Reduced-Intensity Transplants - Red Cell Antigens, Antibodies, and Blood Product Usage.

Introduction Reduced-intensity conditioning (RIC) transplants currently comprise 25–30% of allogeneic transplants in Europe. Previously reported data suggested delayed donor erythroid engraftment and isohaemaglutinin disappearance in RIC transplants, Additionally, reduced blood product usage has been reported. We prospectively studied

• the kinetics of donor red cell engraftment;

• kinetics of recipient- and donor-type isohaemaglutinnins, and

• usage of blood products, in 100 consecutive patients undergoing haemopoietic cell transplantation (HCT) for haematological malignancy at a single centre:

Material and Methods 59 patients had RIC conditioning (37 FB₈C (Fludarabine Busulphan 8mg/kg Campath1H), 22 FMC, Melphalan 140mg/m²), and 41 standard (Std) conditioning (13, TBI 14.4Gy BuCyCampath, 4 BuCy200, 16 BEAM-Campath1H, 8 FB₁₆C, Busulphan 16mg/kg). Emergence of donor red cells and isohaemaglutinine titres were detected by Diamed columns (sensitivity approx. 5%). Bone marrow samples on days 28, 56, and 100 post transplant were used for semisolid culture of erythroid progenitors (BFU-E).

Results. In 50/100 patients (26 RIC and 24 Std) emergence of donor red cell antigens was detectable by serology (19 major and 8 bidirectional ABO mismatches; 22 patients were informative due to a Rh antigen mismatch (10 D, 8 E, 2 C, and 2 c); One had a M-mismatch). Median time for the appearance of donor red cells was 66 days for Std conditioning and 56 days for RIC (not significant). Within the RIC group, there was no significant difference between ABO vs. Rh - mismatched transplants. Similarly, the kinetics of disappearance of recipient-type isohaemaglutinin was not different between RIC vs. Std conditioning (median 82 days for RIC and 69 days for Std). Appearance of donor-type isohaemaglutinin, followed in patients with minor or bidirectional ABO mismatch, was delayed regardless of the conditioning regime: only 3/24 patients had detectable donor-derived anti-A/B after a median of 336 days post transplant.

Patients receiving a RIC regime required significantly less platelet transfusions: 14.4 vs 7.8 units (P= 0.02). There was a trend toward a higher number of RBC units transfused to patients receiving Std than RIC regimes: 14 vs 9 units (P= 0.06), but with substantial variation between different standard regimes.

BFU counts showed a linear increase but the mean count was still subnormal by day 100. within the RIC group, BFU-E counts were not significantly different between ABO identical vs. non-ABO identical transplants. DNA from BFU-E colonies from 87 patient- points has been stored, to be compared with serology and blood lymphoid/myeloid chimerism data.

There were no cases of Pure Red Cell Aplasia (PRCA) in the RIC patients with major ABO mismatch. Only one case of autoimmune haemolytic anaemia was identified in the entire study group, after a median follow up of 345 days.

Conclusions Donor red cell emergence and disappearance of recipient-type anti-A/B are not delayed wit RIC regimes that we use. In keeping with this is the low incidence of post-transplant PRCA. Donor-type anti-A/B production is suppressed, probably due to the effect of Campath 1H, accounting for the absence of severe “passenger lymphocyte” haemolysis. Red cell and platelet usage are markedly decreased in RIC transplants due to reduced myelosuppression.