Clinical review of COVID-19 in children and adolescents with cancer: Experience from a tertiary care center in East India.

Children with underlying cancer are often immunocompromised. Data on severity of coronavirus disease 2019 (COVID-19) in children with cancer and its outcomes is emerging. Treatment protocols of specific cancers are decided based on the infrastructure, availability of supportive-care, and logistic issues of the locality. The purpose of the study was clinical analysis of COVID-19 in children and adolescents with cancer. The retrospective observational study was conducted at a tertiary healthcare-center in East India. Children and adolescents (aged 0-19 years) with cancer and under treatment with reverse-transcriptase-polymerase-chain-reaction (RT-PCR) confirmed COVID-19 between 5-July-2020 and 5-December-2020 were studied. Median age of the 68 identified patients was six years. Acute leukemia was the most common (66%) diagnosis. COVID-19 was asymptomatic/mildly symptomatic in 91% and moderate to severe in only 9% of patients. Fever (87%) was the commonest symptom, followed-by cough/coryza (75%). Three patients with acute myeloid leukemia (AML) and severe/critical COVID-19 and associated neutropenic sepsis were required transfer to the intensive-care-unit (ICU) for management. Three (4.4%) patients succumbed with COVID-19. Delay in treatment was observed in 63.2% of patients, and the median duration of delay was 28 days after acquiring COVID-19. Median time to attain negative COVID-19 RT-PCR was 16 days, and eight patients were repeat positives. While pediatric and adolescent cancer patients on active treatment may have a higher risk of mortality from severe COVID-19 than their healthy counterparts, the risk may be much lower than deemed. It is essential to continue cancer therapy in these children. Delay in treatment remains a concern.

Acquired Pure Red Cell Aplasia Following Recombinant Erythropoietin (Darbepoetin-alfa) Therapy.

Acquired pure red cell aplasia (PRCA) following use of recombinant erythropoietin (rEPO) is distinctly rare and sporadically reported in the literature. We discuss a case of PRCA following the usage of rEPO (darbepoetin-α) during the management of anemia of chronic kidney disease in an elderly male subject with review of literature and a brief insight into proposed pathophysiologic mechanism, diagnosis, and management.

Serotonin syndrome after concomitant treatment with linezolid and meperidine.

Serotonin syndrome has been reported with administration of linezolid and serotonin reuptake inhibitors. Meperidine blocks the neuronal reuptake of serotonin. Serotonin syndrome after concomitant linezolid and meperidine therapy has not been described. We describe serotonin syndrome after concomitant use of linezolid and meperidine in a 27-year-old man with acute leukemia.

Outcome of children with aplastic anemia treated with immunosuppressive therapy.

BACKGROUND: Immunosuppressive therapy (IST) is the alternative treatment in children with aplastic anemia (AA) who do not have an HLA-matched sibling. The aim of this study is to evaluate the outcome of children with AA treated with IST. METHODS: We retrospectively reviewed the hospital records of children with AA from 1984 to 2004, treated at our institution with antithymocyte globulin (ATG), cyclosporine (CS), and short course of prednisone. RESULT: Forty-two patients were treated with IST (24 boys, 18 girls); of whom 26% received G-CSF. The median age at diagnosis was 8.5 years. Sixty-nine, 19, and 12% were diagnosed with severe, very severe, and moderate AA, respectively. Twenty-one percent had hepatitis-associated AA. Median follow-up time was 53.3 months. Sixty-two percent had complete response; 19% had partial response. Two patients relapsed and received a second course of ATG; both had a partial response. The actuarial 5 years survival rate was 67.5%. Two patients developed myelodysplastic syndrome (MDS); both received long-term G-CSF and had partial response after two courses of IST. Fifteen percent of survivors had significant hypertension which persisted after CS was discontinued. CONCLUSIONS: This study shows promising response in children with AA treated with IST; however, the outcome was inferior to our institutional results with hematopoietic stem cell transplantation from a sibling donor. Hypertension and MDS are late complications. Longer follow-up, larger cohorts, and prospective studies are warranted to evaluate late complications and risk factors.

Achievement of target cyclosporine concentrations as a predictor of severe acute graft versus host disease in children undergoing hematopoietic stem cell transplantation and receiving cyclosporine and methotrexate prophylaxis.

This study evaluates our institution's target trough cyclosporine (CSA) concentrations as predictors of severe acute graft versus host disease (aGvHD) in children receiving either matched related or unrelated hematopoietic stem cell transplantation (HSCT). The outcomes of 87 consecutive children who underwent allogeneic HSCT and received CSA and methotrexate as prophylaxis against aGvHD between October 1, 1999 and September 30, 2002 were retrospectively evaluated. The proportion of time that each patient maintained a whole blood CSA concentration within or above the initial target range (105-155 ng/mL or 155-210 ng/mL) was calculated for each of the following time periods: in each week after HSCT from day 0 to +28; in the week preceding engraftment; and in the week preceding the onset of aGvHD. Patients were prospectively evaluated twice weekly for the presence and severity of aGvHD by senior attending physicians. The relationship between potential predictors and the development of severe aGvHD was examined using univariate logistic regression. The main variables of interest were the proportion of time that therapeutic or supratherapeutic CSA concentrations were maintained; median CSA concentrations; the number of methotrexate doses received; and the use of folinic acid rescue. Mean follow-up time was 3.0+/-1.9 years among children who survived beyond day +100. Three variables were significantly associated with the development of severe aGvHD on univariate analysis: initial CSA target concentration [odds ratio (OR), 0.24; P=0.03], proportion of time the target CSA concentration was achieved during the second week after transplant (OR, 0.16; P=0.02), and proportion of time the target CSA concentration was achieved during the week before engraftment (OR, 0.22; P=0.0489). Multivariable analysis demonstrated an inverse relationship between the median CSA concentration during the week before engraftment and the development of severe aGvHD (OR, 0.99; P=0.045). These results suggest that achievement of our CSA target concentrations is important to aGvHD outcomes.

Characteristics and outcomes of acute myelogenous leukemia patients with very late relapse (>5 years).

The clinical characteristics and outcome of 15 patients with acute myelogenous leukemia (AML) who experienced relapse at least 5 years after induction of complete remission (very late-relapse AML) are described. This subgroup represented 3% of all relapsed patients seen at this institution over the same time period. There were eight males in this cohort and the median age at diagnosis was 48 years (range 13 - 77 years). Nine patients had M4/M5 French - American - British (FAB) classification subtype and most had intermediate risk cytogenetics. The median duration of first complete remission (CR-1) was 9 years (range 5.2 - 11.5 years). Thirteen patients (86%) achieved CR-2 with reinduction therapy. The 5-year relapse-free survival and overall survival rates of this cohort were 59% and 51%, respectively. We conclude that very late-relapse AML is a rare event, and that reinduction in these patients is associated with very high CR rates and a potential cure fraction.

Remission of aplastic anemia induced by treatment for Graves disease in a pediatric patient.

Aplastic anemia (AA) is mediated by T-cell autoimmunity in the majority of cases; it is rare and mostly idiopathic in children. We describe a child, who developed AA following Graves' disease which could not be attributed to antithyroid drugs. We hypothesized that both diseases were caused by similar autoimmune process. We monitored the blood counts and did not administer any conventional treatment for AA assuming that the existing anti- hematopoietic stem cell humoral and cellular immunity might subside with induction of remission of Grave's disease. The child went into complete remission with the treatment of the Graves' disease.

Use of recombinant factor VIIa prior to lumbar puncture in pediatric patients with acute leukemia.

The persistence of abnormal coagulation test results after standard treatment with fresh frozen plasma (FFP) poses significant problems in children with acute leukemia requiring a diagnostic lumbar puncture and intrathecal chemotherapy. We report the prophylactic use of a single dose of 90 microg/kg recombinant activated factor VII (rFVIIa) in three children and the rapid correction of abnormal coagulation test results previously not corrected by FFP. Administration of rFVIIa was useful in avoiding a delay of diagnostic lumbar punctures and intrathecal chemotherapy. Hemorrhagic complications and adverse effects of rFVIIa were not observed. Prospective evaluation of this indication and dose appears warranted. (c) 2005 Wiley-Liss, Inc.

DDAVP-induced hyponatremia in young children.

Desmopressin (DDAVP) is used to improve hemostasis in patients with bleeding disorders. The side effects of DDAVP in adults and children are benign. However, there has been concern regarding the development of hyponatremia and seizures after the use of DDAVP in young children. The authors describe three children under 3 years of age who developed hyponatremia (two also developed seizures) following intravenous administration of DDAVP at a standard dose of 0.3 mug/kg. Fluid restriction, avoidance of hypo-osmolar fluid, and close monitoring of fluid and electrolytes for 12 to 24 hours after the administration of DDAVP in children younger than 3 years of age is recommended.

Remote intrapulmonary spread of recurrent respiratory papillomatosis with malignant transformation.

Recurrent respiratory papillomatosis is the most common neoplasm of the larynx in childhood. Extension into lung parenchyma occurs in less than 1% of patients and has a low risk of malignant transformation. Treatment options for intrapulmonary spread have shown limited success. We describe a case of recurrent respiratory papillomatosis with extensive parenchymal involvement and adenosquamous carcinoma in a 14-year-old girl.

Lymphomatous involvement of the heart in children: two cases and a review of the literature.

Primary cardiac lymphoma (PCL) is a rare presentation of lymphoma in children. The emergency nature of its presentation (heart failure and arrhythmias) makes management of this entity difficult. The authors describe two children with lymphoma primarily involving the heart; one patient was a case of PCL and the other was a case of lymphoma involving the heart along with pelvic involvement. These two patients, together with a literature review on the topic, suggest that if the diagnosis of PCL is made early and treatment is expeditiously started, patients may do well.