Allogeneic haematopoietic stem cell transplantation with reduced-intensity conditioning in chronic myeloid leukaemia

Abstract

Introduction. Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for chronic myeloid leukaemia (CML).Aim. Analysis of allo-HSCT outcomes in CML patients following reduced-intensity conditioning (RIC) regimens.Materials and methods. This retrospective study included 110 CML patients who underwent allo-HSCT in 1995–2019. RIC regimens included busulfan (8–12 mg/kg), fludarabine (180 mg/m2) or melphalan (140 mg/m2), fludarabine (180 mg/m2). The median onset time for treatment with tyrosine kinase inhibitors (TKIs) was 60 days after allo-HSCT (30–835). Post-transplant graft-versus-host-disease (GVHD) prevention with cyclophosphamide (Cy) at high doses (PTCy) of 50 mg/kg in 3–4 days after allo-HSCT (D+3, D+4) was ordered in 61 % (n = 67), with antithymocyte globulin (ATGAM) 60 mg/kg — in 17 % (n = 19), with thymoglobulin 5 mg/kg — in 3 % (n = 3) of the patients.Results. In the study cohort, 50 % (n = 55) of the patients had chronic phase 2 and higher (CP ≥ 2), 25 % (n = 27) — accelerated phase (AP), 9 % (n = 10) — blast crisis (BC) phase of the disease. Among CP ≥ 2 patients, 63 % (n = 58) had a BC in history, and 25 % (n = 23) — 2 or more BCs. One-year non-relapse mortality (NRM) was 21 % (95 % CI 15–31). PTCy prevention of GVHD significantly reduced the NRM risk relative to other schemes: 11 % (95 % CI 5–20) vs. 38 % (95 % CI 23–53) (p = 0.001). Acute GVHD II–IV had a rate of 23 % (95 % CI 15–31), chronic GVHD of moderate to severe degree 15 % (95 % CI 9–22). TKIs were used in 49 % (n = 29) cases for relapse prevention, in 40 % (n = 24) — due to the lack of response to allo-HSCT, in 10 % (n = 6) — in relapse. Donor lymphocyte infusion (DLI) was performed in 37 patients mainly in BCR-ABL positive cases (24 %, n = 9) and relapse (49 %, n = 18). Three-year relapse rate was 36 % (95 % CI 26–46), and five-year relapse-free survival (RFS) was 40 % (95 % CI 29–51). Transplantation in AP or BC phase significantly increased the relapse rate (odds ratio 2.4800 (1.2180–5.050), p = 0.012). Five-year overall survival was 52 % (95 % CI 40–62), a clean BC history and PTCy correlated with a higher 5-year overall survival (odds ratios 1.9990 (1.0700–3.7350), p = 0.029, and 0.3126 (0.1670–0.5851), p = 0.0002, respectively).Conclusion. Reduced-intensity conditioning is advantageous in patients with long-term CML and several lines of TKI therapy in history. Post-transplant complication relief is associated with PTCy prevention. Relapse instances, however, complicate the outcomes of allo-HSCT with RIC. Post-transplant TKI and DLI facilitate response in 54 % of the patients. Success of allo-HSCT largely depends on the disease phase (CP, AP, BC) at the time of transplantation.