ABO Identical and Washed Transfusions Are Candidate Strategies to Reduce Early Mortality in Acute Promyelocytic Leukemia (APL)

Background: Despite dramatically improved long term outcomes seen with all-trans retinoic acid therapy in APL, early mortality remains a substantial challenge. Recent data from a single center (Haematologica 2012; 97:133) and the Surveillance, Epidemiology and End Results (SEER) registry (Blood 2011; 118: 1248) report 30 day mortality rates of 26% (n = 18 of 70) and 17% (n = 238 of 1400), respectively. Early deaths are predominately due to hemorrhage. Patients with APL invariably have abnormal laboratory hemostasis tests. The standard of practice is to prophylactically transfuse platelets, plasma and cryoprecipitate to mitigate abnormal platelet counts, PT/PTT and fibrinogen levels. Standard blood bank practice is to transfuse platelets, plasma and cryoprecipitate either without regard to ABO blood group (platelets, cryoprecipitate), or, in some centers, transfusing non-identical universal donor group AB plasma. Evidence from observational studies demonstrate that use of ABO non-identical blood components is associated with increased bleeding. Formation of immune complexes containing ABO antibody, soluble and cellular antigens causes derangement of in vitro measures of platelet function and whole blood clotting. We hypothesized that use of ABO identical blood components and saline washed transfusions (red cells and platelets) would be associated with reduced early mortality in APL by avoidance of transfusion induced hemostatic dysfunction.

Methods: This is a single center cohort study of APL patients treated in an 800 bed university community and referral hospital. Novel approaches to transfusion support, based upon randomized trials, have included implementation of ABO identical platelet transfusions for all patients with acute leukemia in 1990, use of only ABO identical cryoprecipitate in 2005, and washed transfusions of red cells and platelets for all patients with acute leukemia <50 years of age beginning in 2006. Plasma transfusion has always been ABO identical. Two comparison populations were recent literature reports and the New York State Cancer Registry. We characterized 30 day mortality in APL patients seen in our institution since 2000 as a convenience sample comparable to literature reports, beginning roughly when ATRA therapy became uniform for induction therapy. Only patients receiving their induction therapy in our hospital were included.

Results: Of 41 patients we had 2 early (30 day) deaths (5%; a 71-81% reduction from expected). Early mortality at 100 days was 7% (n = 3). The 30 day mortality in the younger cohort <50 years of age (n = 16) receiving washed transfusions was 0%. Restricting the analysis to patients treated since 2006 (ABO identical transfusions; mostly washed) (n=27; mean age: 43 years; median: 41 years; range: 12 to 79), the early mortality rate at 30 days was 3.7%. Long-term survival (5 years) of our APL patients was similar to New York State Cancer Registry and literature reports (80-83%).

Discussion: Patients treated with transfusion regimens including ABO identical blood components, with or without washing, experienced early mortality at 30 days that was strikingly better (reduced by 71% to 86%) than that reported in the recent literature (3.7% to 5% vs. 17% to 26%). If these observed reductions in early mortality are causal, the avoidance of ABO immune complex induced derangements in hemostasis are a plausible contributing mechanism. These promising results provide a rationale for randomized trials of relatively simple and inexpensive approaches to reducing early hemorrhagic mortality in APL: use of ABO identical transfusions and washing to remove supernatant plasma.