Central nervous system (CNS) prophylaxis in children with low risk acute lymphoblastic leukemia (all)

Abstract Between 1972 and 1979, 214 children with acute lymphoblastic leukemia and no evidence of central nervous system (CNS) disease prior to CNS prophylaxis were treated with 2400 rad cranial irradiation and concurrent intrathecal methotrexate. Only nine children developed CNS leukemia; five of them in the CNS only and four concurrently in the CNS and another site. Major acute effects of CNS prophylaxis were seizures in seven patients (3%). Sixty-nine children who had a minimum follow-up of 4 yr were evaluable for late effects of therapy. Small cataracts, incomplete regrowth of hair, and learning disabilities were noted. The latter occurred in 18% of patients, an incidence similar to that encountered in a normal community of school-age children. However, the incidence of learning disabilities in patients who were under 5 yr of age at the time of diagnosis was much higher, 35%. We conclude that the combination of cranial irradiation and intrathecal methotrexate was highly efficacious. The incidence and severity of neuropsychologic abnormalities, the principal late morbidity of this treatment program, varies among reporting institutions. Prospective longitudinal studies of neuropsychologic function are necessary to better define the incidence of abnormalities. Future programs should attempt to decrease late morbidity, but must also assure equal efficacy and improve overall disease-free survival.

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Efficacy and morbidity of central nervous system "prophylaxis" in childhood acute lymphoblastic leukemia: eight years' experience with cranial irradiation and intrathecal methotrexate

Blood ◽

10.1182/blood.v61.2.297.bloodjournal612297 ◽

1983 ◽

Vol 61 (2) ◽

pp. 297-303

Author(s):

A Inati ◽

SE Sallan ◽

JR Cassady ◽

S Hitchcock-Bryan ◽

LA Clavell ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Learning Disabilities ◽

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Cranial Irradiation ◽

Intrathecal Methotrexate ◽

Cns Prophylaxis ◽

Late Morbidity ◽

Prospective Longitudinal

Between 1972 and 1979, 214 children with acute lymphoblastic leukemia and no evidence of central nervous system (CNS) disease prior to CNS prophylaxis were treated with 2400 rad cranial irradiation and concurrent intrathecal methotrexate. Only nine children developed CNS leukemia; five of them in the CNS only and four concurrently in the CNS and another site. Major acute effects of CNS prophylaxis were seizures in seven patients (3%). Sixty-nine children who had a minimum follow-up of 4 yr were evaluable for late effects of therapy. Small cataracts, incomplete regrowth of hair, and learning disabilities were noted. The latter occurred in 18% of patients, an incidence similar to that encountered in a normal community of school-age children. However, the incidence of learning disabilities in patients who were under 5 yr of age at the time of diagnosis was much higher, 35%. We conclude that the combination of cranial irradiation and intrathecal methotrexate was highly efficacious. The incidence and severity of neuropsychologic abnormalities, the principal late morbidity of this treatment program, varies among reporting institutions. Prospective longitudinal studies of neuropsychologic function are necessary to better define the incidence of abnormalities. Future programs should attempt to decrease late morbidity, but must also assure equal efficacy and improve overall disease-free survival.

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Second central nervous system prophylaxis in children with acute lymphoblastic leukemia who relapse after elective cessation of therapy.

Journal of Clinical Oncology ◽

10.1200/jco.1983.1.8.471 ◽

1983 ◽

Vol 1 (8) ◽

pp. 471-476 ◽

Cited By ~ 15

Author(s):

G Rivera ◽

S L George ◽

W P Bowman ◽

D Kalwinsky ◽

J Ochs ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Acute Lymphoblastic Leukemia ◽

Treatment Plan ◽

Lymphoblastic Leukemia ◽

Preventive Treatment ◽

Intrathecal Methotrexate ◽

Cns Prophylaxis ◽

Group A ◽

The Central Nervous System

A treatment plan to achieve better disease control in patients with acute lymphoblastic leukemia (ALL) who relapse after elective cessation of therapy was assessed. The principal modifications were (1) a second preventive treatment of the central nervous system (CNS) at relapse and every six weeks throughout therapy, using intrathecal methotrexate with cytosine arabinoside, and (2) a four-week course of systemic chemotherapy given immediately before therapy was stopped a second time. Twenty-four patients were studied. There have been no meningeal relapses, in contrast to seven among 16 similar patients who were retreated without CNS prophylaxis. Although the median length of second hematologic remission was not significantly different from the outcome in the comparison group, a much higher proportion of patients (eight of 24 versus zero of 17) remain in prolonged reinduced complete remission (48-79 months). Children whose first relapse occurred later than six months after cessation of therapy had significantly longer subsequent remissions. These end results establish the value of intrathecal CNS prophylaxis in relapsed ALL and suggest that a late intensive phase of therapy will extend remissions in a substantial proportion of patients.

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Central nervous system morbidity following an initial isolated central nervous system relapse and its subsequent therapy in childhood acute lymphoblastic leukemia.

Journal of Clinical Oncology ◽

10.1200/jco.1985.3.5.622 ◽

1985 ◽

Vol 3 (5) ◽

pp. 622-626 ◽

Cited By ~ 25

Author(s):

J J Ochs ◽

G Rivera ◽

R J Aur ◽

H O Hustu ◽

R Berg ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Cns Infection ◽

Central Nervous System Relapse ◽

Cns Prophylaxis ◽

Cns Relapse ◽

Cranial Nerve Palsies ◽

Cns Toxicity

The frequency and types of major CNS toxicity and morbidity were analyzed in 107 children with acute lymphoblastic leukemia (ALL) following an isolated primary CNS relapse. Seventy-nine (73%) have had multiple subsequent marrow or CNS relapses requiring intensive and prolonged therapy to the CNS. Median survival time is two years. Of these 79 patients, two thirds have had one or more types of major CNS toxicity, including epileptiform seizures (35), moderate to severe structural abnormalities (24 of 27 evaluated), major motor disabilities (9), blindness (2), CNS infection (6), cranial nerve palsies (2), and intracranial lymphoma (2). The remaining 28 patients (26%) have had no or one additional CNS relapse and have received therapy for a median of eight years. One half of this surviving group of patients have had major CNS toxicity, including seizures (9), major motor disability (2), and intracranial calcifications (12/19). When neuropsychologic evaluations were compared between the 28 survivors and 50 of their contemporaries who had been in initial continuous complete remission, the CNS survivors had significantly lower Full Scale IQ scores (83 +/- 16 v 99 +/- 14, P = less than .001) with similarly lower measures of academic performance. The relative contributions of meningeal leukemia itself and intrathecal or radiation therapy to these effects cannot be determined. Since major CNS sequelae occurred in the majority of patients who had a primary isolated CNS relapse, and the frequency of CNS relapse is dependent on the efficacy of the method of CNS prophylaxis, the best method of avoiding major CNS sequelae is the most effective form of CNS prophylaxis.

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Cerebrospinal Fluid Metabolomics of Central Nervous System Leukemia and Acute Lymphoblastic Leukemia for Probing Biomarker Molecules

SSRN Electronic Journal ◽

10.2139/ssrn.3516118 ◽

2020 ◽

Author(s):

Xiaoli Zhang ◽

Sixi Liu ◽

Chunqing Zhu ◽

Yingying Li ◽

Dongli Ma ◽

...

Keyword(s):

Central Nervous System ◽

Cerebrospinal Fluid ◽

Nervous System ◽

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Biomarker Molecules ◽

Central Nervous System Leukemia

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

Cancers ◽

10.3390/cancers13102333 ◽

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.

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

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2014.075 ◽

2014 ◽

Vol 6 (1) ◽

pp. e2014075 ◽

Cited By ~ 22

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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