Autologous stem cell transplantation followed by consolidation chemotherapy for relapsed or refractory Hodgkin's lymphoma

Abstract

Summary:Relapse remains a major cause of treatment failure after autotransplantation (auto-PBSCT) for Hodgkin's disease (HD). The administration of non-crossresistant therapies during the post-transplant period may delay or prevent relapse. We prospectively studied the role of consolidation chemotherapy (CC) after auto-PBSCT in 37 patients with relapsed or refractory HD. Patients received high-dose gemcitabine-BCNU-melphalan and auto-PBSCT followed by involved-field radiation and up to four cycles of the DCEP-G regimen, which consisted of dexamethasone, cyclophosphamide, etoposide, cisplatin, gemcitabine given at 3 and 9 months post transplant alternating with a second regimen (DPP) of dexamethasone, cisplatin, paclitaxel at 6 and 12 months post transplant. The probabilities of event-free survival (EFS) and overall survival (OS) at 2.5 years were 59% (95% CI ¼ 42-76%) and 86% (95% CI ¼ 71-99%), respectively. In all, 17 patients received 54 courses of CC and 15 were surviving event free (2.5 years, EFS ¼ 87%). There were no treatment-related deaths during or after the CC phase. Post-transplant CC is feasible and well tolerated. The impact of this approach on EFS should be evaluated in a larger, randomized study. PBSCT; auto-PBSCT; high-dose therapy; consolidation chemotherapy; gemcitabine High-dose therapy followed by autologous stem cell rescue has improved the long-term event-free (EFS) and overall survival (OS) for patients with relapsed or refractory Hodgkin's disease (HD). The probability of 5-year progression-free survival (PFS) for patients with HD autografted in first relapse ranged from 37 to 63% in selected series, while the PFS for patients autografted for primary refractory disease ranged from 15 to 50%. From these studies, predictors of better outcome after autotransplantation varied, but included 'minimal' disease status, chemosensitivity, normal LDH levels, good performance status, transplant in first relapse, absence of B symptoms at diagnosis, and administration of involvedfield radiotherapy post transplantation. In addition, factors identified by the International Prognostic Factors Project on advanced HD including low serum albumin, anemia, advanced age, and lymphocytopenia were associated with inferior EFS and OS rates after autotransplantation as well. 23 The chief cause of treatment failure after autotransplantation is relapse or progression of disease, which occurs in about 50% of transplanted patients. The majority of relapses occur in sites of prior disease but new and unusual sites of recurrence have been described including the leptomeninges. 11 To prevent or delay disease relapse after auto-PBSCT, a clinical protocol was developed that contained the following novel features: (1) the standard BEAM (BCNU-etoposide-cytarabine-melphalan) conditioning regimen was modified to include gemcitabine because of its single-agent activity in relapsed/refractory HD; 24 (2) dose-intensive cyclophosphamide and etoposide were used for pre-transplant cytoreduction and stem cell mobilization; (3) involv...

Autologous stem cell transplantation followed by consolidation chemotherapy for patients with multiple myeloma

“…Other studies testing post-transplant consolidation chemotherapy in patients with MM following tandem transplant and in lymphoma patients following single ASCT reported similar rates of 40-50% of patients finishing all planned treatments. [15][16][17] Three (2.9%) cases of secondary MDS/ AML have been documented in our study patients at 5, 3.5 and 1.5 years following transplant. All three patients received o6 months of treatment prior to transplant and did not receive any alkylating agents in past.…”

“…As in other studies of CC, a major limitation of this approach remains inability to deliver all planned treatments (49.5%) for a variety of reasons including early disease progression, medical reasons or patient refusal. [15][16][17] The ability to deliver the planned treatment in almost 70-80% of patients in double transplant studies suggests that this approach may be ultimately better tolerated and easier to deliver. 3,4,7,18 Furthermore, the CC appears to have little impact on those patients relapsing early after transplant, suggesting that intrinsic resistance of myeloma cells to even high-dose chemotherapy is unlikely to be overcome by repetitive cycles of standard chemotherapy.…”

Interferon-α after autologous stem cell transplantation in pediatric patients with advanced Hodgkin's lymphoma

“…In addition, relapses may occur in previously uninvolved sites. Rapoport et al 10 administered four cycles of chemotherapy over a 1-year period in their transplanted patients. Owing to lack of compliance, less than half of the targeted patients actually received the planned treatment.…”

“…Various strategies have been used to reduce the risk of tumor recurrence, without much success. [7][8][9][10][11] Interferon-a (IFN-a) is a biologic agent that has demonstrated activities in a number of malignancies. It produced objective responses and disease stabilization in patients with relapsed and refractory HL.…”

Current Status of Autologous Stem Cell Transplantation in Relapsed and Refractory Hodgkin's Lymphoma

“…The 2.5-year PFS and OS rates were 59.1% and 86.3%, respectively. Of note, the majority of patients did not receive the planned post-ASCT therapy because of refusal, early relapse, or other complications [78].…”