Hematopoietic stem cell transplantation in children with Griscelli Syndrome type 2: Experience and outcomes

Griscelli syndrome is a rare autosomal recessive inherited disorder characterized by hypopigmentation, silver colored hair, and associated immunological deficiency, which proves fatal in the absence of timely intervention. Our patients diagnosed with Griscelli syndrome-2 presented with fever, hepatosplenomegaly, and deranged hematological and biochemical parameters. Both cases underwent detailed investigations comprising of hair mount microscopic examination, degranulation assay, and mutational studies. Our cases showed defective degranulation activity by NK cells and gene mutation analysis revealed RAB27A mutation that causes defect of cytotoxic granule exocytosis from natural killer (NK) and T-cells, manifesting clinically as hemophagocytic lymphohistiocytosis (HLH). Hematopoietic stem cell transplantation in one of the patients resulted in stable chimerism; however, the second case relapsed within a month after SCT. Stem cell transplantation is the only curative therapeutic option for GS2; thus, improvement in posttransplantation management may reduce mortality and posttransplant complications. Hence, any child who presents with partial albinism and clinical features suggestive of HLH, a peripheral blood, hair shaft mount examination along with basic immunological NK and T-cell cytotoxicity assay by flow cytometry will help clinch the diagnosis early. It can subsequently be confirmed by molecular study. Timely therapeutic intervention can prevent relapses and severe infection and improve outcome in these cases.

Paediatric chronic myeloid leukaemia: Is it really a different disease?

Paediatric chronic myeloid leukaemia (CML) has biological and clinical differences from adult CML. Management of paediatric CML presents unique challenges in growing children, and there are no specific guidelines for paediatric CML. This review focusses on the clinical characteristics, diagnostic issues and management of paediatric CML. Major studies that provide the basis of managing paediatric CML are summerized here. Studies conducted on adult CML patients were used to guide the management of places where studies were lacking in paediatric CML. Recently, dasatinib and nilotinib have been approved for treatment of paediatric CML, and their role has been discussed in the current management perspective. Allogeneic transplant, fertility and vaccination in paediatric CML, have also been discussed.

Indicators of malnutrition in children with cancer: A study of 690 patients from a tertiary care cancer center.

BACKGROUND: Large data pertaining to indicators of malnutrition in children with cancer is lacking from India. In view of this, we prospectively analyzed consecutive de novo childhood patients with cancer presenting at a tertiary care center. MATERIALS AND METHODS: Height and weight of each child (n = 690) were compared with World Health Organization child growth standards‑2006 for that particular age and sex to get weight‑for‑age, height‑for‑age, and weight‑for‑height indices and below 2SD of the reference median on these indices were considered as underweight, stunted, and wasted, respectively. Body mass index (BMI) for age was also analyzed for thinness and obesity. RESULTS: Prevalence of malnutrition based on Z‑score for weight‑for‑age, height‑for‑age, weight‑for‑height, and BMI‑for‑age was 30%, 31%, 35%, and 41%, respectively. Weight‑for‑age (underweight) was significantly associated (P = 0.018) with solid tumors. Height‑for‑age, weight‑for‑age, and BMI‑for‑age were significantly associated (P = 0.007, P = 0.016, and P ≤ 0.001, respectively) with rural community. CONCLUSION: Malnutrition was observed in approximately one‑third of children with cancer. Malnutrition is associated with solid tumors and those coming from rural community. Wasting has a higher prevalence in children with cancer in <5 years of age group.

Adiponectin correlates with obesity: A study of 159 childhood acute leukemia survivors from India.

BACKGROUND: Acute lymphoblastic leukemia survivors are predisposed to obesity. However, the exact underlying mechanisms are not known. AIMS: The study was done to assess the role of biomarkers of obesity in acute leukemia survivors. SETTINGS AND DESIGNS: This is a cross‑sectional study conducted at All India Institute of Medical Sciences in survivors of acute leukemia who had completed treatment at least 1 year before enrollment in this study. MATERIALS AND METHODS: Obesity was studied by determining the body mass index. Potential biomarkers were studied by assessing serum leptin, resistin, and adiponectin by enzyme‑linked immunosorbant assay, and the results were compared in obese versus nonobese survivors. STATISTICAL ANALYSIS: Descriptive analysis for baseline demographic factors and Student’s t‑test for comparing the mean levels of biomarkers among the obese and nonobese survivors. RESULTS: One hundred and fifty‑nine acute leukemia patients were enrolled in this study with a median follow‑up of 36.8 months. The median age was 10 (range: 3–18) years, and 123 (77.3%) patients were males. The overall prevalence of overweight/obesity was 26.4%, and this was similar in acute myeloid leukemia and acute lymphoblastic leukemia sub‑groups (26.2% vs. 27.3%, P = 0.9). Mean serum leptin and resistin were similar in obese and nonobese leukemia survivors (3.7 vs. 2.85 pg/mL, P = 0.064; 8.01 vs. 9.33 ng/mL, P = 0.36). However, mean serum adiponectin was significantly lower in obese leukemia survivors (7.97 vs. 11.5 μg/mL, P = 0.023). CONCLUSIONS: Obese leukemic survivors had lower serum adiponectin levels than nonobese survivors. However, serum resistin and leptin levels were similar in the two groups.

Review of spectrum and sensitivity of bacterial bloodstream isolates in children with malignancy: A retrospective analysis from a single center.

BACKGROUND: Febrile neutropenia is a life‑threatening emergency in pediatric cancer patients. Its management is based on established guidelines that emphasize on prompt action. Consideration of local microbiologic spectrum and its susceptibility is pivotal in devising a rational protocol. AIMS: To study the spectrum of bacterial isolates and its antibiotic sensitivity profile in bloodstream infections (BSIs) of pediatric cancer patients. SETTINGS AND DESIGN: Retrospective study. MATERIALS AND METHODS: This study was conducted at a tertiary cancer center for pediatric cancer patients. Blood culture samples sent during the evaluation of patients with clinical diagnosis of febrile neutropenia during the year of 2013 were analyzed. The microbiological and antibiotic sensitivity patterns were studied. RESULTS: A total of 27 isolates represented BSIs out of 412 blood cultures sent (6.5%). These were predominantly Gram‑negative (92%) with Klebsiella contributing to the majority of them. Extended spectrum beta‑lactamase production was seen in 59% of all isolates. Multidrug resistance phenotype was seen in 48%, extreme drug resistance in 32% and pan drug resistance in 16% of Gram‑negative isolates. Klebsiella predominated in all of these isolates. Mortality resulted in 15% isolates, majorly contributed by Klebsiella. Colistin was the most sensitive antibiotic (75% sensitivity) and in significant number of cases the only salvage option. CONCLUSION: Gram‑negative bacteria are the most common etiologic agents. The emergence of drug resistant strains of Klebsiella and the poor sensitivity of most of these strains to common first choice empiric agents is alarming. Low prevalence of Gram‑positive organisms questions the routine use of empiric vancomycin.

Role of extracorporeal irradiation in malignant bone tumors.

Aims and Objectives: Extracorporeal irradiation (ECI) is relatively a rare method used in the management of malignant bone tumors (MBT). It consists of en-bloc removal of the tumor bearing bone segment, removal of the tumor from the bone, irradiation, and re-implantation back in the body. We report our preliminary experience of using ECI for management of MBT. Materials and Methods: From year 2009 to 2010, 14 patients with primary MBT were enrolled into this study. The eligibility criteria included histopathological proof of malignancy, no evidence of distant metastases, and suitability for limb preservation therapy. Surgery was performed about 4 weeks after completion of neoadjuvant chemotherapy. The affected bone segment was resected, irradiated extracorporeally with a dose of 50 Gy and reimplanted. Local control, complications and short-term survival were studied. Functional outcome was assessed by Musculoskeletal Tumor Society (MSTS) scoring system. Results: There were 10 males and four females with median age of 14 years. Histopthologically, nine patients had osteosarcoma (OS) and five had Ewing's sarcoma family of tumors (ESFT). Distribution of primary site was as follows: Femur eight patients, tibia five patients and humerus one patient. At a median follow-up was 22 months, three patients (two OS, one ESFT) had local recurrence. Two patients (14%) developed wound infection in the perioperative period. The 2 year local recurrence free survival was 73% and mean MSTS score was 88. Conclusion: Results of our study suggest that ECI is technically feasible in the management of MBT and provides decent local control and short-term survival rates.

Primary testicular non-Hodgkin lymphoma: a single institution experience from India.

BACKGROUND: Primary testicular non-Hodgkin lymphoma (NHL) is an uncommon extra nodal presentation, constituting 1% of all NHL. Median age at time of presentation is 60 years. Anthracycline based chemotherapies are most frequently used. There is not enough data on use of monoclonal antibody (Rituximab) in testicular NHL. METHODS: We screened approximately eight hundred and fifty NHL cases registered from January 2002 to May 2008 and found six primary testicular NHL patients. These six cases were analyzed for baseline clinical features, investigations, staging, treatment and outcome variables. RESULTS: Median age was 55 years (range 7-72 years) and median duration of symptoms was 3.5 months (range 1-8 months). All patients had testicular swelling and abdominal lymphadenopathy. Five patients (83%) had stage IV and one had stage IE disease. Majority had diffuse large B-cell histology (83%). All patients were treated with anthracycline based combination chemotherapy and CNS prophylaxis after local therapy except one pediatric patient who did not receive any local therapy. Four patients completed therapy and are on follow up while two patients having extensive disease with poor performance status died of neutropenic sepsis after 1-2 cycles of chemotherapy. The surviving four patients achieved complete remission and are without any recurrence with a median follow up of 26 months (1-78 months). CONCLUSION: Primary testicular NHL is an uncommon entity and with current combined modality treatment and CNS prophylaxis, the outcome may be as good as nodal NHL.

Etiopathophysiology of disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) involves activation of clotting as well as fibrinolytic pathways. Thrombosis from thrombin release results in end-organ damage, whereas consumption of coagulation factors results in bleeding. Sepsis is the commonest cause of DIC. The consumption of antithrombin in sepsis abrogates its anti-inflammatory role and so its low level is a poor prognostic marker in sepsis. The increased release of plasminogen activator inhibitor-1 (PAI-1) as seen in sepsis decreases fibrinolysis and promotes increased microvascular thrombosis. Here, we discuss the role of inhibitors of coagulation, cytokines, kinins, complement and vasoactive peptides in DIC.