Shu Huey Chen

Auditory and visual toxicity during deferoxamine therapy in transfusion-dependent patients

Deferoxamine is a chelating agent that has extended the life expectancy of patients with thalassemia. In the 1980s, many investigators reported otologic and visual toxicity caused by deferoxamine. In July 1999 and 2 years later, the authors performed audiologic and ophthalmologic assessments in 30 transfusion-dependent patients receiving deferoxamine therapy (40-50 mg/kg per dose, subcutaneously for 8-10 hours, 4-7 days per week). In 1999, six patients (20%) had deferoxamine-related hearing impairment (>25 dB), all at high frequencies. Because the authors believed the benefits of chelation therapy outweighed the risk of ototoxicity, the dose of deferoxamine was not reduced. Two years later, the hearing impairment had not progressed in any of the patients. There was no association between ototoxicity and ferritin level. No patients had abnormalities of visual acuity or funduscopy in either 1999 or 2001. Based on this experience, deferoxamine at doses lower than 50 mg/kg/d was safe for the eyes and slightly toxic to the ears. The ototoxicity probably relates to individual susceptibility. Regular monitoring of auditory function and close follow-up of abnormal findings are recommended. According to this limited experience, reducing the dose or withdrawing deferoxamine might not be necessary if the hearing loss is stable in the face of ferritin levels above 2,000 ng/mL. Because of the relatively small patient numbers, more data are needed to confirm these conclusions.

Epstein-Barr virus-associated acute renal failure: diagnosis, treatment, and follow-up

We retrospectively reviewed our experience of Epstein-Barr virus (EBV)-associated acute renal failure. Of 165 previously healthy children hospitalized with serologically proven primary EBV infection, 8 had acute renal failure, of whom 5 (group A) did not have virus-associated hemophagocytic syndrome (VAHS), while 3 (group B) did have VAHS. All had complications in four or more organ systems. Two patients in group A had renal biopsies showing acute tubulointerstitial nephritis, and the clinical and laboratory findings in the other 3 group A patients were consistent with acute tubulointerstitial nephritis. Acyclovir was used in 1 patient, but she died of hepatic failure and pulmonary hemorrhage. The other 4 spontaneously recovered renal function after supportive care, including hemodialysis in 1 patient. Our experience does not support the routine use of corticosteroids or antiviral agents in these patients. Children in group B had a relatively normal urinalysis. Renal biopsies were not performed, but their presentations were compatible with acute tubular necrosis. We conclude that EBV should be considered as a possible etiological agent in all children presenting with acute renal failure of unknown cause. The diagnosis depends on a high index of suspicion and careful serological evaluation in atypical cases.

High-dose cytarabine-containing chemotherapy with or without granulocyte colony-stimulating factor for children with acute leukemia.

We sought to determine the role of granulocyte colony‐stimulating factor (G‐CSF) as an adjunct therapy in high‐dose cytarabine‐containing chemotherapy (HD C/T) for children with acute leukemia. Seventeen patients, aged 9 months to 18 years old, 8 ALL and 9 AML, were treated with cytarabine (Ara‐C) 1 g/m2 q12h for 8 doses with mitoxantrone, idarubicin, VP‐16, or asparaginase. A total of 71 courses of HD C/T was given. G‐CSF was not used in 14 courses (Group A). Prophylactic G‐CSF was given in 57 courses (Group B) as 200 μg/m2/d SC started one day after the completion of HD C/T and continued until the neutrophil recovery was maintained. The incidences of sepsis per course in Group A and Group B were 35.7% (5/14) and 40.4% (23/57), respectively. While 2 patients in Group A died of sepsis or pneumonia, none in Group B died. The mortality and delay in chemotherapy were fewer in Group B (P = 0.037 and 0.0006, respectively, Fisher exact test). There was a shorter average number of days of neutrophil <500/cumm, antibiotic usage, fever, and hospital stay in Group B (11, 8, 5, 17 days in Group B vs. 21, 17, 10, 37 days in Group A; P = 0.0001, log‐rank test; 0.0006, 0.0023, 0.0001, Wilcoxon rank sum test, respectively). The incidence of neutropenic fever was lower in Group B, but the difference did not reach statistical significance (P = 0.06, Fisher exact test). We conclude that G‐CSF as an adjunct therapy in HD C/T is effective in reducing mortality, days of neutropenia, antibiotic usage, fever, hospital stay, and frequency of delay in chemotherapy. The efficacy of this treatment approach requires further testing in a randomized, controlled trial. Am. J. Hematol. 58:20–23, 1998.

Long-term Treatment Results of Hepatoblastoma at a Single Institution in Taiwan

From 1990 to 2004, there were 23 consecutive patients with hepatoblastoma treated at Mackay Memorial Hospital in Taipei, Taiwan. There were 7 patients of stage I, 3 of stage II, 13 of stage III, and none had stage IV disease. Two siblings had congenital hepatoblastoma and both survived. Two patients were prematurity. Beckwith-Wiedemann syndrome, isosexual precocity, chronic B hepatitis presented in 1 patient each. In addition to surgery, we used cisplatin 90 mg/m2/d on day 1 and epirubicin 25 mg/m2/d for days 1 to 3 as first-line chemotherapy. Each course was repeated every 3 weeks. Epirubicin was chosen because of its lower cardiotoxicity. Carboplatin/etoposide and vincristine/cyclophosphamide/5-fluorouracil were the second-line chemotherapy for considering cumulative toxicity of first-line chemotherapy. If initial total excision was feasible, postoperative chemotherapy of 4 to 6 courses were given. Three patients died of progressive disease, infection, and relapse 1 each. The median duration of follow-up for 20 survived patients was 94 months. The 5-year event-free and overall survival rates were 73.9%±9.2% (SE) and 87%±7.0%, respectively. Tumor recurred in 5 patients. The commonest toxicity was febrile neutropenia. There was no cardiotoxicity event. In conclusion, with sequential combination of surgery and chemotherapy, the treatment results for hepatoblastoma were satisfactory as compared with other groups.

Childhood Langerhans cell histiocytosis increased during El Niño 1997-98: A report from the Taiwan Pediatric Oncology Group

From 1995-1999, a nation-wide study of Langerhans cell histiocytosis (LCH) in children less than 15 years old was conducted by the Taiwan Pediatric Oncology Group. The demographic and clinical data of 55 cases were analyzed. Thirty-two cases presented from the beginning of 1997 to the end of 1998, when the most severe El Niño in the century occurred. The incidence was higher than expected during this El Niño period (32 cases versus 22 cases, p = 0.003). During 1997-98, most LCH was diagnosed in summer (n = 15), autumn (n = 8), and winter (n = 8) but rarely in spring (n = 1); coincidentally, rainfall was least in winter but peaked in summer. During 1997-98, the most significant increase occurred in the polyostotic LCH subcategory (p = 0.017), with younger ages at diagnosis (p = 0.039). The incidence of LCH cytopenia, fever, and diseases of the skin, liver, spleen or other organs did not differ significantly. Local treatment modality, disseminated diseases and diagnosis during the El Niño of 1997-98 were independent risk factors predicting the recurrence or progression of LCH. Our findings suggest that particular infections or other environmental factors associated with El Niño might be related to the etiology of childhood LCH.

Treatment for childhood acute lymphoblastic leukemia in Taiwan: Taiwan Pediatric Oncology Group ALL-2002 study emphasizing optimal reinduction therapy and central nervous system preventive therapy without cranial radiation

Reinduction therapy has improved the outcomes in children with acute lymphoblastic leukemia (ALL). We sought to determine the optimal course(s) of reinduction therapy for standard‐risk (SR, or “low‐risk” in other groups) patients. Also, we evaluated outcomes using triple intrathecal therapy without cranial radiation (CrRT) for central nervous system (CNS) preventive therapy.

Interferon-α for alarming hemangiomas in infants: Experience of a single institution

Background:  Hemangioma is the most common tumor in infancy. ‘Alarming hemangiomas’ refer to the lesions that potentially impair vital structures or cause life‐endangering complications, and which warrant vigorous treatment. Interferon‐α has been used for alarming hemangiomas at Mackay Memorial Hospital, Taipei, Taiwan, since 1994.

The development of a novel protocol for the treatment of de novo childhood acute myeloid leukemia in a single institution in Taiwan

From November 1, 1995 to July 31, 2004, 49 children with de novo acute myeloid leukemia (AML) were treated at our institution. One patient who was treated by a different protocol was excluded. In total, 48 patients with de novo AML were enrolled in this study. Forty-two patients with AML other than acute promyelocytic leukemia (non-APL) were treated consecutively with 2 novel protocols: Mackay Memorial Hospital (MMH)-AML-96, designed as a pilot phase, and Taiwan Pediatric Oncology Group (TPOG)-AML-97A, on the basis of MMH-AML-96 with minor modifications. Six patients with APL were treated consecutively with 2 protocols, TPOG-APL-97 and APL-2001. As of July 31, 2006, the remission rates were 79%, 92%, and 98% after 1, 2, and 3 courses of induction therapy, respectively. The 5-year overall survival was 64%±6.9% (SE), and the 5-year event-free survival was 60%±7.1%; for non-APL AML, the rates were 62%±7.5% and 59%±7.6%; for APL, 83±15.2 and 67±19.3%. Among the factors analyzed, a complete remission achieved after 1 course of induction therapy, lactate dehydrogenase <500 IU/L at diagnosis, patients without invasive fungal infection during chemotherapy, and male sex were associated with a favorable outcome.

Neuroblastoma with expression of erythropoietin resulting in erythrocytosis.

We report the detection of erythropoietin mRNA in the tumor from a patient with neuroblastoma and erythrocytosis. A 2-year-old girl with neuroblastoma presented with hemoglobin 21.3 g/dL, red blood cells 8.03 x 1012/L, and hematocrit 0.641. The serum erythropoietin level was 26.54 mU/mL. The hemoglobin, hematocrit, and serum erythropoietin level were within normal ranges 3 months after surgical excision of the tumor. RT-PCR analysis showed that erythropoietin mRNA expression in the tumor tissue was as high as that of normal renal tissue. These results conclusively demonstrated that the tumor was the site of the ectopic erythropoietin production.

Pediatric acute lymphoblastic leukemia with t(1;19)/TCF3-PBX1 in Taiwan

In childhood acute lymphoblastic leukemia (ALL), t(1;19)(q23;p13.3) with TCF3‐PBX1 fusion is one of the most frequent translocations. Historically, it has been associated with poor prognosis. Intensive treatment, however, has improved its outcome. We determined the outcome of children with this genotype treated with contemporary intensive chemotherapy in Taiwan.