Delayed neutrophil engraftment in cord blood transplantation with intensive administration of mycophenolate mofetil for GVHD prophylaxis

Okamura, Atsuo; Shimoyama, Manabu; Ishii, Shin‐ichi; Wakahashi, Kanako; Asada, Noboru; Kawano, Hiroyuki; Kawamori, Yuriko; Nishikawa, Sayaka; Minagawa, Kentaro; Katayama, Yoshio; Matsui, Toshimitsu

doi:10.1038/bmt.2010.59

Cited by 9 publications

(9 citation statements)

References 9 publications

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“…The SD was almost equivalent to a dose of 5 lg/kg per day in Japanese patients who weighed an average of 60 kg. Based on previous studies and the promising results of our MMF studies, almost all patients received SD treatment after May 2008 [2,3,[8][9][10][11]. G-CSF was administered at either a SD or HD daily by intravenous infusion from day ?1 until the patients' white blood cell counts reached [5.0 9 10 9 /L.…”

Section: Prophylactic Use Of G-csfmentioning

confidence: 99%

“…at a dose of 17.5 mg/kg (range 12.2-26.0 mg/kg, maximum 3,000 mg per day) or three times a day (t.i.d.) at a fixed dose of 1,000 mg (median 17.1 mg/kg, range 10.0-22.7 mg/kg, total 3,000 mg per day) [8,10]. Tacrolimus was administered at daily dose of 0.03 mg/kg by continuous intravenous infusion from day -1, and then converted to the oral formulation when tolerated.…”

Section: Gvhd Prophylaxismentioning

confidence: 99%

“…Recently, on the basis of pharmacokinetic/pharmacodynamic analyses, we proposed that MMF should be administered three times a day for GVHD prophylaxis in patients receiving PBSCT and BMT, while twice a day administration was recommended in patients receiving single-unit cord blood transplantation (s-CBT) because three times a day often causes delayed neutrophil engraftment [8][9][10]. These studies presented a particularly promising dosing of MMF that would guarantee prevention of graft failure as well as facilitate neutrophil engraftment in s-CBT [10,11].…”

Section: Introductionmentioning

confidence: 99%

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Successful neutrophil engraftment by reduced use of granulocyte colony-stimulating factor after allogeneic hematopoietic stem cell transplantation with mycophenolate mofetil for graft-versus-host disease prophylaxis

et al. 2011

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In allogeneic hematopoietic stem cell transplantation (allo-SCT), most physicians in Japan utilize granulocyte colony-stimulating factor (G-CSF) at a high dose (HD) of 300 μg/m(2) per day for filgrastim to promote faster neutrophil engraftment. However, the necessity of the HD has not been validated under graft-versus-host disease (GVHD) prophylaxis by mycophenolate mofetil (MMF), which can also be expected to facilitate engraftment. In a total of 51 patients, we compared the clinical outcomes between a standard dose (SD) fixed at 300 μg per day and a HD of G-CSF. While time to neutrophil engraftment was not different in the HD and SD groups in patients receiving cord blood transplantation (CBT, 20 vs. 17.5 days, P = 0.243) or bone marrow transplantation (BMT, 11 vs. 10 days, P = 0.227), there seemed to be an increased risk of developing acute GVHD in the HD group with CBT (20 vs. 0%, P = 0.073) and BMT (57 vs. 24%, P = 0.165). Progression-free survival of patients in the HD group was likely to be worse compared with that of the SD group with CBT (P = 0.099). In this study, the clinical benefits of a HD of G-CSF could not be documented, and we find that the use of G-CSF at a SD after allo-SCT with MMF should be prospectively evaluated.

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Section: Prophylactic Use Of G-csfmentioning

confidence: 99%

Section: Gvhd Prophylaxismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Successful neutrophil engraftment by reduced use of granulocyte colony-stimulating factor after allogeneic hematopoietic stem cell transplantation with mycophenolate mofetil for graft-versus-host disease prophylaxis

et al. 2011

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“…2a). As a single assessment point of C 2h , we picked up day 16 because it is about the date of engraftment and the initiation of acute GVHD after allo-SCT. Indeed, strong correlation between AUC 0-24h and day 16 C 2h was observed (r 2 = 0.641, p \ 0.0001), and again day 16 C 2h 2.5 lg/ml represented AUC 0-24h 30 lg h/ml (Fig.…”

Section: Correlation Between Auc 0-24h and C 2hmentioning

confidence: 99%

“…It is now well known that MMF does not cause mucositis and facilitates engraftment possibly attributed to its non-cytotoxicity, which avoids the major problems associated with MTX [7,13,15,16].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics-based optimal dose prediction of donor source-dependent response to mycophenolate mofetil in unrelated hematopoietic cell transplantation

et al. 2011

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Mycophenolate mofetil (MMF) has been widely used for prophylaxis against graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-SCT). However, no clear advantage over methotrexate has been reported, other than reduced incidence of mucositis. We speculated that the wide inter-individual variation of plasma mycophenolic acid (MPA) levels veiled the benefits of MMF. Data from 36 unrelated allogeneic bone marrow (allo-BMT) and cord blood transplantation (CBT) were analyzed retrospectively based on MPA area under the curve (AUC(0-24h)). In allo-BMT, high AUC(0-24h) (>30 μg h/ml) resulted in no incidence of grade II-IV acute/extensive chronic GVHD and tended to show higher overall and disease-free survival, lower relapse rates, and non-relapse mortality. In CBT, AUC(0-24h) less than 30 μg h/ml was sufficient for low incidence of acute/chronic GVHD and high survival. Strong correlation between AUC(0-24h) and C(2h), plasma MPA concentration at 2 h after administration was observed. Single point assessment of C(2h) was shown to provide a useful surrogate of AUC(0-24h) to predict GVHD incidence. The results of this study suggest that individualized MMF dosing in a donor source-dependent fashion may be important for maximizing the benefit of MMF in allo-SCT.

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Pharmacokinetics of intravenous mycophenolate mofetil in allogeneic hematopoietic stem cell-transplanted Japanese patients

Kurata

Yakushijin

Okamura

et al. 2018

Cancer Chemother Pharmacol

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Delayed neutrophil engraftment in cord blood transplantation with intensive administration of mycophenolate mofetil for GVHD prophylaxis

Cited by 9 publications

References 9 publications

Successful neutrophil engraftment by reduced use of granulocyte colony-stimulating factor after allogeneic hematopoietic stem cell transplantation with mycophenolate mofetil for graft-versus-host disease prophylaxis

Successful neutrophil engraftment by reduced use of granulocyte colony-stimulating factor after allogeneic hematopoietic stem cell transplantation with mycophenolate mofetil for graft-versus-host disease prophylaxis

Pharmacokinetics-based optimal dose prediction of donor source-dependent response to mycophenolate mofetil in unrelated hematopoietic cell transplantation

Pharmacokinetics of intravenous mycophenolate mofetil in allogeneic hematopoietic stem cell-transplanted Japanese patients

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