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Melphalan pharmacokinetics and transplant related toxicity during autologous stem cell transplantation

Bone Marrow Transplantation volume 56, pages 7–8 (2021)Cite this article

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We read the recent article by Al Saleh et al., which comments on the timing of melphalan dosing during autologous stem cell transplantation (ASCT) for multiple myeloma with great interest [1]. This retrospective study compared the outcomes of outpatient ASCT in two cohorts of myeloma patients with similar baseline characteristics. Standard doses of melphalan was administered to patients either a median of 18.6 h (range 17.1–23.8) prior to stem cell infusion in the “day-1 cohort”, or with extra 1-day rest in the “day-2 cohort”. The primary outcomes were given as the time to neutrophil and platelet engraftment and treatment related toxicity, including fever and hospitalization requirement. The time to engraftment was defined as the time between stem cell infusion and platelet or neutrophil recovery. The authors reported a longer time to platelet recovery in the “day-1 cohort” [median 17 (16–17) vs 15 (15–16), p < 0.0001] and a similar time to neutrophil recovery between two cohorts [median 16 (15–16) for “day 1” vs 16 (15–16) for “day 2”, p = 0.025]. They also noticed a longer duration of hospital stay (median 7 vs 5 days, p = 0.003) and higher rates of fever in the “day-1 cohort” (69% vs 49%, p = 0.0002).

In our opinion, the reported differences in the engraftment kinetics between two cohorts are so minor that they cannot be translated into a clinical significance. The misinterpreted delay in engraftment in the “day-1 cohort” is probably due to the extra 1-day rest in the “day-2 cohort”, as well (i.e., the earlier the melphalan infusion, the earlier the bone marrow recovery). We suggest the authors to define the engraftment time starting from the day of melphalan administration, rather than stem cell infusion. Then, the stated significance between two cohorts should disappear. However, the longer time of hospitalization and higher rates of fever observed in the “day-1 cohort” require attention and cannot just be explained by a clinically insignificant delay in engraftment.

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References

  1. Al Saleh AS, Sidiqi MH, Lee J, Dispenzieri A, Muchtar E, Buadi FK, et al. Differences in engraftment with day-1 compared with day-2 melphalan prior to stem cell infusion in myeloma patients receiving autologous stem cell transplant. Bone Marrow Transplant. 2020. https://doi.org/10.1038/s41409-020-0916-3.

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Authors and Affiliations

  1. Hematology and Bone Marrow Transplantation Unit, Medicana International Ankara Hospital, Ankara, Turkey

    Ugur Sahin, Ender Soydan & Ayla Gokmen

  2. Department of Hematology, Faculty of Medicine, Ankara University, Ankara, Turkey

    Muhit Ozcan & Onder Arslan

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  1. Ugur Sahin
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Correspondence to Ugur Sahin.

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Sahin, U., Soydan, E., Gokmen, A. et al. Melphalan pharmacokinetics and transplant related toxicity during autologous stem cell transplantation. Bone Marrow Transplant 56, 7–8 (2021). https://doi.org/10.1038/s41409-020-01043-6

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