Intensification of salvage treatment with high‐dose sequential chemotherapy improves the outcome of patients with refractory or relapsed aggressive non‐Hodgkin's lymphoma

Abstract

Summary. The aim of the present study was to retrospectively evaluate whether a high-dose sequential chemotherapy programme (HDS: cyclophosphamide, methotrexate, etoposide) administered prior to autologous transplantation could optimize the salvage of patients with refractory or relapsed aggressive non-Hodgkin's lymphoma. Between 1985 and 1999, 103 patients (median age 43 years, range 16±65) from eight Italian centres and one Swiss centre, with refractory (n 38) or relapsed (n 65) diffuse large B-cell and T-cell lymphoma, were treated using HDS followed by high-dose regimens with autologous haematopoietic stem cell transplantation. Eighty-three patients responded to the HDS regimen (81%, 95% C.I., 73± 88%) and 79 eventually achieved a complete response (CR) after autotransplantation (90%, 95% C.I., 81± 96%). None of 20 cases resistant to HDS attained CR.Treatment-related mortality was 4%. After a median followup of 24 months (range 6±174 months), 3-year estimates of overall survival, event-free survival and disease-free survival were 47% (95% C.I., 36±59%), 44% (95% C.I., 34±54%) and 64% (95% C.I., 50±74%) respectively. Multivariate analysis showed that chemosensitivity to HDS represented the strongest predictor of both CR and survival. This retrospective study shows that salvage treatment using HDS had relatively low toxicity and was associated with remarkable response rates, allowing further effective therapy with high-dose autograft programmes.

Long-term follow-up of patients with peripheral T-cell lymphomas treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation

“…Our results showed a relatively low TRM rate (4.8%), similar to what was reported in previous studies using intensive chemotherapy in the treatment of aggressive lymphomas. [10][11][12][13][14][15][16][17] TRM rates reported by other investigators in PTCL were slightly higher, because they ranged between 10 and 18%. Although such rates were referred to studies on relapsed PTCL, a major concern regarding the use of ASCT in PTCL was represented by the increased risk of severe or even fatal infectious complications, probably owing to a disease-related immunodeficiency.…”

Brazilian experience using high-dose sequential therapy (HDS) followed by autologous hematopoietic stem cell transplantation (ASCT) for malignant lymphomas

“…22,[25][26][27] However, this was not observed for NHL patients, with OS of 41% and a PFS of 31%, similar to those observed by other authors, where OS ranged from 40%-45%. [13][14][15]27,28 This difference in response between HL and NHL patients has not been previously reported. Although the greater prevalence of high-risk patients can justify the worse survival observed in our HL patients, it should have also impacted survival of NHL patients.…”

“…The median day of leukapheresis after HDCY was +13 (Range: [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27], with a median of three sessions (Range ). Twenty-one patients (27%) died after HDCY.…”

“…1,2,[3][4][5][6][7][8] It consists of an intensified debulking phase by sequential administration of high-dose cyclophosphamide (HDCY) followed by high-dose methotrexate (HDMTX), (only for Hodgkin's lymphoma -HL) and high-dose etoposide (HDVP), peripheral blood progenitor cell (PBPC) harvesting, HDS and ASCT. 9 Despite proof of its efficacy reported by several investigators for both HL [10][11][12] and non-Hodgkin's lymphoma (NHL), [13][14][15] there are few studies using this strategy in Brazil and few groups around the world evaluated the use of this therapy with over 5-year follow-up periods. Our aim was to evaluate the effectiveness and toxicity of HDS used as salvage therapy for malignant lymphomas, focusing on overall survival (OS), disease free survival (DFS) and progression-free survival (PFS).…”

Pilot study of tandem high-dose chemotherapy and autologous stem cell transplantation with a novel combination of regimens in patients with poor risk lymphoma

“…High-dose chemotherapy (HDC) with peripheral blood progenitor cell support (PBPC) offers a survival advantage in such patients, but many still die from recurrent disease. 1 Strategies to improve survival in patients with poor risk, relapsed, or chemotherapy-resistant disease include intensified induction followed by HDC with PBPC support, [2][3][4][5] HDC with autografting and immunotherapy, 6 tandem HDC and autografting, [7][8][9][10][11][12] or sequential autologous and nonmyeloablative allogeneic transplantation.…”