Tandem transplant of peripheral blood stem cells for patients with poor-prognosis Hodgkins’s disease or non-Hodgkin’s lymphoma

Abstract

Summary:To improve the results of high-dose therapy with autologous stem cell transplantation, new conditioning regimens with acceptable toxicity must be developed. The aim of this study was to evaluate the feasibility and toxicity of two myeloablative regimens performed at a 2-month interval. After salvage chemotherapy and collection of peripheral stem cell progenitors (median CD34 ؉ cells/kg: 11 ؋ 10 6 /kg), (n ‫؍‬ 15) patients with aggressive non-Hodgkin's lymphoma with poor prognostic factors or refractory Hodgkin's disease (n ‫؍‬ 9) received intensified regimens. The first conditioning regimen, consisting of BCNU-cyclophosphamide-VP16-mitoxantrone was followed by transplantation of a median number of 4 ؋ 10 6 CD34 ؉ cells/kg; then, after a median interval of 56 days, a second preparative regimen, combining busulfan-aracytine-melphalan or TBI ؉ aracytine-melphalan, was followed by transplantation of a median of 4 ؋ 10 6 CD34 ؉ cells/kg. After regimens 1 and 2, respectively: median time to neutrophil recovery Ͼ500/ l was 11 days (both times); median time to platelet counts Ͼ50 000/ l was 14 and 36 days, but values Ͼ20 000/ l were reached by days 13 and 16 (P ‫؍‬ 0.9); mucositis grade III-IV was observed in 11 and 15 cases. The median number of days with fever Ͼ38؇C was significantly higher (7.8 days) after the second transplant (P Ͻ0.05). Three cases of veno-occlusive disease (VOD) were observed after the second transplant. At a median follow-up of 18 months, 14/24 (58%) patients remained in CR, seven patients had died (two of VOD and five after relapse) and two were alive in relapse. These results indicate that tandem transplants performed at a 2-month interval in poor risk lymphoma can be used with acceptable hematotoxicity. VOD remains the major drawback and hepatotoxic drugs, such as busulfan, should be used with caution. Longer term followup of a larger cohort of patients is needed to ascertain the overall efficacy. Keywords: tandem transplants; Hodgkin's disease; nonHodgkin's lymphoma; veno-occlusive disease Conventional-dose anthracycline-containing chemotherapy associated with radiotherapy has now been well documented to result in long-term disease-free survival in 60-70% of the patients with advanced Hodgkin's disease (HD) 1 and 45-50% of those with unselected aggressive non-Hodgkin's lymphoma (NHL). 2 For NHL patients, prognosis is determined based on the clinical characteristics defined by the International Prognostic Index (IPI), 3 with the survival rate for patients with 0-2 adverse factors ranging from 80 to 60%. However, for patients with Ͼ2 adverse prognostic factors actuarial survival is inferior to 40% and for those with primary refractory disease who fail to achieve complete remission (CR) after standard chemotherapy, the prognosis is poor with conventional salvage chemotherapy. 4 The most promising approach for these very poorrisk patients is the use of high-dose therapy (HDT) followed by autologous stem cell transplant (ASCT). Prospective trials have shown HDT ϩ ASCT to be superior to che...

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

“…7,8,10,11 In a patient population comparable to ours, Fitoussi et al 7 evaluated the feasibility of two myeloablative regimens supported with PBPC in 24 poor-risk or relapsed lymphoma patients. Patients received BCNU (300 mg/m 2 ), cyclophosphamide (6 g/m 2 ), etoposide (1000 mg/m 2 ), together with mitoxantrone (30-45 mg/m 2 ) for the first HDC.…”

“…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, 2-5 HDC with autografting and immunotherapy, 6 tandem HDC and autografting, [7][8][9][10][11][12] or sequential autologous and nonmyeloablative allogeneic transplantation.…”

“…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, 2-5 HDC with autografting and immunotherapy, 6 tandem HDC and autografting, [7][8][9][10][11][12] or sequential autologous and nonmyeloablative allogeneic transplantation.Tandem transplantation as a strategy to improve efficacy was demonstrated in myeloma by Barlogie et al 13 and Attal et al 14 In an attempt to improve outcome in patients with high-risk lymphoma, our group examined the tolerability and efficacy of two regimens, first, mitoxantrone and melphalan (MMt) and second, etoposide, thiotepa, and carboplatin (ETCb), given in sequence with PBPC support in a program of tandem autologous transplantation. As first-line therapy for newly diagnosed poor-risk lymphoma, Corradini et al 15 reported favorable results using myeloablative doses of melphalan and mitoxantrone followed by autografting.…”

Successive double high-dose chemotherapy with peripheral blood stem cell rescue collected during a single leukapheresis round in patients with high-risk pediatric solid tumors: a pilot study in a single center

“…Double HDCT is a novel way to further increase dose intensity to treat chemosensitive high-risk tumors, and this strategy has been evaluated in various tumors including malignant lymphoma, breast cancer, and neuroblastoma. [4][5][6][7] We believe that the second HDCT in double HDCT should be given as soon as possible after the first HDCT to eradicate possible residual tumor and to reduce relapse after HDCT. However, because stem cell collection after the first HDCT is possible only when the bone marrow has fully recovered after the first HDCT and a lot of time is needed for sufficient recovery, the second HDCT may be delayed if precryopreserved stem cells are not available.…”

“…11,12 With this background, double HDCT have been undertaken in an attempt to improve survival of patients with high-risk solid tumors. [4][5][6][7] We believe that the second HDCT in double HDCT should be given as soon as possible after the first HDCT to eradicate possible residual tumor. However, because stem cell collection after the first HDCT is possible only when the bone marrow has fully recovered after the first HDCT, it tends to be delayed as in our patients in the DHG.…”