Abstract
Stem cell transplantation (SCT), indicated for many non-malignant disorders, is limited by donor availability, graft rejection (GR), toxicities of conditioning, morbidity and mortality (TRM), and graft versus host disease (GVHD). To overcome these barriers, we tested a novel conditioning for SCT. It was designed to support engraftment by deleting host immune reactive lymphocytes and macrophages. Campath -1H (anti-CD52 mab) was given on days −21, −20, and −19 (total dose 48 mg), fludarabine (day −8 to −4) (total 150 mg/m2) and melphalan on day −3 (140 mg/m2). Stem cell sources were related/unrelated bone marrow (BM) (8), peripheral blood (PB) (5) and umbilical cord blood (UCB) (3). GVHD prophylaxis was cyclosporine (tapered after 3 months), methylprednisone (tapered after day +28) and methotrexate on days +1, +3, and +6 (except in UCBT). End points studied were engraftment and TRM. Sixteen patients (1.5–40 yrs) with aplastic anemia (5), Hurler's (2), sickle cell anemia, XLAAD, histiocytosis (3), thalassemia, adrenoleukodystrophy, Evan's syndrome and dyserythropoietic anemia were transplanted. Median follow-up was 219 days (66–845). The regimen was tolerated well. All patients that survived >1 month engrafted. Neutrophils (ANC >500/dL) engrafted at 12.5 days; platelets (>50,000/dL) at 21 days (median). Skin GVHD developed in 3 patients and resolved early. Eight patients are off; 4 are tapering immune suppression. All survivors have either stable disease or are cured. One survivor had a normal pregnancy. Two patients died prior to engraftment from previously acquired Pseudomonas infection. Two died of CMV disease and intracranial hemorrhage/refractory thrombocytopenia respectively after engraftment. Other complications were bacterial and viral infections occurring within 100 days. Profound lymphopenia was present 1 month. NK cells recovered by 3 months, CD8+ cells by 6 months, CD4+ and B cells 6–9 months after transplant. Immunoglobulin (Ig M and A) levels reflected B cell numbers; Ig A recovered later than IgM. In summary, successful engraftment despite varied stem cell sources was achieved without significant GVHD using this regimen. Lymphopenia resulted in a significant infection risk early post transplant, requiring close surveillance and intervention. Thus, this transplant regimen is well tolerated and may preserve fertility, making it a promising alternative to conventional SCT.
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Rao, A., Hayashi, R., Grossman, W. et al. Reduced Intensity Conditioning Therapy Using Campath-1H is Successful for Stem Cell Transplantion in Non-Malignant Disorders.. Pediatr Res 56, 669 (2004). https://doi.org/10.1203/00006450-200410000-00036
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DOI: https://doi.org/10.1203/00006450-200410000-00036