Pulmonary toxicity syndrome following CDEP (cyclophosphamide, dexamethasone, etoposide, cisplatin) chemotherapy

Abstract

Summary:We report on three patients with multiple myeloma who developed drug-induced pneumonitis 1-2. months following maintenance (post autologous transplantation) chemotherapy with CDEP (cyclophosphamide, dexamethasone, etoposide, cisplatin) and 6-20 months after exposure to carmustine (BCNU) 300 mg/m 2 , used in combination with melphalan 140 mg/m 2 , as pre-transplant conditioning regimen. All patients had either a proven (two) or suspected (one) fungal pneumonia and were treated with liposomal amphotericin B. Dyspnea, fever and cough were the prominent clinical symptoms, while air-space disease with ground glass appearance was seen radiographically. Histologic features typical for drug-induced lung injury were detected. All patients had a dramatic, clinical and radiographic response to a brief course of corticosteroids. Although CDEP-induced pneumonitis appears to be a rare complication, its early recognition and prompt treatment, as well as its possible association with preceding fungal infection may have important clinical implications. Bone Marrow Transplantation (2001) 28, 399-403. Keywords: non-infective pulmonary toxicity; CDEP chemotherapy; fungal infection Drug-induced pulmonary toxicity, not associated with infection, is a well-described complication of different chemotherapeutic agents. Among them, carmustine (BCNU), cyclophosphamide, bleomycin, busulphan, melphalan and total body irradiation have been implicated. 1 Furthermore, combinations of various agents (even the ones rarely associated with the syndrome) may potentially lead to lung injury through drug interactions. 2 development of this pulmonary toxicity syndrome (PTS). This is further supported by the lack of correlation between severity of PTS in case of BCNU-based high-dose chemotherapy with age, tobacco use or baseline pulmonary function, suggesting that other factors play a role in PTS, in addition to chemotherapy exposure. 3 From this perspective, it was intriguing to observe three patients, with a history of either proven (two) or suspected (one) fungal pneumonia, who developed typical clinical, radiographic and histologic features of PTS 5-11 weeks after treatment with CDEP (cyclophosphamide, dexamethasone, etoposide, cisplatin) chemotherapy, a fairly commonly used regimen which has not so far been associated with non-infective pulmonary toxicity. These patients had a dramatic response to a brief course of corticosteroids. There was no evidence of fungal infection at the time of PTS diagnosis. Patients and methodsBetween August 1997 and February 2000, 231 patients underwent autologous peripheral blood stem cell transplantation (APBSCT), at our institution, for a variety of hematologic malignancies (multiple myeloma, 87; non-Hodgkin lymphoma, 64; Hodgkin's disease, 11; others, 14) and solid tumors (breast carcinoma, 46; others, nine). In the vast majority (200 patients), the same conditioning regimen of BCNU at 300 mg/m 2 and melphalan at 140 mg/m 2 (BCNU/MEL) was applied, followed by post-transplant chemotherapy starting 3 months ...

Drug-Induced Respiratory Disease in Patients with Hematological Diseases

“…The histopathologic features included DAD, alveolar hemorrhage, and dysplasia of type II cells. 212 Fludarabine Fludarabine monophosphate (FAMP), the 2-fluoro, 5 0 phosphate derivative of 9-b-D-arabinofuranosyl adenine (ara-A), is a purine analog used to treat a variety of hematological malignancies, including chronic lymphatic leukemia, other low-grade non-Hodgkin's lymphomas resistant to alkylating agents, and acute leukemias. Acute interstitial pneumonitis due to fludarabine was first described in 1987.…”