To the editor:

Graft-versus-host disease (GVHD) after transfusion of nonirradiated blood products or solid tumor transplantation is a rare but lethal complication associated with mortality of 80% to 90%1-3  and occurs when immunocompetent donor T cells from the graft recognize disparate alloantigens of host cells. This process occurs primarily in immunocompromised hosts. Symptoms are typical of GVHD affecting skin, gut, and liver. Profound pancytopenia due to graft-versus-hematopoiesis effect may occur, described in animal models of transfusion-associated GVHD.4  Therapies to reverse this process are almost uniformly unsuccessful.3  Case reports and small series have documented response with agents such as basiliximab, daclizumab, antilymphocyte antibodies, and granulocyte colony-stimulating factor (G-CSF), though response to these agents is inconsistent.3,5,6 

Our patient was a 60-year-old man with cirrhosis status postorthotopic liver transplantation (OLT). At day 20 after OLT the patient reported abdominal pain and emesis and had a fever. His white blood cell count (WBC) was 11.3 k/μL (ANC of 8.89 k/μL), hematocrit was 31%, and platelet count was 337 k/μL. Infectious workup and empiric antibiotics were started. At day 27 the patient developed a generalized, dusky morbilliform rash with reticulated morphology (biopsies showed cytotoxic dermatitis compatible with GVHD grade 2-3) and odynophagia (laryngoscopy revealed mucositis). His WBC nadired to 0.02 k/μL on day 39 (Figure 1). A bone marrow biopsy revealed marked hypocellularity (< 10%) with residual hematopoiesis showing apoptotic bodies, consistent with GVHD. To secure the diagnosis of alloantigen-induced marrow aplasia, 4 specimens were submitted for single tandem repeat (STR) analysis7 : (1) a buccal swab (recipient DNA); (2) donor DNA–Allogen labs; (3) peripheral blood; and (4) T-cell enriched fraction from peripheral blood. Peripheral blood DNA showed mixed chimerism (11% donor DNA), and the T cell–enriched fraction (81% donor DNA) confirmed the diagnosis of GVHD. The patient remained profoundly pancytopenic despite high-dose steroids, filgrastim support, and rabbit antithymocyte globulin.3,8  Because of the patient's deteriorating condition and lack of response to other therapies, his case was discussed in the transplantation peer review group. Off-label use of the immunosuppressant alefacept was recommended. Rationale and potential side effects were discussed with the patient, who gave consent and subsequently received 30 mg alefacept, followed by 3 additional doses of 30 mg every 3 days. After the initial alefacept dose, his blood counts improved over 9 days to a WBC of 7.49 k/μL and platelet count of 31 k/μL. His counts remain stable 13 months later. It is provocative to note the rapidity and durability of his response after alefacept dosing.

Figure 1

Timeline of count nadir and count recovery with respect to administration of immunosuppressive agents.

Figure 1

Timeline of count nadir and count recovery with respect to administration of immunosuppressive agents.

Close modal

Alefacept is a novel dimeric fusion protein produced by recombinant DNA technology in a Chinese hamster ovary. It comprises the extracellular CD2-binding portion of the human leukocyte function antigen-3 (LFA-3) linked to the Fc portion of human-IgG1, and selectively targets memory T cells. It is approved for the treatment of psoriasis,9  and has been studied in patients with steroid resistant/dependent GVHD after HSCT (hematopoietic stem cell transplantation) with some success.10  Given the dismal responses seen with conventional immunosuppressive treatments for GVHD after transfusion or solid organ transplantation,1,3  alefacept may offer a reasonable treatment alternative in a setting cwhere outcomes have generally been fatal. Its use may also provide a clinical model for bone marrow failure states.

Acknowledgment: The authors thank Dr Ramon Tiu, who helped with the graphic illustration.

Contribution: All authors contributed to the work.

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Correspondence: Dr Christy J. Stotler, Cleveland Clinic Foundation, 9500 Euclid Ave, Desk R35, Cleveland, OH 44195; e-mail: stotlec@ccf.org.

1
Taylor
 
AL
Gibbs
 
P
Bradley
 
JA
Acute graft versus host disease following liver transplantation: the enemy within.
Am J Transplant
2004
, vol. 
4
 (pg. 
466
-
474
)
2
Alter
 
HJ
Klein
 
GK
The hazards of blood transfusion in historical perspective.
Blood
2008
, vol. 
112
 (pg. 
2617
-
2626
)
3
Smith
 
DM
Agura
 
E
Netto
 
G
, et al. 
Liver transplant-associated graft-versus-host disease.
Transplantation
2003
, vol. 
75
 (pg. 
118
-
126
)
4
Chen
 
J
Lipovsky
 
K
Ellison
 
FM
, et al. 
Bystander destruction of hematopoietic progenitor and stem cells in a mouse model of infusion induced bone marrow failure.
Blood
2004
, vol. 
104
 (pg. 
1671
-
1678
)
5
Sudhindran
 
S
Taylor
 
A
Delriviere
 
L
, et al. 
Treatment of graft-versus-host disease after liver transplantation with basiliximab followed by bowel resection.
Am J Transplant
2003
, vol. 
73
 (pg. 
1024
-
1029
)
6
Rinon
 
M
Maruri
 
N
Arrieta
 
A
, et al. 
Selective immunosuppression with daclizumab in liver transplantation with graft-versus-host disease.
Transplant Proc
2002
, vol. 
34
 (pg. 
109
-
110
)
7
Schrager
 
JJ
Vnencak-Jones
 
CL
Graber
 
SE
, et al. 
Use of short tandem repeats for DNA fingerprinting to rapidly diagnose graft-versus-host disease in solid organ transplant patients.
Transplantation
2006
, vol. 
81
 (pg. 
21
-
25
)
8
Young
 
NS
Calado
 
RT
Scheinberg
 
P
Current concepts in the pathophysiology and treatment of aplastic anemia.
Blood
2006
, vol. 
108
 (pg. 
2509
-
2519
)
9
Shear
 
NH
Fulfilling an unmet need in psoriasis: do biologicals hold the key to improved tolerability?
Drug Safety
2006
, vol. 
29
 (pg. 
49
-
66
)
10
Shapira
 
MY
Resnick
 
IB
Bitan
 
M
, et al. 
Graft-versus-host disease. rapid response to alefacept given to patients with steroid resistant or steroid dependent acute graft-versus-host disease: a preliminary report.
Bone Marrow Transplant
2005
, vol. 
36
 (pg. 
1097
-
1101
)
Sign in via your Institution