Reassessing Blood Product Irradiation in Haploidentical Transplantation: A Single-Center Perspective

Background: Transfusion-associated graft-versus-host disease (TA-GVHD) in hematopoietic cell transplantation (HCT) remains a concern traditionally mitigated using blood product irradiation. Recent advances in leukoreduction techniques question this need, especially in resource-limited settings. Two recent reports by Jaime-Pérez et al. and Elliot et al. showed that irradiation may not be as necessary as it was thought (1,2), This observational study evaluated the incidence of TA-GVHD after transfusing non-irradiated leukodepleted blood products to haploidentical transplant recipients, considering that immunosuppression is usually more intense in this kind of patients.

Study Design and Methods: This ambispective study assessed TA-GVHD incidence in haploidentical HCT patients receiving leukodepleted, non-irradiated blood components. Clinical records from 2018 to 2023 were retrospectively analyzed -regardless of age, gender and diagnosis. A prospective evaluation of residual leukocytes in blood components obtained from June to November 2023 was performed to validate our leukodepletion method. The leukodepletion method consisted of filtering packed red blood cells (PRBC) and platelets through a third-generation leukodepletion filters IMUGARD-IIIRC and IMUGARD-III PL from Terumo BCT (Shibuya, Tokyo, Japan), respectively. Platelet apheresis was obtained using Terumo BCT's Trima and Spectra Optia cell separators, which performed the leukodepletion before storage. Residual leukocytes were determined by cytofluorometry on the MACSQuant Analyzer 10 Flow Cytometer (Bergisch Gladbach, North Rhine-Westphalia, Germany) with the BD Leucocont Kit test (San Jose, CA, USA), within a 48-hour window after the filtration process was completed

Results: 150 patients were included, no cases of TA-GVHD were reported after using non-irradiated blood products. The median age of the population was 23 years, being 54% male (n=81) and 46% female (n=69). The median follow-up was 27.08 weeks. The incidence of grade 3-4 acute and moderate-severe chronic GVHD in our study were 12.7% (n=19) and 2.7% (n=4), respectively. The cumulative incidence of death was 34.7% (n=52) with an overall survival of 4.1 years (CI 95%, 3.7- 4.4 years).

72 patients (48%) received PRBC with a median of 2 (range= 1-13). All patients received platelet apheresis with a median of 2 (range= 1-64). There were no reported grade 3-4 transfusion-associated adverse reactions in any patient.

Residual leukocyte assessment post-leukodepletion showed an effective reduction from 594 WBC/µL to 0.09 WBC/µL (3.17 log reduction, or 99.93% reduction) in platelet concentrates and from 3,890.36 WBC/µL to 0.30 WBC/µL a (3.78 log reduction or 99.98% reduction) in PRBC. A reduction to 1.44 WBC /µL was reported in the platelet apheresis.

Conclusion: Since immunosuppression in haploidentical transplant recipients is more intense and could confer a higher risk of TA-GVHD(3) we decided to study this kind of patient. No cases of TA-GVHD were found. Using state-of-the-art leukoreduction strategies the need for blood product irradiation in transplant recipients should be questioned. Aside from the additional economic benefits and logistical ease reported in other studies, these findings support leukoreduction as a primary preventive measure. Further randomized trials are warranted to validate these findings.

References:

1. Jaime-Pérez JC, Villarreal-Villarreal CD, Salazar-Riojas R, Méndez-Ramírez N, Vázquez-Garza E, Gómez-Almaguer D. Increased Bacterial Infections after Transfusion of Leukoreduced Non-Irradiated Blood Products in Recipients of Allogeneic Stem Cell Transplants after Reduced-Intensity Conditioning. Biology of Blood and Marrow Transplantation. 2015 Mar 1;21(3):526–30.
2. Elliot J, Narayan S, Poles D, Tuckley V, Bolton‐Maggs PHB. Missed irradiation of cellular blood components for vulnerable patients: Insights from 10 years of SHOT data. Transfusion (Paris). 2021 Feb 21;61(2):385–92.
3. Wiersum-Osselton JC, Slomp J, Frederik Falkenburg JH, Geltink T, van Duijnhoven HLP, Netelenbos T, et al. Guideline development for prevention of transfusion-associated graft-versus-host disease: reduction of indications for irradiated blood components after prestorage leukodepletion of blood components. Br J Haematol. 2021 Dec 1;195(5):681–8.