Accelerated Total Lymphoid Irradiation-containing Salvage Regimen for Patients With Refractory and Relapsed Hodgkin Lymphoma: 20 Years of Experience

Abstract

Purpose We report the long-term results of integrated accelerated involved-field radiotherapy (IFRT) followed by total lymphoid irradiation (TLI) as part of the high-dose salvage regimen followed by autologous bone marrow transplantation (ABMT) or autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (HL). Methods and Materials From 11/1985 to 07/2008, 186 previously unirradiated patients with relapsed/refractory HL underwent salvage therapy on four consecutive IRB-approved protocols. All patients had biopsy-proven primary refractory or relapsed HL. After standard-dose salvage chemotherapy (SC), accelerated IFRT (18–20 Gy) was given to relapsed/refractory sites, followed by TLI (15–18 Gy) and high-dose chemotherapy (HDT). Overall survival (OS) and event-free survival (EFS) were analyzed by Cox analysis and disease-specific survival (DSS) by competing risk regression. Results With a median follow-up of 57 months among survivors, 5- and 10-year OS was 68% and 56%, 5- and 10-year EFS was 62% and 56%, and 5- and 10-year cumulative incidence of HL-related deaths was 21% and 29%, respectively. On multivariable analysis, complete response (CR) to SC was independently associated with improved OS and EFS. Primary refractory disease and extranodal disease were independently associated with poor DSS. Eight patients had grade ≥3 cardiac toxicity with 3 deaths. Ten patients developed second malignancies, five of whom died. Conclusion Accelerated IFRT followed by TLI and HDT is an effective, feasible, and safe salvage strategy for patients with relapsed/refractory HL with excellent long-term OS, EFS, and DSS. CR to SC is the most important prognostic factor.

Treatment patterns and disease outcomes for pediatric patients with refractory or recurrent Hodgkin lymphoma treated with curative-intent salvage radiotherapy

“…However, there is particular concern for longterm morbidity in the younger population leaving important questions regarding outcomes and optimal RT volume, dose, and sequencing with transplant. For example, use of accelerated TLI with or without IFRT as a component of salvage therapy in radiation-naïve patients has resulted in excellent survival outcomes [18]; however, this this less suitable for children, given potential for unacceptable toxicities [33]. Several retrospective studies have examined the role of salvage IFRT in the peri-transplant setting, and some reports have demonstrated PFS advantage with the addition of IFRT [34][35][36].…”

“…Variables identified in children and adolescents include progressive disease during frontline therapy [5] and response to initial salvage chemotherapy [20]. Results have been mirrored in adult settings ( [18]). Other factors associated with poor survival in pediatric patients include extranodal disease at time of treatment failure, a mediastinal mass at time of transplant, and presence of B symptoms at relapse [23,37].…”

“…Factors supporting salvage RT include lack of RT cross-resistance in many chemotherapy-refractory patients [10][11][12][13][14] and predominantly nodal recurrence at initial disease sites [15][16][17]. Nodal failure has influenced RT field design; for example, total lymphoid irradiation (TLI) has been employed as "quasisystemic therapy" to treat nodal-restricted recurrent disease in radiation-naïve patients before they undergo AHCT [18]. However, data increasingly suggest that some "low-risk" relapse patients, can be treated effectively with standard frontline chemotherapy regimens and limited RT, typically involved-field RT (IFRT) or involved-site RT (ISRT), alone [5,[19][20][21][22].…”

Treatment of Hodgkin Lymphoma Relapsed after Autologous Stem Cell Transplantation

“…Irradiation of localized persisting lesions after auto-HCT can be considered a valid approach for those patients with lesions in metabolic PR, in order to achieve minimal residual disease [46][47][48].…”

Should all patients with HL who relapse after ASCT be considered for allogeneic SCT? A consult, yes; a transplant, not necessarily

“…There are multiple studies supporting the incorporation of RT as a part of salvage treatment; however, because there is a lack of phase 3 data, medical oncologists continue to not use this modality for fear of long-term side effects. [4][5][6][7] In second and later lines of therapy, this rationale is naïve because these patients die of HL as opposed to treatment-related side effects. ln fact, this is increasingly relevant because current treatment approaches for early-stage HL is positron imaging tomography (PET)-adapted, with 3 to 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine alone as standard of care, provided the result on PET imaging is favorable.…”