Risk factors for thromboembolism and pulmonary artery hypertension following splenectomy in children with hereditary spherocytosis.

BACKGROUND: The aim was to study risk-factors for vascular thrombosis and incidence of pulmonary artery hypertension (PAH) in splenectomized children with hereditary spherocytosis (HS) at a single center. PROCEDURE: Pre- and post-splenectomy hemoglobin and platelet counts were recorded. Post-splenectomy lipid-profile, fibrinogen, D-dimer, CRP and anti-coagulant-protein levels were compared to established controls. Echo-Doppler was performed for PAH. RESULTS: Twenty-six children with HS had undergone splenectomy; the mean age at surgery was 7.9 ± 3.7 years. Nineteen of the 26 were prospectively investigated at a median duration of 4.5 years (range: 4 months to 19 years) following splenectomy. Thrombocytosis was observed in 19 (73%), whereas no patient had erythrocytosis at the last follow-up visit. Total cholesterol, LDL-C, HDL-C, and triglyceride levels were not deranged (P ≥ 0.3). Mean CRP levels (males: 2.8 ± 0.5; females: 2.1 ± 0.5 mg/L) were significantly higher than described for normal children (P < 0.001). Six (23%) patients had a positive D-dimer assay. Protein S, anti-thrombin-III and fibrinogen were in range. A single patient had a borderline low protein C activity. Lupus anticoagulant and anti-cardiolipin antibody assays were negative. The mean tricuspid regurgitant jet velocity (TRJV) was 1.8 ± 0.55 meter per second (range: 0-2.4). None had a TRJV ≥2.5 meter per second to suggest PAH. CONCLUSIONS: There was no evidence of PAH, dyslipidemia, elevation of fibrinogen or a reduction in anti-coagulant proteins, at a median follow-up duration of 4.5 years following splenectomy in children with HS. However, elevated CRP level (42%), persistent thrombocytosis (73%) and elevated D-dimer levels (23%) were observed. These have been recognized as risk factors for cerebrovascular and coronary heart disease.

Unusual sites of relapse in pre-B acute lymphoblastic leukemia.

Relapses of acute lymphoblastic leukemia (ALL) in unusual sites can be challenging to diagnose. We present unusual relapses occurring in children with ALL treated in a single institution over a 22-year period. Of 172 relapses, 9 (5.2%) were at unusual sites (nonmarrow, testes, central nervous system). The most common site of relapse was ocular (66%). The median symptom-to-diagnosis interval was 20 days. Two of 9 children attained second remission. A possibility of relapse should be considered when evaluating unusual symptoms in a child with underlying ALL.

HbSD-Punjab: clinical and hematological profile of a rare hemoglobinopathy.

PURPOSE: Compound heterozygous HbSD-Punjab is an uncommon hemoglobinopathy encountered in Indians. Limited literature is available about its clinical course. The aim of this study was to describe the clinical and hematological profile of HbSD-Punjab patients from North India. MATERIALS AND METHODS: HbSD-Punjab patients diagnosed in the hematology clinics between year 2000 and 2010 were reviewed retrospectively. The diagnosis was established using high-performance liquid chromatography, molecular analysis, and family screening. Clinical details, laboratory parameters, and therapy details were recorded from case records. RESULTS: Ten patients were identified. Median age at onset of symptoms was 3.5 years (interquartile range [IQR], 1.9 to 7.2). Clinical presentation included: anemia in 3, painful vaso-occlusive crisis in 2, acute chest syndrome in 2, and 3 were diagnosed incidentally. All had moderate to severe anemia (mean hemoglobin [Hb]: 6.8 ± 1.2 g/dL). Eight required red cell transfusions (median: 3 [IQR, 2 to 8]). On high-performance liquid chromatography, median HbF, HbD, and HbS were 12.1% (IQR, 9 to 18.3), 39.7% (IQR, 35 to 42), and 38.5% (IQR, 29 to 43). Five patients received hydroxyurea (HDU), median dose: 20 mg/kg/d (IQR, 18 to 23) with median duration of 7 months (IQR; 6, 45). Increment in Hb and reduction in painful crisis was observed in response to HDU. CONCLUSIONS: HbSD-Punjab has a heterogeneous clinical presentation. Anemia and sickle crises are quite common. HDU may be considered for those presenting with severe phenotype.

Acute lymphoblastic leukemia with pancytopenia at presentation: clinical correlates, prognostic impact, and association with survival.

Acute lymphoblastic leukemia has a wide variety of presentations. There is paucity of any data addressing pancytopenia at presentation in acute lymphoblastic leukemia. In this study we assessed 84 patients with pancytopenia at presentation. They had a significantly lower incidence of bulky disease at presentation. A significantly higher fraction of these patients (n=66, 78.57%) opted for therapy (P=0.005) as compared with the rest. The estimated mean survival in patients presenting with pancytopenia (67.2±17.2 mo) was significantly higher (P=0.031, log-rank test) as compared with that of other patients (47.2±7.4 mo). Pancytopenia was an independent predictor of better survival (P=0.043) in multivariate analysis.

Hodgkin lymphoma in children: experience in a tertiary care centre in India.

BACKGROUND: In developing countries Hodgkin lymphoma (HL) has been seen to have a high male to female ratio, younger age at presentation, a high proportion of patients in advanced stage of disease, constitutional symptoms, and predominance of mixed cellularity histologic type. The results of treatment appear to be comparable to the results attained in developed nations. METHODS: Children with HL who were diagnosed and treated at our center between 1990 and 2006 were retrospectively analyzed. RESULTS: A total of 206 children with a mean age of 7.9±2.6 (range, 3 to 16) years were treated for HL. Among them, 52% presented with advanced-stage (stages III and IV) disease, 54% had B symptoms, and 69.6% had mixed cellularity type of HL. Multiagent chemotherapy was the mainstay of treatment. The 5-year overall survival and event-free survival rates were 92.7% and 77.75%, respectively. Children with early-stage disease and absence of B symptoms had a better overall survival of 97.7% each, as compared with 87.2% and 88.2% in those with late-stage disease and B symptoms, respectively. CONCLUSIONS: Even though developing countries have a different epidemiological profile, the outcome is good. Chemotherapy alone has shown excellent results in children with HL.

Serum galactomannan assay for the diagnosis of invasive aspergillosis in children with haematological malignancies.

Diagnostic efficacy of Galactomannan (GM) assay for invasive aspergillosis (IA) is variably reported. Data from developing countries are scant. Children with haematological malignancies and fever were enrolled prospectively. Blood sample for GM was drawn on the day of admission; levels were measured with Platellia Aspergillus enzyme immunoassay. Diagnostic criteria were adapted from EORTC-MSG-2002. Proven, probable and possible episodes were considered as the disease group. One hundred febrile episodes in 78 patients were evaluated. The mean age was 6.1 years. Majority (75%) episodes were in patients with acute lymphoblastic leukaemia. One episode each was diagnosed with proven and probable IA, while 23 were diagnosed with possible IA. Best results were obtained with a cut-off value of 1.0, with sensitivity, specificity, positive and negative predictive value of 60%, 93%, 75 and 87 respectively. The sensitivity dropped to 40%, at cut-off value of 1.5 and specificity was 38%, at a cut-off of 0.5. A higher value of GM correlated with pulmonary nodules (P = 0.037) and mortality (P = 0.001). GM assay is adjunctive to clinical/radiological evidence. A negative GM assay may not reassure the physician against the use of amphotericin in patients with febrile neutropenia, as it does not exclude the diagnosis of clinically relevant other fungal infections, particular mucormycosis.

Wilms tumor: five-year tumor-free survival on a modified SIOP protocol from an Indian university hospital.

BACKGROUND AND PURPOSE: Wilms tumor is one of the most common solid malignancies of childhood. The long-term result of the surgical treatment of this tumor with adjuvant chemotherapy and radiation has been reported from many western centers. However, there is paucity of literature on the long-term outcome of treatment for this tumor from the developing world. We planned a prospective study that started in 1999 to evaluate the 5-year tumor-free survival of Wilms tumor treated on a fixed protocol from a university hospital in India. METHODS: All consecutive children with Wilms tumor who were seen by any of the 3 investigators (2 pediatric oncologists, 1 pediatric surgeon) between 1999 and 2003 at the Advanced Pediatric Centre were included in the study. Each patient was entered into a database. Their demographic profile and events during the treatment and follow-up were recorded. This was later analyzed. CONCLUSIONS: Seventy-five percent 5-year tumor-free survival has been achieved within the limitations of treatment in the developing world. The morbidity during therapy was 10% and the mortality 5%. This was based on the treatment of this common childhood malignancy at Chandigarh on a modified International Society of Pediatric Oncology protocol.

Hypereosinophilia: more than meets the eye.

INTRODUCTION: Eosinophilia has myriad causes and is occaisonally seen in association with malignancies. Acute myeloid leukemia presenting with eosinophilia has rarely been reported in children. CASE: Authors herein present a case of a 5-year-old boy who presented with marked peripheral eosinophilia with symptoms of organ infiltration. Extensive work-up was needed before the diagnosis was established in this patient. DISCUSSION: Through this case report, we want to emphasize that peripheral eosinophilia could be a dilemma challenging clinical skills and often needing vigorous perusal for the diagnosis.

Efficacy of deferasirox in North Indian ß-thalassemia major patients: a preliminary report.

Deferasirox (DFX) is a relatively new iron chelator approved by the US Food and Drug Administration for treatment of children >2 years of age. Prospective studies in Asian Indian children are limited. The ß-thalassemia patients receiving regular transfusions in the thalassemia ward of an advanced pediatric center were included in this study. Monitoring of side effects was carried out by assessing monthly transaminases and serum creatinine levels. Hemoglobin levels were determined before blood transfusion. Thirty patients of transfusion-dependent thalassemia were eligible for the final analysis. The male:female ratio was 3.3:1, and ages ranged from 2.0 to 21 years. The serum ferritin (SF) level at the start of therapy was 2657.7±1414.6 (mean±SD). The mean dose of DFX was 21.57 mg/kg/d (range, 17.2 to 27.2 mg/kg/d). Common side effects noted were gastrointestinal manifestations in 5 (16.6%) and skin rash in 2 (6.6%) patients. There was an increase in serum creatinine in 2 patients, and treatment was interrupted in 1. Reversible cytopenia was observed in 1 patient. In 13/30 patients, an initial increase in SF was observed. A decrease in SF levels compared with initial value was seen in only 8 patients at a follow-up of 24 months, at a median dose of 28.8 mg/kg/d. Thus, DFX is a relatively safe oral iron chelator that can be used in Asian Indians, with gastrointestinal problems like diarrhea and abdominal pain as the most common side effects. Treatment requires individualization with careful dose escalation and proper monitoring.

Rubinstein-Taybi syndrome: Clinical profile of 11 patients and review of literature.

BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a rare congenital neurodevelopmental disorder, characterized by postnatal growth deficiency, typical dysmorphic features, broad thumbs and toes, and mental retardation. Very few cases are reported in literature from developing countries. Diagnosis is often delayed due to non-familiarity with the characteristic features of this syndrome. AIMS: To report 11 cases of RSTS and to review the current literature. SETTINGS AND DESIGN: Retrospective study conducted in genetic and metabolic unit of a tertiary care teaching hospital in north India over a period of 3½ years. MATERIALS AND METHODS: 11 patients with diagnosis of RSTS were identified, and their case sheets were reviewed. RESULTS: Developmental delay was presenting complaint in 10 patients, and seizure in 1 case. 7 patients had microcephaly (head circumference below -3 SD), and a prominent beaked nose was seen in 9 patients. The intelligence quotient (IQ) varied from 22-62 in 7 patients who had mental retardation. The most notable features in hands were broadness, shortening, and flattening of the distal phalanx of thumbs or great toes. Additionally, we also noted webbing of neck, microphthalmia, and pachygyria (on MRI brain) in 1 patient each. CONCLUSIONS: The diagnosis of RSTS is primarily clinical and based on characteristic phenotype that is often combined with a variety of somatic anomalies. An early diagnosis facilitates appropriate genetic counseling and in planning the management.

Xmn1-G γ polymorphism and clinical predictors of severity of disease in ß-thalassemia intermedia.

BACKGROUND: To determine the prevalence of Xmn1-(G)γ polymorphism in North Indian children and adolescents with ß thalassemia intermedia (TI) and to correlate it with disease severity. METHODS: All patients of thalassemia intermedia presenting to the pediatric hematology clinic of a tertiary care hospital in North India were enrolled. Clinical severity of their disease was assessed by a phenotypic score proposed by Phadke and Agarwal. They were classified according to status of their Xmn1-(G)γ polymorphism as Xmn1-(G)γ +/+, Xmn1-(G)γ +/-, and Xmn1-(G)γ -/- by molecular analysis. RESULTS: A total of 104 patients were enrolled. Severe TI was seen in 56.7% (59) patients, while 43.3% (45) had non-severe TI. Jaundice was more frequent in severe TI than in non-severe TI. Xmn1-(G)γ +/+ was present in 25.9% (25) patients. The frequency of the Xmn1-(G)γ +/- and Xmn1-(G)γ -/- was 22% and 37.3% in severe TI children. The corresponding frequencies were 31.1% and 42.2% in non-severe TI group respectively. No significant correlation was observed between the Xmn1-(G)γ polymorphism and severity of thalassemia, age at onset of symptoms, age at diagnosis, age at first transfusion, transfusion frequency or average hemoglobin levels. HbF level was significantly higher in Xmn1-(G)γ +/+ and Xmn1-(G)γ +/- patients. CONCLUSIONS: This study showed that although the prevalence of Xmn1-(G)γ polymorphism is high in ß thalassemia intermedia patients, it alone could not predict clinical severity in TI patients. Further refinement and validation of clinical scoring system is necessary for guiding appropriate management.

Long-term response to deferiprone therapy in Asian Indians.

Deferiprone (L1) has been used in several countries for iron chelation therapy for over one decade. Long-term results on the drug are lacking. In the present study, data of 110 patients on deferiprone (L1) for up to 17 years were analyzed. On a mean L1 dose of 70.2 mg/kg/day (range 44-100), serum ferritin level showed a very steady decrease with time from an initial mean (+/-SD) of 3,033.61 +/- 1,468.04 ng/ml to final of 1,665.08 +/- 949.93 ng/ml after a mean (+/-SD) of 6.1 +/- 3.8 years. In total, 13 patients discontinued L1 therapy. Major complications of L1 requiring permanent discontinuation of treatment included arthropathy (n = 8, 7.2%) and neutropenia/agranulocytosis (n = 5, 4.5%). Lesser complications permitting continued L1 treatment included transient mild leucopenia or thrombocytopenia (n = 3) and gastrointestinal problems (n = 5). There were a total of three deaths attributed to agranulocytosis. Although the complications associated with L1 treatment are significant and require close monitoring, they do not preclude effective long-term therapy in the vast majority of patients. A longer duration of therapy is required for effective response in chronically iron-overloaded patients. Further well-controlled prospective studies of L1 are required to identify factors affecting individual response to therapy.

Stroke in a young boy with ß-thalassemia intermedia secondary to moyamoya syndrome.

Moyamoya disease is a rare cerebrovascular disorder, characterized by stenosis or occlusion of cerebral arteries. Well described with sickle cell anemia, its association with other hemoglobinopathies is a rarity. We report a 5-year-old boy with ß-thalassemia intermedia, on hydroxyurea therapy, who presented with a stroke. Magnetic resonance angiography findings were consistent with bilateral moyamoya disease. The literature with regard to the pathogenesis and options of management is reviewed.

Premature epiphyseal fusions in beta thalassaemia.

Thalassemia patients are now living longer due to better transfusion methods and diagnostic awareness. To see whether this longevity is associated with orthopaedic disability, especially physeal growth defects, we examined 105 patients aged between 5-25 years for evidence of clinically detectable premature epiphyseal fusions (PEF). Ours is a center focussed on transfusion dependent beta thalassemia (TDBT) patient management, and so detailed transfusion records related to age at first transfusion, regularity of transfusions and pre-transfusional haemoglobin (Hb) levels were available. Five (4.7%) patients had deformities or limb length discrepancies, which lead to the detection of PEF. All patients with PEF had pre transfusion haemoglobin levels of less than 8 gm/dL. On comparing with the literature, we found that the prevalence of clinically detectable PEF in TDBT patients has decreased with better blood transfusion regimes. Though the pathogenesis of PEF is yet to be conclusively established, it is apparent that better control of the disease to maintain pre-transfusional haemoglobin levels consistently above 8 gm/dL in the first decade, can decrease the occurrence of PEF.

Spontaneous hematomyelia in a child with hemophilia A: a case report.

Hemorrhagic complications in patients with hemophilia have been occasionally reported in the spinal column and the spinal cord. Treatment is based on prompt replacement therapy as the occurrence and development of neurologic dysfunction are related to the length of time between the onset of symptoms and the factor replacement. We report case of a 7-year-old hemophilic boy who presented with flaccid paraparesis resulting from thoracic hematomyelia. The patient showed gradual improvement on medical management with cryoprecipitate infusions. This case calls attention to the need for prompt diagnosis of rarely reported spinal hematomyelia based on clinical manifestations and radiologic features and highlights its management options in patients with hemophilia.