Hodgkin Lymphoma in Children Under 5 Years: Do They Behave Differently?

The median age of presentation for Hodgkin lymphoma (HL) is lower in developing countries with a higher proportion under 5 years of age possibly attributable to the high prevalence of Epstein-Barr virus-driven disease. It is unclear whether the clinical presentation and outcomes of this cohort are different with concern regarding late effects being most pronounced in this age group. We report the outcome of children under 5 years of age enrolled in the InPOG-HL-15-01, the first multicentric collaborative study for newly diagnosed children and adolescents with HL from India. Thirty-five (9%) of the study population was younger than 5 years with a striking male preponderance of 34:1. They were less likely to have bulky disease, mediastinal or splenic involvement. The outcomes appear to be at least as favorable as in the older patient group. Efforts need to be made to evolve treatment strategies that spare this very young cohort from potential late effects.

Once-a-Day Ceftriaxone-Amikacin Combination as Empiric Antibiotic Therapy to Enable Outpatient Management of Febrile Neutropenia in Children-16-Year Experience from a Single Institute.

Shailesh KanvindeBackground To enable outpatient department (OPD) management of febrile neutropenia (FN), we used once-a-day (OD) ceftriaxone-amikacin (CFT-AMK) as empiric antibiotic therapy. Our experience over 16-year period is presented. Methods This was a retrospective study conducted from January2002 to December2017. Inclusion criteria were <18 years of age, undergoing cancer chemotherapy, and having FN. Exclusion criteria were FN after palliative chemotherapy, bone marrow transplantation, or at diagnosis of malignancy. Empiric CFT-AMK was used in all, except those having respiratory distress, hypotension, altered sensorium, paralytic ileus, or clinical evidence of peritonitis. Admission criteria were age <1 year, acute myeloid leukemia (AML) chemotherapy, poor performance status, need for blood transfusions, convenience, insurance, or persistent fever >48 to 72 hours after CFT-AMK. Outcomes analyzed were response (defervescence within 48-72 hours), OPD management, antibiotic upgrade, and mortality. AML diagnosis, >7 days to absolute neutrophil count >0.5 × 10 9 /L, poor performance status, and malignancy not in remission were considered high-risk FN criteria. Results CFT-AMK was given in 877/952 (92.2%) FN episodes. Seventy-six percent had hematolymphoid malignancies. Response, antibiotic upgrade, and mortality were seen in 85.7 and 65.5% ( p < 0.0001), 15 and 45.5% ( p < 0.0001), and 0 and 2% ( p = 0.003) of low- and high-risk patients, respectively. Treatment was started in OPD in 52%, of which 21.6% required subsequent admission. Of those initially admitted, early discharge (hospital stay < 5 days) was possible in 24.6%. Forty-one percent episodes were managed entirely on OPD. Overall, 80% of low-risk and 42% of high-risk episodes received treatment wholly or partially on OPD. Conclusion Our results show empiric OD CFT-AMK allows OPD management for most of the low-risk and a proportion of high-risk FN following chemotherapy in children, without compromising clinical outcomes.

A comprehensive molecular study identified 12 complementation groups with 56 novel FANC gene variants in Indian Fanconi anemia subjects.

Fanconi anemia (FA) is a rare autosomal or X-linked genetic disorder characterized by chromosomal breakages, congenital abnormalities, bone marrow failure (BMF), and cancer. There has been a discovery of 22 FANC genes known to be involved in the FA pathway. This wide number of pathway components makes molecular diagnosis challenging for FA. We present here the most comprehensive molecular diagnosis of FA subjects from India. We observed a high frequency (4.42 ± 1.5 breaks/metaphase) of chromosomal breakages in 181 FA subjects. The major clinical abnormalities observed were skin pigmentation (70.2%), short stature (46.4%), and skeletal abnormalities (43.1%), along with a few minor clinical abnormalities. The combination of Sanger sequencing and Next Generation Sequencing could molecularly characterize 164 (90.6%) FA patients and identified 12 different complementation groups [FANCA (56.10%), FANCG (16.46%), FANCL (12.80%), FANCD2 (4.88%), FANCJ (2.44%), FANCE (1.22%), FANCF (1.22%), FANCI (1.22%), FANCN (1.22%), FANCC (1.22%), FANCD1 (0.61%) and FANCB (0.61%)]. A total of 56 novel variants were identified in our cohort, including a hotspot variant: a deletion of exon 27 in the FANCA gene and a nonsense variant at c.787 C>T in the FANCG gene. Our comprehensive molecular findings can aid in the stratification of molecular investigation in the diagnosis and management of FA patients.

Cytomegalovirus infection as a cause of cytopenia after chemotherapy for hematological malignancies.

OBJECTIVE: Unlike hematopoietic stem cell transplantation, there is very little information on cytomegalovirus (CMV) related cytopenias occurring in patients having acute lymphoblastic leukemia (ALL) or Non Hodgkin's lymphoma (NHL) receiving standard dose chemotherapy (SDCT). We studied the role of CMV infection in cytopenias after SDCT for childhood ALL or NHL. DESIGN: Retrospective study. SETTING: Pediatric Oncology Unit. METHODS: Between January 2007 and March 2010, we screened all children having ALL/NHL having prolonged cytopenia (ANC<1,000/cmm and/or platelets <1,00,000/cmm; >10 days beyond date for next chemotherapy; not explainable on basis of previously administered chemotherapy) for CMV infection. Testing for CMV infection was done by pp65 antigen assay, qualitative or quantitative RT-PCR. CMV positive episodes were analyzed for relationship to previous chemotherapy, clinical features and response to treatment. RESULTS: As defined, 24 episodes of cytopenia were identified. CMV infection was detected in 13/24 (54%) episodes in 9 patients. Duration of cytopenia in patients having CMV infection: 14-126 days (median 28 d). Neutropenia or thrombocytopenia were seen in 11/13 and 13/13 episodes, respectively. Fever (2-20 d) and loose motions (3-60 d) in 11/13 and 9/13 episodes, respectively. Eye examination records were available in 5 children; 3 had simultaneous or delayed chorioretinitis. Gancyclovir was used in all but 1 CMV-positive episode. In treated cases, counts recovered after a median of 8 days (3-56 d). CONCLUSION: Following chemotherapy for ALL/NHL, cytopenia that is prolonged or not explainable on the basis of chemotherapy toxicity should be evaluated for CMV infection.