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Leukopenia within Solid Organ Transplant Recipients
Lauren RileyPharmD. Candidate 2011
February 10, 2011
Objectives
Identify possible risk factors for leukopenia
Understand the impact of leukopenia on transplant recipients
Overview
Discuss solid organ transplant (SOT) including etiology, immunosuppression and complications.
Discuss potential risk factors and outcomes associated with leukopenia.
Present current research and results.
Transplants in all states
1988
1990
1992
1994
1996
1998
2000
2002
2004
2006
2008
2010
0
5000
10000
15000
20000
25000
30000
35000
Organ Procurement Transplant Network [online database]. Accessed February 8, 2011.
Num
ber
of
transp
lants
Transplants in Georgia
1988
1990
1992
1994
1996
1998
2000
2002
2004
2006
2008
2010
0
100
200
300
400
500
600
700
800
Organ Procurement Transplant Network [online database]. Accessed February 8, 2011.
Num
ber
of
transp
lants
Transplant Etiology
Kidney
› Diabetes (20.8%)
› HTN (18.7%)
› PCKD (8.6%)
› FSGS (5.4%)
› Retransplant (6%)
› IgA Nephropathy (3.8%)
› SLE (3.1%)
Liver
› HCV Cirrhosis (21.2%)
› EtOH Cirrhosis (11.7%)
› Cryptogenic Cirrhosis (8%)
› HCC + Cirrhosis (5.8%)
› HCC (2.3%)
› NASH (2%)
Organ Procurement Transplant Network [online database]. Accessed February 9, 2011.
Immunosuppression
Polyclonal Antibodies› anti-thymocyte globulin
Monoclonal Antibodies› basiliximab› daclizumab
Calcineurin Inhibitors› tacrolimus › cyclosporine
Anti-Metabolites› azathioprine› mycophenolate mofetil
Steroids› methylprednisolone› prednisone
Antibiotics› sulfamethoxazole
-trimethoprim› atovaquone› dapsone
Antivirals› ganciclovir› valganciclovir› valacyclovir› acyclovir
Quadruple Therapy Preventative Therapy
Leukopenia and Neutropenia
Defnitions:› Leukopenia: white blood cell (WBC) count < 3.0 x 109 cells/L› Neutropenia: absolute neutrophil count (ANC) < 500 x 106 cells/L
Potential Risk Factors:› Demographics› Medications› Infections
Complications:› Infections› Death
Potential Treatments:› Growth colony stimulating factor› Dose reduction› Treat infection
Medication Induced LeukopeniaStudy Notes Leukopenia Study
Conclusions
VGC (PO)vs, GCV(IV)1
•Non-inferiority•Randomized•Open-label•Multicenter•Prospective
•Total = 11.8%•VGC = 11.6%•GCV = 12.1%
•Comparable safety profiles•VGC is non- inferior to GCV
rATG, MMF, FK-506, steroidsvs.MMF, FK-506, steroids2
•Safety and efficacy•Randomized•Open-label•Single-center•Prospective
• + rATG = 86%• - rATG = 64%
•No statistical difference in efficacy•Only statistically significant AE was leukopenia•rATG should be considered for short course inductions1Asber A, Humar A, Rollag H, et al. Oral valganciclovir is noninferior to intravenous ganciclovir for the treatment of cytomegalovirus
disease in solid organ tranplant recipients. Am J Transplant. 2007; 7: 2106-2113.2Boillot O, Belhassen S, Dumortier J , et al. Thymoglubulin induction in liver transplant recipients with tacrolimus, mycophenolate mofetil, and steroid immunosuppressive regimen: a fiver-year randomized prospective study. Liver Transplant. 2009; 15: 1426-1434.
Management of leukopenia in kidney and pancreas recipients. Hartmann E, Gatesman M, Roskopf-Somerville J, Stratta R, et al.
Hartmann E, Gatesman M, Roskopf-Sommerville J, et al. Management of leukopenia in kidney and pancreas transplant recipients.Clin Transpl. 2008; 22: 822-828.
Leukopenia in solid organ transplant recipients: identifying incidence and evaluating risk factors
Investigators:Lauren Riley, Pharm.D. Candidate 2011 Sarah Saxer, Pharm.D.Erika Meredith, Pharm.D.Christopher Hughes, M.D.
PRELIMINARY RESULTS – February 10, 2011
Purpose
To determine the risk factors involved with the development of leukopenia status-post abdominal transplant (kidney, liver, liver/kidney, pancreas, kidney/pancreas).
Primary Objectives
Identify the incidence of leukopenia status-post abdominal transplant.
Secondary Objectives
Determine risk factors involved in the development of leukopenia.› demographics› medication usage› co-morbidities
Examine the correlation between outcomes and leukopenia.› infection rate › hospital readmission rate› mortality› co-morbidities
Study Design
Single-center, retrospective chart review
Inclusion
› Received an abdominal transplant between May 1, 2008 and July 31, 2009 at Emory University Hospital
Exclusion
› Received a non-abdominal transplant
› Less than 18 years old
› Leukopenic before transplant
Data Collection Baseline demographic
information› Race› Height› Weight› Age› Smoking status
Laboratory information› WBC› ANC› SCr› GFR› BUN› CrCl
Average daily medication doses› mycophenolate mofetil
(MMF)› mycophenolic acid (MPA)› azathioprine (AZA)› cyclosporine (CSA)› tacrolimus (FK-506)› sirolimus (SIR)› sulfamethoxazole-
trimethoprim (SMX-TMP)› valganciclovir (VGC)› ganciclovir (GCV)› prednisone (PRED)› hydrocortisone (HC)
Total medication doses› anti-thymocyte globulin
(rATG)› methylprednisolone (MTP)› growth colony stimulating
factor (GCSF)
Results
Total Baseline Demographics
Male
› n = 109
Average age
› 49.4 years
African American
› n= 55
Average BMI
› 29.7 kg/m2
Smoked
› n = 8
Average WBC
› 7.9 x 109 cells/L
Incidence of Leukopenia
Total Liver Kidney0
20
40
60
80
100
120
140
160
180
Non-leukopenic
Leukopenic
75.9%
59.5%
67.7%
Baseline Demographics
Leukopenicn = 113
Non-leukopenicn = 54
Sex: Male (%) 76 (67) 33 (61)
Age (yr), mean 50 (+/- 11.9) 48.1 (+/- 13.9)
BMI (kg/m2), mean 30 38.9
Race: African American (%) 38 (34) 17 (31)
Smokes (%) 5 (4.4) 3 (5.5)
WBC (x109 cells/L), mean (range)
7.2 (3 – 41.6)
9.4 (3 – 23.4)
ImmunosuppressantsLeukopenic
n = 113Non-leukopenic
n = 54
Polyclonal Antibodies, n (%)•rATG
45 (39.8) 22 (40.7)
Calcineurin Inhibitors, n (%)•FK-506•CSA
109 (96.4)7 (6.2)
52 (96.3)5 (9.3)
Antimetabolites, n (%)•MMF•MPA•AZA
111 (98.2)1 (0.9)3 (2.7)
52 (96.3)4 (7.4)
0
mTOR inhibitor, n (%)•SIR 3 (2.7) 1 (1.9)
Steroids, n (%)•PRED•HC
98 (86.7)11 (9.7)
49 (90.7)6 (11.1)
Preventative Medications
Leukopenicn = 113
Non-Leukopenicn = 54
Antibiotic, n (%)•SMX-TMP 104 (92) 52 (96.3)
Antivirals, n (%)•GCV•VGC
60 (53.1)98 (86.7)
15 (27.8)41 (75.9)
Incidence of Neutropenia
Neutropenia identified in 4 patients› 3 liver recipients› 1 kidney recipient
No neutropenia identified at 6-months post-transplant
ANC range 22-360 x 106 cells/L
Post-transplant Infections
Total Liver Kidney0
20
40
60
80
100
120
140
160
180 170
88 82
45
19 26
Leukopenic
Non-leukopenic
Hospital Readmissions
Total Liver Kidney0
20
40
60
80
100
120
140
160141
98
82
51
18
33
Leukopenic
Non-leukopenic
Conclusion
Medications and demographics may contribute to leukopenia.
Patients with leukopenia have higher infection and readmission rates.
Future analysis include trending medication doses compared to leukopenia and evaluating the relationship with comorbidities.
Questions?