Mobilization Success and Bariers for Autologous Hematopoietic Stem Cell Transplantation in a Constrained-Resource Nation

Abstract

<h3>Introduction</h3> Autologous stem cell transplantation (ASCT) is a well-established therapy for various hematologic and solid malignancies. Optimal mobilization and harvest of peripheral blood-stem cells (PBSC) is crucial. A failed mobilization attempt (MA) can preclude transplantation in up to 40% of cases, however, novel agents have increased success rates. The aim of our study was to evaluate factors impacting MA failure and remobilization efficacy in a resource-constrained setting. <h3>Methods</h3> Retrospective single-center study including patients with at least one MA of PBSC for ASCT between June 2010 to June 2019. <h3>Results</h3> Inclusion criteria were met by 158 patients. Median age at MA was 37y and 61.4% were male. ASCT indication was hematologic in 84.8%: lymphoma in 37.3%, monoclonal gammopathy in 32.9%, and acute leukemia in 14.6%. Relapsed or primary refractory disease was the indication in 51.9%. A 25.3% had previous exposure to radiotherapy. Status of disease at MA was in 48.1% complete response, while 8.9% (<i>n=14</i>) had less than a partial response (Figure 1). At first MA, the median level of CD34 was 16.1 × 10⁶/L. G-CSF, chemotherapy (CT) and plerixafor (PLX) were used in 85%, 11.8% and 3.2%. MA was successful (>2 or >4 × 10⁶ CD34/kg harvested in ≤3 aphereses) in 64.6% and 32.3%, with a median harvest in the whole cohort of 3.5 × 10⁶ CD34/kg (Figure 2). Factors associated with MA failure were: BMI ≥25 (<i>p=0.03</i>), high BSA (<i>p=0.016</i>), hematologic malignancy as ASCT indication (<i>p=0.013</i>), pre-MA WBC <4 × 10⁹/L (<i>p=0.032</i>), pre-apheresis CD34 <10 × 10⁶ cells/L (<i>p<0.001</i>), and MA with G-CSF or CT (<i>p=0.05</i>). No relation to CT regimens or number of cycles was seen except for lymphoma cases (<i>p=0.025</i>) (Figure 3). Of patients that failed MA, 66.1% (<i>n=36</i>) underwent a second MA. Of these, 85.3% were non-mobilizers to G-CSF and the remainder to CT. Of non-mobilizers to G-CSF, 44.8% (<i>n=13</i>) were rechallenged, to the remainder CT (37.9%) or PLX (17.2%) was added. Of non-mobilizers to CT, due to economic constraints or toxicity, 60% (<i>n=3)</i> received G-CSF while the remaining were rechallenged. Overall 41.7% and 19.4% cases had a successful second MA for >2 or >4 × 10⁶ CD34/kg, with no difference in outcome between mobilization agents used (<i>p=0.132)</i>. <h3>Conclusion</h3> In this cohort, anthropometry, hematologic disease, number of CT cycles, and WBC count; in addition to use of G-CSF as unique agent in MA was related to lower rates of successful PBSC harvesting. These findings should guide decision making process on mobilization agent, as limiting or delaying ASCT and requiring additional MA directly impact disease outcomes and higher costs. Reduced rates of success on second MA, despite increased use of CT and PLX were observed. The significant loss of benefit of PLX highlights the need to direct our efforts on preemptive action. Cost-effective, resource-stratified approaches are required to maximize adequate harvesting and subsequent access to ASCT.