Janel Long-Boyle, PharmD

Professor of Clinical Pharmacy

Department of Clinical Pharmacy

Elisabeth Fall

[email protected]

Phone: +1 415 640-1569

490 Illinois Street, Rm 33E

UCSF Box 0613

San Francisco, CA 94158

United States

Links

UCSF Profiles

Affiliations

What I do

I am a translational scientist with research interests that include pediatric cancer therapeutics, pharmacokinetics, pharmacodynamics, pharmacogenomics, and clinical trial design. The majority of my research is focused around the chemotherapeutic and immunosuppressive agents used in the conditioning regimens of pediatric hematopoietic cell transplantation (HCT). Specifically, I am interested in how patient specific covariates such as age, renal function, or genetic variants involved in drug metabolism or distribution may influence drug clearance in the pediatric HCT population.

Departmental research area

clinical research

My research expertise

pharmacokinetics, pharmacodynamics, Pediatric Pharmacology, pediatric hematology, Oncology, bone marrow transplantation

Clinical expertise

hematology, Oncology, bone marrow transplantation

Professional background

Degrees

PhD, Experimental and Clinical Pharmacology, University of Minnesota, 2009

PharmD, University of Minnesota, 2006

BS, Biochemistry, University of Minnesota, 2000

Licensure and certifications

Licentiate in Pharmacy, California State Board of Pharmacy, 2010

Licentiate in Pharmacy, Minnesota, 2006

Biography

Dr. Boyle is a translational scientist with research interests that include pediatric cancer therapeutics, pharmacokinetics, pharmacodynamics, pharmacogenomics, and clinical trial design. The majority of her research resides within the complex setting of hematopoietic cell transplantation (HCT) and is focused around chemotherapeutic and immunosuppressive agents used in the preparative regimens of pediatric HCT. Specifically, Dr. Boyle studies how covariates such as age, renal function, or genetic variants involved in drug metabolism or distribution may influence drug clearance in the pediatric HCT population.

Research keywords

Oncology
Pharmacokinetics-Pharmacodynamics
Hematopoietic Cell Transplantation
Hematology
Pediatric Pharmacology
Mycophenolic Acid
Chimerism
Tandem Mass Spectrometry
Adenine Nucleotides
Arabinonucleosides
Hematopoietic Stem Cell Transplantation
Immunosuppressive Agents
Patient-Specific Modeling
Metabolic Diseases
Transplantation Conditioning
Busulfan
Biological Models
Melphalan
Vidarabine
Antineoplastic Agents, Alkylating

1.	UCSF Gary Rifkind Research Award for Junior Faculty, UCSF School of Pharmacy, 2012
2.	Early Career Award, Thrasher Research Fund, 2010-2012

Publications

Huang L, Winger BA, Cheah V, Gingrich D, Marzan F, Lu Y, Cooper JC, Aweeka F, Long-Boyle J. Quantification of N, N' N"-triethylenethiophosphoramide, N, N"-triethylenephosphoramide, cyclophosphamide, and 4-hydroxy-cyclophosphamide in microvolume human plasma to support neonatal and pediatric drug studies. J Chromatogr Open. 2022 Nov; 2.

Mike JK, Wu KY, White Y, Pathipati P, Ndjamen B, Hutchings RS, Losser C, Vento C, Arellano K, Vanhatalo O, Ostrin S, Windsor C, Ha J, Alhassen Z, Goudy BD, Vali P, Lakshminrusimha S, Gobburu JVS, Long-Boyle J, Chen P, Wu YW, Fineman JR, Ferriero DM, Maltepe E. Defining Longer-Term Outcomes in an Ovine Model of Moderate Perinatal Hypoxia-Ischemia. Dev Neurosci. 2022; 44(4-5):277-294.

Li S, Dvorak CC, Lu Y, Chan D, Gobburu JVS, Long-Boyle J, Apsel Winger B. Population Pharmacokinetics of Melphalan for Pediatric Patients Undergoing Hematopoietic Cell Transplantation. J Clin Pharmacol. 2022 07; 62(7):873-882.

Bognàr T, Bartelink IH, Egberts TCG, Rademaker CMA, Versluys AB, Slatter MA, Kletzel M, Nath CE, Cuvelier GDE, Savic RM, Dvorak C, Long-Boyle JR, Cowan MJ, Bittencourt H, Bredius RGM, Güngör T, Shaw PJ, Ansari M, Hassan M, Krajinovic M, Hempel G, Marktel S, Chiesa R, Théoret Y, Lund T, Orchard PJ, Wynn RF, Boelens JJ, Lalmohamed A. Association Between the Magnitude of Intravenous Busulfan Exposure and Development of Hepatic Veno-Occlusive Disease in Children and Young Adults Undergoing Myeloablative Allogeneic Hematopoietic Cell Transplantation. Transplant Cell Ther. 2022 04; 28(4):196-202.

Brooks JT, Keizer RJ, Long-Boyle JR, Kharbanda S, Dvorak CC, Friend BD. Population Pharmacokinetic Model Development of Tacrolimus in Pediatric and Young Adult Patients Undergoing Hematopoietic Cell Transplantation. Front Pharmacol. 2021; 12:750672.

Takahashi T, Illamola SM, Jennissen CA, Long SE, Lund TC, Orchard PJ, Gupta AO, Long-Boyle JR. Busulfan dose Recommendation in Inherited Metabolic Disorders: Population Pharmacokinetic Analysis. Transplant Cell Ther. 2022 02; 28(2):104.e1-104.e7.

Bankova AK, Pang WW, Velasco BJ, Long-Boyle JR, Shizuru JA. 5-Azacytidine depletes HSCs and synergizes with an anti-CD117 antibody to augment donor engraftment in immunocompetent mice. Blood Adv. 2021 10 12; 5(19):3900-3912.

Apsel Winger B, Long SE, Brooks J, Gupta AO, Dvorak CC, Long-Boyle JR. A Guidance for Concomitant Drug Reconciliation Prior to Allogeneic Hematopoietic Cell Transplantation in Children and Young Adults. Front Pediatr. 2021; 9:713091.

Higham CS, Collins G, Shimano KA, Melton A, Kharbanda S, Winestone LE, Huang JN, Dara J, Long-Boyle JR, Dvorak CC. Transplant-associated thrombotic microangiopathy in pediatric patients: pre-HSCT risk stratification and prophylaxis. Blood Adv. 2021 04 27; 5(8):2106-2114.

Apsel Winger B, Shukla P, Kharbanda S, Keizer RJ, Goswami S, Cowan MJ, Dvorak CC, Long-Boyle J. The Relationship Between Busulfan Exposure and Achievement of Sustained Donor Myeloid Chimerism in Patients with Non-Malignant Disorders. Transplant Cell Ther. 2021 03; 27(3):258.e1-258.e6.

Ramsey LB, Ong HH, Schildcrout JS, Shi Y, Tang LA, Hicks JK, El Rouby N, Cavallari LH, Tuteja S, Aquilante CL, Beitelshees AL, Lemkin DL, Blake KV, Williams H, Cimino JJ, Davis BH, Limdi NA, Empey PE, Horvat CM, Kao DP, Lipori GP, Rosenman MB, Skaar TC, Teal E, Winterstein AG, Owusu Obeng A, Salyakina D, Gupta A, Gruber J, McCafferty-Fernandez J, Bishop JR, Rivers Z, Benner A, Tamraz B, Long-Boyle J, Peterson JF, Van Driest SL, IGNITE Pharmacogenetics Working Group. Prescribing Prevalence of Medications With Potential Genotype-Guided Dosing in Pediatric Patients. JAMA Netw Open. 2020 12 01; 3(12):e2029411.

Shukla P, Dvorak CC, Long-Boyle J, Kharbanda S. Lower Exposure to Busulfan Allows for Stable Engraftment of Donor Hematopoietic Stem Cells in Children with Mucopolysaccharidosis Type I: A Case Report of Four Patients. Int J Mol Sci. 2020 Aug 06; 21(16).

Shukla P, Goswami S, Keizer RJ, Winger BA, Kharbanda S, Dvorak CC, Long-Boyle J. Assessment of a Model-Informed Precision Dosing Platform Use in Routine Clinical Care for Personalized Busulfan Therapy in the Pediatric Hematopoietic Cell Transplantation (HCT) Population. Front Pharmacol. 2020; 11:888.

Contreras CF, Long-Boyle JR, Shimano KA, Melton A, Kharbanda S, Dara J, Higham C, Huang JN, Cowan MJ, Dvorak CC. Reduced Toxicity Conditioning for Nonmalignant Hematopoietic Cell Transplants. Biol Blood Marrow Transplant. 2020 09; 26(9):1646-1654.

Wang H, Long-Boyle J, Winger BA, Nicolaides T, Mueller S, Prados M, Ivaturi V. Population Pharmacokinetics of Vemurafenib in Children With Recurrent/Refractory BRAF Gene V600E-Mutant Astrocytomas. J Clin Pharmacol. 2020 09; 60(9):1209-1219.

Nicolaides T, Nazemi KJ, Crawford J, Kilburn L, Minturn J, Gajjar A, Gauvain K, Leary S, Dhall G, Aboian M, Robinson G, Long-Boyle J, Wang H, Molinaro AM, Mueller S, Prados M. Phase I study of vemurafenib in children with recurrent or progressive BRAFV600E mutant brain tumors: Pacific Pediatric Neuro-Oncology Consortium study (PNOC-002). Oncotarget. 2020 May 26; 11(21):1942-1952.

Mamcarz E, Zhou S, Lockey T, Abdelsamed H, Cross SJ, Kang G, Ma Z, Condori J, Dowdy J, Triplett B, Li C, Maron G, Aldave Becerra JC, Church JA, Dokmeci E, Love JT, da Matta Ain AC, van der Watt H, Tang X, Janssen W, Ryu BY, De Ravin SS, Weiss MJ, Youngblood B, Long-Boyle JR, Gottschalk S, Meagher MM, Malech HL, Puck JM, Cowan MJ, Sorrentino BP. Lentiviral Gene Therapy Combined with Low-Dose Busulfan in Infants with SCID-X1. N Engl J Med. 2019 04 18; 380(16):1525-1534.

Wang H, Jones AK, Dvorak CC, Huang L, Orchard P, Ivaturi V, Long-Boyle J. Population Pharmacokinetics of Clofarabine as Part of Pretransplantation Conditioning in Pediatric Subjects before Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2019 08; 25(8):1603-1610.

Dvorak CC, Long-Boyle J, Dara J, Melton A, Shimano KA, Huang JN, Puck JM, Dorsey MJ, Facchino J, Chang CK, Cowan MJ. Low Exposure Busulfan Conditioning to Achieve Sufficient Multilineage Chimerism in Patients with Severe Combined Immunodeficiency. Biol Blood Marrow Transplant. 2019 07; 25(7):1355-1362.

Huang L, Cheah V, Chan D, Marzan F, Dvorak CC, Aweeka FT, Long-Boyle J. Determination of melphalan in human plasma by UPLC-UV method. Cancer Chemother Pharmacol. 2019 05; 83(5):905-910.

Boehme J, Le Moan N, Kameny RJ, Loucks A, Johengen MJ, Lesneski AL, Gong W, Goudy BD, Davis T, Tanaka K, Davis A, He Y, Long-Boyle J, Ivaturi V, Gobburu JVS, Winger JA, Cary SP, Datar SA, Fineman JR, Krtolica A, Maltepe E. Correction: Preservation of myocardial contractility during acute hypoxia with OMX-CV, a novel oxygen delivery biotherapeutic. PLoS Biol. 2019 Jan; 17(1):e3000119.

Zakinova A, Long-Boyle JR, French D, Croci R, Wilson L, Phillips KA, Kroetz DL, Shin J, Tamraz B. A Practical First Step Using Needs Assessment and a Survey Approach to Implementing a Clinical Pharmacogenomics Consult Service. J Am Coll Clin Pharm. 2019 Jun; 2(3):214-221.

Boehme J, Le Moan N, Kameny RJ, Loucks A, Johengen MJ, Lesneski AL, Gong W, Goudy BD, Davis T, Tanaka K, Davis A, He Y, Long-Boyle J, Ivaturi V, Gobburu JVS, Winger JA, Cary SP, Datar SA, Fineman JR, Krtolica A, Maltepe E. Preservation of myocardial contractility during acute hypoxia with OMX-CV, a novel oxygen delivery biotherapeutic. PLoS Biol. 2018 10; 16(10):e2005924.

Czechowicz JA, Long-Boyle JR, Rosbe KW, Mathes EF, Frieden IJ, Shimano KA. Sirolimus for management of complex vascular anomalies - A proposed dosing regimen for very young infants. Int J Pediatr Otorhinolaryngol. 2018 Feb; 105:48-51.

Spiekerkoetter E, Sung YK, Sudheendra D, Scott V, Del Rosario P, Bill M, Haddad F, Long-Boyle J, Hedlin H, Zamanian RT. Randomised placebo-controlled safety and tolerability trial of FK506 (tacrolimus) for pulmonary arterial hypertension. Eur Respir J. 2017 09; 50(3).

Cowan MJ, Dvorak CC, Long-Boyle J. Opening Marrow Niches in Patients Undergoing Autologous Hematopoietic Stem Cell Gene Therapy. Hematol Oncol Clin North Am. 2017 10; 31(5):809-822.

Ivaturi V, Dvorak CC, Chan D, Liu T, Cowan MJ, Wahlstrom J, Stricherz M, Jennissen C, Orchard PJ, Tolar J, Pai SY, Huang L, Aweeka F, Long-Boyle J. Pharmacokinetics and Model-Based Dosing to Optimize Fludarabine Therapy in Pediatric Hematopoietic Cell Transplant Recipients. Biol Blood Marrow Transplant. 2017 Oct; 23(10):1701-1713.

Vo KT, Karski EE, Nasholm NM, Allen S, Hollinger F, Gustafson WC, Long-Boyle JR, Shiboski S, Matthay KK, DuBois SG. Phase 1 study of sirolimus in combination with oral cyclophosphamide and topotecan in children and young adults with relapsed and refractory solid tumors. Oncotarget. 2017 Apr 04; 8(14):23851-23861.

Bartelink IH, Lalmohamed A, Long-Boyle JR, Boelens JJ. Busulfan after HSCT in children and young adults - Authors' reply. Lancet Haematol. 2017 03; 4(3):e103-e104.

Bartelink IH, Lalmohamed A, van Reij EM, Dvorak CC, Savic RM, Zwaveling J, Bredius RG, Egberts AC, Bierings M, Kletzel M, Shaw PJ, Nath CE, Hempel G, Ansari M, Krajinovic M, Théorêt Y, Duval M, Keizer RJ, Bittencourt H, Hassan M, Güngör T, Wynn RF, Veys P, Cuvelier GD, Marktel S, Chiesa R, Cowan MJ, Slatter MA, Stricherz MK, Jennissen C, Long-Boyle JR, Boelens JJ. Association of busulfan exposure with survival and toxicity after haemopoietic cell transplantation in children and young adults: a multicentre, retrospective cohort analysis. Lancet Haematol. 2016 Nov; 3(11):e526-e536.

McCune JS, Bemer MJ, Long-Boyle J. Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics of Immunosuppressants in Allogeneic Hematopoietic Cell Transplantation: Part II. Clin Pharmacokinet. 2016 May; 55(5):551-93.

Sanghavi K, Wiseman A, Kirstein MN, Cao Q, Brundage R, Jensen K, Rogosheske J, Kurtzweil A, Long-Boyle J, Wagner J, Warlick ED, Brunstein CG, Weisdorf DJ, Jacobson PA. Personalized fludarabine dosing to reduce nonrelapse mortality in hematopoietic stem-cell transplant recipients receiving reduced intensity conditioning. Transl Res. 2016 09; 175:103-115.e4.

Spiekerkoetter E, Sung YK, Sudheendra D, Bill M, Aldred MA, van de Veerdonk MC, Vonk Noordegraaf A, Long-Boyle J, Dash R, Yang PC, Lawrie A, Swift AJ, Rabinovitch M, Zamanian RT. Low-Dose FK506 (Tacrolimus) in End-Stage Pulmonary Arterial Hypertension. Am J Respir Crit Care Med. 2015 Jul 15; 192(2):254-7.

Long-Boyle JR, Savic R, Yan S, Bartelink I, Musick L, French D, Law J, Horn B, Cowan MJ, Dvorak CC. Population pharmacokinetics of busulfan in pediatric and young adult patients undergoing hematopoietic cell transplant: a model-based dosing algorithm for personalized therapy and implementation into routine clinical use. Ther Drug Monit. 2015 Apr; 37(2):236-45.

Miyagi SJ, Long-Boyle JR. Predicting Pediatric Drug Disposition-Present and Future Directions of Pediatric Physiologically-Based Pharmacokinetics. Drug Metab Lett. 2015; 9(2):80-7.

Huang L, Lizak P, Dvorak CC, Aweeka F, Long-Boyle J. Simultaneous determination of fludarabine and clofarabine in human plasma by LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Jun 01; 960:194-9.

French D, Sujishi KK, Long-Boyle JR, Ritchie JC. Development and validation of a liquid chromatography-tandem mass spectrometry assay to quantify plasma busulfan. Ther Drug Monit. 2014 Apr; 36(2):169-74.

Griffith LM, Cowan MJ, Notarangelo LD, Kohn DB, Puck JM, Pai SY, Ballard B, Bauer SC, Bleesing JJ, Boyle M, Brower A, Buckley RH, van der Burg M, Burroughs LM, Candotti F, Cant AJ, Chatila T, Cunningham-Rundles C, Dinauer MC, Dvorak CC, Filipovich AH, Fleisher TA, Bobby Gaspar H, Gungor T, Haddad E, Hovermale E, Huang F, Hurley A, Hurley M, Iyengar S, Kang EM, Logan BR, Long-Boyle JR, Malech HL, McGhee SA, Modell F, Modell V, Ochs HD, O'Reilly RJ, Parkman R, Rawlings DJ, Routes JM, Shearer WT, Small TN, Smith H, Sullivan KE, Szabolcs P, Thrasher A, Torgerson TR, Veys P, Weinberg K, Zuniga-Pflucker JC, workshop participants. Primary Immune Deficiency Treatment Consortium (PIDTC) report. J Allergy Clin Immunol. 2014 Feb; 133(2):335-47.

Savic RM, Cowan MJ, Dvorak CC, Pai SY, Pereira L, Bartelink IH, Boelens JJ, Bredius RG, Wynn RF, Cuvelier GD, Shaw PJ, Slatter MA, Long-Boyle J. Effect of weight and maturation on busulfan clearance in infants and small children undergoing hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2013 Nov; 19(11):1608-14.

Huang L, Lizak P, Aweeka F, Long-Boyle J. Determination of intracellular fludarabine triphosphate in human peripheral blood mononuclear cells by LC-MS/MS. J Pharm Biomed Anal. 2013 Dec; 86:198-203.

Frymoyer A, Verotta D, Jacobson P, Long-Boyle J. Population pharmacokinetics of unbound mycophenolic acid in adult allogeneic haematopoietic cell transplantation: effect of pharmacogenetic factors. Br J Clin Pharmacol. 2013 Feb; 75(2):463-75.

Law J, Cowan MJ, Dvorak CC, Musick L, Long-Boyle JR, Baxter-Lowe LA, Horn B. Busulfan, fludarabine, and alemtuzumab as a reduced toxicity regimen for children with malignant and nonmalignant diseases improves engraftment and graft-versus-host disease without delaying immune reconstitution. Biol Blood Marrow Transplant. 2012 Nov; 18(11):1656-63.

Kim H, Long-Boyle J, Rydholm N, Orchard PJ, Tolar J, Smith AR, Jacobson P, Brundage R. Population pharmacokinetics of unbound mycophenolic acid in pediatric and young adult patients undergoing allogeneic hematopoietic cell transplantation. J Clin Pharmacol. 2012 Nov; 52(11):1665-75.

Long-Boyle J, Huang J, Rydholm N, Smith A, Orchard P, Tolar J, Jacobson P. Pharmacokinetics of clofarabine in patients with high-risk inherited metabolic disorders undergoing brain-sparing hematopoietic cell transplantation. J Clin Pharmacol. 2011 May; 51(5):679-86.

Long-Boyle JR, Green KG, Brunstein CG, Cao Q, Rogosheske J, Weisdorf DJ, Miller JS, Wagner JE, McGlave PB, Jacobson PA. High fludarabine exposure and relationship with treatment-related mortality after nonmyeloablative hematopoietic cell transplantation. Bone Marrow Transplant. 2011 Jan; 46(1):20-6.

Jacobson P, El-Massah SF, Rogosheske J, Kerr A, Long-Boyle J, DeFor T, Jennissen C, Brunstein C, Wagner J, Tomblyn M, Weisdorf D. Comparison of two mycophenolate mofetil dosing regimens after hematopoietic cell transplantation. Bone Marrow Transplant. 2009 Jul; 44(2):113-20.

Jacobson P, Long J, Rogosheske J, Brunstein C, Weisdorf D. High unbound mycophenolic acid concentrations in a hematopoietic cell transplantation patient with sepsis and renal and hepatic dysfunction. Biol Blood Marrow Transplant. 2005 Dec; 11(12):977-8.

Jacobson P, Rogosheske J, Barker JN, Green K, Ng J, Weisdorf D, Tan Y, Long J, Remmel R, Sawchuk R, McGlave P. Relationship of mycophenolic acid exposure to clinical outcome after hematopoietic cell transplantation. Clin Pharmacol Ther. 2005 Nov; 78(5):486-500.

Slungaard A, Fernandez JA, Griffin JH, Key NS, Long JR, Piegors DJ, Lentz SR. Platelet factor 4 enhances generation of activated protein C in vitro and in vivo. Blood. 2003 Jul 01; 102(1):146-51.