Chronic Myeloid Leukemia: Clinico-Hematological Profile from Southern Pakistan

Background: Chronic myeloid leukemia is a form of chronic myeloproliferative disorder described by the presence of specific haematological and cytogenetic markers. It is a very common blood neoplasm that usually requires a basic clinical history, review, and regular blood examination to diagnose. If detected early, it has a high cure rate. Objective: To assess the clinical and laboratory features of chronic phase chronic myeloid leukemia patients. Study Design: Cross-sectional study Place and Duration of Study: Department of Haematology, Liaquat National Hospital and Medical College, Karachi 1st January 2012 to 31st December 2016 Methodology: One hundred and forty four chronic myeloid leukemia patients visited the study site during this period, of which 132 were in the chronic phase and met the eligibility criteria. The patient’s data, including age, gender, clinical and laboratory parameters were obtained. Results: One hundred and fifteen (87.1%) had constitutional symptoms, predominantly fatigue and abdominal discomfort. The clinical presentation displayed splenomegaly among 89.3% of patients with a mean spleen span of 18.9±3.7 cm and massive splenomegaly in 32.5% of patients. Haematological presentation at baseline showed that the mean haemoglobin level of the enrolled patients was 9.6±2.0g/dl, TLC was 167.6±123.3x109/l, and platelet count was 398.7±281.9x109/l. Furthermore, 19.4%of patients were anaemic, and hyperleukocytosis was detected in 24.2%. High LDH, hyperuricemia and elevated serum creatinine were present in 38.6%, 40.9%, and 14.3%, respectively. Conclusion: Unlike the western countries, chronic myeloid leukemiais more prevalent in a very young age group in Pakistan. The chronic myeloid leukemia patients displayed variable clinical and haematological presentation. Constitutional symptoms and splenomegaly were consistent features among the majority of patients. Keywords: Chronic myeloid leukemia, Clinico-hematological, Pakistan

Polycythaemia Rubra Vera With Incisional Hernia Surgery- A Very Rare Case Report

Polycythaemia rubra vera is a chronic myeloproliferative disorder that is characterized by excessive red cell production and unlike other forms of polycythaemia, it can cause both bleeding and thrombosis in the same patient. Only few cases have been reported in the literature where polycythaemia rubra vera with surgery was performed successfully .The ideal peri-operative management is currently unknown. Here we present a case of 50 yrs old lady with polycythaemia rubra vera underwent open mesh repair for incisional hernia. After operation, the patient developed hemorrhagic complications needing resuscitation with blood and plasma expander. The patient was managed efficiently. Considering its very rarity, we are reporting the case. J Dhaka Medical College, Vol. 27, No.2, October, 2018, Page 218-222

Increased Prevalence of t(8;9)(p21-23;p23-24) Translocations within 9p24 Abnormalities in Patients with Myeloid Malignancies Identified from the Mitelman Database

Background: Advances in detailing the interaction between tumor cells and host immune system has led to the potential of targeted immunotherapy. One target is the programmed death 1 (PD-1) pathway, which cancer cells up-regulate to evade T-cell-mediated immune response. Blockade of PD-L1 or PD-L2 has shown efficacy in solid tumors, as well as classic Hodgkin's lymphoma (cHL) and primary mediastinal b-cell lymphoma (PMBCL). In cHL and PMBCL, amplification or rearrangement of chromosome 9p24.1 is implicated in their pathogenesis. The genes PDL1 and PDL2 are located on 9p24.1, along with JAK2, which further induces PDL1 and PDL2. Targeted inhibitors of JAK2 are utilized in some myeloid malignancies (MM), mostly as gain of function point mutations. The aim of this study is to determine the prevalence of and classify 9p24.1abnormalities across subtypes of MM to guide future studies for targeted therapy. Methods: A service of the National Cancer Institute, theMitelman Database of Chromosome Aberrations and Gene Fusions in Cancer database is manually updated from the literature and organized into three sub-databases: cases of chromosomal aberrations, molecular biology and clinical associations, and references. We searched for the 9p24 breakpoint within hematologic malignancies with no other search limits and subsequently divided the cases into myeloid and lymphoid subtypes. The incidence of rearrangements and additions in chromosome 9p24 for myeloid subtypes were determined. Those with either incidence >0.5% ort(8;9)(p21-23;p23-24) translocations are reported. Results: 9p24 alterations occurred in 92 of 25,284 cases (<0.4%) of MM across 24 subtypes, with 22 (<0.1%) of these additions. Of subtypes with at least 100 cases, 9p24 alterations in chronic myeloproliferative disorder, NOS (7/326, 2.1%) and idiopathic myelofibrosis (3/311, 1.0%) were the most common. Chronic myeloid leukemia (CML),t(9;22),myelodysplastic syndrome and acute myeloid leukemia (aml) had <1% incidence of 9p24 rearrangements and additions. Myelodysplastic/myeloproliferative disease, NOS (5/61, 8.2%), atypical CML (4/61, 6.6%) and chronic eosinophilic leukemia (CEL)/hypereosinophilic syndrome (4/65, 6.2%) contained the most frequent 9p24 alterations. Notably,t(8;9)(p21-23;p23-24) translocations accounted for 21/92 (22.8%) MM 9p24 alterations and were seen in 8 subtypes:myelodysplastic/myeloproliferative disease, NOS (5 cases), CEL/hypereosinophilic syndrome (4), atypical CML (3), chronic myeloproliferative disorder, NOS (3), aml-m1 (2), aml-m2 (2), aml-m6 (1), and idiopathic myelofibrosis (1). One patient with aml-1 and one with chronic myeloproliferative disorder was found with t(9;22)(p24;q11). Conclusions: Despite a low incidence of 9p24 rearrangements and additions across all MM within the Mitelman database, t(8;9)(p21-23;p23-24) translocations were seen in 8 MM subtypes and accounted for 22.8% of observed alterations. This translocation results in the fusion of PCM1-JAK2, leading to activation of Janus Kinase 2. Other than two patients with t(9;22)(p24;q11), harboring fusion of BCR-JAK2,no other rearrangements involving JAK2 were identified.While the use of JAK2 inhibitorruxolitinib has been described in 3 patients with t(8;9)(p21-23;p23-24), 2 with chronic eosinophilic leukemia and 1 with myeloproliferative disease, other MM subtypes with this translocation have not been evaluated. Further, no study has assessed such cases with FISH and other testing to streamline potential forPD-L1 or PD-L2 inhibitors. This data supports the utility of theMitelman database to identify alterations that can be further evaluated for targeted therapy and clinical trials. Disclosures No relevant conflicts of interest to declare.

Long-term Use of Anagrelid in Essential Thrombocythemia Treatment of a Child Under 12 Months

Abstract 5072 Essential thrombocythemia (ET) is currently classified as a chronic myeloproliferative disorder. Anagrelide is a novel platelet lowering agent that has recently been approved for use n ET. We present the case of ET in an 8 –month- old girl, who was treated with Anagrelid for 13 months. The girl was admitted to hospital because of elevated platelet count. She had stomach pains periodically. On admission the child's condition was good but on palpation her stomach was sore and her spleen was enlarged. Laboratory investigations showed an elevated platelet count (1. 5m) and hypercalemia (6. 3mEq/l). Thrombopoetin was normal. Acesan was added to the treatment. A morphology performed after 1 month revealed further elevation of platelets (up to 2. 65m). On the basis of laboratory investigations, bone-marrow biopsy and trepanobiopsy, we eliminated an oncological disease and infectious diseases of connective tissues. On bone-marrow investigation, acquired mutation of JAK2 (V617F) tyrosine kinase was diagnosed, which confirmed ET. On account of the growing number of platelets, which was life - threatening, we decided to administer anagrelid, starting with a dose of 0. 25 mg per day. The number of platelets decreased to 1. 4m, so the dose was increased to 0. 25 mg twice daily after 3 weeks. At present, after 37 months of anagrelide treatment, the number of platelets in the child ranges between 400 and 650. The patient visits our, department for monthly check-up (morphology, biochemical tests, ECG and echocardiography). In international literature there is no information on the use of Anagrelid in ET treatment of children under 12 months old. However, on the basis of our observations and initial results of treatment, it seems that the above protocol for Anagrelid administration is safe for infants of this age. Disclosures: No relevant conflicts of interest to declare.

Idiopathic myelofibrosis mimicking hemolytic anemia

Idiopathic Myelofibrosis is an infrequent chronic myeloproliferative disorder characterized by varying degrees of bone marrow fibrosis and extra medullary hematopoiesis, with the fibrosis being a reactive phenomenon to a neoplastic proliferation of a pluripotent hematopoietic stem cell. Idiopathic Myelofibrosis is heterogeneous in presentation and clinical course, with anemia being one of the most important problems. We present a case of a 59 year old male who presented with severe anemia, the peripheral blood picture mimicking hemolysis with numerous schistocytes and teardrop cells.Journal of Pathology of Nepal (2012) Vol. 2, 323-327DOI: http://dx.doi.org/10.3126/jpn.v2i4.6888

Celiac Artery Thrombosis and Superior Mesenteric Artery Stenoses with Essential Thrombocythemia: A Case Report

Thrombosis of the celiac artery trunk is a rare cause of acute abdominal pain. Thrombosis of the celiac artery carries a high mortality and morbidity when the diagnoses and treatment are delayed. It is frequently associated with other cardiovascular events. The most common etiology is atherosclerosis. 20–30% of cases may have symptoms of chronic mesenteric ischemia. Main goal of the treatment is to reestablish the diminished or stopped mesenteric blood flow and to avoid end-organ ischemia. Essential thrombocythemia is a chronic myeloproliferative disorder characterized by marked increase in thrombocyte number and clinical presentation may be with thrombotic episodes, hemorrhage, or both. To our knowledge this is the first report of celiac artery thrombosis and superior mesenteric artery stenoses in a patient with essential thrombocythemia. The patient was managed successfully with surgical treatment.

The CYTO-PV: A Large-Scale Trial Testing the Intensity of CYTOreductive Therapy to Prevent Cardiovascular Events in Patients with Polycythemia Vera

Polycythemia vera (PV) is a chronic myeloproliferative disorder whose major morbidity and mortality are thrombohaemorragic events. Current guidelines advise maintaining hematocrit (HCT) level below 45% in males and 42% in females. Such targets lean on pathophysiological reasoning, while evidence from ECLAP and PVSG-01, the two largest prospective studies in this disease, suggests no difference in the rate of thrombosis in patients maintained at different HCT values below 50%–52%. Cytoreductive therapy in PV (CYTO-PV) is a multicenter, randomized, and controlled trial assess the benefit/risk profile of cytoreductive therapy with phlebotomy or HU aimed at maintaining HCT < 45% versus maintaining HCT in the range 45%–50%. CYTO-PV is being conducted in the framework of the Gruppo Italiano Malattie Ematologiche nell'Adulto (GIMEMA) and is funded by the Italian Drug Agency (AIFA). It is an independent trial with broad recruitment criteria to mimic clinical practice. We describe here the study and its advancement status. Conclusions. Clinical research in rare disease can be carried out with limited funds, provided a research hypothesis is felt as clinically relevant by a scientific community willing to share knowledge on the outcome of clinical practice, thus producing scientific results useful to improve treatment and prognosis of patients.