Intrabone transplant of cord blood stem cells establishes a local engraftment store: a functional PET/FDG study

Abstract

Background: Despite advancements in comprehension of molecular mechanisms governing bone marrow (BM) homing of hematopoietic stem cells, cord blood transplant (CBT) suffers from a slow rate of hematopoietic recovery. Intrabone (i.b.) injection has been proposed as a method able to improve speed of BM engraftment with respect to conventional i.v. protocols. However, the mechanisms underlying this benefit are largely unknown.

Aim: To verify whether i.b.-CBT determines a local engraftment able to predict the reconstitution of recipient hematopoiesis.

Design and methods: Twenty-one patients with hematologic malignancies received i.b. injection into both iliac crests of 3.2 ± 0.68 ∗ 107/kg cord blood cells. One month following i.b.-CBT, PET-CT imaging was performed. Maximal standardized uptake values (SUVs) were assessed in BM of both iliac crests and in all lumbar vertebrae.

Results: Maximal SUV within iliac crests was higher than in lumbar vertebrae (4.1 ± 1.7 versus 3.2 ± 0.7, resp., P = 0.01). However, metabolic activity in these two different BM districts was significantly correlated (r = 0.7, P < 0.001). Moreover, FDG uptake values within the injection site closely predicted platelet recovery 100 days after i.b.-CBT (r = 0.72, P < 0.01).

Conclusions: The metabolic activity of injected BM predicts the subsequent rate of hematopoietic recovery after i.b.-CBT, suggesting a pivotal role of the local engraftment in the reconstitution of recipient hematopoiesis.

Figure 1

(a) Bone marrow (BM) segmentation of both iliac crests (bottom) and five lumbar vertebrae (top), using PET-CT images. Analyzed volumes are shown in green for the former and blue for the latter. (b) Metabolic activity trend patient by patient in the injected sites compared with remote BM; maximal SUVs in the iliac crests were slightly but significantly higher than in the lumbar spine. On the contrary, the same analysis (c) showed the opposite results in controls.

Figure 2

Whole body PET maximum intensity projections of a patient (a) and a control subject (b). Tracer retention in iliac crests is clearly visible in the patient and not in the control subject.

Figure 3

Correlation existing between maximal standardized FDG uptake values (SUV) within iliac crests and lumbar vertebrae. The tight correlation between injected sites and lumbar vertebrae metabolism confirmed a close parallelism between the degree of BM glucose consumption in these two different districts.

Figure 4

Correlation between follow-up platelets counts (day 100) and metabolic activity in both the iliac crests at day 30 after IB-CBT; maximal SUVs in the injected sites were significantly and directly correlated with the follow-up platelets recovery.

Figure 5

Lack of correlation between late follow-up platelets count (day 100) and maximal SUVs in lumbar vertebrae; the metabolic activity in the remote BM did not predict the late hematopoietic recovery.