Refractory Hodgkin Research Articles

P1090: CAMRELIZUMAB (CAM) COMBINED WITH GEMOX CHEMOTHERAPY RESULTS IN HIGH COMPLETE METABOLIC RESPONSE RATES IN RELAPSED/REFRACTORY CLASSIC HODGKIN LYMPHOMA (CHL): A PHASE II TRIAL

Background: Approximately 30-35% of patients with classic Hodgkin Lymphoma will prove refractory to frontline therapy or relapse subsequently. Traditional second-line chemotherapy regimens result in complete response rates about 20-40%. Achievement of complete metabolic response (CMR) assessed by PET/CT imaging prior to hematopoietic stem cell transplant (HSCT) predicts favorable progression free survival (PFS) and overall survival (OS). PD‐1 antibody has shown remarkable efficacy in relapsed or refractory hodgkin lymphoma (R/R HL). Aims: we designed a clinical trial to evaluate the efficacy and safety of PD‐1 antibody camrelizumab combined with GEMOX chemotherapy in R/R HL patients. The preliminary results had been obtained. Methods: This is an open‐label, single‐center, non‐randomized, phase 2 study (NCT04239170). The main inclusion criteria included age ≥ 18, ECOG < 2, histopathology confirmed classical HL, no more than 3 lines of previous chemotherapy treatment, having measurable lesion(s) assessed by Lugano 2014 criteria and preparing to receive autologous stem cell transplantation (ASCT). Patients were treated with 2 cycles of camrelizumab (CAM, 200 mg IV, q2w) followed by 2 cycles (28-day cycle) of CAM (IV, day 1 and day 15) combined with standard GEMOX (gemcitabine 1000 mg/m2 and oxaliplatin 100mg/m2, IV, day 1 and day 15). Patients achieved CR were transferred to stem cell mobilization/collection stage; patients achieved PR/SD could have another cycle of CAM plus GEMOX, patients who achieved PR/CR underwent stem cell mobilization/collection. For patients waiting more than 4 weeks for ASCT, 1-2 cycles of CAM monotherapy were allowed. The primary endpoint is the proportion of patients who achieved PET‐CT‐confirmed complete response (CR) according to Lugano 2014 criteria. Results: From March 2020 to December 2021, 30 patients were enrolled. One patient withdrew informed consent. The median age of remaining 29 patients was 34 years old (ranged from 22 to 63), with a male‐to‐female ratio of 16:13. At the first tumor response evaluation, 69% (20/29) patients achieved CR and 17% (5/29) patients achieved partial response (PR), resulting an overall response rate (ORR) of 86%. Only one patient had progression disease (PD). The patients who achieved PR or stable disease (SD) received an additional cycle of CAM plus GEMOX treatment, and one patient who had PR in the first evaluation was found to achieve CR. Up to now, collection of the autologous hematopoietic stem cells was completed in thirteen patients. With a cutoff date of February 10, 2022, the 1-year (progression-free survival) PFS rate was 74% and the 1-year (overall survival) OS rate was 100%, median PFS and OS were not reached with too few events (Figure). Most adverse events (AEs) were of grade 1 to 2. Common AEs included reactive capillary endothelial proliferation (RCEP), alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) elevation, vomiting, nausea, hyperuricemia (all > 30%). Hematologic AEs included neutropenia (> 34%). No grade 4 or above AEs occurred. Grade 3 AE occurred in 6 patients, including 1 pulmonary infection, 1 nausea, 1 fever, 1 hypertriglyceridemia, 1 ALT elevation, and 1 neutropenia. Serious adverse events included 1 case of interstitial pneumonia (grade 2) and 1 case of fever (grade 3) resulting in hospitalization. Image:Summary/Conclusion: Camrelizumab combined with GEMOX chemotherapy showed encouraging clinical efficacy and tolerable toxicity in R/R HL patients and merited further study.

Brentuximab Vedotin Plus Bendamustine: As Salvage Regimen for Relapsed or Refractory Hodgkin Lymphoma, King Abdulaziz Medical City - Jeddah - KSA Experience

INTRODUCTION:In advanced stage Hodgkin's Lymphoma (HL), 30% of patients experience recurrence post upfront ABVD 1.Patients with sensitive disease to salvage chemotherapy typically proceed to ASCT with curative intent 2. Achievement of CR is one of the strongest predictor of favorable outcome after ASCT3-4. Recently brentuximab vedotin plus bendamustine (BvB) became an attractive option for relapsed/refractory HL with promising efficacy and non-overlapping toxicity profiles 5-6. CONTEXT: No PubMed searchable articles regarding use of BvB in relapsed/refractory Hodgkin lymphoma in Saudi Arabia could be found. OBJECTIVE:To determine overall response rate( ORR ) , PFS and OS. Secondary objective was to determine if there was a better response rate when BvB was used as a first salvage. DESIGN:Retrospective cohort analysis. PATIENTS:Patients with relapse /refractory hodgkin lymphoma received BvB as salvage between year 2016 and 2018 were included. Chemotherapy software and medical records were reviewed for clinical data. Twenty four patients were identified. One patient was excluded due to incomplete medical information. Patients were divided into two groups based on their indication for salvage therapy either refractory or relapse, and another two groups based on whether they received BvB as a first salvage or subsequent salvage. Brentuximab vedotin dose was 1.8 mg /kg on day 1 and bendamustine dose was 90 mg/m2 on day 1,2 every 21 days. RESULTS: Twenty-three patients (13 primary refractory and 10 relapsed) were included in this analysis. Median age at diagnosis was 28 years. After a median of 3 cycles of combination therapy BvB, the ORR was 82.6%. Ten patients (43%) achieved CR and 9 patients (39%) achieved PR. Patients who received BvB as a first salvage (65%) achieved 86.7% overall response , while ORR was 75% when BvB was given as subsequent salvage with border line P- value. After a median of 11 months follow-up, the estimated 1-year progression-free survival was 83% and 90% OS. Two patients (8.6%) experienced infusion-related reactions during second cycle. CONCLUSIONS:BvB represents a very effective regimen for high risk relapsed or refractory HL patients; in achieving higher CR rates when used as a first salvage, with manageable toxicity profile. REFERENCES Gordon LI, Hong F, Fisher RI, et al. Randomized phase III trial of ABVD versus Stanford V with or without radiation therapy in locally extensive and advanced-stage Hodgkin lymphoma: an intergroup study coordinated by the Eastern Cooperative Oncology Group (E2496). J Clin Oncol. 2013; 31(6):684-691.Hoppe RT, Advani RH, Ai WZ, et al; National comprehensive cancer network. Hodgkin lymphoma, version 2.2015. J Natl Compr Canc Netw. 2015;13(5):554-586.Moskowitz CH, Matasar MJ, Zelenetz AD, et al. Normalization of pre-ASCT, FDG-PET imaging with second-line, non-cross-resistant, chemotherapy programs improves event-free survival in patients with Hodgkin lymphoma. Blood. 2012;119(7):1665-1670.Moskowitz CH, Nimer SD, Zelenetz AD, et al. A 2-step comprehensive high-dose chemo- radiotherapy second-line program for relapsed and refractory Hodgkin disease: analysis by intent to treat and development of a prognostic model. Blood. 2001;97(3):616-623.Ann S. LaCasce, Gregory Bociek,Ahmed Sawas,et al.Brentuximab vedotin plus bendamustine: a highly active first salvage regimen for relapsed or refractory Hodgkin lymphoma. Blood.2018 Jul 5;132(1):40-48.O'Connor OA, Lue JK, Sawas A, et al.Brentuximab vedotin plus bendamustine in relapsed or refractory Hodgkin's lymphoma: an international, multicentre, single-arm, phase 1-2 trial,Lancet Oncol.2018 Feb;19(2):257-26. Disclosures No relevant conflicts of interest to declare.

Post Transplant Brentuximab Maintenance Appears More Effective Than Post Transplant Salvage Brentuximab for Relapsed/Refractory Hogkin's Lymphoma

POST TRANSPLANT BRENTUXIMAB MAINTENANCE APPEARS MORE EFFECTIVE THAN POST TRANSPLANT SALVAGE BRENTUXIMAB FOR RELAPSED /REFRACTORY HODGKIN LYMPHOMAAmanda Chidiac1, Radwan Massoud1, Mohamad Haidar1, Elie Fares1, Ali Bazarbachi1 and Jean El Cheikh11Bone Marrow Transplantation Program, American University of Beirut Medical Center, Beirut, LebanonKeywords: Hodgkin Lymphoma, Relapsed/Refractory, Brentuximab.Context: Brentuximab Vedotin (BV) is a chimeric anti CD30 IgG1 antibody, conjugated to synthetic antitubulin momomethyl auristatin. BV is approved for the treatment of classical HL in relapse either after autologous stem cell transplantation (ASCT) or after two lines of combination chemotherapy in transplant ineligible patients. The AETHERA trial revealed increased PFS when BV is used as maintenance therapy after ASCT.Objective: Compare the effectiveness of BV as maintenance or salvage therapy after ASCT for relapsed/refractory (R/R) HL.Design: A retrospective analysis conducted on patients with R/R HL treated with BV after ASCT either as maintenance or salvage therapy. Analysis after a median follow up of 12 months is reported.Setting: The study was conducted in a single institution; American University of Beirut Medical Center (AUBMC) after IRB approval.Patients: The study included 15 adult patients with R/R HL treated with BV with the following indications:á Maintenance therapy after ASCT in high risk patientsá Salvage therapy for relapse after ASCT or allo-SCTIntervention: BV at 1.8mg/kg IV every 4 weeks for the above indications.Main outcome measures: response rate (RR), overall survival (OS) and progression free survival (PFS).Results: Nine high-risk patients (60%) received 4 cycles of BV as maintenance therapy post ASCT. Six additional patients (40%) in relapse after ASCT (n=5) or after allo-SCT (n=1) received BV as salvage therapy for an average of 4 cycles (range 3-21). Patients characteristics are listed on Table 1. RR was 33% in 6 patients who received BV as salvage post SCT. Two patients proceeded with allo-SCT in the salvage group. After a median follow up of 9 months, only 2 patients (22%) in the maintenance group progressed and all patients are still alive. Conversely, in the salvage group, 4 patients (67%) progressed and 1 patient developed secondary AML and died.Conclusion: BV therapy showed an efficacy only as maintenance treatment after auto-SCT but was less successful when used as post-transplant salvage in R/R HL. Four cycles of maintenance may suffice. Prospective trials with larger samples are warranted to support these findings. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Post Transplant Brentuximab Maintenance Appears more Effective than Post Transplant Salvage Brentuximab for Relapsed /Refractory Hodgkin Lymphoma

Abstract POST TRANSPLANT BRENTUXIMAB MAINTENANCE APPEARS MORE EFFECTIVE THAN POST TRANSPLANT SALVAGE BRENTUXIMAB FOR RELAPSED /REFRACTORY HODGKIN LYMPHOMA Amanda Chidiac1, Radwan Massoud1, Mohamad Haidar1, Elie Fares1, Ali Bazarbachi1 and Jean El Cheikh1 1Bone Marrow Transplantation Program, American University of Beirut Medical Center, Beirut, Lebanon Keywords: Hodgkin Lymphoma, Relapsed/Refractory, Brentuximab. Context: Brentuximab Vedotin (BV) is a chimeric anti CD30 IgG1 antibody, conjugated to synthetic antitubulin momomethyl auristatin. BV is approved for the treatment of classical HL in relapse either after autologous stem cell transplantation (ASCT) or after two lines of combination chemotherapy in transplant ineligible patients. The AETHERA trial revealed increased PFS when BV is used as maintenance therapy after ASCT. Objective: Compare the effectiveness of BV as maintenance or salvage therapy after ASCT for relapsed/refractory (R/R) HL. Design: A retrospective analysis conducted on patients with R/R HL treated with BV after ASCT either as maintenance or salvage therapy. Analysis after a median follow up of 12 months is reported. Setting: The study was conducted in a single institution; American University of Beirut Medical Center (AUBMC) after IRB approval. Patients: The study included 15 adult patients with R/R HL treated with BV with the following indications: a Maintenance therapy after ASCT in high risk patients a Salvage therapy for relapse after ASCT or allo-SCT Intervention: BV at 1.8mg/kg IV every 4 weeks for the above indications. Main outcome measures: response rate (RR), overall survival (OS) and progression free survival (PFS). Results: Nine high-risk patients (60%) received 4 cycles of BV as maintenance therapy post ASCT. Six additional patients (40%) in relapse after ASCT (n=5) or after allo-SCT (n=1) received BV as salvage therapy for an average of 4 cycles (range 3-21). Patients characteristics are listed on Table 1. RR was 33% in 6 patients who received BV as salvage post SCT. Two patients proceeded with allo-SCT in the salvage group. After a median follow up of 9 months, only 2 patients (22%) in the maintenance group progressed and all patients are still alive. Conversely, in the salvage group, 4 patients (67%) progressed and 1 patient developed secondary AML and died. Conclusion: BV therapy showed an efficacy only as maintenance treatment after auto-SCT but was less successful when used as post-transplant salvage in R/R HL. Four cycles of maintenance may suffice. Prospective trials with larger samples are warranted to support these findings. Download : Download high-res image (224KB) Download : Download full-size image Disclosures No relevant conflicts of interest to declare.

Risk factors predicting outcomes for primary refractory hodgkin lymphoma patients treated with salvage chemotherapy and autologous stem cell transplantation.

We aimed to identify risk factors that predict functional imaging (FI) response to salvage chemotherapy and evaluate outcomes following autologous stem cell transplant (ASCT) in primary refractory Hodgkin Lymphoma (HL). From 1 October 1994 to 10 July 2015, 192 primary refractory HL patients were treated on sequential second line protocols. Event-free survival (EFS) and overall survival (OS) were calculated from the date of histological confirmation of refractory disease. Covariates were analysed for relationship with FI response and EFS. By intent-to-treat, the median EFS was 8·9years and OS 10·4years with 41% having positive post-salvage FI. On multivariate analysis, the presence of B symptoms and bulk ≥5cm predicted for positive FI, with odds ratios of 2·15 and 2·03, respectively. For the 167 (87%) transplanted patients, 60% had a negative pre-ASCT FI. Median EFS and OS were not reached with at a median follow-up of 3·6years in surviving patients. Both stage IV refractory disease and persistent FI abnormality pre- ASCT were associated with worse outcomes: 3-year EFS was 84%, 54% and 28% for zero, 1 and 2 risk factors, respectively (P<0·001). Further studies are needed to validate our prognostic model and to determine optimal therapy for patients with multiple risk factors.

The Oral Mtor Inhibitor Everolimus in Relapsed and Refractory Hodgkin Lymphoma- Compassionate Use in 8 Centers in Brazil

Purpose- Everolimus is an oral antineoplastic agent that targets the raptor mammalian target of rapamycin (mTORC1). The phosphatidylinositol 3-kinase/mTOR signal transduction pathway has been demonstrated to be activated in tumor samples from patients with Hodgkin Lymphoma (HL). The goal of this study was to evaluate the response, time of response, toxicity and overall survival in patients with refractory disease using everolimus out of clinical trial, in a compassionate use.Patients and Methods- Patients were eligible if they had refractory and active Hodgkin disease. Patients received everolimus 10 mg PO daily. Dose reductions were allowed. Time to response assessement was defined by each center until progression (this was defined by each doctor, some have considered to keep the drug until clinical progression and not radiological progression of the disease). Patients could remain on drug until progression or toxicity.Results- Thirty three patients were enrolled. Median age at the time of everolimus start was 29 years (range, 20-70). Patients had received a median of 5 prior therapies (range, 3-7) , 81% had undergone prior autologous stem cell transplant and 4 patients had undergone alogenic trasnplantation. The ORR was 51% (95% CI: 24-71%) with 14 patients achieving a PR, 3 patient achieving a CR and 10 with stable disease. Thirteen patients used the drug for more than 1 year. Patients received a median of 14 cycles of therapy and 3 remains on therappy at 36 months showing a great tolerability of the drug. The median DR for the responders (CR/PR) was 10 months. The most commons site effects were trombocitopenia and hypercholesterolemia. Three patients had pulmonar toxicity. The adverse events grade III and IV ocurred in 30% of the patients.Conclusions- Everolimus has single-agent activity in relapsed/refractory HL, even in real lyfe and clinical practice and provides proof-of-concept that targeting the mTOR pathway in HL is clinically relevant. DisclosuresOff Label Use: everolimus for refractory hodgkin lymphoma.

Primary refractory hodgkin lymphoma and autologous stem cell transplantation: results of the single-center prospective study

Today the role of single or double Autologous Stem Cell Transplantation (ASCT) in patients (pts) with refractory Hodgkin Lymphoma (HL) is still unclear. Aim. To present the results of a single-center prospective trial which aim was to show the significance of single and double ASCT in patients with HL, who did not achieve complete response after first-line chemotherapy. Material and Methods. Between 2007 and 2014 62 patients were enrolled in the study. First ASCT was administered to 53 patients, 10 of those 53 patients received second ASCT. Results. 5-year overall survival (OS) and progression-free survival (PS) were 52 and 27% after single ASCT versus 38 and 30% after double ASCT respectively. According to our study extensive previous treatment (radiotherapy and chemotherapy) followed by ASCT had a negative prognostic impact on overall survival (OS) (p=0.03). Moreover, initial response to the first ASCT was found to be an independent prognostic factor of OS (p=0.004). According to our results, achievement ofpartial response or disease stabilization after the first ASCT was the main indication for double ASCT. In this case second ASCT is preferable to alternative treatment (p=0.004). Disease progression (PD) after the first ASCT seems to be a contraindication to the necessity of the second course of ASCT as low effectiveness and high level of toxicity do not improve treatment results in comparison to alternative treatment (p=0.6). Achievement of complete remission associated with disease free long-term survival and high quality of life. Achievement of complete remission was crucial at any treatment stage. Conclusion. ASCT is an effective treatment option for patients who never achieved CR. Second ASCT is a treatment of choice for patients with PR/SD after 1st ASCT. Nevertheless second ASCT does not improve outcome for patients with PD after 1st ASCT. Alternative variants of treatment are needed for this patient group.

13‐ICML Satellite symposia programs (updated on May 9, 2015)

13‐ICML Satellite symposia programs (updated on May 9, 2015)

Current role of autologous and allogeneic stem cell transplantation for relapsed and refractory hodgkin lymphoma.

Classical Hodgkin lymphoma (cHL) is a relatively rare disease, with approximately 9,200 estimated new cases and 1,200 estimated deaths per year in the United States. First-line chemo-radiotherapy leads to cure rates approaching 80% in patients with advanced-stage disease. However, 25 to 30% of these patients are not cured with chemotherapy alone (i.e., the ABVD regimen) and show either primary refractoriness to chemotherapy, early disease relapse or late disease relapse. Second-line salvage high-dose chemotherapy (HDC) and autologous stem cell transplantation (SCT) have an established role in the management of refractory/relapsed cHL, leading to durable responses in approximately 50% of relapsed patients and a minority of refractory patients. However, due to the poor responses to second-line salvage chemotherapy and dismal long-term disease control of primary refractory and early relapsed patients, their treatment represents an unmet medical need. Allogeneic SCT represents, by far, the only strategy with a curative potential for these patients; however, as discussed in this review, it’s role in cHL remains controversial. Despite a general consensus that early relapsed and primary refractory patients represent a clinical challenge requiring effective treatments to achieve long-term disease control, there has been no consensus on the optimal therapy that should be offered to these patients. This review will briefly discuss the clinical results and the main issues regarding autologous SCT as well as the current role of allogeneic SCT.

Comparison of Outcomes of HLA-Matched Related, Unrelated, or HLA-Haploidentical Related Hematopoietic Cell Transplantation following Nonmyeloablative Conditioning for Relapsed or Refractory Hodgkin Lymphoma

We compared the outcome of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) for patients with relapsed or refractory Hodgkin lymphoma (HL) based on donor cell source. Ninety patients with HL were treated with nonmyeloablative conditioning followed by HCT from HLA-matched related, n=38, unrelated, n=24, or HLA-haploidentical related, n=28 donors. Patients were heavily pretreated with a median of 5 regimens and most patients had failed autologous HCT (92%) and local radiation therapy (83%). With a median follow-up of 25 months, 2-year overall survivals, progression-free survivals (OS)/(PFS), and incidences of relapsed/progressive disease were 53%, 23%, and 56% (HLA-matched related), 58%, 29%, and 63% (unrelated), and 58%, 51%, and 40% (HLA-haploidentical related), respectively. Nonrelapse mortality (NRM) was significantly lower for HLA-haploidentical related (P=.02) recipients compared to HLA-matched related recipients. There were also significantly decreased risks of relapse for HLA-haploidentical related recipients compared to HLA-matched related (P=.01) and unrelated (P=.03) recipients. The incidences of acute grades III-IV and extensive chronic graft-versus-host disease (aGVHD, cGVHD) were 16%/50% (HLA-matched related), 8%/63% (unrelated), and 11%/35% (HLA-haploidentical related). These data suggested that salvage allogeneic HCT using nonmyeloablative conditioning provided antitumor activity in patients with advanced HL; however, disease relapse/progression continued to be major problems. Importantly, alternative donor stem cell sources are a viable option.

The value of augmented preparative regimens combined with an autologous bone marrow transplant for the management of relapsed or refractory hodgkin disease: A southwest oncology group phase II trial

Several single-institution pilot studies have suggested that augmented preparative regimens, including those containing total body irradiation combined with an autologous bone marrow transplantation, are superior to standard regimens for the treatment of relapsed or refractory Hodgkin disease. On the basis of these data, we undertook, in the cooperative group setting, a phase II trial of augmented preparative regimens for patients experiencing treatment failure with conventional chemotherapy. Eighty-one patients with either sensitive or refractory (induction failures or chemoresistant) relapse received etoposide (60 mg/kg), cyclophosphamide (100 mg/kg), and either total body irradiation (12 Gy) or, if previously irradiated, carmustine (15 mg/kg), followed by an autologous bone marrow transplantation. Progression-free (PFS) and overall (OS) survival were estimated, and a Cox regression model was used to assess potential prognostic variables. The 5-year PFS and OS for the 74 eligible patients treated at 20 Southwest Oncology Group centers were 41% (95% confidence interval [CI], 29%–53%) and 54% (95% CI, 43%–65%), respectively, despite a median remission after initial chemotherapy of only 6 months. The 3-year OS for those whose induction therapy failed was 72% (95% CI, 52%–93%). There was 1 (1.4%) early treatment-related death, 2 late deaths due to lung toxicity, and only 1 death due to myelodysplasia. There were no differences in PFS or OS on the basis of regimen or chemosensitivity. A Cox prognostic factor analysis determined that >2 prior regimens, relapse in a radiated field, and extranodal disease were adverse prognostic factors. Among the 46 patients who received prior radiotherapy, the 5-year OS was 38% (95% CI, 14%–61%) for patients with 2 or 3 adverse factors, versus 60% (95% CI, 42%–78%) for those with 0 factors or 1 adverse factor. Augmented preparative regimens seem promising for the treatment of relapsed or refractory Hodgkin disease, without an increase in regimen-related mortality. A poor-prognosis group was identified that should be treated with novel therapies.

769 High dose therapy and autologous bone marrow transplantation for relapsed or refractory hodgkin's disease: The impact of total body irradiation and involved field radiation therapy

One hundred patients with relapsed/refractory Hodgkin's disease (HD) were treated with either high dose carmustine(BCNU)/etoposide(VP16)/cyclophosphamide(Cy) or fractionated total body irradiation (fTBI)/Vpl6/Cy prior to autologousbone marrow transplantation (ABMT). In addition, 24 patients received involved field radiation therapy (RT) prior to (n = 18) or following (n = 6) ABMT. With a median follow-up of 30 months, 3-year actuarial freedom from relapse (FFR) and overall survival (OS) for the entire group are 65% and 63% respectively. By multivariate analyses, factors associated with recurrence were pleural disease ( P = 0.009), pulmonary metastases ( P = 0.004) and a poor response to cytoreductive therapy ( P = 0.003). FFR and OS following BCNU/VP16/Cy (67% and 62%) or fTBI/VP16/Cy (60% and 60%) were similar ( P = 0.51 and P = 0.49). A median RT dose of 30 Gy (range 14.4 Gy–45 Gy) was given to 67 sites in the 24 patients. Local failure occurred within 4 irradiated sites (6%) in two patients (8%). In patients with Ann Arbor stages I–III disease (n = 62), RT was associated with a trend toward improved FIR (92% -vs-67%, P = 0.09) and OS (86% -vs- 59%, P = 0.13). Among patients not previously irradiated (n = 39), RT was associated with a significant improvement in FFR (85% -vs- 55%, P = 0.05) and OS (93% -vs- 54%, P = 0.03). Treatment related mortality (including 2nd malignancies) was similar with or without fTBI (15% -vs- 14%) or RT (17% -vs-13%). In conjunction with high dose therapy and ABMT, RT is well tolerated, effectively controls local/regional disease, and may improve survival in selected patients.