Successful unrelated bone marrow transplantation for a patient with chronic granulomatous disease and associated resistant pneumonitis and Aspergillus osteomyelitis

Abstract

Summary:We describe the successful treatment of a 20-year-old patient with chronic granulomatous disease (CGD), by unrelated bone marrow transplantation (UBMT). The patient is relatively old compared to other CGD patients treated with BMT. He had had repeated serious infections from early childhood and was diagnosed as CGD, gp91-phox deficiency. Prolonged antibiotic-resistant pneumonitis worsened when the patient was 18 years old. In addition, he suffered Aspergillus osteomyelitis and acute renal failure due to amphotericin B. He received 94 granulocyte transfusions from 94 adult donors and the infections gradually improved. In September 1998, at 20 years of age, he underwent UBMT from an HLA 6 antigen-matched male donor, with CY and TBI conditioning. He received MTX and CsA as prophylaxis against GVHD. No serious complications occurred and rapid engraftment was achieved. Acute GVHD (grade 2, at day 19) and chronic GVHD (limited, at day 192) occurred. However, both were easily controlled. The patient is alive and well with no late rejection 26 months after UBMT. Bone Marrow Transplantation (2001) 28, 83-87. Keywords: chronic granulomatous disease; unrelated bone marrow transplantation; aspergillosis; granulocyte transfusions Chronic granulomatous disease (CGD) is a primary immunodeficiency disease characterized by recurrent severe bacterial and fungal infections during early childhood. CGD is caused by dysfunctional phagocytosis that is a result of defective NADPH oxidase. Deficiency of this oxidase causes a marked reduction in the phagocyte respiratory burst resulting in defective microbial killing. IFN-␥, supportive therapy and prophylactic administration of therapeutic agents such as sulfamethoxazole-trimethoprim have improved the prognosis.

Hematopoietic stem cell transplantation from matched unrelated donors in chronic granulomatous disease

“…However, in the absence of a family donor, the use of alternative donors for HSCT is only rarely considered so far due to the concern of increased transplantation associated risks such as higher toxicity and more severe GvHD. Published reports with successful HSCT from a MUD in CGD patients between the ages of 8 months and 39 years are few and mostly single case reports [7][8][9][10][11][12][13][14].…”

Advances in treatment for chronic granulomatous disease

“…The majority of these transplants have occurred from 2000 on and have a median follow-up of 25 months. (personal communication) An additional 50 patients outside of the US and Canada are reported in various publications including single case reports and a survey of the European experience [31][32][33][34][35][36][37][38][39][40][41][42][43][44] with an overall survival rate of 94% and a success rate of 43 out of the 50 achieving stable donor engraftment. The longest reported follow up to date from the Europeans is 5 years in a patient transplanted using a HLA-matched sibling and a Busulfan/Cytoxan-based conditioning regimen.…”

Invasive Fungal Infections in Patients with Chronic Granulomatous Disease

“…Primary cutaneous aspergillosis due to A. fumigatus occurred in three cases, all of them in relation to direct inoculation of disrupted skin [78][79][80]. In four patients A. fumigatus caused isolated brain abscesses [7,22,57,73]. It should be emphasized that the symptoms can be very indolent ranging from mild fever and headache in the absence of any localizing neurologic signs [57], up to isolated seizures mimicking intracranial tumor [58].…”