6. Human leukocyte antigen matching in unrelated donor hematopoietic cell transplantation. Petersdorf EW, Malkki M. Semin Hematol. 2005;42:76-84.

This review provides up to date information on the significance of HLA matching for unrelated HSCT. However, the data are derived from BMT and PBSC transplants. In this setting, the presence of donor-recipient mismatching is associated with increased risk of post-transplant complications including graft rejection, acute and chronic GVHD and mortality; these risks are increased with multiple HLA mismatches. The authors point out that when donor matching for HLA alleles is feasible, overall transplant outcome is superior. For data on HLA matching in umbilical cord blood transplantation, see citation #4 on previous page.

7. Unrelated donor hematopoietic cell transplantation: marrow or umbilical cord blood? Grewal SS, Barker JN, Davies SM, Wagner JE. Blood 2003; 101:4233-4244.

Limited HLA mismatch appears to be better tolerated with cord blood grafts compared to marrow or peripheral blood. However, current opinion is that the single most important factor influencing time to hematopoietic recovery is the nucleated cell content of the graft relative to recipient size. The effect of HLA mismatch on engraftment is less clear. Nevertheless, analysis of HLA mismatch in one study and in a more recent review update with 861 unrelated cord blood transplants, revealed a relationship between HLA match and engraftment. The median time to neutrophil recovery with 6 antigen-matched grafts was 23 days compared with 28 days with mismatched grafts. However, no association between engraftment characteristics and number of HLAs mismatched (one vs more than one HLA mismatch) was observed.

8. National Marrow Donor Program HLA-matching guidelines for unrelated marrow transplants. Hurley CK, Baxter Lowe LA, Logan B, Karanes C, Anasetti C, Weisdorf D, Confer DL. Biol Blood Marrow Transplant. 2003;9:610-5.

This is an authoritative review by sophisticated investigators (three of whom are among the faculty of the Second Annual International Cord Blood Transplantation Symposium – click on logo on Home Page for details). Although the guidelines refer to marrow transplants, some comments are pertinent to cord blood transplants.

Under the heading, “How Long Do I Search for Donors?” the authors state the following: If an acceptably matched donor cannot be identified within the current NMDP registry, it is very unlikely that newly recruited donors will match the patient in a useful time frame. The NMDP donor file contains 5 million donors and each NMDP search also evaluates an additional 3.5 million donors listed in Bone Marrow Donors Worldwide, so patients who do not find a match in this pool must have infrequent haplotypes. The likelihood that a recipient’s type will be represented in newly added recruits when it did not appear in the initial file of 5 million is exceedingly low. Therefore, it is recommended that alternative treatment options be reevaluated when the initial search does not reveal a well matched donor. The alternative options recommended are unrelated cord blood transplantation, a partially matched related donor transplantation, or nontransplant therapy. Therefore the clinician must judge whether, for example, an unrelated cord blood transplant or chemotherapy has the best chance of favorable outcome a given patient.

The authors also point out that a prolonged search time may expose patients, such as those with acute leukemia, to additional toxic chemotherapy, an increased risk of infection, and risk of relapse. (See Annotated Bibliography, Topic VI. Availability and time required to obtain cord blood versus bone marrow.)

9. Factors associated with outcomes of unrelated cord blood transplant: guidelines for donor choice. Gluckman E, Rocha V, Arcese W, Michel G, Sanz G, Chan KW, Takahashi TA, Ortega J, Filipovich A, Locatelli F, Asano S, Fagioli F, Vowels M, Sirvent A, Laporte JP, Tiedemann K, Amadori S, Abecassis M, Bordigoni P, Diez B, Shaw PJ, Vora A, Caniglia M, Garnier F, Ionescu I, Garcia J, Koegler G, Rebulla P, Chevret S; Eurocord Group. Exp Hematol. 2004;32:397-407.

The authors (all 29 of them!) analyzed 550 UCBTs for hematologic malignancies reported to the Eurocord Registry with the goal of determining optimal cord blood donor selection. Their objective was to delineate an algorithm to help clinicians choose the best cord blood unit, with emphasis on the effects of cell dose and HLA disparities. Outcomes analyzed were hematopoietic recovery, GVHD, relapse, 100 day TRM, and overall survival. The results confirmed previous findings on the association of nucleated cell dose with the speed and probability of neutrophil and platelet recovery. A higher CD34 cell dose resulted in a higher probability of aGVHD, although the authors cautioned that this observation must be confirmed in unicentric studies because of interlaboratory variation in measurements of CD34+ cells and grading of GVHD. However, contrary to previous reports, the prognostic influence of cell dose when predicting survival or TRM disappeared when considered in multivariable analyses.

There was an association between the number or type of HLA disparities with engraftment and aGVHD grade III-IV and with relapse, the later suggesting a graft-vs-leukemia effect. However, TRM and survival were not associated with HLA disparities, in agreement with previously reported data. However, these findings appear to contradict a report based on a series of 562 UCBTs in which HLA disparities were not associated with the probability of neutrophil recovery and GVHD, but with 1-year TRM. Thus, there is difficulty in establishing, from the available data, consensual guidelines for donor choice based on HLA incompatibilities.

It has been suggested that cell dose and number of HLA mismatches interact mutually on engraftment and on other outcomes. Thus a higher cell dose in the graft could partially overcome the negative impact of HLA for each level of HLA disparity; however, this hypothesis has not been proved. The authors found no statistical evidence of any interaction between cell dose and HLA disparities (p = 0.81).

Survival was related to the transplant center as well as to the period of transplantation, with a decreased mortality after 1998 compared to before 1998 (p = 0.02).

Would a cord blood unit with 4 x 10⁷/kg nucleated cells (NCs) but no HLA disparities be preferable to a cord blood unit with 6 x 10⁷ NCs but one HLA disparity? The authors state that no accurate answer to this point can be determined from their data.

The authors conclude that their results show that two major factors, cell dose and HLA, can be used to choose a cord blood unit. A higher the number of cells and a lower the number of HLA disparities will increase the probability of engraftment; a higher the number of HLA disparities will increase the incidence of acute GVHD grade III-IV and decrease the risk of relapse.

Page 1 | 2

TOP OF PAGE