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

1983 ◽  
Vol 1 (8) ◽  
pp. 471-476 ◽  
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.

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

Blood ◽  
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

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.

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

Blood ◽  
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.

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.

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

1987 ◽  
Vol 13 (10) ◽  
pp. 1443-1449 ◽  
Author(s):  
Philip Littman ◽  
Peter Coccia ◽  
W. Archie Bleyer ◽  
John Lukens ◽  
Stuart Siegel ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Low Risk ◽  
Cns Prophylaxis

Long-term results of the APO protocol (vincristine, doxorubicin [adriamycin], and prednisone) for treatment of mediastinal lymphoblastic lymphoma.

1983 ◽  
Vol 1 (9) ◽  
pp. 537-541 ◽  
Author(s):  
H J Weinstein ◽  
J R Cassady ◽  
R Levey
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Cranial Irradiation ◽  
Lymphoblastic Lymphoma ◽  
Long Term Results ◽  
Intrathecal Methotrexate ◽  
Remission Induction ◽  
The Central Nervous System

Twenty-one patients with biopsy-proven mediastinal lymphoblastic lymphoma were treated with the APO protocol (vincristine, doxorubicin, and prednisone). Treatment consisted of two years of therapy with a modified doxorubicin-containing acute lymphoblastic leukemia regimen with preventive cranial irradiation and intrathecal methotrexate. The median age in the group was 13 years (range, 2.5-22 years). Complete remission was obtained in 20 of 21 patients. Three patients required mediastinal irradiation for successful remission induction. Six patients have subsequently relapsed: two in the central nervous system, one in the central nervous system and testicle, one in the testicle, one in the pleura, and one in the abdomen. The median follow-up is six years (range, 16 months to 9.5 years) and a Kaplan-Meier estimate of disease-free survival at three years is 58% +/- 23% (2 SE).

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