scholarly journals The Role of Genetic Polymorphisms ofTPMTandNUDT15Genes in Adult Patients with Ph-Negative Acute Lymphoblastic Leukemia in Russia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 21-22
Author(s):  
Ekaterina S. Kotova ◽  
Olga A. Gavrilina ◽  
Igor A Yakutik ◽  
Andrey B. Sudarikov ◽  
Elena N. Parovichnikova ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Genetic Polymorphisms ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Rt Pcr ◽  
Significant Toxicity ◽  
Allele Specific ◽  
Better Than

Context: TPMTandNUDT15polymorphisms are involved in the toxicity and therapeutic efficacy of thiopurine drugs (6-mercaptopurine (6-MP)). The frequencies of polymorphisms of these genes are different across diverse populations. The role ofTPMTandNUDT15genes in adult patients (pts) with Ph-negative acute lymphoblastic leukemia (ALL) in Russia is still unclear. Objective:Evaluation of frequency and significance ofTPMTandNUDT15polymorphisms in the cohort of adult Ph-negative ALL pts treated by the RALL-2016 protocol. Design and Patients:Since April 2017 till July 2020 56 adult Ph-negative ALL patients treated by RALL-2016 protocol were included in the research ofTPMTandNUDT15polymorphisms. Median age was 32 у (range, 18-54), m/f: 39 (70%) / 17 (30%). B-ALL/LBL were diagnosed in 26 (46,4%) pts, T-ALL- in 26 (46,4%) and MPAL- in 4 (7,2%). Genomic DNA was extracted from peripheral blood samples of given pts. Genetic polymorphisms inNUDT15(*2, *3)and TPMT(*2, *3A, *3B, *3C)genes were detected using the allele-specific RT-PCR. The dose of 6-MP was calculated only for 54 pts from 56 (one of these pts stopped the therapy and another received the 1 st phase of induction by RALL-2016 without 6-MP). According to the RALL-2016 protocol 6-MP dose correction imply: if the level leukocytes<2,0*109/l, thrombocytes <100*109/l pts got 50% from the required dose. The therapy of 6-MP was stopped, if the level leukocytes <1,0*109/l, thrombocytes <50*109/l. On the 2 induction therapy by the protocol, the doses of 6-MP were calculated only for 47 pts with CR. The group of pts who didn't have remission on the 36 day by the protocol took the drug without corrections. Results:From 54 pts CR rate was 87 % (n=47) and resistance - 13% (n=7). One patient died in CR. The frequency ofTPMTandNUDT15polymorphisms in study group was 17,8 % (n=10): 6 (23%) of 26 pts with B-ALL, 3 (11,5 %) of 26 pts -T-ALL and 1 (25%) of 4 pts - MPAL. In our cohort these polymorphisms were found significantly more frequently in pts with B-ALL (p<0.001). These polymorphisms were detected in 8 (80%) men and 2 (20%) women (p=0.432). All detected polymorphisms were presented as heterozygous variants:NUDT15*3was in 2 (20%) pts,TPMT*2-1(10%),TPMT*3A-6 (60%),TPMT*3C-1 (10%). The doses of 6-MP in 5 pts withTPMTandNUDT15and 42 pts withWTwere 54% (27-89%) vs 71% (25-100%), respectively. Statistics analysis didn't show correlation between the 6-MP toxicity (difference of the fact dose of 6-MP therapy) and the polymorphisms in our cohort (fig.1). The frequency of resistance cases didn't different in cohort with/withoutTPMTandNUDT15polymorphisms in 3 (37, 5%) from 8 pts and 4 (10, 5%) from 42 pts, respectively. Only 1 patient with heterozygousTPMT*2died in CR due to toxicity and infection. Two-years overall survival (OS) in pts with the genetic polymorphisms was worse 75 % than in pts without them - 83,6% (p=0,67) (fig.2). Conclusions:In our study the frequency ofTPMTandNUDT15polymorphisms in adult pts with Ph-negative ALL was 17,8%. The statistical analysis showed that polymorphisms of these genes were detected more frequently in pts with В-ALL. Only one patient withTPMT*2had significant toxicity on the therapy of 6-MP and died in CR. However, we don't know whether this is due to deficient 6-MP metabolism. We didn't find a correlation between the 6-MP toxicity and the polymorphisms in our pts. There is a tendency that OS within 2-years in pts withoutTPMTandNUDT15polymorphisms is better than in the group of pts with them. But our cohorts are small and require further study. Keywords:acute lymphoblastic leukemia, toxicity, 6-mercaptopurine,TPMT,NUDT15 Disclosures No relevant conflicts of interest to declare.

scholarly journals Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia

Blood ◽  
2015 ◽  
Vol 125 (16) ◽  
pp. 2486-2496 ◽  
Author(s):  
Nathalie Dhédin ◽  
Anne Huynh ◽  
Sébastien Maury ◽  
Reza Tabrizi ◽  
Kheira Beldjord ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
Key Points ◽  
First Complete Remission

Key Points SCT in first complete remission is associated with 69.5% 3-year overall survival in high-risk ALL adult patients treated with intensified pediatric-like protocol. Poor early MRD response is a powerful tool to select patients who may benefit from SCT in first complete remission.

Statistically Significant Differences In Toxicities Between L- and PEG Asparaginase In Adult Patients with Acute Lymphoblastic Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2121-2121 ◽  
Author(s):  
Gustavo A. Rivero ◽  
Kayleen Bailey ◽  
Amanda Blackford ◽  
Amy Seung ◽  
Steven D. Gore ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Liver Function ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Liver Function Tests ◽  
Adult Patients ◽  
Treatment Regimens ◽  
Glucose Levels ◽  
Post Induction ◽  
And Gender

Abstract Abstract 2121 Background: The use of asparaginase (ASP) in treatment regimens for adult acute lymphoblastic leukemia (ALL) patients (pts) is a challenge due to its toxicity profile. Adverse events associated with ASP use include hypersensitivity reactions, coagulation disorders, hepatotoxicity, pancreatitis and hyperglycemia. Life-threatening complications compromise completion of treatment, and even pt suitability for bone marrow transplantation if required. We report our single institution experience with ASP acute toxicities in adult pts diagnosed with ALL. Methods: From 1993–2007, 135 pts (median age 38 years; range 18–76) were treated with ASP as part of their ALL directed regimen, of which 84 (62%) and 51 (38%) received L and Peg-ASP, respectively. Approximately 794 and 51 doses of L- and Peg-ASP were given, respectively. Acute toxicities were graded according to CTCAE version 3.0 at pre, peak (7d) and post (14d) ASP treatment. Grade 1 (G1) through grade 4 (G4) toxicities were evaluated during both induction and intensification. For each patient, the number and proportion of all toxicities (G1-G4) were calculated. Results: There was a higher frequency of toxicities with L- compared to Peg-ASP after controlling for age and gender. The average proportion of G2-G4 toxicities was 25% for L-ASP pts compared to 13% for Peg-ASP (p < 0.001). G3 toxicities were seen in 78% (65/82) of pts receiving L-ASP and 50% (26/52) with Peg-ASP (p=0.02), and G4 toxicities were seen in 23% (19/83) and 8% (4/52) of L-ASP and Peg-ASP pts, respectively (p=0.07). Additionally, a greater proportion of L-ASP vs Peg-ASP pts (42% v 3%) had elevation of liver function test (ALT) at the post-induction time point (p < 0.001). Similar results were seen for AST, Alk phos and glucose levels (all p values < 0.05). Decreased fibrinogen levels were also seen more frequently in patients receiving L-ASP (57%) vs Peg-ASP (30%) patients (NS). The proportion of laboratory measurements that were G2 toxicity or higher increased with age for L-ASP (0.2% per year, p=0.05) but not Peg-ASP pts (0.06% per year, p=0.55). However, when adjusting for dose agent, the proportion of G2-G4 toxicities was 0.14% higher with each increasing year of age (p=0.05). Furthermore, males also had a greater proportion of G2-G4 toxicities since there was a 4.4% lower rate of toxicities reported for females as compared to males (p=0.05). Notably, higher grade toxicities were seen in pts with increasing age with either L- or Peg-ASP. The median ages for L-ASP pts with a G2, G3 and G4 were 40.5, 41 and 55 years. The median age for those pts who received L-ASP and experienced a G4 toxicity vs those pts who received L and had no G4 toxicities was 55 years old vs 39 (p=0.018). The median ages for Peg-ASP pts with G2, G3, and G4 toxicities were 32, 34 and 57 years respectively. With both L- and Peg-ASP groups combined, the median age for those pts having a G3 toxicity vs those pts without any G3 toxicities was 40 vs 32 years (p=0.012) and for G4 toxicity was 55 vs 36 years (p=0.001). Conclusions: In adult ALL pts who receive ASP, therapy with L-ASP was associated with (1) increased liver function tests including ALT, AST and alk phos as well as a trend for lower fibrinogen levels post induction therapy and (2) a higher likelihood of G4 toxicities as compared to therapy with Peg-ASP. Regardless of the dosing agent, higher grade toxicities were seen in pts with increasing age, although this was most notable in patients who received L-ASP. Male pts receiving ASP were also more likely to suffer from G2 or higher toxicities as compared to female pts. The use of either L- or Peg ASP should be closely monitored in adult patients with ALL and if toxicities arise, it is likely that the older patients will suffer from higher grade toxicities. Disclosures: No relevant conflicts of interest to declare.

Outcome After First Relapse In Adult Patients with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3084-3084
Author(s):  
Shinichi Kako ◽  
Heiwa Kanamori ◽  
Naoki Kobayashi ◽  
Akio Shigematsu ◽  
Yasuhito Nannya ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Median Duration ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Salvage Chemotherapy ◽  
Adult Patients ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
First Relapse

Abstract Abstract 3084 With modern intensive chemotherapy, 78% to 93% of adult patients with acute lymphoblastic leukemia (ALL) achieve complete remission (CR). However, the disease-free survival rate is only 30% to 40% due to the high rate of relapse. A part of relapsed patients can achieve second remission (CR2) with salvage therapy, and allogeneic hematopoietic stem cell transplantation (HSCT) in CR2 will be the only curative strategy. Prognosis after relapse in adult patients with ALL is considered to be extremely poor, but reports as to the outcome after relapse have been limited. To elucidate the outcome of relapsed patients and prognostic factors after relapse, we retrospectively collected and analyzed clinical data from 69 institutions in Japan on patients with Philadelphia-chromosome (Ph) negative ALL, aged 16–65 years, who relapsed after first CR (CR1) between 1998 and 2008. A total of 332 patients were included in this study. The median age of them was 35 years, and 165 patients were male. Median duration of CR1 was 290 days (range 15–7162 days), and median follow-up time after relapse was 319 days (range 3–3689 days). Fifty-eight and 4 of them relapsed after allogeneic and autologous HSCT in CR1, respectively. The overall survival (OS) rate was not significantly different between patients who relapsed after allogeneic HSCT in CR1 and those who relapsed after chemotherapy only (50.0% vs. 43.4% at 1 year and 10.6% vs. 16.3% at 5 year, respectively). Among 270 patients who relapsed after chemotherapy only, 234 patients received salvage chemotherapy after relapse, and 123 patients achieved CR2 (52.5%). Sixty-two patients out of those 123 patients underwent allogeneic HSCT in CR2. Median duration between the achievement of CR2 with salvage chemotherapy and allogeneic HSCT in CR2 was 76 days. OS rate was significantly better in patients who underwent allogeneic HSCT in CR2 following salvage chemotherapy than those who did not (74.1% vs. 55.1% at 1 year and 44.7% vs. 11.6% at 5 year, respectively) by a landmark analysis limiting patients who were surviving without disease at 76 days after the achievement of CR2. In multivariate analysis of factors that included allogeneic HSCT in CR2 following salvage chemotherapy as a time-dependent covariate, lower white blood cell count at relapse (less than 10000/μl) and allogeneic HSCT in CR2 were associated with better OS rate among patients who achieved CR2 following salvage chemotherapy. Forty-six patients underwent allogeneic HSCT in non-CR after receiving salvage chemotherapy. A part of them survived long, and 5 year OS rate was 20.9%. In conclusion, the prognosis of adult patients with relapsed Ph-negative ALL is poor. Allogeneic HSCT after first relapse could improve the prognosis. Disclosures: No relevant conflicts of interest to declare.

Accumulation Of Gene Alterations Of TP53, Crebbp and IKZF1 Is a Prognostic Factor In Adult Acute Lymphoblastic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1386-1386
Author(s):  
Kenji Tokunaga ◽  
Shunichro Yamaguchi ◽  
Taizo Shimomura ◽  
Hitoshi Suzushima ◽  
Yutaka Okuno ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Genomic Dna ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Statistical Significance ◽  
Philadelphia Chromosome ◽  
Gene Mutations ◽  
Genetic Alterations ◽  
Adult Patients ◽  
Genomic Deletions

Abstract Aims Mutations of the genes associating with cell differentiation or proliferation are recognized as factors of tumorigenesis or prognosis in hematological malignancies. In pediatric acute lymphoblastic leukemia (ALL), alterations of IKZF1 (a factor of lymphocyte differentiation), TP53 (a cell cycle regulator) and CREBBP (a histone modifier) are found as possible prognostic markers for stratification of treatments. On the other hand, in adult ALL, clinical significance of such alterations remains to be determined. In the present work, we examined whether the mutations in those genes affected the incidence and prognosis in adult ALL patients. Methods We investigated 87 adult patients with newly diagnosed ALL treated with JALSG protocols between 1986 and 2011. Age ranged from 15 to 86 years, with a median of 51 years. We obtained cDNA and genomic DNA from the peripheral blood or bone marrow mononuclear cells at diagnosis. CREBBP mutations are dominantly identified in the histone acetyltransferase (HAT) domain. HAT domain in the CREBBP gene was amplified by PCR using cDNA and was subjected to direct sequencing. Additionally other histone modifiers, EZH2, EED, and UTX, were sequenced as the same as in CREBBP. TP53 exons 5 – 8 and 10, in which mutations were commonly reported, were sequenced using genomic DNA. We amplified IKZF1 using RT-PCR for detecting aberrant dominant negative isoforms: Ik6 and Ik10. Genomic deletions of IKZF1 were assessed with RQ-PCR or genomic DNA PCR. We compared clinical profiles between patients with and without such gene mutations. The present study was approved by the Institutional Review Boards and informed consent was obtained from each patient according to guidelines based on the revised Declaration of Helsinki. Results In 87 adult patients with ALL, alterations of CREBBP, EED, TP53 and IKZF1 were detected in 7 (9.5%), 3 (4.8%), 6 (6.9%) and 42 (50%), respectively. None of EZH2 and UTX mutation was found. The alterations of CREBBP and IKZF1 at diagnosis in adult patients were more frequent than those in pediatric patients ever reported. Some gene mutations were not found frequently. Each gene mutation per se did not significantly affect prognosis. We tried to predict the prognosis by scoring gene mutations and chromosomal abnormalities. Philadelphia chromosome (Ph) has great impact to prognosis of patients with ALL. We scored the number of mutated genes and Ph for each patient. As the score was higher, adult patients with ALL had poorer relapse-free survival (P=0.0439) and OS (P=0.4819), but statistical significance was not detected in this small cohort. Conclusions and Discussion Single gene mutations, such as IKZF1, can predict the prognosis in pediatric ALL. In adult ALL, however, only few gene mutations are reported to be promising prognostic factors which have impacts to treatment outcomes. Scoring system may be a useful method for predicting prognosis and stratifying treatment in adult ALL. Our study implies the possibility that a variety and heterogeneity of genetic alterations in adult ALL are associated with the pathogenesis for treatment resistance and prognostic marker of adult ALL. Disclosures: No relevant conflicts of interest to declare.

Second Primary Malignancies In Adult Acute Lymphoblastic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3871-3871
Author(s):  
Binay K. Shah ◽  
Krishna B Ghimire
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
General Population ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Adult Patients ◽  
P Value ◽  
Second Primary ◽  
Adult Age ◽  
Absolute Excess Risk ◽  
Second Primary Malignancies

Abstract Background Pediatric acute lymphoblastic leukemia (ALL) patients have higher rates of second primary malignancies. There is limited data on second primary malignancies (SPM) among adult patients with ALL. This study was conducted to evaluate SPM in adult ALL patients using US Surveillance, Epidemiology and End Results (SEER) cancer registry database. Methods We analyzed the SEER 13 Registries using multiple primary standardized incidence ratio (MP-SIR) session. We analyzed secondary cancer rates among adult ALL patients during the period 1992 - 2010. We used SEER*Stat software provided by national cancer institute for statistical analysis. Results There were 3,259 adult (age ≥20 years) ALL patients reported in SEER database during 1992-2010. Among them, 65 ALL patients developed 75 second primary malignancies. Fifty-nine ALL patients developed 1 SPM each, 3 ALL patients developed 2 SPM each, 2 ALL patients developed 3 SPM each and 1 ALL patient developed 4 SPM. All site cancers were significantly higher among adult ALL patients compared to general population with observed/expected ratio (O/E): 1.47, p value< 0.05, an absolute excess risk of 24.43 per 10,000 populations. Similarly, oral cavity cancer, respiratory system cancer and hematological SPM were significantly higher in ALL patients than expected in general population. (Table) Conclusions Adult patients with ALL have higher rates of second primary malignancies compared to general population. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Targeting Nucleolin for Reversal of Chemotherapy Resistance in Acute Lymphoblastic Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5058-5058
Author(s):  
Jianda Hu ◽  
Yanxin Chen ◽  
Zhengjun Wu ◽  
Lingyan Wang ◽  
Jingjing Wen ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Acute Lymphoblastic Leukemia ◽  
Drug Sensitivity ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Mrna Level ◽  
Chemotherapy Resistance

Chemotherapy resistance is considered to be the principal cause of ineffective treatment in acute lymphoblastic leukemia (ALL). Nucleolin (NCL) is high expression andplays oncogenic roles in most cancers. However, less research on the role of NCL in hematologic malignancies was noted. Our previous studies have showed that overexpression of NCL was associated with worse prognosis in the patients with acute leukemia and NCL expressionwashigher in resistant HL-60/ADR than in sensitive HL-60 cells. The potential mechanisms of NCL in chemotherapy resistance have yet to be revealed. Here we presented that expression of NCL was associated positively with chemotherapy resistance and poor prognosis in ALL. Overexpressed NCL at both mRNA and protein level was relevant to a poorer overall survival (OS) and relapse free survival (RFS), indicating NCL as an independent prognostic marker in ALL. mRNA level of NCL in de novo ALL was quantitatively higher than in complete remission(CR) status, and refractory/relapse ALL had the highest level. Upon above clinical data, we further investigated the mechanism(s) by which NCL regulated drug resistance in ALL cells. Remarkably, NCL expression was higher in resistant ALL cells relative to sensitive parental cells. When treated with ADM, NCL level was decreased in sensitive parental cells while unchanged in resistant cells. Overexpressing NCL suppressed drug sensitivity, altered drug effluxion and decreased intracellular drug accumulation, while inhibition of NCL led to a completely reversed appearance, more intracellular Adriamycin(ADM) mean fluorescence intensity (MFI) and percentage of ADM accumulated cells population. Overexpression of NCL increased significantly the IC50 of ADM. The IC50 of ADM on Jurkat-NCL-overexpression(OE), Jurkat-NCL-knockdown(KD), Molt-4-NCL-OE, Molt-4-NCL-KD, Nalm-6-NCL-OE, Nalm-6-NCL-KD were 1.362±0.271μg/ml, 0.077±0.010μg/ml, 4.863±0.733μg/ml, 0.081±0.018μg/ml, 0.237±0.042μg/ml and 0.046±0.002μg/ml, respectively (P <0.05). Involvement of ATP-binding cassette (ABC) transporters was proved in NCL mediated drug resistance. Silencing NCL resulted in a decrease of P-gp, MRP1, LRP and BCRP in ALL cells, and NCL overexpression increased the MRP1, LRP and BCRP. The Akt/mTOR and ERK signaling pathways were involved in this procedure. Notably, co-IP assays confirmed the NCL-Ras, NCL-ERK and NCL-BCRP interaction. For intervention study, aptamer AS1411, a NCL inhibitor, could reduce drug resistance in ALL cell lines and primary ALL cells.Moreover, AS1411 treatment decreased BCRP protein expression. Furthermore, the ALL leukemia models that nude mice engrafted with Nalm-6 cells and NCG mice engrafted with Luc+ Nalm-6 cells were established, then treated with ADM plus AS1411 or control CRO for comparison drug sensitivity and survival. Growth of subcutaneous xenograft tumors was inhibited in those treated with AS1411 or ADM, compared to their respective controls treated with CRO or PBS. The stronger inhibition effect was observed in those treated with AS1411 combined with ADM. For Luc+Nalm-6 derived ALL model, leukemia progression was suppressed in mice treated with AS1411 and AS1411 combined with ADM. AS1411and ADM, especially combination of AS1411 and ADM, could improve survival of the leukemic mice compared to those treated with PBS. The results showed that NCL targeted by AS1411 sensitized ADM treatment and prolonged survival in vivo. In summary, our findings revealed NCL as a survival predictor and the novel role of NCL in ALL chemo-resistance. NCL may be a potential target for improving outcome in ALL. Disclosures No relevant conflicts of interest to declare.

scholarly journals Frequency of p190 and p210 BCR-ABL Fusions Genes in Acute Lymphoblastic Leukemia in a Long Group of Adults and Childhood

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5273-5273 ◽  
Author(s):  
Rosa Maria Arana-Trejo ◽  
Gregorio Ignacio ◽  
Raquel Amador-Sánchez ◽  
Jorge Cruz-Rico ◽  
Maria-Paula Hernández ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Fusion Transcript ◽  
Age Group ◽  
Fusion Genes ◽  
Rt Pcr ◽  
Pcr Multiplex ◽  
The Impact

Abstract The Ph chromosome is a translocation (9;22)(q34;q11), that results in the constitutive activation of the BCR/ABL tyrosine kinase. The incidence of BCR/ABL in Acute Lymphoblastic Leukemia (ALL) increases with age, from less than 5% in younger children to 20-30% in older adults, with a peak incidence in patients aged 35-50 years. BCR/ABL1 has diverse breakpoints, in adult patients with Ph+ ALL the p190BCR/ABL transcript e1a2/e3a2 may be documented in 50-70%; p210BCR/ABL b2a2/b3a2 in 15-30% of patients and <1% having both breakpoint. Childhood patients with Ph+ ALL fusion genes present p190BCR/ABL transcipt e1a2/e3a2 in 90% and the remaining present other fusion transcrit or co-expression of both p190 and p210 BCR-ABL. OBJETIVE. The aim of this study was identify the occurrence of fusion genes to p190 and p210 BCR-ABL rearrangements in adult and childhood patients with ALL. METHODS. We include between 2008-2015 870 patients with ALL de novo from seven different hospitals from México, the 45% (394) were childood and the rest 55% (476) were adults. All patients were studied to RT-PCR multiplex and nested in RNA for fusion transcripts 190 and p210 BCR-ABL, at diagnosis, according to the international BIOMED-1 protocol. RESULTS. From 870 patients with ALL, the most frequent subtype FAB were L2 (87%) and second L1 (13%). The immunophenotype by B-ALL was to 80%, bilineal in 5% and the rest have not data. The overall incidence to BCR-ABL in both children and adults with ALL were to 17% [147/870]. The analysis by age group were; in 476 adults with ALL, their average age was 37 years old (range 17-84 years) and their incidence of BCR-ABL positive was 20% (95/476 cases). The distributions by type of fusion transcript were 83% p190 and 17% p210; we did not observe co-expression of transcripts to BCR-ABL. In children patients the average age was 9 years old (range 0.1-16 years), the incidence of BCR-ABL was 13.2% (52/394 cases). The distributions by type of fusion transcript to BCR-ABL were p190 78.8%; p210 13.4% and their co-expression by both isoforms 8%. CONCLUSION. The 20% frequency for BCR-ABL1 in adults with ALL is concordant with others reports published, with values from 17% to 37% with predominancy of p190 (83%). In our pediatric patients group with ALL, document a frequency of 13.2% by BCR-ABL1 positive; it is higher than other populations reporting 5-10%. The distributions of fusion transcript p190 and p210 coincides with previous prevalence estimates in other countries where p190 transcript was the most frequent. But the coexpression of both isoforms [p190/p210] were 8% it has not been reported in this age group with ALL. In conclusion, we recommend to identify the BCR-ABL transcript type in every patients with ALL at diagnosis, using a RT-PCR verified method for P190/p210 and followed the patient by mesure the impact clinical and will be adjust the treatment like o plus the cytogenetic studies. Disclosures No relevant conflicts of interest to declare.

ACUTE LYMPHOBLASTIC LEUKEMIA In Qatar: Clinico-Pathological PROFILE and OUTCOME

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4233-4233
Author(s):  
Mohamed A. Yassin ◽  
Firyal Ibrahim ◽  
Mina M. Al-Badri ◽  
Hanadi Rafii El-Ayoubi ◽  
Rami T Kamzoul
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Marrow Transplant ◽  
Adult Patients ◽  
Treatment Modalities ◽  
Final Conclusion ◽  
Allogeneic Bone ◽  
Female Ratio

Abstract Abstract 4233 Background: advances in immunophenotyping, cytogenic, and molecular genetics have not only considerably improved our knowledge of the pathophysiology of acute leukemia’s, but have also contributed to a refined classification of acute lymphoblastic leukemia(ALL)subtypes and outcome. With the different treatment modalities complete remission (CR) rates of 80–85%and leukemia –free survival (LFS) rates of 30–40%can be achieved in adult acute lymphoblastic leukemia (ALL). Aim: to study the clinico-pathological features and outcomes of adult patients patients with acute lymphoblastic leukemia in Qatar Patients & METHODS: thirty adult patients (age>14 years) diagnosed as all at AL-AMAL Hospital, the oncology hematology center in Qatar, the periode betweenJan06 and Jan 2011 were Retrospectively studied with respect to their clinical. morphological, immunopathologica features at presentation and their treatment outcomes, diagnosis was based on combined morphologic, immunophenotyping and cytogenetic studies.treatment protocols used were BFM mainly for adolescent patients,GMALL and UKALL 12 for adults. RESULTS: ALL constituting 25% of all acute leukemia cases diagnosed during the period the study. the median age was 28.5 years with a male to female ratio 21.six were Qatari and 24 non-Qatari. the most common presentation was with symptomatic anemia and fever (63.3%).laboratory features at presentation revealed.WBC.>30*109/L in13((43.3%).Immunophenotyping showed that 25(83.3%)were B-ALL, only one case9450was of the matureB-phenotype(Burkitt is),twenty two (80%) were CD10positive (common/pre Bsubtypes),two were CD10 negative PreB.non were subtype as proBALL.diagnosis of T-ALL was established in 5 (16.7%)patients.aberrantexpression was noted in14 cases (46.6%)combined expression of both CD13&CD33 being the most common seen in seven cases (50%).OUT OF THE 22 CASES 954.550.Five(22.7) had t (9.22)and one (4.5%)t (4.11).normal in 10(45.5%).thirteen patient travelled before having treatment. two pretreatment death (septic shock. two elderly patients with co morbidities were considered for palliative treatment.13patients were treated in doha, 11 out of 13 (84%)went into complete remission (CR) and two (16%) underwent successful allogeneic bone marrow transplant abroad. CONCLUSION: Although.the series is small to have a final conclusion, however, this study showed that almost all of our ALL cases are of the favorable immunological subtypes (common/ pre ALL) with high CR rate. Disclosures: No relevant conflicts of interest to declare.

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