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

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Organ Procurement Transplant Network [online database]. Accessed February 8, 2011.

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lants

Transplants in Georgia

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Organ Procurement Transplant Network [online database]. Accessed February 8, 2011.

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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?