Richa Jain

Hyperleukocytosis: Emergency Management

Hyperleukocytosis is defined as peripheral blood leukocyte count exceeding 100,000/mm3. Acute leukemia is the most common etiology in pediatric practice. Hyperleukocytosis is a medical emergency. The increased blood viscosity, secondary to high white cell count and leukocyte aggregates, results in stasis in the smaller blood vessels. This predisposes to neurological, pulmonary or gastrointestinal complications. In addition, patients are at risk for tumor lysis syndrome due to the increased tumor burden. Initial management includes aggressive hydration, prevention of tumor lysis syndrome, and correction of metabolic abnormalities. A red cell transfusion is not indicated in a hemodynamically stable child, as it adversely affects the blood viscosity. Leukapheresis is the treatment of choice for a very high count, or in patients with symptomatic hyperleukocytosis. The technical expertise required, a relative difficult venous access in younger children, risk of anticoagulation and possible non-availability of the procedure in emergency hours are limitations of leukapheresis. However, it is a rewarding procedure and performed with relative ease in centers that perform the procedure frequently. An exchange transfusion is often a practical option when hyperleukocytosis is complicated with severe anemia. The partial exchange aids in correcting both, without the risk of volume overload or hyperviscosity, which are the limitations of hydration and blood transfusion, respectively. Etiology and management of hyperleukocytosis in relevance to the pediatric emergency room is outlined.

Cytomegalovirus Retinitis in an ALL child on exclusive chemotherapy treated successfully with intravitreal ganciclovir alone.

A child suffering from acute lymphoblastic leukemia on treatment with exclusive chemotherapy presented with vision-threatening cytomegalovirus (CMV) retinitis in 1 eye. Prompt diagnosis and treatment with 3 weekly doses of 2 mg/0.1 mL intravitreal ganciclovir resulted in successful healing of CMV retinitis with restoration of visual acuity. In children with acute lymphoblastic leukemia on exclusive chemotherapy without hematopoietic stem cell transplantation, CMV retinitis has been reported in only 1 case in literature. This child was treated successfully with intravenous ganciclovir. This report highlights the use of successful intravitreal ganciclovir in pediatric age group to avoid side effects of systemic ganciclovir.

Cytomegalovirus disease in children with acute lymphoblastic leukemia

ABSTRACT Viral infections are an underrecognized problem in children on standard chemotherapy for acute lymphoblastic leukemia (ALL). In countries with high baseline seroprevalence of cytomegalovirus (CMV) such as India, it may be an important pathogen leading to fever, end-organ damage, and cytopenia. Data regarding the incidence and manifestations of CMV disease in pediatric ALL patients are scanty. The authors prospectively assessed all children on chemotherapy for ALL with prolonged febrile neutropenia (FN) for CMV disease over a 3-year period. Children with end-organ damage, including pneumonia, retinitis, and colitis, were also evaluated. Quantitative and qualitative polymerase chain reaction (PCR) from blood, body fluids, or tissue was done along with ophthalmologic evaluation. CMV disease was detected in 10% of the children with prolonged FN. In addition, other children were identified due to end-organ damage, lung and eye being the common organs of involvement. Time of CMV reactivation was essentially during nonintense phase of chemotherapy. Lymphopenia was present in most children, and prolonged lymphopenia was associated with relapse of CMV infection after therapy. The authors conclude that CMV is an important pathogen in children on standard chemotherapy for ALL. It has a good outcome with early detection and directed therapy. Parenteral ganciclovir is needed for a period of 14–21 days to prevent recurrence.

Systematic evaluation of paediatric cohort with iron refractory iron deficiency anaemia (IRIDA) phenotype reveals multiple TMPRSS6 gene variations

Systematic screening identified patients with an iron refractory iron deficiency anaemia (IRIDA) phenotype and genotype in iron‐deficient children in the Indian subcontinent. Cases of moderate to severe microcytosis and anaemia with no obvious cause and normal C‐reactive protein, HbA2 and tissue transglutaminase antibody levels (n = 550) were put on a trial of oral iron for 4 weeks. Sixty of these 550 cases (11%) were variably refractory to oral iron therapy (<10 g/l Hb rise) at 4–6 weeks and were subsequently evaluated for plasma iron, ferritin and hepcidin levels. The mean age of this cohort was 2.06 years. Low‐normal to normal ferritin and normal to high hepcidin levels were noted in 25/60 (41.6%) and 47/60 (78.3%), respectively. An IRIDA phenotype was noted in 38.3% (23/60) based on standard criteria. TMPRSS6 gene sequencing in 20 cases with IRIDA phenotype revealed 9 potentially deleterious intronic and two benign exonic variations in 12/20 cases (60%). Of these, 4 intronic and both exonic variations were noted in multiple cases and are likely to act synergistically leading to an IRIDA phenotype. However, given that only 38% (23/60 cases) of cases with iron refractoriness had IRIDA phenotype, a balanced approach is needed and other causes for refractoriness should be investigated before genetic studies for TMPRSS6 are undertaken.

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.

Improving the safety of high-dose methotrexate for children with hematologic cancers in settings without access to MTX levels using extended hydration and additional leucovorin

A lack of access to methotrexate levels is common in low‐ and middle‐income countries (LMIC), relevant for 80% of children with cancer worldwide. We evaluated whether high‐dose methotrexate (HD‐MTX) can be administered safely with extended hydration and leucovorin rescue, with monitoring of serum creatinine and urine pH.

High frequency of intermediate and poor risk copy number abnormalities in pediatric cohort of B-ALL correlate with high MRD post induction

Copy number abnormalities (CNAs) and recurrent fusion transcripts are important genetic events which define and prognosticate B-Cell Acute Lymphoblastic Leukemia (B-ALL). We evaluated CNAs and fusion transcripts in 67 pediatric B-ALL cases and correlated the data with standard risk factors and early treatment outcome parameters. Common fusion transcripts ETV6-RUNX1, E2A-PBX, BCR-ABL1 and MLL-AF4 were examined by RT-PCR and noted in 15%, 15%, 13% and 1.4% of all cases respectively. CNAs in IKZF1, PAX5, EBF1, BTG1, RB1, CDKN2A/B and genes from PAR1 region viz., CSF2RA, IL3RA,P2RY8, SHOX region and CRLF2 were analyzed by multiplex ligation dependent probe amplification assay and were detected in 70% (47/67) of cases, with predominantly deletions in CDKN2A/B (36%), PAX5 (18%) and IKZF1 (16%). A statistically significant association of intermediate/poor risk CNAs was noted with high WBC count (p = 0.001), NCI group (p = 0.02) and minimal residual disease at Day35 (p < 0.0001). IKZF1 and CDKN2A/B deletion revealed poor EFS of 56% at 24 months as compared to EFS of 80% in rest of the cases (p = 0.05) suggesting their potential role in early risk stratification.

Plasma hepcidin levels in healthy children from Chandigarh, Northern India

Hepcidin is a key molecule involved in iron homeostasis. We measured hepcidin levels in 50 healthy children from Chandigarh, Northern India for establishing normal ranges. Hepcidin ranges (19.96-36.6 ng/mL; 0-2 years) and (9.54-36.15 ng/mL; 2-6 years) with mean (SD) of 32.5 (4.84) ng/mL, and 31.13 (6.62) ng/mL respectively were noted in study participants. The mean (SD) and ranges for plasma hepcidin in boys and girls in the study was 31.01 (6.71) ng/mL (9.54-36.6 ng/mL) and 32.7 (4.14) ng/mL (19-36.2 ng/mL), respectively.

Orbital Mass in a Child With Acute Lymphoblastic Leukemia: A Case Report and Review of the Literature.

Acute lymphoblastic leukemia arising from lymphoid precursor cells of the bone marrow, the lymphoreticular system, and the soft tissue can present with medullary and extramedullary involvement. Extramedullary involvement has the propensity to affect a multitude of organs. Presentation with proptosis secondary to orbital mass in childhood acute lymphoblastic leukemia (ALL) is very rare. We report a child with pre-B cell ALL with an extramedullary soft tissue mass involving both orbits presenting with proptosis, and give a brief overview of the literature about this unusual entity. Rapid investigation and timely initiation of treatment are needed to salvage the eye and the vision. Orbital involvement is considered to confer a poorer prognosis to children with ALL.

Primary paratesticular yolk sac tumor: A case report and review of literature

Paratesticular germ cell tumors are extremely rare. A 12-month-old boy with yolk sac tumor involving only the paratesticular tissue is reported. Pre-operatively raised alpha fetoprotein levels fell to normal levels after high inguinal orchiectomy. This appears to be the youngest and only the 3rd case reported in the English literature.