TY - JOUR
T1 - Changes in granulocyte-monocyte colony-forming cells among leukocyte-interferon-treated chronic myelogenous leukemia patients
AU - Talpaz, M.
AU - Spitzer, G.
AU - Hittelman, Walter N
AU - Kantarjian, H.
AU - Gutterman, J.
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 1986
Y1 - 1986
N2 - Myeloid cytoreduction leading to hematologic remissions is frequently seen among patients with chronic phase Philadelphia-positive chronic myelogenous leukemia (CML Ph') treated with leukocyte interferon (IFN-α). In order to extend our understanding of the events associated with interferon-induced myeloid cytoreductions, we have examined the changes in granulocyte-monocyte colony-forming cells (GM-CFC) in such CML PH' patients. A total of 28 CML Ph' patients in hematologic remissions following IFN-α treatment had a median GM-CFC of 12 (range, 0-182)/l x 105 bone marrow cells. This was significantly lower than the median GM-CFC of 104 (range, 44-815; p < 0.01) in 22 untreated or minimally treated CML Ph' patients and the median of 72 (range, 30-204; p < 0.05) in 18 normal controls. A gradual decline in the GM-CFC numbers from a median of 105 to a median of 1.8 was seen in six responding patients who were studied serially over a median period of 7.5 months. In these patients, we also observed a profound decline in the number of aspirated bone marrow nucleated cells and a decline in the bone marrow cellularity. The effect of treatment interruption for a median of 13 days was studied in five patients. In three of the patients who had received IFN-α for ≤ 6 months, treatment of interruption resulted in rapid increase in the GM-CFC, while the GM-CFC did not change in the remaining two patients, who received IFN-α for one and two years. We conclude that treatment of CML patients with IFN-α resulted in a progressive decline of the bone marrow GM-CFC. The initially expanded pool of committed myeloid stem cells declines gradually, and at the time of hematologic remission the number of GM-CFC/105 nucleated bone marrow cells is lower than that of normal controls. In the early phases of IFN-α treatment, this inhibitory effect is rapidly reversible, but it seems to persist when the treatment is extended over more than one year.
AB - Myeloid cytoreduction leading to hematologic remissions is frequently seen among patients with chronic phase Philadelphia-positive chronic myelogenous leukemia (CML Ph') treated with leukocyte interferon (IFN-α). In order to extend our understanding of the events associated with interferon-induced myeloid cytoreductions, we have examined the changes in granulocyte-monocyte colony-forming cells (GM-CFC) in such CML PH' patients. A total of 28 CML Ph' patients in hematologic remissions following IFN-α treatment had a median GM-CFC of 12 (range, 0-182)/l x 105 bone marrow cells. This was significantly lower than the median GM-CFC of 104 (range, 44-815; p < 0.01) in 22 untreated or minimally treated CML Ph' patients and the median of 72 (range, 30-204; p < 0.05) in 18 normal controls. A gradual decline in the GM-CFC numbers from a median of 105 to a median of 1.8 was seen in six responding patients who were studied serially over a median period of 7.5 months. In these patients, we also observed a profound decline in the number of aspirated bone marrow nucleated cells and a decline in the bone marrow cellularity. The effect of treatment interruption for a median of 13 days was studied in five patients. In three of the patients who had received IFN-α for ≤ 6 months, treatment of interruption resulted in rapid increase in the GM-CFC, while the GM-CFC did not change in the remaining two patients, who received IFN-α for one and two years. We conclude that treatment of CML patients with IFN-α resulted in a progressive decline of the bone marrow GM-CFC. The initially expanded pool of committed myeloid stem cells declines gradually, and at the time of hematologic remission the number of GM-CFC/105 nucleated bone marrow cells is lower than that of normal controls. In the early phases of IFN-α treatment, this inhibitory effect is rapidly reversible, but it seems to persist when the treatment is extended over more than one year.
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M3 - Article
C2 - 3460811
AN - SCOPUS:0022508841
SN - 0301-472X
VL - 14
SP - 668
EP - 671
JO - Experimental Hematology
JF - Experimental Hematology
IS - 7
ER -