All-trans-retinoic acid and arsenic trioxide as initial therapy for acute promyelocytic leukemia

Acute promyelocytic leukemia (APL) is a rare subtype of acute myeloid leukemia (AML). Treatment of pediatric APL is based on the combination of all-trans-retinoic acid (ATRA), an anthracycline and cytosine arabinoside. Arsenic trioxide (ATO) has been studied in adults with newly diagnosed or relapsed APL with excellent response rates both when used as a single agent or in combination with ATRA or ATRA plus chemotherapy. There is little data on combination therapy with ATRA and ATO in pediatric APL. We present a case of an adolescent male with APL who was treated using ATRA and ATO without conventional chemotherapy agents.     

Acute promyelocytic leukemia presenting as a pelvic mass

The case history of a child with acute promyelocytic leukemia (APL) is reported to illustrate both an unusual presentation of APL as a pelvic mass and to review the pathophysiology and treatment of the disease. Therapy of APL consists of chemotherapy, namely adriamycin/daunomycin for remission induction, and of control of disseminated intravascular coagulation. A chloroma, if present, may require local irradiation in addition to chemotherapy. With aggressive management, the number of prolonged remissions may be greater for APL than for any other form of acute myelogenous leukemia (AML), with significant numbers of patients achieving five-year survival.     

Acute promyelocytic leukemia presenting as a pelvic mass.

The case history of a child with acute promyelocytic leukemia (APL) is reported to illustrate both an unusual presentation of APL as a pelvic mass and to review the pathophysiology and treatment of the disease. Therapy of APL consists of chemotherapy, namely adriamycin/daunomycin for remission induction, and of control of disseminated intravascular coagulation. A chloroma, if present, may require local irradiation in addition to chemotherapy. With aggressive management, the number of prolonged remissions may be greater for APL than for any other form of acute myelogenous leukemia (AML), with significant numbers of patients achieving five-year survival.     

Treatment of an Acute Promyelocytic Leukemia Relapse Using Arsenic Trioxide and All-Trans-Retinoic in a 6-Year-Old Child

In adult therapy, arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA) are recognized as active treatment of relapsed acute promyelocytic leukemia (APL). The efficacy of this combination in pediatric APL has not yet been well established. We report the case of a 6-year-old girl with relapsed APL, with a PML-RARα mutation, treated with a combination of ATO and ATRA. Over a period of 5 months, she received in total, 75 doses of intravenous ATO and 40 doses of oral ATRA. Currently, 22 months after relapse, she is still in complete remission. Here, we describe treatment of a relapsed APL in a child with limited treatment of ATO and ATRA and review the literature.     

Acute intestinal pseudo-obstruction after induction treatment of relapsed acute promyelocytic leukemia with arsenic trioxide

Arsenic trioxide (As(2)O(3)) is an effective agent for the treatment of relapsed acute promyelocytic leukemia (APL). We report a patient with intestinal pseudo-obstruction, which occurred while treating relapsed APL with As(2)O(3). A 6-year-old female with relapsed APL developed paralytic ileus, hyperleukocytosis, and a high fever while being treated with As(2)O(3). Although As(2)O(3) was discontinued and dexamethasone was administered, vomiting and abdominal distension worsened. An ileostomy was performed and diffuse patch-like infiltrations on the bowel surface were noted. Pathologic findings revealed APL cells involving the entire intestinal layers. This case history suggests that As(2)O(3) when used for reinduction therapy for APL may adversely affect the intestine and cause acute intestinal pseudo-obstruction.     

Febrile seizures]

The febrile seizures (FS) of the child are frequent. Their management is essentially based on the rigorous analysis of their characteristics, the clinical evaluation of the patient like on the collection of the family antecedents. In the case of "simple" FS, the forecast, always favourable, reduce the indications of assessment or treatment, including under possible repetitions. The possibility of an infection of the central nervous system must however always be isolated. In the case of "complicated" FS, the more important risk of later epilepsy makes often necessary of complementary explorations, as well as a treatment. Genetic predispositions were highlighted. In the case of a favourable forecast, contrast always large between the benignity of the FS and the parental dramatic experience. It must be taken into account in the evaluation and the choice of the therapeutic attitude.     

Fryns Syndrome: A Lethal Birth Defect with Variable Phenotypic Expressions in Siblings

Fryns syndrome (FS) is a multiple congenital anomaly syndrome, inherited as an autosomal recessive defect with variable expression. The authors report a newborn with FS, whose mother had two previous affected pregnancies with the infants having variable phenotypic expression. FS is characterized by craniofacial dysmorphism, diaphragmatic hernia and distal limb hypoplasia. This is the first published report from India describing a case of FS with familial recurrence, which would serve further to illustrate the clinical variability of this disorder.     

Long-term remission after first-line single-agent treatment with arsenic trioxide of relapsed acute promyelocytic leukemia in an 8-year-old boy

Arsenic trioxide (ATO) has been proven to be highly effective in adults with newly diagnosed or relapsed acute promyelocytic leukemia (APL). Only very limited data are published on the use of ATO as a single agent for first-line therapy of relapsed APL. The authors present a case of a 8-year-old boy with a bone marrow relapse of APL 7 years after first diagnosis, who achieved durable molecular remission with ATO as single agent: induction therapy for 12 weeks, consolidation for 4 weeks, then 6 cycles of 10 days over a period of 6 months. In total, 140 doses of ATO (0.15 mg/kg/day) were given (21 mg/kg). Consecutive promyelocytic leukemia-retinoic acid receptor α (PML-RARα) RT-PCR analyses were negative with a follow-up of 48 months. Acute or late side effects of arsenic were not observed. At present, the boy is in complete remission 4 years after the diagnosis of the relapse.     

Long-Term Remission After First-Line Single-Agent Treatment with Arsenic Trioxide of Relapsed Acute Promyelocytic Leukemia in an 8-Year-Old Boy

Arsenic trioxide (ATO) has been proven to be highly effective in adults with newly diagnosed or relapsed acute promyelocytic leukemia (APL). Only very limited data are published on the use of ATO as a single agent for first-line therapy of relapsed APL. The authors present a case of a 8-year-old boy with a bone marrow relapse of APL 7 years after first diagnosis, who achieved durable molecular remission with ATO as single agent: induction therapy for 12 weeks, consolidation for 4 weeks, then 6 cycles of 10 days over a period of 6 months. In total, 140 doses of ATO (0.15 mg/kg/day) were given (21 mg/kg). Consecutive promyelocytic leukemia–retinoic acid receptor α (PML-RARα) RT-PCR analyses were negative with a follow-up of 48 months. Acute or late side effects of arsenic were not observed. At present, the boy is in complete remission 4 years after the diagnosis of the relapse.     

Acute promyelocytic leukemia following chemotherapy for EBV-associated hemophagocytic lymphohistiocytosis

We report a case of chemotherapy-related acute promyelocytic leukemia (APL) following therapy with VP-16/etoposide for EBV-associated hemophagocytic lymphohistiocytosis (HLH). A 17-month-old male presented with fever and lymphadenopathy. Bone marrow and liver biopsies showed hemophagocytosis. He responded well to chemotherapy including dexamethasone, VP-16/etoposide, and cyclosporine. One and a half year later, he developed fever and pancytopenia. Clinical work-up revealed APL with t(15;17)(q22;q12);PML-RARα translocation. He underwent chemotherapy for APL and is in remission 8 years after diagnosis. Alternative non-leukemogenic agents to effectively treat HLH would be desirable.     

Frasier syndrome in a pre-menarchal girl: laparoscopic resection of gonadoblastoma

Frasier syndrome (FS) is characterized by male pseudohermaphroditism, slowly progressing nephropathy, and frequent development of gonadoblastoma. These patients are, however, often diagnosed when evaluated for primary amenorrhea. We report the case of FS in a pre-menarchal girl at the age of 6 years. Ultrasound examinations were performed and were inconclusive as to the presence or size of the gonads. Diagnostic laparoscopy was performed and the presence of bilateral streak gonads was documented and a bilateral salpingo-oophorectomy was performed. The postoperative course was uneventful. Histological examination of the streak gonads confirmed the presence of gonadoblastoma. To our knowledge, this is the first case in the literature of a pre-menarchal patient diagnosed with FS and a laparoscopic bilateral gonadoblastoma resection. Laparoscopic aspects regarding safe streak gonad removal in the pediatric population have been elaborated.     

全面性癫癎伴热性惊厥附加症一家系随访分析

目的　探讨全面性癫伴热性惊厥附加症 (GEFS )的临床意义。方法　回顾性分析GEFS 一家系的临床发作情况 ,作详细的体格检查。进行脑电图、2 4h动态脑电监测 ,部分患者作头颅CT检查。结果　先证者Ⅳ12 ,以抽搐频发 3d入院 ,生后 8个月开始高热惊厥 (FS)。此次发作为无热性频发全面性强直 阵挛发作。该家系 5代共 36人 ,其中有 14名患者 ,男 8例 ,女 6例 ;患者年龄 4岁 5个月～ 82岁 ,除Ⅰ2 发作类型不详外 ,Ⅱ2 、Ⅲ1、Ⅲ4、Ⅲ6、Ⅳ1、Ⅳ11、Ⅳ17为FS ,Ⅳ2 、Ⅳ12 、Ⅳ13 、Ⅳ14 为FS ,Ⅴ1为FS 和失神发作。除Ⅳ13 、Ⅳ14 目前给予丙戊酸镁治疗外 ,其他患者已减量停药或未用药 ,均无发作。全家系成员智能发育、全身及神经系统检查均正常。 3例行头颅CT检查 ,均正常。结论　GEFS 为常染色体显性遗传性疾病 ,具有显著的遗传异质性和表型异质性。认识该综合征对诊断和鉴别诊断儿童时期的癫具有重要的临床意义     

儿童抗磷脂抗体阳性13例报告

目的 探讨儿科抗磷脂抗体(antiphospholipid antibodies,APL)阳性病例的特点,以提高临床诊治水平。方法 2000～2002于我科就诊的13例APL阳性的病例,6～13岁,男7例,女6例,对其临床资料进行总结分析。结果 (1)13例中有8例原发病为系统性红斑狼疮(systemic lupus erythematosus,SLE),2例原发病为急性链球菌感染,3例未找到原发病因,考虑为原发APL。(2)本组原发病为SLE的8例患儿抗中性粒细胞胞浆抗体(antineutrophil cytoplasmic autoantibodies,ANCA)均为阴性。(3)对8例APL阳性伴血小板减少,皮肤黏膜瘀点、瘀斑的病例,给予大剂量丙种球蛋白(WIG)静脉滴注,进行免疫调节治疗;对5例APL阳性伴血管血栓、血栓血管炎症状者,则积极进行抗凝、抗栓治疗,多取得较好的临床疗效。结论 儿科APL阳性病例以继发性多见,SLE是最多见的原发疾病。APL阳性可以多种疾病形式出现。对APL阳性的患儿应区别对待,根据不同病因、病情分别进行以抗凝、抗栓为主或以免疫调节为主的治疗,可以尽快的改善临床症状,改善预后。     

All-trans retinoic acid-induced inflammatory myositis in a patient with acute promyelocytic leukemia

All-trans retinoic acid (ATRA), a component of standard therapy for acute promyelocytic leukemia (APL), is associated with potentially serious but treatable adverse effects involving numerous organ systems, including rare skeletal muscle involvement. Only a handful of cases of ATRA-induced myositis in children have been reported, and none in the radiology literature. We present such a case in a 15-year-old boy with APL, where recognition of imaging findings played a crucial role in making the diagnosis and facilitated prompt, effective treatment.     

Same sibling marrow following cord allogeneic transplantation as therapy for second relapse acute promyelocytic leukemia in a pediatric patient

Optimal therapy for relapsed APL in pediatric patients is controversial. Allogeneic HSCT is an alternative, with event‐free survival of 70–75%. We report a pediatric patient with APL who relapsed 28 months after CBT from her sibling and then was treated with BMT from the same donor. Bone marrow was selected for higher cell dose, donor availability, and partial donor chimerism. Persistent molecular remission was achieved, currently at 65 months after BMT. This case suggests the potential role of GVL activity in APL and illustrates the use of different cell sources from the same donor in allogeneic transplantation for pediatric patients.     

全面性癫癎伴热性惊厥附加症一家系随访分析

目的探讨全面性癫伴热性惊厥附加症(GEFS )的临床意义。方法回顾性分析GEFS 一家系的临床发作情况,作详细体格检查。进行脑电图、24 h动态脑电监测,部分患者作头颅CT检查。结果先证者Ⅳ12,以抽搐频发3 d入院,生后8个月开始高热惊厥(FS)。此次发作为无热性频发全面性强直-阵挛发作。该家系5代共36人。其中有14例患者;男8例,女6例;年龄4岁5个月~82岁,除Ⅰ2发作类型不详外,Ⅱ2、Ⅲ1、Ⅲ4、Ⅲ6、Ⅳ1、Ⅳ11、Ⅳ17、Ⅴ2为FS,Ⅳ2、Ⅳ12、Ⅳ13、Ⅳ14为FS ,Ⅴ1为FS 和失神发作。除Ⅳ13、Ⅳ14目前予丙戊酸镁治疗外,其他患者已减量停药或未用药,均无发作。全家系成员智能发育、全身及神经系统检查均正常。3例行头颅CT检查,均正常。结论GEFS 为常染色体显性遗传性疾病,具有显著遗传异质性和表型异质性。认识该综合征对诊断和鉴别诊断儿童时期癫具有重要的临床意义。     

Effect of dialysis on all trans retinoic acid levels in a child with acute promyelocytic leukemia and renal failure

All trans retinoic acid (ATRA) combined with chemotherapy has become the mainstay of treatment for patients with acute promyelocytic leukemia (APL). Renal dysfunction (RD) is commonly seen in patients with APL. We describe a patient with APL and multi-organ failure, who was on chronic veno-venous hemofiltration followed by hemodialysis (HD) and later peritoneal dialysis (PD), who received ATRA. ATRA levels were assessed as the body clearance of ATRA in children on HD and/or PD was unknown. Neither HD nor PD significantly affected ATRA levels, suggesting that dose modifications of ATRA may not be necessary for children with these forms of renal replacement therapy.     

Genital ulcers after treatment with all-trans-retinoic acid in a child with acute promyelocytic leukemia

All-trans-retinoic acid (ATRA) has been shown to improve the outcome of patients with acute promyelocytic leukemia (APL). However, various adverse effects of ATRA treatment have been noted, such as scrotal and genital ulcers in adult patients. The authors report genital ulcers that developed in a child with APL after ATRA treatment. An 8-year-old girl with APL was treated with ATRA for 21 days and after discontinuation of ATRA treatment she developed genital ulcers. Systemic and local antibiotic pomades were applied and the lesions improved within 15 days. In conclusion, genital ulcers may develop in children with APL as a complication of ATRA treatment and physicians should be alert to this possibility.     

GENITAL ULCERS AFTER TREATMENT WITH ALL-trans-RETINOIC ACID IN A CHILD WITH ACUTE PROMYELOCYTIC LEUKEMIA

All-trans-retinoic acid (ATRA) has been shown to improve the outcome of patients with acute promyelocytic leukemia (APL). However, various adverse effects of ATRA treatment have been noted, such as scrotal and genital ulcers in adult patients. The authors report genital ulcers that developed in a child with APL after ATRA treatment. An 8-year-old girl with APL was treated with ATRA for 21 days and after discontinuation of ATRA treatment she developed genital ulcers. Systemic and local antibiotic pomades were applied and the lesions improved within 15 days. In conclusion, genital ulcers may develop in children with APL as a complication of ATRA treatment and physicians should be alert to this possibility.