HLA-mismatched hematopoietic SCT without in vitro T-cell depletion for myelodysplastic syndrome

Abstract

Allogeneic hematopoietic SCT (HSCT) is currently the only curative treatment for myelodysplastic syndrome (MDS). However, many patients cannot find an HLA-matched donor. We have developed a new protocol for HLA-mismatched (including haploidentical) HSCT using G-CSF-primed BM plus G-CSF-mobilized PBSCs without in vitro T-cell depletion. A total of 36 patients diagnosed with high-risk MDS (RAEB (refractory anemia with excess blasts) or RAEBt (RAEB in transformation)) underwent transplantation from HLA-mismatched family donors. All patients achieved sustained myeloid engraftment. The cumulative incidence of grades II-IV acute GVHD (aGVHD) was 60% and that of grades III and IV aGVHD was 15%. The 2-year cumulative incidence of chronic GVHD was 56%. After a median follow-up of 17 months, 4 patients had relapsed and died and 25 patients were still alive. The 2-year probability of leukemia-free survival (LFS) was 65%. Patients transplanted within 7 months of diagnosis had better LFS (89 vs 43% ). Severe aGVHD decreased the LFS significantly by increasing non-relapse mortality (NRM). This study confirms that HLA-mismatched HSCT is a treatment option for MDS. Patients with high-risk MDS benefit from receiving HSCT early in the course of the disease.

G-CSF-primed BM for allogeneic SCT: revisited

“…88,89 Similar results were also reported in 36 myelodysplastic syndrome high-risk/RAEB-t (refractory anemia with excess blasts in transformation) patients who underwent transplantation from combined GBM with GPB (5 μg/kg per day G-CSF for 4-5 days) haplotype-mismatched sibling donors. 90 Rapid and sustained engraftment, without significant increase of GVHD, was also reported in 29 patients with combined GBM with GPB by Wang et al 91 The same team further confirmed their findings in another one-arm study of 756 patients, who received unmanipulated combined GBM and GPB (5 μg/kg per day G-CSF for 6 days). In that study, the median time for neutrophil and platelet engraftment was 13 and 16 days, respectively.…”

HLA-haploidentical hematopoietic SCT from collateral related donors without in vitro T-cell depletion for hematological malignancies

“…There was no difference in the incidence and severity of aGVHD and cGVHD with HLA disparity, which was consistent with our previous results. [3][4][5][6][7][8][9] Although not being statistically significant, there are trends for a difference in diagnosis repartition between the CRD and IRD group (P ¼ 0.079). This may have an impact on GVHD occurrence.…”

“…[3][4][5] By this protocol, promising results have been achieved. [6][7][8][9] In this study, we compared the clinical outcomes of patients with hematological malignancies who underwent HLAhaploidentical HSCT, between CRD (n ¼ 30) and immediate related donor (IRD) groups (n ¼ 120) in the GIAC protocal.…”

Allogeneic hematopoietic cell transplantation for myelodysplastic syndrome: the past decade

“…Survival was 42% for patients with <15% myeloblasts and 0% for more advanced disease; day-100 (1-year) TRM was 9% (32%). Chen et al reported on 36 patients with high-risk MDS who underwent HLA-mismatched/HLA-haploidentical HCT with G-CSF-primed marrow and G-CSF-mobilized PBPCs, and showed a 2-year RFS of 65% [73]. Patients transplanted within 7 months of diagnosis had better outcomes (89% RFS) than those transplanted later (43%).…”