Granulocyte Colony-Stimulating Factor Is Safe and Well Tolerated Following Allogeneic Transplantation in Patients with Sickle Cell Disease

• Published in: Blood 2020-11, Vol.136 (Supplement 1), p.33-33
• Main Authors: Shah, Niketa C., Bhoopatiraju, Sweta, Abraham, Allistair, Anderson, Eric Jon, Andreansky, Martin, Bhatia, Monica, Chaudhury, Sonali, Cuvelier, Geoff D.E., Godder, Kamar, Grimley, Michael, Hale, Gregory, Kamani, Naynesh, Jacobsohn, David, Ngwube, Alexander I., Skiles, Jodi L., Yu, Lolie C., Shenoy, Shalini
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2020-142696

▪ Background: Granulocyte colony-stimulating factor (G-CSF) is used after hematopoietic cell transplantation (HCT) to enhance neutrophil recovery in patients rendered neutropenic by the agents used in the preparative regimen (PMID: 9187067). G-CSF is contraindicated in patients with sickle cell disease (SCD) due to reported life-threatening complications ascribed to sickle vasculopathy, presumably secondary to leukocytosis and granulocyte activation (PMID: 11880644). Complications include severe vaso-occlusive pain crises, splenic engorgement, rupture, and death (PMID: 19513902). Individuals with sickle trait tolerate G-CSF without toxicity (PMID: 29743574, PMID: 27167356).The safety/toxicity of using G-CSF to enhance neutrophil recovery following HCT for SCD has not been previously described in the context of vasculopathy that is present in recipients but whose hematologic milieu is altered by transfusions and donor product infusion. Aim/Method: The hypothesis that G-CSF use would be safe in SCD patients following HCT was tested in a multicenter trial (NCT 03128996). Patients underwent HCT from matched or one-antigen mismatched (at HLA-A, -B, -C, -DRB1 if marrow; -A, -B, -DRB1 loci if cord) related or unrelated donor products between 2004 and 2019 following reduced intensity conditioning (RIC) which included hydroxyurea, alemtuzumab, fludarabine, melphalan +/- thiotepa. The regimen results in short-term marrow suppression followed by recovery. GVHD prophylaxis included tacrolimus, short-course methotrexate or mycophenolate or prednisone, and since 2018, abatacept. All patients underwent transfusions prior to commencing conditioning to reduce Hemoglobin S (Hb S) levels to 1.5x103 cells/mL on 3 successive days. The clinical course, outcomes, and toxicities in the first 100 days post-HCT were evaluated as best representing the period of G-CSF influence on SCD recipients. Results: Sixty-four patients with SCD were evaluated post-HCT. The median age at HCT was 10.67 years (range, 1-21). HCT was performed for stroke/increased transcranial doppler velocity (N=32), acute chest syndrome (N=24) and vaso-occlusive episodes (VOE) (N=38). Twenty-nine and 35 patients received related and unrelated donor HCT respectively; 24 were mismatched at one antigen or allele locus. Graft sources included marrow (46), cord (12), peripheral blood (3), marrow + cord (2) and CD34