1. Sequential therapy combining clofarabine and T-cell-replete HLA-haploidentical haematopoietic SCT is feasible and shows efficacy in the treatment of refractory or relapsed aggressive lymphoma
- Author
-
Georg Ledderose, Haas M, Friederike Mumm, Nicole Engel, Tobias Herold, Dusan Prevalsek, Roland Reibke, Anna-Katharina Zoellner, Max Hubmann, Christina Rieger, Andreas Hausmann, Wolfgang Hiddemann, Johannes C. Hellmuth, Susanne Fritsch, Martin Dreyling, and Johanna Tischer
- Subjects
Adult ,Male ,Melphalan ,Oncology ,Antimetabolites, Antineoplastic ,medicine.medical_specialty ,medicine.medical_treatment ,Aggressive lymphoma ,Hematopoietic stem cell transplantation ,Disease-Free Survival ,HLA Antigens ,Recurrence ,hemic and lymphatic diseases ,Internal medicine ,Humans ,Medicine ,Clofarabine ,Autologous transplantation ,Aged ,Retrospective Studies ,Transplantation ,Chemotherapy ,Adenine Nucleotides ,business.industry ,Lymphoma, Non-Hodgkin ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Allografts ,Surgery ,Fludarabine ,Survival Rate ,Female ,Arabinonucleosides ,business ,medicine.drug - Abstract
Prognosis is poor for patients with biologically aggressive Non-Hodgkin lymphoma (NHL), refractory to chemotherapy or relapsed after autologous transplantation, especially when no disease control before allogeneic transplantation is achieved. In 16 patients (median age 53, median prior regimes 5) with relapsed or refractory non-remission NHL, we analysed retrospectively the efficacy of a sequential therapy comprising clofarabine re-induction followed by a reduced-intensity conditioning with fludarabine, CY and melphalan, and T-cell-replete HLA-haploidentical transplantation. High-dose CY was utilized post-transplantation. All patients engrafted. Early response (day +30) was achieved in 94%. Treatment-related grade III-IV toxicity occurred in 56%, most commonly transient elevation of transaminases (36%), while there was a low incidence of infections (19% CMV reactivation, 19% invasive fungal infection) and GVHD (GVHD: acute III-IV: 6%; mild chronic: 25%). One-year non-relapse mortality was 19%. After a median follow-up of 21 months, estimated 1- and 2-year PFS was 56 and 50%, respectively, with 11 patients (69%) still alive after 2 years. In summary, sequential therapy is feasible and effective and provides an acceptable toxicity profile in high-risk non-remission NHL. Presumably, cytotoxic reinduction with clofarabine provides enough remission time for the graft-versus lymphoma effect of HLA-haploidentical transplantation to kick in, even in lymphomas that are otherwise chemo-refractory.
- Published
- 2015