6Umbilical cord blood transplantation from unrelated donors in adult patients with chronic myeloid leukaemia
Section snippets
Haematopoietic engraftment
Although UCB units contain, approximately, 10-fold fewer progenitor cells compared with bone marrow or mobilised peripheral blood grafts, numerous studies have demonstrated that sustained engraftment can be achieved in the vast majority of patients, both in children [9] and in adults *[10], *[11]. However, fear of graft failure and delayed time to neutrophil and platelet recovery are major limitations of UCBT. Various strategies have been designed to improve engraftment [12], [13], [14], [15]
Graft-versus-host disease (GVHD)
UCB allows a relatively high HLA disparity between donor and recipient, without significantly increasing the risk of graft-versus-host disease (GVHD). It has been postulated that this permissive effect could be due to the naivety of the T-cell population in UCB. This unique characteristic gives UCB its best advantage: it substantially increases the chance to find a suitable donor for those patients in need of allogeneic HSCT. In fact, most studies have described a lower incidence of GVHD for
Non-relapse mortality (NRM)
NRM after UCBT is high and remains the most important limitation of this transplant modality. In addition, NRM seems particularly striking in patients with CML. Indeed, a Eurocord analysis of 171 adults undergoing UCBT for a variety a haematological malignancies found that the 2-year CI of NRM was significantly higher (76%) for patients with CML compared with those with acute leukaemia (44%) [8]. Further, the New York Blood Center reported that the overall incidence of transplantation-related
Relapse and GVL effect
The low lymphocyte content of UCB grafts and the lower incidence of GVHD after UCBT in comparison with other stem cell sources led to early concerns regarding a possible increased risk of relapse for patients with haematological malignancies transplanted with UCB. However, this fear has not been substantiated by data *[10], *[11], *[21]. Because CML is a somewhat homogenous disease with an intrinsic sensitivity to the GVL effect, it offers a unique possibility to investigate immune-mediated
Survival
Although information is still limited, there are mature enough data to confirm that a significant proportion of CML patients undergoing UCBT can be cured. In general, estimated dynamic foot stabiliser (DFS) after prolonged follow-up has ranged from 38% to 41% *[5], *[6]. As expected, disease phase at the time of transplantation had a tremendous impact on survival. In fact, patients transplanted in any CP had a long-term DFS of 52% and 59%. For that reason, patients with advanced phase of the
Conclusions and future directions
UCBT from unrelated donors can be a curative treatment for a substantial number of patients with CML. Cell dose and disease stage at transplant are the most critical factors influencing outcome. Thus, cell dose should be the most important factor to consider when selecting an UCB unit for a patient with CML. A high NRM remains the most important limitation of this transplant modality. However, it is likely that the use of TKIs will reduce post-transplant toxicity and allow patients to enter
Conflict of interest statement
None to declare.
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2013, Advances in the Treatment of Chronic Myeloid LeukemiaChronic myeloid leukemia (CML)
2012, Leukemia and Related Disorders: Integrated Treatment Approaches