Cyclosporine A (CsA) 2-h concentrations vary between patients without correlation to graft-versus-host disease after allogeneic haematopoietic stem cell transplantation
TLDR
Interindividual variations in CsA uptake and metabolism may explain the wide variation of C2 levels without prediction for increased risk for severe aGVHD or infectious complication when C0 guided the CsSA dosing.Abstract:
Cyclosporine A (CsA) therapy based on 2-h concentrations (C2) after oral administration has demonstrated low acute rejection rates after solid organ transplantation We analysed the correlation between C2 and trough (C0) levels of oral CsA therapy in samples obtained twice in consecutive weeks from 58 patients during their first admission for allogeneic haematopoietic stem cell transplantation Also 8-h concentration curves were obtained from 23 patients The mean (range) CsA dose was 332 (167–763) and 255 (113–575) mg/day for patients with matched unrelated donor (MUD) and human leukocyte antigen identical sibling donor (Sib), respectively Median (range) C0 and C2 were 254 (145–332) and 898 (419–1466) ng/ml in MUD patients, and 130 (93–265) and 554 (196–988) ng/ml in Sib patients In MUD patients with either aGVHD grade <II or ⩾II, the median C2 were 915 (419–1466) and 890 (519–1399) ng/ml, respectively In Sib patients with aGVHD grade <II or grade ⩾II, the median C2 were 552 (404–718) and 539 (196–988) ng/ml, respectively The median C2 levels were comparable in patients with or without severe infections Interindividual variations in CsA uptake and metabolism may explain the wide variation of C2 levels without prediction for increased risk for severe aGVHD or infectious complication when C0 guided the CsA dosingread more
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Journal ArticleDOI
Stem cell transplantation
TL;DR: This book will help contemporary HSC transplanters to widen their knowledge and, hopefully, to improve their clinical results, and all the clinical sections, both on allogeneic and autologous HSC transplants, are upto-date and with no exceptions excellent.
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Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics of Immunosuppressants in Allogeneic Hematopoietic Cell Transplantation: Part II.
TL;DR: Future pharmacokinetic/dynamic research of postgraft immunosuppressants should include ‘–omics’-based tools: pharmacogenomics may be used to gain an improved understanding of the covariates influencing pharmacokinetics as well as proteomics and metabolomics as novel methods to elucidate pharmacodynamic responses.
Journal ArticleDOI
Assessment of the Cylex ImmuKnow cell function assay in pediatric heart transplant patients.
Joseph W. Rossano,Susan W. Denfield,Jeffrey J. Kim,Jack F. Price,John L. Jefferies,Jamie A. Decker,E. O'Brian Smith,Sarah K. Clunie,Jeffrey A. Towbin,William J. Dreyer +9 more
TL;DR: The CICFA is not predictive of AR or significant infections in pediatric heart transplant patients and cannot be recommended as part of the routine management of pediatric heart transplants patients.
Journal ArticleDOI
The use of pharmacokinetic models in paediatric onco-haematology: effects on clinical outcome through the examples of busulfan and cyclosporine.
TL;DR: Results of clinical outcome of previous studies performed to optimize busulfan and CsA therapy by controlling their pharmacokinetic variability by means of maximum a posteriori (MAP) Bayesian individualization of both drugs are presented.
Journal ArticleDOI
CsA exposure is associated with acute GVHD and relapse in children after SCT
Annemieke Willemze,Rogier R. Press,Arjan C. Lankester,R.M. Egeler,J. den Hartigh,J. M. J. J. Vossen +5 more
TL;DR: Monitoring CsA exposure early after HSCT and adjusting the Cs a dose to a predefined target trough level and AUC may provide a tool to influence GVHD/GVL balance.
References
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Journal ArticleDOI
Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors.
Glucksberg H,Rainer Storb,Alexander Fefer,C. D. Buckner,Paul E. Neiman,Clift Ra,Lerner Kg,Thomas Ed +7 more
TL;DR: The results show that despite histocompatibility matching and methotrexate therapy, GVHD remains a serious and often fatal complication of marrow transplantation.
Journal ArticleDOI
Chronic graft-versus-host syndrome in man: A long-term clinicopathologic study of 20 seattle patients
Howard M. Shulman,Keith M. Sullivan,Paul L. Weiden,George B. McDonald,Gary E. Striker,George E. Sale,Robert C. Hackman,Tsoi Ms,Rainer Storb,E. Donnall Thomas +9 more
TL;DR: Three patients had limited chronic GVHD with relatively favorable prognosis characterized by localized skin involvement and/or hepatic disease without chronic aggressive histology, but most patients, however, had extensive disease with a progressive course.
Journal ArticleDOI
HLA-DR typing by PCR amplification with sequence-specific primers (PCR-SSP) in 2 hours: an alternative to serological DR typing in clinical practice including donor-recipient matching in cadaveric transplantation.
Ole Olerup,Henrik Zetterquist +1 more
TL;DR: DR "low-resolution" typing by the PCR-SSP technique is ideally suited for analyzing small numbers of samples simultaneously and is an alternative to serological DR typing in routine clinical practice including donor-recipient matching in cadaveric transplantations.
Journal ArticleDOI
Methotrexate and Cyclosporine Compared with Cyclosporine Alone for Prophylaxis of Acute Graft versus Host Disease after Marrow Transplantation for Leukemia
Rainer Storb,H. Joachim Deeg,John Whitehead,Frederick R. Appelbaum,Patrick G. Beatty,William I. Bensinger,C. Dean Buckner,Reginald A. Clift,Kristine Doney,Vernon T. Farewell,J. D. Hansen,Roger Hill,Lawrence G. Lum,Paul J. Martin,Robert W. McGuffin,Jean E. Sanders,Patricia S. Stewart,Keith M. Sullivan,Robert P. Witherspoon,Gary Yee,E. Donnall Thomas +20 more
TL;DR: It is concluded that the combination of methotrexate and cyclosporine is superior to cyclOSporine alone in the prevention of acute graft versus host disease after marrow transplantation for leukemia, and that this therapy may have a beneficial effect on long-term survival.
Journal ArticleDOI
Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects
Peter A. McSweeney,Peter A. McSweeney,Peter A. McSweeney,Dietger Niederwieser,Dietger Niederwieser,Dietger Niederwieser,Judith A. Shizuru,Judith A. Shizuru,Judith A. Shizuru,Brenda M. Sandmaier,Brenda M. Sandmaier,Brenda M. Sandmaier,Arthur J. Molina,Arthur J. Molina,Arthur J. Molina,David G. Maloney,David G. Maloney,David G. Maloney,Thomas R. Chauncey,Thomas R. Chauncey,Thomas R. Chauncey,Ted Gooley,Ted Gooley,Ted Gooley,U Hegenbart,U Hegenbart,U Hegenbart,Richard A. Nash,Richard A. Nash,Richard A. Nash,Jerald P. Radich,Jerald P. Radich,Jerald P. Radich,John L. Wagner,John L. Wagner,John L. Wagner,Steven Minor,Steven Minor,Steven Minor,Frederick R. Appelbaum,Frederick R. Appelbaum,Frederick R. Appelbaum,William I. Bensinger,William I. Bensinger,William I. Bensinger,Eileen Bryant,Eileen Bryant,Eileen Bryant,Mary E.D. Flowers,Mary E.D. Flowers,Mary E.D. Flowers,George E. Georges,George E. Georges,George E. Georges,F. Carl Grumet,F. Carl Grumet,F. Carl Grumet,Hans-Peter Kiem,Hans-Peter Kiem,Hans-Peter Kiem,Beverly Torok-Storb,Beverly Torok-Storb,Beverly Torok-Storb,Cong Yu,Cong Yu,Cong Yu,Karl G. Blume,Karl G. Blume,Karl G. Blume,Rainer Storb,Rainer Storb,Rainer Storb +71 more
TL;DR: A novel allografting approach, based on the use of postgrafting immunosuppression to control graft rejection and GVHD, has dramatically reduced the acute toxicities of allogRAFTing.