scholarly journals Association between the TPMT*3C (rs1142345) Polymorphism and the Risk of Death in the Treatment of Acute Lymphoblastic Leukemia in Children from the Brazilian Amazon Region

Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1132
Author(s):  
Darlen Cardoso de Carvalho ◽  
Luciana Pereira Colares Leitão ◽  
Fernando Augusto Rodrigues Mello Junior ◽  
Alayde Vieira Wanderley ◽  
Tatiane Piedade de Souza ◽  
...  
Keyword(s):  
Native American ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Brazilian Amazon ◽  
Childhood All ◽  
Risk Of Death ◽  
Native American Ancestry ◽  
High Contribution ◽  
Tpmt Gene

Acute lymphoblastic leukemia (ALL) is the leading cause of death from pediatric cancer worldwide. However, marked ethnic disparities are found in the treatment of childhood ALL with less effective results and higher mortality rates being obtained in populations with a high level of Native American ancestry. Genetic variations of the patient can affect resistance to ALL chemotherapy and potentially play an important role in this disparity. In the present study, we investigated the association of 16 genetic polymorphisms with the cell and metabolic pathways of the chemotherapeutic agents used in the treatment of ALL with the risk of death in treating childhood ALL in patients with a high contribution of Amerindian ancestry, coming from the Brazilian Amazon. The study included 121 patients with B-cell ALL treated with the BFM-2002 protocol. We are the first to identify the association between the TPMT gene rs1142345 polymorphism and the high risk of death in treating childhood ALL. Patients with the CC genotype had an approximately 25.5 times higher risk of dying during treatment of the disease than patients with other genotypes (p = 0.019). These results may help elucidate how the patient’s genetic characteristics contribute to the mortality disparity in populations with a high contribution of Native American ancestry. The rs1142345 variant of the TPMT gene could be used as a potential marker to early stratify patients at high risk of death in treating childhood ALL in the investigated population.

scholarly journals “SOCIOECONOMIC FACTORS AFFECTING SURVIVAL IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA FROM NORTH-EAST INDIA”

2020 ◽  
pp. 1-3
Author(s):  
Partha Sarathi Roy ◽  
Munlima Hazarika ◽  
Rakesh Kumar Mishra ◽  
BhargabJyoti Saikia ◽  
Gaurav Kumar
Keyword(s):  
Overall Survival ◽  
Developing Countries ◽  
Acute Lymphoblastic Leukemia ◽  
Socioeconomic Factors ◽  
Lymphoblastic Leukemia ◽  
Childhood All ◽  
Female Ratio ◽  
Risk Of Death ◽  
Lower Socioeconomic ◽  
Pediatric All

Acute lymphoblastic leukemia (ALL) is a highly curable childhood cancer with a survival rate of nearly 80% in developed countries but is around 45% in developing countries. This retrospective study analyzed the association between demographic and socioeconomic factors with survival in pediatric ALL. All confirmed cases of pediatric ALL (age <18 years) registered at Dr. B Borooah Cancer Institute between 2010 to 2017 were analyzed using data collected from hospital-based cancer registry and case records. Seventy-five confirmed cases of pediatrics ALL were eligible for the study. The median age of presentation was six years with a male: female ratio 1.9:1. Overall survival at 4-years was 43.8%, with a median survival of 25 months. A trend for higher 4-year overall survival was seen in female children (54.1% versus 37.9%, p=0.097). Patients from rural areas (44% versus 39.5%, p=0.308), with higher maternal education (83.3% versus 41.1%, p=0.161) and patients who did not abandon treatment (49.1% versus 31.2%, p=0.497) had better survival, but the differences were not significant. Four years overall survival in upper-middle, lower-middle, upper-lower, and lower class were 85.7%, 74.9%, 38.1%, and 7.7% respectively (upper-middleversus lower socioeconomic class, p=0.0001).Multivariate analyses confirmed a statistically significant relationship between socioeconomic status and survival, with the upper-middle group had a 90% decreased risk of death compared to the lower socioeconomic group. There is an urgent need for a proper definition of the problems of childhood ALL to introduce appropriate policies for improving survival in developing countries.

scholarly journals Homozygous Deletion of the p16/MTS1 Gene in Pediatric Acute Lymphoblastic Leukemia Is Associated With Unfavorable Clinical Outcome

Blood ◽  
1997 ◽  
Vol 89 (11) ◽  
pp. 4161-4166 ◽  
Author(s):  
Ursula R. Kees ◽  
Paul R. Burton ◽  
Changlong Lü ◽  
David L. Baker
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Clinical Outcome ◽  
Lymphoblastic Leukemia ◽  
Homozygous Deletion ◽  
Cell Phenotype ◽  
P16 Gene ◽  
Childhood All ◽  
Risk Of Death ◽  
Increased Risk

Abstract The p16 gene (MTS1, CDKN2, p16INK4A, CDKI) encoding an inhibitor of cyclin-dependent kinase 4 (cdk4) has been found to be deleted in various types of tumors, including leukemia, and is thought to code for a tumor suppressor gene. Our preliminary findings on eight pediatric patients with acute lymphoblastic leukemia (ALL) suggested that the survival of patients carrying a homozygous p16 gene deletion was significantly inferior to that of those without a deletion. The present study on 48 patients tested the hypothesis that the clinical outcome for pediatric ALL patients is correlated with the presence or absence of the p16 gene. Overall, nine of 48 children (18.3%) carried a homozygous p16 deletion. Such deletions were significantly more common (P = .003) among T-ALL patients (five of eight, 62.5%) than among precursor-B-ALL patients (four of 40, 10.0%). Of nine patients exhibiting p16 deletions, eight (88.9%) were classified as high-risk patients by the recognized prognostic factors of age, white blood cell count, and T-cell phenotype. The 4-year event-free survival in the study population as a whole was 72.7%. Without adjustment for other risk factors (univariate model), the presence of a homozygous p16 deletion was associated with a markedly increased probability of both relapse (P = .0003) and death (P = .002). These findings raise the question of whether the p16 deletion itself confers an increased risk of relapse after adjusting for the known risk factors. In this analysis, the estimated risk multiplier factor for relapse in patients carrying the p16 deletion was 14.0 (P = .0004) and for the risk of death 15.6 (P = .0008). We therefore conclude that the presence of a homozygous p16 deletion may well be an important risk factor for both relapse and death in childhood ALL, and that its prognostic effect is not a consequence of confounding by other factors already known to influence outcome in this disease.

scholarly journals ANALYSIS OF INDUCTION PHASE GLUCOCORTICOID USE ON ADRENAL SUPPRESSION IN PEDIATRIC PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

2017 ◽  
Vol 52 (1) ◽  
pp. 7
Author(s):  
Octaviana Simbolon ◽  
Yulistiani Yulistiani ◽  
I DG Ugrasena ◽  
Mariyatul Qibtiyah
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Risk Group ◽  
Lymphoblastic Leukemia ◽  
High Risk Group ◽  
Adrenal Suppression ◽  
Induction Phase ◽  
Childhood All ◽  
Cortisol Levels ◽  
Standard Risk

Glucocorticoids play an important role in the treatment of acute lymphoblastic leukemia (ALL). However, supraphysiological doses may cause suppression of the adrenal. Adrenal suppression resulting in reduced cortisol response may cause an inadequate host defence against infections, which remains a cause of morbidity and mortality in children with ALL. The occurrence of adrenal suppression before and after glucocorticoid therapy for childhood ALL is unclear. The aim of this study is to analysis the effect of glucocorticoid on cortisol levels during induction phase chemotherapy in children with acute lymphoblastic leukemia. A cross-sectional, observational prospective study was conducted to determine the effect of glucocorticoid on cortisol levels in children with acute lymphoblastic leukemia. Patients who met inclusion criteria were given dexamethasone or prednisone therapy for 49 days according to the 2013 Indonesian Chemotherapy ALL Protocol. Cortisol levels were measured on days 0, 14, 28, 42 and 56 of induction phase chemotherapy. There were 24 children, among 31 children recruited, who suffered from acute lymphoblastic leukemia. Before treatment, the means of cortisol levels were 228.95 ng/ml in standard risk group (prednisone) and 199.67 ng/ml in high risk group (dexamethasone). In standard risk group, the adrenal suppression occurs at about day 56. There was a significant decrement of cortisol levels in high risk group in days 14, 28, 42 against days 0 of induction phase (p=0.001). Both groups displayed different peak cortisol levels after 6 week of induction phase (p=0.028). Dexamethasone resulted in lower cortisol levels than prednisone during induction phase chemotherapy in children with acute lymphoblastic leukemia.

scholarly journals Nonrandom abnormalities of chromosome 9p in childhood acute lymphoblastic leukemia: association with high-risk clinical features

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 409-415 ◽  
Author(s):  
SB Murphy ◽  
SC Raimondi ◽  
GK Rivera ◽  
M Crone ◽  
RK Dodge ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
High Risk ◽  
Clinical Features ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Cell Phenotype ◽  
Term Survival ◽  
Childhood All ◽  
Chromosome 9P

To assess the frequency and significance of nonrandom abnormalities of chromosome 9p in childhood acute lymphoblastic leukemia (ALL), we analyzed our experience with 398 consecutive cases with completely banded karyotypes. Forty cases (10%) with abnormalities of 9p were identified: 26 with deletions, nine with unbalanced translocations resulting in the loss of 9p material, and five with apparently balanced reciprocal translocations. As compared with children with ALL lacking 9p abnormalities, these 40 cases were significantly older, had higher initial circulating WBC counts, more “lymphomatous” disease characteristics (including presence of a mediastinal mass in 15%. T- cell phenotype in 26%, splenomegaly greater than 8 cm in 25%), an increased failure rate in the first 2 to 3 years after diagnosis, and a higher incidence of extramedullary relapse. Conversely, lymphomatous ALL cases were twice as likely (19% v 8%) to have an abnormality of chromosome 9p than ALL cases lacking lymphomatous features (P = .01). The finding of an abnormal chromosome 9p, however, was not specific for lymphomatous ALL or T-cell lineage, because most cases were neither lymphomatous nor T-cell, and the overall Kaplan-Meier distribution of treatment failures for abnormal 9p cases was not statistically significantly different from control ALL cases receiving the same treatment who lacked abnormalities of 9p (P = .06, by log-rank test). We conclude that nonrandom abnormalities of chromosome 9p, especially a breakpoint in 9p21–22, occur with increased frequency in childhood ALL in association with some high-risk clinical features. Despite this association, the chromosome anomaly is nonspecific in its syndrome delineation and confers no major adverse consequence on long-term survival of childhood ALL treated with modern therapy. However, due to an apparently increased hazard of involvement of the CNS (eight of 17 failures), it may be inadvisable to lessen the intensity of CNS preventive therapy for this group of patients.

scholarly journals Ancestry and TPMT-VNTR Polymorphism: Relationship with Hematological Toxicity in Uruguayan Patients with Acute Lymphoblastic Leukemia

2020 ◽  
Vol 11 ◽  
Author(s):  
Gabriela Burgueño-Rodríguez ◽  
Yessika Méndez ◽  
Natalia Olano ◽  
Agustín Dabezies ◽  
Bernardo Bertoni ◽  
...  
Keyword(s):  
Native American ◽  
Acute Lymphoblastic Leukemia ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Variable Number Tandem Repeat ◽  
Maintenance Phase ◽  
Variable Number ◽  
Hematological Toxicity ◽  
Ancestry Informative Markers ◽  
Native American Ancestry

6-Mercaptopurine (6-MP) is a thiopurine drug widely used in childhood acute lymphoblastic leukemia (ALL) therapy. Genes such as TPMT and NUDT15 have an outstanding role in 6-MP metabolism. Mutations in both genes explain a significant portion of hematological toxicities suffered by ALL Uruguayan pediatric patients. A variable number tandem repeat in the TPMT promoter (TPMT-VNTR) has been associated with TPMT expression. This VNTR has a conservative architecture (AnBmC). To explore new causes of hematological toxicities related to ALL therapy, we genotyped the TPMT-VNTR of 130 Uruguayan pediatric patients. Additionally, individual genetic ancestry was estimated by 45 ancestry-informative markers (AIMs). Hematological toxicity was measured as the number of leukopenia events and 6-MP dose along the maintenance phase. As previously reported, we found TPMT*2 and TPMT*3C alleles were associated to TPMT-VNTR A2BC and AB2C, respectively. However, contrasting with other reports, TPMT*3A allele was found in a heterogeneous genetic background in linkage equilibrium. Patients carrying more than 5 A repeats present a significant higher number of leukopenia events among patients without TPMT and/or NUDT15 variants. Native American ancestry and the number of A repeats were significantly correlated with the number of leukopenia events. However, the correlation between Native American ancestry and the number of leukopenia events was lost when the number of A repeats was considered as covariate. This suggests that TPMT-VNTR alleles are more relevant than Native American ancestry in the hematological toxicity. Our results emphasize that TPMT-VNTR may be used as a pharmacogenetic biomarker to predict 6-MP-related hematological toxicity in ALL childhood therapy.

scholarly journals Intrachromosomal Amplification of Chromosome 21 in Childhood Acute Lymphoblastic Leukemia: Study of 3 Cases

2021 ◽  
pp. 592-598
Author(s):  
Aleksandra Mroczkowska ◽  
Monika Lejman
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
B Cell ◽  
Single Nucleotide Polymorphism Array ◽  
Lymphoblastic Leukemia ◽  
Chromosome 21 ◽  
Genetic Diagnostics ◽  
Cell Precursor ◽  
Childhood All ◽  
Fish Method

Acute lymphoblastic leukemia (ALL) is the most common malignancy of childhood. The presence or absence of a characteristic genetic abnormality usually observed in childhood ALL plays a very important role in determining the prognosis and stratification for treatment. Intrachromosomal amplification of chromosome 21 (iAMP21) is an uncommon high-risk chromosomal abnormality than can occur only in 2% of childhood B-cell precursor lymphoblastic leukemia. Molecular genetic analysis and the fluorescence in situ hybridization (FISH) technique are the basic methods used to detect the presence of the most common genetic abnormalities, the presence or absence of which has an impact on the patient’s classification into the appropriate risk group. This work presents 3 BCP-ALL iAMP21-positive patients who were detected during routine genetic diagnostics using the FISH method and microarray test. iAMP21 is associated with a poor prognosis and high risk for relapse. Children with B-cell precursor lymphoblastic leukemia with this genetic entity are associated with a delayed treatment response. The FISH method and single-nucleotide polymorphism array provides a useful method to detect characteristic genetic changes.

Role of MRD Monitoring in Childhood Acute Lymphoblastic Leukemia after Allogeneic Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 983-983 ◽  
Author(s):  
Adriana Balduzzi ◽  
Sonia Bonanomi ◽  
Monica Manenti Tech ◽  
Maria Dassi ◽  
Giovanni Cazzaniga ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Hematopoietic Cell Transplantation ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Conditioning Regimen ◽  
Allogeneic Transplantation ◽  
Childhood All ◽  
Log Reduction ◽  
Long Time

Abstract Relapse of acute lymphoblastic leukemia (ALL) after allogeneic transplant has very poor prognosis; whether early prediction of relapse by means of minimal residual disease (MRD) analysis could allow effective treatment is still to be assessed. Eighteen patients at high risk of relapse were prospectively monitored in a single transplant center. MRD analysis and clinical follow up were completed for the first series of 11 patients. This includes 9 males and 2 females (median age 11ys, range 2–16) who received allogeneic hematopoietic cell transplantation (HCT) from compatible (5), one locus mismatched (1) or haploidentical (1) related or unrelated (4) donor for ALL in 1st (5), 2nd (4), or 3rd (2) complete remission (CR), after conditioning regimen containing total body irradiation (TBI) and etoposide (9) or others, and GVHD prophylaxis consisting of cyclosporine, associated with ATG in transplant from other than compatible related donor. Grafts consisted of unmanipulated bone marrow (9), containing a median of 6.6x106CD34+/Kg (range 1.7–8.6) and 57.2x106CD3+/Kg (range 24.4–96.2), or peripheral (1), containing 11x106CD34+/Kg and 174x106CD3+/Kg, or positively selected peripheral (1) containing 12x106CD34+/Kg and 0.04x106CD3+/Kg. Five patients developed grade II–IV acute GVHD, requiring ATG in 4 cases. Five of 11 patients are alive in CR at a median of 15 months (range 11–21), 1 died in CR at 7 months, 5 relapsed at a median of 8 months (range 3–23), and 3 of them died. Patients were monitored by clone-specific RQ-PCR of one (4) or two (7) Ig/TcR markers, with a sensitivity of at least 10−4. At the time of transplant 7 patients were positive at the analysis of the MRD, while 4 were negative; patients were monitored at 1, 3, 6, 9 and 12 months after transplantation, or according to clinical requirements. Among the 4 MRD negative patients, 1 remained negative and is in CR at 19 months, 1 became positive 6 months after unrelated transplant and relapsed 2 months later, 1 relapsed 30 months after haploidentical transplant, a long time after MRD monitoring had stopped, while 1 died in CR. Among the 7 MRD positive patients, 2 remained always MRD positive and relapsed 3 and 7 months after transplant, and 5 experienced MRD negativity at a certain time after transplant; 1 of 5 became MRD positive at the 6th month after transient negativity and relapsed 3 months later, 3 of 5 became negative since the 1st or 3rd month, remained negative, and are alive in CR at 9, 12, and 13 months after transplant, while the remaining 1 alternated negative and positive MRD results and is in CR at 6 months. In 5 patients quantitative MRD data allowed early immunosuppression tapering or discontinuation, yielding severe GVHD in 1, and DLI treatment was planned in 2, but refused in 1; 2 of these 5 are in CR, while 3 relapsed, despite 1 experienced transient MRD 1-log reduction and 1 negativization. In conclusion, MRD monitoring after BMT might direct either early immunosuppression tapering or DLI for prevention of relapse in high risk childhood ALL transplanted patients.

Minimal Residual Disease Detected Prior to Transplantation Is Associated with Adverse Outcome in Pediatric Acute Lymphoblastic Leukemia.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3246-3246
Author(s):  
Jennifer H Foster ◽  
Anne Woolfrey ◽  
Brent Wood ◽  
Blythe Thomson
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Minimal Residual Disease ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Color Flow ◽  
Relapse Risk ◽  
Risk Of Death ◽  
Number Of Patients ◽  
Minimal Residual

Abstract Background: Acute lymphoblastic leukemia (ALL) is the most common form of malignancy in children. Advances in treatments have made ALL the disease highly curable; however for those patients who relapse, hematopoeitic stem cell transplantation (HSCT) offers a reasonable chance of cure. Minimal residual disease (MRD) detection by Multiparametric Flow Cytometery (MPF) is being used for risk adapted treatment decisions in many ALL trials. We present a series of 31 pediatric ALL patients who had morphologic and MPF evaluation of disease burden prior to ablative HSCT. Methods: Thirty one patients were treated at Children’s Hospital and Regional Medical Center, Seattle, WA for relapsed or very high risk ALL, were in complete morphologic remission, and received an ablative HSCT from May 2006-May 2008. Twelve patients were in second or third complete remission (CR) and 19 were in first CR. Eleven patients received a matched related donor, 20 patients received a unrelated donor graft. All patients underwent marrow evaluation including morphology and MPF within four weeks of their transplant date. The MPF was done by 7 or 9 color flow cytometry using the following reagents for B lineage: CD10, CD19, CD20, CD34, CD38, CD58 and CD45 and for T lineage: CD2, CD3, CD4, CD5, CD7, CD8, CD34, CD56, and CD45. Transplant regimens were total body irradiation-based (1320 cGy) with either cyclophosphamide (n=24) or fludarabine (n=6). MRD+ was any detectable leukemia >0.01% of cells. All patients were in morphologic remission (< 5% blasts) at time of transplant. Events were defined as relapse or deaths. Results: 21 patients were MRD-, 10 were MRD+. The 2 year event free survival (EFS) for the entire group was 56% (+/−22%). The EFS at 20 months for those patients in CR1 and CR2/3 were 62% (+/−32%) and 40% (+/−32%), respectively. EFS, relapse risk and non relapse mortality was analyzed with respect to MRD status: MRD+ (n=10) MRD- (n=21) p value EFS 36% (+/−32%) 68% (+/−26%) 0.037 Relapse Risk 48% (+/−36%) 13% (+/−16%) 0.036 Non-relapse Mortality 30% (+/−36%) 23% (+/−26%) 0.45 Discussion: We present a single institution series of patients treated for high risk or relapsed ALL who underwent disease evaluation prior to HSCT with MPF. With the small number of patients evaluated, it appears that any amount of disease detected by MPF was an adverse risk factor for recurrence. Those patients who were MRD+ experienced a higher risk of death from relapse, however, experienced no difference in non-relapse mortality. Resistant disease as detected by MRD analysis at time of transplant is a marker for poor outcome.

scholarly journals Nonrandom abnormalities of chromosome 9p in childhood acute lymphoblastic leukemia: association with high-risk clinical features

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 409-415 ◽  
Author(s):  
SB Murphy ◽  
SC Raimondi ◽  
GK Rivera ◽  
M Crone ◽  
RK Dodge ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
High Risk ◽  
Clinical Features ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Cell Phenotype ◽  
Term Survival ◽  
Childhood All ◽  
Chromosome 9P

Abstract To assess the frequency and significance of nonrandom abnormalities of chromosome 9p in childhood acute lymphoblastic leukemia (ALL), we analyzed our experience with 398 consecutive cases with completely banded karyotypes. Forty cases (10%) with abnormalities of 9p were identified: 26 with deletions, nine with unbalanced translocations resulting in the loss of 9p material, and five with apparently balanced reciprocal translocations. As compared with children with ALL lacking 9p abnormalities, these 40 cases were significantly older, had higher initial circulating WBC counts, more “lymphomatous” disease characteristics (including presence of a mediastinal mass in 15%. T- cell phenotype in 26%, splenomegaly greater than 8 cm in 25%), an increased failure rate in the first 2 to 3 years after diagnosis, and a higher incidence of extramedullary relapse. Conversely, lymphomatous ALL cases were twice as likely (19% v 8%) to have an abnormality of chromosome 9p than ALL cases lacking lymphomatous features (P = .01). The finding of an abnormal chromosome 9p, however, was not specific for lymphomatous ALL or T-cell lineage, because most cases were neither lymphomatous nor T-cell, and the overall Kaplan-Meier distribution of treatment failures for abnormal 9p cases was not statistically significantly different from control ALL cases receiving the same treatment who lacked abnormalities of 9p (P = .06, by log-rank test). We conclude that nonrandom abnormalities of chromosome 9p, especially a breakpoint in 9p21–22, occur with increased frequency in childhood ALL in association with some high-risk clinical features. Despite this association, the chromosome anomaly is nonspecific in its syndrome delineation and confers no major adverse consequence on long-term survival of childhood ALL treated with modern therapy. However, due to an apparently increased hazard of involvement of the CNS (eight of 17 failures), it may be inadvisable to lessen the intensity of CNS preventive therapy for this group of patients.

Impact of chromosomal translocations on prognosis in childhood acute lymphoblastic leukemia.

1991 ◽  
Vol 9 (12) ◽  
pp. 2183-2192 ◽  
Author(s):  
C M Rubin ◽  
M M Le Beau ◽  
R Mick ◽  
M A Bitter ◽  
J Nachman ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Intensive Therapy ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Chromosomal Translocations ◽  
Leukemic Cells ◽  
Childhood All ◽  
Wbc Count

The presence of a chromosomal translocation in the leukemic cells at diagnosis of acute lymphoblastic leukemia (ALL) in children is associated with a high risk for treatment failure. We have reexamined the relationship between translocations and prognosis in 146 children with ALL who received risk-based therapy such that high-risk patients were treated with intensive drug schedules. In univariate analysis, multiple factors were associated with a relatively poor event-free survival (EFS) including age less than 2 years or greater than 10 years (combined group), WBC count greater than 10 x 10(9)/L, French-American-British (FAB) morphologic classification L2, absence of common ALL antigen (CALLA, CD10) expression, absence of hyperdiploidy with a chromosome number of 50 to 60, and presence of the specific translocations t(4; 11)(q21;q23) or t(9;22)(q34;q11) (combined group). However, there was no disadvantage with respect to EFS in patients with translocations compared with those who lacked translocations (73% at 4 years in both groups). Furthermore, when patients with specific cytogenetic abnormalities for which the prognostic significance has been well established (hyperdiploid 50 to 60, t(4;11), and t(9;22] were removed from the analysis, the remaining group with other translocations had a better EFS than the remaining group lacking translocations, although this was not statistically significant (81% v 65% at 4 years, P = .24). In a multivariate analysis, a model including WBC count and FAB classification was the strongest predictor of EFS. The presence or absence of translocations was not an independent predictor of EFS and did not contribute to the ability of any model to predict EFS. In conclusion, when effective intensive therapy is used to treat childhood ALL with high-risk clinical features, categorization of patients on the basis of chromosomal translocations without attention to the specific abnormality is not useful as a prognostic factor.

Sign in / Sign up

Export Citation Format

Share Document