Outcome of second line therapy for pediatric patients with Hodgkin lymphoma who relapse following ABVD based therapy

Background: Treatment outcomes for patients with newly diagnosed Hodgkin lymphoma have improved significantly. This, however, means that the number of patients relapsing following modern therapy is small and the information regarding their clinical characteristics and treatment outcome is limited.Methods: Clinical information for patients with HL treated on an ABVD protocol were retrospectively collected. For those patients who suffered relapse or progression, data relating to this event, the treatment received and the outcome were collected and reviewed.Results: Between May 1990 and December 2006 230 children (years) were treated for HL at our institution. 30 patients suffered treatment failure; 21 relapses and 9 progressions (PD). The median time to failure was 1.1years (0.05–7.29 yrs); 0.58 years for patients who progressed and 1.4 years for relapsing patients. 16 patients maintained their stage at relapse, 9 relapsed at a lower stage and 5 at a higher stage. 24 patients were subsequently treated with chemotherapy alone, one with XRT alone and 4 received CMT. One patient with progressive disease did not receive any salvage therapy. Chemotherapy protocols used included APPE (n=13), COPP (n=6), ESHAP (n=2), MOPP (n=2), COPPABV (n=2), MOPPABV (n=1) and ABVD/COPP (n=1). One patient with a nodular lymphocyte predominance HL progressed as a DLBCL and was treated on a NHL protocol. 10 patients subsequently underwent SCT (9 autologous and one allogeneic). 19/29 patients achieved CR post 2nd line therapy, while 5 each had PR and PD. OS at 6 years is 65.7%. Outcome for patients with PD was significantly worse than for those who relapsed (47.6% v. 73.2%; p=0.048). There was no difference in outcome for those patients who underwent SCT compared with those who did not (63% v. 66.4%; p=NS).Conclusion: A majority of pediatric patients with HL who relapse following ABVD therapy can be salvaged. Outcome for patients following chemotherapy alone was no different from those who underwent SCT; therefore the necessity for SCT needs to be evaluated based on risk stratification.Disclosures: No relevant conflicts of interest to declare

Hodgkin lymphoma in very young children: Clinical characteristics and outcome of treatment

In developed nations, Hodgkin lymphoma (HL) is rare in \u3c5-year olds and represent a minority in developing countries. Little is reported about the biology and behavior of these very young patients compared with older children. 18.75% of our pediatric HL patients (0 - 14 years) were \u3c5 years at diagnosis. This group had more boys, similar incidence of B-symptoms and stage distribution, less mediastinal involvement and bulky disease, and more mixed cellularity subtype than older children. Treatment included chemotherapy (CT; n = 55), combined modality therapy (CMT; n = 12) and XRT only (n = 2). Ten-year EFS and OS was 81.5% and 90.4%, respectively, versus 75.5% and 90.5% for older children (p \u3e 0.5). A trend toward better survival was seen with CMT, using very LD-XRT, than with CT (OS 100% vs. 86.4%[p = 0.3]; EFS 90.9% vs. 81.0%[p = 0.4]). Although CT could be effective in a subset of LR patients, LD-XRT may be needed to effectively treat most of these patients. This dose reduction may reduce XRT-related toxicity, which can be significant in very young children

Treatment of a clinically determined lower-risk stage III non-lymphoblastic Non-Hodgkin lymphoma with less intensive therapy does not impact negatively on outcome

Stage III NHL was divided into lower-risk (LR) or high-risk (HR) groups. Results of treatment were retrospectively reviewed for patients between 1993 through 2000. An intensive multiagent protocol was used for IIIHR, and a CHOP-based, milder treatment for IIILR. Most LR therapy was outpatient, while treatment for HR patients was primarily inpatient. Five year EFS and OS for HR (n = 29) and LR (n = 23) groups was 86.2% and 95.6% (P = 0.26), and 93.1% and 100%, respectively (P = 0.4). LR had less toxicity. While these results need prospective confirmation, the data shows that less intensive therapy of a LR group of stage III NHL may not impact negatively on outcome

Clinical characteristics and outcome of pediatric patients with stage IV Hodgkin lymphoma

Background and objectives: While treatment outcomes for patients with Hodgkin lymphoma (HL) have improved remarkably, patients with disseminated disease still have a poorer outcome. Stage IV HL is often reported with other \u27advanced stage\u27 categories, confusing the specific contribution of disease dissemination to the outcome. This single-institution report looks at characteristics and outcomes of this specific category.Patients and methods: The medical records of pediatric HL patients (\u3c 14 years) from 1975 through 2003 were retrospectively reviewed and the data analyzed.Results: Stage IV patients (n = 67) had more poor-risk characteristics than patients in stages I-III (n = 300) (B symptoms 86.6% vs. 19.3%, bulky disease 57.6% vs. 45.5% and mediastinal mass 77.6% vs. 29.7%; P \u3c .001 for all characteristics). The liver was the most common extralymphatic site (in 51.5% of patients with stage IV disease. Stage IV patients received chemotherapy (CT) alone (n = 55) or combined modality therapy (CMT) (n = 12). Fifty-four patients (80.6%) achieved complete remission, 2 (3%) partial remission, 10 (14.9%) had progressive disease and 1 was lost to follow up. Overall survival was 79.4% and event-free survival (EFS) was 63.9% at 5 years. There was a non-significant benefit for CMT (OS = 91.7% v. 77.1%, P = .3; EFS = 70.7% v. 62.7%, P = .3). Ten of 12 relapsed and only 1 of 10 progressive disease patients were salvaged. On multivariate analysis, failure to achieve complete remission with CT was associated with a poorer outcome.Conclusion: Stage IV disease is associated with poor risk features and confers a worse outcome than stage I-III disease. Achievement of complete remission with CT is an important prognostic feature. Slow responders may require novel and/or aggressive therapy to achieve complete remission

Pediatric Hodgkin lymphoma patients treated with ABVD chemotherapy with or without low-dose radiation therapy

The ABVD protocol is probably the most effective chemotherapy (CTX) regimen for the treatment of Hodgkin Lymphoma (HL), however the dose and volume, and indeed the need for radiation therapy (XRT) in combination remains uncertain. Pediatric patients (0–14 years) at our institution have been treated with ABVD either with or without XRT, based on the treating physician’s decision. Patients receiving XRT were usually given one or two cycles less of CTX than those without. Since 1998 we have used 1500cGy as the dose of XRT, however the field was determined by the radiation oncologist. Between 1990 and 2003, 152 patients were treated according to the ABVD protocol. Of these, 64 were treated with CTX alone, while 88 also received radiation as consolidation therapy (Combined modality therapy; CMT). Of those who received XRT 63 were administered a dose of 1500cGy. The remaining 25 received various higher doses (1655cGy: 1, 2400cGy: 9, 2500cGy: 10, 3500cGy: 3, 3680cGy: 1, 3980cGy:1). Patients who were treated with CMT were older (mean age 9.2 v. 7.4 years; p\u3c0.05), had less B-symptoms (10.2% v. 26.6%; p\u3c0.05), but not more bulky disease (43.2% v. 34.4%; p=0.2). CTX group had more patients with stage III and IV disease, while CMT group had more stage II disease (p\u3c0.05). With a median follow-up of 4 years, the actuarial overall survival (OS) and event free survival (EFS) at 5 years for all the patients is 97.3% and 88.0%, respectively. The OS and EFS for the patients treated with CTX and CMT were 95.3% v. 98.8% (p=0.4) and 85.1% v. 90.2% (p=0.3), respectively. We next looked at the patients who received only 1500cGy of radiation therapy. Of the 63 patients, 29 received extended field radiation (EFXRT) and 34 involved field radiation (IFXRT). Patients who received radiation were administered a median of two cycles of ABVD less than those who did not (median 4 v. 6 cycles; mean 4.3 v. 5.1, p\u3c0.05). OS at 5 years for the patients treated by CTX v. CMT/EFXRT v. CMT/IFXRT is 95.3%, 96.6% and 100%, respectively (p=0.3). The EFS for the same groups is 85.1%, 86.2% and 90.1% (p=0.4).Conclusion: Pediatric patients with HL can be treated successfully with minimal or no XRT. These results need to be confirmed in a prospective clinical trial

High throughput tissue microarray analysis of FHIT expression in diffuse large cell B-cell lymphoma from Saudi Arabia

Recent studies have suggested a potential prognostic role of alterations of the fragile histidine triad (FHIT) gene in diffuse large B-cell lymphoma. To evaluate possible mechanisms of FHIT inactivation and to further clarify its potential prognostic relevance, we analyzed a set of 114 diffuse large B-cell lymphoma with clinical follow-up information. Tissue microarrays were analyzed by immunohistochemistry for protein expression, and corresponding DNA samples were analyzed for FHIT promotor hypermethlyation. Reduced or absent FHIT expression was found in 75 of 114 diffuse large B-cell lymphoma (66%), but was unrelated to clinical tumor stage or patient prognosis. FHIT promotor hypermethylation was observed in 29 of 93 (23%) interpretable diffuse large B-cell lymphoma. Hypermethylation was not significantly correlated to protein expression loss, which could be explained by competing mechanisms for FHIT inactivation in a substantial fraction of non FHIT hypermethylated diffuse large B-cell lymphoma. Hypermethylation was significantly associated with poor prognosis of diffuse large B-cell lymphoma patients and predominantly seen in nongerminal center diffuse large B-cell lymphoma (27%), but less frequent (13%) in germinal center diffuse large B-cell lymphoma. In summary, these data suggest that promotor hypermethylation is responsible for reduced FHIT expression in a substantial subset of diffuse large B-cell lymphoma, which is primarily composed of nongerminal center subtype with poor patient prognosis