Abstract
Purpose
Fulminant invasive fungal sinusitis (IFS) is an aggressive disease seen in patients who are severely neutropenic. The use of granulocyte transfusions to address neutropenia-associated IFS has been described for almost 2 decades. The objectives are to provide our experience using granulocyte transfusions in patients with IFS and to provide a current review of the literature.
Materials and methods
A retrospective chart review was performed at the Medical College of Wisconsin to identify patients who received granulocyte transfusions for IFS. Data collected included age, original diagnosis, IFS pathogen, dates, transfusion number, reason for discontinuation, additional therapies, last known follow-up, and status at last known follow-up. A Medline search and manual review of citations within bibliographies was also performed.
Results
A total of 20 patients received granulocyte transfusions at the Medical College of Wisconsin between October 2003 and June 2009; 3 of these patients received granulocyte transfusions for fulminant IFS. A total of 22 reported cases of IFS treated with granulocyte transfusions exist in the current literature.
Conclusions
Although limitations to the use of granulocyte transfusions exist, they still represent a viable treatment option in individuals who fail to respond to more conventional therapies.
1
Introduction
Fulminant invasive fungal sinusitis (IFS) is a potentially devastating disease process seen in patients who are severely neutropenic. These patients are often neutropenic because of hematologic malignancies and/or their respective treatments. Current treatment includes antifungal medications including amphotericin B and triazoles (voriconazole, posaconazole, etc), white blood cell colony–stimulating factors, and surgical debridement.
Parikh et al from Emory University reported their experience with IFS patients, outlining treatment algorithms, potential therapies, and prognostic factors. In their report, as well as in others, the most important predictor of recovery from IFS is the recovery of the absolute neutrophil count.
The use of granulocyte transfusions to address neutropenia was first described in 1965 . This involves collecting neutrophils and polymorphonuclear leukocytes from donors and transfusing them into the neutropenic recipients. Use of granulocyte transfusions has come in and out of favor over the past several decades, and the first report of granulocyte transfusions for patients with IFS came in 1992.
The objectives of this report are to provide our experience over the past 6 years using granulocyte transfusions in patients with IFS and to provide a current review of the literature on granulocyte transfusions for IFS.
2
Methods
A retrospective chart review was performed at the Medical College of Wisconsin and its affiliates, The Blood Center of Wisconsin, Children’s Hospital of Wisconsin, and Froedtert Hospital. Institutional review board approval was obtained from the Medical College of Wisconsin (PRO 11303) (covering Children’s Hospital of Wisconsin and Froedtert Hospital) as well as from the Blood Center of Wisconsin (BC 09–19).
The names of patients receiving granulocyte transfusions through the Blood Center of Wisconsin were obtained, and their charts were reviewed for the reason for the transfusion(s). The charts of those individuals who received granulocyte transfusions for IFS were further reviewed for the following factors: age at transfusion, original diagnosis, IFS pathogen, granulocyte transfusion dates, number of transfusions, reason for discontinuing the transfusion, additional therapies (medical, surgical), last known follow-up date, and status at last known follow-up.
At the Medical College of Wisconsin and the Blood Center of Wisconsin, our harvest protocol includes contacting a nonmatched, granulocyte donor and performing an infectious disease screening. This is typically done 1 day before the planned harvest. During that visit, the donors are given a dose of granulocyte-macrophage colony–stimulating factor to help stimulate granulocyte production. The Blood Center of Wisconsin does not administer corticosteroids to encourage peripheral migration of polymorphonuclear cells. The donor returns the following day, once the screening tests have been completed and donates the granulocytes. These are then processed and transfused into the patient.
We cross-referenced patients by International Classification of Diseases, Ninth Revision , code to determine the number with the diagnosis of “unspecified mycoses” (117.9) and “sinusitis” acute or chronic (461.8 and 473, respectively) to try to identify the number of patients with IFS.
A Medline search was performed using the terms granulocyte transfusion and cross-referencing it with invasive fungal sinusitis . In addition, a manual review of citations within bibliographies was performed.
2
Methods
A retrospective chart review was performed at the Medical College of Wisconsin and its affiliates, The Blood Center of Wisconsin, Children’s Hospital of Wisconsin, and Froedtert Hospital. Institutional review board approval was obtained from the Medical College of Wisconsin (PRO 11303) (covering Children’s Hospital of Wisconsin and Froedtert Hospital) as well as from the Blood Center of Wisconsin (BC 09–19).
The names of patients receiving granulocyte transfusions through the Blood Center of Wisconsin were obtained, and their charts were reviewed for the reason for the transfusion(s). The charts of those individuals who received granulocyte transfusions for IFS were further reviewed for the following factors: age at transfusion, original diagnosis, IFS pathogen, granulocyte transfusion dates, number of transfusions, reason for discontinuing the transfusion, additional therapies (medical, surgical), last known follow-up date, and status at last known follow-up.
At the Medical College of Wisconsin and the Blood Center of Wisconsin, our harvest protocol includes contacting a nonmatched, granulocyte donor and performing an infectious disease screening. This is typically done 1 day before the planned harvest. During that visit, the donors are given a dose of granulocyte-macrophage colony–stimulating factor to help stimulate granulocyte production. The Blood Center of Wisconsin does not administer corticosteroids to encourage peripheral migration of polymorphonuclear cells. The donor returns the following day, once the screening tests have been completed and donates the granulocytes. These are then processed and transfused into the patient.
We cross-referenced patients by International Classification of Diseases, Ninth Revision , code to determine the number with the diagnosis of “unspecified mycoses” (117.9) and “sinusitis” acute or chronic (461.8 and 473, respectively) to try to identify the number of patients with IFS.
A Medline search was performed using the terms granulocyte transfusion and cross-referencing it with invasive fungal sinusitis . In addition, a manual review of citations within bibliographies was performed.
3
Results
A total of 20 patients received granulocyte transfusions at the Medical College of Wisconsin between October 2003 and June 2009. Three of these patients received granulocyte transfusions for fulminant IFS ( Tables 1 and 2 ). Ages ranged from 14 to 59 years. Diagnoses included acute lymphocytic lymphoma, multiple myeloma, and non-Hodgkin lymphoma. Two patients had Mucor as the IFS pathogen, and the third patient had Aspergillus . Diagnosis was based on histopathologic evaluation, not culture, so speciation is not possible. All 3 patients were taken to the operating room for endoscopic evaluation and surgical debridement. The number of surgical debridements ranged from 1 to 6 depending on the extent of fungal involvement. The number of granulocyte transfusions ranged from 3 to 6. Two patients had spontaneous returns of their absolute neutrophil counts; thus, the transfusions were stopped. The third patient developed respiratory complications from the transfusions, and they were discontinued. At the last follow-up, all 3 patients were deceased. The 2 patients who had return of their neutrophil counts died of their malignancies with no evidence of IFS. The third individual died of the underlying malignancy and extension of the Mucor .
| Patient | Age at transfusion | Original diagnosis | IFS pathogen | Other therapies | Extent of fungal involvement | No. of surgical debridements |
|---|---|---|---|---|---|---|
| MCW1 | 14 y | Acute lymphocytic leukemia | Mucor | Posaconazole GMCSF | Nasal cavity paranasal sinuses orbit brain | 6 |
| MCW2 | 51 y | Multiple myeloma | Mucor | Posaconazole micafungin | Nasal cavity paranasal sinuses | 1 |
| MCW3 | 59 y | Non-Hodgkin lymphoma | Aspergillus | Posaconazole micafungin Ampho B GCSF | Nasal cavity paranasal sinuses orbit infratemporal fossa | 3 |
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