Advanced stage nodular lymphocyte predominant Hodgkin lymphoma in children and adolescents: clinical characteristics and treatment outcome - a report from the SFCE & CCLG groups.

Advanced stage nodular lymphocyte predominant Hodgkin lymphoma (nLPHL) is extremely rare in children and as a consequence, optimal treatment for this group of patients has not been established. Here we retrospectively evaluated the treatments and treatment outcomes of 41 of our patients from the UK and France with advanced stage nLPHL. Most patients received chemotherapy, some with the addition of the anti CD20 antibody rituximab or radiotherapy. Chemotherapy regimens were diverse and followed either classical Hodgkin lymphoma or B non-Hodgkin lymphoma protocols. All 41 patients achieved a complete remission with first line treatment and 40 patients are alive and well in remission. Eight patients subsequently relapsed and 1 patient died of secondary cancer (9 progression-free survival events). The median time to progression for those who progressed was 21 months (5·9-73·8). The median time since last diagnosis is 87·3 months (8·44-179·20). Thirty-six (90%), 30 (75%) and 27 (68%) patients have been in remission for more than 12, 24 and 36 months, respectively. Overall, the use of rituximab combined with multi-agent chemotherapy as first line treatment seems to be a reasonable therapeutic option.

Relapsed or poorly responsive nodular lymphocyte predominant Hodgkin lymphoma in children and adolescents - a report from the United Kingdom's Children's Cancer and Leukaemia Study Group.

There is a paucity of data on the treatment outcome in children with relapsed or poorly responsive nodular lymphocyte predominant Hodgkin lymphoma (nLPHL). This retrospective report evaluates the treatment outcome in a national cohort of children with relapsed or poorly responsive nLPHL. A total of 37 patients, 22 with relapsed and 15 with poorly responding disease, are the subjects of this report. Of the 22 patients with relapsed nLPHL, 11 had relapsed after primary excision biopsy, 10 after chemotherapy and 1 after chemotherapy and involved field radiotherapy. The majority had localized disease at relapse. The median time to relapse was 8 months after chemotherapy and 11 months after excision biopsy. Seven of the 15 patients with poorly responding nLPHL had variant histology. Three patients with initial poor response did not receive any further treatment and have had no disease progression. Transformation to diffuse large B cell lymphoma, in addition to evolution from typical to variant nLPHL occurred in one patient each. Thirty-four patients have been successfully re-treated with second chemotherapy or radiotherapy. Multiple relapses were uncommon but treatable. Relapse or poorly responsive nLPHL is fully salvageable with either additional chemotherapy and or radiotherapy.

Childhood and Adolescent nodular lymphocyte predominant Hodgkin lymphoma - A review of clinical outcome based on the histological variants.

Nodular lymphocyte predominant Hodgkin lymphoma (nLPHL) comprises approximately 10-12% of all childhood Hodgkin lymphoma. As the majority have low stage disease recent years have seen a de-escalation of treatment intensity to avoid treatment-related morbidity. This report evaluates treatment outcome in children with histopathological variants of nLPHL after therapy de-escalation. Biopsies from 60 patients were reviewed and histology categorized as typical (n = 47; 78%) or variant nLPHL (n = 13; 22%). Furthermore, presence of immunoglobulin D (IgD) expression by the lymphocyte predominant (LP) cells was assessed in 41 patients. Treatment outcomes were compared according to treatment received and histopathology of nLPHL. Compared to typical nLPHL, children with variant nLPHL had higher stage disease at diagnosis (stage III: 3/13; 23% vs. 3/47; 6%, P = 0·11), lower complete response rates (6/13; 46% vs. 38/47; 81%, P = 0·029) and higher relapse rates (2/13; 15% vs. 2/47; 4%, P = 0·20). Additionally, IgD expression by LP cells was associated with poorer treatment response and was more commonly seen in patients with variant nLPHL. (11/13; 85% vs. 15/28; 54%, P = 0·08). Variant histology appears to be indicative of a poorer prognosis in patients with early stage disease, and may be an important factor to take into account when moving towards reduced intensity treatment for nLPHL.

Treatment outcome in children and adolescents with relapsed Hodgkin lymphoma--results of the UK HD3 relapse treatment strategy.

The purpose of this national retrospective study was to evaluate the outcome in children with relapsed or primary refractory Hodgkin lymphoma [HL] after a primary chemotherapy alone treatment strategy. Between 2000 and 2005, 80 children with relapsed [n = 69] or primary refractory [n = 11] HL were treated on a standardized treatment protocol of 4-6 cycles of EPIC [etoposide, prednisolone, ifosfamide and cisplatin] chemotherapy. Radiotherapy was recommended to all relapsed sites. High dose therapy with stem cell rescue [SCT] was recommended for patients with poor response. The 5-year overall survival [OS] and progression-free survival from relapse was 75·8% [64·8-83·9] and 59·9% [48·3-69·7] respectively. Duration of first remission was strongly associated with OS; risk of death was decreased by 53% [Hazard ratio (HR): 0·47, 95% confidence interval (CI): 0·19-1·18] for those with a time from end of treatment to relapse of 3-12 months (compared to <3 months) and reduced by 80% (HR 0·20, 95% CI: 0·04-0·90) for those >12 months after end of treatment. Other poor prognostic factors included advanced stage disease at relapse and B symptoms at first diagnosis. The most important factor associated with salvage failure was time to relapse. Survival outcome in children with primary refractory HL is poor.

Treatment outcome after low intensity chemotherapy [CVP] in children and adolescents with early stage nodular lymphocyte predominant Hodgkin's lymphoma - an Anglo-French collaborative report.

PURPOSE: To examine whether three cycles of a low-intensity chemotherapy consisting of cyclophosphamide [500 mg/m(2) - day 1], vinblastine [6 mg/m(2) - days 1 and 8] and prednisolone [40 mg/m(2) - days 1-7] (CVP) is safe and therapeutically effective in children and adolescents with early stage nodular lymphocyte predominant Hodgkin lymphoma [nLPHL]. PATIENTS AND METHODS: Fifty-five children and adolescents with early stage nLPHL [median age 13 years, range 4-17 years] diagnosed between June 2005 and October 2010 in the UK and France are the subjects of this report. Staging investigations included conventional cross sectional as well as 18 fluro-deoxyglucose [FDG] PET imaging. Histology was confirmed as nLPHL by an expert pathology panel. RESULTS: Of the 45 patients, who received CVP as first line treatment, 36 [80%, 95% Confidence Interval [CI]: (68; 92)] either achieved a complete remission [CR] or CR unconfirmed [CRu], the remaining nine patients achieved a partial response. All nine subsequently achieved CR with salvage chemotherapy [n=7] or radiotherapy [n=2]. Ten patients received CVP at relapse after primary treatment that consisted of surgery alone and all achieved CR. To date, only three patients have relapsed after CVP chemotherapy and all had received CVP as first line treatment at initial diagnosis. The 40-month freedom from treatment failure and overall survival for the entire cohort were 75.4% (SE ± 6%) and 100%, respectively. No significant early toxicity was observed. CONCLUSIONS: Our results show that CVP is an effective chemotherapy regimen in children and adolescents with early stage nLPHL that is well tolerated with minimal acute toxicity.

Clinical outcome in children and adolescents with Hodgkin lymphoma after treatment with chemotherapy alone - the results of the United Kingdom HD3 national cohort trial.

PURPOSE: To assess the efficacy of a standardised hybrid chemotherapy treatment programme for Hodgkin lymphoma (HL) in a national series of children and adolescents. PATIENTS AND METHODS: The 381 assessable patients, treated between March 2000 and April 2005 in the United Kingdom Children's Cancer Study Group trial, were reviewed to evaluate overall survival (OS), disease free survival (DFS) and deaths. Protocol treatment for stages 2-4 offered a hybrid programme of ChlVbPP (chlorambucil, vinblastine, prednisolone, procarbazine) alternating with ABVcD (doxorubicin, bleomycin, vincristine, dacarbazine). Patients with stage I disease only were offered involved field radiation alone or hybrid chemotherapy. RESULTS: With a median follow up of 5.1 years (range 0.5-8.4 years), the 5 years OS and DFS for all patients was 97% and 78%, respectively. By multivariate analysis, mediastinal and stage IV disease at presentation were the only factors that affected achieving a complete response. The 5-year DFS rate for patients with stage IV disease was 55% whilst patients with mediastinal disease had a 2-fold higher risk of an event. CONCLUSIONS: This study demonstrated that multi-agent chemotherapy alone is insufficient treatment for patients with mediastinal and stage IV disease.

Long-term outcome in children with Hodgkin's lymphoma: the United Kingdom Children's Cancer Study Group HD82 trial.

BACKGROUND: The aim of United Kingdom Children's Cancer Study Group (UKCCSG) HD82 was to establish the efficacy of chlorambucil/vinblastine/procarbazine/prednisolone (ChlVPP) in the treatment of childhood Hodgkin's lymphoma stages II-IV and radiotherapy (RT) alone in stage I patients. We report on the status of these patients to a follow-up of 20 years. METHODS: Treatment consisted of 35Gy involved-field RT for stage I and ChlVPP alone for stages II-IV. Adjuvant RT (35Gy) was administered to those with bulky mediastinal disease. RESULTS: Of the 358 patients, the 10-year EFS/OS per stage is I (65.4%/92.6%), II (80.0%/93.3%), III (68.8%/85.0%), IV (45.5%/72.7%). The corresponding 20-year OS rates are similar with a combined (all stage) rate dropping from 89.3% to 89.0% over the decade. The cumulative 20-year malignancy rate is 7.29%. CONCLUSION: Single modality treatment provided relatively low EFS at 10-years but comparable long-term OS, relative to contemporary published combined modality regimens, for stages I-III but not for stage IV patients.