scholarly journals Prognostic Value and Outcome for ETV6/RUNX1-Positive Pediatric Acute Lymphoblastic Leukemia: A Report From the South China Children’s Leukemia Group

2021 ◽  
Vol 11 ◽  
Author(s):  
Kun-yin Qiu ◽  
Hong-gui Xu ◽  
Xue-qun Luo ◽  
Hui-rong Mai ◽  
Ning Liao ◽  
...  
Keyword(s):  
South China ◽  
Prognostic Value ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Early Response ◽  
Response To Therapy ◽  
Negative Group ◽  
Factors Affecting ◽  
Positive Group ◽  
Excellent Outcome

PurposeTo analyzed the outcome of ETV6/RUNX1-positive pediatric acute B lymphoblastic leukemia (B-ALL) with the aim of identifying prognostic value.MethodA total of 2,530 pediatric patients who were diagnosed with B-ALL were classified into two groups based on the ETV6/RUNX1 status by using a retrospective cohort study method from February 28, 2008, to June 30, 2020, at 22 participating ALL centers.ResultsIn total, 461 (18.2%) cases were ETV6/RUNX1-positive. The proportion of patients with risk factors (age <1 year or ≥10 years, WB≥50×109/L) in ETV6/RUNX1-positive group was significantly lower than that in negative group (P<0.001), while the proportion of patients with good early response (good response to prednisone, D15 MRD < 0.1%, and D33 MRD < 0.01%) in ETV6/RUNX1-positive group was higher than that in the negative group (P<0.001, 0.788 and 0.004, respectively). Multivariate analysis of 2,530 patients found that age <1 or ≥10 years, SCCLG-ALL-2016 protocol, and MLL were independent predictor of outcome but not ETV6/RUNX1. The EFS and OS of the ETV6/RUNX1-positive group were significantly higher than those of the negative group (3-year EFS: 90.11 ± 4.21% vs 82 ± 2.36%, P<0.0001, 3-year OS: 91.99 ± 3.92% vs 88.79 ± 1.87%, P=0.017). Subgroup analysis showed that chemotherapy protocol, age, prednisone response, and D15 MRD were important factors affecting the prognosis of ETV6/RUNX1-positive children.ConclusionsETV6/RUNX1-positive pediatric ALL showed an excellent outcome but lack of independent prognostic significance in South China. However, for older patients who have the ETV6/RUNX1 fusion and slow response to therapy, to opt for more intensive treatment.

Augmented Berlin-Frankfurt-Munster therapy abrogates the adverse prognostic significance of slow early response to induction chemotherapy for children and adolescents with acute lymphoblastic leukemia and unfavorable presenting features: a report from the Children's Cancer Group.

1997 ◽  
Vol 15 (6) ◽  
pp. 2222-2230 ◽  
Author(s):  
J Nachman ◽  
H N Sather ◽  
P S Gaynon ◽  
J N Lukens ◽  
L Wolff ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Early Response ◽  
Response To Therapy ◽  
Intensive Chemotherapy ◽  
Event Free Survival ◽  
Free Survival ◽  
Cancer Group ◽  
Avascular Necrosis Of Bone

PURPOSE Compared with previous Children's Cancer Group (CCG) acute lymphoblastic leukemia (ALL) trials, therapy based on the Berlin-Frankfurt-Munster (BFM) 76 trial has effected an improvement in event-free survival (EFS). In an attempt to improve EFS further, CCG investigators formulated an augmented BFM (A-BFM) regimen that provides prolonged, intensified postinduction chemotherapy relative to the CCG-modified BFM regimen. PATIENTS AND METHODS We tested A-BFM in 101 patients with ALL and unfavorable presenting features that showed slow early response (SER) to induction therapy who attained remission on day 28. Their outcome was compared with that of 251 concurrent patients with unfavorable presenting features, a rapid early response to therapy (RER), and remission by day 28, treated with CCG-BFM with or without cranial radiation (CRT). RESULTS The 4-year EFS rate from the end of induction for SER patients treated with A-BFM was 70.8% +/- 4.6%. Seventeen patients remain in continuous remission beyond 5 years. Vincristine (VCR) neurotoxicity developed in 50% of patients, but was rarely debilitating. Allergies to Escherichia coli L-asparaginase (L-ASP) occurred in 35% of patients. Avascular necrosis of bone (AVN) developed in 9% of patients. In comparison, a concurrent RER group treated with standard BFM +/- CRT had a 4-year EFS rate of 73.1% +/- 4.6%. CONCLUSION The toxicity of A-BFM is significant, but acceptable. Compared with historical control SER patients treated with CCG-modified BFM, A-BFM therapy appears to produce a significant improvement in EFS. This is the first study to show that intensive chemotherapy, as given in the A-BFM regimen, can abrogate the adverse prognostic significance of SER.

Early Response Characteristics and Blast Cytogenetic FEatures In 5,377 Children with Standard Risk Acute Lymphoblastic Leukemia (SR-ALL): A Children's Oncology Group (COG) Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 414-414
Author(s):  
Kelly W. Maloney ◽  
Mignon L. Loh ◽  
Elizabeth Raetz ◽  
Michael J. Borowitz ◽  
Meenakshi Devidas ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Induction Therapy ◽  
Research Funding ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Philadelphia Chromosome ◽  
Early Response ◽  
Response To Therapy ◽  
Intrathecal Therapy ◽  
Post Induction

Abstract Abstract 414 The COG uses clinical characteristics, blast cytogenetic features and early response to therapy, as measured by bone marrow (BM) morphology on days 8, 15 and 29 and BM minimal residual disease (MRD) measured by flow cytometry in one of two central COG reference laboratories on day 29 of induction in order to modulate the intensity of post-induction therapy for children with ALL. A slow early response (SER) to therapy was defined by M2/M3 BM on day 15 or MRD ≥ 0.1% on day 29. The COG AALL0331 trial accrued 5377 children with NCI SR- ALL (age 1–10 years with an initial white blood cell count of <50,000/microliter) between 4/11/2005 and 5/28/2010. Induction therapy consisted of dexamethasone (6mg/m2/day × 28 days), PEG asparaginase (2500 units/m2 × 1), vincristine (1.5 mg/m2 weekly × 4) and intrathecal therapy (cytarabine on day 0 and methotrexate on days 8 and 29) according to age based dosing. Those patients with a day 29 M2 BM (5–25% blasts) or MRD ≥1% received two additional weeks of induction therapy using the same agents with one added dose of daunorubicin (25 mg/m2). Children with an M3 marrow (>25% blasts) on day 29, or an M2 marrow or MRD ≥1% on day 43 after 2 weeks of extended induction therapy were classified as induction failures. Following the first month of therapy, patients were assigned to different risk groups for post-induction therapy. We examined the correlations between clinical features, leukemic blast cytogenetic features (favorable: ETV6-RUNX1 and trisomies 4, 10, and 17 or unfavorable: MLL rearrangements, BCR-ABL1 and hypodiploidy), and response to induction therapy. MRD at end induction was ≥ 0.1% more frequently in patients with the absence of either ETV6-RUNX1 (10.4% vs. 3.5%, P<0.0001) or trisomies 4, 10, and 17 (TT) (9.5% vs 5.9%, p=0.0001) or among those who harbored MLL rearrangements (26.1% vs. 8.5%, p=0.0004). MRD > 0.1% at end induction was seen in 23.3% of hypodiploid patients and 32.4% of Philadelphia chromosome + or BCR-ABL1 + patients. In addition, those who had an M2/M3 marrow at day 15 (36.7% vs. 5.9%, p <0.0001) were more likely to have MRD ≥ 0.1% at end induction. There was no difference in the proportion of boys and girls with MRD ≥0.1% (8.5% vs. 8.1%). Only 114/5082 (2.2%) children received extended induction. Induction failures were rare, occurring in only 37/5075 (0.7%) of patients. Induction failures defined by an M3 marrow on day 29 occurred in 6/5123 patients, while induction failures at day 43 after extended induction, occurred in 31/5067 (0.61%) patients (day 43 M2 marrow: 2, day 43 MRD ≥1%: 29). (see Table 1). Conclusions: Inferior MRD responses were associated with the absence of favorable blast cytogenetics and slow initial responses (M2/3 marrow) on day 15 of induction consistent with the known prognostic significance of these variables. Overall, NCI SR patients on AALL0331 had a very low incidence of induction failures, as measured either by bone marrow morphology or by MRD≥1% at day 43. However, the use of MRD identified additional patients who had a suboptimal response to induction, allowing for early augmentation of therapy. Disclosures: Borowitz: genzyme: Research Funding; becton-dickinson: Research Funding; Alexion: Consultancy; beckman-coulter: Research Funding. Mattano:pfizer: Employment.

scholarly journals PROGNOSTIC VALUE OF PROTEASE ACTIVATED RECEPTOR-1 IN EGYPTIAN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA

2014 ◽  
Vol 6 (1) ◽  
pp. e2014029 ◽  
Author(s):  
Adel Abd Elhaleim Hagag
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Flow Cytometric Analysis ◽  
Newly Diagnosed ◽  
Negative Group ◽  
Positive Group ◽  
Egyptian Children ◽  
Wide Range ◽  
Protease Activated Receptor 1

Background: Acute Lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid progenitor cells that proliferate and replace the normal hematopoietic cells of the bone marrow. Protease-activated receptor 1 (PAR-1), is atypical member of this family of receptors that mediate cellular responses to thrombin and related proteases. PAR1 is expressed by a wide range of tumor cells and can promote tumor growth, invasion and metastasis. The aim of this work was to study the role of PAR-1 expression in newly diagnosed ALL patients. Patients and methods: This study was conducted on 44 children with newly diagnosed ALL who were admitted to Hematology Unit, Pediatric department, Tanta University Hospital including 24 males and 20 females with their age ranged from 4-17 years and their mean age value of 9.06±3.26 who were divided into two groups; PAR-1 positive group (18 patients) and PAR-1 negative group (26 patients). All patients were subjected to complete history taking, thorough clinical examination, bone marrow aspiration and flow cytometric analysis for detection of PAR-1 expression by malignant cells. Results: PAR-1 was positive in 18 cases (41%) and negative in 26 cases (59%) of studied patients. This study showed no significant relation between PAR-1 expression and age, sex and most of the clinical data including hepatomegaly, splenomegaly and purpura while generalized lymphadenopathy was significantly higher in PAR-1 positive group. PAR-1 positive expression was associated with some bad prognostic laboratory parameters including higher hemoglobin, higher white blood cells, higher peripheral blood and bone marrow blast cells, higher serum LDH and lower platelets count. No significant association was detected between PAR-1 expression and immunophenotyping. There were significantly higher remission rates in PAR-1 negative group and significantly higher relapse and death rates in PAR-1 positive group. Conclusion: From this study, it could be concluded that PAR-1 expression on ALL cells represents an important adverse prognostic factor. Recommendations: PAR-1 expression should be routinely investigated for better prognostic assessment of ALL patients at diagnosis and should be taken in consideration in designing future therapeutic strategies based on patients- specific risk factors.

Chemotherapy-Phased Imatinib Pulses Improve Long-Term Outcome of Adult Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: Northern Italy Leukemia Group Protocol 09/00

2010 ◽  
Vol 28 (22) ◽  
pp. 3644-3652 ◽  
Author(s):  
Renato Bassan ◽  
Giuseppe Rossi ◽  
Enrico M. Pogliani ◽  
Eros Di Bona ◽  
Emanuele Angelucci ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Adult Patients ◽  
Negative Group ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Positive Group ◽  
Disease Free

Purpose Short imatinib pulses were added to chemotherapy to improve the long-term survival of adult patients with Philadelphia chromosome (Ph) –positive acute lymphoblastic leukemia (ALL), to optimize complete remission (CR) and stem-cell transplantation (SCT) rates. Patients and Methods Of 94 total patients (age range, 19 to 66 years), 35 represented the control cohort (ie, imatinib-negative [IM-negative] group), and 59 received imatinib 600 mg/d orally for 7 consecutive days (ie, imatinib-positive [IM-positive] group), starting from day 15 of chemotherapy course 1 and from 3 days before chemotherapy during courses 2 to 8. Patients in CR were eligible for allogeneic SCT or, alternatively, for high-dose therapy with autologous SCT followed by long-term maintenance with intermittent imatinib. Results CR and SCT rates were greater in the IM-positive group (CR: 92% v 80.5%; P = .08; allogeneic SCT: 63% v 39%; P = .041). At a median observation time of 5 years (range, 0.6 to 9.2 years), 22 patients in the IM-positive group versus five patients in the IM-negative group were alive in first CR (P = .037). Patients in the IM-positive group had significantly greater overall and disease-free survival probabilities (overall: 0.38 v 0.23; P = .009; disease free: 0.39 v 0.25; P = .044) and a lower incidence of relapse (P = .005). SCT-related mortality was 28% (ie, 15 of 54 patients), and postgraft survival probability was 0.46 overall. Conclusion This imatinib-based protocol improved long-term outcome of adult patients with Ph-positive ALL. With SCT, post-transplantation mortality and relapse remain the major hindrance to additional therapeutic improvement. Additional intensification of imatinib therapy should warrant a better molecular response and clinical outcome, both in patients selected for SCT and in those unable to undergo this procedure.

Negative prognostic value of glutathione S-transferase(GSTM1 and GSTT1) deletions in adult acute myeloid leukemia

Blood ◽  
2002 ◽  
Vol 100 (8) ◽  
pp. 2703-2707 ◽  
Author(s):  
Maria Teresa Voso ◽  
Francesco D'Alo' ◽  
Rossana Putzulu ◽  
Luca Mele ◽  
Alessandra Scardocci ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Prognostic Significance ◽  
Response To Therapy ◽  
Induction Treatment ◽  
Chain Reactions ◽  
Response To Chemotherapy ◽  
Homozygous Deletions ◽  
Acute Myeloid

Glutathione S-transferases (GSTs) are enzymes involved in the detoxification of several environmental mutagens, carcinogens, and anticancer drugs. GST polymorphisms resulting in decreased enzymatic activity have been associated with several types of solid tumors. We determined the prognostic significance of the deletion of 2 GST subfamilies genes, M1 and T1, in patients with acute myeloid leukemia (AML). Using polymerase chain reactions, we analyzed theGSTM1 and GSTT1 genotype in 106 patients with AML (median age, 60.5 years; range, 19-76 years). The relevance ofGSTM1 and GSTT1 homozygous deletions was studied with respect to patient characteristics, response to therapy, and survival. Homozygous deletions resulting in null genotypes at theGSTM1 and GSTT1 loci were detected in 45 (42%) and 30 (28%) patients, respectively. The double-null genotype was present in 19 patients (18%). GST deletions predicted poor response to chemotherapy (P = .04) and shorter survival (P = .04). The presence of at least one GST deletion proved to be an independent prognostic risk factor for response to induction treatment and overall survival in a multivariate analysis including age and karyotype (P = .02). GST genotyping was of particular prognostic value in the cytogenetically defined intermediate-risk group (P = .003). In conclusion, individuals with GSTM1 or GSTT1 deletions (or deletions of both) may have an enhanced resistance to chemotherapy and a shorter survival.

A New Method To Evaluate the Prognostic Value of Response to Prednisone Pre-Treatment in Adult (15–60 Yrs) Patients with Acute Lymphoblastic Leukemia: Results of the GIMEMA LAL 2000 Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1829-1829 ◽  
Author(s):  
Giovanna Meloni ◽  
Simona Iacobelli ◽  
Paola Fazi ◽  
Marco Vignetti ◽  
Francesco Di Raimondo ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Reduction Rate ◽  
Disease Free Survival ◽  
Treatment Phase ◽  
High Dose ◽  
Blast Count ◽  
Pre Treatment ◽  
Wbc Count

Abstract The prognostic significance of the response to initial prednisone treatment in adult ALL has been recently emphasized. Prednisone response is usually defined on the basis of the peripheral leukemic blast count. The threshold value for the defintion as good or poor prednisone response is 1000 blasts/mmc on day 8 of prednisone pre-treatment. The drawback of this definition is the difficulty of classifying patients with less than 1000 blasts at diagnosis. In the LAL2000 GIMEMA study we therefore evaluated whether the blast reduction rate, which is not affected by the initial blast level, could be a factor with comparable prognostic value. The protocol design provided a 7-day (−6 to 0) pre-treatment phase with an escalating dose of prednisone up to 60 mg/sqm. On day 1 before starting the induction the response was assessed both according to the absolute blast count (&lt; versus ≥ 1000/mmc) (criterion 1) and according to the blast reduction rate ≥ 75% (criterion 2) in the peripheral blood. The induction included high dose Daunorubicin; for patients in complete remission (CR) this was followed by consolidation with high dose ARA-C, chemo and radio prophylaxis of the central nervous system, and periodical reinduction over a three years maintenance period. Patients with adverse cytogenetic features [i.e. t(9;22), t(4;11), t(1;19)] who achieved a CR were treated according to the HAM protocol that included high dose ARA-C and Mitoxantrone followed by Imatinib for Ph+ ALL and by allogeneic or autologous hemopoietic stem cells transplantation for the others. Between September 2000 and December 2003 a total of 368 patients were evaluable for response to induction. The median age was 35 years (15–60) and median WBC count 15′109/L (0.3–872); 72 (20%) were T ALL and 121 (33%) had cytogenetic high risk features (104 (86%) Ph+, 4 (3%) t(4;11) and 13 (11%) t(1;19)). Eighty-seven percent of the patients were evaluable for response to steroid pre-treatment: ’responders’ were 75% according to criterion 1 (blast &lt;1′109/L on day 0), and 80% according to criterion 2 (blast reduction rate ≤75% on day 0). The overall CR rate was 83%. The probability of response was significantly higher in prednisone responders with respect to non responders according to both criteria: 87% versus 63% (p&lt;0.0001) according to criterion 1, 85% versus 68% (p=0.001) according to criterion 2. Also the post CR outcome was better in steroid responders, regardless of the definition. Using criterion 1, median disease-free survival (DFS) was 24 months in responders and 11 months in non responders; using criterion 2, median DFS was 23 months in responders and 12 months in non responders. Both criteria were significantly related to DFS in a multivariate analysis adjusted for cytogenetic risk and WBC count at diagnosis (&gt;=/&lt;50). In conclusion, our study confirms that the sensitivity to steroids is an independent prognostic factor for the outcome of adult ALL; moreover, we propose an alternative method of its evaluation with respect to the one currently used. This method has the advantage of allowing to classify all patients, regardless of the initial blasts level, and shows a comparable prognostic value.

Early Response to Therapy Is Significantly Associated with Genetic Subtype of Acute Lymphoblastic Leukemia: A Report from the Children’s Oncology Group.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 758-758
Author(s):  
Mignon L. Loh ◽  
Elizabeth Raetz ◽  
Meenakshi Devidas ◽  
Stephen B. Linda ◽  
Michael J. Borowitz ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Real Time ◽  
Induction Therapy ◽  
Classification System ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Early Response ◽  
Response To Therapy ◽  
Oncology Group ◽  
Genetic Features

Abstract Improved outcomes for children with acute lympboblastic leukemia (ALL) have been achieved, in part, from adaptation of risk-stratified therapy. The Children’s Oncology Group (COG) has implemented a real-time risk classification system (AALL03B1) using a combination of NCI-Rome risk criteria, blast cell genetic features, and early treatment response to determine the intensity of post-induction therapy. Between December 29, 2003 and June 1, 2007, more than 4,000 children over 1 year of age with B-precursor ALL were enrolled on AALL03B1, including 2293 (62%) with NCI Standard Risk (SR) and 1406 (38%) with NCI High Risk (HR) features who were subsequently enrolled on companion clinical trials. The most favorable genetic features used in AALL03B1 were identified in legacy COG studies and included TEL/AML1(TEL) or triple trisomies of chromosomes 4, 10, and 17 (TT). Unfavorable genetic features included the presence of BCR/ABL, MLL rearrangements, or extreme hypodiploidy (DNA index <.81 or chromosomes <44). Overall, 26% of patients were TEL+ and 24.7% had TT. These genetic subsets occurred more frequently in NCI SR vs. HR patients (30.7% and 30.9% vs. 14.5% and 11.7% respectively). Children achieving an M1 day 15 bone marrow (BM) who also had minimal residual disease (MRD) < 0.1% measured by flow cytometry on day 29 of induction therapy were deemed rapid early responders (RER), while those with either an M2/M3 day 15 marrow or MRD > 0.1% at day 29 were defined as slow early responders (SER). Among the favorable cytogenetic subsets, patterns of early response differed. The presence of TEL was significantly associated with an RER to induction therapy in both NCI SR and HR groups (p< 0.0001), while the presence of TT was not (p=0.058). For NCI SR patients, the presence of TEL was significantly associated with the achievement of an M1 bone marrow by day 8 (50.9% of TEL+ pts vs. 41.2% of TEL- pts, p< 0.0001). Patients with an M1 or M2 BM on day 29 who had MRD >1% received extended induction (EI) for two weeks followed by an additional evaluation of BM morphology and MRD at day 43 of induction. One hundred and nineteen patients received EI, with 40% having NCI SR features at diagnosis. Of the patients who received EI, 63% achieved an M1 marrow with MRD < 1% by day 43 and were eligible to continue on protocol therapy. This was more likely to occur in NCI SR patients (77% vs. 55%, p<0.013). Not surprisingly, 31% of the NCI HR patients receiving EI were BCR/ABL positive, and the presence of BCR/ABL was associated with a slower early response overall. While the presence of the BCR/ABL was associated with a greater likelihood of EI, MLL rearrangements and hypodiploidy were not. These data indicate that early response to induction therapy differs among genetic subsets of pediatric patients with newly diagnosed ALL. In addition a centralized classification system allows for robust collection of data from local and centralized reference laboratories that can be used for real time treatment assignment of ∼2000 patients/year with ALL from > 220 COG institutions.

Acute Lymphoblastic Leukemia (ALL) with t(8;14)(q11.2;q32): B-Lineage Disease with High Proportion of Down Syndrome. A Children’s Oncology Group (COG) Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1477-1477
Author(s):  
Yoav H. Messinger ◽  
Rodney Higgins ◽  
Meenakshi Devidas ◽  
Stephen P. Hunger ◽  
Andrew J. Carroll ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Trisomy 21 ◽  
Lymphoblastic Leukemia ◽  
Critical Role ◽  
Prognostic Significance ◽  
Philadelphia Chromosome ◽  
Chromosome 8 ◽  
Excellent Outcome ◽  
Children With Down Syndrome ◽  
B Lineage

Abstract Recurrent chromosome translocations play a critical role in the pathogenesis of ALL and many translocations have important prognostic significance. The t(8;14)(q11.2;q32) is a recurrent translocation that fuses the chromosome 8 CEBPD (CCAAT enhancer binding protein delta) gene to the IgH (immunoglobulin heavy chain) gene, leading most likely to deregulated CEPD expression. We previously reported the clinical data of 10 such patients (Leukemia, 2000;14:238–240). Using the COG ALL cytogenetics database we expand the report to include 22 patients (13 females and 9 males) with the t(8;14)(q11.2;q32). All patients with available immunophenotyping data (n=20) had B-lineage ALL. The median age at diagnosis was 9.2 years (range: 1.6 months – 17.1 years). Median diagnostic white blood cell count (WBC) was 9,950 (range: 700–172,000). Of the 22 patients, 7 were NCI standard risk and 15 were high risk. The most common additional cytogenetic abnormality was trisomy 21. Of the ten cases with trisomy 21, seven were constitutional (Down Syndrome), thus confirming previous reports that a significant fraction of t(8;14) patients (7/22; 31.8%) have Down Syndrome, which is much higher than the 3% (80/2811) overall rate of children with Down Syndrome in a recent COG ALL trial (p&lt;0.0001). In addition to the Down Syndrome cases, one case with phenotypic Turner syndrome had a mosaic constitutional r(Y)(p11q11.2); thus, eight cases (36%) had constitutional abnormalities. Secondary abnormalities included additional X (n=5); additional 5 (n=3); Philadelphia chromosome (n=1). Two cases had a second der(14)t(8;14) and two had loss of the der(8) t(8;14), consistent with the der(14)t(8;14) as the significant abnormality. Four cases (18%) had 9p deletions compared with 11% in the overall ALL population, and two cases (9%) had abnormalities of 13q compared with 2% in the overall population. Numerically, the cases were pseudodiploid (n=12) and hyperdiploid (n=10). Children with Down Syndrome had superior estimated 5-year event-free survival of 100%, compared to non-Down patients with 50.1±17.7% (p=0.04). Overall survival was also different but did not reach statistical significance: 100% vs. 60.9±17.0% (p=0.088). In summary, the rare t(8;14)(q11.2;q32) is associated with B-lineage phenotype and occurs with greatly increased frequency in children with Down Syndrome, who have an excellent outcome with standard COG therapy as compared to non-Down Syndrome patients with this translocation.

Karyotypic and Molecular Cytogenetic Findings in Childhood T-Cell Acute Lymphoblastic Leukemia (ALL): The Schneider Children’s Medical Center of Israel (SCMCI) Experience

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4861-4861
Author(s):  
Bati a Stark ◽  
Marta Jeison ◽  
Jaquelina Heker ◽  
Jacques Mardoukh ◽  
Gili Halevi-Berko ◽  
...  
Keyword(s):  
T Cell ◽  
Cytogenetic Analysis ◽  
Medical Center ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Response To Therapy ◽  
Mature Stage ◽  
Poor Responders ◽  
Fish Analysis ◽  
Prognostic Information

Abstract Introduction: Although outcome of Childhood T-ALL has improved significantly, it is still almost impossible to cure a relapsing patient. Currently, early response to therapy is considered the strongest predictor of outcome. Cytogenetics may contribute additional prognostic information in T-cell ALL. We used classical and molecular cytogenetics to screen the aberrations in T-ALL and study their correlation with immunophenotype and outcome. Methods: Cytogenetic analysis on cultured fresh BM specimens was performed as part of the routine diagnostic workup for every new ALL patient. Cytogenetic preparations were analyzed (part from archival material) by Fluorescence-In-Situ-Hybridization (FISH) on interphase nuclei, using commercially kits for: BCR/ABL1, MLL (Vysis), TLX1(HOX11), TLX3(HOX11L2), SIL-TAL1, TCRA/D on 14q11, TCRB on 7q34 (DakoCytomation) and P16 deletion on 9p21 (Cytocell). Results: Between Jan 1990 to April 2008, 79 newly diagnosed T-ALL patients, age 0.7–19 years, were treated at the SCMCI with 3 Israeli National Protocols based on the modified ALL-BFM 90/95 and IC-BFM 2002 studies. Five years EFS (median follow-up 8.5 yrs) is 71.9% (SE 5%), with 85.9% (SE 5.3%) for the MR group (prednisone-good-responders) (60% of patients), and 49.6% (SE 9.6%) for the HR group (prednisone-poor-responders) (40% of patients). Cytogenetic analysis was successful in 77 patients, and karyotype was abnormal in 59 (77%). In 19/59 pts (30%) 14q11 was involved: of them, four pts -t(11;14)(p13?15?;q11) (LMO1/2), three − t(10;14)(q24;q11)(TLX1), two − t(1;14)(p32;q11) (TAL1). Other non random translocations included: t(7;10)(q34;q24)-1pt and t(9;12)(q34;p13) with ABL1/ETV6 involvement – 1pt. By FISH analysis TLX1 split was detected in 2/33 samples, SIL-TAL1 fusion and TAL1 translocation in 5/55 samples, TLX3 split in 8/56 samples and MLL split in 6/61 samples. Additional secondary aberrations included 9p deletion in 16/55 samples, of them three pts had TLX3 split, three with SIL-TAL1 fusion/translocation, and one with t(9;12). del(9p) did not appear with the MLL split group. Episomal ABL1 amplification was detected in 2/63 samples, and in one of them it accompanied TLX3 split. Hyperdiploidy of &lt;50 chromosomes and segmental numerical changes were frequent. By the European Group for the Immunological Characterization of Leukemias, the EGIL classification for T-ALL, 5% of patients had immature phenotype, 35% - Pre-T, 34% - cortical and 24% - mature stage. Of the 4pts with LMO1/2, three were Pre-T and one relapsed. All 4 pts with TLX1 involvement had cortical immunophenotype and none have relapsed. The 5 pts with TAL1 and 6 pts with MLL split exhibited various phenotypic stages and no relapse occurred among them. In contrast, of the 8 pts with TLX3 split, 4 (50%) relapsed within 2 years. In conclusion: The findings of non random primary translocations and the combinations with recurrent secondary genetic aberrations, suggest specific multistep pathways in leukomogenesis of T-Cell leukemia. In the context of the present intensive treatment based on the BFM protocols, only the TLX3 split group fared worse, but a larger study is needed to evaluate the prognostic significance of the various cytogenetic subgroups in T-ALL.

Prevalence and Clinical Characterization of CD20 and CD22 Expression in Pediatric Precursor B-Cell Acute Lymphoblastic Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4872-4872
Author(s):  
Melissa S Rayburg ◽  
Daniel Marmer ◽  
Jun Mo ◽  
Richard McMasters ◽  
Teresa Smolarek ◽  
...  
Keyword(s):  
B Cell ◽  
Pediatric Population ◽  
Lymphoblastic Leukemia ◽  
Strong Association ◽  
Prognostic Significance ◽  
Response To Therapy ◽  
White Blood Count ◽  
Published Data ◽  
Prognostic Features ◽  
Cd20 Expression

Abstract Immunophenotypic classification of leukemia has important therapeutic and prognostic implications. In B-cell malignancies, CD20 and CD22 also represent therapeutic targets. CD20 expression in adult patients with B lineage ALL has been associated with a poor prognosis. The data are conflicting in the pediatric population and may be impacted by the type of therapy employed. A recent study of pediatric patients treated in consecutive St Jude Children’s Research Hospital Total Therapy ALL regimens observed excellent outcomes and no prognostic significance for CD20 expression (Jeha et al. Blood2006, 108:3302–3304). We retrospectively analyzed 50 consecutive patients aged 4 months to 28 years with precursor-B ALL treated with contemporary risk-adapted BFM-based ALL regimens for whom flow cytometric, genetic, and early response data were available. Cases were defined as positive for CD20 and/or CD22 expression if surface expression was identified in more than 20% of leukemic blasts. We found that CD22 was expressed at high levels (68–99%) in all patients evaluated. CD20 expression was positive in 27 (54%) of patients. CD20 expression did not correlate with known NCI prognostic features, including presenting white blood count or age. All 3 patients with BCR-ABL translocation ALL were CD20 positive. Consistent with previously published data, neither of the 2 patients with MLL-AF4 translocation were CD20 positive. There was no association of CD20 expression with trisomy 4/10/17 or TEL-AML1 status. We did not observe an association between CD20 expression and rapid early bone marrow response to therapy at day 8 or 15; 47/50 patients were in remission at day 29. At a median follow-up time of 48 months 46/50 patients were alive without relapse. These limited data do not suggest a strong association between CD20 expression and known prognostic features or early treatment response in pediatric precursor-B ALL treated with contemporary BFM therapy platforms. However, our findings of frequent expression of CD22 on precursor-B ALL blasts from children supports its consideration as a target for immunotherapy approaches in high risk or relapsed disease.

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