Michelle Hudspeth

Pancytopenia with myelodysplasia due to copper deficiency.

We present a case of pancytopenia in a 9‐month‐old infant with total parenteral nutrition (TPN) dependence due to short bowel syndrome. Bone marrow examination revealed left‐shifted myeloid maturation, erythroid and myeloid dysplasia with normal iron stores. Serum copper level was 2 µm/dl (normal range 90–190 mcg/dl). After supplementation, copper levels normalized at 143 mcg/dl, and the macrocytic anemia, neutropenia, and thrombocytopenia resolved. Copper deficiency should be considered in the differential diagnosis of cytopenias and myelodsyplasia, particularly in the growing number of pediatric patients with TPN dependency or malabsorption. Pediatr Blood Cancer 2008;51:693–695.

Post-hematopoietic stem cell transplant immunization practices in the Pediatric Blood and Marrow Transplant Consortium†

A survey of National Marrow Donor Program transplant centers in 1995 demonstrated a wide range of immunization practices in post‐hematopoietic stem cell transplant (HSCT) recipients, which led to the 2000 Centers for Disease Control and Prevention (CDC) recommendations for vaccination after HSCT. We surveyed the principal investigators of the Pediatric Blood and Marrow Transplant Consortium (PBMTC) to identify immunization practice patterns after HSCT and assess compliance with the 2000 CDC guidelines.

Successful treatment of late, recurrent wilms tumor with high-dose chemotherapy and autologous stem cell rescue in third complete response.

Wilms tumor relapses are infrequent, occurring in approximately 15% of favorable histology patients. Very few cases of late recurrent relapse exist in the literature. Long-term survival after autologous stem cell rescue ranges from 40% to 73%, but there are very few reports of patients transplanted in their third complete response. We report a late recurrent relapse of Wilms tumor successfully treated with high-dose chemotherapy and autologous stem cell rescue in his third complete response who remains disease free 15 months posttransplant.

A Novel Mutation in Type II Methemoglobinemia

Type II methemoglobinemia is a somatic deficiency of cytochrome b5 reductase with severe global neurologic impairment. We report a novel mutation in exon 3 of the CYB5R3 gene on chromosome 22 consisting of homozygous 1-base pair (bp) deletion noted as c.215delG; p.Gly72AlafsX100. The patient had improvement of gross motor skills, chewing, and swallowing that may be due to the initiation of daily ascorbic acid therapy. We hypothesize that a possible response to ascorbic acid may be related to the effect of making additional ferrous iron available for its role as a cofactor in carnitine synthesis.

Folinic acid administration after MTX GVHD prophylaxis in pediatric allo-SCT.

Cyclosporine (CsA) and MTX are commonly used for GVHD prophylaxis in pediatric allo-SCT. Mucositis and hepatic toxicity frequently restrict the delivery of the fourth dose of MTX. Folinic acid (FA) may ameliorate MTX toxicity. We conducted a retrospective chart review of all pediatric patients who received CsA and MTX for GVHD prophylaxis from January 2000 to July 2010. Patients treated before July 2007 (N=29) did not receive FA and those treated from July 2007 onward did receive FA (N=18). Patients who received FA were significantly more likely to receive day +11 MTX (odds ratio (OR) 10.42, 95% confidence interval (CI): 1.21–262.27) but there was no significant difference in Grade III–IV GVHD between the two groups (OR 1.15, 95% CI: 0.08–18.14). FA did not impact relapse-free survival (RFS) (P=0.82). Increased likelihood of receiving day +11 MTX suggests that FA ameliorates MTX toxicity, such as severe mucositis. FA administration for MTX GVHD prophylaxis should be studied in a prospective, randomized fashion.

Phacomatosis Pigmentokeratotica: A Mosaic RASopathy with Malignant Potential

Phacomatosis pigmentokeratotica (PPK) is a rare epidermal nevus syndrome characterized by the co‐occurrence of a nevus sebaceous arranged along the lines of Blaschko with a speckled lentiginous nevus (SLN). We report a novel KRAS mutation in a patient with a large nevus sebaceous and an SLN who subsequently developed a vaginal botryoid rhabdomyosarcoma, an association not previously reported in the literature. This case expands our knowledge of the genetic basis for phacomatosis, in which mutations in HRAS have been previously described, although this report provides evidence that activating mutations in KRAS or HRAS may cause PPK. This report confirms that PPK is a mosaic RASopathy with malignant potential and raises the question of whether screening for other RAS‐associated malignancies should be performed for all children with PPK.

Two cases of Vici syndrome associated with Idiopathic Thrombocytopenic Purpura (ITP) with a review of the literature

Vici syndrome is a rare congenital disorder first described in 1988. To date, 31 cases have been reported in the literature. The characteristic features of this syndrome include: agenesis of the corpus callosum, albinism, cardiomyopathy, variable immunodeficiency, cataracts, and myopathy. We report two Hispanic sisters with genetically confirmed Vici syndrome who both developed Idiopathic Thrombocytopenic Purpura. To our knowledge, this is an immunologic process that has been previously undescribed within the phenotype of Vici syndrome and should be added to the spectrum of variable immune dysregulation that can be found in these patients.

Analysis of factors affecting immune recovery and initial response to tetanus after DTaP vaccination in pediatric allogeneic HSCT patients

Transfer of donor immunity after allo‐HSCT is limited, requiring re‐vaccination after HSCT. The CDC 2009 guidelines introduced earlier vaccination post‐HSCT with a uniform vaccination strategy. This study objective was to describe predictors of immune recovery and initial response to tetanus after DTaP vaccination post‐HSCT. We conducted a retrospective chart review of pediatric allo‐HSCT patients transplanted between July 1, 2007–June 30, 2012 who survived >1 yr without relapse (N = 27). Response to tetanus one month after the initial dose of DTaP was defined as a ≥4 fold increase in tetanus titers ≥1 month after vaccination. Wilcoxon rank‐sum exact test and Kruskall–Wallis tests were used to analyze CD4, CD8, and CD19 counts. Exact conditional logistic regression was utilized to analyze initial tetanus vaccination response. A statistically significant increase in median CD4, CD8, and CD19 counts occurred from six to 12 months post‐HSCT (p ≤ 0.0001, 0.005, 0.004). Only 36% of patients had initial tetanus vaccination response at first attempt post‐HSCT. None of the variables tested were statistically significant in predicting initial tetanus response to vaccination. There was no association between predictors of immune recovery or transplant variables and initial tetanus response. A uniform vaccination strategy is unlikely to provide protective antibodies for many post‐HSCT patients and should be evaluated in larger studies.

Pancytopenia after allogeneic bone marrow transplant due to copper deficiency.

Pancytopenia occurring 1 year or later after allogeneic bone marrow transplantation typically prompts a primary consideration for relapse. We present the case of a 15-year old-girl who underwent transplantation for therapy-related myelodysplasia secondary to Ewing sarcoma treatment who developed pancytopenia with myelodysplasia 1 year after transplant due to copper deficiency. Copper deficiency is an important consideration in the evaluation of pancytopenia and myelodysplasia in pediatric patients.

Severe pruritus and hypothermia as the primary manifestations of Human Herpes Virus-6 encephalitis after pediatric cord blood transplantation

Severe pruritus and hypothermia as the primary manifestations of Human Herpes Virus-6 encephalitis after pediatric cord blood transplantation