Fanconi anemia: myelodysplasia as a predictor of outcome.

The adverse potential of the development of myelodysplastic syndrome (MDS) in Fanconi anemia (FA) was examined in a retrospective study of 41 FA patients who had bone marrow morphology and chromosomes reviewed by a single group. Thirty-three patients had adequate cytogenetic studies, and 16 (48%) had one or more abnormal studies: nine initially, and seven more on follow-up. Cytogenetic clonal variation was frequent, including disappearance of clones, clonal evolution, and appearance of new clones. The estimated five-year survival with a cytogenetic clone is 0.40, compared to 0.94 without a clone. Morphologic myelodysplasia (MDS), independent of a cytogenetic clone, was found in 13/41 patients (32%). The estimated five-year survival with MDS is 0.09, versus 0.92 without MDS. Leukemia developed in three patients whose initial cytogenetic clones prior to leukemia were t(1;18), t(5;22) and monosomy 7; the one with t(1;18) also had MDS. Our results focus on marrow morphology, and suggest that morphologic MDS may be more important than classical cytogenetics in prediction of an adverse outcome.

Dyskeratosis congenita.

Dyskeratosis congenita is a rare genodermatosis. Malignant deterioration and hematologic complications are well-described features of this syndrome. Correct recognition is essential for proper management. A review of diagnostic considerations and treatment guidelines is presented.

Dyskeratosis congenita: clinical and genetic heterogeneity. Report of a new case and review of the literature.

Dyskeratosis congenita (DC) is a rare form of ectodermal dysplasia consisting of dystrophic nails, hyperpigmentation, and leukoplakia often associated with aplastic anemia. DC is considered to be an X-linked recessive trait, but affected females suggest genetic heterogeneity. We report an additional female with DC and review the world literature, indicating transmission in X-linked recessive, autosomal recessive, and autosomal dominant manners. The clinical and genetic aspects of DC are heterogeneous, and different patterns of inheritance are associated with distinct clinical manifestations. DC should be considered in the diagnosis of a patient with any features of the syndrome regardless of gender. Conversely, DC should be considered in patients with aplastic anemia at any age.

Comparison of the cellularity and presence of residual leukemia in bone marrow aspirate and biopsy specimens in pediatric patients with acute lymphoblastic leukemia (ALL) at day 7-14 of chemotherapy.

BACKGROUND: Many pediatric chemotherapy protocols for treatment of ALL require a bone marrow examination at day 7 or day 14 after initiation of therapy. The usefulness of a bone marrow biopsy, in addition to an aspirate, has been a frequently asked question. PROCEDURE: This study addresses the evaluation of bone marrow cellularity and presence of residual leukemia in both aspirate and biopsy specimens in 45 consecutive pediatric patients (ages 1-19 years, 19 females, and 26 males) with ALL 7-14 days after initiation of therapy. DISCUSSION: 20/45 patients showed evidence of residual leukemia by bone marrow biopsy; 16/20 (80%) of these had evidence of residual leukemia in the aspirate specimen. Of the 4 aspirate specimens that did not demonstrate residual leukemia, 2 had <5% blasts and 2 had too few cells in the aspirate for evaluation. Of the 25/45 bone marrow biopsy specimens with no detectable residual leukemia, 14 of the aspirates had <5% blasts, and 11 had too few cells in the aspirate for evaluation. 13/45 (29%) of the aspirates had too few cells for a differential count. The bone marrow cellularity judged from the aspirate specimen was considered to be low (0-1+) in 34/45 patients. Of these 34 patients, the bone marrow biopsy showed hypocellularity (<20% cellularity) in 12/34, moderate cellularity (20-79% cellularity) in 14/34, and hypercellularity (>79% cellularity) in 8/34. CONCLUSIONS: We conclude that both the bone marrow aspirate and biopsy specimens provide important information in evaluating the response to chemotherapy in pediatric patients with ALL at day 7-14 of induction chemotherapy. The aspirate alone may be misleading in terms of cellularity in many patients and may not provide evidence of residual leukemia.

Successful treatment of a primary cardiac leiomyosarcoma with ifosfamide and etoposide.

PURPOSE: Primary cardiac leiomyosarcoma is a rare malignant tumor in childhood. Patients with unresectable or partially resected cardiac leiomyosarcoma typically have a poor prognosis. The role of chemotherapy in the treatment of these patients has not been well defined. PATIENT AND METHODS: A 6-week-old infant with an incompletely resected cardiac leiomyosarcoma was treated postoperatively with ifosfamide and etoposide. RESULTS: The patient is disease-free and without apparent late effects 5 years following the completion of therapy. CONCLUSION: The combination of ifosfamide and etoposide warrants further evaluation in patients with leiomyosarcoma.

The effect of ABO and Rh blood type on the response to intravenous immune globulin (IVIG) in children with immune thrombocytopenic purpura (ITP).

PURPOSE: Immune thrombocytopenic purpura (ITP) is a common childhood illness characterized by thrombocytopenia secondary to shortened platelet survival. Medical therapy includes corticosteroids, intravenous immune globulin (IVIG), and IV Rho (D) immunoglobulin (anti-D). Individuals with Rh-negative blood generally do not respond to treatment with anti-D, but little information is currently available regarding the potential relationship between blood type and response to IVIG. This study was designed to characterize the relationship between ABO and Rh blood type and the response to IVIG in children and adolescents with newly diagnosed ITP. PATIENTS AND METHODS: A retrospective chart review was performed for 52 children and adolescents with newly diagnosed ITP initially treated with IVIG by the Division of Pediatric Hematology-Oncology at Robert Wood Johnson University Hospital in New Brunswick, New Jersey. RESULTS: There were no significant differences in response rate or clinical outcome by ABO blood group or Rh type in children with ITP who received IVIG monotherapy as their initial treatment. CONCLUSIONS: ABO blood group and Rh type do not appear to be prognostic factors when IVIG monotherapy is the initial treatment for childhood ITP.

Pharmacokinetics of intravenous recombinant human granulocyte colony-stimulating factor (rhG-CSF) in children receiving myelosuppressive cancer chemotherapy: clearance increases in relation to absolute neutrophil count with repeated dosing.

Limited evidence suggests increased efficacy of rhG-CSF by subcutaneous (SQ) compared with intravenous (IV) administration. To examine the possibility that rapid elimination of IV rhG-CSF could substantially shorten the duration of systemic exposure and could explain a difference in pharmacodynamics, we characterized the pharmacokinetic profile of IV rhG-CSF for comparison to that previously reported for SQ administration. Twelve children were randomly assigned to receive 10 or more days of IV rhG-CSF at dosages of 5 or 10 microg/kg a day beginning 24 hr after chemotherapy. Enzyme-linked immunosorbent assay (ELISA) was used to measure rhG-CSF concentrations in timed serum samples on days 1 and 10. Pharmacokinetic parameters were estimated by nonlinear, least squares regression. All serum concentration-time profiles were best described by a two-compartment model of elimination. Mean t1/2beta values ranged from 3.68 +/- 0.86 to 22.4 +/- 12.0 hr. ANC was correlated with log CLT (r = 0.72, P < 0.05), and inversely with log dose-adjusted AUC (r = 0.75, P < 0.05) and log dose-adjusted Cmax (r = -0.65, P < 0.05). Estimated duration of serum rhG-CSF concentrations above 1 ng/ml exceeded 24 hr for all but the 5 microg/kg cohort on day 1. Pharmacokinetic parameters of IV rhG-CSF are similar to those previously reported for SQ administration in children treated with myelosuppressive cancer chemotherapy. Daily IV administration should be a suitable alternative route of administration in this patient population.

Radiologic placement of a low profile implantable venous access port in a pediatric population.

PURPOSE: To evaluate the feasibility and complications of placement of a low-profile venous access port in the chest in children requiring long-term venous access. METHOD: A low-profile peripheral arm port (PAS port; Sims Deltec, St. Paul, MN, USA) was implanted in the chest in 22 children over a 4-year period. The mean age of the study group was 6 years (range: 9 months to 20 years). Ports were placed for the administration of chemotherapy, hyperalimentation and frequent blood sampling. Sonographic guidance was used to access the internal jugular or subclavian vein in each case. A review of all inpatient and outpatient charts was undertaken to assess catheter performance and complications. RESULTS: Access to the central venous circulation was successfully achieved in each case without complication. Ports remained implanted for 6579 catheter-days (mean: 299 days). Ten ports have been removed. Of three patients (13%) experiencing device-related infections (0.45 infections/1000 catheter days), two (9.1%) were unresponsive to antibiotics and removed (0.3 infections/1000 catheter days). One port was removed because of pain in the shoulder adjacent to the port implantation site. One port was removed because of difficult access. The final port was removed in order to place a dual-lumen catheter prior to bone marrow transplant. Twelve ports remain implanted. Aspiration occlusion occurred in four patients (18%). Deep venous thrombosis did not occur in any patient. CONCLUSION: Low-profile chest ports placed by interventional radiologists in the interventional radiology suite can be placed in children as safely as traditional chest ports placed in the operating room. The incidence of infection, venous thrombosis and aspiration occlusion is comparable to that of ports placed operatively.