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

Abstract

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

Non-myeloablative hematopoietic cell transplant for treatment of nonmalignant disorders in children

“…Overall, 7 patients have survived from 16 to 26 months, there were 2 deaths related to the procedure from pneumococcal pneumonia and GVHD, respectively, anda third patient who rejected the gran died anera second transplant. A similar approach was reported by Nagler that resulted in full chimerism with no GVHD in a child with CGD [27].…”

Treatment of chronic granulomatous disease with myeloablative conditioning and an unmodified hemopoietic allograft: a survey of the European experience, 1985-2000

“…The 4 deaths occurred only in the group of patients with pre-existing fungal infections refractory to all conventional treatments. We can therefore conclude that HLA-genoidentical HSCT, hitherto reported only in individual CGD patients, [6][7][8][9][10][11][17][18][19][20][21][22] is a valid alternative to conventional treatment.…”

Effective donor lymphohematopoietic reconstitution after haploidentical CD34+-selected hematopoietic stem cell transplantation in children with refractory severe aplastic anemia

“…Other investigators have reported stem cell boosts, 28 DLI, 29 or CD34 þ -enriched DLI 30 as an effective therapy for declining donor chimerism, poor graft function, or mixed chimerism. Anti-T cell therapy with ATG and CAMPATH proved ineffective at stabilizing mixed chimerism in patient 2.…”