Outcomes of 9/10 Mmud Allo-HCT Using Ptcy-TK Prophylaxis. Results from a Single Institution
Authors: Pinto Filipe , Pedraza Alexandra , Suarez-Lledo Maria , Guardia Laia , Charry Paola , Cid Joan , Lozano Miquel , Corrius Gerard , De Llobet Noemí , Carreras Enric , Rosiñol Dachs Laura , Fernández-Avilés Francesc , Rovira Montserrat , Martinez Carmen , Salas Maria Queralt , Esteve Reyner Jordi 
Published: December 2024

INTRODUCTION

The use of PTCY-based prophylaxis in allo-HCT, regardless of donor type, is becoming prevalent due to its efficacy in preventing GVHD. However, data supporting the effectiveness of this prophylaxis in allo-HCT performed with 9/10 HLA-mismatched unrelated donors (MMUD) remain limited. In 2013, our institution implemented the use of PTCY combined with tacrolimus (TK) and mycophenolate mofetil (MMF) (PTCY-TK-MMF) for MMUD peripheral blood (PB) allo-HCT with notable success. In 2014, to minimize infectious complications while maintaining effective GVHD prevention, we discontinued the use of MMF and adopted dual prophylaxis with standard doses of PTCY and TK (PTCY-TK).

This study examines the outcomes of 103 adults undergoing MMUD allo-HCT with PTCY at our institution, focusing on the impact of HLA disparity on the likelihood of transplant complications.

METHODS

This retrospective study included all patients undergoing PB allo-HCT from 9/10 MMUD donors and receiving PTCY-based prophylaxis at our institution between 2013 and 2023. A 9/10 MMUD was defined as a donor-recipient match for 4 out of 5 alleles (HLA-A, -B, -C, -DRB1, and -DQB1) at high-resolution DNA typing. Seven (6.8%) patients received PTCY-TK-MMF, while 96 (93.2%) received dual prophylaxis with PTCY-TK. TK was maintained until day +90 and then tapered progressively until day +180, in the absence of GVHD. Data were updated in July 2024.

RESULTS

The median age was 53 years (range: 18-74) with 29 (%)patients aged 60 or older. Sixty-one (59.2%) patients were male, and acute myeloid leukemia (n=33, 32.0%) followed by acute lymphoblastic leukemia (n=24, 23.3%) were the most prevalent baseline diagnoses. 62 (60%) patients had a KPS &lt;90% and 19 (18%) an HCT-CI &gt; 3. Overall, class I mismatch was present in 89 (86.4%) patients and class II mismatch in 14 (13.6%) patients. 55 (53.4%) adults receivedreduced intensity conditioning (RIC) regimens, and 101 (98.0%) PB stem cell grafts.

The median time to neutrophil and platelet engraftment was 18 and 16 days, respectively. Four (3.9%) patients had primary graft failure (3 with locus A disparity and the other one with B). Infectious complications were prevalent among these patients showing a day +30 cumulative incidence (Cum.Inc)of bacterial bloodstream infections of 40.8%, and a day +180 Cum. Inc of HHV-6 reactivation/infection, grades 2-4 BK hemorrhagic cystitis, and proven/probable pulmonary fungal infection of 16.5%, 20.4%, and 13.7%, respectively. The days+180 Cum.Inc of CMV reactivation and disease were 52.4% and 6.8%. However, since letermovir prophylaxisimplementation in 2021, only 1 (5.8%) patient had CMV reactivation and it occurred after its discontinuation.

The Cum.Inc of grades II-IV and III-IV acute GVHD (aGVHD) at day +100 and moderate/severe chronic GVHD (cGVHD) at 2 years were 33.0%, 9.7%, and 12.6%, respectively. Using PTCY-TK was associated with comparable GVHD prevention than using triple-based prophylaxis composed by PTCY-TK-MMF (day +100 grades II-IV: 33.0% vs. 33.3%, P=0.995 / grades III-IV: 9.6% vs. 11.1%, P=0.85/ and 2-year mod/sev cGVHD: 12.7% vs. 12.5%, P=0.962).

With a median follow-up of 4.45 years, 25 (24%) patients relapsed and 40 (39%) died. The 3-year overall survival (OS), non-relapse mortality (NRM), and cumulative incidence of relapse (CIR) were 61.8%, 22.9%, and 22.3%, respectively.

The impact of HLA disparity on outcomes was investigated according to class I or II donor/recipient HLA-mismatch, showing that when using PTCY-based prophylaxis, the infusion of class I HLA MMUD products did not significantly impact outcomes (1-year NRM: 20.3% vs. 15.9%, P=0.842 / 1-year CIR: 12.4% vs. 36.5%, P=0.075 / 1-year OS: 70.7% vs. 62.9%, P=0.473) and GVHD incidences; although rates of moderate/severe cGVHD were lower in patients who received class II MMUD products (day +100 grades II-IV: 32.6% vs. 35.7%, P=0.839 / grades III-IV: 10.1% vs. 7.1%, P=0.74 / and 2-year mod/sev cGVHD: 14.8% vs. 0, P=0.153).

CONCLUSION

Our data support the use of dual GVHD prophylaxis composed of PTCY-TK in MMUD allo-HCT, demonstrating satisfactory GVHD prevention and survival rates. Notably, the infusion of class I HLA MMUD products did not significantly impact outcomes when using PTCY-based prophylaxis.