title: The modification of high-dose therapy shortens the duration of neutropaenia by delay of leucocyte nadir.
abstract: Infections during neutropaenia contribute still significantly to mortality and morbidity after high-dose therapy and autologous stem cell transplantation. Further acceleration of haemopoietic recovery seems impossible for biological reasons. Another approach to shorten neutropaenia could be to remove drugs from high-dose therapy protocols with strong contribution to immunosuppression and neutropaenia and unproven antineoplastic activity. In this retrospective matched-pair analysis, conventional busulphan/cyclophosphamide (Bu/Cy) high-dose therapy was compared to single-agent busulphan conditioning before autologous stem cell transplantation. This modification led to a significant shorter neutropaenic interval by protraction of cell decrease and to a significant mitigation of neutropaenia. After single-agent busulphan conditioning, leucocytes dropped below 1/nl at median 1.5 days later when compared to the patients from the busulphanBu/Cy control group (P=0.001). In a significant percentage of patients (n=6, 60%) leucocytes did not fall below 0.5 cells/nl at any time. In contrast, all patients from the Bu/Cy control group experienced deep neutropaenia (P=0.004). Thrombocytopaenia and requirement for transfusions of platelets or red cells were not influenced. Antineoplastic activity seemed to be preserved as determined by survival analysis. In conclusion, modification of high-dose regimen with the intention to shorten neutropaenia with preserved antitumour activity could be an approach to reduce infection-related morbidity and mortality and to consider economic necessities.
authors.affiliation: Department of Internal Medicine C (Haematology and Oncology, Marrow Transplantation), Ernst-Moritz-Arndt-University Greifswald, Ferdinand-Sauerbruch-Strasse, Greifswald 17475, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Kiefer
authors.forename: W H
authors.initials: WH
authors.lastname: Krüger
authors.forename: F
authors.initials: F
authors.lastname: Schüler
authors.forename: C
authors.initials: C
authors.lastname: Lotze
authors.forename: C
authors.initials: C
authors.lastname: Hirt
authors.forename: G
authors.initials: G
authors.lastname: Dölken
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002066:Busulfan / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics; D007239:Infections / Q000191:economics / Q000209:etiology / Q000401:mortality / Q000473:pathology; D007958:Leukocyte Count; D008232:Lymphoproliferative Disorders / Q000097:blood / Q000150:complications / Q000191:economics / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control; D017713:Platelet Transfusion; D012189:Retrospective Studies; D033581:Stem Cell Transplantation / Q000191:economics / Q000401:mortality; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced / Q000191:economics / Q000401:mortality / Q000628:therapy; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000191:economics / Q000379:methods; D014182:Transplantation, Autologous
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D002066:Busulfan