Chronic granulomatous disease 100% corrected by displacement bone marrow transplantation from a volunteer unrelated donor

Abstract

A boy whose chronic granulomatous disease (CGD) manifested in infancy, and whose elder brother had died at 7 years of age, had phagocytes with complete lack of functional cytochrome B-245 and which could not be induced by interferon gamma to achieve adequate staphylococcal killing. He underwent an elective displacement bone marrow transplant from a volunteer unrelated donor at the age of 8 months. This has achieved 100% replacement of the CGD granulocytes by those of the normal volunteer and the boy has since had a normal childhood for 3 years. Six previous transplants for CGD are briefly reviewed and illustrate that the host abnormal marrow must be completely displaced using an adequate dose of busulphan to ensure 100% stable engraftment of the donor's marrow and that this is best done under elective conditions before septic foci and irreversible organ damage have occurred. Criteria need to be developed to identify early those patients likely to have severe morbidity.

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

“…[9][10][11][12][13][14][15][16][17][18][19] In these cases, complications occurring after transplant generally correlated with the severity of the basic disease: patients with recurrent bacterial and fungal infections gradually leading to organ disability had a worse outcome than patients transplanted early on in the course of the disease. [9][10][11][12][13][14][15][16][17][18][19] The indication, therefore, is that BMT should preferably be performed early on in the disease, if the procedure-related risks can be reduced.…”

“…1,[7][8][9] Allogeneic bone marrow transplantation is a therapeutic option that has been used in CGD patients since 1976 with varying results. [9][10][11][12][13][14][15][16][17][18][19] However, the procedure continues to be controversial for CGD, as well as other genetic diseases, as it still carries a considerable risk to the recipient, and some physicians feel that it should be restricted to selected, very severe, cases in which prophylactic therapy is problematic. 17,20 Generally speaking, BMT results in CGD are better when the patient is transplanted in an infection-free interval, before septic foci and irreversible organ damage have occurred.…”

“…17,20 Generally speaking, BMT results in CGD are better when the patient is transplanted in an infection-free interval, before septic foci and irreversible organ damage have occurred. 9,16 The common notion is that the abnormal host marrow must be completely displaced by adequate doses of myeloablative agents, mainly busulfan and cyclophosphamide, before transplant in order to ensure 100% stable engraftment of the donor's marrow. 9,19 However, the myeloablative conditioning tends to result in increased organ toxicity, transplant-related complications, morbidity and mortality, especially in CGD patients with recurrent bacterial and fungal infections.…”

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

“…[1][2][3][4] However, control of therapy- There has been an increase in the number of reports of successful hematopoietic stem cell transplantation (HSCT) for patients with CGD. [5][6][7][8][9][10][11][12] Most of these patients receive transplants from HLA-identical siblings during the first decade. There are few reports of unrelated bone marrow transplantation (UBMT).…”

Successful treatment of invasive aspergillosis in chronic granulomatous disease by granulocyte transfusions followed by peripheral blood stem cell transplantation

“…[1][2][3] Bone marrow transplantation in CGD can be curative and has been successful in several cases. [4][5][6][7][8][9][10][11] However, it carries a substantial risk of morbidity and mortality due to the toxicity of the preparative regimen, especially in patients who already are debilitated as a consequence of severe and recurrent infections.…”