Assessment of Incidence Toxoplasma Gondii Infection and Outcomes in Allogeneic Stem Cell Patients
Authors: Ahmed Sairah , Shpall Elizabeth J , Gulbis Alison , Jones Roy , Martinez Charles S. , Rondon Gabriela , Rezvani Katayoun , Oran Betul , Olson Amanda , Shah Nina , Parmar Simrit , Popat Uday R. , Alousi Amin M. , Nieto Yago , Hosing Chitra M. , Bashir Qaiser , Kebriaei Partow , Qazilbash Muzaffar H. , Champlin Richard E. , Mulanovich Victor E. 
Published: October 2019

Abstract
Background
Toxoplasma gondii infection is a catastrophic infectious complication with a high rate of mortality in immune compromised patients and particularly stem cell transplant (SCT) recipients. Incidence of infection is variable from 0.1 % to 6% and higher in Europe and Latin America compared to US. Mortality rate is 60-90% in SCT patients compared to 30% in AIDS patients (Clin Infect Dis 2005;40:67–68). Most cases of toxoplasmosis among SCT recipients are due to disease reactivation from previously acquired infection. Per ASBMT guidelines of 2009, incidence of clinical reactivation is 2-6% of seropositive recipients, and cord blood recipients are at highest risk. Allogeneic SCT candidates should be tested for toxoplasma IgG antibody and patients who are seropositive should be treated empirically if develop CNS or pulmonary lesions. The introduction of trimethoprim/sulfamethoxazole (TMP/SMX) prophylaxis (Br J Haematol 2002;117:370–386) has led to a decrease of toxoplasmosis, however patients can still develop infection while on TMP/SMX. This is a rare infectious complication in recipients of allogeneic SCT, and can be difficult to diagnose.
Methods
We retrospectively reviewed patients who received an allogeneic (allo) SCT at MD Anderson from 1994 to 2013. In period from 1994-2009 routine serologic testing for toxoplasma was not done and from 2010 – 2013 SCT patients were routinely tested for toxoplasma IgG antibody. Diagnosis made in first cohort by: autopsy (3), brain biopsy (4), PCR CSF and cytopathology (1), PCR blood (1). Diagnosis in second cohort was made by PCR blood (5), PCR CSF (5), autopsy (1), characteristic findings on imaging + improvement on therapy (1).
Results
From 1994-2009 nine of 3623 allo SCT patients had a clinical toxoplasma infection, of which 4 were international patients and 5 were from the US; total incidence of 0.25%; 4/246 international patients: 1.6% and 5/3380 US patients 0.15% (p=0.002). In time period from 2010-2013 of 1047 transplanted patients, 9 cases of toxoplasma diagnosed of which 3 patients from high incidence countries. Time to presentation is bimodal; early (1 month) and late (3-6 months) post transplant.
From 1994-2009, 9 patients presented with toxoplasma infection of which 8 died - 3 presented with disseminated infection/pulmonary symptoms while 6 had neurologic symptoms. Type of donor: matched related donor (MRD) (6), matched unrelated donor (MUD) (1), haploidentical donor (2).
In the 2nd cohort 2 cases didn't have serology done but serology in entire patient population revealed toxoplasma IgG (+) equaled 97/1047 (9.2%), clinical cases of all tested patients, 7/1047 (0.7%) and all clinical cases with positive toxoplasma IgG pretransplant 7/97 for an incidence of 7.2%.
From 2010-2013, 9 patients presented with toxoplasma infection, 4 died of toxoplasmosis while 5 survived of which 1 died of relapse. Five patients presented with sepsis, 2 with pneumonia and 1 with myocarditis, while 8 patients had CNS symptoms including meningoencephalitis and classic presentation of brain lesions. Six patients had concomitant CMV reactivation and 3 were on corticosteroids. Remaining patients had no other predisposing conditions. Type of donor: MRD (1), MUD (5), haploidentical (2), cord blood (1). Three cases were second transplants and all those patients died. The 5 patients who survived all received treatment within 6 days of presentation. (Table 1)
Conclusions
The most common presentations of toxoplasma infection in SCT patients are meningoencephalitis and sepsis. Only 2 patients in our most recent patient population had classic brain disease. Five of nine survived in our more recent cohort compared to 1/9 in previous time period. It appears that delayed treatment (³6 days) may be related to increased mortality. Although toxoplasma infection in SCT patients carries a high mortality, identifying patients at higher risk and early treatment may improve outcomes.
TABLE 1 Type of transplant SCT to illness Site of infection Days to Treatment Primary Cause of Death MUDSCT 33 Sepsis/Pneumonia 6 Protozoal infection MUDSCT (2nd) 94 Brain 4 MUDSCT 100 Meningoencephalitis 2 MUDSCT 166 Brain UNK HAPLO 34 Sepsis/CNS 4 HAPLO (2nd) 165 Sepsis/CNS NO TX Autopsy: Cardiac/Lung/CNS Toxo MUDSCT 13 Sepsis/ meningoencephalitis 6 Autopsy: Recurrence/persistence of disease Cord 30 Sepsis/Meningitis 7 Protozoal infection AlloMRD (2nd) 10 Meningoencephalitis 8 Protozoal infection

Disclosures
No relevant conflicts of interest to declare.