Effectiveness and Toxicity of High-Dose Cyclophosphamide in Obese Versus Non-Obese Patients Receiving Allogeneic Hematopoietic Cell Transplant

High-dose cyclophosphamide (Cy) is a common component of conditioning regimens that patients receive prior to hematopoietic cell transplant (HCT).  Due to concerns for increased risk of toxicity, obese patients at Virginia Commonwealth University Health System (VCUHS) receive doses of Cy based on an adjusted body weight (ABW; ABW = [(total body weight [TBW] – ideal body weight [IBW]) x 0.4] + IBW) whereas non-obese patients receive doses based on TBW.  However, these practices are inconsistent with the American Society of Clinical Oncology (ASCO) 2012 guidelines, which recommend that obese patients receive full-dose chemotherapy.  Interestingly, these guidelines excluded patients with hematological malignancies undergoing HCT from their literature review.  Using a retrospective medical record review, we examined whether there is a difference in effectiveness and toxicity between obese and non-obese patients who receive high-dose Cy prior to HCT. 

The primary objective of this study was to determine if there is a difference in toxicity between obese versus non-obese patients during the first 60 days following transplant.  Toxicity was measured as a composite endpoint of overall toxicity, which was comprised of any grade 3 or 4 non-hematological toxicity, the incidence of pulmonary, hepatic, renal, or cardiac toxicity, and each component individually.  Secondary objectives were to compare the differences in effectiveness between obese and non-obese patients assessed by relapse at day +100, relapse at one year, death at one year, chimerisms at days +30, +60, and +90, and the incidence of acute graft versus host disease (aGVHD).  We also sought to evaluate the difference in time to engraftment and rates of infection between groups.  Chi-squared test and Fisher’s exact test were used to assess the primary and secondary endpoints and two-sample t-tests were used to assess time to engraftment. 

Sixty-one patients met the inclusion criteria.  Of these, 28 were considered to be obese while 33 were considered to be non-obese.  Mean BMI was 24.7 ± 2.5 in non-obese patients and 32.5 ± 4.3 in obese patients.  The mean Cy dose in non-obese and obese patients was 56.80 ± 10.4 mg/kg and 48.55 ± 3.3 mg/kg of TBW, respectively.  The rate of overall toxicity was greater in the obese patients compared to non-obese patients (82% vs 52%, OR 4.3 [95% CI 1.3-14.1]), which was driven by a significantly greater incidence of renal dysfunction (79% vs 48%, OR 3.9 [95% CI 1.3-12.1]).  There were no differences in rates of grade 3 or 4 toxicity, hepatic dysfunction, or any measure of effectiveness between groups.  Although obese patients are at increased risk of toxicity, they appear to achieve the same effectiveness as non-obese patients.  Since the increased risk of toxicity is due to increases in grade 2 renal toxicity, there is no evidence to support changing the dosing practices at VCUHS.