title: Therapeutic platelet transfusion versus routine prophylactic transfusion in patients with haematological malignancies: an open-label, multicentre, randomised study.
abstract: BACKGROUND
  Routine prophylactic platelet transfusion is the standard of care for patients with severe thrombocytopenia. We assessed the effect of a new strategy of therapeutic platelet transfusion on the number of transfusions and safety in patients with hypoproliferative thrombocytopenia.
  
  
  METHODS
  We did a multicentre, open-label, randomised parallel-group trial at eight haematology centres in Germany. Patients aged 16-80 years, who were undergoing intensive chemotherapy for acute myeloid leukaemia or autologous haemopoietic stem-cell transplantation for haematological cancers, were randomly assigned via a computer-generated randomisation sequence to receive either platelet transfusion when bleeding occurred (therapeutic strategy) or when morning platelet counts were 10×10(9) per L or lower (prophylactic strategy). Investigators undertaking interventions were not masked to group assignment. The primary endpoint was the number of platelet transfusions. Analysis was by intention to treat. This trial is registered, NCT00521664.
  
  
  RESULTS
  197 patients were assigned the prophylactic strategy and 199 the therapeutic strategy. Of 391 patients analysed, the therapeutic strategy reduced the mean number of platelet transfusions by 33·5% (95% CI 22·2-43·1; p<0·0001) in all patients (2·44 [2·22-2·67] in prophylactic group vs 1·63 [1·42-1·83] in therapeutic group), 31·6% (18·6-42·6; p<0·0001) in those with acute myeloid leukaemia (2·68 [2·35-3·01] vs 1·83 [1·58-2·10]), and 34·2% (6·6-53·7; p=0·0193) in those who had had autologous transplantation (1·80 [1·45-2·15] vs 1·18 [0·82-1·55]. We noted no increased risk of major haemorrhage in patients who had undergone autologous transplantation. In those with acute myeloid leukaemia, risk of non-fatal grade 4 (mostly CNS) bleeding was increased. We recorded 15 cases of non-fatal haemorrhage: four retinal in each transfusion group, and one vaginal and six cerebral in the therapeutic group. 12 patients died in the study: two from fatal cerebral haemorrhages in the therapeutic group, and ten (five in each treatment group) unrelated to major bleeding.
  
  
  CONCLUSIONS
  The therapeutic strategy could become a new standard of care after autologous stem-cell transplantation; however, prophylactic platelet transfusion should remain the standard for patients with acute myeloid leukaemia. The new strategy should be used by some haematology centres only if the staff are well educated and experienced in the new approach and can react in a timely way to first signs of CNS bleeding.
  
  
  BACKGROUND
  Deutsche Krebshilfe eV (German Cancer Aid).
authors.affiliation: Medical Clinic 5, Haematology and Oncology, Klinikum Nüremberg, Nüremberg, Germany. wandt@klinikum-nuernberg.de
authors.forename: Hannes
authors.initials: H
authors.lastname: Wandt
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schaefer-Eckart
authors.forename: Knut
authors.initials: K
authors.lastname: Wendelin
authors.forename: Bettina
authors.initials: B
authors.lastname: Pilz
authors.forename: Martin
authors.initials: M
authors.lastname: Wilhelm
authors.forename: Markus
authors.initials: M
authors.lastname: Thalheimer
authors.forename: Ulrich
authors.initials: U
authors.lastname: Mahlknecht
authors.forename: Anthony
authors.initials: A
authors.lastname: Ho
authors.forename: Markus
authors.initials: M
authors.lastname: Schaich
authors.forename: Michael
authors.initials: M
authors.lastname: Kramer
authors.forename: Martin
authors.initials: M
authors.lastname: Kaufmann
authors.forename: Lothar
authors.initials: L
authors.lastname: Leimer
authors.forename: Rainer
authors.initials: R
authors.lastname: Schwerdtfeger
authors.forename: Roland
authors.initials: R
authors.lastname: Conradi
authors.forename: Gottfried
authors.initials: G
authors.lastname: Dölken
authors.forename: Anne
authors.initials: A
authors.lastname: Klenner
authors.forename: Mathias
authors.initials: M
authors.lastname: Hänel
authors.forename: Regina
authors.initials: R
authors.lastname: Herbst
authors.forename: Christian
authors.initials: C
authors.lastname: Junghanss
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001772:Blood Cell Count; D005260:Female; D019337:Hematologic Neoplasms / Q000097:blood / Q000150:complications / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy; D008297:Male; D008875:Middle Aged; D017713:Platelet Transfusion; D013921:Thrombocytopenia / Q000628:therapy; D055815:Young Adult