Primary Central Nervous System Burkitt Lymphoma in HIV Positive Pediatric Patient: A Rare Case Report.

Burkitt lymphoma is a high-grade B-cell lymphoma with aggressive course of disease and primarily systemic nodal involvement. Primary Burkitt lymphoma with isolated central nervous system (CNS) involvement and that too in pediatric population has been rarely reported. Here, we present a case of a primary Burkitt lymphoma involving brain in an human immunodeficiency virus-positive pediatric patient who was on antiretroviral therapy. Currently, there are no established protocols or guidelines for management of primary CNS Burkitt lymphoma thus posing challenges in the management of such cases. Our patient was successfully treated by surgical resection followed by chemotherapy and radiotherapy.

Clinical and epidemiological profile of neuroendocrine tumors: An experience from a regional cancer center from Western India.

BACKGROUND: Most of the data on neuroendocrine tumors (NETs) are from the Western literature. Indian studies regarding clinicopathological characteristics and treatment outcomes are lacking. METHODS: This is a prospective observational study of all new patients with NETs (except small-cell lung cancer) registered at our tertiary care cancer institute from November 2014 to November 2016. A total of 97 new patients were registered, of which 20 were lost to follow-up before starting any planned treatment. Epidemiological and clinicopathological features of all these 97 patients were studied, and the remaining 77 patients were analyzed for treatment response and survival analysis. RESULTS: The median age at diagnosis was 49 years (20-74 years) with male preponderance (M: F = 1.85:1). The most common primary site of origin was pancreas (34/97 = 35%), followed by unknown primary origin (19%), small intestine (9%), and pulmonary (6%). Of 97 patients, 91 (93.8%) presented with nonfunctional symptoms, 3 (3.1%) had purely functional symptoms, and 3 (3.1%) presented with both functional and nonfunctional symptoms. The most common presenting symptom was abdominal pain (59.7%), followed by jaundice (9.3%), whereas watery diarrhea (83.3%) and flushing (66.7%) were the most common functional symptoms. Sixty-six percent (64/97) of cases were metastatic at presentation. A strong correlation was noted between the primary site of origin and metastatic presentation (P = 0.016). Chemotherapy was the most common primary therapy (40.2%), followed by surgery (28.6%), watchful waiting (15.6%), and somatostatin analogs (11.7%). The median event-free survival was highest for patients undergoing surgery (10 months). CONCLUSIONS: The clinicopathological profile of NETs in the Indian population differs from Western countries. Majority of patients present with metastatic disease, thus representing a need for creating awareness among patients and medical fraternity and formulating Indian guidelines for optimized treatment.

Solitary Plasmacytoma of Bone Involving Spine in a 12-year-old Boy: Report of a Rare Case and Review of Literature.

Solitary plasmacytoma of the bone (SPB) is a rare plasma cell neoplasm representing only about 5% of plasma cell neoplasia. It usually presents as a lytic lesion mainly localized within the axial skeleton. SPB is exceedingly rare in young individuals, and only few cases have been reported so far in patients younger than 20 years of age. In view of rarity of disease, definitive treatment guidelines have not been established. We hereby report a case of SPB involving of lumbar vertebra (L5) in a 12-year-old boy. He was initially treated with antilymphoma therapy and curative radiotherapy considering as primary bone lymphoma. However, he had local recurrence with paraparesis after 9 months which was diagnosed as solitary bone plasmacytoma for which he was treated with decompressive laminectomy and chemotherapy (bortezomib, lenalidomide, and dexamethasone). The purpose of this article is to report a rare case of SPB in a pediatric patient and to review the available literature and treatment options. SPB should be considered in the differential diagnosis of osteolytic bone lesions even in young patients.

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 patient's 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.

Safety and Efficacy of Eltrombopag in Post-hematopoietic Stem Cell Transplantation (HSCT) Thrombocytopenia.

Twelve adult patients (median age 29.5 years) were started on Eltrombopag 25-50 mg/day for post-hematopoietic stem cell transplantation (HSCT) thrombocytopenia. All patients were having primary thrombocytopenia after HSCT. No patient had other secondary cause for thrombocytopenia. Two patients were allogenic subsets (1 acute myeloid leukemia i.e., AML and 1 aplastic anemia), and 10 were autologous transplants (3 multiple myeloma, 6 lymphoma and 1 AML). Nine patients were males, three were females. The median time of starting Eltrombopag was 21 days post-stem cell infusion (range day +17 to +60) at a median platelet count of 9,000/cmm (range 3,000-11,000/cmm). The median duration for treatment was 29 days. Median total dose of 812.5 mg was received by patients and they had a median platelet increment of 36,000/cmm. We observed that there were no adverse effects in these patients and there was a gradual increase in platelet count so that none of the patients had any complication due to thrombocytopenia. The cost of treatment was less than the cost of extended hospitalization and irradiated single donor platelet transfusion.

Improving Outcome of Aplastic Anaemia with HLA-Matched Sibling Donor Hematopoietic Stem Cell Transplantation: An Experience of Gujarat Cancer and Research Institute (GCRI).

Fifteen patients, with a median age of 19 years having severe aplastic anaemia (SAA) underwent human leucocyte antigen (HLA) identical sibling donor hematopoietic stem cell transplantation (HSCT) using conditioning regimens containing cyclophosphamide with antithymocyte globulin (ATG) or a combination of fludarabine and cyclophosphamide with or without ATG during December 2007 to May 2013. Cyclosporine and mini methotrexate were used as graft versus host disease (GVHD) prophylaxis. Graft source included peripheral blood stem cells in 11, bone marrow in 3 and both in 1. One patient had primary graft failure while 14 patients were engrafted with a median neutrophil and platelet engraftment time of 13.5 days. One patient had secondary graft rejection. Acute GVHD occurred in 3 patients and chronic GVHD in 4. One year death rate in engrafted patients was 14.28 %. At a mean follow-up of 21.2 months, 12 (80 %) are alive and well. One of the donors was a patient of haemophilia but the disease did not occur in the recipient. The graft was successful and the recipient is alive till date.

Unrelated Umbilical Cord Blood Transplant for Children with ß-Thalassemia Major.

Beta thalassemia major, one of the most prevalent hemoglobinopathy throughout the word, can be cured by allogenic stem cell transplantation (SCT) (Bone Marrow Transplant 36:971-975, 2005). Many patients, however, lack a suitably matched related sibling donor. Unrelated umbilical cord blood (UCB) can be used as an alternative stem cell source for these patients. This report describes SCT for nine children with beta-thalassemia major using partially HLA-matched unrelated UCB. Conditioning included oral busulfan 16 mg/kg (day -10 to -7), cyclophosphamide (Cy) 200 mg/kg (day -5 to -2), fludarabine 90 mg/kg (day -13 to -11), and antithymocyte globulin (rabbit) 7.5 mg/kg (day -3 to -1). The infused cell dose was 10.71 × 10(7)/kg total nucleated cells (TNC) (range 6.5-17 × 10(7)/kg TNC). The patients ranged in age from 1.5 to 7 years, in weight from 10.5 to 17 kg. A second transplant with two unrelated cord blood units was attempted in two patients who had primary graft failure. The retransplant recipients were preconditioned with i.v Cy 120 mg/kg (day -3 to -2). Five of the nine patients engrafted promptly with 50-100 % donor chimerism (56 %). They engrafted at a median of 17 days (range 12-19). One patient is transfusion free for 36 months; a second patient is transfusion free for 18 months and a third is transfusion free for 9 months. There was no transplant related mortality. Four of the nine children had autologous recovery without engraftment. Primary graft rejection is the major complication. Post transplant complications were mild hepatic veno-occlusive disease, acute GVHD grade II, and CMV interstitial pneumonia. The chronic GVHD was limited and could be controlled by Methylprednisolone combined with Mycophenolate. The lack of a marrow donor registry in India makes UCBT from related and unrelated donors a good alternative. Transplant should be delayed until the child is at least 18 months of age. The dose of UCB stem cells is the most important factor for engraftment. UCB has the advantages of rapid availability and low risk of severe GVHD despite donor-recipient HLA disparity (Transplant Proc 37:2667-2669, 2005). We demonstrate the feasibility of this procedure in the setting of a developing country.

Acquired pure red cell aplasia in a patient of rheumatoid arthritis.

Pure red cell aplasia (PRCA) is characterized as a normocytic anemia associated with reticulocytopenia and the absence of erythroblasts in the bone marrow. PRCA can be induced by various causes such as thymoma, connective tissue disease, viral infection, lymphoma, and adverse drug reactions. There have been only a few reports of PRCA associated with rheumatoid arthritis (RA). We report a 45 year old female presented with symptomatic anemia of several months duration on a background of long standing seropositive deforming RA. Bone marrow examination revealed marked suppression of erythroid precursors with normal myeloid and megakaryocytic series, thereby confirming PRCA. Anemia improved following therapy with prednisolone 1 mg/kg/day. This article also reviews the current status of therapy in acquired PRCA.

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.

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. METHOD: FLT3 protein was quantified by flow cytometry on leukemic blasts using CD135 antibody in 160 patients with acute leukemia. RESULTS: We demonstrated FLT3 protein expression (>20%) in 82% of acute myeloid leukemia (AML), 60% of B-lineage acute lymphoblastic leukemia (B-ALL), 23% of T-lineage acute lymphoblastic leukemia (T-ALL) and 80% of biphenotypic leukemia. Further, FLT3 expression was seen to be significantly higher in AMLM2, M4, and M5 than in AMLM3. In B-ALL, FLT3 was found to be higher in pro-B-ALL and lower in early B-ALL. A CD34 expression >20% was associated with FLT3 positive B-ALL. When correlated with disease status, all patients in the relapsed AML group had FLT3 > 20% at diagnosis. Unlike AML, the relapsed group of B-ALL showed a lower incidence of FLT3 than the remission group. CONCLUSION: In summary, our data imply that there is frequent overexpression of the FLT3 protein in AML and B-ALL patients of Indian origin. In future, the FLT3 protein level may be used to select patients for whom FLT3 inhibitor therapy may be indicated.