Philadelphia chromosome in relapsed childhood acute lymphoblastic leukemia: a matched-pair analysis. Berlin-Frankfurt-Münster Study Group.

1997 ◽  
Vol 15 (6) ◽  
pp. 2231-2237 ◽  
Author(s):  
B Beyermann ◽  
H P Adams ◽  
G Henze
Keyword(s):  
Risk Factor ◽  
Acute Lymphoblastic Leukemia ◽  
Cell Count ◽  
Independent Risk Factor ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Blast Cell ◽  
Matched Pair ◽  
Matched Pair Analysis ◽  
Pair Analysis

PURPOSE The translocation t(9;22)(q34;q11), known as Philadelphia chromosome (Ph1) or its molecular equivalent the expression of BCR-ABL-mRNA, is one of the most striking and well-characterized cytogenetic abnormalities in leukemia. Although investigated for more than 30 years, it remains unclear whether the Ph1 is an independent risk factor for outcome of leukemia or not. METHODS A matched-pair analysis was performed within a homogeneous group of patients, which consisted of children who presented with a first relapse of acute lymphoblastic leukemia (ALL) who were treated according to ALL relapse trials (ALL-REZ BFM) protocols. A total of 307 patients were eligible for this analysis: 30 positive and 277 negative for Ph1. Positive patients were matched exactly for time point of relapse (on [during] or off [after cessation of] front-line therapy), site, and immunophenotype, and as close as possible for duration of first remission, peripheral blast-cell count, WBC count, and year of relapse diagnosis. RESULTS The probability of event-free survival is 0.46 at 5 years for negative and 0.11 for positive patients, respectively (P = .0006). Multivariate analysis showed risk ratios of 4.229 for relapse on therapy, 3.561 for Ph1 and/or expression of BCR-ABL- mRNA, 1.691 for high peripheral blast-cell count, and 0.232 for bone marrow transplantation. CONCLUSION It was shown that the Ph1 is indeed an independent risk factor in childhood relapsed ALL. There are striking similarities between these patients and children at initial diagnosis, as well as adult patients. Therefore, it is highly suggestive that the Ph1 is also an independent risk factor under all of these circumstances.

Relapse of TEL-AML1–Positive Acute Lymphoblastic Leukemia in Childhood: A Matched-Pair Analysis

2001 ◽  
Vol 19 (13) ◽  
pp. 3188-3193 ◽  
Author(s):  
Karl Seeger ◽  
Arend V. Stackelberg ◽  
Tillmann Taube ◽  
Dirk Buchwald ◽  
Gabriele Körner ◽  
...  
Keyword(s):  
Risk Factor ◽  
Acute Lymphoblastic Leukemia ◽  
Independent Risk Factor ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Matched Pair ◽  
Prognostic Parameters ◽  
Matched Pair Analysis ◽  
Pair Analysis ◽  
Time Point

PURPOSE: The aim of this study was to investigate whether, in relapsed childhood acute lymphoblastic leukemia (ALL), the frequent genetic feature of TEL-AML1 fusion resulting from the cryptic chromosomal translocation t(12;21)(p13;q22) is an independent risk factor. PATIENTS AND METHODS: A matched-pair analysis was performed within a homogeneous group of children with first relapse of BCR-ABL–negative B-cell precursor (BPC) ALL treated according to relapse trials ALL-Rezidiv (REZ) of the Berlin-Frankfurt-Münster Study Group. A total of 249 patients were eligible for this study: 53 (21%) were positive for TEL-AML1, and 196 (79%) were negative. Positive patients were matched for established most-significant prognostic determinants at relapse, time point, and site of relapse, as well as age and peripheral blast cell count at relapse. RESULTS: Fifty pairs matching the aforementioned criteria could be determined. The probabilities with SE of event-free survival and survival at 5 years for matched TEL-AML1 positives and negatives are 0.63 ± 0.10 versus 0.38 ± 0.10 (P = .09) and 0.82 ± 0.09 versus 0.42 ± 0.19 (P = .10), respectively. These results were confirmed by multivariate analysis, revealing an independent prognostic significance of time point and site of relapse (both P < .001) but not of TEL-AML1 expression (P = .09). CONCLUSION: TEL-AML1 expression does not constitute an independent risk factor in relapsed childhood BCP-ALL after matching for relevant prognostic parameters. It undoubtedly characterizes genetically an ALL entity associated with established favorable prognostic parameters. High-risk therapeutic procedures such as allogeneic SCT should be considered restrictively.

Unrelated donor stem cell transplantation compared with chemotherapy for children with acute lymphoblastic leukemia in a second remission: a matched-pair analysis

Blood ◽  
2003 ◽  
Vol 101 (10) ◽  
pp. 3835-3839 ◽  
Author(s):  
Anja Borgmann ◽  
Arend von Stackelberg ◽  
Reinhard Hartmann ◽  
Wolfram Ebell ◽  
Thomas Klingebiel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Matched Pair ◽  
Event Free Survival ◽  
Free Survival ◽  
Matched Pair Analysis ◽  
Pair Analysis

Abstract Allogeneic stem cell transplantation (SCT) is frequently considered as treatment for relapsed childhood acute lymphoblastic leukemia (ALL). For patients without a matched sibling donor, SCT from unrelated donors (UD-SCT) has been increasingly performed during the past years. However, UD-SCT–related mortality and morbidity is still considerable, and the question remains as to which patients are at such high risk of recurrence that UD-SCT is indicated and, conversely, which patients do not require transplantation for long-term disease control. A matched-pair analysis was performed among patients treated according to Acute Lymphoblastic Leukemia Relapse Berlin-Frankfurt-Münster (ALL-REZ BFM) Study Group protocols after first relapse with chemotherapy or UD-SCT. Altogether 81 pairs were identified that could be matched exactly for site of relapse and immunophenotype, and as closely as possible for duration of first remission, age, diagnosis date, and peripheral blast cell count at relapse. No significant difference in the probability of event-free survival (pEFS) between UD-SCT and chemotherapy existed regarding 28 pairs with an intermediate prognosis (0.39 ± 0.10 vs 0.49 ± 0.11,P = .105), whereas the pEFS was significantly different in the 53 pairs with a poor prognosis (0.44 ± 0.07 vs 0.00 ± 0.00, P < .001). The major reasons of treatment failure among patients who underwent UD-SCT were therapy-related death (TRD; 24/81) and relapses (20/81). In contrast, TRD rarely occurred in patients treated with chemotherapy alone (3/81), but relapse was much more common (62/81). In conclusion, UD-SCT provides better event-free survival for children with high-risk relapsed ALL. However, there is no clear advantage of UD-SCT in patients with intermediate prognosis.

Role of Matrix Metalloproteinase MMP-2, MMP-9 and Tissue Inhibitor of Metalloproteinase (TIMP-1) in Clinical Progression of Pediatric Acute Lymphoblastic Leukemia

2021 ◽  
Author(s):  
Maha Saleh ◽  
Mohamed Khalil ◽  
Mona S. Abdellateif ◽  
Emad Ebeid ◽  
Eman Z. Kandeel
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cell Count ◽  
Cancer Progression ◽  
Lymphoblastic Leukemia ◽  
Multivariate Logistic Regression Analysis ◽  
Blast Cell ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Tissue Inhibitor ◽  
Pediatric Acute Lymphoblastic Leukemia ◽  
Pediatric All

Abstract Background: Matrix metalloproteinases (MMPs) play a crucial role in cancer progression and metastasis, however their role in pediatric Acute lymphoblastic leukemia (ALL) is still unrevealed.Methods: The diagnostic, prognostic and predictive value of tissue inhibitor of metalloproteinase (TIMP-1), MMP-2, MMP-9 and CD34+CD38- CSCs were assessed in bone marrow (BM) samples of 76 ALL children using Flow Cytometry analysis. Results: There was a significant increase in TIMP-1 [1.52 (0.41-10) versus 0.91(0.6-1.12); respectively, P<0.001], and CSCs CD84+CD38- [1 (0.03-18.6) versus 0.3 (0.01-1.1), P<0.001] expression in ALL patients compared to controls. While there were no significant differences regarding MMP-2 and MMP-9 expression between the two groups. The sensitivity, specificity, AUC of MMP-2 were (80.3%, 53.3% and 0.568, P=0.404), and that of MMP-9 were (53.9%, 40% and 0.660, P=0.053). While that of TIMP-1 were (78.9%, 100% and 0.892, P<0.001), and that of CSCs CD34+ CD38- were (78.9%, 73.3% and 0.855, P<0.001). There was a significant association between MMP-2 overexpression and MRD at day-15, increased BM blast cell count at diagnosis and at day-15, (P=0.020, P=0.047 and P=0.001). Increased TIMP-1 expression associated with the high-risk disease (P<0.001), increased BM blast cell count at diagnosis and at day-15 (P=0.033 and P=0.001), as well as MRD at day 15 and day 42 (P<0.001 for both). CD34+CD38- CSCs associated with MRD at day-15, increased BM blast cell count at diagnosis and at day-15 (P=0.015, P=0.005 and P=0.003). TIMP-1 overexpression associated with shorter DFS and OS rates (P=0.009 and P=0.048). Multivariate logistic regression analysis showed that both TIMP-1 [OR: 4.224, P=0.046], and CD34+CD38- CSCs [OR: 6.873, P=0.005] are independent diagnostic factors for pediatric ALL.Conclusion: TIMP-1 and CD34+CD38- CSCs could be useful independent diagnostic markers for pediatric ALL. Also, TIMP-1 is a promising prognostic marker for poor outcome of the patients.

scholarly journals Cytokine Release Syndrome Is an Independent Risk Factor Associated With Platelet Transfusion Refractoriness After CAR-T Therapy for Relapsed/Refractory Acute Lymphoblastic Leukemia

2021 ◽  
Vol 12 ◽  
Author(s):  
Yadan Liu ◽  
Bin Liang ◽  
Yan Liu ◽  
Guoqing Wei ◽  
Wenjun Wu ◽  
...  
Keyword(s):  
Risk Factor ◽  
Acute Lymphoblastic Leukemia ◽  
Platelet Transfusion ◽  
Independent Risk Factor ◽  
Lymphoblastic Leukemia ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
Car T ◽  
Grade 3 ◽  
Platelet Transfusions

Background: Chimeric antigen receptor T cell (CAR-T) therapy is successful in improving treatment outcomes for relapsed/refractory acute lymphoblastic leukemia (R/R ALL). However, toxicities associated with CAR-T therapy are being increasingly identified. Pancytopenia is one of the most common complications after CAR-T therapy, and platelet transfusions are an essential part of its supportive care.Study Design and Methods: This study aimed to assess the effectiveness of platelet transfusions for R/R ALL patients at our single center and identify associated risk factors. Overall, 44 R/R ALL patients were enrolled in this study, of whom 26 received CAR-T therapy and 18 received salvage chemotherapy.Result: Patients in the CAR-T group had a higher incidence of platelet transfusion refractoriness (PTR) (15/26, 57.7%) than those in the chemotherapy group (3/18, 16.7%) (p = 0.007). For patients receiving CAR-T therapy, multivariate analysis showed that the grade of cytokine release syndrome (CRS) was the only independent risk factor associated with PTR (p = 0.007). Moreover, higher peak serum IL-6 and IFN-γ levels suggested a higher risk of PTR (p = 0.024 and 0.009, respectively). Patients with PTR received more platelet infusion doses than those without PTR (p = 0.0426). Patients with PTR had more grade 3–4 bleeding events than those without PTR (21.4 vs. 0%, p = 0.230), and the cumulative incidence of grade 3–4 bleeding event was different (p = 0.023).Conclusion: We found for the first time that PTR is associated with the CRS grade. Improved knowledge on the mechanisms of PTR after CAR-T therapy is needed to design a rational therapeutic strategy that aims to improve the efficiency of transfusions.

Sign in / Sign up

Export Citation Format

Share Document