Cord blood transplants: early recovery of neutrophils from co-transplanted sibling haploidentical progenitor cells and lack of engraftment of cultured cord blood cells, as ascertained by analysis of DNA polymorphisms

Abstract

Summary:The number of infused cells is a very important factor in cord blood transplant (CBT) engraftment. Prior ex vivo expansion of aliquots of transplanted cord blood (CB) units is being investigated as a procedure to increase engraftment potential, but results are difficult to evaluate due to a lack of markers for assessing the contribution of expanded cells. We transplanted five patients, infusing the best available CB unit and cells from a second donor simultaneously. In two patients, these cells were obtained from another frozen CB unit by CD34+ positive selection and culture expansion; the other three patients received uncultured highly purified haploidentical CD34+ cells. The first two patients had DNA from the culture expanded CB cells detected only for a few days around day +11 when the absolute neutrophil count (ANC) was Ͻ200/l; thereafter and when the ANC was Ͼ500/l, only donor DNA from the uncultured CB was detected. For the other three patients, DNA analysis showed early and transient granulocyte engraftment of haploidentical cells, progressively replaced by the CB-derived granulocytes. We concluded that: (1)

Cord blood transplants supported by co-infusion of mobilized hematopoietic stem cells from a third-party donor

“…This limitation may be overcome by the co-infusion of a relatively low number of T-cell-depleted mobilized hematopoietic stem cells (MHSC) from a third-party donor (TPD). [1][2][3] Here we report results of engraftment, morbidity and survival of a total of 55 consecutive patients transplanted in our center using this strategy between March 1999 and October 2007. These data confirm and extend results reported previously on the value of the procedure to achieve high rates of engraftment and full chimerism of single unit CBT in adults after myeloablative conditioning.…”

Quantitative monitoring of multi-donor chimerism: a systematic, validated framework for routine analysis

“…1,[4][5][6][7][8][9] These results are difficult to interpret because insufficient details are provided in any study regarding the ad hoc computational procedures followed, the accuracy of the results or whether the measurements were assessed for reliability. It is uncertain whether any previous study analyzed loci with shared alleles, despite their common occurrence in DD HSCTs.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13] However, the complex chimeric states associated with these transplants engender novel quantitative problems for the monitoring laboratory. The most challenging issue in analyzing multi-donor chimeras is the almost universal occurrence of shared alleles, that is, STR peaks (bands) with identical alleles from more than one DNA source.…”

“…It is most commonly exemplified in DD cord blood transplants, and combined cord blood and haploidentical transplants. [1][2][3][4][5][6][7][8][9][10][11][12][13] However, similar complex chimeric states can occur after sequential singledonor HSCTs and in the setting of feto-maternal chimerism (CHM) followed by HSCT. [14][15][16][17][18][19] Despite their advantages, such clinical achievements also engender new challenges for post-transplantation monitoring, particularly in regard to the molecular evaluation of chimeric status.…”

Future of cord blood for oncology uses

“…Fernandez et al [26][27][28] reported the co-infusion of large numbers of highly purified CD34 þ progenitors from haploidentical donors in the setting of myeloablative transplantation with one UCB unit. The median time to neutrophil recovery was 10 days.…”