Diagnosis and Management of Acquired Aplastic Anemia: Consensus Statement of Indian Academy of Pediatrics.

JUSTIFICATION: In India, there is a lack of uniformity of treatment strategies for aplastic anemia (AA), and many children are managed only with supportive care due to non-availability of hematopoietic stem cell transplantation (HSCT). PROCESS: Eminent national faculty members were invited to participate in the process of forming a consensus statement in Hyderabad in July, 2016. Draft guidelines were circulated to all members, and comments received in a online meeting in October, 2020 were incorporated into the final draft. These were approved by all experts. Objective: To facilitate appropriate management of children with acquired aplastic anemia. RECOMMENDATIONS: Key recommendations are: i) A bone marrow biopsy is must to make a diagnosis of AA; ii) Rule out inherited bone marrow failure syndromes (IBMFS), connective tissue disorders, viral infections, paroxysmal nocturnal hemoglobinuria (PNH), drug or heavy metal induced marrow suppression in all cases of AA; iii) Conservative approach to transfusions should be followed, with a target to keep hemoglobin >6 g/dL in children with no co-morbidities; iv) HLA-matched sibling donor HSCT is the preferred choice of treatment for newly diagnosed very severe/ severe AA; v) In absence of HLA-matched family donor, a matched unrelated donor (MUD) transplant or immunosuppressive therapy (IST) should be considered as alternate choice based on physician expertise; vi) Fludarabine, cyclophos-phamide and anti-thymocyte globulin (ATG) based conditioning with cyclosporine and methotrexate as graft versus host disease (GvHD) prophylaxis is the preferred regimen; vii) Horse ATG and cyclosporine are the recommended drugs for IST. One should wait for 3-6 months for the response assessment and consideration of next line therapy.

Pediatric Hemophagocytic Lymphohistiocytosis - A Single Center Study.

OBJECTIVE: To describe the epidemiological features, outcomes and prognostic factors in diagnosis of pediatric hemophagocytic lymphohistiocytosis (HLH). METHODS: 118 children fulfilling the inclusion criteria for HLH were identified from review of hospital records for period January, 2010 to December, 2019. RESULT: Median age at diagnosis was 4 years (range13 days-15 years). Presenting features were fever (100%), hepatosplenomegaly (91%), neurological symptoms (23%), bicytopenia (76%), transaminitis (67.3%), increased soluble interleukin-2 receptor) (sIL-2R) (78%) and hemophagocytosis on bone marrow (75%). Median follow-up duration was 13.5 months (3 days to 102 months). Primary HLH was identified in 27 (23%) patients. Etiology of secondary HLH was infections in 53 (45%), rheumatologic illnesses in 21 (18%) and malignancies in 8 (6%) children. Treatment modalities were steroid only (25%), anti-infectious agent (58%), multi-agent chemotherapy (43%) and HSCT (40%); mortality among above treatment groups were 25%, 58%, 43% and 40%, respectively. 15 patients (13%) had relapsed/refractory HLH who were treated with salvage chemotherapy and hematopoietic stem cell transplantation (HSCT). The overall mortality rate was 39%; mortality within 30 days seen in 23%. Estimated overall survival (OS) and event free survival (EFS) at 3 years were 62% and 61%, respectively. CONCLUSION: Pediatric HLH is an aggressive disease with high mortality. Hyponatremia, hyperbilirubinemia, coagulopathy and increased sIL2 receptor level at diagnosis predicts poor outcome.

Clinical Profile and Outcome of Childhood Autoimmune Hemolytic Anemia: A Single Center Study.

OBJECTIVE: To analyze clinical and laboratory parameters, and treatment outcomes of children with autoimmune hemolytic anemia (AIHA). METHODS: Retrospective analysis of 50 children aged 0-18 years. Monospecific direct antiglobulin test (DAT) and investigations for secondary causes were performed. Disease status was categorized based on Cerevance criteria. RESULTS: Median (range) age at diagnosis was 36 (1.5-204) months. AIHA was categorized as cold (IgM+,C3+/cold agglutinin+) (35%), warm (IgG+ with/without C3+) (28%), mixed (IgG+, IgM+, C3+) (15%) and paroxysmal cold hemoglobinuria (4%). Primary AIHA accounted for 64% cases. Treatment modalities included steroid (66%), intravenous immunoglobulin (IVIg) (4%), steroid+IVIg (4%), and steroid+rituximab (4%). Treatment duration was longer for secondary AIHA than primary (11 vs 6.6 months, P<0.02) and in patients needing polytherapy than steroids only (13.3 vs 7.5 months, P<0.006). During median (range) follow-up period of 73 (1-150) months, 29 (58%) remained in continuous complete remission, 16 (32%) remained in complete remission. CONCLUSIONS: Infants with AIHA have a more severe presentation. Monospecific DAT and a thorough search for an underlying cause help optimize therapy in most patients of AIHA.

Oral Ondansetron in Management of Dehydrating Diarrhea with Vomiting in Children Aged 3 Months to 5 Years: A Randomized Controlled Trial.

OBJECTIVES: To evaluate the role of oral ondansetron in facilitating successful rehydration of under-5-year-old children suffering from acute diarrhea with vomiting and some dehydration. STUDY DESIGN: Children (n = 170) aged 3 months to 5 years with acute diarrhea with vomiting and some dehydration were enrolled in this double blind, randomized, placebo-controlled trial. The participants were randomized to receive either single dose of oral ondansetron (n = 85) or placebo (n = 85) in addition to standard management of dehydration according to World Health Organization guidelines. Failure of oral rehydration therapy (ORT), administration of unscheduled intravenous fluids, and amount of oral rehydration solution intake in 4 hours were the primary outcomes. Secondary outcome measures included duration of dehydration correction, number of vomiting episodes, adverse effects, and caregiver satisfaction. RESULTS: Failure of ORT was significantly less in children receiving ondansetron compared with those receiving placebo (31% vs 62%; P < .001; relative risk 0.50, 95% CI 0.35-0.72). Almost one-half of the children in the ondansetron group received intravenous fluids compared with those in the placebo group, but it was not statistically significant (P = .074; relative risk 0.56, 95% CI 0.30-1.07). The oral rehydration solution consumption was significantly more in the ondansetron group (645 mL vs 554 mL; mean difference 91 mL; 95% CI: 35-148 mL). Patients in the ondansetron group also showed faster rehydration, lesser number of vomiting episodes, and better caregiver satisfaction. CONCLUSION: A single oral dose of ondansetron, given before starting ORT to children <5 years of age with acute diarrhea and vomiting results in better oral rehydration. TRIAL REGISTRATION: Clinical Trial Registry of India: CTRI-2011/07/001916.