Thiotepa and cyclophosphamide with stem cell rescue for consolidation therapy for children with high-risk neuroblastoma: a phase I/II study of the Pediatric Blood and Marrow Transplant Consortium.

PURPOSE: We report the results of a phase I/II stem cell rescue trial for patients with high risk neuroblastoma. PATIENTS AND METHODS: Fifty-one patients with a median age of 2.3 years (range 1 to 20) who were in their first complete remission (CR) (n = 8), very good partial remission (VGPR) (n = 23), partial remission (PR) (n = 5), or subsequent CR/PR (n = 7) after receiving a platinum-based induction regimen were consolidated with high dose chemotherapy and stem cell rescue. They received an ablative regimen of thiotepa (300 mg/m2/day for 3 days) and cyclophosphamide (1500 mg/m2/day for 4 days) followed by either purged marrow (n = 16), unpurged bone marrow (BM) (n = 23), or peripheral blood stem cell (PBSC) rescue (n = 13). The median nucleated cell doses administered were 2.7 x 10(8)/kg for unpurged marrow (range 1.1 to 13), 1.7 x 10(8)/kg for purged marrow (range 0.8 to 6.4), and 2.1 x 10(8)/kg for the PBSC (range 1.1 to 13). RESULTS: Engraftment was achieved for all patients. The time to achieve an absolute neutrophil count (ANC) >500 x 10(9)/l was 19 days for patients who received purged BM (range 13 to 18), 17.5 days for patients who received unpurged BM (range 9 to 38), and 13 days for patients who received PBSC (range 9 to 25). An unsustained platelet count >20 x 10(9)/l was attained in 33.5 days by patients who received purged BM (range 13 to 100), 35 days for patients who received unpurged BM (range 14 to 128), and 20 days for patients who received PBSC (range 11 to 64). There was one infectious death in the unpurged marrow group caused by aspergillosis pneumonia, but none in the other two groups. Progressive disease (PD) developed in 21 patients at a median of 271 days (range 31 to 1230). The remaining 29 patients are progression-free at a median follow-up of 1190 days (range 530 to 2383). CONCLUSION: We conclude that this regimen is well tolerated, and that progression-free survival (PFS) with this chemotherapy-only regimen compares favorably with regimens containing total body irradiation (TBI).

Trichoderma longibrachiatum infection in a pediatric patient with aplastic anemia.

Trichoderma longibrachiatum infection of the skin in an 11-year-old child with severe aplastic anemia and prolonged neutropenia is reported. The patient received systemic antifungal therapy and underwent bone marrow transplantation. To our knowledge, this is the first description of T. longibrachiatum infection in a pediatric patient. It also is the first case successfully treated with medical therapy. A review of the literature suggests that Trichoderma spp. are recognized as human pathogens with increasing frequency, particularly for immunocompromised patients, and should be considered in the differential diagnosis of fungal infections in the pediatric population.

Hepatic angiosarcoma in a child: successful therapy with surgery and adjuvant chemotherapy.

We report a 3-year and 11-month-old Caucasian female, who initially presented with an unresectable hepatic angiosarcoma. After three courses of chemotherapy with adriamycin/cisplatin, the tumor decreased in size considerably, allowing complete surgical resection. She also received postoperative chemotherapy with alternating cycles of ifosfamide/etoposide, cisplatinum/adriamycin, and vincristine/actinomycin D/cyclophosphamide for 18 months. She remains disease-free for greater than 44 months from the initial diagnosis. Our experience suggests that total excision of the tumor, together with an aggressive chemotherapy regimen, can improve the disease-free survival for children with this highly malignant vascular tumor of the liver.

Epiglottitis following preparation for allogeneic bone marrow transplantation.

We describe a 7-year-old boy who developed acute, airway-threatening, non-infectious epiglottitis following high-dose cytosine arabinoside and total body irradiation preparative regimen for allogeneic BMT. Unlike gastrointestinal symptoms and oropharyngeal mucositis, acute epiglottitis is a previously unreported early complication following allogeneic BMT preparation. The pathogenesis of epiglottitis in our patient was presumably multifactorial, resulting from the combination of chemotherapy and irradiation. We recommend that this diagnosis be considered in the differential diagnosis of patients with significant upper airway symptoms following BMT preparation.

The role of tranexamic acid in the treatment of giant hemangiomas in newborns.

Giant hemangiomas occurring in the neonatal period often present a therapeutic challenge, especially when confounded by consumptive coagulopathy (Kasabach-Merritt syndrome). We treated three infants with tranexamic acid after therapy with corticosteroids was ineffective. One patient had a partial response. The remaining two developed progressive disease.

Paecilomyces lilacinus catheter-related fungemia in an immunocompromised pediatric patient.

Paecilomyces lilacinus catheter-related fungemia in an immunocompromised child is reported. The presence of a central venous catheter and the patient's immunocompromised status were felt to be predisposing factors for this unusual infection. To our knowledge, this is the first description of P. lilacinus catheter-related fungemia, and our patient may be the youngest reported patient with this mycosis who was cured.

Essential thrombocythemia in a child: management with anagrelide.

Essential thrombocythemia (ET) is a rare disorder in children. An 11-year-old white boy was first seen in January 1986 with symptoms of abdominal pain. His platelet count was 1.5 million/mm3. Other hematological values and coagulation studies, including bleeding time, were normal. There was laboratory evidence of mild platelet dysfunction. Using the criteria of the Polycythemia Vera Study Group, a diagnosis of ET was made. He developed frequent headaches. Aspirin was prescribed for the next 2 years at varying doses and frequency. During the period, platelet counts ranged between 1 and 3 million/mm3. In view of progressive headaches and evidence of increasing platelet dysfunction, further treatment was indicated. The use of a new agent, anagrelide, reported effective in adults with ET, resulted in amelioration of symptoms and improvement in quantitative and qualitative platelet control with no significant untoward effects.

Bone marrow transplantation in childhood leukemia using reverse isolation techniques.

Between 1979 and 1986, 29 pediatric patients underwent bone marrow transplantation at Texas Children's Hospital using routine reverse isolation. Laminar air flow rooms, prophylactic antibiotics, and gut sterilization were not utilized. The diagnoses included acute lymphocytic leukemia (ALL) (16 patients), acute nonlymphocytic leukemia (ANLL) (10 patients), and chronic myelogenous leukemia (CML) (three patients). All patients had fever during hospitalization. There were 11 episodes of bacteremia in seven patients giving a bacteremia rate of 37.9%. Moderate-to-severe (grade II-IV) acute graft-versus-host disease (GVHD) was seen in eight patients (27.6%). The incidence of infection and GVHD during the first 100 days post-transplantation is comparable to published reports from centers utilizing rigid isolation and sterilization of the gut. It is suggested that bone marrow transplantation may be done using standard reverse isolation techniques without increasing the morbidity or mortality of the procedure.