Diagnostic Cerebrospinal Fluid Examination in Children With Acute Lymphoblastic Leukemia: Significance of Low Leukocyte Counts With Blasts or Traumatic Lumbar Puncture

2003 ◽  
Vol 21 (2) ◽  
pp. 184-188 ◽  
Author(s):  
Britta Bürger ◽  
Martin Zimmermann ◽  
Georg Mann ◽  
Joachim Kühl ◽  
Lutz Löning ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lumbar Puncture ◽  
Cox Regression ◽  
Lymphoblastic Leukemia ◽  
Cranial Irradiation ◽  
Event Free Survival ◽  
Cns Involvement ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Leukocyte Counts

Purpose: To determine the significance of leukemic blasts or traumatic lumbar puncture (TLP) in diagnostic CSF of children enrolled in the Berlin-Frankfurt-Münster (BFM) Acute Lymphoblastic Leukemia–BFM-95 trial. Patients and Methods: A total of 2,021 patients were retrospectively evaluated according to initial central nervous system (CNS) status. Patients were classified as follows: CNS1 (CNS negative, n = 1,605), CNS2 (≤ 5 WBC/μL CSF with blasts, n = 103), CNS3 (CNS positive, n = 58), TLP+ (TLP with blasts, n = 135), or TLP− (TLP without blasts, n = 111). Patients with CNS2 and TLP+ status were eligible for two additional doses of intrathecal (IT) methotrexate (MTX). CNS3 patients received additional IT MTX and cranial irradiation (18 Gy). Results: CNS2, CNS3, and TLP+ groups contained a higher percentage of patients with unfavorable characteristics. Cox regression analysis identified TLP+ and CNS3 status as prognostically significant (CNS3): risk ratio (RR) = 2.3; 95% confidence interval [CI], 1.4 to 3.6; P = .0005; TLP+: RR = 1.5; 95% CI, 1.02 to 2.2; P = .04. Overall 5-year event-free survival (EFS) is 79%, for CNS1 it is 80%, and for TLP− it is 83%. CNS2 patients have an EFS of 80%, but the cumulative incidence of relapses with CNS involvement is higher compared with CNS1 patients (0.10 v 0.04). TLP+ patients have a significantly reduced EFS (73%, P = .003) because of an increased incidence of CNS relapses. CNS3 patients suffer from more systemic and CNS relapses (EFS 50%). Conclusion: CNS2 patients have the same prognosis as patients with CNS1 status, whereas the EFS of TLP+ patients is inferior to CNS1 but superior to CNS3 patients (P = .001). Both subgroups may have benefitted from additional IT MTX.

Prognostic Significance of Blasts in the Cerebrospinal Fluid Without Pleiocytosis or a Traumatic Lumbar Puncture in Children With Acute Lymphoblastic Leukemia: Experience of the Dutch Childhood Oncology Group

2006 ◽  
Vol 24 (15) ◽  
pp. 2332-2336 ◽  
Author(s):  
D. Maroeska W.M. te Loo ◽  
Willem A. Kamps ◽  
Anna van der Does-van den Berg ◽  
Elisabeth R. van Wering ◽  
Siebold S.N. de Graaf
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lumbar Puncture ◽  
Cox Regression ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Event Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Significant Difference

Purpose To determine the significance of blasts in the CSF without pleiocytosis and a traumatic lumbar puncture in children with acute lymphoblastic leukemia (ALL). Patients and Methods We retrospectively studied a cohort of 526 patients treated in accordance with the virtually identical Dutch protocols ALL-7 and ALL-8. Patients were classified into five groups: CNS1, no blasts in the CSF cytospin; CNS2, blasts present in the cytospin, but leukocytes less than 5/μL; CNS3, blasts present and leukocytes more than 5/μL. Patients with a traumatic lumbar puncture (TLP; > 10 erythrocytes/mL) were classified as TLP+ (blasts present in the cytospin) or TLP− (no blasts). Results Median duration of follow-up was 13.2 years (range, 6.9 to 15.5 years). Event-free survival (EFS) was 72.6% (SE, 2.5%) for CNS1 patients (n = 304), 70.3% (SE, 4.7%) for CNS2 patients (n = 111), and 66.7% (SE, 19%) for CNS3 patients (n = 10; no significant difference in EFS between the groups). EFS was 58% (SE, 7.6%) for TLP+ patients (n = 62) and 82% (SE, 5.2%) for TLP− patients (n = 39; P < .01). Cox regression analysis identified TLP+ status as an independent prognostic factor (risk ratio, 3.5; 95% CI, 1.4 to 8.8; P = .007). Cumulative incidence of CNS relapses was 0.05 and 0.07 in CNS1 and CNS2 patients, respectively (not statistically significant). Conclusion In our experience, the presence of a low number of blasts in the CSF without pleiocytosis has no prognostic significance. In contrast, a traumatic lumbar puncture with blasts in the CSF specimen is associated with an inferior outcome.

scholarly journals Dasatinib Plus Intensive Chemotherapy in Children, Adolescents, and Young Adults With Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia: Results of Children’s Oncology Group Trial AALL0622

2018 ◽  
Vol 36 (22) ◽  
pp. 2306-2314 ◽  
Author(s):  
William B. Slayton ◽  
Kirk R. Schultz ◽  
John A. Kairalla ◽  
Meenakshi Devidas ◽  
Xinlei Mi ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Cranial Irradiation ◽  
Intensive Chemotherapy ◽  
Event Free Survival ◽  
Free Survival ◽  
Risk Patients ◽  
Standard Risk ◽  
Philadelphia Chromosome Positive

Purpose Addition of imatinib to intensive chemotherapy improved survival for children and young adults with Philadelphia chromosome–positive acute lymphoblastic leukemia. Compared with imatinib, dasatinib has increased potency, CNS penetration, and activity against imatinib-resistant clones. Patients and Methods Children’s Oncology Group (COG) trial AALL0622 (Bristol Myers Squibb trial CA180-204) tested safety and feasibility of adding dasatinib to intensive chemotherapy starting at induction day 15 in patients with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia age 1 to 30 years. Allogeneic hematopoietic stem-cell transplantation (HSCT) was recommended for patients at high risk based on slow response and for those with a matched family donor regardless of response after at least 11 weeks of therapy. Patients at standard risk based on rapid response received chemotherapy plus dasatinib for an additional 120 weeks. Patients with overt CNS leukemia received cranial irradiation. Results Sixty eligible patients were enrolled. Five-year overall (OS) and event-free survival rates (± standard deviations [SD]) were 86% ± 5% and 60% ± 7% overall, 87% ± 5% and 61% ± 7% for standard-risk patients (n = 48; 19% underwent HSCT), and 89% ± 13% and 67% ± 19% for high-risk patients (n = 9; 89% underwent HSCT), respectively. Five-year cumulative incidence (± SD) of CNS relapse was 15% ± 6%. Outcomes (± SDs) were similar to those in COG AALL0031, which used the same chemotherapy with continuous imatinib: 5-year OS of 81% ± 6% versus 86% ± 5% ( P = .63) and 5-year disease-free survival of 68% ± 7% versus 60% ± 7% ( P = 0.31) for AALL0031 versus AALL0622, respectively. IKZF1 deletions, present in 56% of tested patients, were associated with significantly inferior OS and event-free survival overall and in standard-risk patients. Conclusion Dasatinib was well tolerated with chemotherapy and provided outcomes similar to those with imatinib in COG AALL0031, where all patients received cranial irradiation. Our results support limiting HSCT to slow responders and suggest a potential role for transplantation in rapid responders with IKZF1 deletions.

Physicians Compliance During Maintenance Therapy in Children with Down Syndrome and Acute Lymphoblastic Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2577-2577
Author(s):  
Cathrine Bohnstedt ◽  
Mette Levinsen ◽  
Susanne Rosthøj ◽  
Bernward Zeller ◽  
Mervi Taskinen ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Acute Lymphoblastic Leukemia ◽  
Maintenance Therapy ◽  
Lymphoblastic Leukemia ◽  
Target Range ◽  
Event Free Survival ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Children With Down Syndrome ◽  
Kaplan Meier

Abstract Abstract 2577 Children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) have an inferior prognosis compared to non-DS ALL patients. We reviewed Methotrexate (MTX)/Mercaptopurine (6MP) maintenance therapy data for children with DS treated according to the NOPHO ALL92 or the NOPHO ALL2000 protocols between 1992 and 2007. The five year event-free survival (pEFS5y) for the DS patients was inferior to the non-DS patients (0.50 ± 0.07 vs 0.77 ± 0.01, p<0.001). The 48 DS patients in 1st remission at the beginning of maintenance therapy had pEFS10y below the 522 non-DS control patients (pEFS10y: 0.58, 95%-CI 0.43–0.77 vs. 0.83, 95%-CI 0.80–0.86, p<0.0001). The DS patients received lower median doses of MTX (Median: 11.8 vs 15.4, p<0.0001) and 6MP (median: 45.6 vs. 59.4, p<0.0001). In Cox regression analysis male gender, presence of DS, and high median maintenance therapy white blood cell levels (mWBC) were associated with increased risk for relapse. The mWBC hazard ratio for DS-ALL patients was 2.0, p<0.0005). This supports that DS children with ALL should be treated as vigorously as non-DS ALL patients. Obtaining WBC levels within target range could potentially increase their cure rates. Figure 1: Kaplan-Meier curves for event free survival for DS and non-DS children. Figure 1:. Kaplan-Meier curves for event free survival for DS and non-DS children. Non-DS 513 464 443 433 418 DS 47 25 19 12 6 Disclosures: No relevant conflicts of interest to declare.

Prognostic Factors in CD10 Negative Precursor B-Cell Acute Lymphoblastic Leukemia in Children: Data from Three Consecutive Trials ALL-BFM 86, 90, and 95.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1957-1957
Author(s):  
Anja Möricke ◽  
Richard Ratei ◽  
Wolf-Dieter Ludwig ◽  
Jochen Harbott ◽  
Arndt Borkhardt ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Prognostic Factors ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Cox Regression ◽  
Lymphoblastic Leukemia ◽  
Cns Involvement ◽  
Total N ◽  
Cox Regression Analysis ◽  
Cell Acute Lymphoblastic Leukemia

Abstract The overall unfavorable prognosis of CD10 negative (CD10−) precursor B-cell acute lymphoblastic leukemia (BCP-ALL) is well known. We analyzed 4473 pediatric patients (pts) <18 years (y) with BCP-ALL and immunophenotyping of CD10 enrolled from 1986 to 2000 in three consecutive ALL-BFM trials to explore prognostic factors in the CD10− subset. CD10 negativity was defined by CD10 expression in <20% of blasts. 233 pts (5.2%) were CD10−. In comparison to CD10 positive (CD10+) BCP-ALL pts, CD10− pts comprised more infants (age <1y 34% vs. 1%, p(X2)<0.001), more cases with hyperleukocytosis (WBC ≥100/nl 43% vs. 6%, p<0.001), more CNS involvement (CNS positive 10% vs. 2%; p<0.001) and an impaired treatment response (prednisone poor response (PPR) 22% vs. 5%, p<0.001; induction failure 6% vs. 1%, p<0.001). Estimated probability of 5 years event free survival (5y-pEFS) was significantly lower in pts with CD10− as compared to CD10+ BCP-ALL (49±3% vs 81±0.6%, p(log-rank)<0.001). Cox regression analysis including age, WBC, prednisone response (PR) and MLL/AF4 status as covariables revealed CD10 negativity as independent prognostic factor (RR 1.5, 95% confidence interval (CI) 1.1–2.1, p=0.01). Further analyses were performed within the CD10− group: 83% of infants and 60% of pts ≥1y were successfully analyzed for MLL/AF4. MLL/AF4 was detected in 55% of pts <1y and 27% of pts ≥1y. The well known risk factors for BCP-ALL (sex, age, WBC, CNS involvement, MLL/AF4 and PPR) also had prognostic impact within the CD10− group: n* 5y-pEFS* (%) SE (%) p (log-rank) *5 pts w/o reinduction were excluded sex female 109 55 5 0.022 male 119 40 5 age <1y 78 25 5 <0.001 ≥1y 150 62 4 WBC <100/nl 128 62 4 <0.001 ≥100/nl 100 33 5 CNS neg 181 54 4 0.011 pos 21 33 10 MLL/AF4 neg 95 53 5 0.001 pos 61 29 6 PR good 170 57 4 <0.001 poor 50 30 6 Out of a number of immunophenotypic markers, analyzed at different expression cut-off points, CD24 at missing or weak expression of <40% and CD65 at high expression of ≥40% were significantly correlated with unfavorable clinical characteristics and worse outcome within the CD10− group. Significant correlation with PR could only be demonstrated for expression of CD24, which is presumed to act as negative regulator in B-cell development through mediation of apoptosis. age<1y* WBC ≥100/nl* MLL/AF4 pos* PPR# pEFS§ n/total (%) n/total (%) n/total (%) n/total (%) % ±SE * all p(X2)<0.01, #CD24 p=0.01, CD65 n.s., §all p(log-rank]<0.001 CD24 <40% 37/77 (48) 52/77 (68) 33/56 (59) 24/73 (33) 32 ±5 CD24 ≥40% 34/122 (28) 35/122 (29) 18/76 (24) 20/119 (17) 59 ±5 CD65 <40% 56/180 (31) 67/180 (37) 39/120 (33) 39/175 (22) 30 ±7 CD65 ≥40% 22/44 (50) 32/44 (73) 21/34 (62) 10/41 (24) 54 ±4 Including age, WBC, PR and MLL/AF4 status as covariables, out of the analyzed markers only CD65 proved to be an independent prognostic factor in CD10− BCP-ALL (Cox regression analysis: RR 1.5, 95% CI 1.1–2.9, p=0.018). The identification of additional prognosis associated immunophenotypic markers may contribute to further refinement of treatment strategies for CD10− BCP-ALL pts.

Clinical significance of translocation t(1;19) in childhood acute lymphoblastic leukemia in the context of contemporary therapies: a report from the Children's Cancer Group.

1998 ◽  
Vol 16 (2) ◽  
pp. 527-535 ◽  
Author(s):  
F M Uckun ◽  
M G Sensel ◽  
H N Sather ◽  
P S Gaynon ◽  
D C Arthur ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Free Survival ◽  
Cancer Group ◽  
Improved Outcomes ◽  
B Lineage ◽  
The Individual

PURPOSE The nonrandom translocation t(1;19) has been associated with poor outcome in pediatric B-lineage acute lymphoblastic leukemia (ALL). Because most patients treated by contemporary therapies now achieve improved outcomes, we have reassessed the prognostic significance of t(1;19). PATIENTS AND METHODS Cytogenetic data were accepted for 1,322 children (<21 years old) with newly diagnosed ALL enrolled between 1988 and 1994 on risk-adjusted studies of the Children's Cancer Group (CCG). Forty-seven patients (3.6%) were t(1;19) positive (+); 1,275 (96.4%) were t(1;19) negative (-). Clinical characteristics and treatment outcome were compared using standard methods. RESULTS Translocation (1;19)+ patients were more likely than t(1;19)- patients to be 10 years of age or greater (P < .001) or CD10+ CD19+ CD34- (P < .0001), or nonwhite (P = .02). Patients with a balanced t(1;19) were less likely to be hyperdiploid than patients with an unbalanced der(19)t(1;19). Event-free survival (EFS) was similar for the overall group of t(1;19)+ and t(1;19)- patients, with 4-year estimates of 69.5% (SD, 6.8%) and 74.8% (SD, 1.3%; P = .48), respectively. However, patients with unbalanced der(19)t(1;19) had significantly better outcomes than patients with balanced t(1;19): 4-year EFS were 80.6% (SD, 7.1%) and 41.7% (SD, 13.5%), respectively (P = .003). These differences were maintained within the individual studies analyses and after exclusion of t(1;19)+ patients whose cells were hyperdiploid with more than 50 chromosomes. CONCLUSION The overall group of t(1;19)+ patients, as well as the subgroup with an unbalanced der(19)+ (1;19) had outcomes similar to that of t(1;19)- patients, whereas patients with balanced t(1;19) had poorer outcomes. Thus, although the overall prognostic significance of t(1;19) has been obviated by contemporary risk-adjusted protocols, the balanced t(1;19) translocation remains an adverse prognostic factor.

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.

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