Leukocytosis Post Engraftment Is Associated with Increased Mortality Among Adult Allogeneic Hematopoietic Cell Transplant (HCT) Reciepients
Authors: Solh Melhem M. , Khaled Yasser 
Published: October 2019

Abstract
Abstract 4536
Elevated white blood cell count is considered an independent risk factor for thrombotic events among patients with hematological malignancies undergoing intensive chemotherapy, as well as autologous or allogeneic hematopoieitc cell transplant. Engraftment among allogeneic HCT recipients is associated with endothelial damage, cytokine release and elevated white count. The impact of persistent leukocytosis after engraftment on survival and transplant related complications such as graft versus host disease is not well established.
In this study, we retrospectively reviewed the charts of 74 consecutive patients who underwent allogeneic HCT in a single center between 2009 and 2011. Neutrophil engraftment was defined as an absolute neutrophil count of 0.5 ×103/μl for 3 consecutive days. Patients blood counts were assessed for 60 days post engraftment (three times per week). Persistent Leukocytosis (group A) was defined as a white blood cell count of >10 ×103/μl for more than four days. Patients who had leukocytosis for three or less days were called group B. Conditioning regimens included myeloablative MA (Fludarabine/Busulfan or cytoxan/total body irradiation) and reduced intensity RIC (fludarabine/busulfan or fludarabine/cytoxan/low dose TBI). Graft versus host disease prophylaxis included methotrexate/tacrolimus for myeloablative and tacrolimus/Mycophenolate for reduced intensity conditioning.
The median age was 51 years (range: 18–74 years). Graft source included matched related (n=24), Unrelated donor (n=48) and cord blood (n=2). 36 patients received MA conditioning and 37 had RIC conditioning. Median follow up for the cohort was 556 days. Median time to neutrophil engraftment was 13 days. 22 patients had persistent leukocytosis (group A) during the first 60 days post engraftment. The two groups did not differ in terms of age, gender, diagnosis (acute leukemia versus other), disease risk and conditioning regimen (table 1). Group A had a higher proportion of related donor source (50% versus 31%; p=0.05). One year overall survival was significantly worse in group A (40.6% versus 74.7%; p=0.009). Grade II-IV acute graft versus host disease was higher among group A patients (68% versus 48%; p=0.18) although not statistically significant. The cause of death among patients with persistent leukocytosis included acute GVHD (n=6), relapse (n=5), infection (n=2) and thrombosis (n=1).
In conclusion, Persistent leukocytosis post engraftment in allo HCT recipients is associated with worse overall survival and may be an independent risk factor for acute GVHD. Despite a larger proportion of related donors among the leukocytosis group, our data showed a trend towards higher incidence of acute GVHD. The exact mechanism leading to prolonged leukocytosis is not clear and further studies to confirm the association between leukocytosis and clinical outcomes are warranted.
Table 1. Clinical and Transplant Related Characteristics of Group A and Group B Patients Group A Group B P value Leukocyte count >10 × 103/μl for ≥4 days Leukocyte count >10 × 103/μl for ≤ 3 days Number of Patients 22 51 Diagnosis Aplastic anemia 0 2 0.191 Acute Leukemia 19 35 MDS/MPD 1 3 Lymphoma/CLL 1 9 MM 1 2 Graft Source Related 11 12 0.05 Unrelated 10 38 Cord Blood 1 1 Conditioning regimen RIC Conditioning 13 23 0.39 MA Conditioning 9 28 Time to Neutrophil engraftment (Days) 13 12 GVHD Prophylaxis Tacro/MMF 13 23 Tacro/Methotrexate 9 28 0.46 Median follow up (Days) 533 567 Cause of Death GVHD 6 3 0.03 Relapse 5 9 0.86 Infection 2 2 Thrombosis 1 0 MDS: myelodysplastic syndrome; MPD: myeloproliferative disorder; CLL: chronic lymphocytic leukemia; RIC: reduced intensity conditioning; MA: myeloablative; GVHD: graft versus host disease; CSA: cyclosporine; MMF: mycophenolate; 1 P value for acute leukemia versus all others.

Disclosures:
Solh: Celgene: Speakers Bureau. Khaled:Celgene and Takeda Pharmacutical: Honoraria, Speakers Bureau.