Mukul Aggarwal

Hairy cell leukemia: A decade long experience of North Indian Hematology Center.

Introduction: Hairy cell leukemia is a rare chronic B-cell disorder that follows an indolent but progressive course. This disorder is characterized by pancytopenia, splenomegaly, bone marrow fibrosis and the presence of atypical lymphoid cells with hairy projections in peripheral blood, bone marrow and spleen. Treatment is mainly with nucleoside analog cladribine, which induces complete remission in up to 85% cases. Materials and Methods: This is a retrospective analysis of Hairy cell Leukemia cases diagnosed and treated in the Department of Hematology, All India Institute of Medical Sciences, New Delhi between 2002 and 2013. Various parameters such as clinical features, laboratory parameters including complete blood cell count, bone marrow findings, cytochemistry, immunophenotyping by flowcytometry or immunohistochemistry, treatment protocol and complications secondary to treatment and relapse were reviewed. Results: A total of 35 cases were diagnosed during this period of 12 years of which 27 received cladribine and went in to remission. Median follow-up duration was 26 months. 5 (18%) cases had a relapse and all relapsed cases achieved second remission with cladribine; however, there was no case of second malignancy in our cohort. Conclusion: Cladribine has emerged as the treatment of choice for hairy cell leukemia given that the overwhelming majority of patients achieve long-lasting complete remissions. Upon relapse, these patients could be successfully salvaged with cladribine retreatment.

Unusual Presentation of Hairy Cell Leukemia: A Case Series of Four Clinically Unsuspected Cases

Hairy cell leukemia (HCL) is characterized by pancytopenia and usually associated with massive splenomegaly, however the same may not be true in the clinical settings. Here we report four cases of HCL and all of them were without the classical clinical feature of splenomegaly. This is an observational study conducted between January 2013 to March 2014 where we could diagnose ten cases of HCL in Department of Hematology, All India Institute of Medical Sciences, New Delhi. Of these, four cases attracted attention because of absence of classical clinical features of HCL. Of the four cases, three presented with weakness/fatigability while fourth patient presented with recurrent respiratory tract infection. Surprising finding in these cases was absence of splenomegaly, both clinically and on imaging which demerit the suspicion of HCL clinically. All four had bi/pancytopenia and bone marrow examination coupled with immunophenotypic analysis confirmed the diagnosis of HCL. Three patients received chemotherapy with cladribine and achieved complete hematological remission. One patient did not receive chemotherapy due to poor general condition and was subsequently lost to follow up. To conclude, HCL can and do present without splenomegaly and this should not restrain one from suspecting HCL based on histomorphology which needs to be further confirmed by ancillary techniques. This finding in our series could be because these cases were picked early in their natural course of the disease. A high index of suspicion is essential for diagnosing and appropriately managing such cases.

Evaluation of platelet surface glycoproteins in patients with Glanzmann thrombasthenia: Association with bleeding symptoms

Background & objectives: Glanzmann thrombasthenia (GT) is a rare, inherited autosomal recessive disorder characterized by qualitative or quantitative deficiency of integrin αIIbβ3 [glycoprotein IIb (GPIIb)/IIIa, CD41/CD61] diagnosed by absent or reduced platelet aggregation to physiological agonists, namely, collagen, adenosine-di-phosphate, epinephrine and arachidonic acid. The objective of this study was to quantitate platelet surface GPs, classify GT patients and relate the results with the severity of bleeding and platelet aggregation studies. Methods: Fifty one patients of GT diagnosed by platelet aggregation studies were evaluated for the expression of CD41, CD61, CD42a and CD42b on platelet surface by flow cytometry. The association between the clinical phenotype based on bleeding score and GT subtype on flow cytometric evaluation was assessed. Results: Twenty four (47%) patients of GT were classified as type I (as CD41/CD61 were virtually absent, <5%), six (11.8%) patients as type II (5-20% CD41/CD61) and 21 (41.2%) as type III or GT variants as they had near normal levels of CD41 and CD61. Type III GT patients had significantly lower numbers of severe bleeders (P=0.034), but the severity of bleeding did not vary significantly in type I and II GT patients. In all GT patients, mean CD41 expression was found to be lower than mean CD61 expression (P=0.002). Interpretation & conclusions: Type I GT was found most common in our patients and with lowered mean CD41 expression in comparison with CD61. Type III GT patients had significantly lower numbers of severe bleeders, but the severity of bleeding did not vary significantly in type I and II GT patients.

Re-evaluation of Need for Bone Marrow Examination in Patients with Isolated Thrombocytopenia Contributors

Diagnosis of immune thrombocytopenia (ITP) is based on clinical suspicion and normal peripheral smear except for thrombocytopenia. Bone marrow examination is carried out to rule out leukemia, myelodysplastic syndrome or aplastic anemia. However, in most cases, clinical diagnosis is not altered after the bone marrow reports. Hence, this present study was carried out to evaluate the justification for bone marrow examination in the setting of isolated thrombocytopenia. All patients presenting to the hematology OPD with isolated thrombocytopenia and suspected diagnosis of ITP, between October 2011 and April 2013, were included in the study. Data was collected from bone marrow reports and outpatient records. A total of 353 cases were found. 319 cases had features of typical ITP and the rest had some form of organomegaly and/or lymphadenopathy. Bone marrow examination in all cases revealed normal hematopoietic elements and prominence of megakaryocytes including juvenile forms with no novel diagnosis in any patient. Routine use of bone marrow examination in the diagnostic workup of isolated thrombocytopenia is not required in our center even if steroids are planned as a first line therapy. However, a detailed history, thorough examination with complete hemogram and peripheral smear examination are essential.

Unusual massive bone marrow fibrosis in acute promyelocytic leukemia following arsenic trioxide therapy

Bone marrow fibrosis has been associated with different types of non-neoplastic conditions like granulomatous and autoimmune diseases and a variety of neoplastic disorders such as acute megakaryoblastic leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma and myeloproliferative neoplsms. Therapy induced fibrosis is a rare phenomenon. Here we report a case of an incidentally diagnosed acute promyelocytic leukemia (APL) with t(11;17) which was treated with arsenic trioxide (ATO) for 45 days. However, the patient did not go into remission and developed massive fibrosis of bone marrow. Literature search does not reveal such documented marrow fibrosis following therapy with ATO in a case of APL.

Hepatosplenic gamma delta T-cell lymphoma in a boy with visceral leishmaniasis: a case report

IntroductionHepatosplenic gamma delta T-cell lymphoma is a rare peripheral T-cell lymphoma of cytotoxic T-cell origin with an aggressive clinical course. Chronic immunosuppression has been proposed as a possible pathogenetic mechanism. No association of hepatosplenic gamma delta T-cell lymphoma with visceral leishmaniasis has been described in the past. We describe a case of an adolescent boy with hepatosplenic gamma delta T-cell lymphoma with leukemic presentation, who was diagnosed to have visceral leishmaniasis, 9 months prior to presentation at our center. To the best of our knowledge this is the first report of hepatosplenic gamma delta T-cell lymphoma with a prior history of visceral leishmaniasis in the medical literature.Case presentationA 13-year-old Indian boy presented to the hematology out-patient department with a history of progressive abdominal distension of 9 months’ duration and low grade fever of 2 months’ duration. He was a known case of visceral leishmaniasis and was treated with some clinical improvement in the past. However, his symptoms recurred and he was diagnosed to have hepatosplenic gamma delta T-cell lymphoma at our center. Cytogenetic analysis showed characteristic karyotype of isochromosome 7.ConclusionsChronic antigen stimulation due to visceral leishmaniasis may have led to an expansion of gamma delta T cells in our patient, and immunophenotypic analysis of bone marrow aspirate and characteristic karyotype helped to achieve the diagnosis. The aim of this case report is to highlight the rare association of hepatosplenic T-cell lymphoma with visceral leishmaniasis.

Incidence and clinical profile of tuberculosis after allogeneic stem cell transplantation

Patients post allogeneic stem cell transplantation (alloSCT) are expected to be at high risk of tuberculosis (TB) owing to underlying immunosuppression. We conducted a retrospective study in patients post alloSCT for clinical features and factors associated with TB.

Haplo-identical Hematopoietic Stem Cell Transplant is a Possible Cure in a Patient with Relapsed Hemophagocytic Lymphohistiocytosis Syndrome

Hemophagocytic lymphohistiocytosis (HLH) is a lifethreatening hyperinflammatory syndrome of uncontrolled immune responses resulting in hypercytokinemia because of underlying primary or acquired immune defect. Currently, the only cure for primary or relapsed HLH is allogenic stem cell transplantation (AlloSCT) [1]. Our report concerns a 13-year-old boy with a relapsed distinctively blurred HLH [2], who achieved prolonged complete remission (CR) after haplo-identical stem cell transplant (Haplo-SCT) following salvage chemotherapy. A previously healthy 11-year-old boy, the youngest son of a healthy nonconsanguineous parents without family history of HLH/similar disorders in first/second-degree relatives was hospitalised at a local hospital with complaints of 106 F fever and hepatosplenomegaly and found to have Brucella infection and histiocyte proliferation in bone marrow (BM). On further investigations, he had raised serum triglyceride, serum ferritin, and low fibrinogen levels, on the basis of which he was diagnosed with HLH. Cerebrospinal fluid was normal. The genetic mutations of HLH were not tested for parents did not give consent for same. He received chemotherapy using HLH2004 protocol and achieved CR. On routine follow up, he was found to have relapse of HLH without any underlying infective stimulus, after 25 months of initial therapy for which he received etoposide-based salvage chemotherapy and attained a second complete remission. Thereafter he was referred to us for alloSCT. He had no HLA matched donor in the family, but had 3/6 HLA match with his mother with negative donor specific anti-HLA antibodies screen. Considering the relapsed nature of HLH and in need of alloSCT lacking a matched HLA donor from family, he received a Haplo-SCT using T cell replete peripheral blood stem cell (PBSC) from his mother with a CD34 cell dose of 6.06 9 10 cells/kg after Fludarabine, cyclophosphamide and TBI (FluCyTBI) conditioning. For GvHD prophylaxis, cyclophosphamide at day ? 3 and ? 4 post SCT was employed. ANC and Platelet Engraftment was achieved at day ? 16 and ? 21 of SCT respectively, and was further confirmed by 100% donor karyotype on FISH for XX analysis of peripheral blood at day ? 30. Acute GvHD (aGvHD), overall grade II with skin and gut involvement, became apparent at day ? 16 which was managed with corticosteroids. By day ? 120, he developed aGvHD of liver, which progressed to grade IV despite being on corticosteroids, etanercept and basiliximab and was controlled after Anti thymocyte globulin (ATG) therapy. He had no major infections except for chronic otitis media and UTI with Enterococcus fecalis. Currently, he has mild chronic GvHD involving oral mucosa and eyes requiring minimal immunosuppression and is disease free with maintenance of complete chimerism at day ? 840 of Haplo-SCT. Use of alloSCT for HLH has remarkably improved the survival and prognosis of patients. Henter et al. [3] demonstrated 62% survival rate at 3 years and 10% of graft failure (GF) among 65 HLH patients treated with alloSCT. Ouachée-Chardin et al. [4] reported a series of 48 primary HLH patients who received alloSCT out of which 60% received haplo-SCT, was found associated with increased treatment related toxicity, poor prognosis and 22% GF rate. Uppuluri et al. [5] reported a case of 2 young children with & Rayaz Ahmed rayazhemat@gmail.com

Priapism Associated with Homozygous Hb E State: A Causal Association or an Incidental Finding?

Dear editor, Priapism, that is, persistent penile erection that continues hours beyond, or is unrelated to, sexual stimulation, is a relatively uncommon disorder and is a medical emergency. Typically, only the corpora cavernosa are affected [1]. The term priapism was derived from the Greek god Priapus, son of Aphrodite who was born with oversized genitals [2]. The haematological causes for priapism include Sickle cell anaemia, Leukaemia, Multiple myeloma, Paroxysmal nocturnal haemoglobinuria, Thalassaemia, Thrombocythemia and Henoch–Schonlein purpura [3]. As far as hemoglobinopathies are concerned, priapism is most often encountered in sickle cell disease in 38–42 % of cases followed by sickle/beta thalassemia [4, 5]. Priapism is also noted in patients with sickle cell trait even though the incidence is low as compared with sickle cell anaemia [6–9]. However, so far priapism in Hb E homozygosity is not reported in literature. In this correspondence we intend to bring to notice an unusual association of priapism with Hb E homozygosity. A 27 years old male, resident of North Eastern part of India was referred to our haematology OPD to rule out any underlying haematological disorder as the individual had an episode of priapism 3 months ago. The patient had an episode of unprovoked painful persistent erection for more than 8 h for which he sought medical advice. The surgeon at that medical center had managed with therapeutic needle aspiration from corpora cavernosa combined with flushing of cavernosa with normal saline to clear the sludged blood. The patient’s symptom subsided subsequently with the intervention and was referred to our center for further evaluation. On detailed clinical history, the individual was not on any medication for chronic illnesses; neither was he abusing any psychoactive drugs, alcohol, no history of prior trauma to the perineal region. His physical examination revealed mild pallor. There was no hepatosplenomegaly or lymphadenopathy. Systemic examination did not reveal any abnormality. On USG abdomen, spleen was not reported as enlarged (Span 13 cms). On investigations, haemoglobin, total leucocyte count and platelet count were 9.1 gm/dL, 7.1 9 10/lL and 118 9 10/lL respectively. Peripheral smear examination revealed microcytic hypochromic red cells and target cells with normal differential leucocyte count and reticulocyte count of one percent. There were no sickle cells or atypical cells in peripheral smear and sickling test was also negative. Subsequently Hb HPLC was performed which revealed with Hb A2 ? E of 92.6 % (Retention time3.68 min), Hb A of 6 % (Retention time 2.29 min) and Hb F (Retention time 1.06 min) of 1.6 % (Fig. 1; Table 1). This was followed by parental study which revealed Hb A2 ? E in mother and father of 29 and 27 % respectively suggestive of both parents being heterozygous for Hb E, S. Venkatesan A. Purohit (&) M. Aggarwal P. K. Singh T. Seth H. P. Pati Department of Hematology, All India Institute of Medical Sciences, New Delhi, India e-mail: purohitabhi80@gmail.com

Haploidentical stem cell transplant: Established treatment, expanding horizons

Haploidentical stem cell transplantation offers an oppurtunity for transplant for almost all patients for whom transplant is indicated. Traditionally, it is associated with higher incidence of graft failure, graft vs host disease and non relapse mortality as compared to matched donor transplant. However, recent advances in the field have tried to mitigate these issues and offer haploidentical transplant as a safe and viable option. In this review, we shall discuss the basics of haploidentical transplantation, how to choose the best donor amongst various haploidentical donors available and understand the various recent advances in the field of haploidentical transplantation and how they addressed the problems associated with it and make it a feasible alternative to matched sibling or unrelated transplant in various diseases.