Earlier studies reported related poor survival as a significant medical outcome and observed a short relapsed period within 1?12 months in all of the adult BCP-ALL individuals concurrent with the BCR-ABL fusion gene and CDKN2 deletion [5, 31]. to evaluate the complete remission rate of individuals following a period of treatment. Treatment protocol According to the National Comprehensive Malignancy Network (NCCN) Guideline Version 1.2014 Acute Lymphoblastic Leukemia [8], a 4-week induction therapy (vincristine, daunorubicin or idarubicin, l-asparagines, and prednisone) was given to all individuals having a supplementary dose of imatinib 400?mg qd per day or dasatinib 100? mg qd per day once a day time. All individuals were then treated with consolidation therapy including Hyper CVAD A plan (cyclophosphamide, vincristine, daunorubicin, and dexamethasone) and alternately Hyper CVAD B plan (high-dose methotrexate and cytarabine) following total remission. Our study enrolled 96 cohorts undergoing their 1st or second remission and who required allogenic hematopoietic stem cell transplantation (Allo-HSCT). The procedure required that all cohorts with diagnosed ALL should undergo central nervous system (CNS) prophylaxis. Follow-up of the ALL cohorts ran till August 1, 2015 (median follow-up: 25.6?weeks, range: 1.2C78.9?weeks). Confirmed total molecular response (CMR) was defined as lower than 0.0032?% [9]. Statistical analysis SPSS 17.0 software (SPSS Inc., Chicago, IL, USA) was used to evaluate the statistical difference of categorical variables between patient organizations with the Pearson Chi-square analysis and Rabbit Polyclonal to GPR37 Fisher precise test. Disease-free survival (DFS) was determined from your date of total remission to the 1st relapse. The KaplanCMeier method and Log Deoxycholic acid sodium salt rank checks were performed to compare overall survival (OS) between the organizations, and a value of less than 0.05 was considered statistically significant. Results Characteristics of individuals One hundred thirty-five newly diagnosed Ph-positive B-cell ALL individuals (age 18C65, median 33.4) were enrolled. The characteristics of the individuals are summarized in Table?1. Of the 135 instances analyzed, 44 (32.6?%) individuals showed that they were service providers of CDKN2 deletion. No significant variations were observed for age and gender between CDKN2 deletion service providers and non-carriers. The median white blood cell (WBC) count was 54.1??109/L (range: 0.8~353.0). However, the initial WBC counts and hepatosplenomegaly rate of CDKN2 deletion were significantly higher than those of individuals with no deletion (valuewhite blood cell aComparison between CDKN2 deletion service providers and non-carriers Immunophenotypic Deoxycholic acid sodium salt analysis Of the 135 individuals analyzed in our study, 127 received immunophenotypic analysis, and the results are summarized in Table?2. CD20 manifestation was defined as 20?% cells that are positive with CD20. Within the subgroup of CDKN2 deletion, 25 of 42 (59.5?%) individuals analyzed expressed CD20, and our results showed that there were significant differences between the individuals with and without CDKN2 deletion in terms of CD20 manifestation (valuevalueallogeneic hematopoietic stem cell transplantation aComparison between CDKN2 deletion service providers and non-carriers The influence of CDKN2 deletion on different TKI treatments Among 44 CDKN2 deletion individuals, 26 instances received imatinib treatment and 18 instances received dasatinib treatment, and our results showed no difference in CR, CMR, and relapse rates between individuals who received imatinib and those who received dasatinib treatment. Also, no variations were observed in the OS and DFS (Table?4). Table 4 Influence of CDKN2 deletion by different TKI treatments valuecomplete remission, allogeneic hematopoietic stem cell transplantation, disease-free survival, overall survival Influence of CDKN2 deletion on DFS and OS The median follow-up for 135 adults was 25.6?weeks (1.2C78.9?weeks). The relapse rate in the CDKN2 deletion subgroup was higher than in the subgroup with no CDKN2 deletion (59.1 versus 35.2?%, total remission Influence of CD20 manifestation on BCR-ABL-positive B-ALL with CDKN2 deletion Forty-two individuals out of 44 CDKN2 deletion individuals received immunophenotypic analysis. Analysis of the 42 instances showed that CDKN2 deletion individuals with CD20 expression experienced an inferior OS and DFS than the individuals without CD20 expression. OS and DFS curves are demonstrated in Figs.?4 and ?and5.5. Our study showed no significant difference in relapse between the CD20-positive and CD20-negative organizations (total remission Conversation In the pre-TKI era, the prognosis of BCR-ABL-positive B-ALL offers been shown to be extremely unfavorable with 7?years of OS 50?% [10]. Recently, loss of tyrosine kinase receptor in Ph-positive cells was found to result in the development.CD20 expression was defined as 20?% cells that are positive with CD20. shown higher white blood cell (WBC) count, enhanced rates of hepatosplenomegaly (and signals; b hemizygous cells presented with loss of one transmission; c homozygous cells presented with a loss of both signals (p16) and only retained with two signals (chromosome 9); d and transmission fusion (BCR/ABL+) Real-time quantitative polymerase chain reaction The BCR-ABL manifestation levels of BCR-ABL were recognized by real-time quantitative polymerase chain reaction (RT-PCR) (Qiagen, Hilden, Germany). ABL was chosen as an internal control. The results were presented with a percentage of BCR-ABL/ABL. It was used to evaluate the complete remission rate of patients following a period of treatment. Treatment protocol According to the National Comprehensive Cancer Network (NCCN) Guideline Version 1.2014 Acute Lymphoblastic Leukemia [8], a 4-week induction therapy (vincristine, daunorubicin or idarubicin, l-asparagines, and prednisone) was given to all patients with a supplementary dose of imatinib 400?mg qd per day or dasatinib 100?mg qd per day once a day. All patients were then treated with consolidation therapy including Hyper CVAD A scheme (cyclophosphamide, vincristine, daunorubicin, and dexamethasone) and alternately Hyper CVAD B scheme (high-dose methotrexate and cytarabine) following complete remission. Our study enrolled 96 cohorts undergoing their first or second remission and who required allogenic hematopoietic stem cell transplantation (Allo-HSCT). The procedure required that all cohorts with diagnosed ALL should undergo central nervous system (CNS) prophylaxis. Follow-up of the ALL cohorts ran till August 1, 2015 (median follow-up: 25.6?months, range: 1.2C78.9?months). Confirmed complete molecular response (CMR) was defined as lower than 0.0032?% [9]. Statistical analysis SPSS 17.0 software (SPSS Inc., Chicago, IL, USA) was used to evaluate the statistical difference of Deoxycholic acid sodium salt categorical variables between patient groups with the Pearson Chi-square analysis and Fisher exact test. Disease-free survival (DFS) was calculated from the date of complete remission to the first relapse. The KaplanCMeier method and Log rank assessments were performed to compare overall survival (OS) between the groups, and a value of less than 0.05 was considered statistically significant. Results Characteristics of patients One hundred thirty-five newly diagnosed Ph-positive B-cell ALL patients (age 18C65, median 33.4) were enrolled. The characteristics of the patients are summarized in Table?1. Of the 135 cases analyzed, 44 (32.6?%) patients showed that they were carriers of CDKN2 deletion. No significant differences were observed for age and gender between CDKN2 deletion carriers Deoxycholic acid sodium salt and non-carriers. The median white blood cell (WBC) count was 54.1??109/L (range: 0.8~353.0). However, the initial WBC counts and hepatosplenomegaly rate of CDKN2 deletion were significantly higher than those of patients with no deletion (valuewhite blood cell aComparison between CDKN2 deletion carriers and non-carriers Immunophenotypic analysis Of the 135 patients analyzed in our study, 127 received immunophenotypic analysis, and the results are summarized in Table?2. CD20 expression was defined as 20?% cells that are positive with CD20. Within the subgroup of CDKN2 deletion, 25 of 42 (59.5?%) patients analyzed expressed CD20, and our results showed that there were significant differences between the patients with and without CDKN2 deletion in terms of CD20 expression (valuevalueallogeneic hematopoietic stem cell transplantation aComparison between CDKN2 deletion carriers and non-carriers The influence of CDKN2 deletion on different TKI treatments Among 44 CDKN2 deletion patients, 26 cases received imatinib treatment and 18 cases received dasatinib treatment, and our results showed no difference in CR, CMR, and relapse rates between patients who received imatinib and Deoxycholic acid sodium salt those who received dasatinib treatment. Also, no differences were observed in the OS and DFS (Table?4). Table 4 Influence of CDKN2 deletion by different TKI treatments valuecomplete remission, allogeneic hematopoietic stem cell transplantation, disease-free survival, overall survival Influence of CDKN2 deletion on DFS and OS The median follow-up for 135 adults was 25.6?months (1.2C78.9?months). The relapse rate in the CDKN2 deletion subgroup was higher than in the subgroup with no CDKN2 deletion (59.1 versus 35.2?%, complete remission Influence of CD20 expression on BCR-ABL-positive B-ALL with CDKN2 deletion Forty-two patients out of 44 CDKN2 deletion patients received immunophenotypic analysis. Analysis of the 42 cases showed that CDKN2 deletion patients with CD20 expression had an inferior OS and DFS than the patients without CD20 expression. OS and DFS curves are shown in Figs.?4 and ?and5.5. Our study showed no significant difference in relapse between the CD20-positive and CD20-negative groups (complete remission Discussion In the pre-TKI era, the prognosis of BCR-ABL-positive B-ALL has been shown to be extremely unfavorable with 7?years of OS 50?% [10]. Recently, loss of tyrosine kinase receptor in Ph-positive cells was found to result in the development of ALL [11]. The development.
