Treatment of transfusion-dependent congenital dyserythropoietic anemia Type I patients with pegylated interferon alpha-2a.

OBJECTIVE: Pegylated IFN-α2a has been reported in two case reports as being efficacious in treating CDA-I patients. This study aims to assess its efficacy on a series of CDA-I patients. METHODS: Study sample consisted of seven CDA type 1 transfusion-dependent patients. They received pegylated interferon alpha-2a at an initial dose of 90-180 µg once a week, tapered according to clinical response and side effects. Good response was defined as Hb ≥ 10 g/dL for ≥3 months, partial response was defined as 7 ≤ Hb<10 g/dL for ≥3 months, and no response was defined as HB < 7 g/dL for over 3 months on treatment. Time to response was defined as the time needed to achieve hemoglobin levels ≥ 10 g/dL without transfusion. Patients were evaluated periodically by abdominal ultrasounds to rule out liver adenomas. RESULTS: Five patients (71%) had a good response to treatment. One patient stopped treatment due to side effects. One patient had partial response. One patient, with more severe phenotype and poor compliance, had poor response to treatment. No abnormal findings were found in ultrasound examination. No effect on serum ferritin level could be established. CONCLUSION: Pegylated interferon α2a therapy is efficacious in CDA-I patients with a reasonable safety profile.

Proton pump inhibitors use suppresses iron absorption in congenital dyserythropoietic anemia.

Congenital dyserythropoietic anemia type I (CDA I) is associated, as other anemic noninflammatory states, with ineffective erythropoiesis and increased iron absorption, which may lead to complication of iron overload. The latter complication requires iron-chelating therapy, which may be associated with adverse effects and toxicity. Gastric acid production is known to be an important factor that facilitates non-heme iron absorption. The purpose of this study was to examine whether treatment with proton pump inhibitors (PPIs) can decrease iron absorption in patients with CDA I. Eight CDA I patients (4 boys) aged 12-18 years with mild iron overload (not yet requiring chelating therapy) received 20 mg/d omeprazole for 6 months. Blood samples were obtained for ferritin, C-reactive protein, hemoglobin, calcium, and magnesium at baseline, at the end of months intervention and 6 months after its cessation. The mean ferritin level decreased from 585 ± 180 ng/ml at baseline to 522 ± 172 ng/ml at the end of 6-month treatment and 660 ± 256 ng/ml 6 months after cessation of omeprazole treatment (p  =  0.009). Omeprazole treatment caused a nonsignificant reduction in the mean iron level (iron 159 ± 42, 136 ± 54,167 ± 34 µg/dl, p  =  0.302). However, mean hemoglobin level was mildly but significantly reduced (Hg 10.0 ± 0.8, 9.55 ± 1.0, 10.4 ± 10.7 g/dl, p  =  0.002). No adverse effects were reported. Our investigation suggests that administration of PPI to patients with CDA I may reduce iron absorption and may lower iron overload and the need for chelation therapy.

Persistent pulmonary hypertension of the newborn associated with severe congenital anemia of various etiologies.

Among the many associated features of persistent pulmonary hypertension of the neonate (PPHN), severe congenital anemia has been described only occasionally and is not included in the list of conditions that may cause PPHN in the neonate. We describe the clinical course of a group of 12 full-term neonates with PPHN and congenital anemia due to congenital dyserythropoietic anemia (7/12), α thalasemia (1/12), Diamond-Blackfan (1/12), and epsilon gamma delta beta thalassemia (3/12). The association of congenital anemia and PPHN is more common than previously thought; it can exist with various etiologies and severity of anemia. Congenital anemia has not been described until now as a cause or risk factor for PPHN; it should be considered as such alone or in combination with other known causes to be recognized early and treated appropriately to improve outcome. In families with known cases of congenital anemia due to the above-mentioned diagnosis, closer prenatal follow-up should be offered to anticipate possible fetal distress and/or fetal anemia and PPHN after birth.

The role of angiogenesis in the transformation of plexiform neurofibroma into malignant peripheral nerve sheath tumors in children with neurofibromatosis type 1.

PURPOSE: The role of angiogenesis in the transformation of peripheral neurofibroma (PNF) to malignant peripheral nerve sheath tumor (MPNST) in neurofibromatosis type 1 (NF1) remains elusive and forms the objective of this study. EXPERIMENTAL DESIGN: Archival tissue from 5 children with NF1 and PNF, who developed MPNST between the ages of 8 and 15 years were analyzed for differences in microvasculature. The role of proangiogenic growth factors such as Vascular Endothelial Growth Factor (VEGF), and its receptors Flk-1 and Flt-1, and vessel maturity, defined as von Willebrand factor (vWf), α-smooth muscle actin+ (SMA+), were evaluated by immuno-histochemistry. RESULTS: A qualitative evaluation of the vasculature showed predominantly α-SMA+/vWf+ more stable vessels in PNF, and an irregular meshwork of α-SMA-/vWf+ endothelial cells structures in MPNST. In NF and PNF tumor cells were VEGF-, in contrast to VEGF+ tumor cells in MPNST. If present, the VEGF stain was confined mainly to the perivascular spaces in PNF, unlike the mainly stromal VEGF stain in MPNST. VEGF receptors also manifested a tumor stage-specific pattern. Flk-1 and Flt-1 were restricted to the mature, well-formed vasculature in PNF, but exhibited a diffuse pattern in MPNST. CONCLUSION: Our study provides a rare opportunity to document consistent and histologically detectable differences in the vascular organization of PNF and MPNST. It permits a pair-wise evaluation of the malignant conversion of benign PNF into its malignant counterpart, in the same patients. The phenotypic variations and characteristics of the vessels in these tumors are consistent with the idea that a strong proangiogenic drive contributes to the progressive growth in MPNST.

Derivative (22)t(3;22)(q12;p11.1) in desmoplastic medulloblastoma.

Medulloblastoma is a malignant invasive embryonal tumor of the cerebellum, representing 15-30% of pediatric brain tumors. An i(17q) abnormality appears in 40% of medulloblastomas, and usually not as a sole aberration; however, cytogenetic data for medulloblastoma are limited. Cytogenetic work-up of tumors is an important tool for diagnosis and prognosis, and in some cases has led to the development of new therapeutic modalities. In the present case, cytogenetic analysis of a medulloblastoma revealed an unbalanced karyotype in all cells analyzed: 46,XY,der(22)t(3;22)(q12;p11.1). This sole unbalanced translocation led to partial trisomy of 3q. The significance of this finding and its role in the pathogenesis of medulloblastoma need further clarification.

Trisomy 8 as a sole aberration in embryonal rhabdomyosarcoma (sarcoma botryoides) of the vagina.

Sarcoma botryoides (SB) is a subtype of embryonal rhabdomyosarcoma (ERMS), which belongs to the most common soft-tissue sarcoma in infancy and childhood, the rhabdomyosarcoma (RMS). Most of the vaginal RMS belong to SB, which is five times more common than the cervical ERMS. To date, there is no doubt regarding the significance and importance of chromosomal aberrations in cancer. So far, to our knowledge, no specific chromosomal changes have been reported for ERMS in general and for SB in particular. We describe cytogenetic results of a case of vaginal SB affecting a 1-year-old girl. A clone of trisomy 8 was found in all the analyzed cells as the only chromosomal aberration. The significance of this finding is discussed.

The effects of guided written disclosure on psychological symptoms among parents of children with cancer.

This study examines whether structured writing about receiving a diagnosis and treatment for pediatric cancer reduces distress among highly distressed parents of children with cancer (PCWC). Eight PCWC completed measures of posttraumatic stress symptoms (PTSS) and depressive symptoms at two baselines, and again after writing, with 1-month gaps between assessments. Using a guided disclosure protocol (GDP), parents were asked to write about receiving the diagnosis first in a chronological manner, then to explicitly label their emotions at the time of diagnosis and explain the impact of the child's illness on their life. Finally, they were asked to reflect on current feelings, future coping ability, and personal growth. Although symptoms of distress did not change between baselines, significant reductions were found in PTSS from the first baseline to postwriting, but not in depression. This preliminary study suggests that the GDP may reduce PTSS in distressed PCWC.

Sleep disruption and objective sleepiness in children with beta-thalassemia and congenital dyserythropoietic anemia.

BACKGROUND: Sleep fragmentation and periodic leg movement syndrome (PLMS) have been reported in adults with iron deficiency anemia. Little is known about sleep function and daytime sleepiness in children with chronic anemia such as beta-thalassemia or congenital dyserythropoietic anemia type 1 (CDA-1). OBJECTIVES: To investigate if children and adolescents who have beta-thalassemia (major or intermedia) or CDA-1 experience sleep fragmentation and objective daytime sleepiness and also to investigate if children and adolescents with beta-thalassemia have obstructive sleep apnea. METHODS: Ten patients (7 males and 3 females) with beta-thalassemia (mean [SD] age, 10.4 [7.3] years), 10 patients (7 males and 3 females) with CDA-1 (mean [SD] age, 13.5 [5.1] years), and 13 healthy volunteer control children(7 males and 6 females) (mean [SD] age, 10 [4] years) underwent nocturnal polysomnographic studies. A multiple sleep latency test was performed for 6 patients who had beta-thalassemia and 8 patients who had CDA-1. RESULTS: Both patient groups, that is, those who had beta-thalassemia and those who had CDA-1, had multiple arousals during sleep (mean [SD], 27.8 [11.4] events per hour and 23.8 [11.8] events per hour, respectively) compared with the control subjects (12.1 [6.6] events per hour) (P<.002). Thirty-eight percent (10.6 events per hour) of the arousals in patients with beta-thalassemia and 25% (6.0 events per hour) of the arousals in patients with CDA-1 were induced by periodic limb movements during sleep. In the control group, most (98%) arousals were spontaneous and unrelated to any definable event. The multiple sleep latency test average was 7.8 minutes for patients with beta-thalassemia (n = 6) and 10.7 minutes for patients with CDA-1 (n = 8). Five patients with beta-thalassemia and 4 patients with CDA-1 underwent a second polysomnographic study on the next night to confirm reproducibility. There was no significant change in the total number or index of arousals and no difference in the severity of the periodic limb movements during sleep compared with the results of the first polysomnographic study. CONCLUSION: Children and adolescents with beta-thalassemia or CDA-1 have evidence of impaired sleep function that is partially due to periodic limb movements during sleep and arousals that result in objective diurnal sleepiness.