Chemotherapy Dose Adjustment For Obese Patients Undergoing Hematopoietic Stem Cell Transplantation (HSCT): A Survey On Behalf Of The ALWP Of The EBMT
Authors: Shem-Tov Noga , Labopin Myriam , Moukhtari Leila , Ciceri Fabio , Esteve Jordi , Giebel Sebastian , Gorin Norbert-Claude , Schmid Hansjoerg , Shimoni Avichai , Nagler Arnon , Mohty Mohamad 
Published: October 2019

Rates of obesity have substantially increased in recent years. Pharmacokinetics of drugs including chemotherapy is different in obese patients due to alteration in the clearance and volume of distribution. Thus, appropriate chemotherapy dosing for obese patients with malignant diseases is a significant issue. Limiting chemotherapy doses in overweight and obese patients may negatively influence the outcomes in these patients. ASCO has recently published clinical practice guidelines for conventional chemotherapy dosing for obese patients with cancer indicating that up to 40% of obese patients received reduced chemotherapy doses that are not based on actual body weight (ABW) [Grigg A, JCO 2012]. Concerns about toxicity or overdosing in obese patients, based on the use of ABW, are unfounded. Moreover, there is a paucity of information addressing the pharmacokinetics of high dose chemotherapy in obese patients undergoing hematopoietic stem cell transplantation (HSCT). A rather small international survey of drug dosing schemes among transplant centers revealed that there is no consensus regarding appropriate dose adjustment for obese patients [Grigg A, Leuk Lymphoma 1997]. Also, there is limited data on outcomes in obese versus non-obese patients in various small retrospective studies.
For this reason, the ALWP of the EBMT constructed an electronic survey for assessing current practice of dose adjustment of chemotherapy in patients undergoing HSCT, in transplant centers and for planning retrospective analysis and prospective studies in the future.
Fifty six EBMT centers from 27 countries filled the online survey. Among the 56 centers, the percentage of obese patients was less than 10% in 22 centers (40%), between 10 to 19% in 23 centers (42%) and more than 20% in 10 centers (17%). Forty five centers declared they adjust chemotherapy dose for obese patients (80.5%) and only 11 (19.5%) declared they do not adjust dose. Among centers which adjust dose, most uses BMI as the parameter for defining obesity (28 centers, 62%), others use percentage over the actual body weight (ABW) as the basis for defining obesity (11 centers, 24.5%), both BMI and ABW (3 centers, 6.7%) or other parameter (3 centers, 6.7%). Most of the centers that use BMI for adjusting dose define BMI > 30 kg/m2 as the cut-off value (formal definition for obesity), only one center uses morbid obesity (BMI > 40 kg/m2), and the remainder uses other cut-off values. Among 11 centers who use ABW, 9 use ABW more than 120% of ideal body weight for adjustment. Eighty four percents of the centers use one level of obesity for adjustment while the rest uses 2 levels. The method for determining the weight for chemotherapy calculation was actual body weight (ABW) in 16 centers, ideal body weight (IBW) in 10 centers, IBW + 25% of difference between IBW and ABW (IBW+0.25*(ABW-IBW)) in 16 centers and other methods in the rest. Among centers that use dose adjustment, 44% also cap the dose at 2 m2 for chemotherapy dose based on BSA while 56% do not cap. On the contrary, most of the centers (9/11) that do not adjust dose for weight also do not cap the BSA at 2 m2. Seventy nine percents of responding centers use the same approach to dose adjustments for myeloablative, reduced intensity (RIC) or non myeloablative (NMA) conditioning, while 21% reduce the dose less for RIC or NMA conditioning. For Busulfan dose only 7 centers monitor pharmacokinetics (pk). Eleven centers use ideal body weight for calculation, 17 centers use actual weight and 18 centers correct weight according to percentage over actual body weight.

Conclusion
This EBMT survey reveal large diversity among transplant centers regarding dose adjustment practice for high dose conditioning chemotherapy. Most of the EBMT centers use dose adjustment for obese patients and about half of them also cap BSA at 2 m2, while capping is uncommon in the centers that do not adjust dose. Thus, the range of the final dose is very wide. Even for Busulfan where dose is calculated normally according to ideal body weight, the diversity of dose given for obese patients is wide. Our next step is to analyze outcomes of transplantation according to dose adjustment practice and subsequently to formulate a methodology for future prospective studies.

Disclosures:
No relevant conflicts of interest to declare.