Atovaquone for Prophylaxis of Toxoplasmosis after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

Toxoplasmosis and infections by other opportunistic agents such as Pneumocystis jirovecii constitute life-threatening risks for patients after allogeneic hematopoietic stem cell transplantation. Trimethoprim/sulfamethoxazole (TMP-SMX) has been well established for post-transplant toxoplasmosis and pneumocystis prophylaxis, but treatment may be limited due to toxicity. We explored atovaquone as an alternative and compared it with TMP-SMX regarding toxicity and efficacy during the first 100 days after transplantation in 155 consecutive adult stem cell recipients. Eight patients with a prior history of TMP-SMX intolerance received atovaquone as first-line prophylaxis. TMP-SMX was used for 141 patients as first-line strategy, but 13 patients (9.2%) were later switched to atovaquone due to TMP-SMX toxicity or gastrointestinal symptoms. No active toxoplasmosis or active P. jirovecii infection developed under continued prophylaxis with either TMP-SMX or atovaquone. However, for reasons of TMP-SMX and/or atovaquone toxicity, 7 patients were unable to tolerate any efficacious toxoplasmosis prophylaxis and therefore obtained inhalative pentamidine as P. jirovecii prophylaxis but no toxoplasmosis prophylaxis. Importantly, 2 of these patients developed severe toxoplasmosis. In summary, atovaquone appears as a valid alternative for at least some post-transplant patients who cannot tolerate TMP-SMX. This should be further confirmed by multicenter trials.

A matched case–control study of toxoplasmosis after allogeneic haematopoietic stem cell transplantation: still a devastating complication

“…In our series, 17.4% were breakthrough TXP, in accordance with 12% of breakthrough TXP reported by Gajurel et al [7]. Breakthrough TXP might reflect suboptimal dosing of prophylaxis related to inadequate oral absorption, mainly caused by gastrointestinal aGvHD, or drug interruptions because of haematotoxicity and gastrointestinal intolerance [7,19,20].…”

“…High-dose trimethoprim-sulfamethoxazole (320/1600 mg/day) was shown to delay neutrophil recovery after HSCT [16] and a rather small (n ¼ 3) descriptive study reported that trimethoprim-sulfamethoxazole 160/800 mg/day impaired in vitro colony formation of peripheral blood stem cells [17]. However, retrospective studies (160/800 mg or 320/1600 mg thrice weekly) did not evidence significant delay in engraftment compared with no prophylaxis or atovaquone (1500 mg/day) [18,19].…”

Toxoplasma Encephalitis following Tandem Autologous Hematopoietic Stem Cell Transplantation: A Case Report and Review of the Literature

“…Prophylaxis should ideally be started as soon as feasible after allo-HSCT but no later than engraftment and continued for at least six months, as about 10% of cases occur within one month and 90% of cases occur during within six months [ 26 ]. If engraftment is delayed and TMP/SMX cannot be given due to myelosuppression, atovaquone [ 27 ] can be used until engraftment, followed by TMP/SMX. A more controversial issue is the need for prophylaxis in ASCT recipients; such a policy is debatable due to the low incidence of toxoplasmosis in this setting and the consequent lack of experience.…”

Failure of primary atovaquone prophylaxis for prevention of toxoplasmosis in hematopoietic cell transplant recipients

“…In one study of PJP prophylaxis, none of the 16 patients in the atovaquone arm (1500 mg 3 times a week) developed toxoplasmosis, but this study was conducted in low-risk autologous HCT recipients who generally do not even require Toxoplasma prophylaxis (9). A recent study showed no breakthrough toxoplasmosis in 22 patients after allo-HCT while on atovaquone prophylaxis (1500 mg daily) (10). Unfortunately, pre-HCT Toxoplasma serology of these patients is not mentioned, and thus it is not clear how many of these patients were at a high risk for reactivation.…”