic HES was made after excluding secondary causes of eosinophilia. However, the first patient was complicated with multiple venous thrombosis and intravenous heparin was started which was later changed to subcutaneous low molecular weight heparin (LMWH). The patient developed pleural effusion and consolidation. Intravenous Tazoscin, tablet Prednisolone and tablet Hydroxyurea was started and the patient responded well. Despite treatment, two weeks later, suddenly the patient collapsed and unfortunately succumbed. On the other hand, the second patient was complicated with fever, thrombocytopenia, haemolytic anaemia, acute renal failure and neurological deficit which were part and parcel of thrombotic thrombocytopenic purpura (TTP). Plasma exchange was commenced and patient’s condition had slowly improved. Nevertheless, the hypoxia which she sustained during the multiple episodes of fits had resulted in permanent brain injury and thus requiring a tracheostomy for prolonged ventilatory support. Currently, there is no cure for HES. The main aim of treatment is to minimise the tissue damage caused by the hypereosinophilia. Early diagnosis and intervention are therefore crucial in preventing the spread of the disease and the end-organ damage

Concomitant BCR-ABL and JAK2 V617F in a patient with myeloproliferative neoplasm: a case report

Myeloproliferative neoplasm (MPN) is a clonal proliferation of the haematopoietic stem cells leading to activated tyrosine kinase signaling activity. Myeloproliferative neoplasm is classified into BCR-ABL positive chronic myeloid leukemia (CML) and BCR-ABL negative MPN which harbors JAK2 V617F mutation in most cases. The genetic combination of BCR-ABL and JAK2 V617F mutation is rare with estimated frequency of 0.4% based on recent study. Herein, we reported a case of a man diagnosed with CML detected by fluorescence in-situ hybdridisation (FISH) showing atypical BCR-ABL fusion pattern in 29% nucleated cells (cut-off levels ≥5% for positive signals) in the presence of JAK2 V617F mutation. However, the BCR-ABL transcript was not detected by the conventional reverse transcriptase-polymerase chain reaction (RT-PCR) method which was specific for major fragments. Interestingly, complete hematological remission was not achieved despite initiation of tyrosine kinase inhibitor (Imatinib). In conclusion, it is imperative to scrutinise CML cases for concomitant JAK2 V617F mutation especially patients with atypical clinical or laboratory findings. Therefore, close monitoring with clinical and ancillary technique especially FISH and molecular methods such as DNA sequencing were crucial to help achieve complete hematological, cytogenetic and deep molecular response alongside targeted therapy

Early lineage switch from T-acute lymphoblastic leukaemia to common B-all.

Leukaemic stem cells have heterogenous differentiation potential. The immunophenotypes of blast cells are usually consistent throughout the disease course even at relapse. Rarely, blast cells may undergo a ‘lineage switch’ during the course of disease especially during relapse. We would like to highlight such a case in a 10-year old boy who presented with a two weeks history of lethargy, poor appetite, low grade fever, respiratory distress, cardiac failure, generalized oedema and hepatosplenomegaly. Full blood count showed a leucocyte count of 41.5x109/L and platelet count of 37x109/L. The peripheral blood film showed presence of numerous blast cells. Bone marrow aspiration revealed a hypercellular marrow, which consisted of mainly blast cells with high nuclear to cytoplasmic ratio and inconspicuous nucleoli. Immunophenotyping and cytochemistry results were consistent with the diagnosis of T-cell acute lymphoblastic leukaemia. The patient achieved remission after treatment with UK ALL 97 protocol, regime B chemotherapy. However, he relapsed seven months after the initial diagnosis with 26% blast cells in the bone marrow aspirate. The majority was L1 blast cells admixed with some L2 blast cells. Immunophenotyping was consistent with common precursor B acute lymphoblastic leukaemia. The treatment was changed to a more lineage specific chemotherapy. Nonetheless, the patient never achieved remission and was planned for palliative management. This case illustrated a unique and rare case of rapid lineage switch from T-cell acute lymphoblastic leukaemia to common precursor B-cell acute lymphoblastic leukaemia

Biphenotypic acute leukemia: a report of two cases

We report two cases of biphenotypic acute leukaemia diagnosed in Hospital Universiti Kebangsaan Malaysia (HUKM), their clinical, haematological characteristics and response to chemotherapy. Both patients are middle-aged ladies who presented with hepatosplenomegaly and high white cell count, mainly composed of blast cells. Their bone marrow aspirations were hypercellular comprising of more than 90% heterogenous blast cells. Cytochemical analyses show more than 3% positivity towards peroxidase, with smaller blasts showing block positivity towards PAS. Immunophenotypically, the blasts showed dual expression of CD 33 and CD 19, CD 19 and CD34, intra CD22, intra TdT and intraMPO. One of the patients showed presence of the Philadelphia chromosome on cytogenetic analysis which was confirmed by Fluorecsence In Situ Hybridisation (FISH). Molecular analysis also showed presence of the BCR-ABL fusion protein. Both patients were given combination chemotherapy consisting of daunorubicin and cytosine arabinoside.However, the patient with positive Philadelphia chromosome BCR-ABL did not achieve morphological remission after induction chemotherapy. In view of the poor prognosis of this disease, both the patients were planned for upfront peripheral blood stem cell transplantatio