Page 84 - Haematologica May 2020

A. Magnani et al.
rho=0.94
P-value <0.001
Figure 2. Correlation between HbS in patients after hematopoietic stem cell transplantation (HSCT) and in donors, regardless of the donor’s genotype, divided into group 1 (mixed chimerism [MC] <70%, red dots), group 2 (MC 70-95%, green dots) and group 3 (MC 95-99.5%, blue dots). The line corresponds to y=x. Rho: Spearman's rank correla- tion coefficient.
selective advantage was observed not only in the periph- eral compartment but also in erythroid progenitors/pre- cursors.
Patients with WBC donor chimerism ≤50%
Six patients in group 1 (three with AA donors and three with AS donors) presented with a total WBC donor chimerism level ≤50% (median [range]: 20% [16-44%]) (Table 1, Online Supplementary Table S1). A unique chimerism profile was observed, with higher levels of donor chimerism in the CD3+ cells than in the other line- ages unlike most of the included patients (Online
Supplementary Figure S3-4).
This subgroup of patients was characterized by younger
age at transplant (median [range]: 7.15 years [3.4-10.8]), a longer post-HSCT follow-up period (median [range]: 68.5 months [33-153]), and lower Hb levels (median [range]: 10.1 g/dL [8.4-11.8]), when compared with the other patients in group 1. As mentioned above, HbS levels in these patients were higher than the corresponding donors (Figure 2, Online Supplementary Table S1). For these six patients, the reticulocyte count at last follow-up was greater than 100x109/L; however, this was associated with a Hb level <10 g/dL only in three with very low myeloid chimerism (≤21%) and transplanted with AS donors (patients #2, #8 and #9, Online Supplementary Table S1). In these three cases, reticulocyte count was higher than 150x109/L and associated with an HbS >47.5%. The three patients transplanted with an AS donor (patients #2, #8 and #9) presented a particularly low level of donor myeloid chimerism (5.4%, 10% and 16%, respectively– the lowest levels in the whole cohort) and highest HbS levels (68.1%, 60.6% and 47.5%, respectively) (Online
Supplementary Table S1). The three patients received donor lymphocyte infusions (DLI); this treatment did not modify the donor chimerism and was not associated with graft-versus-host disease (GvHD) occurrence. Two of the patients (#2 and #9) required sporadic RBC transfusions between 24 and 43 months after HSCT. Neither of them has required RBC transfusions since then. The three patients developed hemolytic anemia (patients #2, #8 and #9), but only one had a suspected VOC with liver involve- ment (patient #2; hepatic sequestration was confirmed by a histological assessment). Before HSCT, patient #8 had presented with severe, SCD-related cerebral vasculopathy (bilateral stenosis of the cervical carotid arteries, and aneurism of the internal carotid arteries); this condition was stable after HSCT. Patients #8 and #9 are dizygotic twins who received grafts from different sibling AS donors (HbS fractions in the donors: 44.6% and 43.6%, respectively) at 5 years of age in 2003 and at 4 years of age in 2002, respectively. The level of donor chimerism fell rapidly in both twins, and then stabilized at a value below 20% in the second year post-HSCT. The HbS fraction pro- gressively rose to a value of 60.6% and 47.5% in patients #8 and #9, respectively.
Interestingly, one patient (#6, with an AA donor) dis- played a WBC donor chimerism level as low as 19% and myeloid chimerism of 31% but had a total Hb level of 11.8 g/dL and an HbS percentage of 5.6%.
Our results showed that HbS levels were closely corre- lated with chimerism in the myeloid compartment. The analyses of a subgroup of patients with low donor chimerism suggested that a myeloid chimerism of 30% is sufficient for preventing VOC in transplants from AA donors but not constantly from AS donors; in contrast, the
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