1. Description of Tools pharmaceutical care in Acute Lymphoblastic Leukemia (Pharmacogenomics) Hospital Pediatric Experience Chilean Program Associated   with Antineoplastic Drugs (PINDA)  
Jorge Morales Vallespín
Pharmacy Chief
Hospital Dr. Luis Calvo Mackenna
Santiago, Chile

2. Summary Introduction Childhood Cancer Childhood Cancer in Chile
Experience of Clinical Pharmacy Service .
Pharmacogenomic and Cancer ALL.
Experience HLCM Treatmen and Use Pharmacogenomic TPMT ALL

3. Introduction Childhood Cancer
Rodriguez-Galindo, J Clin Onco. 2015

4. Introduction Childhood Cancer
Rodriguez-Galindo, J Clin Onco. 2015

5. Cancer Chilhood Distribution
Ribeiro, J Clin Onco Jan

6. Introduction Childhood Cancer
Rodriguez-Galindo, J Clin Onco. 2015

7. Summary Introduction Childhood Cancer Childhood Cancer in Chile
Experience of Clinical Pharmacy Service
Pharmacogenomic and Cancer ALL.
Experience HLCM Treatmen and Use Pharmacogenomic TPMT ALL

8. Childhood Cancer in Chile
Leukemia 70%, CNS tumors 17% and Lymphomas (13%)
520 new cases each year, 12/ pts<15 yrs.
5 years EFS for Children and Adolescents (protocols 88  92  96) :
ALL: 60 %  67 %  73 %
Overall: 73 %
Campbell M, Salgado C, Villarroel M, Becker A, Varas M, Silva P. On behalf of PINDA
Best Poster Award. SIOP Sao Paulo, Brasil.
Adult and Childhood Cancer Meeting. Oct 2004, Santiago, Chile

9. National Program for Antineoplastic Drugs for Children (PINDA)
Gubernamental program supported by the Chilean Ministry of health
Started in 1988
13 main centers and 7 satellite centers
Patients in the public system < 15 yrs: 75% of patients with cancer
Infectious Disease, Pathology, Phamacist/CP, Radiotherapy, Surgery and SCT
Campbell M, Salgado C, Villarroel M, Becker A, Varas M, Silva P. On behalf of PINDA
Best Poster Award. SIOP Sao Paulo, Brasil.

10. Oncology Pharmacist 7 Pharmacist IOP Other Hospitals 4 HLCM 1 HRT
1 HRRIO
1 HEGC
Other Hospitals
1 HCBV

11. Our Hospital Pediatric Hospital founded in 1942
201 physically Available beds
Number of discharges (2013): 16,462
National Pediatric Center of:
Hematopoietic Stem Cell Transplantation (1999, SJCRH)
Osteosarcoma HDMTX (12g/m2)
Retinoblastoma (50%)
Cardio-vascular surgery
Kidney and Liver transplantation
Teaching and research hospital based
25 % Pts with Ca of the Public System

12. Clinical Pharmacy Service
Hospital Units
ICU: Pediatric,CV, Neonatal
Oncology Service: in patients and ambulatory
Bone Marrow Transplant Service
Other Unit
Also in Clinical Rounds with the Infectious Disease
Acitivities
Checking of Chemo prescriptions/protocols hospitalized and ambulatory pts
Induction protocols checking in BMT
Pharmacovigilance and active reporting of ADR
PK and dose adjustment of FK, CsA, MMF, Vanco, AMK, and Vori.
HDMTX 5 g/m2 and 12 g/m2 PK and monitoring
Presentations, Education, Research
Drugs Protocols
Clinical Cases Discussion
Presentation in Clinical Meetings
Research: medication errors, Voriconazole, pharmacogenetics.
Education: National, International.

14. Some clinical pharmacy services in oncology
Pharmacokinetics of
antineoplastic drugs
Drugs interactions prevention detection and management
Drug information
Side effects prevention, detection and management
Antimicrobial drug monitoring and adjustment in treatment and prophylaxis
Chemotherapy reconciliation

15. Challenges Faced Clinical Training Programs
More experienced co-workers
Limited Resources: infrastructure, electronic medical records, expensive drugs, PK.
Drug availability
Too much patients and no too many pharmacist.
Traveling of patients

16. More close to the Patients
Medication reconciliation
HDMTX Intercourse targeting
MTX therapy support in ALL and OS pts.
Chemotherapy Drug interactions
Dose Adjustment in Obese Patients
ADR
PG: Vori, TPMT
Antiviral Administration
- Reduce/prevent the chemotherapy associated toxicity
- Change/Improve our durg and chemo protocols
- HDMTX and PG Research

17. Summary Introduction Childhood Cancer Childhood Cancer in Chile
Experience of Clinical Pharmacy Service .
Pharmacogenomic and Cancer ALL.
Experience HLCM Treatmen and Use Pharmacogenomic TPMT ALL

18. Morales, ACCP 2015 Poster Exhibition USA

19. Morales, ACCP 2015 Poster Exhibition USA

20. Silva, ACCP 2015 Poster Exhibition USA

21. Silva, ACCP 2015 Poster Exhibition USA

22. Summary Introduction Childhood Cancer Childhood Cancer in Chile
Experience of Clinical Pharmacy Service .
Pharmacogenomic and Cancer ALL.
Experience HLCM Treatmen and Use Pharmacogenomic TPMT ALL

23. Estimated that 75 – 85% of pharmacokinetic variability is genetic
Wide Variability in Chemotherapy PK
*Children with normal renal and liver function tests, given same IV dosages
of methotrexate (MTX), mercaptopurine, and cytarabine (AraC)
MTX
6MP
ARA C
MTX AUC
Cytarabine AUC
TGN
~5-fold
~30-fold
~10-fold
Estimated that 75 – 85% of pharmacokinetic variability is genetic
Evans et al, Pharmacol Ther 94(2):224-9, 2013
Evans et al, NEJM, 2003

24. To what extent does pharmacogenetic variability contribute to outcomes in ALL?
Relapse
Toxicity
2nd cancer

25. Drugs used in ALL treatment
FDA Approval
Mercaptopurine
1953
Methotrexate
Prednisone
1955
Dexamethasone
1958
Cyclophosphamide
1959
Vincristine
1964
Cytarabine
1969
Asparaginase
1978
Daunorubicin
1979
Etoposide
1983
Clofarabine
2004
Evans et al, Pharmacol Ther 94(2):224-9, 2013

26. Variable PK (PGEN) can influence efficacy
SJCRH Total 10
(Non-randomized)
SJCRH Total 12
(randomized)
1.0
MTX CPss³ 16mM (n=49)
0.8
0.6
Proportion
MTX CPss< 16mM (n=59)
0.4
0.2
P=0.046 1 2 3 4 5
Year
Evans, et al, NEJM, Evans et al, NEJM, 1998

27. Summary Introduction Childhood Cancer Childhood Cancer in Chile
Experience of Clinical Pharmacy Service .
Pharmacogenomic and Cancer ALL.
Experience HLCM Treatmen and Use Pharmacogenomic TPMT ALL

28. Mercaptopurin v/s Polymorphism TPMT*1
Cheok y Evans, 2006

30. METHODOLOGY C.I. ALL Patients HLCM PCR TPMT TPMT Activities
Blood Samples
DNA extraction

31. 8th Bi-Annual  Childhood  Leukemia Symposium, Santiago, Chile Abril 2012

33. In Summary
Ribeiro, J Clin Onco Jan

34. Conclusion
The clinical pharmacy service has experience substantial growth during the last 6 years, increasing the number of pharmacists, monitored patients and pharmacy interventions.
The implementation of a pharmaceutical care service in our outpatient pediatric oncology clinic has lead to identification of drug related problems and medication errors.
Pharmacogenetics is a tool used to help guide and individualize ALL therapy

35. Acknowledgements Shane Cross PharmD, SJRH. Felipe Silva PharmD, HLCM.
Julia Palma MD, HLCM.
Milena Villarroel MD, HLCM.
Gaston K. Rivera MD, SJRH.
Team Oncology Pharmacy (Manuel Azocar PharmD , Patricio García PharmD, Marlon Barraza PharmD, Viviana, María Jesus HLCM)
Laboratory Biochemistry-Pharmacogenomic (Carolina, Daniel, Mauricio)
Brenda L. Zylbersztajn PharmD, CLC.
Romina Valenzuela Investigational Nurse, Uchile.

36. Description of Tools pharmaceutical care in Acute Lymphoblastic Leukemia (Pharmacogenomics) Hospital Pediatric Experience Chilean Program Associated   with Antineoplastic Drugs (PINDA)  
Jorge Morales Vallespín
Pharmacy Chief
Hospital Dr. Luis Calvo Mackenna
Santiago, Chile