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Autologous transplantation has been extensively studied in refractory-relapsed non-Hodgkin lymphoma (NHL).
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High-dose chemotherapy and autologous stem cell transplant comprise a standard of care for patients with chemosensitive, relapsed, diffuse large B-cell lymphoma (DLBCL) (24) (Fig. 12-2). Resistance to salvage chemotherapy, increased lactic dehydrogenase at the time of relapse or progression, prior complete remission (CR) of less than 12 months, and secondary International Prognostic Index (IPI) (ie, at the time of relapse or progression) greater than 1 have been described as adverse predictors of survival (25). In the modern era of exposure to rituximab as part of first-line therapy (R-CHOP), the CORAL study has shown 3-year EFS rates of 25% in chemosensitive relapsed patients undergoing autologous stem cell transplantation (26).
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High-dose chemotherapy in the first CR has also been evaluated for patients with DLBCL and a high IPI (27,28,29,30). While some randomized studies have demonstrated an improvement in EFS, none has shown a benefit in overall survival (OS). Thus, autologous transplantation is not routinely used as consolidation in a first remission for DLCL.
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The role of autologous HPC transplantation remains unclear in the management of patients with chemosensitive, relapsed low-grade lymphoma (eg, follicular lymphoma, FL). The use of high-dose cyclophosphamide (31) and TBI (32) has resulted in a 5-year EFS of 60% but has been largely abandoned due to the risk of secondary malignancies.
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Historically, a major challenge has been the contamination of the autologous graft by malignant cells (33). Recently, systemic treatment with rituximab has reduced the numbers of circulating lymphoma cells, thus yielding effective in vivo purging with high likelihood polymerase chain reaction–negative tumor-free PBPC grafts (34,35).
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Several randomized trials have shown improved outcomes after HDC for chemosensitive relapsed FL (36,37). However, these studies were largely conducted in the prerituxumab era. The role of HDC in this setting in the current era remains unsettled.
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The majority of patients with Hodgkin lymphoma (HL) are curable with first-line therapy (Fig. 12-3). However, up to 20% of patients will not respond to first-line chemotherapy, and 30% will relapse after an initial response (38,39). The use of HDC has been proven to be beneficial in the two settings, with expected long-term EFS of 30% to 40% for patients with primary refractory tumors sensitive to subsequent salvage therapy and of 30% to 65% for patients with chemosensitive relapsed HL (40,41).
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Unfavorable prognostic features for autologous transplant include a first CR shorter than 1 year, extranodal relapse, B symptoms at the time of relapse or progression, bulky (>5-cm) lesions at relapse, and relapse within a prior radiation field. Patients without unfavorable prognostic features have 4-year EFS rates of 70%, compared with less than 20% in patients with adverse features (42). Positron emission tomographic scan uptake at the time of HD has recently emerged as the main prognostic factor (43,44).
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High-dose therapy with autologous HPC transplantation is an established treatment for multiple myeloma, where the use of high-dose melphalan provides OS benefit as consolidation of a response to first-line therapy (45,46,47,48) (Fig. 12-4). To date, no other preparative regimen has been shown to be superior to single-agent melphalan (200 mg/m2) (49). The use of a second course of high-dose melphalan (“tandem” autologous transplants) has been shown to be superior to a single transplant in some (49,50,51), but not all, studies (52), particularly in patients who do not achieve at least a very good partial remission after the first procedure. The timing of transplant has been prospectively investigated in randomized studies. Early (after a brief course of first-line therapy) and late autotransplant (at a time of relapse after prolonged first-line therapy) trials (53) resulted in similar OS, with early autotransplantation offering improved quality of life, shorter duration of chemotherapy, and a longer median EFS. Induction therapy, including novel agents such as bortezomib or lenalidomide, appears to be the most effective induction treatment before HDC. Ongoing randomized trials in the United States and Europe are addressing the question of optimal timing of autologous transplant in the present era of novel agents.
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Several retrospective analyses have demonstrated durable responses of a second salvage course of HDC with autologous SCT for patients with relapsed disease (54). In general, the outcomes appear more favorable for patients who relapse more than 12 months after a first autologous transplant and who respond to subsequent salvage treatment (55). More recently, the first randomized controlled trial has been completed comparing salvage HDC and autologous transplant to salvage conventional chemotherapy (56). In this study, there was a benefit for the transplant arm, with a significant improvement in time to progression.
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Maintenance therapy posttransplant with lenalidomide prolongs EFS and perhaps OS, as shown in several randomized studies (57,58). There is uncertainty about the optimal duration of lenalidomide treatment. Its use after allogeneic stem cell transplantation has been associated with a small risk of secondary malignancies in the French, but not in the US, study.
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The use of HDC for breast cancer or ovarian cancer has been abandoned. In contrast, tandem courses of carboplatin-containing HDC have been successful in curing patients with relapsed or refractory germ-cell tumors. Long-term EFS rates range from 10% for patients with cisplatin refractoriness and other poor-prognostic features to 70% for those with good-risk chemosensitive tumors in first relapse (59).