TY - JOUR
T1 - Sex chromosome loss after allogeneic hematopoietic stem cell transplant in patients with hematologic neoplasms
T2 - A diagnostic dilemma for clinical cytogeneticists
AU - Tang, Zhenya
AU - Medeiros, L. Jeffrey
AU - Yin, C. Cameron
AU - Wang, Wei
AU - Lu, Xinyan
AU - Young, Ken H.
AU - Khoury, Joseph D.
AU - Tang, Guilin
N1 - Publisher Copyright:
© 2016 The Author(s).
PY - 2016/8/8
Y1 - 2016/8/8
N2 - Background: Sex chromosome loss (SCL), including loss of an X chromosome (-X) in females and loss of the Y chromosome (-Y) in males, resulting in a karyotype of 45,X, rarely occurs in patients post an allogeneic hematopoietic stem cell transplant (alloHSCT). However, origin of this abnormal clone and its clinical significance remains unknown. Results: We present 12 cases with SCL who underwent alloHSCT; 9 patients (4 men and 5 women with a median age of 56 years) developed isolated SCL after alloHSCT (Group I), and 3 patients (all women with a median age of 58 years) had a SCL before undergoing alloHSCT after which SCL disappeared (Group II). The primary neoplasms included chronic lymphocytic leukemia (n = 5), acute myeloid leukemia (n = 5), chronic myelogenous leukemia with nodal marginal zone lymphoma (n = 1) and Hodgkin lymphoma (n = 1). According to the donor/recipient relationship, their alloHSCT can be divided into sex-matched, HLA-matched, unrelated donors (n = 2); sex-mismatched, HLA-matched, unrelated donors (n = 4); sex-mismatched, HLA-matched, related donors (2 HLA-identical and 2 HLA-haploidentical cases) and sex-matched, HLA-matched, related donors (2 HLA-haploidentical cases). In Group I, isolated SCL was first detected with a median interval of 3 months (range 1 to 42 months) after the alloHSCT. By the end of clinical follow-up in patients in Group I, 7 patients expired with a median overall survival of 45 months (range 3 to 108 months) after alloHSCT and 33 months (range 0 to 66 months) after SCL detection. In Group II, 1 patient expired with a survival time of 54 months after the alloHSCT. Detection of SCL after alloHSCT can be transient, intermittent or persistent. Conclusions: Interpretation of SCL is challenging in the context of alloHSCT. Chimerism testing is useful in determining the origin of SCL. In the case of SCL with donor/recipient chimerism, deduction of the SCL origin by all means and use of "-?X" or "-?Y" in the ISCN nomenclature are recommended. Clinical follow-up with closely monitoring the SCL by both cytogenetic and molecular analyses is needed.
AB - Background: Sex chromosome loss (SCL), including loss of an X chromosome (-X) in females and loss of the Y chromosome (-Y) in males, resulting in a karyotype of 45,X, rarely occurs in patients post an allogeneic hematopoietic stem cell transplant (alloHSCT). However, origin of this abnormal clone and its clinical significance remains unknown. Results: We present 12 cases with SCL who underwent alloHSCT; 9 patients (4 men and 5 women with a median age of 56 years) developed isolated SCL after alloHSCT (Group I), and 3 patients (all women with a median age of 58 years) had a SCL before undergoing alloHSCT after which SCL disappeared (Group II). The primary neoplasms included chronic lymphocytic leukemia (n = 5), acute myeloid leukemia (n = 5), chronic myelogenous leukemia with nodal marginal zone lymphoma (n = 1) and Hodgkin lymphoma (n = 1). According to the donor/recipient relationship, their alloHSCT can be divided into sex-matched, HLA-matched, unrelated donors (n = 2); sex-mismatched, HLA-matched, unrelated donors (n = 4); sex-mismatched, HLA-matched, related donors (2 HLA-identical and 2 HLA-haploidentical cases) and sex-matched, HLA-matched, related donors (2 HLA-haploidentical cases). In Group I, isolated SCL was first detected with a median interval of 3 months (range 1 to 42 months) after the alloHSCT. By the end of clinical follow-up in patients in Group I, 7 patients expired with a median overall survival of 45 months (range 3 to 108 months) after alloHSCT and 33 months (range 0 to 66 months) after SCL detection. In Group II, 1 patient expired with a survival time of 54 months after the alloHSCT. Detection of SCL after alloHSCT can be transient, intermittent or persistent. Conclusions: Interpretation of SCL is challenging in the context of alloHSCT. Chimerism testing is useful in determining the origin of SCL. In the case of SCL with donor/recipient chimerism, deduction of the SCL origin by all means and use of "-?X" or "-?Y" in the ISCN nomenclature are recommended. Clinical follow-up with closely monitoring the SCL by both cytogenetic and molecular analyses is needed.
KW - -X
KW - -Y
KW - Allogeneic hematopoietic stem cell transplant (alloHSCT)
KW - Chimerism testing
KW - Cytogenetic (CG) analyses
KW - Sex chromosome loss (SCL)
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U2 - 10.1186/s13039-016-0275-3
DO - 10.1186/s13039-016-0275-3
M3 - Article
C2 - 27508005
AN - SCOPUS:84984984974
SN - 1755-8166
VL - 9
JO - Molecular Cytogenetics
JF - Molecular Cytogenetics
IS - 1
M1 - 62
ER -