Impact of the Intensity of Conditioning Therapy On the Outcomes of Patients Aged 40 to 60 Years with Acute Myeloid Leukemia/Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation.

The eligibility of patients to undergo allogeneic hematopoietic cell transplantation (AHCT) is limited by age, co-morbid conditions and performance status. Utilizing reduced and minimal intensity conditioning regimens, older and less fit patients could benefit from this modality with the graft versus leukemia effect.

We performed a retrospective analysis of adults aged 40-60 years with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing AHCT at our center from January 2002 to June 2008. The objective of the study is to compare the overall (OS), relapse free (RFS), acute GvHD free and chronic GvHD free survival between the different conditioning regimens. The regimens are classified according to the definition of CIBMTR as conventional intensity (CIC) or reduced intensity (RIC). High risk disease is defined as patients meeting one of the following criteria: AML with poor risk cytogenetics, secondary AML with preceding hematologic disorder, AML in second complete remission or AML/MDS with preceding malignancy.

There are 106 patients eligible for the study (CIC 67, RIC 39); 56 patients with de novo AML, 22 with MDS and 28 with secondary AML. High risk disease comprised 64% of our study population. The baseline characteristics between the two groups including performance status (Karnofsky Performance Score; CIC 81%, RIC 83%, p=0.08) are not different except for age (mean in years; CIC 50.2, RIC 52.9, p=0.03), graft versus host disease (GvHD) prophylaxis (cyclosporine/alemtuzumab; CIC 16%, RIC 57%, p<0.001), donor type (unrelated donor; CIC 30%, RIC 54%, p=0.04) and Seattle co-morbidity index score (score of ≥3; CIC 12%, RIC 31%, p=0.03). The median follow up duration for all patients was 1.93 years. There is no statistically significant difference in the OS between the two groups (median OS in years; CIC 1.93, RIC 2.59, Log-rank p=0.62). Furthermore, RFS between the two groups were similar (median RFS was not reached in either groups, Log-rank p=0.86). Using Cox-model adjusting for important prognostic factors at baseline (age, disease risk, donor type, performance status, Co-morbidity index score and type of conditioning regimen), only performance status and disease risk are significant for both OS (HR 0.906 [p=0.01] and 2.13 [p=0.04] respectively) and RFS (HR 0.854 [p=0.04] and 6.931 [p=0.007] respectively). The acute GvHD and chronic GvHD free survival curves are not significantly different in the two groups (Log-rank p values are 0.66 and 0.16 respectively).

Despite inferior baseline characteristics in the patients receiving RIC, the outcomes were similar. Disease biology rather than intensity of the conditioning therapy is the determinant of overall survival and relapse risk after AHCT in patients aged 40-60 years with AML/MDS. Prospective randomized studies are needed to determine the superiority of RIC in patients who are deemed suitable to undergo CIC.

No relevant conflicts of interest to declare.