Toxoplasmosis encephalitis following severe graft‐vs.‐host disease after allogeneic hematopoietic stem cell transplantation: 17 yr experience in Fukuoka BMT group

Abstract

Toxoplasmosis is a rare but rapidly fatal complication that can occur following hematopoietic stem cell transplantation (HSCT). Over a 17-yr period at our institutions, a definite diagnosis of toxoplasmosis was made in only two of 925 allogeneic HSCT recipients (0.22%) and none of 641 autologous HSCT recipients. These two patients received a conventional conditioning regimen followed by transplantation from an HLA-matched donor; however, they developed severe graft-vs.-host disease, which required intensive immunosuppressive therapy. Despite prophylactic treatment with trimethoprim/sulfamethoxazole, their immunosuppressive state, as indicated by a low CD4(+) cell count, might have resulted in toxoplasmosis encephalitis. Rapid and non-invasive methods such as a polymerase chain reaction (PCR) test of their cerebrospinal fluid for Toxoplasma gondii and magnetic resonance imaging of the brain were useful for providing a definitive diagnosis and prompt therapy in these patients: one patient stabilized and survived after responding to treatment with pyrimethamine/sulfodiazine whereas the other died of bacterial infection. In addition, retrospective PCR analyses of the frozen stored peripheral blood samples disclosed that detection of T. gondii preceded the onset of disease, indicating routine PCR testing of peripheral blood specimens may be an early diagnostic tool. It should be noted that when patients receiving HSCT have an unexplained fever and/or neurological complications, PCR tests should be considered to avoid cerebral lesions and improve the outcome of the patients.

Toxoplasmosis in allo-SCT patients: risk factors and outcomes at a transplantation center with a low incidence

“…[2][3][4][5][6][7] European and Latin American case series report an incidence of 1-6%, [2][3][4]6 whereas the United States and Japan report incidences of o0.5%. 5,7,8 These differences reflect the great variation in seroprevalence in populations around the world (from o10% to 490%), related mainly to diet and hygiene habits. 1 The seroprevalence of toxoplasmosis among US-born persons declined from 14.1 to 9.0% between the periods of 1988-1994 and 1999-2004.…”

Toxoplasmosis and allogeneic stem cell transplantation: can we do better?

“…It is higher in areas of endemicity, ranging from 6% in Europe [5,6] and 3% in Brazil [7] compared to 50.5% in USA [3,4] or Japan [8]. In one prospective study of seropositive allo-SCT recipients, 16% reactivated the infection over the first 6 months after transplant and 6% developed disease [6].…”

“…The highest risk patients are seropositive allo-SCT recipients who have received cord blood or unrelated donor transplant, T cell depleted transplants, previous alemtuzumab, who have GVHD, or are unable to take trimethoprim/sulphamethaxoazole (TMP/ SMX) Pneumocystis jiroveci prophylaxis [6,7], although toxoplasmosis occurs even in patients receiving TMP/SMX prophylaxis [3,7,8]. Almost half of the cases in one US center occurred in patients born outside of the USA [4].…”

Severe Pulmonary Toxoplasmosis Mimicking Viral Pneumonitis after a Third Allogeneic Stem Cell Transplantation in a Man with Acute Lymphoblastic Leukemia

“…However, in immunocompromised patients, T. gondii may cause fulminant disseminated infection (1). Toxoplasmosis occurring after hematopoietic stem cell transplantation (HSCT) is a rare but often fatal complication (2)(3)(4)(5)(6)(7)(8). In HSCT recipients, toxoplasmosis infection is usually the result of reactivation of a latent infection rather than the development of a primary infection.…”

“…In countries with high endemicity, such as France, specific antibodies can be detected in 50-80% of the general adult population (1,2,9). In Japan, specific antibodies can be detected in only 10% of the population (4,9). Although the incidence of toxoplasmosis after HSCT in Japan is not well established, in the United States (US) and France, the incidence is reported to be 0.3% and 5%, respectively (5,9).…”