Outcome of children with high-risk acute lymphoblastic leukemia (HR-ALL): Nordic results on an intensive regimen with restricted central nervous system irradiation

2003 ◽  
Vol 42 (1) ◽  
pp. 8-23 ◽  
Author(s):  
Ulla M. Saarinen-Pihkala ◽  
G. Gustafsson ◽  
N. Carlsen ◽  
T. Flaegstad ◽  
E. Forestier ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Intensive Regimen

Outcome of the Rotterdam-84 CNS-ALL Chemotherapy Protocol without Radiotherapy for Isolated Central Nervous System Relapsed Acute Lymphoblastic Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1955-1955
Author(s):  
Auke Beishuizen ◽  
Femke K. Aarsen ◽  
Jeanette E.W.M. van Dongen ◽  
Isabelle C. Streng ◽  
Rob Pieters ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Total Duration ◽  
Treatment Protocol ◽  
Severe Toxicity ◽  
Visual Spatial ◽  
Cns Relapse

Abstract Introduction Current protocols use radiotherapy (craniospinal irradiation) as the treatment of choice to cure isolated central nervous system (CNS) acute lymphoblastic leukemia (ALL) relapses. The severe toxicity of this treatment encouraged us to develop a new CNS-ALL protocol without radiotherapy. Patients and methods From Jan 1987 till Aug 2004, 13 children were diagnosed in our centre with an isolated CNS relapse after initial treatment according to standard DCOG-ALL protocols. Treatment of CNS relapse consisted of induction by weekly intrathecal Methotrexate (MTX). At remission, an Ommaya reservoir was implanted and CNS-directed intraventricular sandwich therapy, consisting of MTX day 1; ARA-C day 2 and MTX day 3 (dosage according to age) was given every four weeks for one year. At the same time systemic treatment, based on the ALL-6 protocol (JCO1996;14:911–8), was started in which at week 23, 44 and 65 intensification courses of 6 weeks duration with Teniposide, HD-ARA-C and HD-MTX were inserted. The total duration of treatment is 95 weeks. Six of 13 patients could be assessed for behavior, intelligence, memory, visual-spatial and visual-motor skills before and after treatment using the CBCL and WISC-RN tests among others. Results All 13 patients, 3 girls and 10 boys aged 2.3 till 14.8 years (9 precursor B-ALL and 4 T-ALL), had an early isolated CNS relapse after a median first remission duration of 16 months (range 2–30 months). Nine of them were high risk according to BFM relapse criteria (male, age < 6 years, T-ALL phenotype, relapse < 18 months from diagnosis). At present, eight patients are alive in 2nd complete remission (CR) with a median follow up of 82 months (range 7–189 months). Five patients relapsed, all high risk, of which three died. One died after a secondary AML, one after a bone marrow (BM) relapse in 2nd CR due to fungal sepsis and one after a combined BM and CNS relapse due to streptococcal meningitis/encephalitis during neutropenia. The fourth patient had a second CNS relapse after 42 months in second remission. He is still in 3rd CR for 86 months after an autologous BM infusion. The fifth patient had recently an isolated BM relapse after 11 months in 2nd CR and started systemic reinduction therapy. The 5 years EFS of this study is 57% ± 15% and the 5 years OS 73% ± 14%. Before start of chemotherapy no significant differences in psychological testing were found in comparison with the normal population. After stop chemotherapy significant lower scores were obtained on the domains of perceptual organization and behavior similar to those found in other patients treated for cancer. Furthermore, our treatment protocol has no significant effect on neurocognitive functioning in comparison with craniospinal radiotherapy. Conclusion Sandwich intraventricular therapy together with systemic anti-leukemia therapy without radiotherapy seems to be an effective treatment with minimal neurocognitive disfunctioning for isolated CNS-ALL relapse. Further investigations in a larger group of patients are essential with special emphasis on comparing late effects of this therapy with radiotherapy.

scholarly journals Pharmacogenetics of the Central Nervous System—Toxicity and Relapse Affecting the CNS in Pediatric Acute Lymphoblastic Leukemia

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2333
Author(s):  
Judit C. Sági ◽  
András Gézsi ◽  
Bálint Egyed ◽  
Zsuzsanna Jakab ◽  
Noémi Benedek ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Gene Polymorphisms ◽  
Lymphoblastic Leukemia ◽  
Toxic Encephalopathy ◽  
Inverse Association ◽  
Central Nervous System Toxicity ◽  
Cns Relapse ◽  
The Central Nervous System

Despite improving cure rates in childhood acute lymphoblastic leukemia (ALL), therapeutic side effects and relapse are ongoing challenges. These can also affect the central nervous system (CNS). Our aim was to identify germline gene polymorphisms that influence the risk of CNS events. Sixty single nucleotide polymorphisms (SNPs) in 20 genes were genotyped in a Hungarian non-matched ALL cohort of 36 cases with chemotherapy related acute toxic encephalopathy (ATE) and 544 controls. Five significant SNPs were further analyzed in an extended Austrian-Czech-NOPHO cohort (n = 107 cases, n = 211 controls) but none of the associations could be validated. Overall populations including all nations’ matched cohorts for ATE (n = 426) with seizure subgroup (n = 133) and posterior reversible encephalopathy syndrome (PRES, n = 251) were analyzed, as well. We found that patients with ABCB1 rs1045642, rs1128503 or rs2032582 TT genotypes were more prone to have seizures but those with rs1045642 TT developed PRES less frequently. The same SNPs were also examined in relation to ALL relapse on a case-control matched cohort of 320 patients from all groups. Those with rs1128503 CC or rs2032582 GG genotypes showed higher incidence of CNS relapse. Our results suggest that blood-brain-barrier drug transporter gene-polymorphisms might have an inverse association with seizures and CNS relapse.

scholarly journals CENTRAL NERVOUS SYSTEM INVOLVEMENT IN ADULT ACUTE LYMPHOBLASTIC LEUKEMIA: DIAGNOSTIC TOOLS, PROPHYLAXIS AND THERAPY

2014 ◽  
Vol 6 (1) ◽  
pp. e2014075 ◽  
Author(s):  
Maria Ilaria Del Principe ◽  
Luca Maurillo ◽  
Francesco Buccisano ◽  
Giuseppe Sconocchia ◽  
Mariagiovanna Cefalo ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Intrathecal Injection ◽  
False Negative ◽  
Diagnostic Tools ◽  
Positive Finding ◽  
Cns Involvement ◽  
Hematopoietic Stem

In adult patients with acute lymphoblastic leukemia (ALL), Central Nervous System (CNS) involvement is associated with a very poor prognosis. The diagnostic assessment of this condition relies on the use of neuroradiology, conventional cytology (CC) and flow cytometry (FCM). Among these approaches, which is the gold standard it is still a matter of debate. Neuroradiology and CC have a limited sensitivity with a higher rate of false negative results. FCM demonstrated a superior sensitivity over CC, particularly when low levels of CNS infiltrating cells are present. Although prospective studies of large series of patients are still awaited, a positive finding by FCM appears to anticipate an adverse outcome even if CC shows no infiltration. Current strategies for adult ALL CNS-directed prophylaxis or therapy involve systemic and intrathecal chemotherapy and radiation therapy. Actually, early and frequent intrathecal injection of cytostatic combined with systemic chemotherapy is the most effective strategy to reduce the frequency of CNS involvement. In patients with CNS overt ALL, at diagnosis or upon relapse, allogenic hematopoietic stem cell transplantation might be considered. This review will discuss risk factors, diagnostic techniques for identification of CNS infiltration and modalities of prophylaxis and therapy to manage it. 

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