Impact of hematopoietic chimerism at day +14 on engraftment after unrelated donor umbilical cord blood transplantation for hematologic malignancies

Federico Moscardó, Jaime Sanz, Leonor Senent, Susana Cantero, Javier de la Rubia, Pau Montesinos, Dolores Planelles, Ignacio Lorenzo, Jose Cervera, Javier Palau, Miguel A Sanz, Guillermo F Sanz, Federico Moscardó, Jaime Sanz, Leonor Senent, Susana Cantero, Javier de la Rubia, Pau Montesinos, Dolores Planelles, Ignacio Lorenzo, Jose Cervera, Javier Palau, Miguel A Sanz, Guillermo F Sanz

Abstract

Background: Cord blood transplant is a feasible treatment alternative for adult patients with hematologic malignancies lacking a suitable HLA-matched donor. However, the kinetics of myeloid recovery is slow, and primary graft failure cannot be detected easily early after transplantation. We investigated the impact of hematopoietic chimerism status from unselected marrow cells 14 days after transplantation on predicting engraftment after a cord blood transplant.

Design and methods: Seventy-one adult patients with hematologic malignancies undergoing single-unit unrelated donor cord blood transplantation after a myeloablative conditioning regimen were included in the study. All patients received conditioning regimens based on busulfan, thiotepa and antithymocyte globulin. Chimerism status was assessed analyzing short tandem repeat polymorphisms.

Results: The cumulative incidence of myeloid engraftment at 1 month was significantly lower in patients with mixed chimerism than in those with complete donor chimerism (55% vs. 94%; p<0.0001). For patients achieving myeloid recovery, the median time of engraftment was 16 days when donor chimerism at day + 14 was higher than 90%, compared with 24 days when donor chimerism was below this level (p<0.001). A donor chimerism level of 65% was found to be the best cut-off point for predicting primary graft failure, with a sensitivity of 97% and a specificity of 80%. The incidence of primary graft failure was 67% for patients with less than 65% donor chimerism at day +14 as compared to only 2% for those with more than 65% donor chimerism (p<0.001). Patients with mixed chimerism also had a lower cumulative incidence of platelet engraftment than those with complete chimerism (62% vs. 89%; p=0.01).

Conclusions: Donor-recipient chimerism status at day +14 predicts engraftment after a single-unit cord blood transplant in adults.

Figures

Figure 1.
Figure 1.
Cumulative incidence of myeloid engraftment according to donor chimerism status at day +14. The upper black line indicates the probability of myeloid recovery for patients with complete donor chimerism. The lower gray line indicates the probability of myeloid engraftment for patients with mixed donor chimerism (p<0.0001).
Figure 2.
Figure 2.
Cumulative incidence of myeloid engraftment according to donor chimerism status at day +14. The upper black line indicates the probability of myeloid recovery for patients with more than 65% donor chimerism. The lower gray line indicates the probability of myeloid engraftment for patients with less than 65% donor chimerism (p=0.0009).
Figure 3.
Figure 3.
Cumulative incidence of platelet engraftment according to donor chimerism status at day +14. The upper black line indicates the cumulative incidence of platelet recovery for patients with more than 90% donor chimerism. The lower gray line indicates the cumulative incidence of platelet engraftment for patients with less than 90% donor chimerism (p=0.01).

Source: PubMed

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