Successful allogeneic bone marrow transplantation in a patient with active Coccidioidomycosis

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Coccidioidomycosis (Cocci) is a fungal infection that is endemic to the southwestern United States.1 Although typically these infections are self-limited, in patients who are immunocompromised, these infections can be life-threatening. To date, only three cases of coccidioidomycosis following bone marrow transplantation (BMT) have been published in the literature.2 In each of these patients, there was no evidenc who developed disseminatee of active infection at the time of transplantation. Both patientsd coccidioidomycosis died secondary to infection and active disease has been seen as a potential contraindication to transplantation. We now report the first case of a patient with known evidence of active coccidioidomycosis prior to BMT who subsequently successfully underwent allogeneic transplantation.

A 24-year-old female resident of Phoenix, Arizona was diagnosed with MDS after she presented to the emergency room with acute respiratory and multi-organ failure in May 2000. Chest X-ray revealed bilateral pulmonary infiltrates and cultures obtained by bronchosocopy were positive for coccidioidomycosis. The patient was initially managed with conventional intravenous amphotericin but was intolerant, secondary to hyperpyrexia and delirium. Subsequently, she was treated with fluconazole (400 mg/day); however, 6 days after this therapy, she re-presented to the emergency room with chest discomfort, cough, low-grade fever and active evidence of cocci on CXR. She was hospitalized, treated with intravenous fluconazole (600 mg/day) and then discharged on maintenance therapy of fluconazole 400 mg/day orally. CT scan demonstrated improvement with residual nodules present. In August 2000, she was hospitalized with progression of her MDS to AML, with numerous cytogenetic abnormalities, including trisomy 13. CXR prior to chemotherapy demonstrated near-complete resolution of the previously seen infiltrates. She received chemotherapy with Ara C and Daunorubicin (7 and 3) and during the time of her neutropenia developed persistent fever, new infiltrates on CT scan, and evidence for active cocci on bronchosopy. She received therapy with fluconzaole and was referred to the BMT service.

Pre-transplant evaluation demonstrated an elevated cocci IGG and IGM titers. The CT scan findings (Figure 1) demonstrated multiple nodular densities through both lung fields, consistent with active coccidioidomycosis. Prior to BMT, she was treated aggressively with a lipid amphotericin (Ambisome) at 5 mg/kg/day. She tolerated this without event and received a total of 1.5 g prior to transplantation. The transplant regimen consisted of TBI and busulfan with GVH prophylaxis consisting of cyclosporine and MMF and she received peripheral blood stem cells from her HLA-identical sister. She engrafted to white cells on day +12 and had an ANC of less than 5 × 108/l for 7 days. She continued on treatment as an outpatient until day +55, receiving a total of 11.5 g of Ambisome therapy. Chest CT prior to discharge did not demonstrate evidence of active disease (Figure 2). Despite the need for intermittent steroid therapy due to active and chronic graft-versus-host disease, her current CT scan 3 years post-transplant shows no evidence for active coccidioidomycosis. She has remained on maintenance intraconazole while receiving immunosuppressive therapy.

Figure 1

CT scan demonstrating active coccidioidomycosis bilaterally prior to BMT.

Figure 2

CT scan demonstrating no evidence for coccidioidomycosis post-BMT.

Fungal infection remains a major source of morbidity and mortality following allogeneic BMT.3 The most common organisms are candida and aspergillosis species. Coccidioidomycosis has rarely been described following allogeneic BMT.2 It is an endemic disease in the southwestern United States with most cases in Maricopa and Pima counties (Phoenix and Tucson areas), Fresno, California and in El Paso, Texas.1 With the population boom in Maricopa county and the potential exposure of those who may live in this area during the winter months, it may be anticipated that cocci will be more commonly seen in patients proceeding to transplantation.

The three patients previously described did not have evidence of active infection at the time of transplantation. All three had lived in areas endemic for coccidioidomycosis prior to their transplant although the transplant was performed in a non-endemic area in two of the patients. This suggests that the diagnosis of coccidioidomycosis should be entertained in patients who had previously resided in an endemic area if they have clinical features in keeping with the disease.

The most important factor in successful therapy appears to be treating patients prior to the development of disseminated disease. Both patients in the previous report with evidence of dissemination died despite aggressive therapy. The one patient with pulmonary disease alone was successfully treated with standard antifungal therapy.

Our patient differed from those previously described since they had evidence for active disease immediately prior to transplantation. With aggressive therapy prior to and during transplant, we were able to prevent disease progression and safely allow the patient to undergo transplantation despite the fact that during induction therapy her coccidioidomycosis had worsened.

Recognizing coccidioidomycosis infection prior to and during transplantation may be very difficult. Standard titers are often not diagnostic and skin tests are unreliable in patients who are immunosuppressed. In patients with potential exposure prior to transplant, chest CT scans may be valuable in identifying patients who may have potential active disease. If this is confirmed on bronchoscopy, then aggressive therapy prior to transplant may prevent dissemination and allow for a safe transplantion.

Although the number of patients with coccidioidomycosis is small, recognition of disease prior to BMT appears critical since it allows for early therapy which may make transplantation feasible in this group of patients.


  1. 1

    Galgiani J . Coccidiodomycosis: a regional disease of national importance. Annals of Internal Medicine 1999; 130: 293–300.

  2. 2

    Riley D, Galgiani J, O’Donnell M et al. Coccidiodomycosis in bone marrow transplant recipients. Transplantation 1993; 56:1531–1533.

  3. 3

    Wingard J . Fungal infections after bone marrow transplant. BiolBlood Marrow Transplant 1999; 5: 55–68.

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