Transfusion-Associated Graft-Versus-Host Disease in a Newborn

By zdogan, Tutku; Metin, Fazilet; Dogu, Aysegl; Timur, tin; Yildiz, Elif

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare but usually fatal complication of transfusions [1]. Major risk factors for the development of TA-GVHD are congenital immunodeficiency syndromes, bone marrow transplantation (BMT), transfusion from descendant relatives, intrauterine transfusions, and human leukocyte antigen (HLA)-matched platelet transfusions [2].

A case of TA-GVHD in a newborn who had an exchange transfusion with whole blood from a relative is discussed herein, in the light of a literature review.

A full-term male infant, weighing 3600 g was treated by exchange transfusion for ABO incompatibility at 28.3 mg/dL serum bilirubin level on day 4 of life. Fresh whole blood supplied by his uncle was used for the transfusion. No complications occurred during the transfusion.

On day 22 of life, the patient was readmitted with fever and cutaneous eruptions that had started three days previously. On physical examination, his rectal temperature was 38.5 C, and patchy and macular eruptions extending over the whole body including the head, neck and palms of the hands and soles of the feet, were found (Figure 1).

The liver was palpated 1 cm at mid-clavicular line and conjunctival hyperemia was present. Investigations revealed SGOT: 132 IU/L, GGT: 598 IU/L, LDH: 1305 IU/L. Other biochemical and hematological findings including plasma immunoglobulins were within the normal limits. A sepsis screen was negative, and scalded skin syndrome was suspected. According to the diagnosis appropriate antibiotic therapy with ampicillin and netilmicin was started.

On day 3 of the antibiotics, thrombocytopenia and hypocalcemia developed and C-reactive protein were found to be positive. On day 5 following admission, serum bilirubin was elevated and remained elevated on the subsequent days. In spite of administration of empiric antibiotic therapy, fever persisted and skin lesions progressed to bullous lesions, which was followed by generalized erythroderma.

The possibilities of drug eruption and GVHD were considered and a skin biopsy was performed, which confirmed the diagnosis of grade II acute posttransfusional GVHD. On day 10, pancytopenia developed.

High dose methylprednisolone (20 mg/kg for 3 days, 10 mg/kg for 3 days, 5 mg/kg for 3 days), intravenous immunoglobulin (1 g/kg), antithymocyte globulin (5 g/kg), and granulocyte macrophage colony stimulating factor (10 g/kg subcutaneously) were used for the treatment. Extended spectrum antibiotics (vancomycin 15 mg/kg/dose every 6 hours and meropenem 40 mg/kg/dose every 8 hours), antifungals (AmBisome 3 mg/kg), and antiviral agents (acyclovir 10 mg/kg/dose every 8 hours) were needed for the overwhelming infections. In addition, packed red blood cells, fresh frozen plasma, thrombocyte suspension, and human albumin were used for supplementary therapy. Despite the intense treatment, multi-organ failure developed and the patient died on day 39 of life.

Graft-versus-host disease is an infrequent complication of blood transfusions with an incidence of 0.1% to 1% [3]. This disease was reported in humans in 1959 after allogenic bone marrow transplantation [4]. TA-GVHD results from the engraftment of transfused immunocomponent T lymphocytes in blood transfusion recipients whose immune system is unable to reject them [1]. A recent study demonstrated that the variability of the T cell receptor genes was restricted in each of the four TAGVHD patients studied, suggesting selective proliferation of donor T cells targeted to certain HLA antigens of the recipient [5].

Figure 1. Right leg of the patient with erythamatous and scalded skin.

In neonates the clinical manifestations of TAGVHD are similar to those of children and adults. Recently, Ohto and Anderson identified 27 cases of post-transfusion GVHD and reported that fever occurred at a median of 28 days (range 9-79 days) and rash at a median of 30 days (range 5-116 days) after transfusion, followed by death at 51 days (range 17-135 days) [6]. In the present case, fever and rash developed at 19 days and he died at 39 days. zkan et al. reported a case who developed symptoms 5 days after exchange transfusion with paternal blood and died on day 16 of life [7]. Similarly Jindal et al. described two cases from India with late admission [8]. Also from India, Gupta et al. described three more cases of TA-GVHD with hematological malignancies [9].

The diagnosis of TA-GVHD is made through the evaluation of clinical manifestations combined with relevant laboratory findings, where the gold standard test is biopsy of the skin and liver or a bone marrow aspirate.

Corticosteroids, antithymocyte globulin, cyclosporine and/or growth factors have been recommended for treatment either singly or in various combinations [10]. However, despite various treatment modalities, the rapid and fulminant onset of TA-GVHD associated with pancytopenia and overwhelming infections contribute to the high mortality seen in TA-GVHD. Our patient died on day 39 of life despite aggressive treatment.

Prevention is highly important. Irradiation of blood products is necessary for prevention, which inhibits proliferation of donor lymphocytes. Doses between 1500 cGy and 5000 cGy have been recommended in different countries depending on their requirements for irradiation of cellular blood products [2].

TA-GVHD is a fatal condition but is preventable with early physician awareness and by giving irradiated cellular blood products to neonates at risk.

References

1. Hume HA, Preiksaitis JB. Transfusion associated graft- versushost disease, cytomegalovirus infection and HLA alloimmunization in neonatal and pediatric patients. Transfus Sci 1999;21:73-95.

2. Schroeder ML. Transfusion-associated graft-versus-host disease. BrJ Haematol 2002; 117:275-287.

3. Greenbaum BH. Transfusion-associated graft-versus-host disease: historical perspectives, incidence, and current use of irradiated blood products. J Clin Oncol 1991;9:1889-1902.

4. Mathe G, Bernard J, Schwarzenberg L. [New trials with homologous bone marrow grafts after total irradiation in children with acute leukemia in remission. The problem of the secondary syndrome in man.] [Article in French] Rev Hematol (Paris) 1960;15:115-161.

5. Wang L, Tadokoro K, Tokunaga K, Uchida S, Moriyama S, Bannai M, Mitsunaga S, Takai K, Juji T. Restricted use of Tcell receptor V beta genes in post-transfusion graft-versus-host disease. Transfusion 1997;37:1184-1191.

6. Ohto H, Anderson KC. Post-transfusion graft-versus-host disease in Japanese newborns. Transfusion 1996;36:117123.

7. Ozkan H, ren H, Duman N, zkan , Sarioglu S, Anal O, Simsek A, Sagol O, Irken G. Transfusion-associated graftversus-host disease following exchange transfusion in a newborn. EurJPediatr 1999;158:343.

8. Jindal B, Narang A, Das R. Post-transfusion graft versus host disease-an under recognized entity. Indian Pediatr 2001; 38:179- 183.

9. Gupta A, Bansal D, Dass R, Das A. Transfusion associated graft versus host disease. Indian Pediatr 2004;41:1260-1264.

10. Sohi I, Jacob S. Transfusion associated GVHD. Indian J Pediatr 2005;72:533-535.

TUTKU ZDOGAN1, FAZILET METIN1, AYSEGL DOGU2, ETIN TIMUR3, & ELIF YILDIZ2

1 Department of Neonatology, Ministry of Health Gztepe Teaching Hospital, Istanbul, Turkey, 2 Department of Pediatrics,

Ministry of Health Gztepe Teaching Hospital, Istanbul, Turkey, and 3 Department of Pediatric Hematology, Ministry of

Health Gztepe Teaching Hospital, Istanbul, Turkey

(Received 18 September 2006; revised 12 November 2006; accepted 12 November 2006)

Dr Tutku zdogan

uha iegi sk. No: 8/7

34725, Kiziltoprak

Istanbul, Turkey

Tel: +90 216 418 37 96

Fax: +90 216 326 70 73

E-mail: tutkuozdogan@yahoo.com

Copyright Taylor & Francis Ltd. Mar 2007

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