Successful Allogeneic HSCT in a Patient with Chronic Granulomatous Disease and McLeod Phenotype after Sensitization to Kx- and K- Antigens.

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by the defective generation of active oxygen metabolites by phagocytic cells. CGD can be associated with a condition called McLeod phenotype if a large X-chromosomal deletion includes the genes for gp91phox and the XK-protein. The absence of XK on erythrocyte membranes concomitantly leads to a reduced expression of Kell antigens. If transfused with red cells expressing these proteins, patients with CGD and McLeod phenotype become sensitized which may limit future transfusions. We present a patient with CGD and McLeod phenotype, who had received Kx- (the antigen of XK) and K- positive red cells at the age of 10 months; 9 years later he was given granulocyte transfusions following lung surgery because of pulmonary aspergillosis. Shortly thereafter he required a transfusion of red cells, to which he responded with a severe hemolytic adverse reaction. Antibodies against Kx- and K- antigens were detected. Hematopoietic stem cell transplantation (HSCT) is potentially curative in CGD and was planned for this boy at the age of 14 years because of progressive aspergillosis. Transfusions in this situation can only be given from Kx- and K- antigen negative donors suffering from McLeod syndrome themselves. Resources for these products are extremely limited. Furthermore any transplant would contain Kx- antigen and could potentially boost immunological reactions inducing graft rejection. To cope with these potential complications the following strategy was used: before HSCT autologous red cells as well as bone marrow for an autologous rescue therapy in case of graft rejection were cryopreserved. B-cells were depleted in the patient by two infusions of Mabthera (anti-CD20 antibody). Total body irradiation (12Gy), fludarabine and ATG were given for conditioning. No blood products were necessary during conditioning and before HSCT from a HLA- matched unrelated donor. Transfusions of platelets and red cells from Kx- antigen positive and K- negative donors were well tolerated 11 days after HSCT. No GvHD occurred on prophylaxis with CSA. Hematological and immunological reconstitution with complete donor chimerism was uneventful except a transient episode of immune mediated thrombocytopenia at 5 months after HSCT which responded promptly to steroids. After 10 months of follow up the patient is currently fully engrafted, in an excellent clinical condition and back to school. Conclusion: In patients with X- linked CGD screening for McLeod phenotype needs to be performed prior to transfusion of blood products. Even if sensitization to Kx- and K- antigens has occurred, HSCT can be curative as demonstrated for the first time in this report.