Letter to the Editor

Bone Marrow Transplantation (2009) 44, 765–766; doi:10.1038/bmt.2009.74; published online 4 May 2009

Fatal cerebral zygomycosis breakthrough in a patient with acute lymphoblastic leukemia on voriconazole prophylaxis after cord blood SCT

I Vande Broek1,2 and R Schots1

1Division of Clinical Hematology and BMT Unit, University Hospital Brussels, Brussels, Belgium

Correspondence: IV Broek, E-mail: Isabelle.vandebroek@uzbrussel.be

2IVB is a senior clinical investigator of the Research Foundation Flanders

We have read with great interest the recent article by Trifilio et al.1 on the breakthrough in zygomycosis after the administration of voriconazole in allogeneic stem cell transplant recipients.

We report a case developing this type of complication and illustrating an additional risk factor, which is delayed immune recovery after umbilical cord blood transplantation (UCBTx). The 39-year-old female patient was diagnosed with Ph chromosome positive acute lymphoblastic leukemia in March 2005. She was treated with induction and consolidation chemotherapy, including imatinib and prophylactic cranial radiotherapy. After the completion of consolidation treatment, she was in hematological remission, but had minimal residual disease as detected by PCR for the BCR–ABL transcripts. There was no familial or unrelated donor available. She was allografted with a double UCBTx after myeloablative conditioning, including CY and TBI, in November 2006. During the aplastic phase, the patient developed symptoms of probable fungal infection and was treated with voriconazole, which was continued throughout the whole post-transplant episode. The patient achieved and maintained complete molecular remission. However, she developed grade II acute and subsequent systemic chronic GVHD requiring prolonged treatment with corticosteroids and azathioprine, which was started in February 2007. Persistent mixed chimerism (±50% of each cord blood) was noted, together with a very prolonged immune reconstitution with total CD3+ cells counts not exceeding 200/mm3. At 18 months after SCT, while still on voriconazole, she was admitted with fever and a rapidly progressing neurological syndrome with left hemiplegia, altered consciousness and seizures. MRI imaging showed a mass on the right frontoparietal side with compression of the midline, diffuse concentric contrast captation and central necrosis (Figure 1). Microbiological culture of the brain biopsy as well as cerebrospinal fluid isolated Rhizopus microsporus. Subsequently, in view of the critical clinical situation, the patient was treated with a combination of liposomal amphotericin B and posaconazole, but she rapidly deteriorated and died 2 days after the initiation of treatment. Posaconazole has been added on the basis of several reports indicating clinical activity in zygomycosis infections.2

Figure 1.
Figure 1 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author

Cerebral magnetic resonance imaging ((a) Axial Flair and (b) Coronal T1 after contrast) showing a mass lesion with diffuse concentric margin contrast. There is captation in the right fronto-parietal area, with a large necrotic zone (arrow). The lesion shifts the midline to the left with nearly complete compression of the right lateral ventricle.

Full figure and legend (119K)

Umbilical cord blood is an accepted alternative to BM or mobilized peripheral stem cells as a source of hematopoietic stem cells for allografting patients with hematological malignancies. However, UCBTx is characterized by delayed immune reconstitution, which results from the presence of naive T cells and more potent suppressive T-regulatory cells. Therefore, recipients of UCBTx are more vulnerable to infectious complications, including viral and fungal infections.3, 4 This case report is in line with the paper by Trifilio et al.1 and highlights the risk of unusual fungal infections such as zygomycosis in patients with prolonged administration of voriconazole, especially in case of poor immune recovery such as after UCBTx. It emphasizes the need in such patients to balance the benefits in terms of prevention against the increased risk of breakthrough fatal fungal infections.

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References

  1. Trifilio SM, Bennett CL, Yarnold PR, McKoy JM, Parada J, Mehta J et al. Breakthrough zygomycosis after voriconazole administration among patients with hematologic malignancies who receive hematopoietic stem-cell transplants or intensive chemotherapy. Bone Marrow Transplant 2007; 9: 425–429. | Article | ChemPort |
  2. Rogers TR. Treatment of zygomycosis: current and new options. J Antimicrob Chemother 2008; 61(Suppl 1): i35–i40. | Article | PubMed | ChemPort |
  3. Hamza NS, Lisgaris M, Yadavalli G, Nadeau L, Fox R, Fu P et al. Kinetics of myeloid and lymphocyte recovery and infectious complications after unrelated umbilical cord blood versus HLA-matched unrelated donor allogeneic transplantation in adults. Br J Haematol 2004; 124: 488–498. | Article | PubMed | ISI
  4. Szabolcs P, Niedzwiecki D. Immune reconstitution after unrelated cord blood transplantation. Cytotherapy 2007; 9: 111–122. | Article | PubMed | ChemPort |