Summary
There is little data available regarding children and adolescents with Hodgkin lymphoma (HL) who relapse after combined‐modality treatment, even though they have a substantial chance of cure. ...The purpose of this national retrospective study was to evaluate the outcome of patients with recurrent/refractory HL and determine adverse prognostic factors. From 1990 to 2006, 70 patients (median age 13·9 years) with refractory (n = 31) or first relapse (n = 39) HL were identified. Median time from end of treatment to relapse was 6 months (3–56). Relapses occurred in irradiated areas in 43/70 patients. Salvage therapy consisted of chemotherapy and 50 patients received high‐dose chemotherapy with autologous stem cell transplantation. Radiotherapy was performed in 29 cases, tandem autologous transplantation in five and allograft in three. With a median follow‐up of 40 months (2–140), significant prognostic factors were time to progression/relapse and response to therapy before autograft. Event‐free survival and overall survival in patients with refractory disease, early relapse and late relapse were 35 ± 9%, 67 ± 11%, 76 ± 10% and 48 ± 11%, 89 ± 7% and 80 ± 10%, respectively. As progression <3 months was a major adverse prognostic factor, novel therapeutic approaches are needed for this group of patients. By contrast, patients have substantial chance of long term second remission in case of relapse >3 months.
Summary
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.
Nodular lymphocyte predominant Hodgkin disease (NLPHL) differs clearly from classical Hodgkin lymphoma (cHL) by clinical presentation and more favorable outcome. Patients often present with early ...stage IA or IIA. Extranodal disease and B-symptoms are uncommon. Histologically, NLPHL is characterized by the presence of atypical "lymphocyte predominant cells" (LP cells) or "pop-corn" cells in a non-neoplastic and reactionnal nodular background of small mature B-lymphocytes. LP cells are negative for CD30 and positive for CD20, BCL6 and EMA (in half of the cases). FDG-PET plays an important role in evaluation of cHL and NLPHL for staging, therapy assessment and relapse. Historically, patients with NLPHL have been treated like patients with cHL, but their very favorable prognosis and the risk of late complications of chemotherapy and/or radiotherapy have led to a de-escalation in recent years. Patients with early stage could be treated by surgical adenectomy alone or associated with not intensive chemotherapy. Currently, there is no consensus regarding to the optimal treatment of patients with advanced stage. Rituximab used as monotherapy or in association with chemotherapy has achieved complete or partial responses. The outcome of NLPHL is singular by the frequent occurrence of late relapses and the risk of transformation into aggressive B lymphoma justifying an extended follow-up. Further prospective studies are needed to optimize treatment of these advanced and recurrent forms.
Abstract Purpose To examine whether three cycles of a low-intensity chemotherapy consisting of cyclophosphamide 500 mg/m2 – day 1, vinblastine 6 mg/m2 – days 1 and 8 and prednisolone 40 mg/m2 – 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.
Background: Advanced stage nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) in children and adolescents is a very rare entity and therefore few data about their treatment and outcome are ...available.
Aim of the study: To describe the clinical characteristics and evolution of advanced stage NLPHL in children and adolescents
Methods:A retrospective analysis of clinical data of patients treated in the SFCE and UK CCLG centers
Patients and Results: 32 patients with NLPHL according to the REAL/WHO classification with disease stage ≥ IIB were recorded between 1998 and 2013. Two patients had composite NLPHL and B cell non-Hodgkin lymphoma at diagnosis. Median age was 12 years (range 4-17) and the majority were boys n=28; 88%. Stage distribution was: IIB =2 ( 6%), III =25 (71%) & stage IV =5 (15%). Twenty-seven patients had cervical node involvement while mediastinum involvement was seen in 11 (34% ) patients. B symptoms were seen in 2 and eight patients had ESR >30 mm. Sites of extra nodal localisation were bone, bone marrow, liver and lungs.Standard Hodgkin chemotherapy regimens (CT) were used in 26 patients (81%), combined with rituximab (R) in 5 children (3 to 6 doses) and along with 20Gy involved field radiotherapy in 6 children. NHL chemotherapy regimens were used in 5 patients; R-CHOP n=3, LMB 01 regimen n=1 and other regimen n=1. One patient received rituximab alone (4 doses) and 1 child had no treatment watch and wait strategy. Median follow up is 45 months (5 – 162).
Outcome: Overall survival is 96% and cumulative incidence of an event is 25%. Eight patients relapsed with a median delay of 15 months (5-73), and 3 had a second relapse 9,11 and 48 months respectively after first relapse. One patient treated with chemotherapy alone developed Ewing’s sarcoma and died 2 years later. The only patient treated with rituximab alone relapsed at 22 months. Of note, no relapses were observed in patients who had chemotherapy and rituximab.
Conclusion: Our report shows that while advanced stage NLPHL in children and adolescents is rare, their clinical outcome is very good. Additionally, this report may inform the basis of future treatment of advanced stage NLPHL in children and adolescents.
No relevant conflicts of interest to declare.
Introduction: Lymphocyte predominant Hodgkin's lymphoma (LP) is a rare CD20-positive subtype of Hodgkin's lymphoma which was only recently recognised as a separate disease entity. Most patients ...present with localised stage IA or IIA disease and usually, the disease has a relatively indolent clinical course. Up until recently, children with LP were treated alike classical Hodgkin's lymphoma and received chemotherapy +/− radiotherapy. Two published reports of surgical resection alone in 19 children with LP (Pellegrino 2003, Murphy 2003) suggest that this may be an effective therapeutic option for a select group of children with limited stage disease. Study objectives: Can a proportion of children with limited LP be cured by surgery alone if resection is complete? Is a watch and wait strategy after surgery alone safe for those patients with residual disease after resection? What is the risk of relevant upstaging at relapse and of transformation into an aggressive B-cell lymphoma?
Methods: European study groups participating in the EuroNet-PHL inter-group were requested to report their experience of surgery alone in children with LP. Surgery as single treatment modality has been used on a case by case basis for several years by the SFCE (France), the DAL / GPOH (Germany), and more recently by the UKCCSG (UK). Individual data of 57 patients were collected using a common CRF. 11 cases already published by Pellegrino were updated and are included.
Results: 49 patients with initial stage IA achieved a CR after surgery. In 8 patients (5 in IA, 1 in IIA, 2 in IIIA) resection was incomplete. At a median observation time of 43 months (max. 172 months) all patients are alive. In the CR group 13 relapses were observed, all occurring early within 26 months of resection. Freedom from progression is estimated to be 67% (95% CI 59%; 75%). Of the 8 patients who had incomplete resection 6 patients relapsed (p=0.008), of whom one (initial stage IIIA) relapsed as non-Hodgkin lymphoma. Of the 16 stage IA patients who experienced a relapse, 9 had a local relapse alone and the remaining 7 relapsed with stage II A. The rate of upstaging (B-symptoms or relapse stage > II) was 0% (95%-CI: 0%; 21%).
Conclusion: If complete resection is achieved, a substantial proportion (about 2/3 in our series) of surgically treated stage IA patients experience long-term remission and may be actually cured. Nevertheless, as most of the relapses occurred in the initially involved lymph node region, a better evaluation of the remission status after surgery may be obtained if FDG-PET is combined with CT/MRI. Based on these data we have designed a Europe-wide study in FDG-PET-negative stage IA-IIA LP to prospectively confirm these promising results in a larger cohort.
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