Many studies including European LeukemiaNet4  have classified ACAs in CML into “major” and “minor” route changes.5  The major route ACAs are the most common chromosomal abnormalities (>10% of cases with ACAs) and include trisomy 8, an extra Philadelphia chromosome (Ph), i(17)(q10), and trisomy 19. Based on their impact on treatment and survival, ACAs in CML were stratified into good and poor prognostic groups. They emerged from different phases (Table 2), and the majority of them emerged during the course of CML treatment (Table 3). We analyzed the frequency of ACAs, the phase when the ACAs emerged, and their impact on TKI response and survival. The Medical Research Council Adult and Children’s Leukaemia Working Parties. Although previous studies have indicated that the major route ACAs4,12-14  but not the minor route ACAs12  are associated with poorer prognosis, these studies were often confounded by the concurrent presence of multiple chromosomal changes. In this study, we aimed to study the role of individual common ACAs in CML patients using a systematic approach by which ACAs are stratified based on their impact on survival and treatment response. IVF is usually recommended in such cases. Depending on the time of admission and whether patients were enrolled in clinical trials, they were offered either imatinib or a second-generation TKI such as nilotinib or dasatinib. After our first round of IVF was unsuccessful because none of my eggs survived the transfer it was an extremely disappointing, both physically (I hate needles) and emotionally. Although the number of patients who developed ACAs in AP and BP is relatively small, these patients appeared to have a very poor CCyR and MMR (Table 2). The CCS testing gave us peace of mind that all of the efforts, medications, stress and money that comes with the IVF procedure can result in a thriving child without chromosomal complications. (B-C) Survival comparison in patients with ACAs emerging during CML disease. For patients who developed ACAs during CML course, survival analysis showed that ACAs in group 1 conferred a better overall prognosis than ACAs in group 2 (Figure 4B, P < .0001; Figure 4C, P < .0001). They can raise your chance of having a child with abnormalities. Study: prenatal exposure to air pollutants causes genetic alterations. The exception to this rule was −Y, which was detected at the time of CML diagnosis in 48% of patients. Knowing the potential of various chromosomal abnormalities leading to miscarriage will make you wonder if this is a case that would repeat constantly. The data below are from papers published in the 1980's.Interestingly, recent studies suggest that … As shown in Table 1, the 6 most common ACAs can be divided into 2 groups based on their impact on TKI treatment response. Yaegashi N, Senoo M, Uehara S, Suzuki H, Maeda T, Fujimori K, Hirahara F, Yajima A. J Hum Genet. Other factors such as exposure to toxic chemicals at work or in other environments could also disturb the proper combination of chromosomes. Among 292 cases with single ACAs, trisomy 8 was the most common cytogenetic change (37/292, 12%), followed by an extra Ph (35/292, 12%), −Y (29/292, 10%), 3q26 rearrangements (23/292, 8%), i(17)(q10) (17/292, 6%), and −7/del (7q) (14/292, 5%) (Figure 2A; Table 1). We focused on CML patients that presented with a single ACA at the initial ACAs emergence. Cases with ACAs were stratified based on the numbers of ACAs at the time of initial ACA emergence (A). Ventriculomegaly. A better classification system needs to be explored. As shown in Figure 2D-E, the survival of patients with 2 or more ACAs was closer to the survival of patients in group 2 than that of patients in group 1 (Figure 2D: 2 ACAs vs group 1, P < .0001; >2 ACAs vs group 1, P < .0001; 2 ACAs vs group 2, P = .08; >2 ACAs vs group 2, P = .97; Figure 2E: 2 ACAs vs group 1, P < .0001; >2 ACAs vs group 1, P < .0001; 2 ACAs vs group 2, P = .04; >2 ACAs vs group 2, P = .17). We were then given an option of using donor egg, but we decided to try one more time with mine. Survival comparison between 2 groups with single ACAs based on ACA emerging phase. Live or let die: the cell’s response to p53. In this study, we analyzed the type, frequency, and role of ACAs in the era of TKI therapy. No difference in OS was found between patients with 2 vs >2 ACAs (P = .56). Similarly, men who are 40 or above may have a problem in conceiving a child. REFERENCES These results are consistent with one of our concurrent studies, in which we found that there was no survival difference between BP patients with high- and low-risk ACAs.19  The detailed survival curves including each individual subgroup are shown in supplemental Figure 2C-D. As shown in Table 1, the majority of patients developed ACAs during the course of CML treatment, and only a small subset of patients had ACAs at the time of initial CML diagnosis. Chromosomal abnormalities typically do not recur unless one or both parents has a balanced translocation or similar genetic issue. When these chromosomes present in the zygote are not present in a proper manner, a chromosomal abnormality is said to occur. Additional chromosomal abnormalities in Philadelphia-positive clone: adverse prognostic influence on frontline imatinib therapy: a GIMEMA Working Party on CML analysis [published correction appears in Blood. Depending on your doctor’s recommendations and the test results of your abnormality testing, there may be an option for you to try to conceive again if the chances of an abnormality repeating itself are minimal. I first heard about CCS at the ORM Free Education Seminar and had no idea that the embryos themselves could be tested. At the time of initial ACA emergence, 54% (292/535) of cases had a single ACA, 20% (105/535) had 2 ACAs, and 26% (138/535) had multiple (>2) ACAs (Figure 1A). We then compared their association with survival. 1980 Apr;7(1):13-26. J Clin Med. A value of P ≤ .05 is considered statistically significant. Updated January 6, 2016. National Human Genome Research Institute website. Their clinical characteristics are listed in Table 1. Your risk is higher if you have had a child with an abnormality in the past. Revised international prognostic scoring system for myelodysplastic syndromes. When compared with patients with no ACAs, patients with ACAs showed a worse survival (Figure 1C: no ACA vs 1 ACA, P < .0001; no ACA vs 2 ACAs, P < .0001; no ACA vs >2 ACAs, P < .0001). In parental karyotyping blood from both or either of the parents is taken. We evaluated CML patients admitted to our hospital in the era of TKI therapy. Genet Couns. The definitions of complete cytogenetic response (CCyR) and major molecular response (MMR) were described previously.16. The criteria proposed by the European LeukemiaNet were used, and similar criteria have been widely used by others.12,13,16,18  Briefly, AP is defined as any of the following criteria: (1) 15% to 29% blasts in peripheral blood or bone marrow; (2) 20% or more basophils in peripheral blood or bone marrow; (3) 30% or more blasts plus promyelocytes in peripheral blood or bone marrow, with blasts <30%; (4) platelets <100 × 109/L unrelated to therapy; or (5) clonal evolution with ACAs. In other cases, chances of chromosomal pairing going wrong are quite a rarity to repeat again. Clinical characteristics of CML patients with common ACAs. The study was approved by the Institutional Review Board of MD Anderson Cancer Center. This is the abnormality that is the major culprit behind a majority of cases ending with miscarriages. Management of pregnancies discordant for abnormality: These pregnancies can be managed expectantly or by selective fetocide of the abnormal twin. At 40 years of age: 1 in 100. Patients with inadequate follow-up karyotyping data were excluded for the evaluation of TKI response. In our recent studies, we demonstrated that some minor route changes such as 11q23/MLL16  and 3q26 rearrangements17  are actually associated with TKI resistance and poor prognosis. Detailed statistical analysis to compare survival between patients with different ACAs was performed, and the results with P values are listed in supplemental Tables 3 and 4. This classification system may be useful to guide the clinical management and assess prognosis of CML patients who develop ACAs as a manifestation of clonal evolution. Only three possibilities would result in either one or both twin's being affected: 1) dizygotic twins with one fetus affected, 2) dizygotic twins with both fetuses affected, and 3) monozygotic twins with both fetuses affected.