Background: Induction chemotherapy (IC) in Acute Myeloid Leukemia (AML) leads to significant bone marrow suppression. The standard clinical practice to prevent or manage cytopenia related complications, namely anemia or bleeding, has been red blood cell (RBC) and platelet (PLT) transfusion. Accumulating evidence suggests no advantage to patients (pts) managed with liberal transfusion strategies compared to a restrictive approach. However, prior studies excluded patients with bone marrow failure conditions such as AML; hence it remains unclear whether a similar approach can be extrapolated for AML pts. We undertook this study to evaluate the effects of transfusions on treatment outcomes and complications in AML.
Methods: Adult pts diagnosed with AML (excluding acute promyelocytic leukemia) at the Cleveland Clinic from 01/2008 - 12/2012 who underwent IC with 7+3 (full dose of cytarabine and anthracycline) and had complete adverse event data were included. Variables including demographics, preexisting comorbidities, AML disease characteristics, organ dysfunction (neurologic, cardiac, pulmonary, renal, hepatic, bleeding and thromboembolic events), infections (bloodstream infection, pneumonia and clostridium difficile associated diarrhea) and treatment response [complete remission (CR), incomplete remission (CRi), persistent disease (PD) and 30-day mortality] were assessed. The outcome of interest was any correlation between the total number of PLT and/or RBC transfusions and (i) organ impairment, (ii) infections, and (iii) treatment outcomes during the induction period. Culture confirmed bloodstream infections included vancomycin resistant enterococcus (VRE), gram-positive bacteria (except VRE), gram-negative bacilli and fungemia. Univariable and multivariable logistic regression models adjusted for potential confounders were performed for each outcome category. Odds ratio (OR) with 95% confidence intervals (CI) are reported.
Results: Of 192 pts, 48% (n=93) were female, 85% (n=163) were Caucasian, 54% (n=103) were <60 years, (yrs, range, 19-82), and 17% (n=33) received 2 cycles of induction chemotherapy. Disease characteristics were - de novo AML 89% (n=170) and secondary AML 12% (n=22). Cytogenetic risk groups per CALGB 8461 criteria were - favorable 21% (n=41), intermediate 46% (n=89), unfavorable 24% (n=46), and unknown cytogenetics 8% (n=16). 67% of patients achieved CR (n=128), 15% (n=29) achieved CRi and 14% (n=27) had PD following IC. The median number of RBC and PLT transfusions received during remission induction chemotherapy was 12 RBCs (range 0-49) and 10 PLTs (range 0-62) (figure 1 and 2).
In univariable analysis a higher number of RBC and PLT transfusions was associated with an increased risk of bloodstream infections (OR=1.03; CI,1.01-1.05; p=0.001). In multivariable analysis increased number of transfused RBCs and PLTs was associated with lower CR rates (OR=0.94; CI,0.91-0.97; p<0.001) and slightly increased risk for major adverse cardiac events (OR=1.04; CI,1.02-1.07; p=0.002), pulmonary events (OR=1.04; CI,1.02-14.07; p=0.004), neurologic events (OR 1.14; CI,1.07-1.22; p<0.001) and VRE bacteremia (OR=1.04; CI,1.01-1.08; p=0.005). There was no statistically significant association between transfusion and renal dysfunction (OR 1.02; CI,0.99-1.06, p=0.15), liver injury (OR=1.02; CI,1.00-1.05; p=0.067), thromboembolic events (OR=1.02; CI,0.98-1.05; p=0.28), total number of blood stream infections (OR 1.03; CI,1.00-1.05; p=0.019) and 30-day mortality (OR=0.98; CI,0.93-1.03; p=0.56).
Conclusion: In multivariable analysis the number of RBC and PLT transfusions during AML IC is associated with a slightly increased risk for cardiac, pulmonary and some infectious complications. Higher numbers of transfusions also appear to be associated with lower CR rates. These data can inform future prospective studies designed to determine the benefits and risks of a restrictive transfusion policy in the AML population.
Sekeres:TetraLogic: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees.
Asterisk with author names denotes non-ASH members.