Successful treatment of progressive stage 4s hepatic neuroblastoma in a neonate with intra-arterial chemoembolization

Stage 4s neuroblastoma (NB) is a unique entity seen in infants less than 1 year of age, with metastatic disease confined to liver, skin, or bone marrow. Despite metastatic spread, stage 4s NB has a favorable outcome. An exception to this is seen in neonates who present with progressive enlargement of the liver with secondary respiratory compromise and liver failure. We describe a 4-week-old neonate who presented with 4s NB, with a rapidly enlarging liver, resulting in respiratory and hepatic failure, who had a rapid, sustained, and ongoing response to chemoembolization of the hepatic artery. This approach is feasible at this age, and may be effective in improving the outcome in this group of patients.     

A sequential treatment algorithm for infants with stage 4s neuroblastoma and massive hepatomegaly

Infants with 4s neuroblastoma (NB) and massive hepatomegaly have a guarded prognosis and mortality approaches 30%. We report on eight patients with 4s NB and massive hepatomegaly treated with multiple modalities. One patient had spontaneous tumor regression. Three patients had progressive disease and responded to chemotherapy. Four patients progressed despite intravenous chemotherapy, of whom two died, and two were salvaged with hepatic intra-arterial chemoembolization. Treatment of infants with stage 4s NB with massive hepatomegaly should be individualized based on disease course. A sequential approach with observation, intravenous chemotherapy, and intra-arterial chemoembolization, may improve the outcome of these infants.     

Successful treatment of MYCN amplified, progressive stage 4S neuroblastoma in a neonate with hepatic artery embolization in addition to multimodality treatment

Stage 4S metastatic neuroblastoma (NB) has a favorable prognosis due to a high rate of spontaneous regression. Young infants risk lethal complications arising from hepatomegaly, which can develop rapidly despite treatment. MYCN oncogene amplification confers a significantly worse prognosis. We describe a 4-week-old neonate with MYCN-amplified stage 4S NB complicated by gross hepatomegaly causing rapidly progressive respiratory, hepatic, and renal failure. The child remains in remission 3 years after hepatic artery embolization, radiotherapy, standard, and high-dose chemotherapy. Embolization of the hepatic artery, with classical treatment, is feasible and safe at this age and may contribute substantially to the management of high-risk patients.     

Cytomegalovirus-associated stage 4S neuroblastoma relapsed stage 4

Neuroblastoma is one of the most frequent solid tumors in childhood, rarely recurrent after five years from diagnosis. Cytomegalovirus (CMV), a major pathogen causing congenital birth defects and severe opportunistic diseases, has been shown to have teratogenic, immunodepressive and oncogenic properties. The case of a girl with stage 45 neuroblastoma diagnosed at three months and relapsed as stage 4 five years later is reported. In both circumstances, active CMV infection was revealed by positive CMV-specific IgM and IgA antibodies, CMV-DNAemia and CMV culture. At three months, the patient presented with subcutaneous nodules, hepatosplenomegaly and increased aminotransferase levels, and the opsoclonus-myoclonus syndrome. Mental retardation developed later on. At 5 years, relapsed neuroblastoma was preceded by a mononucleosis-like syndrome concomitant with active CMV infection and decreased levels of immune cells and natural killer activity. Clinical, virologic, and immunologic findings suggest an immune-mediated pathogenic role for CMV in this tumor. © 1995 Wi1ey-Liss Inc.     

Long-term complications in survivors of advanced stage neuroblastoma

BACKGROUND: Few studies have assessed late effects in neuroblastoma (NB) survivors, particularly those with advanced stage disease. METHODS: Retrospective analysis of a cohort of advanced stage NB survivors followed in a late effect clinic at a single institution. Screening tests to detect late effects were tailored depending on the individual's treatment exposures. RESULTS: The study included 63 survivors (31 males). The median age at diagnosis was 3.0 years. The median follow-up from diagnosis was 7.06 years. All patients had surgery and received chemotherapy, 89% received radiation therapy (RT), 62% immunotherapy, and 56% autologous stem cell transplant. Late complications were detected in 95% of survivors and included: hearing loss (62%), primary hypothyroidism (24%), ovarian failure (41% of females), musculoskeletal (19%), and pulmonary (19%) abnormalities. The majority of complications were moderate, with only 4% being life-threatening. Survivors who received cisplatin were at greater risk to develop hearing loss compared to those not so treated (OR 9.74; 95% CI: 0.9-101.6). A total dose of cyclophosphamide greater than 7.4 g was associated with ovarian failure (P = 0.02). CONCLUSIONS: Late complications occur frequently in survivors of advanced stage NB. The majority of these problems are of mild-moderate severity. Long-term follow-up (LFTU) and screening of this population is essential.     

Liver transplantation as a potentially lifesaving measure in neuroblastoma stage 4S

Neuroblastoma (NBL) stage 4s is an incompletely understood phenomenon with variable clinical course. While the majority of patients may undergo spontaneous regression and achieve complete resolution without intensive therapy, a small proportion is at increased risk of developing secondary complications. One such situation is liver insufficiency due to diffuse metastases. We report a patient suffering from NBL 4S who required double lifesaving liver transplantation. Abdominal and respiratory complications due to hepatomegaly are crucial determinants for treatment intensity and duration in 4S NBL [1,2] Nickerson HJ, Matthay KK, Seeger RC, et al. Favorable biology and outcome of stage IV-S neuroblastoma with supportive care or minimal therapy: a Children's Cancer Group study. J Clin Oncol 2000;18:477–486. Hsu LL, Evans AE, D'Angio GJ. Hepatomegaly in neuroblastoma stage 4s: criteria for treatment of the vulnerable neonate. Med Pediatr Oncol 1996;27:521–528. . We provide an algorithm in order to facilitate the clinical decision when dealing with similar potentially life-threatening events.     

Fetal and neonatal neuroblastoma: retrospective review of 271 cases

Neuroblastoma is the foremost malignant neoplasm of the fetus and neonate. The tumor is unique because of its distinctive biologic behavior and many different clinical manifestations. The purpose of this review is to focus on the fetus and neonate to determine the various ways perinatal neuroblastomas differ clinically and morphologically and in their treatment from those found in the older child to show that some forms of the tumor have a better outcome than others. The report attempts to evaluate the influence of site, histology, stage, biologic markers, and treatment on survival.     

4S neuroblastoma: the long-term outcome

BACKGROUND: Stage 4S neuroblastoma is associated with a high rate of spontaneous maturation and involution, with survival rates of 70-90%. There is little long-term follow-up data describing the disease status or late effects. The aim of this study was to assess the clinical outcome and imaging findings in long-term survivors of 4S neuroblastoma. METHODS: The patient population was identified from a single centre over 26 years. Twenty-five of 31 consecutive patients were long-term survivors. Five died from disease progression and one from cerebral palsy related complications. All survivors underwent clinical examination. Abdominal ultrasound scanning, liver function tests, hepatitis viral screen, and urinary catecholamines were performed. RESULTS: The mean age at diagnosis was 8 +/- 9 weeks with a mean age when studied of 11 years and 10 months +/- 8 years. Twenty of 25 had no significant clinical findings, three had disease associated clinical abnormalities (neurological, multiple subcutaneous nodules). Three patients had treatment related effects (small testes, urethral stricture, radiation induced soft tissue hypoplasia, post-surgical Horners syndrome). Persistant adrenal enlargement and calcification was noted in three patients. Twelve patients had abnormal liver ultrasound findings ranging from mildly coarse echotexture to structural changes without evidence of hepatic dysfunction or infection. Treatment did not correlate with abnormal hepatic ultrasound findings. CONCLUSIONS: The majority of long-term survivors of stage 4S neuroblastoma have no clinically or radiologically significant sequelae but do have residual abnormalities. These findings have implications for subsequent management of unrelated medical conditions in this patient group.     

CNS recurrence following CD34+ peripheral blood stem cell transplantation in stage 4 neuroblastoma

We report here central nervous system (CNS) recurrence in neuroblastoma (NBL) after CD34(+) peripheral blood stem cell transplantation (PBSCT). Fifteen stage 4 NBL patients underwent CD34(+) transplantation with myeloablative chemotherapy consisting of carboplatin, etoposide, and melphalan. There were three primary site recurrences and five distant metastases including four brain metastases (two isolated CNS recurrences) at 4-7 months after CD34(+) transplantation. Three of four patients died of CNS progressive disease at 2, 8, and 9 months after recurrence and the remaining single patient was lost to follow-up. CNS recurrence in NBL is fatal and requires identification of risk factors and more effective treatment strategies.     

Successful liver transplantation in an infant with stage 4S(M) neuroblastoma

We report a 2.5‐month‐old infant with bilateral adrenal neuroblastoma, stage 4S(M), with liver metastases and chemotherapy‐induced veno‐occlusive disease leading to cirrhosis requiring liver transplantation. Despite unknown tumour histology and MYCN‐amplification status, we proceeded with liver transplant. This decision was based on clinical suspicion that our patient was MYCN‐negative due to significant tumour regression, and was supported by evidence indicating that MYCN‐amplification is rare in infants with favourable‐stage neuroblastoma. This is the second case report of neuroblastoma requiring liver transplantation; however, in the previously reported case, the diagnosis of neuroblastoma was not established until after transplantation. We discuss this unique case to justify the potential use of life‐saving liver transplants in infants with neuroblastoma. Pediatr Blood Cancer 2013; 60: 515–517. © 2012 Wiley Periodicals, Inc.     

Rituximab for treatment of opsoclonus-myoclonus syndrome in neuroblastoma

Opsoclonus-myoclonus syndrome (OMS) is a rare paraneoplastic syndrome that occurs in 2%-3% of patients with neuroblastoma. The cause of this syndrome is believed to be immune mediated, but the exact mechanism still remains unclear. There is an urgent need to improve our current strategies for treating patients with OMS, as many patients have significant long-term neurologic deficits and behavior disorders with current treatment approaches. Therapies that have shown to improve symptoms in these patients have ranged from ACTH and corticosteroids, to intravenous gammaglobulin and plasmapheresis. We report our experience with Rituximab in a patient with neuroblastoma and OMS.     

~(131)I标记间碘苄胍治疗神经母细胞瘤的疗效和安全性评价

目的观察131I标记间碘苄胍(131I-MIBG)在Ⅳ期神经母细胞瘤患儿应用过程中的临床反应,评价其有效性和安全性。方法选择131I-MIBG SPECT显像阳性的5例Ⅳ期神经母细胞瘤患儿为治疗组,用药前3~5 d常规应用复合碘溶液封闭甲状腺(至用药后7 d),131I-MIBG 1850~7400 MBq(50~200 mCi)溶于250 ml的0.9%氯化钠注射液中静脉滴注,用药后观察临床疼痛、发热、突眼等症状的改善情况,并对血液生化及影像学资料的变化进行比较,评价其有效性和安全性。结果 5例中3例转移性骨痛患儿用药24 h内疼痛消失,3例眼症患儿中有2例单次应用131I-MIBG7400 MBq(200 mCi),均于用药20~30 d后突眼明显缓解,1例患儿视力恢复;颅顶转移灶缩小50%。毒副作用:骨髓抑制出现较高,肾上腺危象出现1例。结论 131I-MIBG对于Ⅳ期神经母细胞瘤患儿控制症状、延缓病情进展具有显著的治疗效果,但应注意毒副作用的发生,及时纠正。对于儿童剂量的确定,有待进一步探讨。     

Langerhans cell histiocytosis in a patient with stage 4 neuroblastoma receiving oral fenretinide

Langerhans cell histiocytosis (LCH) has previously been reported in association with other malignancies. The pathogenesis of LCH and its relationship to other malignancies is poorly understood. We present a novel case of a child who developed an LCH bone lesion while receiving a Phase I protocol therapy with oral fenretinide/Lym‐X‐Sorb (4‐HPR/LXS) powder for neuroblastoma. Pediatr Blood Cancer 2009;53:1111–1113. © 2009 Wiley‐Liss, Inc.     

Analysis of needle versus open biopsy for the diagnosis of advanced stage pediatric neuroblastoma

BACKGROUND: Adequate tissue biopsy is necessary for the appropriate diagnosis and risk stratification of pediatric neuroblastoma (NB). We compared the quality and adequacy of biopsy tissue and complication rates in children with NB who underwent open (OBX) and image-guided needle biopsy (NBX) at our center. METHODS: We retrospectively reviewed all patients diagnosed with stage III and IV NB from September 2001 to August 2004. The 24 patients were divided into two groups: those in whom the diagnosis was initiated using NBX, and those diagnosed using OBX. In addition to demographic data, we collected data pertaining to sufficiency of biopsy tissue for biology studies including: Shimada Classification, MYC-N amplification, and DNA index analysis and complications associated with the procedure. Chi-Square and Student's t-test were used to analyze the categorical and continuous variables, respectively. RESULTS: Of 24 patients, 11 underwent NBX, and 13 patients underwent OBX. Eighteen patients had stage IV disease, 5 patients had stage III disease, and 1 stage IVS. Ten major complications occurred in four NBX patients and six OBX patients. There was no difference in days of narcotic use, time to DAT, or hospital stay between the two groups. Ten patients (seven NBX and three OBX, P = 0.045) had tissue that was insufficient for biology studies. Three of the seven NBX patients underwent a second biopsy for clarification of risk group. CONCLUSIONS: This study demonstrated that more than half of patients undergoing NBX for NB had insufficient tissue for complete histological and molecular classification and that the incidence of procedural complications between NBX and OBX are similar.     

Multimodality treatment for recurrent neuroblastoma in the central nervous system

Survival for patients with recurrent central nervous system (CNS) neuroblastoma remains poor. A single-institutional study demonstrated the potential of multimodality therapy, including compartmental intrathecal radioimmunotherapy (cRIT) with ¹³¹I-3F8 or ¹³¹I-8H9 to increase the survival of neuroblastoma patients with CNS relapse. However, not all patients are able to receive this therapy. We report three patients with CNS neuroblastoma who remain disease-free 3–9 years after receiving multimodality treatment without cRIT. Additional studies to identify patients most likely to benefit from cRIT are warranted.     

Treatment of stage III neuroblastoma with emphasis on intensive induction chemotherapy: A report from the neuroblastoma group of the spanish society of pediatric oncology

From October 87 to April 92, 172 children were admitted in the N-I-87 protocol of the Spanish Society of Pediatric Oncology for the diagnosis and treatment of neuroblastoma. Forty-eight were considered Evans stage III, 33 of them being older than 1 year. All children were treated with induction chemotherapy (IC) and surgery. IC consisted of three courses of high-dose cisplatin-VM-26 alternating with three further courses of cyclophosphamide-doxorubicin (CAD). Infants less than 1 year received the same drugs at lower doses. After surgery, maintenance chemotherapy was administered to all children during 14 months. It consisted of four pairs of drugs rotated every 4 weeks. Radiotherapy was administered exclusively to patients older than 1 year with residual tumor after IC and surgery. Response was evaluated after IC and surgery. In children older than 1 year, response was obtained in 28/33 (88%). Fifteen of them (47%) achieved complete remission (CR), seven (22%) good partial response (GPR), six (19%) partial response (PR); and in three patients (9%) there was progressive disease (PD). Actuarial survival at 48 months was 0.60 ± 0.10 and EFS was 0.61 ± 0.12. Audiologic impairment was considered the worst toxicity. In children less than 1 year the response rate to IC and surgery was 93% (14/15); nine infants obtained complete response and four had GPR. Only one patient experienced PD in the first 6 months of therapy and died. The other 14 are alive and well at a mean follow-up time of 48 months. Chemotherapy toxicity was mild and reversible. © 1995 Wiley-Liss, Inc.