Hematopoietic Cell Transplantation Group Research Articles

Obesity Does Not Preclude Safe and Effective Myeloablative Hematopoietic Cell Transplantation (HCT) for Acute Myeloid Leukemia (AML) in Adults

INTRODUCTION: Obesity is increasingly common in the US and is frequently associated with co-morbid medical conditions that may increase the risk of HCT, often the optimal treatment for AML. HCT risk and outcomes for AML on the basis of body mass index (BMI) have not been well-characterized. Using data from the Center for International Blood and Marrow Transplant Research (CIBMTR), we have previously shown no significant difference in outcomes for autologous HCT for lymphoma among normal weight, overweight, and obese patients (pts) but worse outcomes for underweight pts (Navarro et al, BBMT 2006, 12(5): 541–51). Here, we compare outcomes by weight groups for AML patients who underwent autologous, related, or unrelated HCT.METHODS: Our final population included patients age ≥ 18 who underwent myeloablative unpurged autologous or allogeneic HCT for AML in 1st or 2nd complete remission, primary induction failure, or 1st relapse reported to the CIBMTR from 1995 to 2004. Cord blood HCTs were excluded. Four weight groups were defined based on BMI (BMI=weight (kg)/ height (m2)): underweight <18; normal=18–25; overweight >25–30; and obese >30. Treatment-related mortality (TRM), relapse, leukemia-free survival (LFS), and overall survival (OS) were compared using multivariable proportional hazards regression analysis accounting for patient, disease and HCT-related variables.RESULTS: We included 373 autologous, 2041 related, and 1801 unrelated transplant recipients. Patient-, disease-, and transplant characteristics were well-matched across weight groups and transplant types. Multivariable analysis examining risks (95% confidence intervals) relative to the normal weight group are:HCT TypeNormalUnderweightOverweightObeseAutologousn=164n=5n=112n=81Death–NSNSTreatment failure–NSNSRelapse–NSNSTRM–NSNSRelated Allogeneicn=1161n=31n=543n=268Death1.86 (1.24–2.78)NS1.23 (1.04–1.47)Treatment failure2.08 (1.37–3.15)NS1.19 (1.00–1.42)Relapse2.02 (1.18–3.47)NSNSTRM2.22 (1.17–4.22)NS1.32 (1.02–1.70)Unrelated Allogeneicn=846n=31n=523n=368DeathNSNSNSTreatment failureNSNSNSRelapseNS0.82 (0.68–0.99)0.76 (0.60–0.96)TRMNSNSNS– =not done due to insufficient number of pts; NS=not significant; treatment failure = death or recurrence of disease.CONCLUSIONS: There were no significant differences in risk of TRM, LFS, relapse or OS for normal weight, overweight or obese patient groups who received autologous HCT. Obese recipients of related HCT for AML had increased risk of death, treatment failure, and TRM, though the magnitude was small, an effect was not seen in the unrelated HCT group. Underweight patients who received a related, but not unrelated HCT, fared substantially worse than normal weight patients for all outcomes. It may be that the higher risk of the unrelated HCT 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 limit the ability to better characterize this finding in underweight patients. Disproportionately, fewer transplants have been reported in underweight patients which suggest they experience disease and patient-related factors that preclude transplantation. No differences were observed for incidence of acute or chronic GVHD for any weight group. Overweight and obesity should not be a barrier to HCT; however, caution should be exercised in selecting underweight patients for HCT.

Growth after Hematopoietic Cell Transplantation for Sickle Cell Disease.

Although allogeneic hematopoietic cell transplantation (HCT) has curative potential for sickle cell disease (SCD), the impact on growth in children treated by HCT is important to consider when counseling families about this therapeutic intervention. To investigate this, we compared linear growth after BMT to 3 cohorts of children with SCD. The comparison groups included 68 children with SCD who were measured before enrollment (HUG-KIDS Pre) and during treatment (HUG-KIDS HU) in a phase I-II trial of hydroxyurea for children with symptomatic SCD. The third comparison group included 1887 and 1889 children with height and weight data from the Cooperative Study of Sickle Cell Disease (CSSCD). Fifty-three of 55 surviving patients (20 F, 33M) had growth monitored after HCT. There was no significant difference in the distribution of repeated measurements between males and females, and 2 or more measurements of height and weight were performed in 89% and 92% of patients, respectively. The mean period of follow-up in the HCT and comparison groups was 3.3 ± 2.4 years after HCT, 5.5 ±3.3 years in the CSSCD, 4.0 ± 2.7 years in HUG-KIDS (pre) and 1.8±0.5 years in HUG-KIDS (HU). To accommodate the non-identical distribution of the ages among children treated by HCT, the comparison age range in the CSSCD and HUG-KIDS (HU) cohorts was 5 to 15 years for males, and 6 to 15 years in females, and was 3 to 13 years for males, and 4 to 13 years for females in the HUG-KIDS (pre) cohort. A Hierarchical Linear Model was used to model height and weight over the period of follow-up. Its design allowed for group comparisons of height and weight at baseline and linear growth velocity during the follow-up period. The height and weight data were modeled separately for males and females. At the baseline, there were no significant height or weight differences between the HCT and comparison groups among females, however, males in the HUG-KIDS (pre) group were approximately 4 cm taller than males in the HCT group. In all comparisons except that of males in the HCT and CSSCD groups, there were no strong differences in the linear growth velocity. However, males treated by HCT grew on average 0.67 cm/year more than males in the CSSCD group, and gained on average 1.0 kg/year more weight than males in the CSSCD, and these differences reached statistical significance (p=0.03, p=0.002, respectively). These data support the conclusion that growth after HCT for SCD is not impaired compared to children who receive standard therapy or HU. Moreover, in males, growth was more rapid after HCT than among males enrolled in the CSSCD. This analysis supports the notion that HCT for SCD offers a significant therapeutic benefit without a negative impact on growth.