Natural killer cell regeneration after transplantation with mafosfamide purged autologous bone marrow.
Autologous bone marrow transplantation (ABMT) is used increasingly for the treatment of acute leukemias, lymphomas and solid tumors. Since ABMT is burdened by high risk of relapse, mafosfamide or 4-hydroperoxycyclophosphamide chemical marrow purging is employed. Mafosfamide acts by exerting a potent cytotoxic effect and by promoting apoptosis of leukemic cells. A third proposed mechanism of action involves an effect on immune regeneration in vivo. It was the aim of this study to investigate natural killer (NK) cell regeneration in a group of patients undergoing mafosfamide-purged ABMT. Fifteen patients (8 acute myelogenous leukemia, AML; 4 acute lymphoblastic leukemia, ALL; 3 non-Hodgkin's lymphoma, NHL) were treated with high-dose chemotherapy followed by transplantation with marrow purged with mafosfamide. Prior to ABMT and at different intervals thereafter, NK cell number and function were studied by evaluating the percentage of circulating CD16 positive cells and cytotoxic activity against the leukemic cell line, K562. In comparison to pre-ABMT values, AML patients showed a significant increase in cytotoxic activity, expressed as percentage of chromium release (42.5 +/- 3 vs 32.5 +/- 6, P < or = 0.025 at 4 months) which still persisted at 12 months post-ABMT (54 +/- 6, P < or = 0.05). The behavior of NK functional activity was paralleled by an increase of the percentage of CD16-positive cells (8.4 +/- 2.2 vs 5 +/- 1.3, P < or = 0.05 at 4 months; 12.8 +/- 2.4, P < or = 0.005 at 12 months post-ABMT). Similar significant and long-lasting increments in NK cells were also found in NHL patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Almici
C
C
Department of Hematology, University of Parma, Italy.
Manoni
L
L
Carlo-Stella
C
C
Garau
D
D
Cottafavi
L
L
Rizzoli
V
V
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002452:Cell Count; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*
C048341:mafosfamide; D003520:Cyclophosphamide