scholarly journals Ideal rather than actual body weight should be used to calculate cell dose in allogeneic hematopoietic stem cell transplantation

2006 ◽  
Vol 37 (6) ◽  
pp. 553-557 ◽  
Author(s):  
S Singhal ◽  
L I Gordon ◽  
M S Tallman ◽  
J N Winter ◽  
A O Evens ◽  
...  
Keyword(s):  
Body Weight ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Actual Body ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Actual Body Weight ◽  
Hematopoietic Stem ◽  
Cell Dose

scholarly journals A Case Series and Literature Review of Isavuconazole Use in Pediatric Patients with Hemato-oncologic Diseases and Hematopoietic Stem Cell Transplantation

2019 ◽  
Vol 64 (3) ◽  
Author(s):  
N. Decembrino ◽  
K. Perruccio ◽  
M. Zecca ◽  
A. Colombini ◽  
E. Calore ◽  
...  
Keyword(s):  
Body Weight ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Case Series ◽  
European Organization ◽  
Hematopoietic Stem ◽  
Oncologic Diseases

ABSTRACT We analyzed the use of isavuconazole (ISA) as treatment or prophylaxis for invasive fungal disease (IFD) in children with hemato-oncologic diseases. A multicentric retrospective analysis was performed among centers belonging to the Italian Association for Pediatric Hematology and Oncology (AIEOP). Pharmacokinetic (PK) monitoring was applied by a high-performance liquid chromatography-tandem mass spectrometry (HLPC-MS/MS) assay. Twenty-nine patients were studied: 10 during chemotherapy and 19 after allogeneic hematopoietic stem cell transplantation (HSCT). The patients consisted of 20 males and 9 females with a median age of 14.5 years (age range, 3 to 18 years) and a median body weight of 47 kg (body weight range, 15 to 80 kg). ISA was used as prophylaxis in 5 patients and as treatment in 24 cases (20 after therapeutic failure, 4 as first-line therapy). According to European Organization for Research and Treatment of Cancer (EORTC) criteria, we registered 5 patients with proven IFD, 9 patients with probable IFD, and 10 patients with possible IFD. Patients with a body weight of <30 kg received half the ISA dose; the others received ISA on the adult schedule (a 200-mg loading dose every 8 h on days 1 and 2 and a 200-mg/day maintenance dose); for all but 10 patients, the route of administration switched from the intravenous route to the oral route during treatment. ISA was administered for a median of 75.5 days (range, 6 to 523 days). The overall response rate was 70.8%; 12 patients with IFD achieved complete remission, 5 achieved partial remission, 5 achieved progression, and 3 achieved stable IFD. No breakthrough infections were registered. PK monitoring of 17 patients revealed a median ISA steady-state trough concentration of 4.91 mg/liter (range, 2.15 to 8.54 mg/liter) and a concentration/dose (in kilograms) ratio of 1.13 (range, 0.47 to 3.42). Determination of the 12-h PK profile was performed in 6 cases. The median area under the concentration-time curve from 0 to 12 h was 153.16 mg·h/liter (range, 86.31 to 169.45 mg·h/liter). Common Terminology Criteria for Adverse Events grade 1 to 3 toxicity (increased transaminase and/or creatinine levels) was observed in 6 patients, with no drug-drug interactions being seen in patients receiving immunosuppressants. Isavuconazole may be useful and safe in children with hemato-oncologic diseases, even in the HSCT setting. Prospective studies are warranted.

A New IV Busulfan Fixed Dosing as Part of BuMel or BuCy Conditioning Regimens: A Pharmacokinetic/Pharmacodynamic Study in Pediatric Patients Undergoing Autologous or Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5200-5200
Author(s):  
Gilles Vassal ◽  
Hélène Esperou ◽  
Dominique Valteau-Couanet ◽  
Jean Claude Gentet ◽  
François Doz ◽  
...  
Keyword(s):  
Body Weight ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Graft Rejection ◽  
Dose Adjustment ◽  
Fixed Dose ◽  
Hematopoietic Stem

Abstract Background: Busulfan (Bu) given in myeloablative doses is frequently included in hematopoietic stem cell transplantation (HSCT) regimens for pediatric (Ped) patients (pts). Following administration of oral Bu, plasma concentrations versus time profiles (AUC) vary considerably. Over-exposure is correlated with higher toxicities while under-exposure is associated with graft rejection. The IV formulation of Bu is demonstrated to provide reliable dosing, reducing inter- and intra-pts pharmacokinetic (PK) variability, and thus avoiding therapeutic drug monitoring (TDM) with dose adjustments. In a previous study, a new body-weight based calculation of IV Bu fixed dose was defined to target AUC (900–1500 μM.min) in children [Nguyen L et al. BMT 2004]. The PK results of a new prospective study in children have been presented earlier [Vassal G. et al, ASCO 2005; # 8535] and we report here the results of the investigated PK vs. pharmacodynamic (PK/PD) relationships. Methods: Children received either IVBu/Melphalan (Mel, 140 mg/m2) or IVBu/Cyclophosphamide (Cy, 200 mg/kg) before autologous (auto-) or allogeneic (allo-) HSCT, respectively. IV Bu was infused over 2 h at a dose of 1.0 mg/kg, 1.2 mg/kg, 1.1 mg/kg, 0.95 mg/kg, and 0.8 mg/kg for pts &lt; 9 kg, 9 to &lt; 16 kg, 16 to 23 kg, &gt;23 to 34 kg, and &gt;34 kg strata of weight, respectively. No dose adjustment was allowed. Bayesian Bu AUCs were calculated at doses 1, 9 and 13. The PK/PD analysis was carried out on engraftment and regimen-related toxicities (RRT). Results: Overall, 55 pts with a median age 6 y [0.3 – 17.2], 20 pts ≤ 4 y, were enrolled: 27 and 28 received IVBuMel and IVBuCy, respectively. Bu clearance was confirmed to be widely variable (CV=50%) however the new dosing enabled homogeneous AUCs whatever the patient’s weight, and AUC inter- pts variability was hugely reduced (CV &lt; 20%). In allo-HSCT, all AUCs were &gt; 900 μΜ.min (threshold value for engraftment), and there was no early and/or late graft rejection. Over-exposure was limited (all AUCs &lt; 2100 μΜ.min) and no correlation was observed with the low incidence of VOD in allo- (2/28, 7%) and auto- (4/27, 15%) pts. Of note, 87 % and 91% of AUCs in allo- and auto- pts were &lt; 1500 μΜ.min. In auto-pts, there was a significantly positive correlation (R2=0.35, p&lt; 0.01) between stomatitis severity and AUC. It was also illustrated that higher AUC tended to increase bilirubin value from baseline, but the correlation was weak. No significant correlations were detected with other RRT and efficacy parameters. Conclusions: Body-weight based calculation of IV Bu fixed doses has successfully targeted a therapeutic AUC in children. The high rate of AUC targeting achieved without any PK monitoring and dose adjustment is likely to favourably contribute to the efficacy and safety in IV Bu-based HSCT regimens.

Actual (ABW) or Ideal (IBW) Body Weight to Calculate CD34+ Cell Dose in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation for Myeloma?

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4455-4455
Author(s):  
J. Krishnamurthy ◽  
V. Singh ◽  
O. Frankfurt ◽  
Andrew M Evens ◽  
J. Altman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Body Weight ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Height Loss ◽  
Dose Calculations ◽  
Hematopoietic Stem ◽  
Cell Dose

Abstract CD34+ cell dose calculations for hematopoietic stem cell transplantation (HSCT) are usually based on actual body weight (ABW). We have shown that ideal body weight (IBW) provides a better basis for this in a small population of patients with hematologic malignancies (Ali et al. Bone Marrow Transplant2003;31:861–4). However, a concern has been raised that this may not be applicable in myeloma because of underestimation of IBW as a result of disease-related height loss (Maclean et al. Bone Marrow Transplant2007;40:665–9). We studied this relationship further in 514 myeloma autografts conditioned with 140 or 200 mg/m2 melphalan. The CD34+ cell doses (106/kg) by IBW and ABW were 1.37–39.36 (median 6.03) and 1.15–29.67 (median 4.84) respectively. The difference between ABW and IBW was −25 to +124% (median +26%). The analysis was performed for the entire group as well as after excluding outliers (engraftment before 8 or after 16 days). As Table 1 shows, IBW-based cell doses correlated better with engraftment than ABW-based (higher r2 and F): Table 1: Correlation between the CD34+ cell dose by IBW or ABW and various engraftment endpoints IBW ABW Engraftment endpoint(109/L) r2 F P r2 F P All patients Neutrophils 0.5 0.83 2453 &lt;0.001 0.82 2301 &lt;0.001 Neutrophils 1.0 0.78 1818 &lt;0.001 0.77 1738 &lt;0.001 Platelets 20 0.54 581 &lt;0.001 0.53 569 &lt;0.001 Platelets 50 0.57 610 &lt;0.001 0.55 584 &lt;0.001 Selected (8–16 days) Neutrophils 0.5 (n=497) 0.85 2715 &lt;0.001 0.84 2523 &lt;0.001 Neutrophils 1.0(n=468) 0.85 2617 &lt;0.001 0.84 2462 &lt;0.001 Platelets 20(n=372) 0.85 2215 &lt;0.001 0.85 2027 &lt;0.001 Platelets 50(n=214) 0.85 1197 &lt;0.001 0.84 1078 &lt;0.001 As Table 2 shows, CD34+ cell doses based on IBW as well as ABW significantly affected engraftment when analyzed separately as continuous variables. However, when analyzed together, only the dose based upon IBW retained significance: IBW ABW Engraftment endpoint (109/L) Univariate Multivariate Univariate Multivariate All patients ANC 0.5 1.0471 (P&lt;0.0001) 1.0372 (P=0.18) 1.0591(P&lt;0.0001) 1.0131 (P=0.71) ANC 1.0 1.0532 (P&lt;0.0001) 1.0753 (P=0.008) 1.0606 (P&lt;0.0001) 0.9720 (P=0.42) PIT 20 1.0315 (P=0.0003) 1.0643 (P=0.019) 1.0319 (P=0.003) 0.9603 (P=0.22) PLT 50 1.0436(P&lt;0.0001) 1.0889 (P=0.0006) 1.0422(P=0.0001) 0.9464 (P=0.075) Selected (8–1 6 days) ANC 0.5 1.0627 (P&lt;0.0001) 1.0478 (P=0.076) 1.0793(P&lt;0.0001) 1.0198 (P=0.57) ANC 1.0 1.0687(P&lt;0.0001) 1.0785 (P=0.006) 1.0826(P&lt;0.0001) 0.9874(P=0.73) PIT 20 1.0448 (P&lt;0.0001) 1.0453 (P=0.13) 1.0538(P&lt;0.0001) 0.9993(P=0.99) PLT 50 1.0483(P&lt;0.0001) 1.0684(P=0.051) 1.0535(P=0.0004) 0.9746 (P=0.56) Table 2: Relationship between engraftment and the CD34+ cell dose analyzed as a continuous variable (risk ratio and P value) This observation is important in practice to avoid subjecting a patient to additional mobilization and apheresis procedures if the target cell dose has been met based on IBW. With increasing obesity (half the patients were &gt;25% overweight), accounting for the correct weight is an important practical consideration. Infusion of an appropriate number of cells also allows for extra cells to be retained for possible future use. In this group, if every patient’s height was underestimated by 1 inch (i.e. was increased by 1 inch for the purpose of calculations – assuming an element of kyphosis), IBW of men would have increased by 2.4–6.0% (median 3.2%) and IBW of women by 9.3–17.6% (median 12.4%). This suggests that implications of a height difference for calculating IBW in men are minimal but could be significant in women. We conclude that a CD34+ cell dose based on IBW is a better predictor of engraftment speed than one based on ABW, and IBW should be used as the basis for cell dose calculations in autologous HSCT. Any height loss, especially in myeloma patients, should be taken into account while calculating IBW for this purpose.

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