Comparison of Unrelated Cord Blood and Peripheral Blood Stem Cell Transplantation in Adults with Myelodysplastic Syndrome after Reduced-Intensity Conditioning Regimen: A Collaborative Study from Eurocord (Cord blood Committee of Cellular Therapy & Immunobiology Working Party of EBMT) and Chronic Malignancies Working Party

Abstract

Hematopoietic stem cell transplantation (HSCT) remains the only curative treatment in patients with higher risk myelodysplastic syndrome (MDS), but the choice of the optimal alternative stem cell source is still a subject of debate in patients lacking an HLA-matched sibling donor. Here, we report on a large series of patients with MDS (N = 631) transplanted either with mobilized peripheral stem cells (PBs) from unrelated donors (n = 502) or with umbilical cord blood transplant (UCB, n = 129) as alternative grafts after reduced-intensity conditioning. Neutrophil engraftment was higher after PB (98% versus 78%, P < .0001). Acute graft-versus-host disease (GVHD) was similar after PB (31%) and UCB (29%), and chronic GVHD incidence was higher after PB (41% versus 23%). Two-year nonrelapse mortality was lower after PB (31% versus 42% P = .03). There was a better overall survival (OS) and disease-free survival (DFS) after PB (49% ± 2% versus 30% ± 4%, P < .0001 and 44% ± 2% versus 28% ± 4%, P < .0001). Multivariate analysis confirmed the advantage of PB for treatment-related mortality, OS, and DFS, whereas relative risk of chronic GVHD was similar. A multivariate analysis comparing PB from a 10/10 HLA-matched donor, PB from a 9/10 HLA-matched donor, and UCB showed an advantage on treatment-related mortality, DFS, and OS only in 10/10 PB. We conclude that in MDS patients lacking an HLA-matched sibling donor, PB from a 10/10 HLA-matched unrelated donor is the preferred source of hematopoietic stem cells. HLA-mismatched unrelated donor or cord blood seem to give similar inferior results except for neutrophil engraftment, which is delayed after UCB.

Outcomes after Umbilical Cord Blood Transplantation for Myelodysplastic Syndromes

“…The European Group for Blood and Marrow Transplantation (EBMT) reviewed a group of 129 patients with MDS that underwent UCBT, finding similar results with 2-year probabilities of chronic GVHD, relapse, TRM, DFS, and OS of 23%, 30%, 42%, 28%, and 30%, respectively [14]. One key difference between the two studies, is that a majority (71%) of the patients in the EMBT analysis had progressed to acute myeloid leukemia prior to transplantation, with less than half (48%) of them in remission prior to transplantation.…”

“…There have been few published series solely describing the outcomes of adult patients who have undergone UCBT for MDS [12–14]. In the absence of substantial data, patients that could benefit from UCBT may not be offered the treatment option when they otherwise would be considered for matched related or unrelated donors.…”

Haploidentical transplant in patients with myelodysplastic syndrome

“…8 The European Group for Blood and Marrow Transplantation (EBMT) has previously reported that HLAmismatched unrelated donors can give similar results to UCB donors in MDS patients, but worse outcomes than HLA-matched unrelated donors. 9 A recent Center for International Blood and Marrow Transplant Research (CIBMTR) study reported similar results in acute myeloid leukemia (AML) patients transplanted with haplo with PT-CY vs HLA-matched unrelated donors. 10 A similar comparison in patients with acute leukemia, MDS, chronic leukemia, or lymphoma has been done by Luo et al 11 showing equivalent outcomes for matched-related donors, HLA mismatched-unrelated donors, and haplos according to the Beijing protocol.…”

MDS disease characteristics, not donor source, predict hematopoietic stem cell transplant outcomes

“…Based on these data, the authors concluded that PB MUD donors were the preferred stem cell source compared to UCB in the absence of a sibling donor. 26 While the outcomes of this study highlight a much larger “MDS” patient cohort, it is important to note that 65% of the MDS patients within the entire cohort had progressed to AML prior to transplantation and of those patients only 52% had achieved remission prior to transplant. Specifically within the UCB group 71% had progressed to AML and only 48% had achieved CR prior to transplant.…”

“…This study is thus limited by the heterogeneity of patients/conditioning regimens/supportive care inherent to a registry study and the small number of true MDS patients not progressing to AML receiving an UCB HCT (n=37). 26 Despite these limitations, the analysis importantly highlights surprisingly good outcomes of survival and relapse for such a high risk group of patients with the majority of the MDS patients progressing to AML, only half in remission, and receiving only RIC. Thus, these data suggest that both MUD/UCB RIC transplants can be effective in curing even high risk MDS/AML patients.…”