Personalized pharmacokinetic targeting with busulfan in allogeneic hematopoietic stem cell transplantation in infants with acute lymphoblastic leukemia

Individual busulfan (BU) dosing based on pharmacokinetic (PK) data is preferable for hematopoietic stem cell transplantation (HSCT) conditioning, but information on BU PK in infants is scarce. We report BU PK data on HSCT conditioning for infants with KMT2A -gene-rearrangement-positive acute lymphob...

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Bibliographic Details
Published in:International journal of hematology 2019-09, Vol.110 (3), p.355-363
Main Authors: Takachi, Takayuki, Arakawa, Yuki, Nakamura, Hiroyoshi, Watanabe, Tomoyuki, Aoki, Yuki, Ohshima, Junjiro, Takahashi, Yoshihiro, Hirayama, Masahiro, Miyamura, Takako, Sugita, Kanji, Koh, Katsuyoshi, Horibe, Keizo, Ishii, Eiichi, Mizutani, Shuki, Tomizawa, Daisuke
Format: Article
Language:English
Subjects:
Acute lymphoblastic leukemia
Allografts
Busulfan
Busulfan - administration & dosage
Busulfan - pharmacokinetics
Conditioning
Disease-Free Survival
Dosage
Female
Gene rearrangement
Graft-versus-host reaction
Hematology
Hematopoietic Stem Cell Transplantation
Hematopoietic stem cells
Humans
Infant
Infants
Intravenous administration
Leukemia
Lymphatic leukemia
Male
Medicine
Medicine & Public Health
MLL protein
Oncology
Original Article
Pharmacokinetics
Pharmacology
Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood
Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality
Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy
Sexually transmitted diseases
STD
Stem cell transplantation
Stem cells
Survival Rate
Toxicity
Transplantation
Transplantation Conditioning
Transplants & implants
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Summary:Individual busulfan (BU) dosing based on pharmacokinetic (PK) data is preferable for hematopoietic stem cell transplantation (HSCT) conditioning, but information on BU PK in infants is scarce. We report BU PK data on HSCT conditioning for infants with KMT2A -gene-rearrangement-positive acute lymphoblastic leukemia (MLL-r ALL). Infants showed wide variation in BU PK indices, such as clearance (CL) and volume of distribution ( V d ) value, which are distributed more widely among those who received oral, rather than intravenous (IV), BU. Because the steady state concentration ( C ss ) fluctuates readily in infants, dose re-adjustment based on PK at the initial administration was important even if the initial dose was determined by a PK test. HSCT can be performed safely within the C ss range of 600–900 ng/mL per dose, although it was difficult to fit within the therapeutic index of BU. The clinical outcome of engraftment, graft-versus-host disease, adverse events, including sinusoidal obstruction syndrome, and survival did not correlate with the BU PK data, which paradoxically suggests that remaining within this C ss range helped minimize transplant-related toxicities, while securing engraftment in infants with MLL-r ALL.
ISSN:0925-5710
1865-3774
DOI:10.1007/s12185-019-02684-0