Granulocyte Transfusions in Patients with Chronic Granulomatous Disease Undergoing Hematopoietic Cell Transplantation or Gene Therapy

Abstract

Granulocyte transfusions are sometimes used as adjunctive therapy for the treatment of infection in patients with chronic granulomatous disease (CGD). However, granulocyte transfusions can be associated with a high rate of alloimmunization, and their role in CGD patients undergoing hematopoietic cell transplantation (HCT) or gene therapy (GT) is unknown. We identified 27 patients with CGD who received granulocyte transfusions pre- (within 6 months) and/or post-HCT or GT in a retrospective survey. Twelve patients received granulocyte transfusions as a bridge to cellular therapy. Six (50%) of these patients had a complete or partial response. However, six of 10 (60%) patients for whom testing was performed developed anti-HLA antibodies, and three of the patients also had severe immune-mediated cytopenia within the first 100 days post-HCT or GT. Fifteen patients received granulocyte transfusions post-HCT only. HLA antibodies were not checked for any of these 15 patients, but there were no cases of early immune-mediated cytopenia. Out of 25 patients who underwent HCT, there were 5 (20%) cases of primary graft failure. Three of the patients with primary graft failure had received granulocyte transfusions pre-HCT and were subsequently found to have anti-HLA antibodies. In this small cohort of patients with CGD, granulocyte transfusions pre-HCT or GT were associated with high rates of alloimmunization, primary graft failure, and early severe immune-mediated cytopenia post-HCT or GT. Granulocyte transfusions post-HCT do not appear to confer an increased risk of graft failure. Supplementary Information The online version contains supplementary material available at 10.1007/s10875-022-01261-1.

Of Mycelium and Men: Inherent Human Susceptibility to Fungal Diseases

“…Owing to the refractory nature of IA or some of the other mycoses, granulocyte infusions have been attempted successfully [ 378 , 379 , 380 ], although there may be some reporting bias. Granulocyte infusions can also be given as a bridge to HSCT [ 381 , 382 ], although there is a risk of allo-immunization with subsequent graft failure [ 383 ], or given post-HSCT as a bridge to myeloid reconstitution [ 384 ]. HSCT with concomitant antifungal therapy, without granulocyte infusions, has also been successful [ 385 ].…”

Acute Invasive Pulmonary Aspergillosis: Clinical Presentation and Treatment

“…83 Adverse reactions include acute lung injury (especially when simultaneously administered with AmB) 167 and graft failure in allogeneic HSCT recipients due to alloimmunization. 168 It is hypothesized, on the basis of in vitro and in vivo data, that immune checkpoint inhibitors could have a role in the treatment of IFD, such as IA, in patients with AML. Immune checkpoint inhibitors could attenuate the progression of IA and synergize with antifungal therapy, although evidence from clinical studies is lacking.…”

“…83 Adverse reactions include acute lung injury (especially when simultaneously administered with AmB) 167 and graft failure in allogeneic HSCT recipients due to alloimmunization. 168…”

Granulocyte transfusions in severe aplastic anemia

“…The recently published experience with GT in patients with chronic granulomatous disease at our institution described a similar response rate to GT but, in contrast to our SAA cohort, GT given prior to HSCT were associated with high rates of alloimmunization and primary graft failure. 21 A successful GT strategy requires a sophisticated transfusion medicine department, including a blood collection center with access to a large pool of highly dedicated and motivated granulocyte donors, and rapid turnaround of HLA testing, which can be both cost-prohibitive and labor intensive. As our facility is research-focused and government-funded, there were adequate resources to collect, process, and administer HLA-typed granulocyte products.…”