Marrow engraftment in 100cGy treated hbbth-1/ hbbth-1 thalassemics mice

We have shown that high levels of chimerism can be obtained when 40×106 male BALB/c marrow cells were infused into 100 cGy treated female BALB/c hosts. The Hbbth-1/Hbbth-1 mouse is a thalassemic mutant which was backcrossed onto a C57black/J background. We have evaluated engraftment of 40 million B6.SJL marrow cells into 100 cGy treated Hbbth-1/Hbbth-1 mice. Chimerism was evaluated by determining the % of CD45.1 positive cells. Seven thalassemic mice were transplanted and 6 showed initial engraftment varying from 2.0 to 90% at 3 to 6 weeks post marrow infusion. One mouse lost engraftment by 59 weeks, while two showed initial engraftment at 3 weeks, a decrease over 6–15 weeks and recovery of engraftment at 18.5 weeks. Two mice showed increased hemoglobin and decreased reticulocyte values. One had complete correction of anemia at approximately 39 to 58% chimerism over 18.5 weeks, while the other mouse showed correction of the anemia transiently at 19–20% chimerism (6–9 weeks post transplant). Chimerism was equally distributed between granulocyte (Gr-1 positive), B cell (B220 positive) and erythroid cells (Ter119 positive). Second transplant at 12 weeks of 40 million dose cells did not augment chimerism and 6 transplants of Hbbth-1/Hbbth-1 mice with CBA/J marrow showed no engraftment. These data indicated the feasibility of a low dose irradiation regimen for transplantion in thalassemic mice and showed correction of anemia at chimerism levels as low as 20% donor cells.