Long-term itraconazole prophylaxis against Aspergillus infections in thirty-two patients with chronic granulomatous disease

Mouy, Richard; Veber, Florence; Blanche, Stéphane; Donadieu, Jean; Brauner, Raja; Levron, Jean-Claude; Griscelli, C; Fischer, Alain

doi:10.1016/s0022-3476(05)82023-2

Cited by 148 publications

(65 citation statements)

References 32 publications

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“…18 A Dutch study of itraconazole capsules in 49 adult neutropenic patients undergoing intensive chemotherapy reported five proven SFIs (10%). 9 An American study showed SFI rates of 24% (11/45) in similar patients.…”

Section: Discussionmentioning

confidence: 99%

Itraconazole oral solution as antifungal prophylaxis in children undergoing stem cell transplantation or intensive chemotherapy for haematological disorders

Foot

Veys

Gibson

1999

Bone Marrow Transplant

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Summary:This was an open study of oral antifungal prophylaxis in 103 neutropenic children aged 0-14 (median 5) years. Most (90%) were undergoing transplantation for haematological conditions (77% allogeneic BMT, 7% autologous BMT, 6% PBSC transplants and 10% chemotherapy alone). They received 5.0 mg/kg itraconazole/day (in 10 mg/ml cyclodextrin solution). Where possible, prophylaxis was started at least 7 days before the onset of neutropenia and continued until neutrophil recovery. Of the 103 who entered the study, 47 completed the course of prophylaxis, 27 withdrew because of poor compliance, 19 because of adverse events and 10 for other reasons. Two patients died during the study and another five died within the subsequent 30 days. No proven systemic fungal infections occurred, but 26 patients received i.v. amphotericin for antibiotic-unresponsive pyrexia. One patient received amphotericin for mycologically confirmed oesophageal candidosis. Three patients developed suspected oral candidosis but none was mycologically proven and no treatment was given. Serious adverse events (other than death) occurred in 21 patients, including convulsions (7), suspected drug interactions (6), abdominal pain (4) and constipation (4). The most common adverse events considered definitely or possibly related to itraconazole were vomiting (12), abnormal liver function (5) and abdominal pain (3). Tolerability of study medication at end-point was rated as good (55%), moderate (11%), poor (17%) or unacceptable (17%). Some patients had poor oral intakes due to mucositis. No unexpected problems of safety or tolerability were encountered. We conclude that itraconazole oral solution may be used as antifungal prophylaxis for neutropenic children. Keywords: itraconazole; mycoses; bone marrow transplantation; neutropenia; pediatrics Although advances in cytotoxic chemotherapy, stem cell transplantation and supportive care have greatly improved the survival of children with leukaemia, infections continue

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Section: Discussionmentioning

confidence: 99%

Itraconazole oral solution as antifungal prophylaxis in children undergoing stem cell transplantation or intensive chemotherapy for haematological disorders

Foot

Veys

Gibson

1999

Bone Marrow Transplant

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“…In this paper, we have presented our use of this approach on a child with advanced CGD, with restrictive lung disease and fibrosis due to recurrent pulmonary infections, in whom the accepted treatments of sulphamethazole trimethoprim, itraconazole and interferon-␥, known to improve prognosis and survival, [34][35][36] had failed. The transplant went extremely well, with fast and stable engraftment, partial donor chimerism, minimal transient skin GVHD, and no transplantrelated toxicity.…”

Section: Discussionmentioning

confidence: 99%

Donor lymphocyte infusion post-non-myeloablative allogeneic peripheral blood stem cell transplantation for chronic granulomatous disease

Nagler

Ackerstein

Kapelushnik

et al. 1999

Bone Marrow Transplant

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Summary:Chronic granulomatous disease (CGD) is a primary immunodeficiency disease symptomized by failure to generate superoxide and recurrent bacterial and fungal infections. Allogeneic bone marrow transplantation (BMT) is one of the therapeutic options available. However, it presents considerable risk to the recipient, especially if the patient is already at an advanced stage of disease, after repeated bacterial and fungal infections and organ damage. We present a case report of a 6-year-old child with long-standing CGD, severe clubbing, and jeopardized pulmonary function after multiple bacterial pulmonary infectious episodes, who had failed treatment with sulphamethazole trimethoprim, multiple antibiotic courses, itraconazole, as well as steroid and interferon-␥ therapy. He underwent allogeneic peripheral blood stem cell transplantation (alloPBSCT) from his HLA-matched MLC non-reactive sister following non-myeloablative conditioning. His ANC did not fall below 0.2 ؋ 10 9 /l, his lowest WBC was 0.6 ؋ 10 9 /l, and his platelets did not fall below 28 ؋ 10 9 /l. He had normal engraftment, with no mucositis or organ toxicity. Neither parenteral nutrition nor platelet infusions were necessary. Partial donor chimerism following alloPBSCT was converted to full donor chimerism and superoxide production reverted to normal after donor lymphocyte infusions (DLI) from his HLA-matched sister. Twenty four months post transplant the patient is well, with stable and durable engraftment, 100% donor chimerism, normal superoxide production, no GVHD, and stabilization of his pulmonary condition. We suggest that alloPBSCT preceded by non-myeloablative conditioning and followed by DLI may constitute a successful

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“…The molecule is taken-up by neutrophils and exerts intracellular activity (Perfect et al, 1993). In an open-label study on itraconazole prophylaxis in 30 CGD-patients the rate of Aspergillus infections could be reduced to one-third in comparison with historical controls (Mouy et al, 1994). A randomized, double-blind, placebocontrolled crossover study has recently confirmed these observations (Gallin et al, 2003).…”

Section: Antimycotic Prophylaxismentioning

confidence: 93%

Modern management of chronic granulomatous disease

2008

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SummaryChronic granulomatous disease (CGD) is a rare primary immunodeficiency disorder of phagocytic cells resulting in failure to kill a characteristic spectrum of bacteria and fungi and in defective degradation of inflammatory mediators with concomitant granuloma formation. Current prophylaxis with trimethoprim-sulfamethoxazole, itraconazole and in selected cases additional interferon gamma is efficient, but imperfect. A significant recent progress towards new antibiotic (e.g. linezolid) and antifungal (e.g. voriconazole and posaconazole) therapy will allow survival of most patients into adulthood. Adolescent and adult CGD is increasingly characterized by inflammatory complications, such as granulomatous lung and inflammatory bowel disease, requiring immunosupressive therapy. Allogeneic haematopoietic stem cell transplantation from a human leucocyte antigen identical donor is currently the only proven curative treatment for CGD and can be offered to the selected patients. Gene-replacement therapy for patients lacking a suitable stem cell donor is still experimental and faces major obstacles and risks. However, it may offer some transitory benefits and has helped in a few cases to overcome life-threatening infections.

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Long-term itraconazole prophylaxis against Aspergillus infections in thirty-two patients with chronic granulomatous disease

Cited by 148 publications

References 32 publications

Itraconazole oral solution as antifungal prophylaxis in children undergoing stem cell transplantation or intensive chemotherapy for haematological disorders

Itraconazole oral solution as antifungal prophylaxis in children undergoing stem cell transplantation or intensive chemotherapy for haematological disorders

Donor lymphocyte infusion post-non-myeloablative allogeneic peripheral blood stem cell transplantation for chronic granulomatous disease

Modern management of chronic granulomatous disease

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