Autologous stem cell transplantation (SCT) is commonly used in relapsing non-Hodgkin's lymphoma (NHL) patients with chemosensitivity to a salvage regimen. However, many such patients fail to achieve long-term survival because recurrence is due either to the inability to eliminate tumor cells in the patient or from malignant cells contaminating the infused graft.1, 2 The clinical course of NHL patients with progressive disease after autologous SCT is devastating. In these patients, allogeneic SCT has the advantage of a graft-versus-lymphoma (GVL) effect, a higher frequency of remission, and lower risk of relapse, as compared with autologous SCT. Unfortunately, the high transplantation-related mortality (TRM) of up to 40% and the adverse effects of graft-versus-host disease (GVHD) reduce these benefits.3, 4 Nonmyeloablative SCT (NST) for NHL patients who relapse after autologous SCT is not yet satisfactory.5 Recently, autologous SCT followed by NST has emerged as an innovative approach to treat high-risk NHL in patients previously heavily treated or those with primary refractory disease. This treatment appears effective and has a low TRM.6
We report two cases of NHL who were successfully treated with autografting, followed by NST as a salvage treatment for relapsed NHL after previous autologous SCT.
The first patient was a 41-year-old man who was diagnosed with diffuse large B-cell lymphoma (DLBCL), who achieved a complete response (CR) after eight cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone). After 3 years, he relapsed, received two cycles of ICE (ifosphamide, carboplatin, and etoposide), and again achieved CR. High-dose chemotherapy with BEAM (carmustine, etoposide, cytarabine, and melphalane) was followed by an autologous peripheral blood stem cell transplant (PBSCT). At 19 months after transplantation, he relapsed in the stomach and terminal ileum and was treated with four cycles of the dose-adjusted EPOCH regimen (doxorubicin, vincristine, etoposide, cyclophosphamade, and prednisone) and rituximab (375 mg/m2), resulting in a partial response. He then underwent an autologous PBSCT after high-dose therapy with BUCY (busulfan and cyclophosphamide) and achieved a CR. After 2 months, when stable, he was transplanted with allogeneic PBSC from an HLA-matched sibling donor after nonmyeloablative conditioning with fludarabine and cyclophosphamide. The allograft contained MNC (5.5 × 108/kg), CD34+ (1.0 × 106/kg), and CD3+ (2.8 × 108/kg) cells. Cyclosporine and mycophenolate mofetil were used for acute GVHD prophylaxis. He fully engrafted with complete chimerism with a variable number of tandem repeats (VNTR) on days 28 and 56, respectively, and remained in CR. There was no evidence of acute GVHD. However, extensive chronic GVHD developed in the oral cavity, gut, skin, and eye, and was treated and stabilized with an alternative-day schedule of cyclosporine and prednisolone. At 8 months after NST, he received 4 weekly doses of rituximab (375 mg/m2). He remains in CR 10 months after NST.
The second patient was a 20-year-old man with lymphoblastic lymphoma, initially treated with two cycles of combination chemotherapy with vincristine, adriamycin, ara-C, prednisolone, and L-asparaginase, and achieved a CR. He then received autologous PBSCT and the BEAM regimen. At 16 months after transplantation, his lymphoblastic lymphoma relapsed in the nasal cavity, detected by positron-emission tomography. He received two cycles of chemotherapy with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) and high-dose methotrexate (HDMTX) combined with ara-C, and subsequently underwent autologous PBSCT after intensive therapy with cyclophosphamide and total body irradiation and achieved a CR. He was then transplanted with a graft from an unrelated, HLA-matched donor after nonmyeloablative conditioning with fludarabine and cyclophosphamide and received 15.3 × 108/kg MNC, 14.6 × 106/kg CD34+ cells, and 4.8 × 108/kg CD3+ cells. FK506 and mycophenolate mofetil were used for acute GVHD prophylaxis. He developed acute GVHD in the skin on 38 days, easily controlled with steroids. Chronic GVHD in the oral cavity and skin developed and was effectively treated with FK506/prednisolone. He fully engrafted with complete donor chimerism on days 28 and 56, respectively, and was in sustained CR 9 months after the NST.
The main treatment of lymphoma in patients who relapse after autologous SCT has not been established. Relapse after autografting has a poor prognosis with median survivals of 3–6.2 months reported for patients with NHL.7, 8 This study suggests that cytoreductive autograft followed by NST is a feasible salvage regimen for relapsed NHL after previous autologous transplantation.
This study was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (01-PJ10-PG6-01GN16-0005).