|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 96 No. 2 (July 15), 2000:
pp. 429-436
Myelodysplasia syndrome and acute myeloid leukemia in patients
with congenital neutropenia receiving G-CSF therapy
Melvin H. Freedman,
Mary Ann Bonilla,
Carol Fier,
Audrey Anna Bolyard,
Debra Scarlata,
Laurence A. Boxer,
Sherri Brown,
Bonnie Cham,
George Kannourakis,
Sally E. Kinsey,
Pier Georgio Mori,
Tammy Cottle,
Karl Welte, and
David C. Dale
From the Severe Chronic Neutropenia International
Registry, University of Washington, and the University of Washington
Department of Medicine, Seattle, WA; the University of Michigan Medical
Center, Ann Arbor, MI; St Barnabas Medical Center, West Orange, NJ; the
Clinical Safety Department, Amgen, Inc, Boulder, CO, and Thousand Oaks,
CA; The Hospital for Sick Children and the University of Toronto
Faculty of Medicine, Toronto, Ontario, Canada; the Manitoba Cancer
Treatment and Research Foundation, Winnipeg, Manitoba,
Canada; the Cancer Research Center, University of Ballarat; St James's
University Hospital, Leeds, England; the Istituto Giannina Gaslini,
Genova, Italy; and the Medizinische Hochschule, Hannover, Germany.
Granulocyte colony-stimulating factor (G-CSF) has had a
major impact on management of "severe chronic neutropenia," a
collective term referring to congenital, idiopathic, or cyclic
neutropenia. Almost all patients respond to G-CSF with increased
neutrophils, reduced infections, and improved survival. Some responders
with congenital neutropenia have developed myelodysplastic syndrome and
acute myeloblastic leukemia (MDS/AML), which raises the question of the
role of G-CSF in pathogenesis. The Severe Chronic Neutropenia International Registry (SCNIR), Seattle, WA, has data on 696 neutropenic patients, including 352 patients with congenital
neutropenia, treated with G-CSF from 1987 to present. Treatment and
patient demographic data were analyzed. The 352 congenital patients
were observed for a mean of 6 years (range, 0.1-11 years) while being treated. Of these patients, 31 developed MDS/AML, for a crude rate of
malignant transformation of nearly 9%. None of the 344 patients with
idiopathic or cyclic neutropenia developed MDS/AML. Transformation was
associated with acquired marrow cytogenetic clonal changes: 18 patients
developed a partial or complete loss of chromosome 7, and 9 patients
manifested abnormalities of chromosome 21 (usually trisomy 21).
For each yearly treatment interval, the annual rate of
MDS/AML development was less than 2%. No significant relationships
between age at onset of MDS/AML and patient gender, G-CSF dose, or
treatment duration were found (P > .15). In addition to the
31 patients who developed MDS/AML, the SCNIR also has data on 9 additional neutropenic patients whose bone marrow studies show
cytogenetic clonal changes but the patients are without transformation to MDS/AML. Although our data does not support a cause-and-effect relationship between development of MDS/AML and G-CSF therapy or other
patient demographics, we cannot exclude a direct contribution of G-CSF
in the pathogenesis of MDS/AML. This issue is unclear because MDS/AML
was not seen in cyclic or idiopathic neutropenia. Improved survival of
congenital neutropenia patients receiving G-CSF therapy may allow time
for the expression of the leukemic predisposition that characterizes
the natural history of these disorders. However, other factors related
to G-CSF may also be operative in the setting of congenital neutropenia.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. Germeshausen, C. P. Kratz, M. Ballmaier, and K. Welte
RAS and CSF3R mutations in severe congenital neutropenia
Blood,
October 15, 2009;
114(16):
3504 - 3505.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Beel and P. Vandenberghe
G-CSF receptor (CSF3R) mutations in X-linked neutropenia evolving to acute myeloid leukemia or myelodysplasia
Haematologica,
October 1, 2009;
94(10):
1449 - 1452.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Gajewski, V. V. Johnson, S. G. Sandler, A. Sayegh, and T. R. Klumpp
A review of transfusion practice before, during, and after hematopoietic progenitor cell transplantation
Blood,
October 15, 2008;
112(8):
3036 - 3047.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. C. Link, G. Kunter, Y. Kasai, Y. Zhao, T. Miner, M. D. McLellan, R. E. Ries, D. Kapur, R. Nagarajan, D. C. Dale, et al.
Distinct patterns of mutations occurring in de novo AML versus AML arising in the setting of severe congenital neutropenia
Blood,
September 1, 2007;
110(5):
1648 - 1655.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. P. Touw and M. Bontenbal
Granulocyte Colony-Stimulating Factor: Key (F)actor or Innocent Bystander in the Development of Secondary Myeloid Malignancy?
J Natl Cancer Inst,
February 7, 2007;
99(3):
183 - 186.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Hershman, A. I. Neugut, J. S. Jacobson, J. Wang, W.-Y. Tsai, R. McBride, C. L. Bennett, and V. R. Grann
Acute Myeloid Leukemia or Myelodysplastic Syndrome Following Use of Granulocyte Colony-Stimulating Factors During Breast Cancer Adjuvant Chemotherapy
J Natl Cancer Inst,
February 7, 2007;
99(3):
196 - 205.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Shammo and F. M. Stewart
Hematopoietic growth factors
ASH Self-Assessment Program,
January 1, 2007;
2007(1):
45 - 60.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. D. Emanuel
Drifting precariously due to lost tyrosines
Blood,
January 1, 2007;
109(1):
7 - 8.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Germeshausen, M. Ballmaier, and K. Welte
Incidence of CSF3R mutations in severe congenital neutropenia and relevance for leukemogenesis: results of a long-term survey
Blood,
January 1, 2007;
109(1):
93 - 99.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R M James and S E Kinsey
The investigation and management of chronic neutropenia in children
Arch. Dis. Child.,
October 1, 2006;
91(10):
852 - 858.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. S. Rosenberg, B. P. Alter, A. A. Bolyard, M. A. Bonilla, L. A. Boxer, B. Cham, C. Fier, M. Freedman, G. Kannourakis, S. Kinsey, et al.
The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy
Blood,
June 15, 2006;
107(12):
4628 - 4635.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. E. Newburger
Disorders of Neutrophil Number and Function
Hematology,
January 1, 2006;
2006(1):
104 - 110.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. S. Rosenberg, Y. Huang, and B. P. Alter
Individualized risks of first adverse events in patients with Fanconi anemia
Blood,
July 15, 2004;
104(2):
350 - 355.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kuramoto, D. A. Follmann, P. Hematti, S. Sellers, B. A. Agricola, M. E. Metzger, R. E. Donahue, C. von Kalle, and C. E. Dunbar
Effect of chronic cytokine therapy on clonal dynamics in nonhuman primates
Blood,
June 1, 2004;
103(11):
4070 - 4077.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. V. Relling, J. M. Boyett, J. G. Blanco, S. Raimondi, F. G. Behm, J. T. Sandlund, G. K. Rivera, L. E. Kun, W. E. Evans, and C.-H. Pui
Granulocyte colony-stimulating factor and the risk of secondary myeloid malignancy after etoposide treatment
Blood,
May 15, 2003;
101(10):
3862 - 3867.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. S. Grenda, S. E. Johnson, J. R. Mayer, M. L. McLemore, K. F. Benson, M. Horwitz, and D. C. Link
Mice expressing a neutrophil elastase mutation derived from patients with severe congenital neutropenia have normal granulopoiesis
Blood,
October 16, 2002;
100(9):
3221 - 3228.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kojima, A. Ohara, M. Tsuchida, T. Kudoh, R. Hanada, Y. Okimoto, T. Kaneko, T. Takano, K. Ikuta, and I. Tsukimoto
Risk factors for evolution of acquired aplastic anemia into myelodysplastic syndrome and acute myeloid leukemia after immunosuppressive therapy in children
Blood,
July 18, 2002;
100(3):
786 - 790.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. W. Snow, N. Abraham, M. C. Ma, N. W. Abbey, B. Herndier, and M. A. Goldsmith
STAT5 promotes multilineage hematolymphoid development in vivo through effects on early hematopoietic progenitor cells
Blood,
January 1, 2002;
99(1):
95 - 101.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Ancliff, R. E. Gale, R. Liesner, I. M. Hann, and D. C. Linch
Mutations in the ELA2 gene encoding neutrophil elastase are present in most patients with sporadic severe congenital neutropenia but only in some patients with the familial form of the disease
Blood,
November 1, 2001;
98(9):
2645 - 2650.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. M. Bennett, J. P. Kanki, J. Rhodes, T. X. Liu, B. H. Paw, M. W. Kieran, D. M. Langenau, A. Delahaye-Brown, L. I. Zon, M. D. Fleming, et al.
Myelopoiesis in the zebrafish, Danio rerio
Blood,
August 1, 2001;
98(3):
643 - 651.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. H. A. Hermans, I. P. Touw, D. C. Dale, and A. Aprikyan
Significance of neutrophil elastase mutations versus G-CSF receptor mutations for leukemic progression of congenital neutropenia
Blood,
April 1, 2001;
97(7):
2185 - 2186.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. A. Tschan, C. Pilz, C. Zeidler, K. Welte, and M. Germeshausen
Time course of increasing numbers of mutations in the granulocyte colony-stimulating factor receptor gene in a patient with congenital neutropenia who developed leukemia
Blood,
March 15, 2001;
97(6):
1882 - 1884.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Germeshausen, M. Ballmaier, H. Schulze, K. Welte, T. Flohr, K. Beiske, I. Storm-Mathisen, and T. G. Abrahamsen
Granulocyte colony-stimulating factor receptor mutations in a patient with acute lymphoblastic leukemia secondary to severe congenital neutropenia
Blood,
February 1, 2001;
97(3):
829 - 830.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R Lakshman and A Finn
Neutrophil disorders and their management
J. Clin. Pathol.,
January 1, 2001;
54(1):
7 - 19.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F.-Q. Li and M. Horwitz
Characterization of Mutant Neutrophil Elastase in Severe Congenital Neutropenia
J. Biol. Chem.,
April 20, 2001;
276(17):
14230 - 14241.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
