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I. Abou Dalle et al.
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Figure 3. Long-term changes in hemoglobin levels and transfusion requirements with and without leuprolide. (A-B) Scatterplots of all corresponding peripheral blood hemoglobin (Hgb) levels extracted from health records, collected between induction chemotherapy (day 0) and last follow-up date where each dot represents a single value (blue for leuprolide, red for control). (A) Acute myeloid leukemia (AML) matched cohorts and (B) acute lymphoblastic leukemia (ALL) matched cohorts. Lowess smooth curves were used for indicating longitudinal trajectories of counts and differences were assessed using the generalized estimation equation model. (C-D) Transfusion requirements: differences in the mean number of blood and platelet units given between induction chemotherapy date (day 0) and last follow-up date in AML (C) and ALL (D) comparing matched leuprolide and control cohorts. Each value represents the total number of transfusion units given during this time period for each patient.
group had on average 26.7 units of pRBC compared to 29.9 units in the matched control group (P=0.24), and an average of 21.0 units of pRBC compared to 21.9 units in the same respective groups (P=0.44) (Figure 3D).
Multivariate analysis
Given that numerous factors such dose of leuprolide, age or relapse status for example could affect count recov- ery and the possible association with leuprolide, we per- formed a univariate analysis followed by a multivariate analysis for significant factors impacting long-term count recovery. We examined whether leuprolide dosing (higher cumulative leuprolide dose) or timing of administration of leuprolide (between day -7 and day 15 of induction chemotherapy compared to leuprolide given later) corre- lated with long-term count recovery and found no statisti- cally significant associations in the univariate analysis (Online Supplementary Table S3). Patients with AML who received FMS-like tyrosine kinase 3 (FLT3) inhibitors in addition to their chemotherapy had lower platelet recov- ery (P<0.001). Relapse status, investigated as a time dependent variable, was associated with lower long-term
lymphocyte count and hemoglobin levels in AML (P=0.04 and P=0.01 respectively) and higher neutrophil count recovery in ALL (P=0.001). The full results of the univari- ate analysis are included in Online Supplementary Table S3. We next sought to assess the differential impact of leupro- lide on count recovery when all co-factors are considered. We found that leuprolide administration was independ- ently associated with long-term hemoglobin levels, lym- phocyte and platelet counts in AML (P=0.02, P=0.003, and P=0.005, respectively) and ANC levels in ALL (P=0.049) (Table 2). Additional independent co-factors identified in this analysis for AML included performance status, adverse risk according to the European LeukemiaNet clas- sification, relapse status, and receipt of a FLT3 inhibitor or triplet chemotherapy. For ALL, independent factors included relapse or whether patients had an allogeneic stem cell transplant or were treated with HyperCVAD.
Impact on survival
We found that patients in the leuprolide groups were significantly younger than the respective control groups (Table 1). This was also associated with an improved OS
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