In this contemporary, retrospective, large study in AML patients, we demonstrated that obesity as defined by BMI at time of transplantation does not correlate with worse survival outcomes but that underweight recipients of RD allo HCT have shorter survival compared to patients within the normal BMI range. Similar to our previous study in patients with lymphoma, the current study demonstrates that obesity does not appear to represent a significant barrier to successful HCT for AML.
The impact of obesity on transplant outcomes remains controversial. The HCT-specific comorbidity index developed by Sorror et al included obesity (BMI >35kg/m2
) as one of the components to predict non-relapse mortality at 2 years(19
). This study included 708 patients in the training set who underwent allogeneic HCT for several indications; of these, 2% were obese. The data in this analysis predate the collection of HCT-CI-specific information initiated by CIBMTR in 2007 so no direct comparison is possible. However, transplant-related mortality in our study was not significantly higher in obese AML patients compared to normal weight patients, regardless of the donor type.
In the previous lymphoma study, we observed poorer outcomes in one of the underweight groups. Interestingly, poorer survival outcomes were observed in underweight patients in the RD allo HCT group but not the URD alloHCT group. Because of the small numbers of patients in the RD alloHCT group, there is some imbalance compared to the other weight groups with respect to disease status at time of transplantation with disproportionately more PIF/relapse and CR2 patients, though it is not clear how much this finding accounts for the difference in leukemia-free and overall survival. Such an imbalance of disease status was not seen in the underweight URD alloHCT group. It is noteworthy that the underweight RD alloHCT group had a similar KPS (P = 0.353) and cytogenetic risk (P = 0.327) compared to the other weight groups; these important factors do not appear to account for the difference in survival. It may also be that the higher risk of the URD alloHCT procedure masks important but less obvious risks associated with being underweight whereas in the related donor HCT setting, such risks become manifest. Small numbers of patients and lack of available data pertinent to nutritional status such as serum albumin or TPN use limit the ability to better characterize this observation in underweight patients. Moreover, the analysis does not account for unknown biological factors not included in the model that may be influencing outcomes in the underweight RD allo HCT group.
An important limitation of this study is that any conditioning regimen dose adjustments for overweight and obesity used by the various transplant centers could not be assessed from the CIBMTR data. Since chemotherapy dosing in the conditioning regimen may be based on actual weight or adjusted ideal body weight, clinical outcomes may have been confounded by whether dose adjustments were made for patients with high BMI. There is currently no accepted standard conditioning regimen dose adjustment schema based on weight and various methodologies are used, as was ascertained by Grigg and colleagues(20
). A small study of AML patients undergoing autoHCT without dose adjustment has previously suggested that some adjustment may be beneficial, as the lack of conditioning regimen dose adjustment in that study resulted in unacceptable treatment-related mortality(21
Similar to our previous study in lymphoma, the current study demonstrates that obesity does not appear to represent a significant barrier to successful HCT in AML. This conclusion must be tempered, however, with the acknowledgment that the patients who received myeloablative HCT were likely selected by their transplant centers, and were deemed to be “fit” to withstand the rigors of HCT. The limitations of pre-transplant co-morbidity data within the CIBMTR database preclude an assessment of this issue. Thus, the caveat is that it appears that overweight and obese patients have similar outcomes to normal weight patients when they otherwise appear to be eligible HCT candidates. Obesity alone, however, should not preclude HCT when appropriate for the treatment of AML.