Is nonmyeloablative stem cell transplantation (Nst) Associated with increased risk of delayed hemolysis?

Abstract

Increased risk of delayed hemolysis following conventional minor ABO mismatched allogeneic bone marrow transplantation (BMT) has been found to be associated with peripheral blood stem cell transplantation (PBSCT), non-T-cell depletion, and immunosuppression by Cyclosporin A (CSA) or FK506. We recently demonstrated that it is possible to achieve stable engraftment with mixed or complete chimerism using nonmyeloablative conditioning consisting of Fludarabine, Busulfan and ATG followed by G-CSF mobilized PBSCT, with CSA as the sole anti-GVHD prophylaxis. Four patients (pts.) who under went NST and developed delayed hemolysis are reviewed here. All were male, of median age 18 (4–56) years. Two suffered from βThalassemia major, 1 from AML, and 1 from CML. Three were transplanted from fully matched sibling donors (2 male, 1 female), and one from a 1 locus mismatched family-related female donor. All pts. engrafted with mixed (n=3) or complete (n=1) chimerism. The donors' engrafted with mixed (n=3) or complete (n=1) chimerism. The donors' blood groups were A− (n=2), A+ (n=1) and B+ (n=1), while the recipients' were B−, A+, O+ and AB+, respectively. Clinically significant hemolysis occurred at day 173 (66–240) post-NST. Hemoglobin dropped to 5.3 (5.2–6.3) g/dL, hematocrit to 15.4 (15.3–18.9) %, with 4.1 (2.7–7.8) reticulocytes. All pts. had hyperbilirubinemia and increased LDH levels. Their haptoglobulin dropped to less than 50 mg%. In 3 recipients increased levels of isohemagglutinin IgG titers were observed. The pts. were treated successfully with multiple RBC transfusions, fluids, diuretics, plasma exchange, high dose immunoglobulins, steroids and erythropoietin. Since NST achieves a state of mixed chimerism without ablation of the recipients' B cell response to RBC-mismatched antigens, we conclude that as it may be associated with an increased risk of delayed hemolysis.