Results of minimally toxic nonmyeloablative transplantation in patients with sickle cell anemia and β-thalassemia Robert Iannone, James F Casella, Ephraim.

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Results of minimally toxic nonmyeloablative transplantation in patients with sickle cell anemia and β-thalassemia Robert Iannone, James F Casella, Ephraim J Fuchs, Allen R Chen, Richard J Jones, Ann Woolfrey, Michael Amylon, Keith M Sullivan, Rainer F Storb, Mark C Walters Biology of Blood and Marrow Transplantation Volume 9, Issue 8, Pages 519-528 (August 2003) DOI: 10.1016/S1083-8791(03)00192-7

Figure 1 Hematologic recovery after nonmyeloablative hematopoietic stem cell transplantation (HCT). A, Neutrophil levels after nonmyeloablative HCT are depicted. The duration of having an ANC <0.5 × 109/L was <5 days for most patients. In patient 3, the ANC decreased to 0 after a low dose of CD34+ cells in the marrow inoculum; donor engraftment was never shown. B, Serial platelet count determinations after nonmyeloablative HCT are depicted. After nonmyeloablative HCT, the platelet count was never <50 × 109/L in 4 of 7 patients. Patient 3 experienced profound thrombocytopenia and received multiple platelet transfusions from 20 to 40 days after nonmyeloablative HCT. Biology of Blood and Marrow Transplantation 2003 9, 519-528DOI: (10.1016/S1083-8791(03)00192-7)

Figure 2 Engraftment of donor cells after transplantation. A, The percentages of donor engraftment measured in unfractionated blood and bone marrow mononuclear cell preparations are plotted as a function of time in days after transplantation. Chimerism fraction results from blood and bone marrow samples were closely correlated (r = 0.85). In cases in which blood and marrow measurements were performed on the same day, results from marrow are shown. There was a decrease in donor chimerism 200 days after nonmyeloablative HCT in patients 1 and 2, 60 days after nonmyeloablative HCT in patients 4 and 5, and 120 days after nonmyeloablative HCT in patients 6 and 7. B, The level of donor T-cell chimerism (CD3+ cells) in peripheral blood after nonmyeloablative HCT for patients 4 through 7 is depicted. These low levels contrast with a higher level of donor chimerism among unfractionated mononuclear cells (patients 5 through 7; panel A). Biology of Blood and Marrow Transplantation 2003 9, 519-528DOI: (10.1016/S1083-8791(03)00192-7)

Figure 3 Improvement in hematologic parameters after donor engraftment. The fraction of sickle Hb (S and D) is depicted in relation to serial measurements of Hb concentration, reticulocyte count, and donor chimerism after transplantation. Patients 2 and 6 had Hb SS and donors with Hb AA. Patient 1 has the genotype Hb SDLA and a donor with Hb AS; thus, the percentage of Hb DLA is plotted. Because the fraction of Hb D was equivalent to the fraction of Hb S in sickle erythrocytes before transplantation in this patient, the total fraction of abnormal Hb in recipient cells should be twice what is plotted. A suppression of reticulocytosis was observed among patients who had mixed chimerism, even when the Hb concentration was less than normal. MMF was restarted in patient 6 on day 161 when donor chimerism was noted to have decreased. After several stable donor chimerism measurements, the dose of MMF was decreased on day 182 because of myelosuppression. It was increased on day 224 when donor chimerism was again noted to have decreased, but donor engraftment was lost. d/c indicates discontinued. Biology of Blood and Marrow Transplantation 2003 9, 519-528DOI: (10.1016/S1083-8791(03)00192-7)

Figure 3 Improvement in hematologic parameters after donor engraftment. The fraction of sickle Hb (S and D) is depicted in relation to serial measurements of Hb concentration, reticulocyte count, and donor chimerism after transplantation. Patients 2 and 6 had Hb SS and donors with Hb AA. Patient 1 has the genotype Hb SDLA and a donor with Hb AS; thus, the percentage of Hb DLA is plotted. Because the fraction of Hb D was equivalent to the fraction of Hb S in sickle erythrocytes before transplantation in this patient, the total fraction of abnormal Hb in recipient cells should be twice what is plotted. A suppression of reticulocytosis was observed among patients who had mixed chimerism, even when the Hb concentration was less than normal. MMF was restarted in patient 6 on day 161 when donor chimerism was noted to have decreased. After several stable donor chimerism measurements, the dose of MMF was decreased on day 182 because of myelosuppression. It was increased on day 224 when donor chimerism was again noted to have decreased, but donor engraftment was lost. d/c indicates discontinued. Biology of Blood and Marrow Transplantation 2003 9, 519-528DOI: (10.1016/S1083-8791(03)00192-7)