title: 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.
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.
authors: Ludwig-Maximilians-University Hospital of Munich-Grosshadern, Department III of Internal Medicine, Hematopoietic Stem Cell Transplantation, Munich, Germany.
authors: A-K
authors: AK
authors: Zoellner
authors: Ludwig-Maximilians-University Hospital of Munich-Grosshadern, Department III of Internal Medicine, Hematopoietic Stem Cell Transplantation, Munich, Germany.
authors: S
authors: S
authors: Fritsch
authors: Ludwig-Maximilians-University Hospital of Munich-Grosshadern, Department III of Internal Medicine, Hematopoietic Stem Cell Transplantation, Munich, Germany.
authors: D
authors: D
authors: Prevalsek
authors: Ludwig-Maximilians-University Hospital of Munich-Grosshadern, Department III of Internal Medicine, Hematopoietic Stem Cell Transplantation, Munich, Germany.
authors: N
authors: N
authors: Engel
authors: Ludwig-Maximilians-University Hospital of Munich-Grosshadern, Department III of Internal Medicine, Hematopoietic Stem Cell Transplantation, Munich, Germany.
authors: M
authors: M
authors: Hubmann
authors: Ludwig-Maximilians-University Hospital of Munich-Grosshadern, Department III of Internal Medicine, Hematopoietic Stem Cell Transplantation, Munich, Germany.
authors: R
authors: R
authors: Reibke
authors: Ludwig-Maximilians-University Hospital of Munich-Grosshadern, Department III of Internal Medicine, Hematopoietic Stem Cell Transplantation, Munich, Germany.
authors: C T
authors: CT
authors: Rieger
authors: Ludwig-Maximilians-University Hospital of Munich-Grosshadern, Department III of Internal Medicine, Hematopoietic Stem Cell Transplantation, Munich, Germany.
authors: J C
authors: JC
authors: Hellmuth
authors: Ludwig-Maximilians-University Hospital of Munich-Grosshadern, Department III of Internal Medicine, Hematopoietic Stem Cell Transplantation, Munich, Germany.
authors: M
authors: M
authors: Haas
authors: Ludwig-Maximilians-University Hospital of Munich-Grosshadern, Department III of Internal Medicine, Hematopoietic Stem Cell Transplantation, Munich, Germany.
authors: F
authors: F
authors: Mumm
authors: Ludwig-Maximilians-University Hospital of Munich-Grosshadern, Department III of Internal Medicine, Hematopoietic Stem Cell Transplantation, Munich, Germany.
authors: T
authors: T
authors: Herold
authors: Ludwig-Maximilians-University Hospital of Munich-Grosshadern, Department III of Internal Medicine, Hematopoietic Stem Cell Transplantation, Munich, Germany.
authors: G
authors: G
authors: Ledderose
authors: Ludwig-Maximilians-University Hospital of Munich-Grosshadern, Department III of Internal Medicine, Hematopoietic Stem Cell Transplantation, Munich, Germany.
authors: W
authors: W
authors: Hiddemann
authors: Ludwig-Maximilians-University Hospital of Munich-Grosshadern, Department III of Internal Medicine, Hematopoietic Stem Cell Transplantation, Munich, Germany.
authors: M
authors: M
authors: Dreyling
authors: 1] Ludwig-Maximilians-University Hospital of Munich-Grosshadern, Department III of Internal Medicine, Hematopoietic Stem Cell Transplantation, Munich, Germany [2] Department I of Internal Medicine, Klinikum München-Schwabing, Munich, Germany.
authors: A
authors: A
authors: Hausmann
authors: Ludwig-Maximilians-University Hospital of Munich-Grosshadern, Department III of Internal Medicine, Hematopoietic Stem Cell Transplantation, Munich, Germany.
authors: J
authors: J
authors: Tischer
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D064591:Allografts; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D001087:Arabinonucleosides / Q000008:administration & dosage*; D000077866:Clofarabine; D018572:Disease-Free Survival; D005260:Female; D006680:HLA Antigens; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D000227:Adenine Nucleotides; D000964:Antimetabolites, Antineoplastic; D001087:Arabinonucleosides; D006680:HLA Antigens; D000077866:Clofarabine
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