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Influence Of Comorbidities On Transplant Outcomes In Patients Aged 50 Years Or More After Myeloablative Conditioning Incorporating Fludarabine, Busulfan And ATG

Year: 2010

Type: article

Abstract: Non-myeloablative (NST) and reduced intensity (RIC) regimens are offered to older patients (pts) and/or those with comorbidities because the morbidity and mortality attributable to fully myeloablative conditioning is thought to be unacceptably high. All such patients receive myeloablative protocols in our program, outcomes have been analyzed in order to determine whether this practice is justifiable. Between 1999 and 2008 207 patients (pts) with hematologic malignancy aged 50–66 years (median 56) received blood cell (87%) or marrow transplants after conditioning with Flu 50 mg/m2 daily × 5 and IV Bu 3.2 mg/kg daily × 4. 90 (43%) had additional total body irradiation (TBI) 200 cGy × 2. Graft-versus-host disease (GVHD) prophylaxis was cyclosporin A, methotrexate and Thymoglobulin (Genzyme) 4.5 mg/kg total dose. Donors were matched siblings in 125 (60%) mismatched related in 11 (5%), 10/10 matched unrelated in 54 (26%) and mismatched unrelated in 17(8%). 74 pts (36%) had low-risk (LR, acute leukemia CR1/CR2, CML CP1) disease. As defined by the HCT-CI scoring system 117 (57%) pts scored 0 (low HCT-CI), 68 (33%) 1 or 2 (intermediate HCT-CI) and 22 (11%,) ≥3 (high HCT-CI). Transplant risk factors were similar between intermediate and high HCT-CI groups. As NRM (33% and 33% vs 24% and 48%, p=ns) and DFS (46% and 37% vs 64% and 43%, p=ns) at 1 and 5 years respectively were also similar, outcomes in these 2 groups were combined for more robust analysis. The proportion of pts with LR disease was higher in those with comorbidities (intermediate and high HCT-CI) (49% vs 26%, p=0.0006) than those without. OS was 56% and 39% vs 74% and 54% (p=0.008), DFS 50% and 38% vs 68% and 49% (p=0.03), NRM 31% and 39% vs 15% and 19% (p=0.003) and relapse 26% and 36% vs19% and 39% (p=ns) respectively at 1 and 5 years. In 48 AML pts in CR1 & CR2, 27 (56%) with comorbidities, receiving this protocol with TBI DFS at 5 years was 66%. We conclude that: 1. Comorbidities influence NRM with this regimen although cannot confirm that the high HCT-CI group is at higher risk than the intermediate. 2. Age alone should not be an indication to prefer a less intense protocol particularly in a condition such as AML where there is an effect of regimen intensity on relapse. 3. Although NRM with this regimen is high in older patients with comorbidities, formal comparison with similar patients receiving NST or RIC regimens is warranted.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2009.12.374