Sex chromosome loss after allogeneic hematopoietic stem cell transplant in patients with hematologic neoplasms: a diagnostic dilemma for clinical cytogeneticists

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.