Faculty Bibliography

Alopecia areata is a non-scarring, reversible disorder, presumably caused by an autoimmune attack on anagen hair follicles. Treatments are numerous, and most of these are ineffective. However, the elicitation of contact dermatitis on the affected skin is commonly associated with hair regrowth. A major advance in the study of alopecia areata has been the introduction and characterisation of the C3H/HeJ mouse model that exhibits many features of the human disease. In this study we examined the effects of squaric acid dibutylester treatment on hair follicles and the associated leukocyte infiltrate in alopecia areata mice by light and transmission electron microscopic analysis. This was compared with unaffected normal mice and alopecic untreated mice. Experimental mice were treated unilaterally with the contact allergen squaric acid dibutylester and the skin was assessed after hair regrowth. The characteristic pathological picture of alopecia areata was observed in alopecic but not normal mice. Nine of eleven experimental mice regrew hair on the treated side only and this was associated with a reduction in peri/intrafollicular inflammatory cell infiltrates, hair follicle dystrophy, melanin incontinence/clumping, and an increase in the numbers of hair follicles in full anagen. This normalisation of hair follicle status after treatment reflects the successful reversal of disease in these mice. The mechanism of action of topical immunotherapy with a potent contact allergen such as squaric acid dibutylester still needs to be elucidated, but an altered immune milieu is suspected. This study further validates the C3H/HeJ mouse model of alopecia areata in the search for therapeutic interventions in this common hair follicle disorder

PURPOSE: This report describes the incidence of septic shock in pediatric hematology-oncology patients with positive blood cultures and investigates parameters of potential use in early diagnosis of gram-negative (GN) bacteremia and septic shock. PATIENTS: In a 12-month period, 140 consecutive episodes of septicemia (135 bacterial and 5 fungal) were seen in 100 patients. The absolute neutrophil count (ANC) was > 500/microl in 89 episodes (65%). RESULTS: Septic shock developed in patients with positive blood cultures with an overall incidence of approximately 19%. Of the 12 bacteremic patients who required transfer to the intensive care unit, 83% had a GN isolate recovered. The incidence of septic shock was not significantly lower in the group of patients with ANC > 500/microl. Low serum bicarbonate correlated with GN infection in patients with bacteremia. CONCLUSIONS: GN organisms were the major cause of septic shock in a group of pediatric hematology-oncology patients with positive blood cultures although they were recovered less frequently than gram-positive organisms. In our study, non-neutropenic patients with indwelling catheters were at approximately the same risk for GN shock as neutropenic patients. Monitoring blood carbon dioxide content may be useful in the early diagnosis of GN infection

PURPOSE: Medulloblastoma is a highly lethal disease when it recurs. Very few patients survive with conventional treatment. This study evaluated the use of high-dose carboplatin, thiotepa, and etoposide with autologous stem-cell rescue (ASCR) in patients with recurrent medulloblastoma. METHODS: Chemotherapy consisted of carboplatin 500 mg/m2 (or area under the curve = 7 mg/mL x min via Calvert formula) on days -8, -7, and -6; and thiotepa 300 mg/m2 and etoposide 250 mg/m2 on days -5, -4, and -3; followed by ASCR on day 0. In addition to the study-prescribed therapy, 21 patients received other treatment: neurosurgical resection in seven, conventional chemotherapy in 17, and external-beam irradiation in 11 cases. RESULTS: Twenty-three patients with recurrent medulloblastoma, aged two to 44 years (median, 13 years) at ASCR, were treated. Three patients died of treatment-related toxicities within 21 days of ASCR; multiorgan system failure in two, and Aspergillus infection with venoocclusive disease in one. Seven of 23 patients (30%) are event-free survivors at a median of 54 months post-ASCR (range, 24 to 78 months). Kaplan-Meier estimates of event-free (EFS) and overall survival are 34% +/- 10% and 46% +/- 11%, respectively, at 36 months post-ASCR. CONCLUSION: This strategy may provide long-term survival for some patients with recurrent medulloblastoma

PURPOSE: To evaluate a strategy that avoids radiotherapy in children less than 6 years of age with newly diagnosed malignant brain tumors, by administering myeloablative consolidation chemotherapy with autologous bone marrow reconstitution (ABMR) after maximal surgical resection and conventional induction chemotherapy. PATIENTS AND METHODS: Between March 1991 and April 1995, 62 children (median age, 30 months) with newly diagnosed malignant brain tumors were enrolled onto this trial. Children received conventional induction chemotherapy with vincristine, cisplatin, cyclophosphamide, and etoposide, repeated every 3 weeks for five cycles. Children without disease progression on induction chemotherapy were offered consolidation with myeloablative chemotherapy that incorporated carboplatin, thiotepa, and etoposide followed by ABMR. Irradiation was used only for residual tumor at consolidation or for progressive/recurrent disease. RESULTS: Induction chemotherapy was well tolerated by most patients; however, progression was noted in 17 children (27%) and four (6%) died of treatment complications. Of 37 children who received consolidation chemotherapy with ABMR, 15 are free of disease progression (median post-ABMR without further treatment, >44 months). The remaining 22 all progressed within 15 months of ABMR; three of 37 (8%) died of treatment-related complications. The 3-year overall survival (OS) and event-free survival (EFS) rates from diagnosis for all children are 40% (95% confidence interval [CI], 28% to 52%) and 25% (95% CI, 13% to 37%), respectively. Radiotherapy was administered to 19 of 62 children: 17 for progressive disease (PD) and two for residual disease at the time of ABMR. CONCLUSION: A significant proportion of children with malignant brain tumors can avoid radiotherapy and prolonged maintenance chemotherapy yet still achieve durable remission with this brief intensive chemotherapy regimen