A Single Institution Study of Allogeneic Hematopoietic Stem Cell Transplant for MDS and AML in Patients 60 Years of Age and Older: Impact of Disease Risk Index and Secondary Disease

Background: Allogeneic Hematopoietic cell transplantation (HCT) is potentially curative therapy for MDS and AML. Although the median age at presentation is >65 years, most patients receiving HCT for these disorders are young (<60years). With the availability of Reduced Intensity Conditioning (RIC) many older patients are able to undergo HCT. The older age group is the most rapidly increasing cohort in CIBMTR registry. We analyzed the outcomes of AML and MDS patients' ≥ 60 years who received allogeneic sibling or unrelated donor HCT at our institution between 2009 and 2014. We also evaluated the influence of patient-, disease-, and transplant related factors on outcomes.

Methods: Prospectively collected data available in the BMT databases at Mayo Clinic Florida, Arizona and Rochester as well as individual patient charts were reviewed after IRB approval. Patients with MDS or AML in complete remission at the time of transplant were included; those with active disease, induction failure, or prior transplant were excluded. HCT-specific comorbidity index (HCT-CI) and the disease risk index (DRI- Armand et al. Blood 2012) was noted. Survival estimates were calculated using the Kaplan Meier method. Associations with survival were explored using single variable Cox-regression modeling and log-rank tests.

Results: 80 patients were included; 68 AML and 12 MDS. 31 (39%) were male. Median age 66 years (range 60-75). 33%, 52%, and 13% patients had ECOG status of 0, 1, >2, respectively. Thirty-seven patients (46%) had low or intermediate DRI and 43(54%) had high DRI. Twenty-two (28%), 24 (30%), and 34 (43%) patients had HCT-CI of 0, 1, or >2. There were equal number of sibling and unrelated donors; 85% were full HLA match and 15% with 1 or 2 mismatches; mean age of the donors was 52years (range18-74). Transplant conditioning was fludarabine-containing reduced intensity regimens in 78 (97%), 2 patients received myeloablative conditioning. The source of stem cells was peripheral blood in all patients. A median of 5.87 x10^6 CD34/kg donor cells were infused (range 1.58-10.92 X10^6). All patients received calcineurin inhibitor based GVHD prophylaxis (tacrolimus 56%, cyclosporine 44%); 6 patients also received ATG.

The median follow up of survivors was 13 months. Kaplan Meier estimate of overall survival at 100 days, 1 year, and 2 years was 90%, 64%, and 55%. Cumulative incidence of relapse at 6 months, 1 year, and 2 years was 19.5%, 22.3%, and 27.1%. Relapse free survival at 2 years was 50%. The non-relapse/ treatment related mortality at 6 months, 1 year and 2 years was 11.7%, 15.9% and 15.9%. The rate of acute grade 2-4 GVHD was 30% and chronic GVHD was 39%. Univariate analysis identified secondary disease (compared to de novo) and high DRI(compared to low/intermediate) to be associated with worse mortality - HR 2.54 (1.31-4.93; P = 0.006), and 2.31 (1.13-4.73; P = 0.021), respectively. Probability of overall survival at 6 months, 1 year, and 2 years for patients with de novo disease (n=57) vs. secondary disease (n=23) was 87.1% vs. 64.5%, 71.1 vs. 45.6%, and 63.2 vs. 32.6%, respectively; P= 0.006. There was no effect of donor age, donor type or degree of mis-match on the survival.

Conclusion: Allogeneic HCT is feasible in older patients with MDS and AML utilizing reduced intensity conditioning regimens with acceptable outcomes that are comparable to published results in younger patients. Patients with high DRI and secondary disease have poorer overall survival as compared to those with de novo disease and low/intermediate disease risk index. These data support other studies that age alone does not negatively influence transplant outcomes.