Caspofungin treatment of Pneumocystis pneumonia during conditioning for bone marrow transplantation

Abstract

Pneumocystis pneumonia (PCP) is a well-known compli-cation in AIDS patients, but it is also frequently diagnosedin hemato-oncological patients [1]. High-dose cotrimoxa-zole is the first-line treatment for PCP, but some patientsshow contraindications and drug resistance may appear[2]. Since Pneumocystis jirovecii cannot be cultivated invitro, mutations in the genes involved in folate metabo-lism have been investigated as a possible expression ofcotrimoxazole resistance [3], but the search for a clinicalcorrelate has so far led to equivocal results [4]. There issome doubt as to what may be the best alternative tocotrimoxazole in the treatment of PCP [5]. The presentreport refers to the use of caspofungin to treat a patientwith PCP undergoing bone marrow transplantation (BMT)in whom cotrimoxazole had to be discontinued because ofits myelotoxicity.A 45-year-old male patient with T-lymphoblastic leu-kemia in second complete remission was scheduled to re-ceive an allogeneic BMT from an unrelated HLA-matcheddonor in October 2004. In September, he was admitted tohospital because of acute respiratory failure. Subsequentexamination of bronchoalveolar lavage (BAL) led to thediagnosis of PCP, and a computed tomography (CT) scanshowed diffuse, bilateral, interstitial disease with “groundglass”parenchymaandthickeningoftheinterlobularsepta.Molecular, cultural and cytological investigations of theBAL failed to identify any other pathogen. Transbronchialbiopsy was not performed. High-dose cotrimoxazole wasstarted in combination with methylprednisolone. A bonemarrow aspirate revealed signs of an initial leukemic re-lapse that was treated with weekly vincristine and dailyoral 6-mercaptopurine, which led to a stable bone marrowblast count and the maintenance of normal peripheralhematometry.During cotrimoxazole treatment, the CT findings im-proved significantly but did not normalize, and the drugwas discontinued after 2 weeks because of patient refusal.On 7 October, the patient was discharged for personalreasons, and he continued taking oral cotrimoxazole at adaily dose of 3,840 mg. Two weeks later, a further CTscanshowed persistence of significant lung infiltrates.On 11 November, when the patient was admitted toundergoBMT,apositronemission tomography(PET)scanrevealed the presence of diffuse, active, alveolar disease(Fig. 1) and high-dose intravenous cotrimoxazole wasresumed. On 22 November, standard-dose caspofungin(70mgonthefirstday,followedby50mg/day)wasadded,and a conditioning regimen was started including thio-tepa (15 mg/kg divided into three equal doses on days −8and−7),andcyclophosphamide(50mg/kg/dayondays−4,−3 and −2). A bone marrow aspirate showed a raised butstable blast count. On 29 November, the CT findings wereunchanged, and cotrimoxazole was discontinued. On 30November, BMT was performed, with standard-dose cy-closporine-Aandmethotrexatebeingadministeredasgraft-versus-host disease prophylaxis. During pancytopenia,mixed Enterobacter/coagulase-negative Staphylococcusbacteremia was observed. Polymorphonuclear recoverywasachievedonpost-BMTday25,andplateletrecoveryonday 34, after being delayed by mild microangiopathichemolytic anemia responsive to defibrotide therapy. On22 December, a CT scan showed complete resolution ofthe lung infiltrates. On 5 January, caspofungin was dis-continued and a bone marrow aspirate showed completeremission and full donor chimerism. On 12 January thepatient was discharged. One month later, the leukemiarelapsed; a CTscan did not show any lung infiltrates.A diagnosis of PCP is frequently established in BMTrecipients,inwhomimmunodepressionmayplayaprimaryrole, and also in hematological patients receiving che-motherapy alone [1]. In such cases, cotrimoxazole mayinterfere with the possibility of delivering the subsequent