Clinical Characteristics and Treatment Outcome of Childhood Langerhans Cell Histiocytosis / 대한소아혈액종양학회지

PURPOSE: We analyzed a cohort of patients with Langerhans cell histiocytosis (LCH) to understand the clinical findings, optimal management, and outcome of the disease. METHODS: We performed a retrospective clinical study of LCH from January 1993 to August 2002 at Chonnam National University Hospital. All 39 patients with histologically proven histiocytosis were categorized into Class I (n=22), Class II (n=15) and Class III (n=2) by WHO classification. RESULTS: There were 18 males and 21 females. Mean age at diagnosis was 3.2 years. The common clinical manifestations of Class I were soft tissue swelling, skin rash or nodule, otorrhea; and those of Class II were hepatosplenomegaly, fever, and respiratory symptoms. The most commonly involved organ of Class I was the skeleton; and that of Class II was bone marrow. Abnormal hematologic findings were found in 23 patients, especially in all Class II patients. Infectious etiology was documented in 5 Class II patients (CMV in 3, EBV in 1, mycoplasma in 1). Chemotherapy was given to 19 out of 22 Class I patients. Six of them showed complete remission. Four died during chemotherapy. The overall survival of Class I patients was 78% and that of Class II 63%. Poor prognostic factors of Class I were age 1.5 mg/dL. CONCLUSION: The Langerhans cell histiocytosis is a heterogeneous disorder of significant morbidity and mortality. Early recognition and aggressive medical treatment might improve the survival rate.

Granulocytic Sarcoma in Childhood Acute Myelogenous Leukemia: Clinical Characteristics and Management / 대한소아혈액종양학회지

PURPOSE: Granulocytic sarcoma (GS), an extramedullary tumor consisting of primitive myeloid cells, is a rare manifestation of acute myelogenous leukemia (AML). However, GS can occasionally precede the development of systemic leukemia by weeks to years. The objectives of this study are to describe the frequency, clinical characteristics and survival of AML children with GS from a single Korean institute. METHODS: Retrospective review of all the AML children who presented between January, 1995 and June, 2003 was undertaken. RESULTS: GS developed in 9 children among 118 AML patients (incidence, 7.6%). The median age at diagnosis of AML was 82 months (8 months~13 years) with equal sexual distribution. The sites of GS were scalp (n=4), skull (n=3), paranasal sinuses (n=1), external auditory canal (n=1), spinal epidura (n=1), and spinal intramedulla (n=1). The symptoms related with GS were scalp mass (n=4), paraparesis (n=3), facial nerve palsy (n=3), hearing impairment (n=2), and exophthalmos (n=1). In the case with spinal epidural mass, GS preceded the diagnosis of AML by 15 months. Cytogenetics were available in 8 cases, and t (8; 21) was found in five cases. All cases received systemic chemotherapy, with surgical decompression and radiotherapy for 2 patients involving spine. Seven cases received stem cell transplantations (3, allogeneic bone marrow; 4, autologous peripheral blood). The 5-yr event-free survival was 35.0% by Kaplan-Meier method. All 3 allografted patients are alive (86 mo, 5 mo, 1 mo), while 3 of 4 autografted patients had either died or relapsed. CONCLUSION: GS should be considered in patients with or even without AML who have palpable mass or neurological manifestation. Effective treatment, including allogeneic stem cell transplantation, should be considered to achieve a durable disease control.

Defibrotide Treatment for Hepatic Veno-occlusive Disease after Umbilical Cord Blood Transplantation / 대한소아혈액종양학회지

Veno-occlusive disease (VOD) of the liver is a life-threatening complication occurring early after blood or bone marrow transplantation (BMT). Effective treatment has not been established in case of severe forms of VOD. Defibrotide, a single-stranded polydeoxyribonucleotide, has been used on a compassionate basis in recent clinical trials with promising results. We report here with the first Korean experience of using defibrotide for the treatment of hepatic VOD occurring after unrelated umbilical cord blood transplant in a 2-year-old child with acute lymphoblastic leukemia. Defibrotide was administered for 23 days without any significant side effects with resolution of signs and symptoms of VOD.

2-Chlorodeoxyadenosine for Children with Recurrent or Refractory Langerhans Cell Histiocytosis / 대한소아혈액종양학회지

PURPOSE: Langerhans cell histiocytosis (LCH) is a disorder characterized by the proliferation of activated Langerhans cells. Although current therapies are very effective at inducing remission, multiple recurrences and long-term sequelae are common for young patients. For this reason, more effective therapies based on the pathogenesis of LCH are needed. We investigated the use of 2-chlorodeoxyadenosine (2-CdA), a purine analogue with an antiproliferative effect on histiocytes and lymphocytes, in patients with recurrent or refractory LCH. METHODS: Four children with recurrent or refractory LCH received 2-CdA (5~7 mg/m2/day for 5 days, given as a 24-hr continuous infusion and repeated every 21~28 days for 5~7 courses). RESULTS: All four patients had multiorgan involvement, and were heavily pretreated. Of the two children with recurrent diseases, one had complete response and the other showed no active disease except for the remaining diabetes insipidus. Two infants who showed poor early response to previous combination chemotherapy also responded poorly: partial response in one, and progressive disease resulting in death in the other. Toxicity consisted mainly of myelosuppression, but significant infections did not occur. The peripheral neuropathy was not seen. CONCLUSION: 2-CdA, tolerable in children without significant side effects, might be effective for the treatment of recurrent LCH in children. However, the efficacy in infants with multi-system, refractory diseases needs further study. The feasibility of 2-CdA treatment as the first-line therapy for high-risk diseases, and the possibility of combination with other agents needs to be addressed in the future.

Dyskeratosis Congenita in a Girl / 대한소아혈액종양학회지

Dyskeratosis congenita (DC) is a rare genetic disorder encompassing abnormal skin pigmentation, dystrophic nails, leukoplakia of mucous membranes and others. Bone marrow failure is the cause of early mortality. Moreover, DC is known for its predisposition to malignancy. X-linked recessive, autosomal dominant and autosomal recessive forms of the disease are recognized. We describe here a rare case of DC in a 4-year-old girl showing dark skin, dystrophic toe nails, and mild bone marrow failure. Autosomal recessive disease was suggested as the patient is female, and tests for DKC1 and hTR mutations were negative. Intermittent treatment with oxymetholone and prednisolone for about 26 months resulted in stable hemoglobin and platelet response.

Fatal Bronchiolitis Obliterans with Very Severe Subcutaneous Emphysema and Pneumomediastinum after Unrelated BMT / 대한소아혈액종양학회지

Bronchiolitis obliterans (BO) is a particularly severe complication that occurs in 10% to 15 % of the patients with extensive graft-versus-host disease (GVHD) and is often refractory to treatment. We report herewith a child with chronic GVHD and BO after unrelated BMT. A 8 year-old girl with Ph ALL (Philadelphia-chromosome positive acute lymphoblastic leukemia) underwent an unrelated BMT in the first complete remission. Engraftment was uneventful. Acute GVHD of the skin developed, and was treated with methylprednisolone. No evidence of GVHD flare was documented, and immunosuppression was tapered off by 7 months posttransplant. On 9 months posttransplant, chronic GVHD involving skin, liver, mouth, eyes, gastrointestinal tract, and lungs developed. Despite conservative managements, the patient developed pneumomediastinum and subcutaneous emphysema secondary to severe BO. Her condition continued to deteriorate, and she died of respiratory failure 10 months after transplant. Further studies are required to identify risk factors and to develop newer methods of effective treatment for this rare complication.