Cotrimoxazole myelotoxicity in hematopoietic SCT recipients: time for reappraisal

Fontanet, Aline; Chalandon, Yves; Roosnek, Eddy; Mohty, Bilal; Passweg, Jakob

doi:10.1038/bmt.2010.285

Cited by 20 publications

(16 citation statements)

References 9 publications

(8 reference statements)

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“…However, application of TMP-SMX in the post-transplant period is subject to debate, e.g. due to its possible myelotoxic profile [11,12] . In addition, TMP-SMX is nephro-and hepatotoxic and may also cause allergy or gastrointestinal symptoms [13] .…”

Section: Introductionmentioning

confidence: 99%

Atovaquone for Prophylaxis of Toxoplasmosis after Allogeneic Hematopoietic Stem Cell Transplantation

Mendorf

Klyuchnikov²,

Langebrake³

et al. 2015

Acta Haematol

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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.

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Section: Introductionmentioning

confidence: 99%

Atovaquone for Prophylaxis of Toxoplasmosis after Allogeneic Hematopoietic Stem Cell Transplantation

Mendorf

Klyuchnikov²,

Langebrake³

et al. 2015

Acta Haematol

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“…Myelotoxocity and leucopenia is a much-feared TMP-SMX adverse effect. 26 Only a small number of our patients receiving TMP-SMX chemoprophylaxis developed leucopenia. WCC recovered post discontinuation of TMP-SMX in all but 2 cases that showed partial recovery.…”

Section: Discussionmentioning

confidence: 79%

“…Myelotoxocity and leucopenia is a much‐feared TMP‐SMX adverse effect . Only a small number of our patients receiving TMP‐SMX chemoprophylaxis developed leucopenia.…”

Section: Discussionmentioning

confidence: 82%

Complications and outcomes of trimethoprim–sulphamethoxazole as chemoprophylaxis for pneumocystis pneumonia in renal transplant recipients

et al. 2014

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“…The avoidance of TMP‐SMX for reasons of myelosuppression also appears unfounded, as rates of leukopenia in solid organ transplant cohorts when TMP‐SMX is employed as prophylaxis have been reported at less than 2% . Modern studies have suggested that TMP‐SMX therapy when employed as prophylaxis in hematological malignancy does not impact on the degree or duration of neutropenia . A recent Cochrane review of PJP prophylaxis in the non‐HIV setting found no difference in adverse events requiring discontinuation when comparing TMP‐SMX to no treatment or placebo .…”

Section: Discussionmentioning

confidence: 99%

Dapsone safety in hematology patients: Pathways to optimizing Pneumocystis jirovecii pneumonia prophylaxis in hematology malignancy and transplant recipients

Urbancic

Pisasale

Wight

et al. 2018

Transplant Infectious Dis

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Dapsone may be used for Pneumocystis jirovecii pneumonia (PJP) prophylaxis in hematology patients receiving immunosuppressive therapy or after hematopoietic stem cell transplant (HSCT) in the setting of trimethoprim-sulfamethoxazole (TMP-SMX) adverse drug reaction (ADR) history. Dapsone-induced hematological toxicities such as oxidative hemolysis may limit use in these patients and modern assessments of dapsone allergy cross-reactivity in non-HIV patients with a sulfonamide allergy are largely absent. The aim of this single-centre, retrospective study was to describe dapsone usage in hematology patients requiring PJP prophylaxis, including HSCT recipients, over a 12-month period in terms of indications, incidence of dapsone-attributed oxidative hemolysis, and immune cross-reactivity in those previously labeled with a sulfonamide allergy, as well as describing potential opportunities for first-line TMP-SMX PJP prophylaxis reintroduction. Of 24 patients meeting the study inclusion criteria, 12 (50%) were receiving dapsone PJP prophylaxis post-HSCT. No cases of breakthrough PJP infection were noted. Sixteen patients (67%) were initiated on dapsone to avoid the perceived risk of further myelosuppression with TMP-SMX and five patients (21%) because of prior delayed immune-mediated allergy to TMP-SMX. None experienced rash with dapsone therapy. Six patients (25%) were successfully rechallenged on TMP-SMX, including one patient with prior TMP-SMX-associated rash. Four (17%) patients had confirmed oxidative hemolysis, all resulting in dapsone cessation. Dapsone PJP prophylaxis in hematology patients was effective and safe, with nonlife threatening dapsone-related hemolysis noted in a small number. An absence of sulfonamide allergy cross-reactivity was noted, suggesting greater TMP-SMX rechallenges or desensitization could be considered in those receiving dapsone.

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Cotrimoxazole myelotoxicity in hematopoietic SCT recipients: time for reappraisal

Cited by 20 publications

References 9 publications

Atovaquone for Prophylaxis of Toxoplasmosis after Allogeneic Hematopoietic Stem Cell Transplantation

Atovaquone for Prophylaxis of Toxoplasmosis after Allogeneic Hematopoietic Stem Cell Transplantation

Complications and outcomes of trimethoprim–sulphamethoxazole as chemoprophylaxis for pneumocystis pneumonia in renal transplant recipients

Dapsone safety in hematology patients: Pathways to optimizing Pneumocystis jirovecii pneumonia prophylaxis in hematology malignancy and transplant recipients

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