Hypoalbuminemia and not undernutrition predicts high-dose methotrexate-induced nephrotoxicity in children with acute lymphoblastic leukemia in resource-constrained centers.

BACKGROUND: The standard practice to mitigate high-dose methotrexate (HD-MTX)-induced nephrotoxicity (HMN) in acute lymphoblastic leukemia (ALL) is to monitor levels until serum MTX falls below a predefined threshold. It is not feasible in most resource-constrained centers. Literature on the various factors affecting HMN in these centers is limited, retrospective, and heterogeneous. Though hypoalbuminemia has been postulated as a risk factor for HMN, the relationship of undernutrition with HMN has not been studied. PROCEDURE: This prospective observational study consecutively enrolled children < 12 years old with ALL receiving HD-MTX. Children with preexisting renal disease and exposed to nephrotoxic drugs two weeks preceding HD-MTX infusion were excluded. HD-MTX was administered over 24 hours (BFM-2009 protocol) with 12 hours of prehydration. Solitary MTX levels at 36 hours (MTX36) were outsourced, and 6-8 doses of leucovorin were given six-hourly. Hydration was continued till last dose of leucovorin. Various factors affecting HMN (rise in creatinine to 1.5 times baseline) were recorded: age, sex, type of ALL, risk group of ALL, first dose of MTX, dose of MTX, undernourishment, serum protein, and albumin along with C-reactive protein and MTX36 levels. RESULTS: Forty-four children who received 150 HD-MTX cycles were analyzed. HMN was seen in 14% of cycles. On univariate analysis, undernourishment, MTX36 levels, hypoproteinemia, and hypoalbuminemia were significantly associated with HMN. On multivariate analysis, hypoalbuminemia and MTX36 levels significantly predicted the development of HMN with odds ratios of 4.71 and 1.45. CONCLUSION: Hypoalbuminemia and solitary serum MTX levels predict HMN in centers where serial MTX level monitoring is not feasible.

Transcobalamin deficiency: vitamin B12 deficiency with normal serum B12 levels.

Transcobalamin (TC) deficiency is a rare autosomal recessive inborn error of cobalamin transport which clinically manifests in early infancy. We describe a child with TC deficiency who presented with classical clinical and lab stigmata of inborn error of vitamin B12 metabolism except normal serum B12 levels. He was started on empirical parenteral cobalamin supplements at 2 months of age; however, the definitive diagnosis could only be established at 6 years of age when a genetic evaluation revealed homozygous nonsense variation in exon 8 of the TCN2 gene (chr22:g.31019043C>T).

Incidence of thrombocytopenia following phototherapy in hyperbilirubinemic neonates.

BACKGROUND: Thrombocytopenia has not been conclusively reported as a complication of phototherapy in any of the standard paediatric textbooks. MATERIALS AND METHOD: A prospective study in consecutively enrolled cohort of apparently healthy neonates, who developed indirect hyperbilirubinaemia and required phototherapy. Neonates having a base line platelet count of more than 150,000/mm(3) were included. Neonates having features suggestive of haemolysis, direct hyperbilirubinaemia, sepsis, anti-platelet drugs given to baby or mother, haemangioma, and other congenital anomalies were excluded. Platelet counts were performed at admission, 24 hours, 48 hours, and before discontinuing phototherapy. RESULTS: Out of 100 neonates included in study 35 (35%) had thrombocytopenia and a majority of neonates had mild thrombocytopenia (74%). The thrombocytopenia was seen in 26 (74%) cases during the first 24 hours of phototherapy and usually was not associated with clinical bleed. CONCLUSION: This study establishes an association of phototherapy as a cause of thrombocytopenia in hyperbilirubinaemic neonates. Though the incidence of thrombocytopenia is substantial yet it is clinically insignificant. This study helps the practitioner to be aware of this association and avoid unnecessary investigations, as thrombocytopenia was transient.