Journal List > Korean J Lab Med > v.26(6) > 1011348

Kim, Park, Chi, Lee, Lee, and Seo: Inverse Tendency between Ex Vivo Expansion Potential of Hematopoietic Progenitors and Time to Engraftment after Hematopoietic Stem Cell Transplantation

Abstract

Background

The CD34+ cell dose and infused number of committed progenitor cells in transplantation are important factors in hematologic engraftment. However, the relationship between expansion potential of progenitor cells and hematologic engraftment remains controversial. We evaluated whether expansion potential of progenitor cells is a predictive factor of post-transplantation hematologic engraftment.

Methods

Mononuclear cells isolated from mobilized peripheral blood and bone marrow were cultured with cytokine cocktail for 7 days. Progenitor cells and committed progenitors were analyzed using stem cell markers (CD34 and CD133) and lineage specific markers. Hematologic engraftment was defined as neutrophil counts over 500/μL and platelet counts over 20,000/μL without transfusion. Acute and chronic graft-versus-host disease (GVHD) were investigated.

Results

There was inverse tendency between the number and fold expansion of progenitor cells or committed (granulocytic or megakaryocytic) progenitors and time to engraftment. Especially, fold expansion of CD34+/CD33+ cells was significantly correlated with time to neutrophil engraftment in bone marrow transplantation (r=-0.56, P=0.04). The infused number and fold expansion of lymphoid progenitors were not related to the occurrence of acute or chronic GVHD.

Conclusions

We could not prove that expansion potential of progenitor cells and committed progenitor cells is correlated to hematologic engraftment although there is a correlation between CD34+/CD33+ cells and time to neutrophil engraftment. But, a further study on the value of expansion potential is required because there is an inverse tendency.

References

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Fig. 1.
Three-color flow cytogram for the measurement of hematopoietic progenitor cells. (A) Measurement of CD45+, CD34+ or CD133+(AC133+) cells. (B) Measurement of CD45+, CD34+ and CD19+ cells.
kjlm-26-385f1.tif
Fig. 2.
Correlation of expansion potential of progenitor cells with neutrophil or platelet recovery (days) after bone marrow transplantation (n=14).
kjlm-26-385f2.tif
Table 1.
Number and fold expansion of mononuclear cells and progenitor cells before and after 7-day culture
  N Fold expansion of MNCs Progenitor cells (CD34+ or CD133+)
Fold expansion of progenitor cells
Pre
Post
N (×103/mL) % N (×103/mL) %
mPB 13 4.5 (3.1–5.3) 4.9 1.94 19.2 1.17 2.2
      (3.8–15.7) (0.97–3.14) (10.5–42.3) (0.94–1.44) (1.3–4.7)
BM 14 5.9 (3.1–11.8) 10.6 2.23 26.1 1.40 3.1
      (5.1–15.1) (1.50–3.33) (11.7–44.0) (1.04–1.96) (2.1–5.2)
P-value   0.21 0.36 0.77 0.87 0.36 0.88

The data are expressed as median (interquartile range).

Abbreviations: N, number; MNCs, mononuclear cells; mPB, mobilized peripheral blood; BM, bone marrow.

Table 2.
Expansion potential of progenitor cells in mPB and BM
Subset of progenitor cells Fold expansion
P-value
mPB (N=13) BM (N=14)
CD34+ or CD133+ 2.2 (1.3–4.7) 3.1 (2.1–5.2) 0.88
CD34+/CD13+ 1.4 (1.0–2.1) 3.6 (1.7–6.0) 0.06
CD34+/CD33+ 1.9 (1.0–6.2) 4.5 (1.8–7.9) 0.14
CD34+/CD61+ 18.1 (7.9–50.2) 6.9 (3.0–13.2) 0.55

The data are expressed as median (interquartile range).

Abbreviations: mPB, mobilized peripheral blood; BM, bone marrow.

Table 3.
Correlation of infused number (×106/kg) or expansion potential of lymphoid progenitor cells with the occurrence of acute GVHD
Parameters without aGVHD or with grade 1 aGVHD (N=10) with grade 2–4 aGVHD (N=4) P-value
CD34+/CD19+      
Number 0.88 (0.28–1.39) 0.66 (0.42–0.88) 0.89
Fold expansion 1.3 (0.7–5.1) 3.4 (0.7–6.1) 1.0
CD34+/CD7+      
Number 0.22 (0.14–0.63) 0.43 (0.17–0.56) 0.78
Fold expansion 4.3 (1.6–5.3) 2.2 (1.9–2.2) 0.32

The data are expressed as median (interquartile range).

Abbreviation: aGVHD, acute graft-versus-host disease.

Table 4.
Correlation of infused number (×106/kg) or expansion potential of lymphoid progenitor cells with the occurrence of acute GVHD
Parameters without cGVHD (N=5) with cGVHD (N=6) P-value
CD34+/CD19+      
Number 1.01 (0.62–1.49) 0.47 (0.20–1.07) 0.20
Fold expansion 0.3 (0.2–1.6) 5.0 (1.0–7.2) 0.09
CD34+/CD7+      
Number 0.23 (0.20–1.10) 0.18 (0.11–1.20) 0.47
Fold expansion 1.6 (0.5–7.6) 4.3 (2.2–7.0) 0.11

The data are expressed as median (interquartile range).

Abbreviation: aGVHD, acute graft-versus-host disease.

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