Outcomes of Patients with Chronic Myeloid Leukemia Who Underwent Allogeneic Stem Cell Transplantation in the Tyrosine Kinase Inhibitors Era
Authors: Wernicke German Jose , Enrico Alicia I , Cattaneo Maximiliano , Bendek Del Prete Georgina Emilia , Pelayes Tortosa Sofia , De Luca Teofilo , Bentolila Gonzalo , Castro Martin , Castellanos Leandro Roberto , Saslavsky Martin , Rivas María Marta , Vitriu Adriana , Arbelbide Jorge Alberto , Perez Mariel Ana , Berro Mariano , Basquiera Ana Lisa 
Published: December 2024

Introduction: Since the introduction of tyrosine kinase inhibitors (TKI) agents, the role of allogeneic stem cell transplantation (Allo-SCT) is limited to patients with insufficient TKI response/TKI intolerance in the first chronic phase or those who developed a blast phase (BP).
Objective: We aimed to evaluate the results of Allo-SCT in patients with CML in the TKI era.
Methods: A retrospective study of patients who underwent Allo-SCT was conducted in Argentina between 2010 and 2023 in centers affiliated to GATMO-TC (Grupo Argentino de Trasplante de Médula Ósea y Terapia Celular). Outcomes evaluated were: overall survival (OS), progression free survival (PFS), non-relapse mortality (NRM) and relapse incidence (RI), and incidence of acute and chronic graft versus host disease (GVHD).
Results: Data of 80 patients were analyzed (median age at transplant 42 years; range 17-69; 64% males). Median time from diagnosis to transplant was 31 months (range 1-252) and median number of TKI received before transplant was 2 (range 1-5). (91% imatinib, 88% dasatinib, 46% nilotinib, 23% ponatinib and 1% bosutinib). Indications for transplantation were: no-BP (insufficient TKI response, 26%; TKI toxicity 9%; and accelerated phase, 9%) and BP (55%). A total of 13% had a T315 mutation. Donors were: 67% matched, 12% mismatched unrelated, and 20% familiar haploidentical. Absence of any molecular response was reported in 39%. Most of the patients received a myeloablative conditioning regimen (79%) and only 4 patients (5%) had a high HCT-CI. After a median follow-up of 57 months, 5-year OS was 51% (95% CI 38-62). Inferior OS was observed in patients undergoing Allo-SCT after BP (35%; 95%CI 28-50), vs non-BP (72%;95% 52-85); p&lt;0.001, and no molecular response (35%; 95%CI 17-54) vs at least minimal molecular response (59%; 95%CI 49-73%); p=0.011. Both transplant indication and molecular response at transplant were independent factors in the multivariate analysis (HR 5.1, p=0.003; and HR 3.3, p=0.004). No significant difference was observed by type of donor, age, year of transplant, time to transplant, conditioning regimen, or CD34+ dose. Patients with BP receiving post-transplant TKI maintenance had a similar OS than non-BP patients with/without maintenance vs BP patients without maintenance (63% vs 73% vs 70% vs 6%; p&lt;0.001). At 1 year, NRM was 18% (95%CI 11-27) and RI was 20% (12-30). Mismatched donors were associated with a higher risk of relapse (38%, 95%CI 20-56 vs 11%, 95%CI 5-21; p&lt;0.001), showing no plateau, achieving a 54% at 5 years (95%CI 32-72). At 1 year, cumulative incidence of GVHD was 49% (95%CI 37-59) and 20% (95%CI 11-31) for acute and chronic, respectively.
Conclusions: Patients undergoing Allo-SCT for CML in first chronic phase had more than 70% long term OS. The use of maintenance in patients who developed a blast phase may overcome the poor prognosis of these patients. Relapse incidence may be also increased in patients undergoing ASCT with mismatched donors.