Childhood Hodgkin's Disease Research Articles

Digital Clubbing and Hodgkin Disease in Children: A Case Report and Review of Literature

Introduction: Digital clubbing (hypertrophic osteoarthropathy) as the initial presentation of lymphoma is rarely reported, particularly in children. In this study, we report a patient with intrathoracic Hodgkin Disease (HD) and digital clubbing as the first presentation, and we will review the literature regarding the same condition. Case Presentation: A 10-year-old boy presented with a 2-month history of cough, mild dyspnea, and night sweats, with prominent digital clubbing. A chest x-ray and a computed tomography scan of the chest showed multiple mediastinal masses. A mediastinal lymph node biopsy was done. Pathologic examination was indicative of nodular sclerosis HD. Conclusions: In patients with digital clubbing, intrathoracic malignancies should be considered a differential diagnosis and must be ruled out by precise examination and paraclinical help.

Outcome and Prognostic Factors of Childhood Hodgkin Disease: Experience From a Single Tertiary Center in Thailand.

In childhood, Hodgkin disease (HD) has an excellent outcome in developed countries. There are few studies on outcomes of HD from resource-limited countries. This study aimed to assess clinical outcomes and factors associated with survival rates of childhood HD in a tertiary care center in Thailand. We retrospectively reviewed the medical records of pediatric HD patients between March 1985 and August 2017. Seventy-two children diagnosed with HD were identified. Pretreatment clinical and laboratory factors were assessed by Cox regression analysis to predict event-free survival (EFS) and overall survival (OS). The overall 5-year EFS and OS rate was 70.7% and 75.5%, respectively. Multivariate analysis identified 3 factors predicting inferior EFS: high-risk group (stages III-B, IV-B), splenomegaly, and platelet count >400,000/µL. The prognostic markers were assigned a score of 1 for each factor. For a total score of 0, the 5-year EFS and OS rates were 95% and 86%; scores 2 to 3, 33% and 54%, respectively. In conclusion, our study identified 3 factors predicting inferior EFS. These adverse prognostic factors can be used in clinical practice for predicting outcomes in pediatric HD.

Outcome of Hodgkin's Disease in Children with Chemotherapy alone in a Resource Limited Country

Background: Treatment of Hodgkin's lymphoma involves both chemotherapy and radiotherapy. But radiotherapy in children is associated with risk of development of long-term complications like the development of second malignancy. Novel therapeutic strategies with combination chemotherapy without radiotherapy are being used to reduce such complications while maintaining the optimum response. Objective: To investigate the outcome of treatment of Hodgkin's Lymphoma with combination chemotherapy ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) alone. Patients and methods: A quasi-experimental open label clinical study was done on 48 children with Hodgkin's lymphoma in the Paediatric Haemato-Oncology department of Bangabandhu Sheikh Mujib Medical University (BSMMU) with eight cycle ABVD regime on an outpatient basis over a period of 8 months to see the outcome of treatment. Results: The mean age of the patients was 10.3 years (range 3-16). There were 42 males and 6 females. Mixed cellularity cHL was the commonest histological subtype observed 20/48 (42%) patients. Forty-two (88%) patients achieved complete response (CR), 5 (10%) had partial response (PR) and one patient did not respond at all. Fifteen patients (31%) are known to be dead and the rest are alive and tumour free. Median EFS and OS were not achieved. The EFS and OS at 5 years were 63% and 67% respectively. Conclusion: ABVD combination should be regarded at the present moment as the simplest and most effective drug therapy for treating childhood Hodgkin's disease.

Characteristics and Survival Outcomes of Children With Hodgkin Lymphoma Treated Primarily With Chemotherapy

Hodgkin disease is a malignant tumor of the lymphatic system that comprises ∼6% of childhood cancers. In developing countries, efforts are made to ensure adherence to standard protocol/regimens, study patients' outcomes, and compare with that in developed world. We conducted a retrospective medical records' review of 212 children younger than 20 years presenting to The Indus Hospital in Pakistan with previously untreated Hodgkin lymphoma between August 2000 and December 2012. We collected demographic and other epidemiologic variables such as age, sex, stage, subtype of disease, and survival outcomes. The mean±SD age of patients at time of diagnosis was 9.0±3.8 years with a male to female ratio of ∼4.7:1. In total, 44 (20.8%) patients were 5 years of age or above at presentation. Overall, 131 (61.8%) patients presented with B-symptoms and mixed cellularity was the most frequently diagnosed subtype in 65.1% of cases. In total, 170 (80.2%) achieved full remission after completion of chemotherapy. Patients were treated with alternating cycles of ABVD (Adriamycin, Bleomycin, Vincristine, and Dacarbazine) and COPDAC (Cyclophosphamide, Vincristine, Prednisolone, and Dacarbazine). The majority (n=114, 59.1%) received 6 cycles of chemotherapy, 44 (22.8%) received ≤4 cycles followed by 24 (12.4%) receiving 8 cycles. Radiotherapy was administered only to those patients with significant residual disease at the end of chemotherapy (n=20, 10%). The 5-year overall survival and event-free survival in our cohort was 89.6% and 82.1%, respectively. Our findings suggest that treatment with 4 to 8 alternating cycles of ABVD/COPDAC has an excellent outcome in childhood Hodgkin disease.

HODGKIN DISEASE IN CHILDREN

Background: Hodgkin lymphoma (HL) is a malignant process involving the lympho-reticular system that accounts for 6% of childhood cancers. Infectious agents may be involved, such as human herpes virus 6, cytomegalovirus, and Epstein-Barr virus (EBV). Infection with EBV confers a 4-fold higher risk of developing HL. Objective: To have an idea about the mode of presentation, pathological subtypes, treatment applied and outcome in one center in our country. Methods: A retrospective study was done whereby twenty cases were collected from the Pediatric Oncology Clinic in Al-Imamein AL-Kadhimein Medical City over a period of ten years from the first of January 2007 – end of December 2016. Information was taken from the patient’s records in the Pediatric Oncology Clinic including age at presentation, sex, physical finding, histopathological subtypes, staging , treatment applied and outcome. Results: Among the studied group, 14 cases (70%) were males and 6 cases (30%) were females, male: female ratio equal to 2.3:1, rang of age was between 5-12 years with a peak age at presentation was between 5-7 years, 12 cases (60%). The initial presentation was an enlarged cervical lymph node in 19 of them (95%), histopathologically, most of the patients had mixed cellularity subtype, 9 cases (45%), stage II and stage III comprise the majority of cases 9 cases (45%), 6 cases (30%) respectively, B symptoms were reported in 7 cases (35%). Chemotherapy was the mainstay of treatment with good response and remission, 17 cases (85%). Three cases refractory to treatment (15%) with no response, no death was reported. Conclusion: Male predominance was noticed with younger age group at presentation. The majority presented with enlarged cervical lymph node. Although mixed cellularity was encountered in most of the patients, the response to chemotherapy was good. Rituximab can be used along with chemotherapy for refractory cases and for lymphocyte predominant Hodgkin lymphoma. Keywords: Hodgkin Disease , Children Citation: Abbas SA, Ali RH. Hodgkin disease in Children. Iraqi JMS. 2018; 16(4): 424-429. doi: 10.22578/IJMS.16.4.10

Is carotid stiffness a possible surrogate for stroke in long-term survivors of childhood cancer after neck radiotherapy?

Abstract Background The risk for cerebrovascular late effects among childhood cancer survivors is considerable. According to recent studies it is not clear which marker could be reliable for the screening of cerebrovascular diseases among the long-term survivors of childhood cancer. The purpose of this study is to analyse arterial stiffness and intima-media thickness as possible early markers of later occurring stroke in long-term survivors of childhood cancer after neck radiotherapy. Patients and methods Twenty-three patients, treated for Hodgkin disease (HD) in childhood, were included. They had received radiation therapy to the neck with 20–65 (median 30) Gy. Twenty-six healthy controls, matched in age, sex, body mass index, arterial hypertension, smoking history and total cholesterol levels were compared. Highresolution colour-coded duplex sonography and power Doppler sonography of the carotid arteries were performed and intima-media thickness, number and quality of plaques were measured. Arterial stiffness indices were calculated. Results Plaque deposits and/or arterial wall calcinations were found in 24 out of 43 (55.8%) irradiated vessels in cancer survivors group and 0 out of 52 vessels in the group of healthy controls (p < 0.01). We found significant group differences for all the stiffness parameters we used (P < 0.05), but there was no difference in intima-media thickness between cases and controls (p = 0.92). In a multivariate model, carotid pulse wave velocity was positively associated with smoking. Conclusions The arterial stiffness has appeared as a possible surrogate marker for stroke in long-term survivors of childhood cancer. Smoking habit might have an additional negative influence on vascular aging in the group of patients after neck radiotherapy.

Is Carotid Stiffness a Possible Surrogate for Stroke in Long-term Survivors of Childhood Cancer after Neck Radiotherapy?

BackgroundThe risk for cerebrovascular late effects among childhood cancer survivors is considerable. According to recent studies it is not clear which marker could be reliable for the screening of cerebrovascular diseases among the long-term survivors of childhood cancer. The purpose of this study is to analyse arterial stiffness and intima-media thickness as possible early markers of later occurring stroke in long-term survivors of childhood cancer after neck radiotherapy.Patients and methodsTwenty-three patients, treated for Hodgkin disease (HD) in childhood, were included. They had received radiation therapy to the neck with 20–65 (median 30) Gy. Twenty-six healthy controls, matched in age, sex, body mass index, arterial hypertension, smoking history and total cholesterol levels were compared. Highresolution colour-coded duplex sonography and power Doppler sonography of the carotid arteries were performed and intima-media thickness, number and quality of plaques were measured. Arterial stiffness indices were calculated.ResultsPlaque deposits and/or arterial wall calcinations were found in 24 out of 43 (55.8%) irradiated vessels in cancer survivors group and 0 out of 52 vessels in the group of healthy controls (p < 0.01). We found significant group differences for all the stiffness parameters we used (P < 0.05), but there was no difference in intima-media thickness between cases and controls (p = 0.92). In a multivariate model, carotid pulse wave velocity was positively associated with smoking.ConclusionsThe arterial stiffness has appeared as a possible surrogate marker for stroke in long-term survivors of childhood cancer. Smoking habit might have an additional negative influence on vascular aging in the group of patients after neck radiotherapy.

Паранеопластичні синдроми при лімфомі Годжкіна у дітей

Паранеопластичні синдроми при лімфомі Годжкіна у дітей

Radiation-induced coronary artery disease: a second survivorship challenge?

10.2217/FON.15.121 © 2015 Future Medicine Ltd The role of adjuvant mediastinal radiation (RT) in improving disease-free survival in Hodgkin’s disease and breast cancer (BC) is well known. However, this survival advantage is accompanied by the late cardiac sequelae of radiation. Radiationinduced coronary artery disease (RICAD) is a challenging clinical entity and a major contributor to cardiovascular (CV) mortality in cancer survivors. In this review, we discuss the pathophysiology, surveillance and management challenges of RICAD.

Chondroblastic Osteosarcoma Arising in a Bone Infarct in a Patient with a Prior History of Hodgkin Lymphoma

Osteosarcoma is the most common primary bone cancer affecting adolescent and young adults. The majority of osteosarcomas occur sporadically, although increasing age is associated with a higher risk of secondary osteosarcoma. Common causes of secondary osteosarcoma include pre-existing Paget's disease and prior irradiation. Bone infarct-associated sarcoma (IAS) is a rare subset of secondary sarcoma with few reports to date. We present the case of a 28-year-old male who presented with IAS potentially related to previous steroid exposure from treated Hodgkin disease in childhood. He is currently undergoing neoadjuvant chemotherapy with consideration of a limb-sparing surgery after two cycles.

Bone mineral density in pediatric survivors of Hodgkin and non-Hodgkin lymphomas

PurposeTo assess skeletal mass in survivors of childhood Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL) 1–5 years after treatment, and to identify potential risk factors influencing bone mineral density (BMD). Patients/methodsThis cross-sectional study was conducted in a cohort of 43 survivors (HD=31; NHL=12); mean age: 16.21±4.4. Total body bone mineral content (TBMC) and density (TBBMD), and lumbar spine density (LSBMD) were determined using dual-energy X-ray absorptiometry. ResultsThree of all 43 patients developed low BMD. No significant differences in height, weight, and/or BMD Z-scores were found between HD and NHL survivors, children who received and did not receive radiotherapy, and the groups with different chemotherapeutic blocks. No differences were noted between the Z-scores of BMC (mean±SD: 0.31±1.29 vs. −0.089±0.61, p=0.165), TBBMD (mean±SD: −0.32±1.21 vs. −0.27±0.91, p=0.76), or the LSBMD (mean±SD: −0.183±1.54 vs. −0.17±0.87, p=0.637) in subgroups, in accordance with time after therapy (subgroup I<2 years and subgroup II>2 years after treatment). In HD survivors, age at diagnosis only affected the TBBMD Z-score (a decrease of 0.127 in total BMD Z-score per each year, R2=0.999, p<0.001). ConclusionsChildhood lymphoma survivors demonstrate no significant deficits in bone mass and tend to maintain their BMD within the normal range when presenting during one to five years’ follow-up. However, this specific group requires longitudinal investigation to assess the pattern of peak bone mass achievement and the risk of future bone loss.

Quality of life in long-term survivors following treatment for Hodgkin's disease during childhood and adolescence in the German multicentre studies between 1978 and 2002

The purpose of this study was to cross-sectionally assess quality of life (QoL) in survivors of childhood Hodgkin's disease (HD) in a cohort treated for HD in the successive German-Austrian therapy studies HD-78, HD-82, HD-85, HD-87, HD-90, HD-95, respectively, in accordance with the HD-Interval-Treatment recommendation between 1978 and 2002. Data from QoL questionnaires were provided by 1,202 (66 %) of 1,819 invited survivors. These included the EORTC QLQ-C30 and socio-demographic variables. Data of a homogenous sub-sample (n = 725) defined by age (21-41 years) and event- free-survival (no progress, relapse or secondary malignancies) were compared to an age-adjusted German reference sample (n = 659). While the global and physical QoL scores were comparable to those of the general population, survivors' mean scores were more than 10 points lower on the EORTC QLQ-C30 scales "Emotional" and "Social Functioning". On the symptom scales, higher mean scores, exceeding 10 points, were obtained for the scales "Fatigue" and "Sleep". In general, there was a gender effect showing lower functioning and higher symptom levels in women, most prominently in the group of young women (21-25 years). The results within the group of HD survivors could not be associated with the time since treatment, the age of HD survivors at diagnosis or the extent of therapy burden. Clinicians engaged in follow-up care should be sensitive to aspects of fatigue and related (emotional) symptoms in HD childhood cancer survivors and encourage their patients to seek further support if needed.

OUTCOME OF CHİLDREN WİTH HODGKİN'S DİSEASE. A 30-YEAR EXPERİENCE FROM A SİNGLE PEDİATRİC ONCOLOGY DEPARTMENT

OZET Hodgkin lenfoma (HL) lenf nodlarinin ilerleyici buyumesi ile karakterize olan lenfoid sistem malignensidir. Bu calisma, otuz yillik bir surede Cocuk Onkoloji Departmaninda tani alan ve izlenen HL’li hastalarin degerlendirilmesidir. Cocuk Onkoloji Departmanin¬da tani alip izlenen ve bilgilerine tam olarak ulasilan altmisdort Hodgkin lenfomali hasta calismaya dahil edildi. Tum olgularin evreleme ve histopatolojileri Ann Arbor sistemine gore kayit edildi. Calismamizda hastalarin 42’si erkek (%66), 22’si kiz (%34), ortanca yas 8,1 yil (1,3 yil ile 17,4 yil arasinda) saptandi. Hastalarin %43,8’inde (28 hasta) B semptomlari vardi. Bulky hastalik bir hastada saptandi. Hastalarin 9’u evre I; 17’si evre II, 2’si evre, III ve 25 tanesi evre IV olarak tani kondu, 2 hastanin evreleme bilgisine ula¬silamadi. Ortanca izlem suresi 25 aydi, genel sag kalim %83 bulundu. Cocukluk cagi HL tedavisinde kombine tedaviler ile yuksek sag kalim oranlarina ulasilmistir. Outcome of children with Hodgkin's disease: A 30-year experience from a pediatric oncology department. ABSTRACT Hodgkin's lymphoma is charecterized by progressive enlargement of the lymph nodes. To evaluate the outcome of children with Hodgkin's disease a period of 30-years from a single institution in Samsun. Sixty-four children with Hodgkin's disease, who were diagnosed at the Pediatric Oncology Department were included in the study. All cases were proved by histopathology, and staging was carried out according to the Ann Arbor system. Our series included 42 (66%) males and 22 (34%) females with a median age of 8,1 years (range 1,3-17,4 years). B symptoms were present in 28 (43,8%) children. Bulky disease was noted in 1children. In stage I, nine; in stage II,17; in stage III, 11; in stage 4, 25 patients were dagnosed; two patient’s stages couldn’t detected. At a median follow-up of 25 months, the overall survival was 83%. Combined modality therapy is effective in the treatment of childhood Hodgkin's disease. J. Exp. Clin. Med., 2011; 28:132-140

Maladie de Hodgkin et auto-immunité chez l’enfant : à propos de 11 observations

The association of lymphoma and autoimmune manifestations has been predominantly studied in adults affected by non-Hodgkin lymphoma. Few publications exist in the literature concerning Hodgkin lymphoma, particularly in children and adolescents. The objectives of this study were to define the characteristics of the link between Hodgkin disease and autoimmunity in childhood. The present 25-year retrospective study was conducted in all centers affiliated with the French Society of Paediatric Oncology (SFCE). Eleven children with Hodgkin disease presented manifestations of disimmunity preceding or following their diagnosis. Four patients had thrombocytopenic purpura, the remaining 7 each had a different autoimmune pathology: lupus syndrome, antiphospholipid syndrome with transient ischemic attack, Evans syndrome, leukocytoclastic vasculitis, autoimmune hemolytic anemia, autoimmune thyroiditis, and juvenile idiopathic arthritis. Lymphoma relapse occurred in 3 patients. Two children died, death being directly attributed to the autoimmune disease in 1 case. Our data suggest that development of autoimmunity is related to significant morbidity. Possible pathophysiological mechanisms include lymphocyte proliferation secondary to chronic inflammation, cell-mediated immune deficiency in Hodgkin disease, molecular mimetics, and antineoplastic phenomena are discussed. A study with a larger patient population is needed to identify the group of children at high risk of autoimmunity for whom additional investigations and modified therapy may be indicated.

Late valvular and other cardiac diseases after different doses of mediastinal radiotherapy for hodgkin disease in children and adolescents: Report from the longitudinal GPOH follow-up project of the German-Austrian DAL-HD studies

To analyze the impact of mediastinal irradiation on the incidence of cardiac late effects in long-term survivors of pediatric Hodgkin disease (HD). The study cohort comprised 1,132 survivors of HD who received treatment before 18 years of age in consecutive trials between 1978 and 1995. They had maintained remission without secondary malignancy for 3.1-29.4 years. The cumulative doxorubicin dose was uniformly 160 mg/m(2), the mediastinal radiation dose (MedRD) was 36, 30, 25, 20, or 0 Gy. Follow-up questionnaires complemented by additional contacts served to collect information on late effects from patients and physicians. A central expert panel reviewed all reported cardiac abnormalities. By October 2008, cardiac diseases (CD) had been diagnosed in 50 of 1,132 patients aged 15.0-41.7 (median 32.2) years. The interval since HD therapy was 3.0-28.2 (median 19.5) years. Valvular defects were diagnosed most frequently, followed by coronary artery diseases, cardiomyopathies, conduction disorders, and pericardial abnormalities. The cumulative incidence of CD after 25 years was highest in the MedRD-36 group (21%) decreasing to 10%, 6%, 5%, and 3% in the lower MedRD groups (P < 0.001). Multivariate Cox analysis of several putative risk factors showed MedRD to be the only significant variable predicting for CD-free survival (P = 0.0025). Our results indicate that lower MedRDs are less cardiotoxic. Consequently, reduction of cardiac late effects may be expected with the lower radiation doses used in current HD protocols. Longer follow-up is needed to confirm the present results.

Gonadal function in patients treated for Hodgkin's disease in childhood

BackgroundThe long-term survival of patients treated for Hodgkin`s disease (HD) in childhood is high and the chief concern is now being directed toward the late effects of the treatment, including the endocrine dysfunction.Patients and methods.Testicular and ovarian functions were assessed in 64 long term survivors (24 females, 40 males) treated for HD in childhood in Slovenia between 1972 and 1994. At diagnosis they were 3–16 years old and had gonadal evaluation 4–27 years later at the age of 13–34. Fifty-four (84%) patients received chemotherapy (ChT), 49 in combination with radiation therapy (RT), 10 received RT alone. Gonadal function was assessed by the clinical examination and measurement of serum concentrations of estradiol and testosterone. Serum levels of LH and FSH were determined in the basal state and after the stimulation.ResultsPrimary hypogonadism (PH) was found in 30 (47%) patients. Twenty-four of 40 (60%) males had PH with evidence of damage of germinal epithelium, 4 of them had evidence of damage of Leydig cells (LC) and 10 had evidence of dysfunction of LC as well. PH was found in 6 of 24 (25%) females.ConclusionsAfter therapy for HD PH was more frequent in males than in females. Not only RT but also alkylating agents and procarbazine alone caused damage of LC. Age of patient at the time of treatment was not an important risk factor for gonadal toxicity. Pelvic RT in combination with ChT is the most important risk factor of the development PH both, in males and females.

A Rare Presentation of Central Nervous System in a Pediatric Patient With Hodgkin Disease

Intracranial involvement by Hodgkin disease is rare. We report a pediatric patient with Hodgkin disease who had intracranial disease at presentation. The patient was referred to our hospital with a suspicion of central nervous system tumor. Although the most common presenting feature of intracranial Hodgkin disease is cranial nerve palsy with brain parenchyma being the most common intracranial site of involvement, to our best knowledge no pediatric case of Hodgkin disease presented with isolated cavernous sinus syndrome reported. We report this rare case because of its unusual presentation, in which Hodgkin disease presented with cavernous sinus syndrome. Physicians should consider the probability of Hodgkin disease in children of all ages who present with cavernous sinus syndrome.

4126 Hodgkin disease in children – experience in Croatia

4126 Hodgkin disease in children – experience in Croatia

Autologous stem cell transplant in a patient with Down syndrome and relapsed Hodgkin lymphoma

Children with Down syndrome (DS) are at increased risk for the development of acute leukemia but they rarely develop other hematologic malignancies or solid tumors. Despite aggressive supportive care, DS patients have increased risk of treatment related morbidity and mortality compared to other children. There are few reported cases of Hodgkin disease in children with DS, and no reported cases of successful therapy for patients with relapsed disease. We report on a child with DS and relapsed Hodgkin disease who was successfully treated with high-dose chemotherapy and autologous stem cell transplant.

Subsequent Malignancies in Children Treated for Hodgkin's Disease: Associations With Gender and Radiation Dose

Subsequent malignant neoplasms (SMNs) are a dominant cause of morbidity and mortality in children treated for Hodgkin's disease (HD). We evaluated select demographic and therapeutic factors associated with SMNs, specifically gender and radiation dose. A total of 930 children treated for HD at five institutions between 1960 and 1990 were studied. Mean age at diagnosis was 13.6 years, and mean follow-up was 16.8 years (maximum, 39.4 years). Treatment included radiation alone (43%), chemotherapy alone (9%), or both (48%). We found that SMNs occurred in 102 (11%) patients, with a 25-year actuarial rate of 19%. With 15,154 patient years of follow-up, only 7.18 cancers were expected (standardized incidence ratio [SIR] = 14.2; absolute excess risk [AER] = 63 cases/10,000 years). The SIR for female subjects, 19.93, was significantly greater than for males, 8.41 (p < 0.0001). After excluding breast cancer, the SIR for female patients was 15.4, still significantly greater than for male patients (p = 0.0012). Increasing radiation dose was associated with an increasing SIR (p = 0.0085). On univariate analysis, an increased risk was associated with female gender, increasing radiation dose, and age at treatment (12-16 years). Using logistic regression, mantle radiation dose increased risk, and this was 2.5-fold for female patients treated with more than 35 Gy primarily because of breast cancer. Survivors of childhood HD are at risk for SMNs, and this risk is greater for female individuals even after accounting for breast cancer. Although SMNs occur in the absence of radiation therapy, the risk increases with RT dose.