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Efficacy and safety of high-dose chemotherapy with in vivo purged auto-SCT in relapsed follicular lymphoma: long-term follow-up

Bone Marrow Transplantation volume 45, pages 1119–1120 (2010)Cite this article

Follicular lymphoma (FL) represents 20–25% of all non-Hodgkin's lymphomas. Although response rate to first-line chemotherapy is high, most patients ultimately relapse. After the first relapse, each subsequent therapy can only obtain a remission shorter than the previous.1 The use of high-dose therapy (HDT), hematopoietic progenitor cells (HPCs) transplantation and rituximab at relapse has been shown to improve outcome, with longer OS2 than with conventional chemotherapy. Positive results have been reported recently from prospective trials3 and registry studies,4 but follow-up is short3 or details of therapy are missing.4 Only one group has published data from a randomized study.5 However, this trial was performed in the ‘pre-rituximab’ era, HPCs were ex vivo purged and were not subjected to molecular analysis. In addition, there has been concern about toxicity of the conditioning regimen with a significant increase of secondary tumors and myelodysplastic syndromes after TBI, despite a plateau in remission duration curve.6 Therefore, additional survival data and longer follow-up are needed to assess the role of HDT, HPC transplantation and rituximab for in vivo purging and therapy in relapsed FL (rFL). In addition, clinical and molecular data have to be used to tailor a response-adapted therapy to lessen toxicity.

From 1997 to 2008, we performed rituximab-supplemented HDT and HPC transplantation7 with in vivo purged HPCs in 36 consecutively enrolled, unselected patients with rFL (Table 1), representing more than 90% of all relapsed patients seen at our Institution; only four patients were not treated with this therapy because of older age (>65 years). Minimal residual disease (MRD) was assessed by PCR. Over the past few years, the schedule of HDT7 has been slightly modified mainly to decrease toxicity and to improve safety. After the initial standard-dose phase (2–3 cycles of an anthracycline-containing regimen or DHAP chemotherapy), all patients received high-dose CY (HD-CTX, 7 g/m2), 2 doses of rituximab (375 mg/m2) and underwent HPC harvest. After HD-CTX, all patients were treated with high-dose cytarabine (HD-araC, 1.5–2 g/m2 every 12 h for 5–6 consecutive days), 2 doses of rituximab, and underwent a second HPC harvest. Except for patients obtaining clinical (CR) and molecular (MR) remission after HD-araC, who received no further treatment and proceeded directly to the myeloablative phase, the remaining patients received one more cycle of therapy as detailed in Table 1 before the myeloablative phase. Apart from HD-CTX, each therapy was followed by reinfusion of a small amount of HPCs (2 × 106 CD34+ cells/kg body weight). After conditioning with either BEAM or mitoxantrone plus melphalan, all patients were transplanted: 34 of 36 (94%) patients were transplanted with MRD-negative HPCs (>5 × 106 CD34+ cells/kg body weight). No probe was available for one patient, and one was transplanted with MRD-positive HPCs. HPC transplantation was followed a month later by 2 final doses of rituximab.

Table 1 Patient characteristics, treatment and toxicity
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Authors and Affiliations

  1. Division of Medical Oncology 3, Istituto Nazionale Tumori, Milan, Italy

    M Magni, M Di Nicola, C Carlo-Stella, L Devizzi, A Guidetti, P Matteucci & A M Gianni

  2. Department of Oncology, University of Milan, Milan, Italy

    C Carlo-Stella & A M Gianni

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  1. M Magni
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Correspondence to M Magni.

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Magni, M., Di Nicola, M., Carlo-Stella, C. et al. Efficacy and safety of high-dose chemotherapy with in vivo purged auto-SCT in relapsed follicular lymphoma: long-term follow-up. Bone Marrow Transplant 45, 1119–1120 (2010). https://doi.org/10.1038/bmt.2009.294

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