Allogeneic Hematopoietic Stem Cell Transplant in Patients Older Than 50 Years. Experience of Four Argentinean Centers

Materials and Methods. We retrospectively reviewed 76 medical records of patients older than 50 years receiving an allogeneic HSCT in our centers. We evaluated the following characteristics: sex, age, diagnosis, stage, comorbidities (according to the HCT-CI score), type of donor, histocompatibility, conditioning and immunosupression. We analyzed the incidence and severity of Graft-vs-Host disease (GVHD) and treatment related mortality (TRM) with Chi Square and Overall Survival (OS) and Disease Free Survival (DFS) with Kaplan Meier. For multivariate analysis (MA) we used Cox regression model for time dependant outcomes and logistic regression for dichotomic variables, considering significant a p<0.05.

Results Between March 1998 and June 2012, 76 transplants were performed with a median follow up of 1.9 years. Fourteen patients were older than 60 years, 51 were male, HCT-CI score was 0 (41%), 1 (36%), ≥2 (23%), common diagnosis were AML (35%), MDS (30%) and MPN (20%), 65% were in late stage, 80% received a transplant from a MRD, 37% received FluMel conditioning regimen, 32% FluBu and 12% BuCy, 66% received tacrolimus (Fk) based regimen and 34% cyclosporine. Acute GVHD (aGVHD) incidence was 51%, aGVH grade II-IV 29%. AML patients had a lower incidence of aGVHD (36% vs. 61%, p<0.03) still significant in MA (HR 0.27; 95% CI 0.07-0.98; p=0.04) as well as FluMel conditioning (33% vs. 59%, p=0.02), in contrast to unrelated donor (URD) (aGVHD GII-IV 53% vs. 23%, p=0.02). Chronic GVHD incidence was 33%, extensive in 10%. Early TRM (day 100) was 17% and global 30%. Female patients had lower early TRM (4% vs. 25%, p=0.02) opposite to HCT-CI score ≥2 patients that experienced a higher global TRM (58% vs. 26%, p<0.04) still significant in MA (HR 4.6; 95% CI 1.03-20.9; p=0.04) as well as MPN patients (64% vs. 25%, p<0.01) also significant in MA (HR 7.2; 95% CI 1.20-43.7; p=0.03). OS was 43% (1 year) and 20% (3 years). Patients older than 60 had a higher OS (1/3 years 61/43% vs. 38/14%; p=0.01), while FluBu was associated to a lower OS (1/3 years 25/10% vs. 49/23%, p<0.05), not significant in MA. Regarding immunosuppressant, the use of Fk was associated with a higher OS (1/3 years 44/20% vs. 19/6%, p<0.01) significant in MA (HR 0.45; 95% CI 0.2-0.9; p=0.04)and DFS (1/3 years 33/18% vs. 11/5%, p=0.01).

Conclusion According to the literature, URD is associated with a higher incidence of clinical significant aGVHD (p=0.02) and FluMel presented lower incidence of aGVHD as well as AML patients. Regarding TRM female patients had a lower early TRM and lower HCT-CI score had lower global TRM. FluBu was associated with a lower OS, while Fk patients had a higher OS and DFS. Interestingly patients older than 60 had higher OS not significant in MA, probably due to a better selection: none had HCT-CI higher than 1, only 1 patient received an URD transplant, most of them received Fk base immunosuppressant and all of them received a NMA transplant.