|
|||||||||
|
|
|
|
|
|
|
|
|
|
|
CORRESPONDENCE Recently, Croop et al1 reported the feasibility of
mobilizing and collecting peripheral blood CD34+ progenitor
cells from patients with Fanconi anemia. The authors performed
successful apheresis collection in 6 of 8 patients. They showed that
prolonged granulocyte colony-stimulating factor (G-CSF) administration
(median 10 ± 4 d) and days of apheresis (4 ± 3 d; range, 2-8 d)
were required and that such procedure led to significant adverse
events. This study supported evidence that patients with Fanconi anemia
can be mobilized, but the authors did not answer the question of
whether these hematopoietic progenitors were functional and could
efficiently participate to autologous reconstitution after infusion. In
this scope, data concerning granulocyte-macrophage
colony-forming unit (GM-CFU) assays would have been of great interest. We would like to report our experience with G-CSF-mobilized peripheral
blood CD34+ cells (n = 4) or bone marrow (BM) harvest
(n = 2) in patients with Fanconi anemia, using a standard collection
method. At the time of harvest, none of the patients had
criteria of severe aplastic anemia (defined by hemoglobin level below
80 g/L [8 g/dL], absolute neutrophil count below
0.5 × 109/L, and platelet count below
20 × 109/L) and were transfusion independent (Table
1). All 4 mobilized patients, with a mean age of 17.3 y (range, 4-31 y), received G-CSF at the daily dose of 10 µg/kg for 5 days.
Two of them failed to mobilize, while the other 2 underwent
apheresis with a number of initial peripheral blood CD34+
counts of 9.4/µL and 9.8/µL. Within 2 days of apheresis,
the numbers of total nucleated cells collected in these 2 patients were
84.86 × 109/kg and 90.14 × 109/kg and the
numbers of CD34+ cells were 1.53 × 106/kg
and 0.9 × 106/kg. GM-CFU assays were performed by
seeding 1 × 103 CD34+ cells in a
conventional methylcellulose culture assay in order to determine
myeloid progenitors cell growth. Interestingly,
CD34+ progenitor cells failed to generate GM-CFU colonies
with numbers of 0.42 × 104 or
1 × 104 GM-CFU/kg patient weight, thus suggesting a low
clonogenic capacity of CD34+ cells even in patients without
severe bone marrow failure. We determined that CD34+ cells
from Fanconi anemia patients have 5 to 12 times lower levels of GM-CFU/kg, as compared with 72 patients with hematologic
malignancies for whom apheresis, performed with the same standard
conditions, led to a median of 1.1 × 106
CD34+/kg (median GM-CFU/kg, 5.1 × 104). The
same pattern of dramatic decrease in CD34+ cells
(0.03 × 106/kg and 0.12 × 106/kg) and
GM-CFU (0 × 104/kg) was observed in both patients that
underwent BM harvest. These results contrast with a relatively normal
blood count that cannot be predictive of CD34 cell recovery or
functionality.
Similar to a murine model of FANCC disruption clearly demonstrating a reduced repopulating ability of hematopoietic stem cells,2 our results tend to support the hypothesis of a qualitative and quantitative defect of hematopoietic progenitor cell compartment.
Jérôme Larghero, Jean-Pierre Marolleau, Jean Soulier, Alain Filion, Vanderson Rocha, Marc Benbunan, and Eliane Gluckman
References
1.
Croop JM, Cooper R, Fernandez C, et al.
Mobilization and collection of peripheral blood CD34+ cells from patients with Fanconi anemia.
Blood.
2001;98:2917-2921
2.
Haneline LS, Gobbett TA, Ramani R, et al.
Loss of FancC function results in decreased hematopoietic stem cell repopulating ability.
Blood.
1999;94:1-8   CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
This article has been cited by other articles:
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
 |
 |
|||||||
 |
 |
 |
 |
 |
 |
 |
 |
||
| Copyright © 2002 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
