Karyotypic and fluorescent in situ hybridization study of the centromere of chromosome 7 in secondary myeloid neoplasms

Abstract

BackgroundSecondary myeloid neoplasms comprise a group of secondary diseases following exposure to myelotoxic agents or due to congenital diseases. The improvement of anticancer agents and immunosuppressive drugs seem to be associated with an increased incidence of secondary myeloid neoplasms. Karyotyping of bone marrow is essential for diagnosis and prognosis. Previous use of alkylating agents and radiation are associated with clonal abnormalities such as recurrent unbalanced -5/5q-, -7/7q- and complex karyotypes, whereas topoisomerase-II inhibitors lead to changes such as the balanced 11q23 rearrangement, t(8;21), t(15;17) and inv(16).ObjectiveTo study the clinical and cytogenetic data of patients with secondary myeloid neoplasms who took antineoplastic and/or immunosuppressive drugs or progressed from aplastic anemia.MethodsThe clinical and cytogenetic characteristics of 42 patients diagnosed with secondary myeloid neoplasms in one institution were retrospectively evaluated. Of these, 25, 11 and 6 patients had had oncological diseases, aplastic anemia and other diseases, respectively. Conventional cytogenetic and FISH analyses were performed for monosomy 7.ResultsThe cytogenetic study was conclusive in 32 cases with 84.4% of clonal abnormalities. Monosomy 7 and complex karyotypes were present in 44.4% and 37%, respectively. A high prevalence of unbalanced abnormalities (96.3%) was observed. Monosomy 7 was more prevalent in patients with myelodysplastic syndromes/myeloid neoplasms after aplastic anemia (66.6%). The median survival after diagnosis of myeloid neoplasms was only 5.7 months. Normal cytogenetics was associated to better survival (p-value = 0.03). There was a slightly worse trend of survival for patients with complex karyotypes (p-value = 0.057). Abnormal karyotype was an independent risk factor for poor survival (p-value = 0.012).ConclusionThis study enhances the importance of cytogenetic analysis of patients at the time of diagnosis of secondary myeloid neoplasms.

Myelodysplastic syndrome unrelated to lentiviral vector in a patient treated with gene therapy for sickle cell disease

“…4 The finding of monosomy 7 in this patient is expected in secondary myeloid neoplasia, including following exposure to alkylating agents such as the busulfan. 23 Reports describe MDS in patients with SCD who experienced graft failure and autologous reconstitution post-HLA-haploidentical HSCT using nonmyeloablative conditioning regimens, typically with alkylating agents. One report showed that 2 of 23 patients with hemoglobinopathies (21 with SCD and 2 with thalassemia) who received 400 cGy total-body irradiation and/or posttransplant addition of alkylating agent cyclophosphamide developed high-grade MDS.…”

Secondary myeloid neoplasms: bone marrow cytogenetic and histological features may be relevant to prognosis

“…Five patients (11.9%) had undergone autologous HSCT. The patient characteristics are shown in Table 1 and further information about clinical data are available in a previous publication 22 . The median latency between the primary disease and s-MN was 85 months (range: 23–221 months).…”

“…The results of karyotype and fluorescence in situ hybridization (FISH) studies have already been published. 22 …”

“…The latter was defined as 0 to 3+ and considered positive if any expression was detected (Table 2). Cytogenetics was performed at diagnosis using standard G-banding 21 and karyotypes were classified as normal, abnormal, complex (≥ 3 abnormalities) or monosomy 7 22 . The International Prognostic Scoring System (IPSS) for primary MDS 23 was calculated.…”

“…Cytogenetics was performed at diagnosis using standard G-banding 21 and karyotypes were classified as normal, abnormal, complex (≥ 3 abnormalities) or monosomy 7. 22 The International Prognostic Scoring System (IPSS) for primary MDS 23 was calculated. The IPSS has already been validated for therapy-induced MDS.…”