Sonia Parikh

Clinical relevance of FLT3 receptor protein expression in Indian patients with acute leukemia

Aim:  FLT3 is a receptor tyrosine kinase that plays an important role in the pathogenesis of leukemia. The present study aimed to evaluate the role of FLT3 protein in patients with acute leukemia.

A rare complication in a case of multiple myeloma on therapy with thalidomide and dexamethasone—Reversible posterior lobe leukoencephalopathy

Central nervous system involvement is an unusual manifestation of multiple myeloma. We report a case with a rare manifestation of multiple myeloma in the form of reversible white matter changes of occipital lobes presenting with blindness. This 45-year-old postmenopausal female presented to us (in March 2005) with complaints of lethargy, breathlessness on exertion and generalised bone pains of 3 – 4 months duration. General clinical examination was normal except presence of pallor and pedal edema. Systemic examination was also essentially normal except for presence of a threefinger palpable soft liver enlargement and a just palpable firm spleen. Investigations revealed the following picture: hemoglobin at 5 gm%, total leucocyte count of 5300 with a differential count of 60% polymorphs and 27% lymphocytes and no atypical cells, platelet count of 90000/c.mm. The ESR was 150 mm/hr. Biochemistry was normal except for a serum albumin level of 2.7 gm/dl and a globulin level of 5.3 gm/dl suggesting a reversed albumin/globulin ratio. Serum electrophoresis revealed a prominent monoclonal band. Quantitative serum immunoelectrophoresis revealed significantly high serum IgG levels of 2213 mg/dl (normal level1⁄4 650 – 1500 mg/dl) and a low IgM level of 50 mg/dl (normal level1⁄4 60 – 280 mg/dl). Serum beta-2-microglobulin level was normal (1.85 micro gm/ml). Ultrasound of the abdomen was suggestive of hepatomegaly with fatty infiltration and splenomegaly without alteration of echotexture. Bone marrow aspiration showed hypercellular marrow with infiltration by 95% atypical plasma cells. Conventional cytogenetic study showed normal XX karyotype. FISH study for deletion 13q was negative. Skeletal survey showed multiple punched out lytic lesions in bones. On routine screening, the patient was detected to be hepatitis B surface antigen positive. Considering the diagnosis as multiple myeloma stage III A, she was put on combination therapy with thalidomide and high dose dexamethasone every 28 days (thalidomide at a dose of 200 mg/day and dexamethasone at a dose of 40 mg/day from day 1 to day 4, day 9 to day 12 and day 17 to day 20 on even cycles and day 1 to day 4 only on odd cycles), along with cotrimoxazole prophylaxis and lamivudine for hepatitis B. After two such cycles she had a very good response with improvement in symptoms, resolution of anemia and thrombocytopenia with normalization of hemoglobin and platelets. Serum protein levels and electrophoresis became normal. Repeat quantitative immunoelectrophoresis was also normal. The dose of thalidomide was increased to 300 mg/ day in the third cycle. When she came for fourth cycle she was having sensory symptoms in lower limbs without evidence of motor weakness, suggestive of

Enhancement of the cytotoxic effects of Cytarabine in synergism with Hesperidine and Silibinin in Acute Myeloid Leukemia: An in-vitro approach

OBJECTIVES Acute Myeloid Leukemia (AML) therapy continues to be a daunting challenge. Cytosine Arabinoside (Ara-C) is widely used to treat hematological malignancy in humans, but often becomes ineffective because of increased resistance to the drug which may lead to a worse prognosis. Therefore new strategies are needed to understand the mechanism responsible for drug resistance and to develop new therapies to overcome it. Research evidence based on natural compounds used alone or in combination with current chemotherapeutic agents proved their efficacy to treat and prevent cancer. Hesperidin and Silibinin displayed anti-cancer activity against various types of cancers and cell lines and can be used in combination with Cytarabine with the aim to increase cytotoxicy profile and reduction in drug resistance. Experimental Work: Primary cells obtained from AML patients bone marrow were used to develop in-vitro model and further exposed to various concentration of Cytarabine (10 nM-5000 nM), Hesperidin (0.5 μM-100 μM) and Silibinin (0.5 μM-100 μM) alone and in combination with Cytarabine (Hesperidin-25 μM, Silibinin10 μM) to check cytotoxicity using MTT assay. Synergistic effect was evaluated by Combination Index method. RESULT AND CONCLUSION In-vitro study of Hesperidin and Silibinin indicated their cytotoxicity at IC 50 value 50.12 μM and 16.2 μM, respectively. Combination Index study revealed Hesperidin and Silibinin both showed synergistic potential and decreased the IC 50 value of Cytarabine by ~5.9 and ~4.5 folds, respectively. Both natural compounds showed potential anti-leukemic activity hence may be used for AML therapy alone or in combination with other chemotherapeutic agents.

Successful Allogeneic Hematopoietic Stem Cell Transplantation of a Patient Suffering from Type II Congenital Dyserythropoietic Anemia A Rare Case Report from Western India

The most frequent form of congenital dyserythropoiesis (CDA) is congenital dyserythropoietic anemia II (CDA II). CDA II is a rare genetic anemia in humans, inherited in an autosomally recessive mode, characterized by hepatosplenomegaly normocytic anemia and hemolytic jaundice. Patients are usually transfusion-independent except in severe type. We are here reporting a case of severe transfusion-dependent type II congenital dyserythropoietic anemia in a 5-year-old patient who has undergone allogeneic hematopoietic stem cell transplantation (HSCT) at our bone marrow transplantation centre. Patient has had up until now more than 14 mL/kg/month of packed cell volume (PCV), which he required every 15 to 20 days to maintain his hemoglobin of 10 gm/dL and hematocrit of 30%. His pre-HSCT serum ferritin was 1500 ng/mL and he was on iron chelating therapy. Donor was HLA identical sibling (younger brother). The preparative regimen used was busulfan, cyclophosphamide, and antithymocyte globulin (Thymoglobulin). Cyclosporine and short-term methotrexate were used for graft versus host disease (GVHD) prophylaxis. Engraftment of donor cells was quick and the posttransplant course was uneventful. The patient is presently alive and doing well and he has been transfusion-independent for the past 33 months after HSCT.

A retrospective study of central venous catheters GCRI experience

Background: The use of central venous catheters (CVCs) has greatly improved the quality-of-care in cancer patients, yet these catheters may cause serious infectious and thrombotic complications. The aim of this retrospective study was to study the various types of CVCs and their complications. Materials and Methods: We studied retrospectively 213 cases of CVCs in our institute with their indications, type and complications from August 2010 to July 2011. Results: A total of 213 CVCs were inserted in patients with hematological (62%) and solid organ malignancies (38%). Ninety-eight patients (46%) had peripheral inserted central catheter (PICC), 90 (42%) patients had Hickman catheters and 25 (12%) had a port. The median duration of retention of Hickman catheters was 104 days (3-365 days), for the peripherally inserted central catheters was 59 days (3-100 days) and for the port it was 280 days (45-365 days). Non-infective complications were more than infective (12% vs. 7%). The most common complication was non-infective occlusion and thrombophlebitis. In one patient with PICC thrombosis occurred in the cephalic, radial and ulnar vein and in one patient with port thrombosis occurred in the superior vena cava. Organisms were isolated in 60% (12 out of 20) of cultures. Common organisms isolated were Pseudomonas aeruginosa in 5 (42%), Staphylococcus aureus in 2 (16%), Escherichia coli in 2 (16%) and Aspergillus in 3 (25%) patients. 7 out of 12 infected patients had negative blood cultures within 7 days of antibiotic treatment, 5 patients remained positive for more than 7 days with antibiotics. In 155 patients (73%), the desired treatment protocol was completed and at present there are still 28 patients (13%) with catheters. 5 patients (2.3%) died of febrile neutropenia and septicemia with multi-organ failure. In 5 patients (2.3%), the catheters (1 Port, 1 Hickman and 3 PICC) were prematurely removed because of thrombosis. Conclusion: CVCs are better options to facilitate the long-term vascular access provided infection is prevented with meticulous care and treated promptly with proper antibiotics. Most CVCs is acceptable to patients.

Primary vaginal myeloid sarcoma: a rare case report and review of the literature.

Myeloid sarcoma (chloroma, granulocytic sarcoma, or extramedullary myeloid tumour) is an extramedullary mass forming neoplasm composed of myeloid precursor cells. It is usually associated with myeloproliferative disorders but very rarely may precede the onset of leukemia. Here, we are presenting a rare case of primary vaginal myeloid sarcoma in a geriatric female patient without initial presentation of acute myeloid leukemia (AML). A 68-year-old female patient with ECOG Performance Score of 1 presented with pervaginal bleeding for 20 days. On colposcopic examination, she was found to have mass in the anterior fornix of vagina. A punch biopsy specimen revealed chloromatous infiltration of the vagina. LCA (leukocyte common antigen), MPO (myeloperoxidase), and c-kit were strongly positive on IHC (immunohistochemistry). The patients routine blood investigations were normal including peripheral smear, lactose dehydrogenase, uric acid, 2D echocardiography, conventional cytogenetics, bone marrow aspiration, and biopsy. The patient was given 4 cycles of decitabine (Decitex, manufactured by Sun Pharmaceutical Industries Limited, India), 20 mg/m2 for 5 days at an interval of 28 days. There was a partial response to decitabine according to RECIST criteria. As decitabine therapy was well tolerated, we are continuing in the same way until disease progression without any complications. The patient is undergoing regular follow-up at our centre.

Primary Hepatic Burkitt Lymphoma: A Bizarre Site and Triumph Tale

Primary hepatic Burkitt lymphoma (PHBL) is an extremely rare form extra nodal lymphoma and till now only 11 case reports have been found in the literature. We are reporting an adult female with primary hepatic Burkitts lymphoma, who achieved complete remission after 5 months of combination chemotherapy containing vincristine, cyclophosphamide, doxorubicin, methotrexate, prednisolone and intrathecal chemotherapy. She is under regular follow up at our institute.

Paraneoplastic Recurrent Hypoglycaemic Seizures: An Initial Presentation of Hepatoblastoma in an Adolescent Male—A Rare Entity

Hepatoblastoma (HB) is a rare malignant tumour of the liver and usually occurs in the first three years of life. Hepatoblastoma in adolescents and young adults is extremely rare; nevertheless the prognosis is much worse than in childhood, because these kinds of tumours are usually diagnosed late. Characteristic imaging and histopathological and AFP levels help in the diagnosis of hepatoblastoma. Paraneoplastic features of hepatoblastoma are not uncommon at presentation and include erythrocytosis, thrombocytosis, hypocalcaemia, isosexual precocious puberty, and rarely hypoglycaemia. Even though hypoglycaemia is commonly seen in hepatocellular carcinoma, its association with hepatoblastoma is very rare. We present a case of 15-year-old male patient presenting with complaints of recurrent hypoglycaemic seizures ultimately leading to diagnosis of hepatoblastoma. Managed successfully with neoadjuvant chemotherapy, surgery and adjuvant chemotherapy with adriamycin and cisplatin based regimens. An extensive review of literature in the PubMed and MEDLINE did not reveal much data on paraneoplastic recurrent hypoglycaemic seizures as an initial presentation of hepatoblastomas in adolescents and young adults.

Primary Synovial Sarcoma of Kidney: A Rare Differential Diagnosis of Renomegaly

Synovial sarcomas (SS) are classified as subgroup of soft tissue sarcomas affecting mainly extremities of young adults. Primary SS of kidney are very rare tumours with poor prognosis. Though they have characteristic histology and immunohistochemistry (IHC) due to rarity of incidence it is difficult to diagnose them. Sometimes chromosomal rearrangement studies are required to confirm the diagnosis. We are presenting a case of 41-year-old male who was referred to our cancer centre for evaluation of left renal mass. CT scan of abdomen revealed a large left renal mass encasing the aorta. Biopsy of renal mass revealed poorly differentiated sarcoma and IHC was positive for vimentin, CD99, and BCL2 and negative for AE1, epithelial membrane antigen, and leukocyte common antigen. The patient was clinically inoperable as renal mass was encasing the aorta. So he was subsequently offered palliative chemotherapy in form of ifosfamide and adriamycin. CT abdomen shows partial response after 3 cycles of chemotherapy according to RECIST criteria.

Central retinal artery occlusion, an early sign of crizotinib resistance in an alk positive adenocarcinoma of lung: A rare case report.

About 4% of non‐small‐cell lung carcinomas involve an EML4‐ALK tyrosine kinase fusion gene and occur almost absolutely in carcinomas arising in non‐smokers. Crizotinib, the first inhibitor of anaplastic lymphoma kinase (ALK), ROS1 and c‐Met receptor kinase, has been used in the treatment of ALK‐positive non‐small cell lung cancer. Side effects of crizotinib mostly consist of grade 1–2 gastrointestinal events (nausea, vomiting, diarrhea and constipation), grade 1–2 edema and fatigue; grade 1 visual disorders, rare cases of elevated liver enzymes and pneumonitis. We are presenting a case of adenocarcinoma of lung, who progressed on first‐line chemotherapy and received crizotinib as second line therapy for 9 months. Patient has very good partial response to crizotinib and had some side effects of crizotinib like nausea, vomiting, diarrhea, fatigue, asthenia and anorexia, asymptomatic transaminitis in the first 2 to 3 weeks of therapy and managed symptomatically. But after 9 months, he developed sudden onset left sided vision loss. On fundoscopic examination he was found to have “cherry red spot” and fundus flourescein angiography revealed central retinal artery occlusion (CRAO). After 15 days of vision loss patient developed pleural effusion, and pleural fluid cytology was positive for malignant cells. Visual symptoms are very well known in the literature as side effects of crizotinib, but CRAO is not yet been documented. As this patient is not having any prothrombotic state like diabetes, hypertension, atherosclerosis, hyperhomocysteinemia or any genetic disorders except malignancy. Hypercoagulability disorders are known to be commonly associated with a variety of cancer types including lung cancer. This appears to be a sign of early crizotinib resistance in this patient because there was no history of prior hypercoagulable state. To the best of our knowledge this is the first case report in the world literature, as CRAO presenting as a sign of crizotinib resistance in an adenocarcinoma of lung patient who was on crizotinib.