M. Joseph John

Erythropoietin use and abuse

Recombinant human erythropoietin (rhEPO) is arguably the most successful therapeutic application of recombinant DNA technology till date. It was isolated in 1977 and the gene decoded in 1985. Since then, it has found varied applications, especially in stimulating erythropoiesis in anemia due to chronic conditions like renal failure, myelodysplasia, infections like HIV, in prematurity, and in reducing peri-operative blood transfusions. The discovery of erythropoietin receptor (EPO-R) and its presence in non-erythroid cells has led to several areas of research. Various types of rhEPO are commercially available today with different dosage schedules and modes of delivery. Their efficacy in stimulating erythropoiesis is dose dependent and differs according to the patients disease and nutritional status. EPO should be used carefully according to guidelines as unsolicited use can result in serious adverse effects. Because of its capacity to improve oxygenation, it has been abused by athletes participating in endurance sports and detecting this has proved to be a challenge.

Autoimmune Lymphoproliferative Syndrome: Response to Mycophenolate Mofetil and Pyrimethamine/Sulfadoxine in a 5-Year-Old Child

Autoimmune Lymphoproliferative Syndrome (ALPS) is a rare inherited disorder of disrupted lymphocyte homeostasis characterized by chronic splenomegaly and lymphadenopathy of early onset, hypergammaglobulinemia (Ig G and Ig A), autoimmune phenomena, and expanded populations of TCR-α/β+, CD3+, CD4-, CD8-T cells (Fisher et al. Cell 81:935–946; 1995), called double negative T-cells [(DN) T cells]. We discuss a case of ALPS which showed good response to immunosuppressant drug Mycophenolate-Mofetil in combination with Pyrimethamine/Sulfadoxine.

Knowledge base and practice among clinicians regarding oral anticoagulant therapy: A questionnaire survey

Purpose: To assess the knowledge of clinicians regarding various aspects of anticoagulant therapy. Materials and Methods: This cross-sectional study was done over 2 months among 55 clinicians at a tertiary hospital. A 30 point questionnaire based survey on various aspects of oral anticoagulant therapy was carried out. Clinician practices were also compared between physicians and surgeons. Results: Two thirds (67.3%) of the clinicians were not aware that different strengths of acitrom were not color coded. A majority (85.5%) verbally instructed their patients about the drug. Less than one fifths (18.2%) of the clinicians provided booklets and pamphlets for reference. Only 56.4% of clinicians were aware of the correct target range for INR to be achieved in patients. Dietary and drug history was not documented by 85.6% and 50.9% of clinicians respectively. Surgeons were more likely to give educational booklets to their patients, document a dietary history and instruct patients regarding concomitant alcohol use in comparison with physicians. Twenty (41.7%) clinicians reported that they encounter thrombosis as a complication in patients on OAT while 58.3% of the clinicians in the present study noted bleeding more often. Conclusion: There are significant lacunae in knowledge base among clinicians regarding oral anticoagulant therapy. More emphasis on physician education is needed for safe and optimal OAT in patients.

Non-thrombotic superior sagittal sinus occlusion with intracranial hypertension following metastatic Burkitt's lymphoma.

Intracranial metastasis is a known complication of Burkitts lymphoma, however, superior sagittal sinus invasion by dural metastasis from Burkitts lymphoma is rare. We report a young adult, known case of Burkitts lymphoma, who presented with features of raised intracranial pressure secondary to dural sinus invasion from metastasis. Prompt radiotherapy to these lesions can bring about recanalization of the sinus with elevation of symptoms.

Unrelated and related donor transplantation for beta-thalassemia major: A single-center experience from India

Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment in patients with β‐thalassemia major. A matched sibling or a related donor is usually found in only 25%‐30% of the patients. There are limited data on matched unrelated donor (MUD) transplants from India. We reviewed HSCT outcome in 56 children with TM who underwent 57 transplants at our center. Related donor (RD) (n=43) and MUD (n=14) transplants were performed with TreoFluT‐based conditioning regimen in majority (95%) of patients. Peripheral blood stem cells (PBSC) were the preferred (85%) source of stem cells. The overall survival (OS) at 1 year in RD and MUD groups was 87.6±5.2% and 85.7±9.4% at a median follow‐up of 25 (1‐92) months and 22.5 (1‐50) months, respectively (P=.757). The thalassemia‐free survival (TFS) at 1 year was 87.6±5.2% and 77.1±11.7% with a median follow‐up of 24 (1‐92) and 16.5 (1‐50) months, respectively (P=.487). Although acute (14% vs 64%) and chronic graft‐versus‐host disease (GVHD) (13.9% vs 42.9%), infectious (39.5% vs 71.4%), and non‐infectious (37.2% vs 78.5%) complications are higher in MUD transplant group, the present data show a comparable OS and TFS among RD and MUD group with treosulfan‐based regimen using PBSC grafts.

Extensive Platelet Phagocytosis in a Patient with Immune Thrombocytopenia (ITP) and Concomitant Tuberculosis

Hemophagocytic syndrome is characterized by benign proliferation of mature histiocytes and uncontrolled phagocytosis of the erythrocytes, leukocytes, platelets and/ or their hematopoietic precursors in the bone marrow. Hemophagocytic syndrome can be familial or acquired which is associated with tuberculosis, autoimmune disorders, hematologic malignancies or solid cancers [1]. Although histiocytes in the bone marrow may show phagocytosis of any of the hematopoietic precursors, marked platelet specific phagocytosis is an extremely rare finding. Inhibitory CD47/(signal regulatory protein) SIRP alpha signaling is involved in regulating platelet phagocytosis in ITP [2]. We present a patient with ITP who had concomitant tuberculosis and showed predominant platelet phagocytosis. A 61 years old male with ITP on steroid therapy presented with fever and cough since 2 weeks. He had pallor with no petechiae or purpuric spots. Investigations showed hemoglobin of 102 g/l with normal white cell count and thrombocytopenia (platelets: 58 9 10/l). Bone marrow aspiration showed increase in histiocytes with many of them showing extensive platelet phagocytosis (Fig. 1). Occasional histiocytes also showed erythroblastic phagocytosis (Fig. 1, Inset). Trephine biopsy and clot section showed epithelioid cell granulomata (Fig. 2a, b). Ziehl–Neelsen stain for acid fast bacilli was positive. HRCT chest was suggestive of military tuberculosis. The Fig. 1 Bone marrow aspirate smear showing extensive platelet phagocytosis by histiocytes. An occasional histiocyte also shows engulfment of erythroblasts [Inset]

T Cell Prolymphocytic Leukemia (T-PLL): Cutaneous Involvement in an Uncommon Leukemia

A 70 years old lady presented with multiple neck swellings and abdominal pain for 6 months. Examination showed pallor with bilateral cervical, axillary and inguinal lymphadenopathy. There was moderate hepatomegaly with no splenomegaly. She also had a macular rash over the trunk and limbs. Chest X-ray was normal. Ultrasonogram of the abdomen showed prominent peri-portal lymphadenopathy. Investigations showed hemoglobin of 84 g/l, total leukocyte count of 311 9 10/l and platelets of 119 9 10/ l. Differential count showed 94% lymphoid cells, 4% neutrophils and 2% metamyelocytes. The lymphoid cells were of size 10–14 lm with indented and clefted nuclear outlines, single prominent nucleolus and scanty to moderate cytoplasm (Fig. 1a).Many of the cells showed cerebriform morphology with cytoplasmic blebs in few. Bone marrow aspirate was hypercellular with trilineage hematopoietic depression and diffuse replacement by lymphoid cells with clumped chromatin, inconspicuous nucleoli and scant basophilic cytoplasm. Bone marrow differential count showed: 79% lymphoid cells with few residual erythroid and myeloid hematopoietic cells. Trephine biopsy showed a diffuse infiltrate of lymphoid cells (Fig. 1b). Cytochemistry was not done due to non availability of stains. Immunophenotyping showed lymphoid cells to be positive for CD45, CD3 (93.2%), CD5, CD4 and CD7. CD8, B-cell and myeloid markers were negative. CD52 expression was not studied. Biochemical investigations were normal. Biopsy from the macular rash showed dense peri-appendageal lymphocytic dermal infiltrate with melanin incontinence and no epidermotropism (Fig. 1c). The infiltrate was positive for CD3 (Fig. 1d). CD20 was negative with moderately high (40%) Ki67 index. A diagnosis of T-cell Prolymphocytic leukaemia (T-PLL) was made. The patient was started on Fludarabine and Cyclophosphamide. After the third cycle of chemotherapy, she developed tumor lysis syndrome with renal failure and an infarct in the left lentiform nucleus. In view of the poor prognosis, the relatives took her against medical advice. T-PLL is an uncommon chronic lymphoproliferative disorder with male preponderance and comprises 2% of mature lymphocytic leukemias. The median age at presentation is 65 years. Lymphadenopathy and hepatosplenomegaly are common with skin lesions and effusions seen in 20 and 15% of patients respectively [1, 2]. Patients have leukocytosis with one thirds having associated anemia and thrombocytopenia. Liver function tests are frequently abnormal with raised urate and lactate dehydrogenase levels [2]. Peripheral blood smear shows prolymphocytes with classical T-PLL seen in two-thirds of patients with larger lymphoid cells with irregular outline and cytoplasmic blebs. Remaining patients show small lymphoid cells or have cerebriform nuclei [2–4]. Skin lesions are often seen without epidermotropism [5]. Immunophenotyping in T-PLL shows the most frequent phentotype to be CD4?, CD8(65% cases), CD4?/CD8? (25% cases) and CD8?/CD4(10% cases). Positivity for CD2, CD3, CD5 and CD7 is consistently seen. CD52 expression is usually seen and can be used for targeted therapy with Alemtuzumab. Tdt is negative along with pan B cell markers. Cytogenetic abnormalities seen commonly in T-PLL are t(14;14)(q11;q32) and inv(14). The & Naveen Kakkar kakkar.naveen@gmail.com

Cost Effectiveness of Hematopoietic Stem Cell Transplantation Compared with Transfusion Chelation for Treatment of Thalassemia Major

Hematopoietic stem cell transplantation (HSCT) is the only cure for thalassemia major (TM), which inflicts a significant 1-time cost. Hence, it is important to explore the cost effectiveness of HSCT versus lifelong regular transfusion-chelation (TC) therapy. This study was undertaken to estimate incremental cost per quality-adjusted life-year (QALY) gained with the intervention group HSCT, and the comparator group TC, in TM patients. A combination of decision tree and Markov model was used for analysis. A hospital database, supplemented with a review of published literature, was used to derive input parameters for the model. A lifetime study horizon was used and future costs and consequences were discounted at 3%. Results are presented using societal perspective. Incremental cost per QALY gained with use of HSCT as compared with TC was 64,096 (US

Un-manipulated haploidentical transplant in Wiskott-Aldrich syndrome

986) in case of matched related donor (MRD) and 1,67,657 (US

Hemophagocytosis by Leukemic Blasts in T Cell Acute Lymphoblastic Leukemia: An Unusual Finding.

2579) in case of a matched unrelated donor transplantation. The probability of MRD transplant to be cost effective at the willingness to pay threshold of Indian per capita gross domestic product is 94%. HSCT is a long-term value for money intervention that is highly cost effective and its long-term clinical and economic benefits outweigh those of TC.