Prophylactic Basiliximab on Days +1 and +4 Post-Haploidentical Hematopoietic Stem Cell Transplantation Reduces Incidence of Grade II-IV Acute Graft-Versus-Host Disease in Acute Myeloid Leukemia Patients in Complete Remission (M1, M2, and M4 Subtypes)

Introduction

Haploidentical hematopoietic stem cell transplantation (haplo-HCT) is widely used to treat high-risk acute myeloid leukemia (AML). Acute graft-versus-host disease (aGVHD) is a leading cause of early post-transplant mortality. Basiliximab, a chimeric monoclonal antibody targeting the α chain of the interleukin-2 receptor (CD25), prevents interleukin-2 (IL-2) binding, thereby inhibiting T-cell activation. While Basiliximab is commonly used to treat steroid-refractory aGVHD, its prophylactic use after transplantation, especially across different AML subtypes, is rarely reported.

Methods

This study included AML patients undergoing their first haplo-HCT from March 2016 to December 2023 at Beijing Lu Daopei Hospital and Hebei Yanda Lu Daopei Hospital. Patients received myeloablative conditioning with modified busulfan/fludarabine (BU/FLU) or busulfan/cyclophosphamide (BU/CY), and melphalan regimens. Prophylaxis for aGVHD included cyclosporine (CSA), mycophenolate mofetil (MMF), short-course methotrexate (sMTX). The experimental group received additional Basiliximab (20 mg/d) on days +1 and +4 post-transplant, while the control group did not.

Results

125 patients were included with 99 (51 males and 48 females) in the experimental group and 26 (16 males and 10 females) in the control group. In the experimental group, the median age is 12 (range 1-68) years old, 57 patients (57.6%) were in first complete remission (CR1), 14 (14.1%) in second or greater complete remission (≥CR2), and 28 (28.3%) in non-remission/partial remission (NR/PR). AML subtypes were M1 (5, 5.1%), M2 (33, 33.3%), M4 (21, 21.2%), M5 (28, 28.3%), and M7 (12, 12.1%). 62 patients (62.6%) had 5/10 HLA matches and 37 (37.4%) had ≥6/10 matches. Median haploidentical grafts cell counts were: MNC cells, ×10⁸/kg (14.98, range 7.58-36.82), CD34+ cells, ×10⁶/kg (8.10, range 1.58-29.34) , CD3+ cells, ×10⁸/kg (3.05, range: 0.91-8.44). Neutrophil engraftment occurred in 97/99 (97.98%) patients, with a median time of 14 days (range 9-33). Platelet engraftment occurred at a median of 11 days (range 6-173).

In the control group, the median age was 33 years (range 3-54). Among the patients, 9 (34.6%) were in CR1, 2 (7.7%) in ≥CR2, and 15 (57.7%) in NR/PR. AML subtypes included M1 (0, 0%), M2 (15, 57.7%), M4 (5, 19.2%), M5 (5, 19.2%), and M7 (1, 3.9%). 17 patients (65.4%) had 5/10 HLA matches, and 9 (34.6%) had ≥6/10 matches. Median haploidentical grafts cell counts were: MNC cells, ×10⁸/kg (9.38, range 3.74-19.04), CD34+ cells, ×10⁶/kg (5.09, range 2.76-12.24), and CD3+ cells, ×10⁸/kg (2.17, range 0.68-5.15). Neutrophil engraftment occurred in 23/26 (88.46%) patients, with a median time of 13 days (range 8-25), and platelet engraftment occurred at a median of 12 days (range 10-86).

In patients with pre-transplant CR (including CR1 and ≥CR2), the 100-day incidence of Grade II-IV aGVHD was significantly lower in the experimental group compared to the control group (17.9% vs. 51.5%, P = 0.045). No significant difference was observed in the 100-day incidence of Grade III-IV aGVHD (11.3% vs. 18.2%, P = 0.617). Among NR/PR patients, no difference was noted in the incidence of Grade II-IV (46.4% vs. 46.7%, P =0.988) or Grade III-IV aGVHD (32.1% vs. 40%, P =0.606) between the groups.

In the experimental group, a subgroup analysis by AML subtype showed the following 100-day incidences of aGVHD among 72 patients in CR prior to transplantation: Grade II-IV aGVHD incidences were 0% for M1, 14.3% for M2, 12.5% for M4, 18.2% for M5, and 37.5% for M7. Grade III-IV aGVHD incidences were 0% for M1, 14.3% for M2, 6.3% for M4, 9.1% for M5, and 25% for M7. For patients in NR/PR, the 100-day incidences of Grade II-IV aGVHD were 0% for M1, 33.3% for M2, 20% for M4, 66.7% for M5, and 100% for M7. Grade III-IV aGVHD incidences were 0% for M1, 25% for M2, 20% for M4, 33.3% for M5, and 75% for M7.

Conclusion

Prophylactic Basiliximab on days +1 and +4 post-haplo-HCT effectively reduces the incidence of Grade II-IV aGVHD, particularly in CR-AML patients. The effect is less pronounced in NR/PR patients. The prophylactic benefit is most evident in M1, M2, and M4 AML subtypes, while M7 patients derive less benefit. These findings suggest that prophylactic Basiliximab should be tailored to the patient's AML subtype and pre-transplant status. Further multi-center studies with larger sample sizes are needed for validation.

No relevant conflicts of interest to declare.