Implications of Body Weight Calculations for Autologous Peripheral Blood Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5445-5445
Author(s):  
Lijo Simpson ◽  
Robert C. Wolfe ◽  
Dennis A. Gastineau ◽  
William J. Hogan ◽  
Shaji Kumar

Abstract Background: Obesity is a prevalent health problem and significant heterogeneity is seen in the body weight and BMI among adult patients undergoing autologous stem cell transplantation (SCT). At least two critical steps of the SCT are influenced by the body weight. Stem cell collection targets are usually determined based on the actual body weight and conditioning chemotherapy doses are usually determined based on corrected ideal body weight. One could hypothesize that since the stem cells home to bone marrow, the ideal body weight (IBW) being based on the height may be a better indicator of the stem cell numbers required rather than the actual body weight (ABW). Since chemotherapy doses are calculated based on corrected ideal body weight, and the volume of distribution is higher in obese patients, these patients may have decreased drug exposure and hence a higher risk of progression. Methods: We retrospectively evaluated the engraftment kinetics and response outcome of 306 SCTs done at our institution between March 1998 and October 2001. These included patients who had undergone SCT for multiple myeloma (46%), NHL (34%), HD (6%) and AL amyloidosis (14%). Body weight, height, stem cell dose and engraftment data was obtained from medical records. The stem cell dose received was calculated based on their ABW as well as IBW and correlated with the time to white cell and platelet engraftment. We also evaluated the effect of BMI on the progression free survival after the stem cell transplant using various cut offs. Results: The mean (range) for the ABW, IBW and BMI were 46.6 kg to 189 Kg; 45.5 kg to 94 kg; and 17.5 to 55.8 respectively. Using logistic regression, we estimated the ability of CD34 cell dose by actual and ideal body weight to predict the likelihood of platelet engraftment (50,000) by day 21 post transplant. The coefficients using both the doses were very similar (.391 for ideal and 0.361 for actual). Using Receiver operating characteristic analysis (ROC analysis); we determined the stem cell dose cutoff that best predicted for failure to engraft neutrophils by 21 days post transplantation, median CD34 dose by ABW of 3.6 million/Kg and by IBW of 4.2 million/Kg. Similarly, for failure to engraft platelets by day 30 the cutoffs were 2.89 million/Kg by actual weight and 3.77 million/kg by ideal weight. Among the individuals with actual body weight more than 25% of ideal body weight (n=122, 40%), we calculated the optimal total CD34 dose required and compared to the actual dose infused using both the cutoff sets (286 million vs. 446 million, P < 0.001 using ANC cutoff and 251 million vs. 446 million using the platelet cutoff, P < 0.001). We then examined the effect of BMI on progression free and overall survival from transplant. The progression free and overall survival post transplant was similar for patients with BMI over 30 kg/m2 compared to those below this cutoff. There was no difference when patients with myeloma or lymphoma were studied separately. Conclusion: This study, as in previous studies, confirms that stem cell dose determined on the basis of ideal body weight is comparable to that by actual body weight in terms of engraftment kinetics. In patients significantly above the ideal body weight, it is reasonable to use a target based on ideal body weight which will allow for collection of less numbers of CD34 cells, thus conserving resources. Among patient undergoing stem cell transplant, the practice of using corrected ideal body weight does not appear to compromise the outcome of stem cell transplant.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 352-352 ◽  
Author(s):  
Patrick Stiff ◽  
Joseph Unger ◽  
Stephen Forman ◽  
Michael LeBlanc ◽  
Thomas Miller ◽  
...  

Abstract Little is known about the optimal dosing of chemotherapy agents in patients significantly above their ideal body weight (IBW) who undergo high dose therapy with an autologous or allogeneic hematopoietic stem cell transplant. While dose attenuation is often advocated for overweight patients and appears to reduce acute toxicities, its effect on progression-free and overall survival (PFS/OS) is unknown. Due to a high relapse rate after autografts for relapsed/refractory NHL, SWOG has long investigated the use of augmented preparative regimens that utilize high-dose etoposide based on actual body weight (ABW) of 60 mg/kg, along with 12 Gy of TBI and cyclophosphamide (100 mg/kg) which is dosed on unadjusted IBW. We determined acute toxicities and PFS/OS using this approach in a recently completed study (S9438) of 358 patients undergoing autografts for relapsed/refractory NHL, comparing all grade 5 toxicities, grade 3–4 skin toxicities (known to be associated with high dose etoposide) and all other grade 4 toxicities in patients in this study based on % above IBW. The Devine formula for IBW with an adjustment for patients <5 feet was used. Patients at or below their IBW were dosed using their actual body weight. All patients received the preparative regimen as stated followed by autologous peripheral blood stem cells. Overall there were 31 patients with grade 5 toxicities. This group was a mean 42% above their IBW vs 24% for those surviving transplant (p=.001). Increasing % above IBW predicted grade 5 toxicity (p=.002). Even those at or 10% above their IBW had a higher toxic death rate (10.1 vs 3.6%; p=.04). While increasing weight above IBW did not predict for grade 4 lung, liver, cardiac toxicities or infections (p=.12), it did predict for grade 3/4 skin toxicities (p< .001). Skin toxicity, most commonly hand/foot syndrome was seen at rates up to 27.3% vs 7.3% for those ≥ 50 vs < 50% over IBW (p < .001). However, even those just ≥ 10% over IBW had nearly a 4 fold higher risk of skin toxicity (13.4 vs 3.6%; p=.005). While survival by % over IBW is confounded by comorbidities in overweight patients, we found no evidence of a different 2-year PFS or OS for overweight patients, even those ≥ 50% above IBW (PFS=42 vs 45%, p = .28; OS=52 vs 62%, p = .38). These multicenter trial data do establish a correlation of the ABW dosing of etoposide with significant skin toxicity. Without an apparent later PFS/OS benefit to the use of unadjusted etoposide dosing for overweight patients but higher acute skin toxicity and a higher early death rate, etoposide will be dosed using adjusted IBW [ IBW + .4 (ABW − IBW)] in subsequent studies of this regimen.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4535-4535
Author(s):  
Noga Shem-Tov ◽  
Myriam Labopin ◽  
Leila Moukhtari ◽  
Fabio Ciceri ◽  
Jordi Esteve ◽  
...  

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.


2015 ◽  
Vol 2 (4) ◽  
Author(s):  
David W. Kubiak ◽  
Mohammed Alquwaizani ◽  
David Sansonetti ◽  
Megan E. Barra ◽  
Michael S. Calderwood

Abstract We retrospectively identified 67 patients with severe or morbid obesity (body mass index ≥35 kg/m2) who had received intravenous vancomycin at our institution. We observed that an initial dose of 45 to 65 mg/kg vancomycin per day based upon ideal body weight rather than actual body weight was more predictive of initial trough concentrations between 15 and 20 mcg/mL.


2013 ◽  
Vol 58 (1) ◽  
pp. 88-93 ◽  
Author(s):  
Jennifer K. Ng ◽  
Lucas T Schulz ◽  
Warren E. Rose ◽  
Barry C. Fox ◽  
David R. Andes ◽  
...  

ABSTRACTDaptomycin use at our institution changed to ideal body weight dosing based on a published analysis of pharmacokinetic-pharmacodynamic efficacy target attainment, bacterial ecology, and a desire to reduce drug toxicity. The current study compared outcomes between actual body weight and ideal body weight dosing of daptomycin before and after this intervention. In the evaluable group, 69 patients received doses based on actual body weight and 48 patients received doses based on ideal body weight. Patients were treated for documentedEnterococcusspecies,Staphylococcus aureus, or coagulase-negativeStaphylococcusinfections, including bloodstream, intraabdominal, skin and soft tissue, urinary, and bone. There was no statistically significant difference in clinical success between the groups (88.9% for actual body weight compared to 89.1% for ideal body weight,P= 0.97). After we adjusted for gender, age, body mass index, concomitant 3-hydroxy-3-methylglutaryl–coenzyme A reductase inhibitors, infection type, and organism type, clinical success rates remained similar between groups (adjusted odds ratio of 0.68 in favor of actual body weight, 95% confidence interval [CI] of 0.13 to 3.55). Microbiological outcomes, length of stay, mortality, and adverse effects were also similar between groups. Further studies are warranted to confirm that ideal body weight dosing provides similar outcomes to actual body weight dosing for all patients and types of infections and organisms.


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