Pre-Emptive Granulocyte Transfusions (GTX) in Pediatric Patients with a Chronic Bacterial or Fungal Infection Undergoing a Hematopoietic Stem Cell Transplantation (HSCT).
Authors: Sharon Raphael F. , Vrielink H. , Bierings M. B. , Versluijs A. B. , Boelens J. J. 
Published: April 2020

GTX in patients with severe infections and neutropenia have been previously reported to be a therapeutic modality in these group of patients. Patients undergoing HSCT are at risk of developing infections post-transplantation: bacterial and fungal infections mainly during aplasia, and viral reactivation mainly after aplasia. A chronic dormant bacterial or fungal infection prior to the HSCT is a severe risk factor for reactivation, development of acute GvHD and mortality. Pre-emptive GTX could probably influence the susceptibility for reactivation and therefore influence the outcome of the HSCT.

We here report our experience with pre-emptive GTX in patients with a chronic dormant bacterial or fungal infection undergoing HSCT.

Between 12/2003 and 11/2004, 3 patients (table 1) were treated with pre-emptive GTX prior to HSCT, with a frequency of 3 times a week. From day +7 patients received G-CSF (10 μg/kg). Granulocyte donors (all family donors, age 16–70 years) were screened for CMV (and other viruses), ABO-compatibility and physical condition. They were all asked to sign an informed consent. Preferably ABO-compatible and CMV-negative donors were used where the patient was also CMV negative. In case of ABO-incompatibility anti-A/B was used with a titre ≤ 1:64, except for cases where no other donors were available. Donors were treated with 480 μg G-CSF and 7.5 mg dexamethasone on the evening prior to the apheresis. The target amount of cells harvested was 5*1010/m2

Table 1. GTX characteristics Pt nr/ Diagnosis Chronic infection d start GTX Granulocytes L + 1h L + 1d L+2d Out of aplasia BD = Blackfan-Diamond; L+1h = leukocytes 1 hr post-GTX; L+2d = day 2 post-GTX *1010/m2 (range) *10 9/l (range) *10 9/l (range) *10 9/l day 1/ X-CGD S.aureus −3 6.8(3.8–11) 1.2 (1.1–3.1) 0.5 (0.2–1.8) 0.1 +12 2/ BD Aspergillus −20 5.2(2.8–8) 2.6 (0.7–3.9) 1.0 (0.1–2.4) &lt;0.1 +7 3/ ALL Mucormycosis +1 4.8(2.8–9) 0.6 (0.4–0.6) 0.2 (&lt;0.1–0.3) &lt;0.1 +26

Patient 1 and 3 received respectively a full-graft identical sibling, and a full-graft C-locus mismatched UD, both after myeloablative conditioning. Patient 2 received an identical unrelated donor after reduced intensity conditioning (after unsuccessful first HSCT with poor autologous recovery). All 3 cases underwent the HSCT successfully with a 100% donor chimerism with a follow-up of 8,12 and 18 mth respectively. No flare of the present chronic infection was seen. Although one of the patients had acute GvHD grade 3 (pt 2), no other complications were seen. In addition, no transfusion-related complications were seen. We collected a median of 6.8 * 1010 /m2 (range 2.8–11) granulocytes per transfusion. With this dose, granulocytes were almost continuously present, except in patient 3. Even in patient 1, who only had ABO-incompatible donors with high iso-haemaglutinine levels, no hemolysis or transfusion-related reactions were seen.

It is our firm belief that the outcome of these HSCTs was positively influenced by the GTX. Pre-emptive GTX in patients with dormant, chronic infections prior to HSCT is a feasable, low-toxic method to enable HSCT in these patients. A prospective study is needed to investigate the success of pre-emptive use of GTX and whether the complications are indeed minimal in a large group of patients.