The decision to treat other primary immunodeficiency diseases with HSCT is more difficult because it is difficult to predict the prognosis of a particular patient because of the variability in clinical course of most primary immunodeficiency diseases. This must be weighed with the risks of transplantation. In addition, HSCT for other primary immunodeficiencies is less successful than for SCID because patients typically have some T-cell function and require conditioning with the risks that it entails. The availability of a matched related sibling favors the decision to perform HSCT. Disorders of B cells have not been treated with HSCT because, in many cases, donor B cells do not engraft, and patients usually do well with intravenous immunoglobulin. Regardless a variety of primary immunodeficiencies have been treated with HSCT (see Table 76-1)
Rejection of the grafted cells is the first potential complication of HSCT and depends on the immunocompetence of thepatient, the degree of MHC incompatibility, and the number of cells administered. Preconditioning with myeloablativedrugs, such as busulfan and cyclophosphamide, can preventgraft rejection but may be complicated by pulmonary toxicity and by venoocclusive disease of the liver, which resultsfrom damage to the hepatic vascular endothelium and canbe fatal. Myeloablation results in anemia, leukopenia, andthrombocytopenia, making patients susceptible to infectionand bleeding disorders. Neutropenic precautions should bemaintained and patients supported with red blood cell andplatelet transfusions until the red blood cell, platelet, and neutrophil lineages engraft. Reduced intensity preconditioninghas been used recently to prevent graft rejection and decreasethe adverse effects of myeloablation. B-cell lymphoproliferative disorder can develop after T-cell depleted bone marrowtransplantation. GVHD can arise from an MHC-mismatched transplantation or from mismatch in minor histocompatibility antigens that are not tested for before transplantation.T-cell depletion of haploidentical bone marrow reduces the risk of GVHD. Patients with SCID transplanted withT-cell–depleted haploidentical bone marrow do not usuallydevelop severe GVHD. Acute GVHD begins 6 or more daysafter transplantation and can result from transfusion of non-irradiated blood products in patients with no T-cell function.Acute GVHD presents with fever, skin rash, and severe diarrhea. Patients develop a high, unrelenting fever; a morbilliform maculopapular erythematous rash that is painful andpruritic; hepatosplenomegaly and abnormal liver functiontests; and nausea, vomiting, abdominal pain, and waterydiarrhea. Acute GVHD is staged from grades 1 to 4, depending on the degree of skin, fever, gastrointestinal, and liverinvolvement. Chronic GVHD results from acute GVHD lasting longer than 100 days and can develop without acuteGVHD or after acute GVHD has resolved. Chronic GVHD is characterized by skin lesions (hyperkeratosis, reticularhyperpigmentation, fibrosis, and atrophy with ulceration),limitation of joint movement, interstitial pneumonitis, andimmune dysregulation with autoantibody and immune complex formation.
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