The Favorable Results of Allo-HSCT in TKI-Resistant CML,

Tyrosine kinase inhibitors (TKI) have revolutionized the treatment of chronic myeloid leukemia (CML). However, for patients who fail TKI or progress to advanced phase disease, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only therapeutic option. The rationale of this study was to evaluate results of allo-HSCT in CML patients who have failed TKI treatment. Patients and Methods: 48 CML pts aged 33 (19–52) years who failed previous treatment with TKI (imatinib-37 pts, imatinib+dasatinib-5, imatinib+dasatinib+nilotinib- 3, dasatinib-2, imatinib+nilotinib-1) received allo-HSCT from HLA-matched siblings (15) or from 10/10 (21) and 9/10 (12) HLA-antigens-Matched Unrelated Donors (MUD) in Hematology and BMT Center in Katowice, Poland, from 10.2002 to 03.2011. The myeloablative preparative regimen consisted of treosulfan 3×14 g/m2 plus fludarabine 5×30 mg/m2 (30 pts) or busulfan 4×4 mg/kg plus cyclophosphamide 4×30 mg/kg (18 pts). Standard GVHD prophylaxis consisted of cyclosporine-A, methotrexate and pre-transplant ATG or thymoglobulin in allo-HSCT from MUD. Source of cells was bone marrow (27 pts) or peripheral blood (21 pts) with median 2.6 or 6.7 x10(6)CD34+cells/kg, respectively. Results: All pts engrafted. 100% donor chimerism has been achieved in 40 (83.3%) pts, 97–99% in 4 pts, progressing mixed chimerism was observed in 4 pts. The 5-year estimated overall survival rate was 79%. 9 pts died 9 (1–21) months following allo-HSCT due to infection (5), GVHD (3) or relapse (1). Bio-molecular relapse or progressing mixed chimerism was observed in 6 pts and was treated with 3 to 5 donor lymphocyte infusions (3 pts), post-transplant imatinib (3 pts) or nilotinib (1 pt). Acute GVHD grade I, II, III and IV was observed in 15, 13, 2 and 1 pt (serious aGVHD grade III-IV in 3 pts (6.25%) only); limited and extensive chronic GVHD in 17 (35.4%) and 9 (18.75%) pts, respectively. Other complications in survivors included CMV reactivation (12), hemorrhagic cystitis (3), H. zoster (2), P. jiroveci (1) and cataract requiring surgery (1). 39 pts (81.25%) are alive 44 (3–92) months post-transplant. Conclusions: Allo-HSCT with myeloablative treo/flu or bu/cy conditioning is a feasible and effective curative therapy in TKI-resistant CML. The alternative therapy with allo-HSCT may overcome TKI resistance, providing long-term remission or cure from CML in patients who failed TKI treatment.

No relevant conflicts of interest to declare.