Abstract
Background. Allogeneic transplantation of hematopoietic stem cells (allo-SCT) from an HLA-matched related or unrelated donor is a curative option for patients with high-risk hematological disease. In the absence of an HLA-matched donor, patients have been offered investigational transplant strategies involving alternative donors such as umbilical cord blood (UCB) or family haploidentical SCT (haplo-SCT). Through the years, the search for alternative donors has led the medical community to explore different strategies to provide every patient candidate to allo-SCT with a suitable donor. In patients lacking an HLA-matched donor in a due time, both UCB and family haploidentical donors are raising from investigational into frontline stem cell source for treatment of hematological malignancies. However, no prospective evaluation of the feasibility of these alternative sources is available and transplant centres usually apply an upfront choice between these two available options as the priority modality to offer an allo-SCT to each candidate patient. In our Institution, we adopted the policy to offer a family haplo-SCT to adult patients lacking an HLA-matched donor.
Methods and results. Here we report results of the simulation of a systematic search of a cord blood unit for all the patients that, in the last 2 years, received in our Institution an haplo-SCT.Between January 2006 and July 2008, 62 patients received an haplo-SCT; median age was 53 y (0–20y 2; 21–40y 14; 41–50y 12; 51–60y 20; over 60y 14), median weight 66 kg. All patients were affected by high risk hematological malignancies (41 acute myeloid leukaemia, 9 acute lymphoid leukaemia, 4 myelodisplastic syndrome, 3 chronic myeloid leukaemia, 3 Hodgkin disease, 2 non Hodgkin disease), 23 in complete remission at transplant, 37 in persistence of disease, 3 received transplant as up-front treatment. All the patients received a myeloablative conditioning regimen based on fludarabine-treosulfan-ATG and the overall engraftment rate was 96%. In intention to treat (ITT) analysis all the patients requiring an allo-SCT received an haplo transplant. In our simulation, we searched on BMDW (www.bmdw.org) for an umbilical cord blood unit (UCB-U) according to criteria based on current available guidelines (Barker JN et al, Blood 2005; Gluckman E et al, Curr Opin Immunol, 2006; Brunstein C et al, Blood 2007; Tse W et al, Curr Opin Hematol, 2008). According to these standard criteria, patients and UCB units must be at least 4/6 HLA matched in A, B, and DR beta 1 (DRB1) loci with cell dose ≥3.0×107/kg total nucleated cell (TNC). Regarding the degree of HLA disparity, priority should be given for selecting UCB grafts in the following order: 6/6 > 5/6 > 4/6. If multiple UCB-U with the same level of HLA matching are available, the priority should be given to the UCB-U that are DRB1 matched with higher cell dose. The target cell dose can be reached by the selection of a single UCB unit or a double UCB units. In those patients for whom a second UCB unit could be identified, the second also should have a minimum of 4/6 antigens matched with the patient and with the first unit. For 6 out of 62 patients, we could find a single UCB unit, with median dose of TNC 5.25×107/kg and HLA matched 5/6 (5), 4/6 (1). For 56 patients a double UCB-U was available, with a median TNC dose of 4.90×107/kg and HLA matched 6/6+6/6 (2); 6/6+5/6 (3), 6/6+4/6 (1); 5/6+5/6 (17), 5/6+4/6 (17), 4/6+4/6 (16).
Conclusions.: With the application of protocols of multiple units, UCB source is providing the chance of allogeneic SCT to all candidate patients otherwise receiving Haplo-SCT. A prospective comparison of Haplo versus cord in an ITT model, is warranted to identify the best alternative option in specific disease settings.
Recommendations for a standard UK approach to incorporating umbilical cord blood into clinical transplantation practice: an update on cord blood unit selection, donor selection algorithms and conditioning protocols
