Original Article

Bone Marrow Transplantation (2007) 39, 157–164. doi:10.1038/sj.bmt.1705559

Post-Transplant Events

High-dose caspofungin combination antifungal therapy in patients with hematologic malignancies and hematopoietic stem cell transplantation

A Safdar1, G Rodriguez1, K V I Rolston1, S O'Brien2, I F Khouri3, E J Shpall3, M J Keating2, H M Kantarjian2, R E Champlin3, I I Raad1 and D P Kontoyiannis1

  1. 1Department of Infectious Diseases, Infection Control, and Employee Health, MD Anderson Cancer Center, Houston, TX, USA
  2. 2Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA
  3. 3Department of Blood and Marrow Transplantation, MD Anderson Cancer Center, Houston, TX, USA

Correspondence: Dr A Safdar, Department of Infectious Diseases, Infection Control, and Employee Health, MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. E-mail: asafdar@mdanderson.org

Received 24 July 2006; Revised 12 September 2006; Accepted 12 September 2006.

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Abstract

Pneumocandins have concentration-dependent antifungal activity and higher dose of caspofungin (HD-CAP) in combination with other licensed antifungal therapy (OLAT) may improve response. Thirty-four patients who received HD-CAP were compared with 63 patients who received standard dose (SD)-CAP. There were no differences between the groups in either patient or disease characteristics. Significantly more patients in the HD-CAP arm had extrapulmonary infections (29 vs 8% in SD group; P=0.0053), and non-Aspergillus species infection (21 vs 6%; P=0.05) and had received prior antifungal therapy (71 vs 33%; P=0.0004). No serious adverse reactions were noted in patients receiving HD- or SD-CAP therapy. Twelve weeks after treatment commenced 44% had a complete or partial response compared with 29% in SD-CAP group (P=0.1). Logistic regression analysis showed a significant probability of a favorable outcome at 12 weeks in patients who received HD-CAP (OR 3.066, 95% CI, 1.092–8.61; P=0.033). This may in part reflect higher number of patients in HD group had received granulocyte–macrophage colony-stimulating factor (41 vs 14% in SD group; P=0.04) and/or interferon italic gamma (26 vs 5% in SD group; P=0.003) immune enhancement. Further studies are needed to evaluate efficacy of HD-CAP in severely immunosuppressed cancer patients with invasive fungal infections.

Keywords:

high-dose caspofungin, refractory fungal infection, allogeneic bone marrow transplantation, leukemia, lymphoma, adverse events

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