Cyclophosphamide Dose Weight Adjustment in Morbidly Obese with Lymphoma Is Safe and Yields Favorable Outcomes after Autologous Hematopoietic Cell Transplantation (HCT)

Background:  Evidence based dosing of high-dose Cyclophosphamide (Cy) in obese patients remains elusive and some studies have identified obesity a risk factor for non-relapse mortality (NRM). We studied an adjusted body weight (ABW50) Cy dosing method in morbidly obese patients (body mass index >30) undergoing high dose Cy conditioning and autologous HCT.  

Patients & Methods: We analyzed 147 patients with non-Hodgkin lymphoma (NHL) who received Cy (120 mg/kg IV) + fractionated total body irradiation (TBI; 1320 cGy) conditioning (2001 – 2012) in 3 groups divided by body weight:  not obese (<120% ideal body weight (IBW); n=72), obese (120- 149% IBW; n=46) and morbidly obese (≥150% IBW; n=29).  Patients <150% of IBW were dosed using actual body weight (ABW). In morbidly obese patients, total Cy was calculated using adjusted body weight (ABW50) formula: IBW + 0.5(ABW – IBW). Patients had NHL (diffuse large B cell lymphoma n=57, mantle cell lymphoma n=51 and others n=39) with median age 57 years (range 19-73) and median follow up 2 years (range 1-9 yrs).

Results: NRM at 1 year was 4% and not different in 3 weight groups.  Overall survival (OS) at 4 years for non-obese was 54% (95% CI 40-67), obese 64% (95% CI 44-79), morbidly obese 64% (95% CI 37-82). Cumulative incidence of relapse was similar in 3 groups: 46% (95% CI: 36-55%); 44% (95% CI:28-60%) vs 48% (95% CI: 26-70%). Multivariable regression showed similar OS and relapse when adjusted for gender and disease status (Table). No differences were seen among weight groups regarding incidence of neutrophil and platelet engraftment, hemorrhagic cystitis or cardiac toxicity (congestive heart failure).

Conclusion: We report the first prospective testing of efficacy and safety of weight adjusted correction of Cy dosing using ABW50 formula in morbidly obese receiving high-dose Cy/TBI conditioning. Our data indicate that adjusted Cy dosing yields similar relapse rate, OS and NRM with no significant impact on engraftment or toxicity.  Morbidly obese patients can safely receive adjusted dose Cy.

Weight group	n	BMI	Weight used for Cy dose	Relapse Hazard ratio (95% CI)	p-value	Overall mortality Hazard ratio (95% CI)	p-value
Non-obese ≤120% IBW	72	25 (19-28)	ABW	1.00		1.00
Obese 121 -149 IBW	46	29 (24-42)	ABW	0.97 (0.55-1.74)	0.68	0.72 (0.37 - 1.4)	0.34
Morbidly obese ≥ 150 IBW	29	36 (30-55)	IBW + 0.5 (ABW – IBW)	0.78 (0.39 -1.57)	0.32	0.65 (0.28 - 1.52)	0.32

IBW ideal body weight, ABW actual body weight