Open AccessAllogeneic haematopoietic stem cell transplantation with reduced-intensity conditioning in chronic myeloid leukaemia
Author(s) -
Elena Morozova,
Ю Ю Власова,
М В Барабанщикова,
Kseniia S. Afanaseva,
К. С. Юровская,
Т. Л. Гиндина,
Ildar Barkhatov,
А Л Алянский,
Evgeny Bakin,
Sergey N. Bondarenko,
Ivan S. Moiseev,
Л. С. Зубаровская,
Б. В. Афанасьев
Publication year - 2020
Publication title -
gematologiâ i transfuziologiâ
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.126
H-Index - 5
eISSN - 2411-3042
pISSN - 0234-5730
DOI - 10.35754/0234-5730-2020-65-4-386-402
Subject(s) - medicine , busulfan , thymoglobulin , transplantation , gastroenterology , hematopoietic stem cell transplantation , cyclophosphamide , melphalan , fludarabine , graft versus host disease , chemotherapy , tacrolimus
. 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), udarabine (180 mg/m 2 ) or melphalan (140 mg/m 2 ), udarabine (180 mg/m 2 ). 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 signicantly 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 ve-year relapse-free survival (RFS) was 40 % (95 % CI 29–51). Transplantation in AP or BC phase signicantly 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.