scholarly journals A hypodiploid karyotype in childhood B-cell precursor acute lymphoblastic leukemia

2021 ◽  
Vol 20 (2) ◽  
pp. 97-110
Author(s):  
Yu. V. Olshanskaya ◽  
O. I. Soldatkina ◽  
E. N. Nikitin ◽  
N. M. Timofeyeva ◽  
A. N. A.Kazakova ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Control Group ◽  
Study Group ◽  
Event Free Survival ◽  
Cell Precursor ◽  
Free Survival ◽  
Wbc Count

The detection of genetic markers associated with poor prognosis is crucial to the selection of an appropriate treatment plan for B-cell precursor acute lymphoblastic leukemia (BCP-ALL). A hypodiploid karyotype in patients with BCP-ALL has an unfavorable impact and serves as a criterion for the stratification of patients into a high-risk group. However, the survival rates of patients with a hypodiploid karyotype remain poor. Russian treatment protocols for childhood acute lymphoblastic leukemia do not include a hypodiploid karyotype in risk stratification criteria. In order to determine the prognostic value of a hypodiploid karyotype and the clinical characteristics of BCP-ALL in patients with a hypodiploid karyotype, we analyzed the survival rates of 2,700 patients included in a multicenter study. Our study was approved by the Independent Ethics Committee and the Scientific Council of the D. Rogachev NMRCPHOI of the Ministry of Healthcare of the Russian Federation. All patients underwent karyotyping and fluorescence in situhybridization (FISH) testing. A hypodiploid karyotype was detected in 27 patients. Eighteen out of 27 patients had a hypoploid clone (according to karyotyping results), 2 patients had a doubled near-haploid clone (according to karyotyping and FISH results); in 7 patients with a normal karyotype or in the absence of mitosis, hypodiploidy was determined only by FISH test. BCP-ALL with hypodiploidy is usually associated with increased WBC count at disease onset. The median WBC count in the study group was 24.2 (3.4–206.0) × 109/l vs 10.3 (0.2–1290.0) × 109/l in the control group. The number of patients with initial leukocytosis < 30 × 109/l in the study group was significantly lower than in the control group (p< 0.062). Remission was achieved in 26/27 patients. The event-free survival rates in patients with hypodiploidy were significantly lower than in those without hypodiploidy: 50 ± 11% vs 72 ± 8% (p< 0.0001). The overall survival was 64 ± 10% and 90 ± 1%, respectively (p< 0.0001). The cumulative incidence of relapse in patients with a hypodiploid karyotype was higher (42.6 ± 10.9%) than in the controls (22.3 ± 8.1%) (p< 0.0001). The patients who received more intense treatment for intermediate- and high-risk groups showed better survival rates than those in the standard-risk group: 62 ± 13% vs 40 ± 15% (р= 0.59); the cumulative incidence of relapse according to the risk group was 26.4 ± 12.1% and 60 ± 16.9%, respectively (р= 0.19).The highest risk of relapse was observed in a group that included patients with near-haploidy and low hypodiploidy (26–39 chromosomes; 52.9 ± 14.4%). The event-free survival in this group was 36 ± 13%. The results of treatment of patients with BCP-ALL and hypodiploidy according to the national guidelines turned out to be comparable to the international ones. Patients with BCP-ALL and hypodiploidy should be initially stratified to the most intense treatment arm. In order to identify patients with hypoploidy, standard karyotyping is required; where needed, it can be supplemented by FISH analysis

scholarly journals Impact of Blinatumomab Treatment on Bone Marrow Function in Patients with Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5607
Author(s):  
Hagop M. Kantarjian ◽  
Gerhard Zugmaier ◽  
Monika Brüggemann ◽  
Brent L. Wood ◽  
Heinz A. Horst ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Survival Benefit ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Event Free Survival ◽  
Cell Precursor ◽  
Survival Prognosis ◽  
Free Survival ◽  
Bone Marrow Function

Association of blinatumomab treatment with myelosuppression was examined in this study. Peripheral blood counts were assessed prior to, during, and after blinatumomab treatment in patients with relapsed/refractory Philadelphia chromosome-negative (Ph−) B-cell precursor (BCP) acute lymphoblastic leukemia (ALL; n = 267) and Ph+ BCP-ALL (n = 45) from the TOWER and ALCANTARA studies, respectively, or chemotherapy in patients with Ph− BCP-ALL (n = 109) from the TOWER study; all the patients with relapsed/refractory BCP-ALL and responders achieving complete remission (CR) or CR with partial/incomplete hematological recovery (CRh/CRi) were evaluated. Event-free survival (EFS) and overall survival (OS) were assessed in patients achieving CR and CRh/CRi. Median leukocyte, neutrophil, and platelet counts increased during two blinatumomab cycles but remained low longer after chemotherapy. Among the responders, there was a trend that a greater proportion of patients achieved CR with blinatumomab (Ph−, 76.5%; Ph+, 77.8%) versus with chemotherapy (Ph−, 63.6%). In the TOWER study, the survival prognosis for patients achieving CRh/CRi versus CR with blinatumomab was more similar (median OS, 11.9 (95% CI, 3.9–not estimable (NE)) vs. 15.0 (95% CI, 10.4–NE) months, p = 0.062) than with chemotherapy (5.2 (95% CI, 1.6–NE) vs. 18.9 (95% CI, 9.3–NE) months, p = 0.013). Blinatumomab treatment, with only temporary and transient myelosuppression, resulted in a greater survival benefit than chemotherapy.

scholarly journals Prognostic significance of CD20 expression in childhood B-cell precursor acute lymphoblastic leukemia

Blood ◽  
2006 ◽  
Vol 108 (10) ◽  
pp. 3302-3304 ◽  
Author(s):  
Sima Jeha ◽  
Frederick Behm ◽  
Deqing Pei ◽  
John T. Sandlund ◽  
Raul C. Ribeiro ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Prognostic Impact ◽  
Event Free Survival ◽  
Cell Precursor ◽  
Free Survival ◽  
Cd20 Expression ◽  
Therapy Studies

Abstract CD20 expression is associated with inferior survival in adults with acute lymphoblastic leukemia (ALL). We analyzed the prognostic impact of CD20 expression in 353 children with B-cell precursor ALL treated in 3 consecutive St Jude Total Therapy studies. CD20 expression (> 20%) was found in 169 patients (48%) and was more frequent in patients between 1 and 10 years of age than in those younger than 1 or older than 10 years (P = .001). None of 14 patients with MLL-AF4 expressed CD20. There was no association between CD20 expression and E2A-PBX, TEL-AML1, ploidy, white blood cell count at diagnosis, or sex. In contrast to the experience in adult ALL, our patients with CD20 expression tended to have a better treatment outcome than those without the expression: 5-year event-free survival 84% ± 2.9% versus 78% ± 3.1% (P = .08). These data suggest that CD20 expression is not associated with inferior outcome in pediatric patients treated with contemporary regimens.

scholarly journals Chemotherapy in 998 unselected childhood acute lymphoblastic leukemia patients. Results and conclusions of the multicenter trial ALL-BFM 86

Blood ◽  
1994 ◽  
Vol 84 (9) ◽  
pp. 3122-3133 ◽  
Author(s):  
A Reiter ◽  
M Schrappe ◽  
WD Ludwig ◽  
W Hiddemann ◽  
S Sauter ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Multicenter Trial ◽  
Low Risk ◽  
Event Free Survival ◽  
Free Survival ◽  
Risk Patients ◽  
To Receive

Abstract In trial ALL-BFM 86, the largest multicenter trial of the Berlin- Frankfurt-Munster (BFM) study group for childhood acute lymphoblastic leukemia (ALL), treatment response was used as an overriding stratification factor for the first time. In the previous trial ALL-BFM 83, the in vivo response to initial prednisone treatment was evaluated prospectively. A blast cell count of > or = 1,000/microL peripheral blood after a 7-day exposure to prednisone and one intrathecal dose of methotrexate (MTX) identified 10% of the patients as having a significantly worse prognosis. In trial ALL-BFM 86 patients with > or = 1,000/microL blood blasts on day 8 were included in an experimental branch EG. Patients with < 1,000/microL blood blasts on day 8 were stratified by their leukemic cell burden into two branches, Standard Risk Group (SRG) and Risk Group (RG). SRG patients received an eight- drug induction followed by consolidation protocol M (6-mercaptopurine, high-dose [HD] MTX 4 x 5 g/m2) and maintenance. RG patients were treated with an additional eight-drug reinduction element. For EG patients protocol M was replaced by protocol E (prednisone, HD-MTX, HD- cytarabine, ifosfamide, mitoxantrone). All patients received intrathecal MTX therapy; only those of branches RG and EG received cranial irradiation. In branch RG, patients were randomized to receive or not to receive late intensification (prednisone, vindesine, teniposide, ifosfamide, HD-cytarabine) in the 13th month. During the trial reinduction therapy was introduced in branch SRG, because in the follow-up of trial ALL-BFM 83 the randomized low-risk patients receiving reinduction did significantly better. Nine hundred ninety- eight evaluable patients were enrolled, 28.6% in SRG, 61.1% in RG, 10.3% in EG. At a median follow-up of 5.0 (range 3.4 to 6.9) years, the estimated 6-year event-free survival was 72% +/- 2% for the study population, 58% +/- 5% in branch SRG for the first 110 patients without reinduction therapy, 87% +/- 3% for the next 175 patients with reinduction therapy, 75% +/- 2% in branch RG, and 48% +/- 5% in branch EG. Late intensification did not significantly affect treatment outcome of RG patients; however, only 23% of the eligible patients were randomized. Prednisone poor response remained a negative prognostic parameter despite intensified therapy. The results confirmed the benefit of intensive reinduction therapy even for low-risk patients. The strategy of induction, consolidation, and intensive reinduction may offer roughly 75% of unselected childhood ALL patients the chance for an event-free survival.

Is It Better to Treat Adolescents with Acute Lymphoblastic Leukemia as Old Children or as Young Adults?

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3968-3968 ◽  
Author(s):  
Marta Alves ◽  
Liane Daudt ◽  
Karina L. M. Mazzucco ◽  
Adriano Taniguchi ◽  
Tiago Nava ◽  
...  
Keyword(s):  
Overall Survival ◽  
Young Adults ◽  
Prognostic Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Lymphoblastic Leukemia ◽  
Event Free Survival ◽  
Free Survival ◽  
Poor Risk ◽  
Wbc Count

Abstract PURPOSE: To compare pediatric and adult therapeutic practices in the treatment of acute lymphoblastic leukemia (ALL) in adolescents. PATIENTS AND METHODS: From January 1997 to December 2007, 34 and 11 adolescents (10 to 20 years of age) were treated according to German pediatric BFM 90 and 95 and adult BFM 84 protocols, respectively. Age, B/T lineage, WBC count, complete remission, cytogenetics, and response to steroids were analyzed. Age, B/T lineage and WBC count were similar. Poor risk-cytogenetics (t (9;22),t(4;11) and hypodiploidy less than 45 chromosomes were present only in BFM 90 and 95 group. Among the different prognostic factors, we retrospectively analyzed the effect of the trial on achieving overall survival (OS) and event-free survival (EFS). RESULTS: OS in 10 years and EFS was, respectively, 68.6% and 68.7% for the pediatric protocol and 31.4% and 21.6% for the adult protocol. CONCLUSION: This study’s findings were similar to others in USA, UK, France, Italy and Holland that clearly demonstrate that current pediatric regimens are more effective for adolescents and may contribute to indicate that adolescents should be included in intensive pediatric protocols. Keywords: leukemia, survival, adolescent.

scholarly journals Intensive chemotherapy in children with acute lymphoblastic leukemia. Interim analysis in a referral center in Colombia.

2016 ◽  
Vol 64 (3) ◽  
pp. 417 ◽  
Author(s):  
Angela Maria Trujillo ◽  
Adriana Linares Ballesteros ◽  
Isabel Cristina Sarmiento
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Developed Countries ◽  
Event Free Survival ◽  
Free Survival ◽  
Grade 3 ◽  
Treatment Abandonment ◽  
Cancer In Children

Background: Acute lymphoblastic leukemia is the most common cancer in children. In developed countries, overall survival rates are around 80%, while in developing countries, survival rate is much lower due to high rates of relapse, and abandonment and complications arising from the disease treatment.Objectives: To assess induction mortality, relapse and treatment abandonment. To describe the most frequent side effects of chemotherapy. To evaluate survival rates of patients and compare the findings found in this study with the existing literature.Material and methods: A retrospective cohort study was conducted on patients aged 1 to 18 with acute lymphoblastic leukemia, who received treatment under the BFM ALL IC 2009 protocol at Fundación Hospital La Misericordia (HOMI), from November 2012 to December 2014.Results: 119 patients were included. Death occurred in two cases during induction (1.67%) and in nine (7.7%) due to treatment, all of them caused by infection/sepsis and in complete remission. Six patients abandoned treatment (5%), while seven relapses occurred (5.9%). All patients experienced some type of side effect related to chemotherapy, the most frequent being febrile neutropenia (41.2%) and grade 3-4 infections (15.8%). Overall survival and event-free survival rates were 79.9% and 73.3%, respectively.Conclusions: Evaluating complications of treatment and death allows adopting measures and strategies to reduce such complications.

scholarly journals Pediatric-Based Versus Adult Treatment Protocols in Young Adults (18-40 years) with Standard Risk Acute Lymphoblastic Leukemia: The BC Cancer Agency Experience

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3770-3770 ◽  
Author(s):  
David Simon Kliman ◽  
Michael J Barnett ◽  
Raewyn Broady ◽  
Donna L. Forrest ◽  
Alina S. Gerrie ◽  
...  
Keyword(s):  
British Columbia ◽  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Small Cohort ◽  
Standard Risk

Abstract Introduction In recent decades, overall survival rates for children with acute lymphoblastic leukemia (ALL) have improved dramatically. Unfortunately, older patients have not experienced the same benefit. Recent years have seen investigation into the use of pediatric protocols for younger adults with ALL. Increased toxicity has often limited use to patients 40 years or younger. The Leukemia/Bone Marrow Transplant Program of BC is the referral center for adults with ALL in British Columbia. Approximately 20 patients are newly diagnosed with ALL each year. Until 2008, an adult protocol (known as ALL 89-1) was used in patients over 18 years. Since 2008, pediatric-based chemotherapy has been offered to patients 40 years or younger. We analyzed whether this change altered complete remission (CR), relapse and survival rates. We assessed whether the more intense protocol increased toxicity. Methods A retrospective analysis was performed on patients treated for ALL on a pediatric-based protocol. These protocols (ALL 08-01 and ALL 13-01) were modifications of the Donna Farber Cancer Institute 01-175 protocol. The format included induction with high dose methotrexate, followed by central nervous system (CNS) therapy including cranial irradiation. A single cycle of etoposide and high-dose cytarabine was given. Consolidation and continuation cycles included doxorubicin, asparaginase, vincristine and dexamethasone. Patients were included if they were aged 18-40 years and had standard risk, Philadelphia chromosome negative ALL. Between February 2008 and November 2014, 25 eligible patients were identified. These were compared with the 23 consecutive standard risk patients most recently treated with ALL 89-1. They had been diagnosed between February 2003 and July 2008. Exclusion criteria were age greater than 40 and non-standard risk ALL. Demographic and clinical data were collected on all patients from the Leukemia Program databases. Overall survival (OS) was calculated from time of diagnosis until death. Event free survival (EFS) was calculated from diagnosis until death, induction failure or relapse. Estimation of OS and EFS was performed using the Kaplan-Meier method. Patient characteristics were compared using Chi-squared test or Fisher's exact test. Ethics approval was obtained from the University of British Columbia ethics board. Results The median age of the combined patient group was 24.5 years. There were no statistically significant differences pre-treatment between groups. Combined median follow up was 28.7 months All 25 patients receiving a pediatric protocol achieved a CR, compared to 19 of 22 with the adult protocol. Despite the more intense chemotherapy dosing regimen in the pediatric protocol, there was no increase in hospitalizations, invasive fungal infections or deaths from treatment toxicity (Table 1). There was a trend towards increased thrombotic events in the pediatric-treated group, at 32% versus 9%. These included deep vein thrombosis in 4 patients, pulmonary emboli in 2, and cerebral sinus thrombosis in 2. Relapse occurred in 24% of the pediatric-treated patients and 45% of the adult-treated ones (p=0.215). Allogeneic stem cell transplantation was performed in 4 patients in the former group and 7 in the latter. Nine of these were carried out in CR2 or later, with two patients going into transplant with active disease. Overall survival following transplant was 44%. Two year event free survival was significantly improved in the group treated on the pediatric protocol (Figure 1), at 79% versus 36% (p=0.011). There was a trend towards improved overall survival in this small cohort, at 83% versus 49% (Figure 2). Conclusions A pediatric-based ALL treatment protocol was tolerated in patients up to the age of 40 years. In our centre, this is associated with an increase in EFS, and a trend towards increased OS, even considering the small cohort. We await with interest the results of larger studies investigating the ideal upfront therapy for young patients with ALL. Table 1. Results All Patients N=47 Adult N=22 Pediatric N=25 P Number % Number % Number % CR after induction 44 of 47 94 19 of 22 86 25 of 25 100 .095 Severe infection 20 of 47 43 9 of 22 41 11 of 25 44 .831 Thrombosis 10 of 47 21 2 of 22 9 8 of 25 32 .079 Pancreatitis 2 of 47 4 0 of 22 0 2 of 25 8 .491 Toxicity deaths 3 of 47 6 2 of 22 9 1 of 25 4 .593 Relapse 16 of 47 34 10 of 22 45 6 of 25 24 .215 AlloHSCT 11 of 47 23 7 of 22 32 4 of 25 16 .303 Disclosures No relevant conflicts of interest to declare.

scholarly journals IKZF1plus Defines a New Minimal Residual Disease–Dependent Very-Poor Prognostic Profile in Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia

2018 ◽  
Vol 36 (12) ◽  
pp. 1240-1249 ◽  
Author(s):  
Martin Stanulla ◽  
Elif Dagdan ◽  
Marketa Zaliova ◽  
Anja Möricke ◽  
Chiara Palmi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Event Free Survival ◽  
Cell Precursor ◽  
Free Survival ◽  
Prognostic Profile ◽  
Minimal Residual

Purpose Somatic deletions that affect the lymphoid transcription factor–coding gene IKZF1 have previously been reported as independently associated with a poor prognosis in pediatric B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). We have now refined the prognostic strength of IKZF1 deletions by analyzing the effect of co-occurring deletions. Patients and Methods The analysis involved 991 patients with BCP ALL treated in the Associazione Italiana Ematologia ed Oncologia Pediatrica–Berlin-Frankfurt-Muenster (AIEOP-BFM) ALL 2000 trial with complete information for copy number alterations of IKZF1, PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A, CDKN2B, Xp22.33/Yp11.31 (PAR1 region; CRLF2, CSF2RA, and IL3RA), and ERG; replication of findings involved 417 patients from the same trial. Results IKZF1 deletions that co-occurred with deletions in CDKN2A, CDKN2B, PAX5, or PAR1 in the absence of ERG deletion conferred the worst outcome and, consequently, were grouped as IKZF1plus. The IKZF1plus group comprised 6% of patients with BCP ALL, with a 5-year event-free survival of 53 ± 6% compared with 79 ± 5% in patients with IKZF1 deletion who did not fulfill the IKZF1plus definition and 87 ± 1% in patients who lacked an IKZF1 deletion ( P ≤ .001). Respective 5-year cumulative relapse incidence rates were 44 ± 6%, 11 ± 4%, and 10 ± 1% ( P ≤ .001). Results were confirmed in the replication cohort, and multivariable analyses demonstrated independence of IKZF1plus. The IKZF1plus prognostic effect differed dramatically in analyses stratified by minimal residual disease (MRD) levels after induction treatment: 5-year event-free survival for MRD standard-risk IKZF1plus patients was 94 ± 5% versus 40 ± 10% in MRD intermediate- and 30 ± 14% in high-risk IKZF1plus patients ( P ≤ .001). Corresponding 5-year cumulative incidence of relapse rates were 6 ± 6%, 60 ± 10%, and 60 ± 17% ( P ≤ .001). Conclusion IKZF1plus describes a new MRD-dependent very-poor prognostic profile in BCP ALL. Because current AIEOP-BFM treatment is largely ineffective for MRD-positive IKZF1plus patients, new experimental treatment approaches will be evaluated in our upcoming trial AIEOP-BFM ALL 2017.

Difference in outcome of adolescents (14–17 years) with acute lymphoblastic leukemia (ALL) enrolled in the Italian pediatric (AIEOP) and adult (GIMEMA) multicenter protocols

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9024-9024 ◽  
Author(s):  
A. Testi
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Cure Rate ◽  
Event Free Survival ◽  
Treatment Results ◽  
Free Survival ◽  
Pediatric All ◽  
National Cooperative ◽  
Lower Cure Rate

9024 Background: Progress in the treatment of acute lymphoblastic leukemia (ALL) has led to better survival rates; however, this benefit has not extended in the same proportion to adolescents who retain a lower cure rate, compared to younger patients. Based on some recent reports, adolescents treated on pediatric ALL trials seem to have a significantly better event free-survival (EFS) than those treated on adult trials. Methods: We retrospectively compared the results obtained in 242 adolescents enrolled either in the national cooperative pediatric (AIEOP; n=150) or adult (GIMEMA; n=92) ALL trials, between 4/1996 and 10/2003. Results: The characteristics of the patients at diagnosis in the two groups under examination were comparable except for age (median age: 15 in the AIEOP vs 16 in the GIMEMA trials). Adolescents in the AIEOP protocols had a better complete remission (CR) rate (97%) compared to those treated with the GIMEMA protocols (89%). Overall treatment results estimated at 2 years were significantly superior for patients treated in the pediatric trials: survival 81% vs 71% and EFS 78% vs 47%. This difference was significant also at the multivariate analysis. Conclusions: Our results support, in keeping with other studies, the concept that adolescents with ALL have a better outcome if treated in pediatric trials. No significant financial relationships to disclose.

Heterogeneity Of CXCR4 Expression In Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4952-4952
Author(s):  
Tomasz Szczepanski ◽  
Urszula Malek ◽  
Lukasz Sedek ◽  
Alicja Sonsala ◽  
Joanna Zawitkowska ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Acute Lymphoblastic Leukemia ◽  
Residual Disease ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
Cxcr4 Expression ◽  
Study Group ◽  
Cell Precursor ◽  
Minimal Residual

Abstract Background CXCR4 (CD184) is a receptor specific to the Stromal Derived Factor 1 (SDF-1), a ligand also known as CXCL12. The ligand-receptor interaction has a pleiotropic effect on hematopoietic cell proliferation, migration and activation through several signaling pathways. CXCR4 expression on neoplastic cells might be responsible for their dissemination to particular organs with cells expressing CXCL12 (e.g. lymph nodes, bones, and within bone marrow). In B-cell precursor acute lymphoblastic leukemia (BCP-ALL), expression of CXCR4 was associated with higher capacity of leukemic blasts to seed into bone marrow niches. Aim of the study The study aimed at thorough analysis of CXCR4 expression on BCP-ALL blasts and correlation of CXCR4 expression with the expression of other antigens such as CD66c, CD34, CD10, CD38, CD20 and CD45 as well as with the levels of minimal residual disease on day 15. Patients and Methods The study group consisted of 198 consecutive children aged 0-18 years (median 4.4 years) treated for BCP-ALL in the centers of the Polish Pediatric Leukemia/Lymphoma Study Group. Bone marrow samples obtained at initial diagnosis were stained with monoclonal antibodies (CD58, CD66c, CD34, CD19, CD10, CD38, CD20, CD45, CXCR4) in two 8-color tubes and analyzed with multiparameter flow cytometry (BD FACSCanto II, Becton Dickinson, San Jose, CA, USA) according to the EuroFlow standard protocols. The expression of particular antigens on BCP-ALL blasts was defined by median fluorescence. In 177 patients the samples from day 15 were available and analyzed for the presence of minimal residual disease (MRD) with multicolor flow cytometry. Infinicyt software (Cytognos, Salamanca, Spain) was used for more detailed analyses of the flow cytometric data. Results The expression of CXCR4 in BCP-ALL was highly variable with median fluorescence ranging from 252 to 24 388 (median 4011). There was no obvious correlation of CXCR4 expression with immunophenotype and with  the expression of other analyzed markers (CD66, CD34, CD10, CD38 i CD45). The only borderline significant correlation found was between CXCR4 and CD20 expression. On day 15, 70 children (39%) demonstrated MRD levels below 0.1%, which is consistent with MRD-based low-risk group. Among these patients, 41 children had undetectable MRD already at this time point. In contrary, MRD levels > 10% were recorded in 21 patients (12%), who were stratified to high-risk group, accordingly. Maximal MRD levels recorded at day 15 were 85.6%. In remaining 86 children (49%), MRD levels at day 15 were in-between 0.1% and 10%, which reflects intermediate response to the treatment. There was no correlation between CXCR4 expression and MRD levels at day 15. Conclusion CXCR4 expression on BCP-ALL blasts is highly heterogeneous and is not associated with particular leukemia immunophenotype. Further analyses should characterize clinical features of leukemia and treatment response with regard to CXCR4 expression. The study was supported by Polish National Center of Science grant N N407 687040. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Young Adults With Acute Lymphoblastic Leukemia Have an Excellent Outcome With Chemotherapy Alone and Benefit From Intensive Postinduction Treatment: A Report From the Children's Oncology Group

2009 ◽  
Vol 27 (31) ◽  
pp. 5189-5194 ◽  
Author(s):  
James B. Nachman ◽  
Mei K. La ◽  
Stephen P. Hunger ◽  
Nyla A. Heerema ◽  
Paul S. Gaynon ◽  
...  
Keyword(s):  
Young Adults ◽  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Young Adult ◽  
Lymphoblastic Leukemia ◽  
Event Free Survival ◽  
Free Survival ◽  
Excellent Outcome ◽  
First Remission ◽  
Wbc Count

Purpose Patients 16 to 21 years of age with acute lymphoblastic leukemia (ALL) have an inferior outcome compared with younger children, leading some medical oncologists to advocate allogeneic stem-cell transplantation in first remission for these patients. We examined outcome for young adults with ALL enrolled onto the Children's Cancer Group (CCG) 1961 study between 1996 and 2002. Patients and Methods CCG 1961 entered patients with ALL 1 to 21 years of age with initial WBC count ≥ 50,000/μL and/or age ≥ 10 years. Randomly assigned therapies evaluated the impact of postinduction treatment intensification on outcome. We examined outcome and prognostic factors for 262 young adults with ALL. Results Five-year event-free and overall survival rates for young adult patients are 71.5% (SE, 3.6%) and 77.5% (SE, 3.3%), respectively. Rapid responder patients (< 25% bone marrow blasts on day 7) randomly assigned to augmented therapy had 5-year event-free survival of 81.8% (SE, 7%), as compared with 66.8% (SE, 6.7%) for patients receiving standard therapy (P = .07). One versus two interim maintenance and delayed intensification courses had no significant impact on event-free survival. WBC count more than 50,000/μL was an adverse prognostic factor. Conclusion Young adult patients with ALL showing a rapid response to induction chemotherapy benefit from early intensive postinduction therapy but do not benefit from a second interim maintenance and delayed intensification phase. Given the excellent outcome with this chemotherapy, there seems to be no role for the routine use of allogeneic stem-cell transplantation in first remission for young adults with ALL.

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