Prognostic Value of Complex Karyotype and Monosomal Karyotype in Patients with Adult Acute Lymphoblastic Leukemia Treated with Risk-Adapted Protocols

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4785-4785
Author(s):  
Cristina Motlló ◽  
Josep-Maria Ribera ◽  
Mireia Morgades ◽  
Isabel Granada ◽  
Javier Grau ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Prognostic Value ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Normal Karyotype ◽  
Complex Karyotype ◽  
Cytogenetic Abnormalities ◽  
The Impact ◽  
Monosomal Karyotype

Abstract Abstract 4785 Background The karyotype is an important predictor of outcome in adults with acute lymphoblastic leukemia (ALL). Some groups have reported the negative prognostic value of complex karyotype (CK, defined as ≥5 unrelated chromosomal abnormalities) in adult ALL (Moorman et al, Blood. 2007:109;3189-97). On the other hand, monosomal karyotype (MK, defined as ≥2 distinct autosomal chromosome monosomies or 1 single monosomy in the presence of structural abnormalities) has been associated with a worse outcome in patients with acute myeloid leukemia. We aimed to assess the prognostic value of cytogenetic abnormalities, especially CK and MK, in adults with ALL treated with protocols of the Spanish PETHEMA Group. Patients and Methods The karyotypes of 783 adult ALL patients from 63 Spanish centers treated according to the protocols of the PETHEMA Group between 1993 and 2011 were reviewed. The several PETHEMA protocols were risk-adapted (standard-risk –SR–, high-risk –HR–) or subtype-oriented (Philadelphia chromosome [Ph+] ALL -with or without imatinib-, and Burkitt's ALL [BL]). The impact of the main cytogenetic abnormalities as well as of the CK and MK on complete remission (CR) rate, CR duration, overall survival (OS) and event-free survival (EFS) was analyzed. Results The median age of the series was 33 years (range 15–82) and 448 patients (57.2%) were male. The karyotypes of 560 out of 783 patients were evaluable after review: normal karyotype 153 patients, t(9;22) 120, t(v;11q23) 30, t(8;14), t(8;22) or t(2;8) 47, high hyperdiploidy (>50 chromosomes) 53, low hyperdiploidy (47–50 chromosomes) 52, hypodiploidy (45–39 chromosomes) 32 and extreme hypodiploidy (<39 chromosomes) 2. Twenty-eight patients (8.3% of the 338 evaluable karyotypes) had CK and 54 (11.2% of the 481 evaluable karyotypes) had MK. The CR rate, probability of CR duration, the OS probability and the EFS probability are described in table 1. In our study the CK and the MK did not have any impact on CR, CR duration, OS and EFS. Analysis of OS probabilities at 4 years of the most important cytogenetic abnormalities showed: normal karyotype: 46±5%, t(9;22): 20±12%, t(v;11q23): 26±17%, hyperdiplody: 54±15%, hypodiploidy: 47±27%, t(1;19): 44±31% and t(8;14)/t(8;22)/t(2;8): 48±16% (p<0.001). Conclusions Our study confirms that cytogenetics is a very important tool for risk assessment in adult ALL. Patients with t(9;22) and t(v;11q23) had the worst prognosis and the t(1;19) did not have prognostic significance. The introduction of imatinib in patients with t(9:22) ALL significantly improved their outcome. The CK and the MK were not associated with a worse prognosis in patients treated with risk-adapted or subtype-oriented protocols of the PETHEMA group. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Prognostic Significance of Cytogenetic Abnormalities for Patients with Acute Lymphoblastic Leukemia, a Region-Wide Retrospective Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5202-5202
Author(s):  
Keito Suto ◽  
Akio Shigematsu ◽  
Shuichi Ota ◽  
Ryoji Kobayashi ◽  
Takeshi Kondo ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Elderly Patients ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Age Groups ◽  
Remission Induction ◽  
Complex Karyotype ◽  
Cytogenetic Abnormalities ◽  
The Impact

Background; Cytogenetic abnormalities (CA) have been reported as one of the independent prognostic factors for patients with acute lymphoblastic leukemia (ALL). The most common CA in ALL is the Philadelphia chromosome (Ph). Recently, by the introduction of tyrosine kinase inhibitors for Ph+ALL patients and pediatric-inspired protocol for adolescent/young-adult (AYA) patients, the management of ALL has progressed dramatically. We therefore retrospectively analyzed the impact of CA for patients with ALL in the era of TKIs and pediatric-inspired protocol for AYA. Methods; Clinical data for 512 patients who were diagnosed as having ALL between 2007 and 2017 were collected from 21 centers in Hokkaido, Japan. Patients with lymphoblastic lymphoma and Burkitt leukemia were excluded from this study. Results; The median age of the patients was 55 years (range: 15-84 years). Ninety-two of the patients were pediatric (0-14 years), 86 were AYA (15-35 years), 195 were adult (36-65 years) and 148 were elderly patients (66- years). Cytogenetic (G-banding) results were available in 486 patients. Three hundred forty-seven patients had abnormal karyotypes (AK), and 139 patients had normal karyotype (NK). BCR-ABL, including masked Ph, was positive in 193 patients, and 181 (93.8%) of them were more than 36 years. Abnormalities of -7/del (7), +8, +21, 11q32 (MLL), E2A/PBX1 or complex karyotype were seen in 38, 34, 46, 13, 10 and 94 of the patients, respectively. After a first remission induction therapy, 418 of 467 (89.5%) evaluable patients achieved complete remission (CR), and BCR-ABL+ patients showed better CR rate than those without BCR-ABL (93.7% vs. 87.4%, P=0.04). At the median follow-up of 1180 days (9-4049 days), overall survival (OS) was superior in patients with NK than those with AK (P=0.01), and BCR-ABL+ patients showed poorer OS than those without BCR-ABL (P=0.01). However, by subgroup analyses of the age groups, there were no difference of OS between NK and AK (P=0.56 for pediatric, P=0.19 for AYA, P=0.32 for adult and P=0.98 for elderly). In adult and elderly patients, OS was not different between BCR-ABL+ and BCR-ABL-, though in patients over 70 years, BCR-ABL positivity was associated with superior OS (Hazard ratio, 3.2; 95% confidence intervals, 1.04-4.78, P=0.02). The abnormalities of +8 or +21 showed excellent OS in pediatric or AYA patients, however, they showed poor OS in adult or elderly patients. In adult or elderly BCR-ABL- patients, OS of patients with complex karyotype was inferior to those without complex karyotype. Conclusion; BCR-ABL was not associated with poor outcome in the era of TKI. We need to evaluate the effect of CA on patients' outcome depending on age groups. Disclosures No relevant conflicts of interest to declare.

Prognostic significance of complex karyotype and monosomal karyotype in adult patients with acute lymphoblastic leukemia treated with risk-adapted protocols

Cancer ◽  
2014 ◽  
Vol 120 (24) ◽  
pp. 3958-3964 ◽  
Author(s):  
Cristina Motlló ◽  
Josep-María Ribera ◽  
Mireia Morgades ◽  
Isabel Granada ◽  
Pau Montesinos ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Adult Patients ◽  
Complex Karyotype ◽  
Monosomal Karyotype

Absence of Chromosomal Abnormalities Corresponds to Better Survival in Adult Ph-Negative ACUTE Lymphoblastic Leukemia – Results of the Russian ACUTE Lymphoblastic Leukemia (RALL) Study Group.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2572-2572
Author(s):  
Elena Parovichnikova ◽  
Julia R Davidyan ◽  
Galina A Kliasova ◽  
Andrey N Sokolov ◽  
Vera V Troitskaya ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Chromosomal Abnormalities ◽  
Conflicts Of Interest ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Normal Karyotype ◽  
Risk Groups ◽  
Treatment Schedule ◽  
Blast Count ◽  
The Impact

Abstract Abstract 2572 Adult ALL regardless recent advantages in adolescents and young adults is still considered to be a therapeutical problem. So called “a pediatric-like approach” applied in adult ALL is reported to be more reasonable even in the older adults (up to 55 y). RALL has initiated a prospective multicenter trial for adult Ph-neg ALL based on: 1) evaluation of b/m blast clearance after 7 days of Prednisolone (PRD) prephase and its substitution by Dexamethasone (DEXA) if b/m blast count was >25%; 2) continuous 2,5 years treatment schedule with prolonged L-asparaginase (Σ=590.000 IU); 3) evaluation of the impact of the late intensification (2 courses of HD of methotrexate and ARA-C) on MRD clearance. The study is registered on the ClinicalTrials.gov public site; NCT01193933. From Nov, 2008, till June, 2012, 24 centers enrolled 173 pts: median age 28 y (15–55), 71f/101m, 112 (64,7%) = B-lin, 54 (31,2%) = T-lin, 1 pt -undifferentiated AL (0,6%), 6 - uknown phenotype (3,5%), median LDH=848 ME (72–13061), median L=13,5 (0,6–556*109/l). Cytogenetics was evaluable in 58,3% of pts (n=101) and 46,5% of them (n=47) had normal karyotype (NK). Initial risk group was evaluated in 154 pts among whom 46 patients (29,9%) were in the standard risk (SR) group (WBC <30 for B-Lin, <100 for T-Lin, EGIL BII-III, T-III; LDH < 2N, No late CR, t(4;11)-negative), 109 (60,1%) - in the high risk (HR) group (WBC >30 for B-Lin, >100 for T-Lin, EGIL BI, T-I-II-IV; LDH > 2N, No late CR, t(4;11)-positive). 19/173 pts (11%) were not qualified. The analysis was performed in June, 2012. +8 day b/m blast count was reported in 149 pts and b/m blasts less than 25% were detected in 36,2% of pts. The portion of PRD non-responders was statistically different in SR and HR groups: 24/45 (53,3%) and 68/101 (67,3%) (p=0,01), confirming the initial risk groups identification. Induction results were obtained in 150 pts, and CR rate was identical in both risk groups (SR=86,9%; HR=84,1%) with total 12 induction deaths (8,0%) and 6 resistant leukemias (4,0%). With a median follow-up of 12 mo (1–36 mo) death in CR was reported in 9/132 (6,8%) pts. OS at 36 mo was 58,6%, DFS-68,3%. MRD analysis for clonal IgH and TCR rearrangements was carried out in 25 pts. And as in our previous studies (ASH 2006, abstr 2294) the clearance was slow with only 41,6% pts negative for MRD at day +133 (4mo) of the protocol. Two late intensification courses (day +157 = 5 mo) increased MRD negativity only up to 50%. Such slow MRD clearance did not correspond to higher relapse rate so far. Age, WBC, immunophenotype, LDH, risk group, +8 day b/m blast count, time to CR, time without treatment (<>8days), L-asparaginase cessation did not influence survival. OS and DFS differed in pts with NK vs all other abnormalities: 87,4% vs 57,9% (p=0,002) and 88,9% vs 66,5%, respectively (p=0,02). So, our data demonstrated that ALL-2009 protocol provided 58% 3-years overall survival and 68,3% DFS. In adult Ph-neg ALL normal karyotype predicts better survival. The MRD clearance is very slow while on this protocol. Disclosures: No relevant conflicts of interest to declare.

Value of Cytogenetic Abnormalities in Adult Patients with Philadelphia Chromosome (Ph)-Negative Acute Lymphoblastic Leukemia (ALL) Treated in the Pediatric-Inspired Trials from the Group for Research on Adult ALL (GRAALL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 492-492
Author(s):  
Marina Lafage-Pochitaloff ◽  
Laurence Baranger ◽  
Mathilde Hunault ◽  
Wendy Cuccuini ◽  
Audrey Bidet ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Response To Therapy ◽  
Adult Patients ◽  
Individual Risk ◽  
Complex Karyotype ◽  
Cytogenetic Abnormalities ◽  
11Q23 Abnormalities ◽  
Monosomal Karyotype

Abstract Background: Numerous recurrent chromosomal abnormalities have been described in adult Ph-negative ALL, often observed in small patient cohorts. In the largest MRC/ECOG study (Moorman, Blood 2007), t(4;11)(q21;q23), 14q32 involvement, complex karyotype (≥5 abnormalities), and low hypodiploidy/near triploidy (Ho-Tr) were associated with shorter event-free survival (EFS), while patients with high hyperdiploidy or del(9p) had a better outcome. We aimed to confirm these observations in 955 adult patients (15-60y; median, 35y) with Ph-negative ALL treated in the pediatric-inspired GRAALL-2003/2005 trials. Patients and Methods: Overall, a karyotype was performed for 946 (611 BCP-ALL, and 335 T-ALL), successful for 811 (523 BCP-ALL and 288 T-ALL) and abnormal in 590 patients (387 BCP-ALL and 203 T-ALL). FISH and/or PCR screening for relevant abnormalities and DNA index were also performed, finally allowing for the identification of cytogenetic abnormalities in 677/955 patients (71%). All were centrally reviewed. Ultimately, 857/955 patients (90%; 542 BCP-ALL and 315 T-ALL) could be classified in 18 exclusive primary cytogenetic subsets as detailed below. Endpoints were cumulative incidence of failure (CIF, including primary refractoriness and relapse) and EFS. With a median follow-up of 4 years, 5-year CIF and EFS were estimated in these patients at 31% and 51%, respectively. As some abnormalities, including MLL rearrangements, Ho/Tr, t(1;19)(q23;p13)/TCF3 and complex karyotypes were used to stratify allogeneic stem cell transplantation (SCT) in GRAALL trials, some comparisons were repeated after censoring patients transplanted in first CR at SCT time. Results: The 542 informative BCP-ALL patients were classified as: t(4;11)(q21;q23)/MLL-AFF1 (n=72; 13%); other MLL+ 11q23 abnormalities (n=11; 2%); t(1;19)(q23;p13)/TCF3-PBX1 (#28; 5%); Ho/Tr (n=33; 6%); high hyperdiploidy (n=36; 7%); abnormal 14q32/IGH translocation (n=27; 5%); t(12;21)(p13;q22)/ETV6-RUNX1 (n=2; 0.4%); iAMP21 (n=3; 0.6%); other abnormalities (n=210; 39%); and no abnormality (n=120; 22%). The 315 informative T-ALL patients were classified as: t(10;14)(q24;q11)/TLX1 (n=64; 20%); other 14q11 or 7q34/TCR (n=31; 10%); t(5;14)(q35;q32)/TLX3 (n=29; 9%); t(10;11)(p12;q14)/PICALM-MLLT10 (n=14; 4%); deletion 1p32/SIL-TAL (n=18; 6%); MLL+ 11q23 abnormalities (n=6; 2%); other abnormalities (n=93; 30%); and no abnormalities (n=60; 19%). A complex karyotype was observed in 27/527 (5%) BCP-ALL and 21/298 (7%) T-ALL patients and a monosomal karyotype (as per Breems, JCO 2008) in 82/518 (16%) BCP-ALL and 26/286 (9%) T-ALL patients. In BCP-ALL, trends towards higher CIF and shorter EFS were observed in t(4;11) patients, with or without SCT censoring (HRs, 1.34 to 1.64; p values <0.10). Shorter EFS was observed in 3 subsets: 14q32 (HR, 2.10; p=0.002), Ho/Tr (HR, 1.45; p=0.10), and monosomal karyotype (HR, 1.42; p=0.029), but CIF were not different. This might be related to the older age of patients in these subsets (medians, 43y, 53y and 44y; p=0.029, <0.001 and <0.001, respectively) and worse treatment tolerance. For instance, higher incidences of non ALL-related deaths were observed in patients with 14q32 abnormalities or monosomal karyotype (p=0.031 and 0.067, respectively). Patients with high hyperdiploidy only tended to have lower CIF and longer EFS. Complex karyotype did not impact CIF and EFS, even after SCT censoring. Conversely, in T-ALL, complex karyotypes were associated with shorter EFS (HR, 2.20; p=0.004), even if the difference in CIF did not reach significance. A worse outcome was also observed in patients with t(10;11)(p12;q14)/PICALM-MLLT10 (HR, 2.45 and 2.14; p=0.016 and 0.021, for CIF and EFS respectively). A longer EFS was observed in patients with t(10;14)(q24;q11)/TLX1 (HR, 0.55; p=0.014), with a trend for lower CIF (HR, 0.59; p=0.070), while no inferior outcome was observed in t(5;14)(q35;q32)/TLX3 patients. Conclusion: These results show that, in the context of an intensified pediatric-inspired protocol designed for adult Ph-negative ALL patients, few cytogenetic subsets remained reliably predictive of response to therapy. Differences observed in EFS might partly be due to treatment-related mortality. Combining cytogenetics, molecular genetics and minimal residual disease monitoring could allow for better individual risk assessment (Beldjord, Blood 2014). Disclosures No relevant conflicts of interest to declare.

Secondary Cytogenetic Abnormalities and Outcome in Children with TEL-AML1-Positive Acute Lymphoblastic Leukemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1450-1450
Author(s):  
Oussama A. Abla ◽  
Johann Hitzler ◽  
Charles Ye ◽  
Mohamed Abdelhaleem ◽  
Ronald Grant ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Prognostic Indicator ◽  
Similar Rate ◽  
Chromosome 21 ◽  
Prognostic Impact ◽  
Extra Copy ◽  
Cytogenetic Abnormalities

Abstract The t(12;21) translocation, which results in the fusion of the TEL (ETV6) and AML1 (RUNX1) genes, is present in ~25% of pediatric B-precusor acute lymphoblastic leukemia (ALL) patients. Although initially thought to be a favorable prognostic indicator, the t(12;21) was associated with a similar rate of relapse as t(12;21)-negative pre-B ALL in subsequent studies. While secondary cytogenetic abnormalities are often present, their prognostic significance is unknown. The objective of this study is therefore to examine the type, frequency and prognostic impact of secondary cytogenetic abnormalites in t(12;21)-positive blasts of children with ALL. We studied retrospectively 56 patients diagnosed with t(12;21)-positive ALL at the Hospital for Sick Children between 2000–2005. The mean age at diagnosis was 4.9 years (range &lt;1 to 12 years). Nine patients (16%) presented with a white blood cell count of greater than 50 × 109/L. Cytogenetic studies consisted of a combination of FISH, G-banding and spectral karyotyping. The most frequent secondary cytogenetic changes in patients with t(12;21)-positive ALL were: the deletion of the non-translocated TEL allele (38%), an extra copy of the TEL-AML1 fusion gene (14%). Additional numerical abnormalities were seen in approximately one-third of the cases, with the most common being a gain of chromosome 21(13%). Recurrent deletions of chromosomal regions 6q and 11q were observed (14%). A surprising degree of karyotypic complexity was noted. Three or more additional chromosome abnormalities, two abnormal clonal lines, and complex structural rearrangements involving TEL-AML1 were detected in 28%, 21%, and 9% of patients, respectively. Five children (9%) in this cohort have developed a relapse of ALL. The 5-year event-free survival (EFS) was 83±7%. The 5-year EFS for patients with a deleted second TEL allele or an extra TEL-AML1 fusion was not statistically different. Of note, 4 of the children who relapsed had high-risk features at presentation (NCI criteria). All were treated with chemotherapy protocols developed for lower risk ALL. The realization that TEL-AML1 does not always predict excellent prognosis indicates that an on-going study of patients and their survival, with detailed analysis of complex genetic changes, is necessary for a reliable assessment of the prognostic value of the t(12;21) in pediatric ALL.

Adult Acute Lymphoblastic Leukemia and Cytogenetic Abnormalities in Different Racial and Ethnic Subgroups.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4547-4547
Author(s):  
Deimante Tamkus ◽  
Ahmad Jajeh ◽  
Ebenezer Berko ◽  
David Osafo ◽  
Decebal Griza ◽  
...  
Keyword(s):  
African American ◽  
Acute Lymphoblastic Leukemia ◽  
African Americans ◽  
Lymphoblastic Leukemia ◽  
Normal Karyotype ◽  
Cook County ◽  
Female Ratio ◽  
Cytogenetic Abnormalities ◽  
Hispanic Patients ◽  
Chromosomal Changes

Abstract Inferior survival of African American and Hispanic patients with acute lymphoblastic leukemia (ALL) has been reported. The reason for this is unclear. A retrospective analysis was conducted to see if abnormal cytogenetics account for the differences. We have analyzed cytogenetic studies of 39 adults (16 year and older) with newly diagnosed ALL who were consecutively treated at John Stroger Hospital of Cook County between 1997 and 2005. The study population included 13 (33%) African Americans, 18 (46%) Hispanics, 6 (16%) Caucasians, and 2 (5 %) other ethnic background adults. Male to female ratio was 2:1. Mean age at diagnosis was 26 (range between 16 and 71 years). A clonal cytogenetic abnormality was detected in 27 patients, and 12 patients had normal karyotype. Patients with t (9;22)(q34;q11), BCR-ABL + by FISH, t (4;11)(q21;q23), +8, −7 cytogenetic abnormalities were assigned to an unfavorable cytogenetic group. This group was composed of 14 patients. None of our study patients had favorable cytogenetics: del (12p), t(12p), t(14q11-q23), inv(14)(q11;q32) or t(10;14)(q24;q11). Remaining 25 patients with normal karyotype (n=12) or miscellaneous cytogenetic abnormalities (n=13) were classified as normal risk group. 54 % of African Americans had unfavorable cytogenetics, compared with 33 % Caucasians and 17 % Hispanics. Translocation t (9;22) alone or in association with other cytogenetic abnormalities was most commonly seen. 9 patients had single, and 18 had multiple chromosomal changes. Hispanic group had more complex cytogenetic changes when compared with the African American or Caucasian groups. Unfavorable cytogenetic abnormalities may account for inferior survival in African Americans, but other factors such as compliance or pharmacogenetics should be evaluated, especially in the Hispanic patient population.

Implication of Genetic Variations of Ikzf1, ARIDB5, and CEBPE Genes In the Risk of Childhood Acute Lymphoblastic Leukemia In Korea

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3235-3235
Author(s):  
Dong Kyun Han ◽  
Hee Nam Kim ◽  
Min Ho Shin ◽  
Minenori Eguchi-Ishimae ◽  
Mariko Eguchi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Genetic Variations ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Asian Countries ◽  
Childhood All ◽  
Genomic Variations ◽  
Genotype Frequencies ◽  
The Impact

Abstract Abstract 3235 Background: Recent western studies have showed the implication of the germline genomic variations in IKZF1 gene at 7p12.2, ARIDB5 gene at 10q21.2, and CEBPE gene at 14q11.2 on the risk of childhood acute lymphoblastic leukemia (ALL); the most significant association was observed in the single nucleotide polymorphism (SNP) rs4132601 which located at 3' region of the IKZF1. IKZF1 plays important role in lymphocyte differentiation, proliferation and function, ARIDB5 in embryogenesis and growth regulation, and CEBPE in regulation of myelopoiesis. Genomic variants in these genes are therefore considered to be involved in transcriptional regulation and differentiation of B cell progenitors. However, there have been no reports on the role of germline variations in leukemogenesis of childhood ALL in Asian countries. The aim of this study is to show the impact of these genetic variants on childhood ALL in Korea. Patients and Methods: To examine the association between genetic variations (IKZF1 rs4132601, ARIDB5 rs7089424, and CEBPE rs2239633) and the risk of childhood ALL, we here analyzed 228 children with ALL and 508 healthy individuals in Korea. Results: In ARIDB5 rs7089424, TG and GG genotypes were significantly associated with a risk for ALL (odds ratio [OR], 1.63; 95% confidential interval [CI], 1.07–2.48; P=0.02 for TG genotype, OR, 2.69; 95% CI, 1.42–5.07; P=0.002 for GG genotype). The allele incidence of ARIDB5 rs7089424 was also significantly associated with a risk for ALL (OR, 1.66; 95% CI, 1.24–2.22; P=0.0006). CEBPE rs2239633 TT genotype showed a significant association with a decreased risk for ALL (OR, 0.54; 95% CI, 0.33–0.90; P=0.02 for TT genotype). The allele incidence of CEBPE rs2239633 was also associated with a decreased risk for ALL (OR, 0.77; 95% CI, 0.61–0.97; P=0.02). There was no significant association between IKZF1 rs4132601 polymorphism and a risk for ALL in this study. Conclusion: These results suggest that genomic variations of ARIDB5 and CEBPE may play an important role in the risk for childhood ALL in Korea, compared with findings from western countries showing a significant relation between IKZF1 and childhood ALL. Several factors should be considered to explain a discrepancy between our results and the previous studies, which include different genotype frequencies in polymorphisms and varied susceptibility to ALL in different ethnic groups. Further studies incorporating larger number of cases and analyzing other SNPs or other Asian countries are warranted in childhood ALL. Disclosures: No relevant conflicts of interest to declare.

Monosomal Karyotype In Primary Myelofibrosis Is Prognostically Worse Than Otherwise Unfavorable Karyotype

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3069-3069
Author(s):  
Rakhee Vaidya ◽  
Domenica Caramazza ◽  
Kebede Begna ◽  
Naseema Gangat ◽  
Daniel L. Van Dyke ◽  
...  
Keyword(s):  
Clin Oncol ◽  
Mayo Clinic ◽  
Conflicts Of Interest ◽  
Normal Karyotype ◽  
Primary Myelofibrosis ◽  
Structural Abnormality ◽  
Complex Karyotype ◽  
Trisomy 8 ◽  
First Time ◽  
Monosomal Karyotype

Abstract Abstract 3069 Background: Monosomal karyotype (MK) is defined as the presence of two or more distinct autosomal chromosome monosomies or a single autosomal monosomy associated with at least one structural abnormality (Breems DA et al. J Clin Oncol 2008; 26: 4791). In acute myeloid leukemia (AML), MK has been shown to be prognostically worse than complex or other unfavorable karyotype (Breems DA et al. J Clin Oncol 2008; 26: 4791). In primary myelofibrosis (PMF), complex karyotype or isolated trisomy 8 predicts inferior survival (Hussein K et al. Blood 2010; 115: 496). Objective: To determine if MK in PMF is prognostically distinct from previously defined poor cytogenetic risk categories including complex karyotype and isolated trisomy 8. Methods: The Mayo Clinic database for PMF was used to identify consecutive patients with unfavorable karyotype including complex karyotype and sole trisomy 8. WHO criteria were used for PMF diagnosis and leukemic transformation (Vardiman JW et al. Blood 2009; 114: 937). Results: Among 793 PMF patients with cytogenetic information at the time of their first time referral to the Mayo Clinic, 452 displayed a normal karyotype and 341 (43%) an abnormal karyotype. Of the latter, 41 (12%) displayed complex karyotype and 21 (6%) sole trisomy 8. Among the 41 patients with complex karyotype, 17 (42%) met the criteria for MK and 24 (58%) displayed complex karyotype without monosomies. Overall survival was significantly inferior in patients with MK compared to those with either complex karyotype without monosomies (p=0.02; HR 2.3, 95% CI 1.1–4.8) or trisomy 8 (p=0.02; HR 2.4, 95% CI 1.2–5.1) (Fig. 1). Prognosis among all three groups was significantly worse than patients with normal karyotype (Fig. 1). Leukemia-free survival was also significantly inferior in patients with MK compared to those with either complex karyotype without monosomies (p=0.02; HR 6.9, 95% CI 1.3–37.3) or trisomy 8 (p=0.02; HR 14.8, 95% CI 1.7–130.8) (Fig. 2). LFS in patients with normal karyotype was similar to those with either complex karyotype without monosomies (p=0.31) or trisomy 8 (p=0.86) (Figure 2). Conclusions: Monosomal karyotype in PMF is distinctly associated with extremely poor overall and leukemia-free survivals that are significantly worse than those seen in PMF patients with other unfavorable karyotype including complex karyotype without monosomies and sole trisomy 8 abnormalities. Disclosures: No relevant conflicts of interest to declare.

Concordance and Prognostic Significance of Minimal Residual Disease Detection in Peripheral Blood and Bone Marrow Samples of Infants with MLL-rearranged Acute Lymphoblastic Leukemia Treated By MLL-Baby Protocol

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2404-2404
Author(s):  
Grigory Tsaur ◽  
Alexander Popov ◽  
Tatyana Riger ◽  
Alexander Solodovnikov ◽  
Tatyana Nasedkina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Prognostic Value ◽  
Residual Disease ◽  
Fusion Gene ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Remission Induction ◽  
Gene Transcripts ◽  
Minimal Residual

Abstract Background. Minimal residual disease (MRD) is powerful tool for prediction of treatment outcome in leukemia patients of various age groups, including infants with acute lymphoblastic leukemia (ALL). In the vast majority of cases only bone marrow (BM) samples are used for MRD detection. Objective. To estimate prognostic significance of MRD in peripheral blood (PB) and BM by qualitative detection of different MLL fusion gene transcripts in infant ALL enrolled into MLL-Baby protocol. Methods. Fifty three infants (20 boys and 33 girls) with median age of 5.3 months (range 0.03-11.80) and defined MLL rearrangements were included in the current study. Among them there were 25 patients (47.2%) carrying MLL-AFF1 fusion gene transcripts, 10 (18.9%) MLL-MLLT3-positive cases, 9 (17.0%) MLL-MLLT1-positive cases, 5 (9.4%) MLL-MLLT10-positive cases and 4 (7.5%) MLL-EPS15-positive ones. MRD evaluation was performed by detection of MLL fusion gene transcripts in BM and PB samples using real-time PCR and nested RT-PCR with sensitivity non-less than 1E-04. MRD-negativity was defined as absence of fusion gene transcripts in both assays. Median of follow-up period in the observed group was 5.2 years. Time points (TP) for MRD assessment were as follows: day 15 of remission induction (TP1), at the end of remission induction (TP2), after each course of ATRA administration (TP3-TP7). Informed consent was obtained in all cases. Results. We estimated 142 paired BM/PB samples. 77 samples were double positive, 43 were double negative Thus concordance between MRD results in BM and PB samples achieved 84.5%. Concordance varied between different TPs of MLL-Baby protocol from 79.0% to 100%. The highest concordance rate was at TP4 and TP7 (92.3% and 100%, respectively). Interestingly, all discrepant results (22 samples 15.5%) were BM-positive/PB-negative. Median level of ABL gene, used for normalization, was similar in BM and PB samples (4.85E+04 vs 4.95E+04, respectively, p=0.760). Evaluation of prognostic significance of MRD in BM in TP1-TP7 revealed that TP4 was the earliest TP when discriminative data between MRD-positive and MRD-negative patients were obtained. MRD-positivity at TP4 in BM led to unfavorable outcome. Event-free survival was significantly lower in MRD-positive group (n=22) in comparison to MRD-negative one (n=31) (0.06±0.06 vs 0.70±0.09 p=0.0001), while cumulative incidence of relapse in MRD-positive patients was remarkably higher (0.92±0.01 vs 0.29±0.08, p<0.0001). MRD-positivity at this TP in BM was the only significant factor in the diagnostic model where initial risk factors (age at diagnosis, initial WBC count, immunophenotype, CNS disease, presence of MLL-AF4) were combined to response criteria (number of blast cells at day 8 of dexamethasone prophase and MRD in BM at TP4) (Table). The only TP when MRD data obtained from PB samples had prognostic value was TP6. In this TP cumulative incidence of relapse in MRD-positive patients was significantly higher in comparison to MRD-negative ones (0.88±0.11 vs 0.25±0.13, respectively, p=0.003). However these data did not bring any extra advantages as compared to TP4 in BM. Conclusions. Despite high qualitative concordance rate between MRD detection in BM and PB samples we could not show prognostic value of MRD monitoring in PB by fusion gene transcripts. Univariate and multivariate analysis revealed that MRD-positivity at TP4 in BM was the only significant and independent prognostic factor of unfavorable outcome in the observed group of patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document