Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter to the Editor
  • Published:

Pharmacokinetics of melphalan in myeloma patients undergoing an autograft

Bone Marrow Transplantation volume 40, pages 707–708 (2007)Cite this article

We read with interest the recent publication by Grazziutti et al.1 on the incidence and risk factors of severe oral mucositis in myeloma patients undergoing melphalan-based stem cell transplantation. In that study, a standard melphalan dose of 200 mg/m2 was given to the majority of patients (n=350), but a small number received a lower dose of 140 mg/m2, due to renal impairment (n=31). In the calculations of melphalan dose, actual body weight was used for patients weighing <60 kg and a calculated body weight was used for patients weighing ⩾60 kg. The authors note that this method for dose determination resulted in wide variations in mg/kg melphalan dose (range: 2.4–6.2 mg/kg). High mg/kg melphalan dose and high serum creatinine concentration were both predictors of severe oral mucositis using multiple logistic regression analysis. Both of these factors may therefore be associated with high exposure to melphalan, but a pharmacokinetic analysis was not performed in this study. The authors note the requirement for further studies to understand better the interpatient variability in melphalan exposure and toxicity.

In a multi-institutional trial, we are currently undertaking such a study, researching the pharmacokinetics and pharmacodynamics of melphalan in myeloma patients receiving an autograft. To date, we have recruited 51 patients aged 38–73 years into our trial. A single melphalan dose of 200 mg/m2 was administered to 29 patients, while the remaining 22 patients received lower doses (range: 115–193 mg/m2) due to renal impairment or obesity. The dose was administered as an intravenous infusion over a median of 34 min. Our previously published high-performance liquid chromatographic method2 was used to measure melphalan concentrations in 12 blood samples that were collected at 5, 10, 20, 30, 40 and 50 min and at 1, 2, 3, 4 and 8 h after the infusion end. Melphalan pharmacokinetic parameters, including clearance and area under the concentration versus time curve (AUC0−∞) were then determined using the Kinetica software (Innaphase, Philadelphia, PA, USA). Patient clinical data, including weight and estimated glomerular filtration rate (eGFR), were tested for correlation with melphalan clearance. eGFR was estimated from plasma creatinine concentration, patient age and gender using the abbreviated MDRD equation3 as follows:

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

References

  1. Grazziutti ML, Dong L, Miceli MH, Krishna SG, Kiwan E, Syed N et al. Oral mucositis in myeloma patients undergoing melphalan-based stem cell transplantation: incidence, risk factors and a severity predictive model. Bone Marrow Transplant 2006; 38: 501–506.

    Article  CAS  Google Scholar 

  2. Nath CE, Shaw PJ, Montgomery K, Earl JW . Melphalan pharmacokinetics in children with malignant disease: influence of body weight, renal function, carboplatin therapy and total body irradiation. Br J Clin Pharmacol 2004; 59: 314–324.

    Article  Google Scholar 

  3. Levey AS, Greene T, Kusek JW, Beck GJ . A simplified equation to predict glomerular filtration rate from serum creatinine. J Am Soc Nephrol 2000; 11: 155A.

    Google Scholar 

  4. Ploin DY, Tranchard B, Guastalla JP, Rebattu P, Chauvin F, Clavel M et al. Pharmacokinetically guided dosing for intravenous melphalan: a pilot study in patients with advanced ovarian adenocarcinoma. Eur J Cancer 1992; 28: 1311–1315.

    Article  Google Scholar 

  5. Vassal G, Tranchard B, Valteau-Couanet D, Mahe C, Couanet D, Schoeppfer C et al. Pharmacodynamics of tandem high-dose melphalan with peripheral blood stem cell transplantation in children with neuroblastoma and medulloblastoma. Bone Marrow Transplant 2001; 27: 471–477.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

CE Nath is supported by the Leukaemia Research Support Fund of The Children's Hospital Westmead, and by NH and MRC Project Grant 396702. L Zeng is also supported by NH and MRC Project Grant 396702. We thank the patients who are taking part in this study, the specialists who treat the patients and the nurses who collect the blood samples for melphalan concentration analysis.

Author information

Authors and Affiliations

  1. Department of Biochemistry, The Children's Hospital at Westmead, Westmead, New South Wales, Australia

    C E Nath & L Zeng

  2. Department of Oncology, The Children's Hospital at Westmead, Westmead, New South Wales, Australia

    C E Nath & P J Shaw

  3. Department of Paediatrics and Child Health, University of Sydney, Concord Hospital, Concord, New South Wales, Australia

    P J Shaw

  4. Department of Haematology, Concord Hospital, Concord, New South Wales, Australia

    J Trotman

Authors
  1. C E Nath
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P J Shaw
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Trotman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C E Nath.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nath, C., Shaw, P., Trotman, J. et al. Pharmacokinetics of melphalan in myeloma patients undergoing an autograft. Bone Marrow Transplant 40, 707–708 (2007). https://doi.org/10.1038/sj.bmt.1705797

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705797

This article is cited by

Search

Advanced search

Quick links