Treatment response with sirolimus for a pediatric patient with an EBV‐associated smooth‐muscle tumor after bone marrow transplantation

Epstein–Barr virus–associated smooth‐muscle tumors (EBV‐SMTs) are unique and rare neoplasms described in immunocompromised patients. The case describes a nine‐year‐old female with a history of acute lymphoblastic leukemia with relapse and subsequent allogeneic bone marrow transplantation who presented with multiple EBV‐SMTs of the liver. EBV utilizes the mammalian target of rapamycin (mTOR) pathway for tumor growth, and sirolimus, a mTOR inhibitor, has shown to result in a short‐term response. We now report an extended treatment response with sirolimus in a pediatric patient with an EBV‐SMT.     

Hodgkin's disease in children: Treatment with MOPP and low-dose,extended field irradiation without laparotomy late results and toxicity

The 10 year results of a trial of bimodal treatment of Hodgkin's disease in children with 6 cycles of MOPP and low-dose extended field irradiation, without staging laparotomy, were for 57 children in all stages as follows: survival 85%, relapse-free survival 80%, and survival-free of second relapse 86%. There were three fatal toxic events, two due to viral infection and one to a second malignant tumor (NHL). Three other patients developed a second malignant tumour, and one developed a thyroid adenoma. No patient developed acute leukemia. These results are compared with the results of treatment of surgically staged children by extended field irradiation alone, with bimodal treatment reserved for relapse or advanced disease at diagnosis. Initial bimodal treatment improved the overall 10 year survival free from a second relapse rate by 20% (86% vs. 66%). No major difference in treatment toxicity between these two groups has emerged during the first 10 years of follow-up. We conclude that, except for favourable CS-1 presentations, children with Hodgkin's disease confined to the lymphatic system should be given bimodal treatment, but that the least morbid effective combination remains to be determined.     

Pediatric hodgkin's disease in costa rica: Twelve years' experience of primary treatment by chemotherapy alone,without staging laparotomy

This is a prospective and nonrandomized study in which 86 children with previously untreated Hodgkin's disease (HD) were clinically staged (CS) and treated with chemotherapy (CT) alone. Fifty-two (CS IA-38, IIA-7, IIB-3, IIIA-4) received six courses of cyclophosphamide, vinblastine, procarbazine, and prednisone (CVPP). Ten (CS IA with peripheral nodes) received only three courses of CVPP with a reinforcement of C on day 8. Twenty-four (CS IIIB-18, IVA-2, IVB-4) received six courses of CVPP alternating with six courses of epirubicine, bleomycine, and vincristine (EBO). Surgical staging was not performed in any patient. Two patients (CS IIIB) had partial remission and died from progressive disease. Seventy out of 86 children have not relapsed and are in complete remission with a median follow-up of 65 months (range 13-156 months); 14 children relapsed seven to 37 months from diagnosis (median 16 months); one of them (IV B) died of disease. Thirteen are in second and third remission (median 55 months). Actuarial five year survival rates and relapse-free survival rates are 100% and 90% for CS I to IIIA and 81% and 60% for CS 1MB and IV, respectively. As a result of this study, we can conclude that in developing countries most of the children with HD staged by noninvasive diagnostic techniques can be cured with CT alone as primary treatment and thus will not suffer from the late effects of radiotherapy (RT) and the morbidity of laparotomy and splenectomy. RT alone or with other CT combinations should be considered for children who develop relapse of HD. © 1994 Wiley-Liss, Inc.     

Intracranial Hodgkin's disease in two patients with familial Hodgkin's disease

Intracranial Hodgkin's disease is very rare and is often a terminal event. The case of a 33-year-old man who relapsed in the anterior pituitary gland without other evidence of disease 6 months after extended field radiation therapy for Stage IIA Hodgkin's disease is presented. He remains well with no evidence of disease five years after surgery and chemotherapy for intracranial relapse. The case of a 16-year-old boy with a dural relapse of Hodgkin's disease associated with positive cerebrospinal fluid cytology is also presented. These two patients are members of different families each with multiple cases of Hodgkin's disease. Central nervous system involvement with Hodgkin's disease may be more frequent in familial Hodgkin's disease in which immune deficiency is common. Med. Pediatr. Oncol. 28:255–258. © 1997 Wiley-Liss, Inc.     

Benign proliferative lesions mimicking recurrence of Hodgkin's disease

Salvage treatment in patients with recurrent Hodgkin's disease is more effective when tumor burden is minimal. That is why more intensive follow-up strategies, including frequent imaging tests, have been recently developed for the detection of early relapse. However, as screening procedures become more sensitive, there is an increasing risk of false-positive results, demonstrating nonmalignant proliferative disorders. We describe three young patients who had lymphocyte-predominant or mixed-cellularity Hodgkin's disease and were in clinical complete remission for 2.5–3 years after a combined treatment with chemotherapy and radiation. Imaging tests revealed new gallium-avid lymphadenopathy in the chest in two cases. Pathologically enlarged pelvic lymph nodes were identified in another case, after a diagnosis of recurrent disease in axilla. Those findings were interpreted as relapse, and the patients underwent thoracotomy and laparotomy, respectively, for histologic confirmation. The results showed progressively transformed germinal centers and sarcoid-like lesions, two benign proliferative disorders. When patients with Hodgkin's disease in remission show new lymphadenopathy, even with positive gallium scan, it seems mandatory to obtain tissue for histologic examination, even through invasive procedures such as laparotomy and thoracotomy, to avoid wrong diagnosis and unnecessary treatment. Med. Pediatr. Oncol. 28:187–190 © 1997 Wiley-Liss, Inc.     

Treatment of childhood Hodgkin's disease with ABVD without radiotherapy

Seventeen previously untreated children with Hodgkin's disease were treated with six courses of the combination adriamycin, bleomycin, vinblastine, and DTIC (ABVD), without radiotherapy, from 1984–1987. In all patients, complete remission was attained. After a median follow-up period of 73.5 months (range 59–98 months), five patients had a relapse after 4, 5, 11, 21, and 34 months, respectively, from attainment of complete remission. In 12 patients with stages I and II, two relapses occurred. Three out of five patients with stage III and stage IV developed a relapse. Based upon these results, we conclude that ABVD might be an appropriate treatment for newly diagnosed children with Hodgkin's disease stages I and II. However, for children with stages III and IV, more intensive treatment is needed. Radio-therapy should be withheld for children with refractory disease, residual disease, or relapse. © 1996 Wiley-Liss, Inc.     

Dose‐escalation is needed for gross disease in high‐risk neuroblastoma

1 Background

Locoregional failure is common after subtotal resection in high‐risk neuroblastoma. Although a dose of 21 Gy radiation therapy (RT) is standard for treatment of high‐risk neuroblastoma after gross total resection, the dose needed for local control of patients with gross residual disease at the time of RT is unknown. We sought to evaluate local control after 21–36 Gy RT in patients with high‐risk neuroblastoma undergoing subtotal resection.

2 Methods

All patients with high‐risk neuroblastoma who received RT to their primary site from 2000 to 2016 were reviewed. Of the 331 patients who received consolidative RT to their primary site, 19 (5.7%) underwent subtotal resection and were included in our analysis. Local failure (LF) was correlated with biologic prognostic factors and dose of RT.

3 Results

Median follow‐up among surviving patients was 6.0 years. Median RT dose was 25 Gy (range, 21 Gy–36 Gy). The 5‐year cumulative incidence of LF among all patients was 17.2%. LF at 5 years was 30% in those who received <30 Gy versus 0% in those who received 30–36 Gy (P = 0.12). There was a trend towards improved local control in patients with tumor size ≤10 cm at diagnosis (P = 0.12). The 5‐year event‐free and overall survival were 44.9% and 68.7%, respectively.

4 Conclusion

After subtotal resection, patients who received less than 30 Gy had poor local control. Doses of 30–36 Gy are likely needed for optimal control of gross residual disease at the time of consolidative RT in high‐risk neuroblastoma.     

Chemotherapy and irradiation in childhood Hodgkin's disease.

Eighty children aged less than 16 years with newly diagnosed Hodgkin''s disease were treated between 1974 and 1982. Complete remission occurred in 95%, with actuarial five year overall survival of 94%, and relapse free survival of 82%: median follow up was 4.8 years. Sixty one children were staged clinically while 19 had staging laparotomies before treatment. Most received combined modality treatment with Ch1VPP chemotherapy (chlorambucil, vinblastine, procarbazine, and prednisolone) followed by irradiation of initial bulk disease. Nodular sclerosis predominated in both sexes, accounting for 60% of the total. Girls with stage IV disease, nodal sclerosis histology, and bulky mediastinal masses had a relatively poor prognosis. Ten children have relapsed, and three prolonged (6 to 7 years) second remissions have been observed. Four died of disease, and one from infection. Clinical staging, avoiding splenectomy, reduced the risk of serious infections. Our current policy is to treat stage IA disease with local irradiation and all other stages with chemotherapy, adding irradiation for bulky mediastinal disease.     

Unusual secondary tumors after childhood lymphoid malignancy

Second malignant neoplasms (SMN) in individuals who survived childhood cancer have been reported with increasing frequency during the last decades. The overall probability of developing second malignancy for children treated for cancer was estimated at about 2–5% at 25 years. In children, the tumors most often associated with the development of SMN are retinoblastoma and Hodgkin's disease. We report two cases of unusual second tumors in two patients cured of lymphoid malignancy: one boy cured of acute lymphoblastic leukemia developed mediastinal ganglioneuroma nine years later and one girl had gastric carcinoma seven years after Hodgkin's disease. Both developed a tumor in nonirradiated areas. Gastric carcinoma and ganglioneuroma are not reported as recurrent SMN in survivors after childhood cancer, with one single case of gastric carcinoma and one of ganglioneuroblastoma having been reported as second tumor in survivors after childhood cancer. © 1995 Wi1ey-Liss Inc.     

Second Malignant Neoplasms in Patients Treated for Childhood Leukemia: A Population-based Cohort Study from the Nordic Countries

ABSTRACT. Among a cohort of 981 children who were followed up 4.3–26.5 years after cessation of antileukemic therapy, eight patients in remission of acute lymphoblastic leukemia (ALL) developed a distinctively new malignant disease. The second malignant neoplasms (SMN) included brain tumors, basal cell carcinomas, thyroid cancer, leiomyo-sarcoma and finally rhabdomyosarcoma in a patient who also had suffered from Hodgkin's disease while still on antileukemic treatment. Cranial radiation had been given to 58.4% of the patients in the study group, which consisted of 895 ALL patients who had completed various chemotherapy protocols. With one exception, the SMN appeared after 7.5–16.5 years at a location previously exposed to radiotherapy (RT). The estimated cumulative risk of SMN appearing within 20 years after diagnosis was 2.9%, and the corresponding risk for cases with RT was 8.1% compared to 0.3% for those without ( p = 0.05). In a Cox regression analysis, the incidence rate ratio of SMN between patients with and without RT was 6.7 (95% CI = 0.8, 57.7). Based on age-, year- and sex-specific cancer incidence figures for Norway, the overall standardized incidence rate ratio (SIR) of SMN after treatment for ALL was 5.9 (95% CI = 2.2, 12.9). The number of brain tumors among patients who had received cranial radiation was nearly 27 times greater than expected, whereas no such tumors were seen after chemotherapy. Individuals treated for childhood ALL are at increased risk of a new malignancy, and this seems mainly to be associated with previous irradiation.     

Second malignant neoplasms in patients treated for childhood leukemia. A population-based cohort study from the Nordic countries. The Nordic Society of Pediatric Oncology and Hematology (NOPHO).

Among a cohort of 981 children who were followed up 4.3-26.5 years after cessation of antileukemic therapy, eight patients in remission of acute lymphoblastic leukemia (ALL) developed a distinctively new malignant disease. The second malignant neoplasms (SMN) included brain tumors, basal cell carcinomas, thyroid cancer, leiomyosarcoma and finally rhabdomyosarcoma in a patient who also had suffered from Hodgkin's disease while still on antileukemic treatment. Cranial radiation had been given to 58.4% of the patients in the study group, which consisted of 895 ALL patients who had completed various chemotherapy protocols. With one exception, the SMN appeared after 7.5-16.5 years at a location previously exposed to radiotherapy (RT). The estimated cumulative risk of SMN appearing within 20 years after diagnosis was 2.9%, and the corresponding risk for cases with RT was 8.1% compared to 0.3% for those without (p = 0.05). In a Cox regression analysis, the incidence rate ratio of SMN between patients with and without RT was 6.7 (95% CI = 0.8, 57.7). Based on age-, year- and sex-specific cancer incidence figures for Norway, the overall standardized incidence rate ratio (SIR) of SMN after treatment for ALL was 5.9 (95% CI = 2.2, 12.9). The number of brain tumors among patients who had received cranial radiation was nearly 27 times greater than expected, whereas no such tumors were seen after chemotherapy. Individuals treated for childhood ALL are at increased risk of a new malignancy, and this seems mainly to be associated with previous irradiation.     

Non-Hodgkin's lymphoma: current management

Around 100 new cases of non-Hodgkin's lymphoma are diagnosed each year in the UK, accounting for 7% of childhood cancer. Immunophenotype and stage are used to determine treatment, current treatment resulting in more than 70% long-term survival. The extent of disease at diagnosis is the most important prognostic factor. Patients with localized disease have an excellent prognosis regardless of histology, with a 5-year survival rate of around 90%. The use of intensive multi-agent chemotherapy has improved the outcome for patients with more advanced disease. However, children who relapse after intensive treatment have a poor outcome despite aggressive attempts at salvage treatment. Future advances in treatment require multinational trials in order that treatment can be refined to reduce toxicity for those children with an expected good outcome, and to develop new strategies for children who relapse.     

Late recurrence in Hodgkin's disease: A report of two cases

Two cases of Hodgkin's disease are described who relapsed 22 and 19 years after regional radiation therapy. One of the patients also developed a carcinoma of the large bowel soon after first relapse. The importance of long follow-up and documentation of cause of death in Hodgkin's disease is stressed.     

Hodgkin's disease presenting in epitrochlear nodes

Two cases of Hodgkin's Disease (HD) presenting in epitrochlear nodes are described, and compared to four similar cases gleaned from the literature. The nodular sclerosis type of HD was present in 5 of the 6 patients. Of the four patients staged with laparotomy, two had infradiaphragmatic disease. A treatment approach using radiation alone for patients with disease limited to the epitroclear region is presented, and anatomical considerations of the treatment technique are given.     

儿童急性早幼粒细胞白血病PML-RARα融合基因跟踪检测的临床意义(英文)

目的　探讨跟踪检测急性早幼粒细胞白血病 (APL)特有的PML RARα融合基因在发现APL早期复发和指导APL临床治疗方面的意义。方法　 1 0例APL患儿用全反式维甲酸 (ATRA)和 (或 )其它化疗药物进行诱导缓解、巩固治疗和维持治疗 ,并进行随访。在病程的不同阶段采集骨髓标本进行形态学检查 ,并应用RT PCR方法检测PML RARα融合基因。结果　随访时间为 1 4～ 1 5 6月 (中位时间 4 2月 ) ,5年无病生存率为 5 6 .0 %±1 6 .5 %。 1 0例APL患儿完全缓解 (CR)率为 90 % ,早期死亡 1例。 9例CR病人中 4例在CR后 1 4～ 4 2月复发 ,4例在连续完全缓解 4～ 5年后已停药 ,停止治疗时间为 1 8～ 96月。 1例CR ,仍在继续治疗中。 9例CR患儿中 ,8例在病程中PML RARα转为阴性 ,1例持续阳性。 4例复发病人中 ,2例复发前持续阳性 ,2例在病程中由阴性转为阳性。 5例仍生存的患儿中 ,1例在病程中PML RARα由阴性转为阳性 ,2例分别在持续完全缓解 36和 4 2月仍呈阳性 ,这 3例患儿经治疗干预后均转阴 ,且长期生存。结论　对APL患儿跟踪检测PML RARα可早期发现分子复发 ,及时干预治疗可避免血液学复发。     

Sparing strategy does not compromise prognosis in pediatric localized synovial sarcoma: experience of the International Society of Pediatric Oncology, Malignant Mesenchymal Tumors (SIOP-MMT) Working Group

Background

The aim of this analysis was to identify if the modified indications of radiotherapy (RT) or radical surgery compromised survival in pediatric synovial sarcoma (SS).

Procedure

Children with non‐metastatic SS, prospectively enrolled in three trials, were analyzed. After primary surgery or biopsy, they received chemotherapy. RT was planned after chemotherapy in patients who had not achieved a complete response (CR). The considered outcome was 5‐year overall survival (OS) and event‐free survival (EFS).

Results

Eighty‐eight patients were identified. Primary tumors were mainly located in limbs (66%). The first‐line therapy for 65 patients was primary resection. Of the 49 patients who had gross tumor resection, 43 received adjuvant chemotherapy, and 8 had RT. All of the 39 patients with macroscopic residual disease received chemotherapy, then only surgery (n = 12) ± RT (n = 22). The 5‐year EFS and OS rates were 68% and 85%, respectively. The TNM stage was a prognostic factor for relapse, whereas primary site of the tumor and TNM stage were prognostic factors for death.

Conclusions

Only 32% of survivors received RT. OS was similar to published data. Omission of RT may be considered in younger children, to limit the potential sequelae in patients with tumors less than 5 cm in size initially submitted to marginal resection. This strategy may also be considered in initially unresected cases, when the tumor is resected at delayed surgery with microscopically free margins, and in patients in complete remission after primary chemotherapy. Pediatr Blood Cancer 2011; 57: 1130–1136. © 2011 Wiley Periodicals, Inc.     

Hodgkin's disease in children: treatment with MOPP and low-dose, extended field irradiation without laparotomy. Late results and toxicity

The 10 year results of a trial of bimodal treatment of Hodgkin's disease in children with 6 cycles of MOPP and low-dose extended field irradiation, without staging laparotomy, were for 57 children in all stages as follows: survival 85%, relapse-free survival 80%, and survival-free of second relapse 86%. There were three fatal toxic events, two due to viral infection and one to a second malignant tumor (NHL). Three other patients developed a second malignant tumour, and one developed a thyroid adenoma. No patient developed acute leukemia. These results are compared with the results of treatment of surgically staged children by extended field irradiation alone, with bimodal treatment reserved for relapse or advanced disease at diagnosis. Initial bimodal treatment improved the overall 10 year survival free from a second relapse rate by 20% (86% vs. 66%). No major difference in treatment toxicity between these two groups has emerged during the first 10 years of follow-up. We conclude that, except for favourable CS-1 presentations, children with Hodgkin's disease confined to the lymphatic system should be given bimodal treatment, but that the least morbid effective combination remains to be determined.     

Risk of recurrence and survival after relapse in patients with Ewing sarcoma

Background

The prognosis in patients with relapsed Ewing sarcoma is unfavorable. Our investigation identifies factors predicting for the outcome following relapse.

Procedure

We analyzed type of relapse, time to relapse and overall survival after relapse (OSr) in 714 patients with first recurrence. All patients had been treated within the Cooperative Ewing Sarcoma Studies (CESS) 81 or 86, or the European Intergroup CESS (EICESS 92). OSr time was calculated from diagnosis of first relapse to last follow‐up or death.

Results

Median follow‐up time from diagnosis of primary disease was 2.2 years (mean = 4.0; range: 0.2–24.9). Relapse sites were local in 15%, combined local and systemic in 12%, and systemic in 73%. Among patients with a localized primary tumor, 20% relapsed locally, while 12% showed combined and 68% systemic relapse. When the primary disease was disseminated, 82% developed systemic, 13% combined, and 5% local relapse. Five‐year OSr was 0.13 (SE = 0.01). Outcome following local relapse, with a 5‐year survival rate of 0.24 (P < 0.001), was superior to outcome after systemic or combined recurrence. Five‐year OSr was 0.07 (SE = 0.01) in patients who relapsed 0–2 years after the diagnosis of primary disease, as compared to a 5‐year OSr of 0.29 (SE = 0.03) when relapse occurred later.

Conclusions

5‐year OSr in Ewing sarcoma is poor (<0.2). Prognostically favorable factors are: late onset (>2 years) and strictly localized relapse. Pediatr Blood Cancer 2011; 57: 549–553. © 2011 Wiley‐Liss, Inc.     

Results of a changing treatment philosophy for children with stage I Hodgkin's disease: a 35-year experience

Over the last four decades, significant changes have occurred in the management of childhood stage I Hodgkin's disease. Between 1949 and 1984, 50 children, ages 4 to 16 years, were treated for stage I Hodgkin's disease at The University of Texas M. D. Anderson Cancer Center. Nineteen children had clinically staged (CS) disease. Thirty-one patients were pathologically staged (PS). Thirty-four children were treated with radiotherapy only, 12 were treated with both radiotherapy and chemotherapy, and 3 patients were treated with combination chemotherapy alone. All patients were followed from 32 to 311 months (median 170 months). Five-, 10-, and 15-year actuarial survival rates for all patients were 94, 89, and 84%, respectively. The corresponding freedom from relapse (FFR) rates were 76, 69, and 69% respectively. The 10-year actuarial survival and FFR rates for CS patients were 79 and 42%. The corresponding rates for PS patients were 97 and 86%. In patients with PSI disease, actuarial 10-year FFR rates of 100% were obtained either with regional radiotherapy alone or with combination chemotherapy and involved field radiotherapy. The following delayed adverse effects of treatment were observed: growth abnormalities in 17, aspermia in 3, thyroid abnormalities in 11 (two carcinomas), and second malignancies beyond the radiotherapy fields in 2. We conclude with a recommendation of combined chemotherapy and involved field radiation for children who have not fulfilled their growth potential, to achieve high cure rates, while minimizing morbidity.     

Postpubertal gluten challenge in coeliac disease.

Altogether 38 postpubertal children with coeliac disease were rebiopsied. Mucosal abnormality in nine (24%) of them indicated poor adherence to the diet. Gluten challenge with a diet containing a normal amount of gluten was performed in those 29 patients with a normal mucosa. During challenge, rebiopsy was done when reticulin antibodies turned positive (mean 0.6 years, range 0.2-2.0) or at the end of the two year study. Histologically a clear relapse into coeliac disease was seen in all 23 patients who were positive for reticulin antibodies. At this time gliadin antibodies were positive in all but two. Sixteen (70%) of those who relapsed were completely asymptomatic. Three girls and one boy did not relapse within two years, indicating the possible recovery from coeliac disease to be 11%. All four had undergone gluten challenge earlier in childhood, after initial diagnosis and mucosal recovery, and this had resulted in mucosal relapse. To establish definite postpubertal recovery from coeliac disease in cases with normal mucosa at two years from challenge, further follow up studies of reticulin antibodies and later rebiopsy are needed. The reticulin antibody test seems to be suitable for prediction of mucosal relapse in coeliac disease.