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Treatment strategies involving dose intensification have recently demonstrated improvements in cure compared with older trials. However, dose-intensive therapy is associated with increased acute and long-term toxicities, particularly in pediatric patients. The Children's Cancer Group initiated this pilot study to assess the feasibility and toxicity...
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Background:
Children with Hodgkin lymphoma (HL) have excellent survival rates in high-income countries, but there are minimal outcome data in South African patients. Differing approaches to treatment are used in centres across South Africa, and the South African Children's Cancer Study Group (SACCSG) embarked on a programme to audit outcomes to im...
Purpose: Pediatric Hodgkin lymphoma (HL) is a highly curable malignancy. Outcomes for pediatric HL may
vary between developed and developing countries for multiple reasons. This study was conducted to
ascertain the outcomes of children with HL at our center and to identify risk factors for recurrent disease.
Methods: We analyzed the outcomes of 172...
The HD9 trial of the German Hodgkin Study Group compared two different doses (baseline and escalated) of the bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) chemotherapy regimen in 1,196 patients with advanced-stage Hodgkin's lymphoma (HL). The previous analysis with 5 years median follow-up...
Purpose
Pediatric Hodgkin lymphoma (HL) is a highly curable malignancy. Outcomes for pediatric HL may vary between developed and developing countries for multiple reasons. This study was conducted to ascertain the outcomes of children with HL at our center and to identify risk factors for recurrent disease.
Methods
We analyzed the outcomes of 172...
First‐line treatments for classical Hodgkin lymphoma (HL) include ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) and BEACOPPescalated (escalated dose bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, prednisone). To further improve overall outcomes, positron emission tomography‐driven strategies and ABVD or BEAC...
Citations
... Доля пациентов с рецидивом заболевания или отсутствием полного эффекта составляет 20-25% [3]. Интенсификация программной химиотерапии для пациентов с распространенными стадиями ЛХ позволила улучшить результаты лечения, однако не менее значимой проблемой остается обеспечение высокого качества жизни и снижение риска отдаленных эффектов терапии [4]. ...
... Более высокую выживаемость без прогрессирования имели также пациенты, получившие режимы интенсивной химиотерапии Stanford V (5-летняя выживаемость без прогрессирования 89%) [10] и escBEACOPP (3-летняя БСВ 82%) [4,11]. 5-летний опыт лечения детей и молодых взрослых группы высокого риска лимфомы Ходжкина в Республике Беларусь Результаты нашего пилотного исследования показали, что интенсификация химиотерапии по схеме escBEACOPP оказалась высокоэффективной у детей и молодых взрослых с IV стадией ЛХ. ...
Введение. Пациенты с распространенным опухолевым процессом ЛХ представляют главную целевую группу для поиска неблагоприятных прогностических факторов, новых подходов в диагностике и лечении.Цель исследования. Улучшить отдаленные результаты лечения пациентов детского возраста и молодых взрослых с первично распространенной ЛХ путем использования интенсивной риск-адаптированной терапии.Материалы и методы. Представлен анализ результатов лечения детей и молодых взрослых с IV клинической стадией классической лимфомы Ходжкина (ЛХ) в Республике Беларусь за 5-летний период. В анализ включены 20 пациентов с IV стадией ЛХ (0–21 год), получавших лечение в Республиканском научно-практическом центре детской онкологии, гематологии и иммунологии (РНПЦДОГИ) с августа 2016 по декабрь 2021 г. Медиана возраста составила 15,3 года. Пациенты от 0 до 21 года с IV стадией ЛХ получали программную терапию в рамках протокола ЛХ-2017. Предложенная концепция терапии подразумевала использование системной полихимиотерапии по схеме BEACOPP-эскалированный (escBEACOPP): блеомицин, этопозид, доксорубицин, циклофосфамид, винкристин, прокарбазин, преднизолон – для интенсификации лечения на этапе индукционной терапии.Результаты. За 5-летний период: бессобытийная выживаемость пациентов с IV стадией ЛХ была (94±6)%, общая выживаемость составила (95±1)%, показатель кумулятивной частоты рецидива констатирован на уровне (6,2±6)%.Заключение. Примененная терапевтическая стратегия интенсификации системной полихимиотерапии продемонстрировала клиническую эффективность и хорошую переносимость у большинства пациентов. Однако малая группа пациентов и относительно короткий период наблюдения не позволяют в полной мере оценить позднюю токсичность лечения, что требует дальнейшего наблюдения за исследуемой когортой.
Patients with advanced LH tumor process represent the main target group for the search for unfavorable prognostic factors, new approaches in diagnosis and treatment in order to improve the results of therapyPurpose. To improve the long-term results of treatment of children and young adults with primary LH by using intensive risk-adapted therapy.Materials and methods. The analysis of the results of treatment of patients with IV clinical stage of classical Hodgkin’s lymphoma (LH) in children and young adults in the Republic of Belarus for a 5-year period is presented. The analysis included 20 patients with stage IV LH (0–21 years old) who were treated at the Republican Scientific and Practical Center of Pediatric Oncology, Hematology and Immunology (RNPCDOGI) from August 2016 to December 2021. The median age was 15.3 years. Patients with stage IV LH received program therapy under the HL-2017 protocol. The proposed therapy concept implied the use of systemic polychemotherapy according to the scheme BEACOPP escalated (escBEACOPP): bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone) to intensify treatment at the stage of induction therapy.Results. Over a 5-year period: the event-free survival of patients with stage IV LH was (94±6)%, the overall survival was (95±1)%, the cumulative recurrence rate was found at (6,2±6)%.Conclusion. The obtained results of treatment of patients with a widespread tumor process of LH show the high efficiency of the used program of intensification of systemic polychemotherapy. The applied therapeutic strategy has demonstrated clinical efficacy and good tolerability in most patients. It should be noted that a small group of patients and a relatively short follow-up period do not allow to fully assess the late toxicity of treatment, which requires further monitoring of the study cohort.
... over 90% [6][7][8][9][10]. Contemporary radiation techniques with involved-field radiotherapy (IFRT) or involved-nodal radiotherapy (INRT) have lower risks of long-term toxicities. ...
Purpose:
To analyze the clinical outcomes and long-term toxicity of pediatric patients with Hodgkin lymphoma after combined-modality treatment (CMT) with involved-field or involved-nodal radiotherapy (RT).
Materials and methods:
We retrospectively reviewed the records of 27 pediatric Hodgkin lymphoma patients who received CMT at a single institution between January 1990 and July 2017. Patients with stage I-III received a heterogeneous chemotherapy regimen depending on their risk group followed by 19.8-36 Gy RT, with the dose based on their response to the chemotherapy before RT. An optional 9-20 Gy boost was delivered to residual sites. The risk group was determined based on the initial stage, the presence of bulky disease, and any B symptoms. We evaluated overall survival, event-free survival, and long-term toxicities.
Results:
A total of 27 patients completed the CMT. At a median follow-up of 125 months (range, 9 to 337 months), the estimated 5-year event-free survival and overall survival were 88.9% and 96.3%, respectively. Late symptomatic cardiopulmonary toxicity was not observed, and only one patient was positive on a subclinical obstructive pulmonary function test. The incidence of hypothyroidism was 58.3% among 12 patients with an available thyroid function test. There was one papillary thyroid cancer diagnosed 7.2 years after treatment.
Conclusion:
CMT for pediatric Hodgkin lymphoma with involved-field and involved-nodal RT achieved an excellent survival with only modest long-term toxicity. Smaller-field RT seemed to decrease long-term toxicities and had good local control.
... Patients with metabolic progression on interim PET (in the form of new sites of disease) underwent treatment escalation to four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisolone, procarbazine (BEACOPP) regimen. 12 In patients treated with escalated BEA-COPP, end-of-treatment PET-CT was performed and RT was avoided if the Deauville score was 1. 11 ...
Purpose:
Treating pediatric Hodgkin lymphoma (HL) involves a delicate balance between cure and reducing late toxicity. Fluorodeoxyglucose positron emission tomography (PET) combined with computed tomography (CT) identifies patients with early response to chemotherapy, for whom radiotherapy may be avoided. The role of PET-CT in upfront risk stratification and response-adapted treatment is evaluated in this study.
Methods:
Patients with HL, who were younger than 18 years, were included. PET-CT was performed at baseline and after two cycles of chemotherapy. Patients were stratified into three risk groups: group 1 (stage I or II with no unfavorable features); group 2 (stage I or II with bulky disease/B symptoms); and group 3 (stage III/IV). A doxorubicin, bleomycin, vinblastine, dacarbazine-based regimen was used in early disease. A cyclophosphamide, vincristine, prednisolone, procarbazine, doxorubicin, bleomycin, vinblastine-based regimen was used in advanced disease.
Results:
Forty-nine patients were included. Fifteen (31%), seven (14%), and 27 (55%) patients were included in groups 1, 2, and 3, respectively. Among 36 patients who underwent staging by PET-CT at diagnosis, seven (19%) patients were upstaged and one (3%) patient was downstaged by PET compared with CT. On the basis of negative interim PET responses, 39 (80%) patients were treated without radiotherapy. The 3-year event-free survival for the entire cohort was 91% (± 5.2%) and overall survival was 100%.
Conclusion:
PET-CT is an excellent stand-alone staging modality in HL. The omission of radiotherapy can be considered in patients who achieve metabolic remission on interim PET.
... In addition, populations are different among studies, mainly for patients' age (sometimes both adults and children) and underlying malignancy. However, the recently observed incidence increase could be at least partially explained by improved diagnostics [38,42] and intensification of antineoplastic regimens [25,52,53] . Anyway, NE is more frequently described in hematologic malignancies [7,22,23,38,40,42,50] , in children on specific drugs or drug combinations (e.g., granulocyte-colony-stimulating factor and topotecan, topotecan and idarubicin, cyclophosphamide and hydrocortisone, cyclophosphamide and methotrexate, cyclophosphamide and carboplatin, carboplatin and methotrexate; anthracyclines, cytosine arabinoside, steroids) [42,51,53] administered in the 2-3 wk preceeding the onset of symptoms [38,54] , and in the presence of mucositis [54] . ...
... However, the recently observed incidence increase could be at least partially explained by improved diagnostics [38,42] and intensification of antineoplastic regimens [25,52,53] . Anyway, NE is more frequently described in hematologic malignancies [7,22,23,38,40,42,50] , in children on specific drugs or drug combinations (e.g., granulocyte-colony-stimulating factor and topotecan, topotecan and idarubicin, cyclophosphamide and hydrocortisone, cyclophosphamide and methotrexate, cyclophosphamide and carboplatin, carboplatin and methotrexate; anthracyclines, cytosine arabinoside, steroids) [42,51,53] administered in the 2-3 wk preceeding the onset of symptoms [38,54] , and in the presence of mucositis [54] . Different factors are associated with severe clinical presentation [22,26,38,42,[55][56][57] , as summarized in Table 2. Before year 2000 50%-100% mortality was reported, but in the last years this proportion has been reduced from 50% to 30%,or even lesser [7,22,25,26,38,41,47] , probably as a consequence of earlier diagnosis and improved treatment strategies. ...
Aim:
To review gastrointestinal and liver infections in children undergoing antineoplastic chemotherapy. To look at gut microflora features in oncology children.
Methods:
We selected studies published after year 2000, excluding trials on transplanted pediatric patients. We searched English language publications in MEDLINE using the keywords: "gastrointestinal infection AND antineoplastic chemotherapy AND children", "gastrointestinal infection AND oncology AND children", "liver infection AND antineoplastic chemotherapy AND children", "liver abscess AND chemotherapy AND child", "neutropenic enterocolitis AND chemotherapy AND children", "thyphlitis AND chemotherapy AND children", "infectious diarrhea AND children AND oncology", "abdominal pain AND infection AND children AND oncology", "perianal sepsis AND children AND oncology", "colonic pseudo-obstruction AND oncology AND child AND chemotherapy", "microflora AND children AND malignancy", "microbiota AND children AND malignancy", "fungal flora AND children AND malignancy". We also analysed evidence from several articles and book references.
Results:
Gastrointestinal and liver infections represent a major cause of morbidity and mortality in children undergoing antineoplastic chemotherapy. Antineoplastic drugs cause immunosuppression in addition to direct toxicity, predisposing to infections, although the specific risk is variable according to disease and host features. Common pathogens potentially induce severe diseases whereas opportunistic microorganisms may attack vulnerable hosts. Clinical manifestations can be subtle and not specific. In addition, several conditions are rare and diagnostic process and treatments are not standardized. Diagnosis may be challenging, however early diagnosis is needed for quick and appropriate interventions. Interestingly, the source of infection in those children can be exogenous or endogenous. Indeed, mucosal damage may allow the penetrance of endogenous microbes towards the bowel wall and their translocation into the bloodstream. However, only limited knowledge of intestinal dysbiosis in oncology children is available.
Conclusion:
The diagnostic work-up requires a multimodal approach and should be implemented (also by further studies on new biomarkers) for a prompt and individualized therapy.
... All studies using very aggressive chemotherapy regimens, including the classical MOPP/ABV, BEACOPP, or ABVD followed by IFRT showed a 5-year EFS ranging from 59% to 95% and an 5-year OS over 90%. The omission of IFRT is significantly associated with a worse outcome [35,[37][38][39]42,43,45,46] (Table III). ...
Epidemiologic and molecular findings suggest that classical Hodgkin's lymphoma (CHL) is not a single disease but consists of more than one entity and may occur in different clinical settings. This review analyzes similarities and disparities among CHL entities arising in different host's conditions with respect to pathobiology parameters, therapeutic options, and outcome. For the purpose of this analysis, CHL entities have been subdivided according to the immune status of the host. In nonimmunosuppressed hosts, according to the age, CHL include pediatric, adult, and elderly forms, whereas, in immunosuppressed hosts, according to the type of immunosuppression, CHL include human immunodeficiency virus (HIV)-associated, iatrogenic, and post-transplant types. CHL entities in different settings are similar in morphology of neoplastic cells, expression of activation markers, and aberrations/activation of NFKB, JAK/STAT, and P13K/AKT pathways, but differ in the association with Epstein-Barr virus (EBV) infection, persistent B-cell phenotype, and cellular background composition. Large B-cell lymphomas resembling CHL may also be observed in the same clinical settings. These lesions, however, do not fulfill the diagnostic criteria of CHL and clinically display a very aggressive behavior. In this article, current treatment options for the CHL entities, especially for elderly CHL and HIV-associated CHL, are specifically reviewed. ABVD remains the gold standard both in nonimmunosuppressed or immunosuppressed hosts even if there are several data suggesting a possible improvement in outcome using the aggressive BEACOPP regimen in advanced stages. Refractory CHL, a clinical condition that may occur throughout the entire spectrum of CHL, is discussed separately.
... Intensification of chemotherapy should also be considered judiciously as the toxicity of therapy may be different in children as compared to adults. This was clearly suggested when the BEACOPP regimen, which is gaining standard therapy status in adult advanced stage disease, was tested in the pediatric population [23]. While early tumor control was excellent, there was an increase in the incidence of typhlitis resulting in one death, suggesting higher regimen-related toxicity in children as compared to adults. ...
Primarily a disease of adults, Hodgkin's lymphoma (HL) contributes significantly to pediatric malignant diseases, particularly in developing countries where the incidence is higher. The treatment has evolved and now most patients are treated with chemotherapy; the optimal use additional radiation therapy (XRT) is being questioned, and it is likely that XRT will be reserved for a subset of higher risk patients. Patients with advanced disease have lower outcomes, which have improved with chemotherapy intensification. This has the potential for increasing acute and long-term toxicity. Treatment strategies for HL should be risk and response stratified, aiming at reduction of toxic effects.
... O uso do BEACOPP causa efeitos tóxicos agudos sobre a medula óssea e, além disso, há também maior toxicidade tardia, com risco de leucemia secundária, infertilidade e toxicidade cardíaca e pulmonar. 14 O tratamento do LH de estadiamento avançado continua em discussão, sendo o ABVD associado ou não ao MOPP ainda utilizado em muitos países. 15 O DH-II-90 preconiza o uso de radioterapia em campo envolvido e em doses baixas para os pacientes de baixo estadiamento, e, para aqueles de estadiamento IV ou B, radioterapia estendida. ...
The challenge of new protocols for Hodgkin's lymphoma (HL) treatment is to decrease the toxicity without impairing the results. The DH-II-90 protocol was designed to treat children and adolescents with HL. The objectives of this work were: 1) to assess the overall and event free survival of patients with newly diagnosed HL treated with the DH-II-90 protocol, 2) to assess the overall and event free survival by stage, age, presence of bulky disease, mediastinal mass, B symptoms, dose and type of radiotherapy, and 3) to describe late effects, data collected from the patients' charts. Sixty-eight patients with HL, from 0 to 21 years of age (median age 9 yr, 20F:48M) were treated with ABVD and involved-field radiotherapy for low-risk patients, and ABVD plus MOP or COP and extended field radiotherapy for high-risk patients. Stage distribution was: nine (13.2%) stage I A; 29 (42.6%) II A; five (7.4%) II B; nine (13.2%) III A; ten (14.7%) III B; two (2.9%) IV A and four (5.9%) IV B. The 10-year overall survival was 96.1% ± 3.8% for the low-risk group and 93.3% ± 4.5% for the high-risk group (p= 0.402). The 10-year event free survival was 88.9% ± 5.2% for high-risk and 86.5% ± 6.3% for low-risk patients (p= 0.969). The presence of mediastinal mass and more than 2100 cGy radiation doses had negative impact on event free survival (p= 0.020 and p= 0.014, respectively).Thyroid gland dysfunction was frequently observed and there were two cases of thyroid carcinoma. The DH-II-90 protocol is effective, but, due to the late effects presented by this group of patients, further modifications of the therapy schedule are required.
... 22 A legacy Children's Cancer Group trial has reported excellent early efficacy of response-based BEACOPP. 25 Even those patients whose therapy was modified after achieving CR with 4 BEACOPP (adding 4 ABVD for females or 2 ABVD with low-dose radiation therapy for males) still received procarbazine and were exposed to a higher cumulative doxorubicin dose than early responders treated on P9425. ...
... Our treatment paradigm was unique at its inception with its focus on early response after 9 weeks, measured to detect primary chemosensitivity. This approach diverges from the traditional "response at the end of chemotherapy" used to determine need for additional chemotherapy 20,27 or radiation therapy 8,[20][21][22]25,27 (Table 6). Dorffel et al assessed response at 8 weeks but only in the lowest-risk population. ...
... It is possible that better response assessment will allow us to further reduce therapy for good responders. Although recent pediatric trials 8,20,22,25,27 have attempted to identify patients who may not need radiation therapy, Nachman et al 20 and Dorffel et al 22 found a reduction in EFS for those who did not receive radiation. The former trial 20 randomized patients to receive or not receive radiation based on achieving CR; it had to be stopped early because of the reduction in EFS. ...
Current treatment strategies for Hodgkin lymphoma result in excellent survival but often confer significant long-term toxicity. We designed ABVE-PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide) to (1) enhance treatment efficacy by dose-dense drug delivery and (2) reduce risk of long-term sequelae by response-based reduction of cumulative chemotherapy. Efficient induction of early response by dose-dense drug delivery supported an early-response-adapted therapeutic paradigm. The 216 eligible patients were younger than 22 years with intermediate- or high-risk Hodgkin lymphoma. ABVE-PC was administered every 21 days. Rapid early responders (RERs) to 3 ABVE-PC cycles received 21 Gy radiation to involved regions; RER was documented in 63% of patients. Slow early responders received 2 additional ABVE-PC cycles before 21 Gy radiation. Five-year event-free-survival was 84%: 86% for the RER and 83% for the slow early responders (P = .85). Only 1% of patients had progressive disease. Five-year overall survival was 95%. With this regimen, cumulative doses of alkylators, anthracyclines, and epipodophyllotoxins are below thresholds usually associated with significant long-term toxicity. ABVE-PC is a dose-dense regimen that provides outstanding event-free survival/overall survival with short duration, early-response-adapted therapy.
... Children and adolescents with localized and advanced Hodgkin lymphoma (HL) have an excellent prognosis with overall survival rates exceeding 90%. [1][2][3][4][5] In this age group, even patients with recurring disease have a fair chance of cure using various risk-stratified approaches. 6 Autologous hematopoietic stem cell transplantation (HSCT) is increasingly used as salvage therapy also in children 7,8 with poor risk features, although the 2 randomized studies demonstrating superior event-free survival (EFS) and progression-free survival (PFS) after high-dose therapy (HDT) and HSCT included only adult patients. ...
Ninety-one children and adolescents 18 years or younger after allogeneic hematopoietic stem cell transplantation (HSCT) for relapsed or refractory Hodgkin lymphoma (HL) were analyzed. Fifty-one patients received reduced intensity conditioning (RIC); 40 patients received myeloablative conditioning (MAC). Nonrelapse mortality (NRM) at 1 year was 21% (+/- 4%), with comparable results after RIC or MAC. Probabilities of relapse at 2 and 5 years were 36% (+/- 5%) and 44% (+/- 6%), respectively. RIC was associated with an increased relapse risk compared with MAC; most apparent beginning 9 months after HSCT (P = .01). Progression-free survival (PFS) was 40% (+/- 6%) and 30% (+/- 6%) and overall survival (OS) was 54% (+/- 6%) and 45% (+/- 6%) at 2 and 5 years, respectively. Disease status at HSCT was predictive of PFS in multivariate analysis (P < .001). Beyond 9 months, PFS after RIC was lower compared with MAC (P = .02). Graft-versus-host disease did not affect relapse rate and PFS. In conclusion, children and adolescents with recurring HL show reasonable results with allogeneic HSCT. Especially patients allografted in recent years with good performance status and chemosensitive disease show highly encouraging results (PFS: 60% +/- 27%, OS: 83% +/- 15% at 3 years). Because relapse remains the major cause of treatment failure, additional efforts to improve disease control are necessary.
... Further support for the importance of appropriate therapy comes from the combined data from the German Hodgkin's Study Group HD9/HD12 and CCG 59704 trials in which dose intensive chemotherapy with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (BEA-COPP) were utilized for high-risk HL. In these studies, a markedly better 5-year EFS for age 16-21 years of 88-93% was observed, with OS approaching 100% (Kelly et al, 2002;Diehl et al, 2003;Sposto et al, 2005). ...
Lymphoma is the most common malignancy among adolescents, accounting for >25% of newly diagnosed cancers in the 15-19 year age group. Hodgkin lymphoma (HL) accounts for the majority (two-thirds) of cases, while the remainder of patients have one of four subtypes of non-Hodgkin lymphoma (NHL): diffuse large B-cell lymphoma (DLBCL) including primary mediastinal B-cell lymphoma (PMBL), Burkitt lymphoma (BL), lymphoblastic lymphoma (LL) or anaplastic large cell lymphoma (ALCL). Epidemiology, histology, treatment and outcome differ between HL and NHL, as well as among the various subtypes of NHL. Adolescent lymphoma is particularly interesting because it often shares features with both childhood and adult lymphoma. As medical oncologists and paediatric oncologists often follow divergent treatment plans, disagreements may arise between practitioners as to how best treat the adolescent group. Additional complicating factors associated with the adolescent years, such as lack of insurance, issues pertaining to body image, and concerns about fertility, can also hinder prompt, appropriate medical management. This review details the complexities associated with the diagnosis and treatment of adolescent lymphoma and updates the state of the science, with particular emphasis on epidemiology, diagnosis, and proper management of HL and the various subtypes of NHL.
