Pharmacodynamics of tandem high-dose melphalan with peripheral blood stem cell transplantation in children with neuroblastoma and medulloblastoma.

Abstract:

:Repeated high-dose (HD) chemotherapy with peripheral blood stem cell (PBSC) transplantation is a new modality aimed at increasing both the dose and its intensity in the treatment of chemosensitive tumours. The aim of this study was to evaluate the tolerance, pharmacokinetics (PK) and pharmacodynamics (PD) of HD single-agent melphalan administered over two consecutive courses (C1 and C2) in children. Twenty-one patients (10 girls) with a median age of 4.1 years (range 8 months-14 years) were entered into this study. Five had metastatic neuroblastoma (NB) and 16 a cerebral primitive neuroectodermal tumour (PNET). Melphalan was given at a dose of 100 mg/m(2) every 21 days. PBSCs were infused at a median number of 2.98 x 10(6) CD34(+) cells/kg. Forty courses, ie 21 C1 and 19 C2, were administered. Both courses were well tolerated. The median duration of ANC < 500/microl was 7 and 6 days after C1 and C2, respectively. Platelet recovery (not mandatory to continue the HD strategy) was achieved in 52% of courses. GI toxicity was mild to moderate. The melphalan AUC ranged from 177 to 475 microg small middle dotmin/ml (no difference between C1 and C2). Prolonged neutropenia was associated with a young age (P < 0.001) and a low amount of CFU-GM (P = 0.002). A long time to platelet recovery was associated with a high AUC (P = 0.004) and a young age (P = 0.02). Grade 1 or 2 GI toxicity was associated with a high AUC (P = 0.015). Partial remission was observed in 11/14 patients with measurable cerebral PNET. In conclusion, tandem HD melphalan is feasible and safe in children, and achieved a high response rate in cerebral PNET. The observed PK-PD relationships may help us design PK-guided outpatient treatment.

journal_name

Bone Marrow Transplant

authors

Vassal G,Tranchand B,Valteau-Couanet D,Mahé C,Couanet D,Schoeppfer C,Grill J,Kalifa C,Hill C,Ardiet C,Hartmann O

doi

10.1038/sj.bmt.1702806

subject

Has Abstract

pub_date

2001-03-01 00:00:00

pages

471-7

issue

5

eissn

0268-3369

issn

1476-5365

journal_volume

27

pub_type

临床试验,杂志文章
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    pub_type: 杂志文章

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    更新日期:2000-08-01 00:00:00

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    pub_type: 杂志文章

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    更新日期:2017-04-01 00:00:00

  • Increased incidence of acute graft-versus-host disease with the continuous infusion of cyclosporine A compared to twice-daily infusion.

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    pub_type: 杂志文章

    doi:10.1038/sj.bmt.1704374

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    更新日期:2004-03-01 00:00:00

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    pub_type: 杂志文章

    doi:10.1038/sj.bmt.1702726

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    更新日期:2001-01-01 00:00:00

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    更新日期:1997-07-01 00:00:00

  • Allogeneic hematopoietic cell transplantation outcomes for children with B-precursor acute lymphoblastic leukemia and early or late BM relapse.

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    pub_type: 杂志文章

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    更新日期:2011-07-01 00:00:00

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    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

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    authors: Wallace G,Khandelwal P,Myers KC,Perentesis EMR,Lane A,Teusink-Cross A,Smiley K,Davies SM,Jodele S

    更新日期:2021-01-08 00:00:00

  • Non-radiotherapy conditioning with stem cell transplantation from alternative donors in children with refractory severe aplastic anemia.

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    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/sj.bmt.1704792

    authors: Urban C,Benesch M,Sykora KW,Schwinger W,Lackner H

    更新日期:2005-03-01 00:00:00

  • Bone marrow graft as a source of allogeneic hematopoietic stem cells in patients undergoing a reduced intensity conditioning regimen.

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    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/bmt.2014.193

    authors: Gomez E,Duléry R,Langlois C,Coiteux V,Terriou L,Magro L,Gauthier J,de Berranger E,Duhamel A,Yakoub-Agha I

    更新日期:2014-12-01 00:00:00

  • Upfront stem cell transplantation for newly diagnosed multiple myeloma with del(17p) and t(4;14): a study from the CMWP-EBMT.

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    pub_type: 杂志文章

    doi:10.1038/s41409-020-01007-w

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  • Tacrolimus pharmacokinetics in BMT patients.

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    journal_title:Bone marrow transplantation

    pub_type: 临床试验,杂志文章,随机对照试验

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    更新日期:1998-01-01 00:00:00

  • Juvenile myelomonocytic leukemia: analyses of treatment results in the EORTC Children's Leukemia Cooperative Group (CLCG).

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    journal_title:Bone marrow transplantation

    pub_type: 杂志文章,多中心研究

    doi:

    authors: Lutz P,Zix-Kieffer I,Souillet G,Bertrand Y,Dhooge C,Rubie C,Mazingue F,Marguerite F,Machinaud-Lacroix F,Rialland X,Plouvier E,Behar C,Vilmer E,Philippe N,Otten J

    更新日期:1996-12-01 00:00:00

  • Turkish Transplant Registry: a comparative analysis of national activity with the EBMT European Activity Survey.

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    pub_type: 杂志文章,评审

    doi:10.1038/bmt.2008.144

    authors: Arat M,Arpaci F,Ertem M,Gürman G,Turkish Transplant Registry.

    更新日期:2008-08-01 00:00:00

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    pub_type: 杂志文章

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    更新日期:2005-11-01 00:00:00

  • The clinical diagnosis of acute graft-versus-host disease: a diversity of views amongst marrow transplant centers.

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    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:

    authors: Atkinson K,Horowitz MM,Biggs JC,Gale RP,Rimm AA,Bortin MM

    更新日期:1988-01-01 00:00:00

  • Thrombotic microangiopathy following allogeneic bone marrow transplantation is associated with intensive graft-versus-host disease prophylaxis.

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    doi:10.1038/sj.bmt.1701359

    authors: Paquette RL,Tran L,Landaw EM

    更新日期:1998-08-01 00:00:00

  • Secondary myelodysplastic syndrome following bone marrow transplantation: report of two cases.

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    pub_type: 杂志文章

    doi:

    authors: Chan T,Juneja S,Wolf M,Januszewicz E,Cooper I

    更新日期:1994-02-01 00:00:00

  • Kaposi's sarcoma following allogeneic bone marrow transplantation.

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    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:

    authors: Helg C,Adatto M,Salomon D,Roux E,Miralbell R,Chapuis B,Saurat JH

    更新日期:1994-12-01 00:00:00

  • Systemic candidiasis with candida vasculitis due to Candida kruzei in a patient with acute myeloid leukaemia.

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    pub_type: 杂志文章

    doi:10.1038/sj.bmt.1701539

    authors: Gregory RK,Powles RL,Treleaven JG,Smith ML,Mortimer PS,Wotherspoon A,Riley U

    更新日期:1999-01-01 00:00:00

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    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/sj.bmt.1701502

    authors: Schulte C,Reinhardt W,Beelen D,Mann K,Schaefer U

    更新日期:1998-12-01 00:00:00

  • Reduced-intensity allogeneic stem cell transplantation for patients aged 50 years or older with B-cell ALL in remission: a retrospective study by the Adult ALL Working Group of the Japan Society for Hematopoietic Cell Transplantation.

    abstract::We retrospectively assessed the outcome and pretransplantation predictors of the outcome in 118 patients aged ≥ 50 years who received fludarabine-containing reduced-intensity allo-SCT (RIST) for B-cell ALL in the first or second CR. Eighty patients received transplants from unrelated donors. Seventy-eight patients wer...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/bmt.2013.140

    authors: Kanamori H,Mizuta S,Kako S,Kato H,Nishiwaki S,Imai K,Shigematsu A,Nakamae H,Tanaka M,Ikegame K,Yujiri T,Fukuda T,Minagawa K,Eto T,Nagamura-Inoue T,Morishima Y,Suzuki R,Sakamaki H,Tanaka J

    更新日期:2013-11-01 00:00:00

  • Engraftment syndrome: a common cause for rash and fever following autologous hematopoietic stem cell transplantation for multiple sclerosis.

    abstract::Autologous hematopoietic stem cell transplantation (HSCT) is currently being evaluated as a therapy for patients with progressive multiple sclerosis (MS) at risk of debilitating neurological impairment. While preliminary results from a few studies have been reported, little is known about toxicities or outcome of HSCT...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/sj.bmt.1703324

    authors: Oyama Y,Cohen B,Traynor A,Brush M,Rodriguez J,Burt RK

    更新日期:2002-01-01 00:00:00

  • Effects of cryopreservation on subsets of fetal liver cells.

    abstract::Human fetal livers from 6 to 13 weeks postconception were analysed before and after cryopreservation. The percentages of cell subsets, detected by MoAbs, did not change significantly after cryopreservation. Compared with BM, fetal liver contained significantly smaller subsets of cells identified by MoAbs, with two exc...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:

    authors: Ek S,Ringdén O,Markling L,Dahlberg N,Pschera H,Seiger A,Sundström E,Westgren M

    更新日期:1993-05-01 00:00:00

  • Rapid helper T-cell recovery above 200 x 10 6/l at 3 months correlates to successful transplant outcomes after allogeneic stem cell transplantation.

    abstract::The current study evaluates the role of quantitative measurement of peripheral lymphocyte subsets, especially CD4+ helper T-cell recovery, in predicting transplant outcomes including overall survival (OS) and non-relapse mortality (NRM) after allogeneic stem cell transplantation. A total of 69 allogeneic recipients we...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/sj.bmt.1705381

    authors: Kim DH,Sohn SK,Won DI,Lee NY,Suh JS,Lee KB

    更新日期:2006-06-01 00:00:00

  • GI complications in pediatric patients post-BMT.

    abstract::This retrospective study comprehensively examined hepatic and gastrointestinal complications post-bone marrow transplant (BMT) in a heterogeneous group of 132 pediatric patients that underwent 142 transplants. Hyperbilirubinemia occurred in 28% of this population with clinically evident jaundice in 16%. Acute graft-ve...

    journal_title:Bone marrow transplantation

    pub_type: 杂志文章

    doi:10.1038/sj.bmt.1705004

    authors: Barker CC,Anderson RA,Sauve RS,Butzner JD

    更新日期:2005-07-01 00:00:00