Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Myelodysplastic Syndrome: Impact of Age and Conditioning

Introduction: Myelodysplastic syndromes (MDS) are one of the main indications for allogeneic hematopoetic cell transplantation (HCT). With the introduction of reduced intensity conditioning regimens (RIC) this curative therapy is increasingly used in elderly (≥60 years) or comorbid patients (pts).

Methods: Here we retrospectively analyzed data obtained in 81 consecutive adult MDS patients (f=32, m=49) that underwent allogeneic HCT using either myeloablative (MAC) regimens (Busulfan (Bu)/Cyclophosphamid (Cy) (n=13), Cy (n=1); Cy/Total Body Irradiation (TBI) 12Gray (n=6)) or RIC (FLAMSA/Fludarabin (Flu)/Bu (n=3); Flu/Bu (n=28); Flu/TBI (n=5); Flu/Thiotepa/Melphalan (Mel) (n=2); Flu/Treosulfan (n=12), FLAMSA/Bu/Cy (n=1), Flu/Cy/TBI (n=2), Flu/Mel (n=2)). For graft versus host disease (GVHD) prophylaxis, calcineurin inhibitor combined with mycophenolate mofetil (n=24) or methotrexate (n=41) and anti-thymocyte globulin (n=60) were used.

Results: Median age at first diagnosis of patients was 53 years (range 21-72). Pts were grouped in 2 age categories: pts <60 years (group A, n=57) and >60 years (group B, n=24). Pts suffered from MDS/CMML 5q, n=2; CMML I, n=3; CMML II, n=2; RAEB I, n=21; RAEB II, n=21; RCMD, n=27; RCUD, n=2. Median IPSS score in group A and B was 1.4. 32% of group A and 35% of group B had an IPSS Score below 2. Mean HTC-CI in group A was 1.4, in group B 1.7. Grafts either from matched related (A, n=18, B, n=2), matched unrelated (MUD; A, n=25, B, n=13) or mismatched unrelated (MMUD; A, n=7, B, n=9) donors were used. Conditioning in group A was MAC (n=20) or RIC (n=31) whereas all patients in B received RIC. No significant age-associated influence was observed with regard to median survival (A, 44 months; B, 26 months; p=0.7) or estimated 3 year overall survival (OS) (A, 33%; B, 19%; p=0.3). Median observation time of patient alive was 40 months (range 3-168 month). Cumulative incidences of non-relapse mortality adjusted for relapse as competing risk showed no significant difference for group A and B. Progression free survival was not significantly different between the groups (A, 20 months; B 12 months; p=0.25). Kaplan-Mayer Analysis showed no difference in OS between risk groups; however, progression free survival was significantly lower in the group with IPSS >2 (7 vs 22 months, p=0.02). Within 100 days, neither in A nor B non-relapse mortality (NRM) was documented. The use of a MMUD appeared to have a negative but not significant influence in older pts on OS (3-year OS in A: MUD 75% vs. MMUD 25%, p=1.00; B: MUD 100% vs MMUD 0%, p=0.2). Incidence of GvHD ≥II was in 14% vs. 6% in A and B. Incidence of chronic GVHD was 42% in A (limited=12, extensive=12) and 37% in B (limited=4, extensive=5).

Conclusion: RIC represents a promising treatment option in elderly MDS pts and allows for allogeneic HCT even in comorbid pts. Age had no negative impact on survival. Interestingly, IPSS score has an influence on progression free survival in patients.