Routine Prophylactic Platelet Transfusions Are Not Necessary in Patients with Acute Myeloid Leukemia - A Therapeutic Transfusion Strategy Is Safe and Cost Effective.
Authors: Wandt Hannes , Frank Markus , Schaefer-Eckart Kerstin , Wilhelm Martin 
Published: April 2020

During the last three years 60 patients with newly diagnosed acute myeloid leukemia (except FAB M3) were included in a therapeutic platelet transfusion protocol for a total of 101 cycles of intensive chemotherapy. All pts. without major bleeding during induction chemotherapy were included. The start of the new platelet transfusion protocol was the day after induction or day 1 of consolidation chemotherapy. Therapeutic platelet transfusions (apheresis single donor platelets) were given in case of bleeding (more than petechial) or when retinal bleeding with deterioration of vision occured. Routine prophylactic platelet transfusions were not given regardless of the morning platelet count. Platelet transfusions should only be given prophylactically (platelet count &lt; 10/nl) when fever &gt; 38.5 °C, fungal pneumonia, plasmatic coagulation disorders or when major unexspected headache occured. When diagnostic biopsies were planed the platelet count should be &gt; 20/nl. The use of Aspirin and nonsteroidal antirheumatic agents were avoided.

Pts. received 74 cycles of induction chemotherapy (D 45–60 mg/m2 x 3 and AraC 100 mg/m2 c.i. x 7 or Mitoxantrone 10mg/ m2 x 5, AraC 100mg/m2 x 8, Etoposide 100mg/ m2 x 5) and 27 cycles of consolidation therapy (high dose AraC 1–3 g/m2 every 12 hours for 5–6 days in combination with Mitoxantrone or m-Amsa). Median age was 51 (17–72) years and 67% obtained a complete remission. Median duration of thrombocytopenia &lt;20 and &lt;10/nl was 8 and 5 (0–63) days resulting in a total of 1066 and 758 days of severe thrombocytopenia, respectively. Median platelet count before major bleeding events was 8.9/nl (4–18). Maximal bleeding WHO grade II and III was documented in 36% and 6% of all 101 chemotherapy cycles. Life threatening bleeding WHO grade IV was not observed. This incidence of bleeding events compares favorably with published data with the standard prophylactic platelet transfusion strategy. Therapeutic transfusions were mainly necessary (84%) for gastrointestinal hemorrhages (25%), epistaxis (21%), increasing hematoma (21%), stomatitis (17%). Main indications for prophylactic transfusions were fever (64%), diagnostic interventions (13%) and fungal pneumonia (12%). We did not see an increased incidence of bleeding events during fever episodes. Therefore pts. with fever who are clinically stable and without bleeding signs should not be routinely transfused when the platelet count is below 10/nl.

The mean and median number of apheresis platelet transfusions per chemotherapy cycle was only 3 and 2 (range 0–21), respectively.

Conclusion: The proposed therapeutic platelet transfusion strategy in this pilot study is safe in AML pts. during induction and consolidation chemotherapy. Compared with historical controls (Wandt H et al. Blood.1998; 91:3601) the number of transfusions can be reduced by about 50%. Fever per se must not be a trigger for prophylactic platelet transfusion in future studies. A prospective randomized study is therefore now in Germany in progress comparing the standard routine prophylactic with the new therapeutic platelet transfusion strategy.