HLA-matched sibling transplantation with BM and CD34+-purified PBSCs in adult patients with high-risk severe aplastic anemia to overcome graft rejection without an increase in GVHD

Abstract

The transplantation of a large number of stem cells can overcome graft rejection but with the increased risk of GVHD. In this study, we analyzed the outcome of 32 adult patients with acquired severe aplastic anemia (SAA) who were at a high risk for graft rejection, including multiple transfusions (median 147 units, range 20-680) and long disease duration (median 67 months, range 3-347), and who had received both BM and CD34 þ -purified PBSCs from an HLA-matched sibling donor to reduce graft rejection. T cells in PBSCs were depleted using a magnetic-activated cell sorting method (CliniMACS system). Conditioning regimens consisted largely of CY and antithymocyte globulin (ATG) with fludarabine (FLU) or procarbazine (PCB). With a median follow-up of 89 months, the 8-year probability of survival was 87.5%. Neutrophils and plts promptly recovered, and none of the patients developed graft failure. The cumulative incidences of acute and chronic GVHD were 9.4 and 18.0%, respectively. Sustained engraftment and excellent survival without an apparent increase in the rate of GVHD in high-risk patients using the current approach showed that high-dose SCT with both BM and CD34 þ -purified PBSCs may yield better outcomes in heavily transfused and/or allo-immunized patients with SAA.

The use of a fludarabine‐based conditioning regimen in patients with severe aplastic anemia – a retrospective analysis from three Indian centers

“…The use of PBSC or purified CD 34 + PBSC has been shown previously to improve engraftment and reduce rejection in patients with SAA who have been multiply transfused . Despite the use of PBSC as the graft source, the incidence of grade II–IV acute GVHD was only 26.7%, which is very similar to data published both from the CIBMTR and from the EBMT . The incidence of acute GVHD can probably be further reduced with the addition of drugs such as alemtuzumab to the conditioning although there may be higher rates of graft failure .…”

Preliminary evaluation of a highly automated instrument for the selection of CD34+ cells from mobilized peripheral blood stem cell concentrates

“…The mean proportion of CD341 cells in the Clini-MACS Prodigy-and CliniMACS Plus-selected products was similar in our study and in that of Spohn and colleagues: 93.6% versus 93.9%, respectively, for the Clini-MACS Prodigy and 95.7% versus 95.9% for the CliniMACS Plus. 14 Cho and colleagues 15 found that the mean proportion of CD341 cells in the CliniMAC Plus-selected products was 95.8%, Dvorak and colleagues 16 found the median proportion of cells expressing CD341 antigen in CliniMAC Plus-selected products was 97% (range, 87%-99%), and for the Blood and Marrow Transplant Clinical Trials Network the median was 96.7% (range, 61.5%-99.8%). 17 In our study the mean recovery of CD341 cells from the mobilized PBSC concentrates by the CliniMACS Prodigy was 51.4 6 8.2% compared to 65.1 6 15.7% with the CliniMACS Plus.…”

Comparable outcomes between younger (⩽40 years) and older (>40 years) adult patients with severe aplastic anemia after HLA-matched sibling stem cell transplantation using fludarabine-based conditioning

“…PBSC graft was occasionally used for previously heavily-transfused patients. 21 For GVHD prophylaxis, cyclosporin A (5 mg/kg IV at day − 1, then 3 mg/kg IV from day 0) with dose adjustments targeting a trough level of 200-250 ng/mL plus short-course methotrexate (10 mg/m 2 IV at days 1, 3, 6 and 11) were administered. When patients could tolerate oral intake of medication, cyclosporin A was switched to the equivalent-dose oral form targeting a trough level of 150-200 ng/mL.…”