Intrathecal Chemotherapy-Related Myeloencephalopathy in a Young Child with Acute Lymphoblastic Leukemia

A 26-year-old male with a history of pre-B cell acute lymphoblastic leukemia and seizures presented with second relapse of acute lymphoblastic leukemia and central nervous system involvement, 19 years after the initial diagnosis. Over the next two months, the patient received six doses of triple intrathecal chemotherapy (cytarabine, methotrexate, and hydrocortisone), three concurrently with continuous blinatumomab in the second month. Approximately 12 days after blinatumomab initiation, he developed central nervous system toxicity manifesting as speech impairment, altered mental status, incontinence, and diffuse weakness. Blinatumomab was discontinued, and he was started on dexamethasone. Within the next couple of months, his neurologic status recovered, and he was able to perform all of his baseline activities without limitation. Unfortunately, the patient eventually expired after further relapse approximately one year later. To our knowledge, this is the first published case report of severe neurotoxicity in a patient who was given blinatumomab concurrently with intrathecal chemotherapy.

Download Full-text

Traumatic lumbar puncture at diagnosis adversely affects outcome in childhood acute lymphoblastic leukemia

Blood ◽

10.1182/blood.v96.10.3381 ◽

2000 ◽

Vol 96 (10) ◽

pp. 3381-3384 ◽

Cited By ~ 113

Author(s):

Amar Gajjar ◽

Patricia L. Harrison ◽

John T. Sandlund ◽

Gaston K. Rivera ◽

Raul C. Ribeiro ◽

...

Keyword(s):

Treatment Outcome ◽

Acute Lymphoblastic Leukemia ◽

Lumbar Puncture ◽

Lymphoblastic Leukemia ◽

Prognostic Indicator ◽

Intrathecal Chemotherapy ◽

Intrathecal Therapy ◽

Newly Diagnosed ◽

Diagnostic Lumbar Puncture ◽

Blast Cells

Abstract The effect of traumatic lumbar puncture at the time of initial diagnostic workup on treatment outcome in children with newly diagnosed acute lymphoblastic leukemia (ALL) was investigated. The findings of the first 2 lumbar punctures performed on 546 patients with newly diagnosed ALL treated on 2 consecutive front-line studies (1984-1991) at St Jude Children's Research Hospital were retrospectively reviewed. Lumbar punctures were performed at the time of diagnosis and again for the instillation of first intrathecal chemotherapy. The event-free survival (EFS) experience for patients with 1 cerebrospinal fluid (CSF) sample contaminated with blast cells was worse than that for patients with no contaminated CSF samples (P = .026); that of patients with 2 consecutive contaminated CSF samples was particularly poor (5-year EFS = 46 ± 9%). In a Cox multiple regression analysis, the strongest prognostic indicator was 2 consecutive contaminated CSF samples, with a hazard ratio of 2.39 (95% confidence interval, 1.36-4.20). These data indicate that contamination of CSF with circulating leukemic blast cells during diagnostic lumbar puncture can adversely affect the treatment outcome of children with ALL and is an indication to intensify intrathecal therapy.

Download Full-text

Treatment of late bone marrow relapse in children with acute lymphoblastic leukemia: a Pediatric Oncology Group study

Blood ◽

10.1182/blood.v81.3.602.602 ◽

1993 ◽

Vol 81 (3) ◽

pp. 602-609 ◽

Cited By ~ 54

Author(s):

PD Sadowitz ◽

SD Smith ◽

J Shuster ◽

MD Wharam ◽

GR Buchanan ◽

...

Keyword(s):

Bone Marrow ◽

Acute Lymphoblastic Leukemia ◽

Pediatric Oncology ◽

Lymphoblastic Leukemia ◽

Randomized Study ◽

Intrathecal Chemotherapy ◽

Primary Therapy ◽

Oncology Group ◽

Continuation Therapy ◽

Pediatric Oncology Group

Abstract Children with acute lymphoblastic leukemia (ALL) who have completed 2.5 to 3 years of initial chemotherapy have an off-therapy relapse rate of approximately 20%. In an attempt to improve the survival of children with a late bone marrow (BM) relapse (ie, occurring greater than 6 months after cessation of primary therapy), the Pediatric Oncology Group designed a randomized study to compare the efficacy of doxorubicin/prednisone and cytarabine/teniposide in a multidrug retreatment chemotherapy program. Treatment consisted of remission reinduction with vincristine, prednisone, and doxorubicin, central nervous system prophylaxis with triple intrathecal chemotherapy, and continuation therapy (for 132 weeks) with alternating cycles of oral 6- mercaptopurine/methotrexate and intravenous vincristine/cyclophosphamide. Patients received intermittent courses of either prednisone/doxorubicin (regimen 1) or teniposide/cytarabine (regimen 2) during continuation therapy and a late intensification phase with either vincristine, prednisone, and doxorubicin (regimen 1) or teniposide and cytarabine (regimen 2). One hundred two of 105 evaluable patients (97%) achieved a second complete remission. Twenty- eight of 50 patients on regimen 1 have failed compared with 28 or 52 patients on regimen 2 (log-rank analysis, P = .68), indicating that this trial was inconclusive as to which treatment regimen was superior. The overall 4-year event-free survival for children with a late BM relapse was 37% +/- 6%. Age less than 10 years at initial diagnosis (P < or = .001), white blood cell count less than 5,000/microL at relapse (P = .036) and duration of first remission greater than 54 months (P = .039) were independently associated with a more favorable outcome. While the randomized trial was inconclusive, prolonged second complete remissions were secured in more than one-third of children with a late BM relapse of ALL. The prognostic factors identified may help select children with a late BM relapse who can be successfully retreated with chemotherapy alone.

Download Full-text

Long-Term Outcome in Children With Relapsed ALL by Risk-Stratified Salvage Therapy: Results of Trial Acute Lymphoblastic Leukemia-Relapse Study of the Berlin-Frankfurt-Münster Group 87

Journal of Clinical Oncology ◽

10.1200/jco.2005.01.1031 ◽

2005 ◽

Vol 23 (31) ◽

pp. 7942-7950 ◽

Cited By ~ 187

Author(s):

Hagen Graf Einsiedel ◽

Arend von Stackelberg ◽

Reinhard Hartmann ◽

Rüdiger Fengler ◽

Martin Schrappe ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Early Time ◽

Multicenter Trial ◽

Cranial Irradiation ◽

Intrathecal Chemotherapy ◽

Term Outcome ◽

Long Term Outcome ◽

Leukemia Relapse ◽

Time Point

Purpose Approximately 20% of children with acute lymphoblastic leukemia (ALL) suffer a relapse, and their prognosis is unfavorable. Between 1987 and 1990, the multicenter trial Acute Lymphoblastic Leukemia-Relapse Study of the Berlin-Frankfurt-Münster Group (ALL-REZ BFM) 87 was conducted to establish a uniform treatment for these children in Germany and Austria. Patients and Methods Of 207 registered patients, 183 patients were stratified into three groups according to the protocol: A, early bone marrow (BM) relapse (n = 56); B, late BM relapse (n = 101); C, isolated extramedullary relapse (n = 26). Treatment consisted of risk-adapted alternating short-course multiagent systemic and intrathecal chemotherapy, cranial irradiation, if indicated, and conventional maintenance therapy. Additionally, 24 patients with an exceptionally poor prognosis (early BM or any relapse of T-cell ALL) were treated with individual regimens. In 35 patients, stem-cell transplantation was performed. Results The probability of event-free survival (EFS) and overall survival of all registered patients at 15 years was 0.30 ± 0.03 and 0.37 ± 0.03, respectively, with significant differences between the strategic groups (A, 0.18 ± 0.05 and 0.20 ± 0.05; B, 0.44 ± 0.05 and 0.52 ± 0.05; C, 0.35 ± 0.09 and 0.42 ± 0.10). Despite risk-adapted treatment, an early time point of relapse and T-lineage immunophenotype were significant predictors of inferior EFS in uni- and multivariate analyses. Conclusion With the ALL-REZ BFM 87 protocol, more than one-third of patients may be regarded as cured from recurrent ALL with second complete remissions lasting more than 10 years. Immunophenotype and time point of relapse are important prognostic factors that allow us to adapt more precisely treatment intensity to individual prognosis in future trials.

Download Full-text

Acute and long-term neurological complications in children with acute lymphoblastic leukemia

Bangladesh Medical Research Council Bulletin ◽

10.3329/bmrcb.v34i3.1858 ◽

1970 ◽

Vol 34 (3) ◽

pp. 90-93 ◽

Cited By ~ 1

Author(s):

A.T.M. Atikur Rahman ◽

M.A. Mannan ◽

Samia Sadeque

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Treatment Protocol ◽

Neurological Complications ◽

Intrathecal Chemotherapy ◽

High Dose ◽

Remission Period ◽

Dose Methotrexate ◽

Complications Rate

The pattern of acute and long-term neurological complications in 133 children with acute lymphoblastic leukemia (ALL) treated with two treatment protocol was reviewed. Twenty patients developed neurological complications. Nine out of 20 patients received MRC UK ALL X and the remaining 11 received MRC UK ALL XI protocol. There was no difference of neurological complications between MRC UKALL X and UK ALL XI protocol groups. The numbers of patients who developed neurological complications during induction of remission period were 11 of 133 patients (8.2%). 122 patients were observed during the maintenance period of treatment (from 6 months to 36 months). Six out of 122 patients developed neurological complications during this period. 88 patients were followed for a period of up to 6 months after the cessation of chemotherapy, i.e., in the late period. Neurological complications were found in 3 during this period. Neurological complications rate was 4 times higher in the relapsed group than in the no relapsed group (p < 0.05). Systemic chemotherapy (including vincristine, high-dose methotrexate) and intrathecal chemotherapy seem to be the most common predisposing factors.Keywords: Acute lymphoblastic leukemia; children; neurological complicationOnline: 29-1-2009DOI: 10.3329/bmrcb.v34i3.1858Bangladesh Med Res Counc Bull 2008; 34: 90-93

Download Full-text

Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St Jude Children's Research Hospital

Blood ◽

10.1182/blood-2004-04-1616 ◽

2004 ◽

Vol 104 (9) ◽

pp. 2690-2696 ◽

Cited By ~ 310

Author(s):

Ching-Hon Pui ◽

John T. Sandlund ◽

Deqing Pei ◽

Dario Campana ◽

Gaston K. Rivera ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Cumulative Dose ◽

Lower Risk ◽

Lymphoblastic Leukemia ◽

Cranial Irradiation ◽

Intrathecal Chemotherapy ◽

Remission Induction ◽

Cns Relapse ◽

Risk Patients ◽

Total Therapy

Abstract St Jude Total Therapy Study XIIIB for childhood acute lymphoblastic leukemia (ALL) incorporated more stringent risk classification, early intensification of intrathecal chemotherapy, reinduction treatment, and the addition of dexamethasone to postremission therapy to increase the proportion of event-free survivors without jeopardizing their quality of life. Cranial irradiation was reserved for the 12% of patients who had T-cell ALL and a presenting leukocyte count of 100 × 109/L or more, or CNS-3 (5 or more leukocytes/μL with identifiable blast cells in an atraumatic sample or the presence of cranial nerve palsy) status. Among the 247 consecutive patients enrolled in the study, 117 were classified as having lower-risk leukemia and received mainly antimetabolite-based continuation therapy; the 130 cases with higher-risk leukemia received more intensive continuation chemotherapy with multiple drug pairs administered in weekly rotation. The 5-year event-free survival estimate was 80.8% ± 2.6% (SE); the 8-year rate was 78.6% ± 5.8%. The 5-year cumulative risk of an isolated central nervous system (CNS) relapse was 1.7% ± 0.8%, and that of isolated plus combined CNS relapse was 3.0% ± 1.1%. The 5-year cumulative risks of etoposide-related myeloid malignancies were 1.8% ± 1.3% in the lower-risk patients who received a cumulative dose of 1.2 g/m2 and 5.0% ± 2.0% in the higher-risk patients who received a cumulative dose of up to 14.4 g/m2 (P = .18). Independent adverse prognostic features included the presence of MLL-AF4 or BCR-ABL fusion gene and minimal residual leukemia of 0.01% or more at the end of the 6-week remission induction phase. Our results suggest the efficacy of early intensification of intrathecal chemotherapy and provide the basis for studies omitting cranial irradiation altogether. (Blood. 2004;104:2690-2696)

Download Full-text

#395 Sex-related differences in intelligence, memory and learning strategies in children treated for acute lymphoblastic leukemia by brain irradiation and/or intrathecal chemotherapy

Journal of Pediatric Hematology/Oncology ◽

10.1097/00043426-199907000-00073 ◽

1999 ◽

Vol 21 (4) ◽

pp. 322

Author(s):

P. Robaey ◽

S. Prdcourt ◽

Larnothe ◽

A. Moghrabi

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Learning Strategies ◽

Lymphoblastic Leukemia ◽

Intrathecal Chemotherapy ◽

Memory And Learning ◽

Brain Irradiation

Download Full-text

Recurrent perichondritis as a debut «mask» of acute lymphoblastic leukemia in a young child (clinical case)

Modern pediatrics. Ukraine ◽

10.15574/sp.2019.104.83 ◽

2019 ◽

pp. 83-88

Author(s):

N.G. Chumachenko ◽

◽

T.L. Marushko ◽

O.V. Golovchenko ◽

V.N. Fisun ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Young Child ◽

Clinical Case ◽

Lymphoblastic Leukemia

Download Full-text

Extended intrathecal methotrexate may replace cranial irradiation for prevention of CNS relapse in children with intermediate-risk acute lymphoblastic leukemia treated with Berlin-Frankfurt-Münster-based intensive chemotherapy. The Associazione Italiana di Ematologia ed Oncologia Pediatrica.

Journal of Clinical Oncology ◽

10.1200/jco.1995.13.10.2497 ◽

1995 ◽

Vol 13 (10) ◽

pp. 2497-2502 ◽

Cited By ~ 66

Author(s):

V Conter ◽

M Aricò ◽

M G Valsecchi ◽

C Rizzari ◽

A M Testi ◽

...

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Cranial Irradiation ◽

Intrathecal Chemotherapy ◽

Intrathecal Methotrexate ◽

Intermediate Risk ◽

Intensive Chemotherapy ◽

Free Survival ◽

Cns Disease ◽

Cns Relapse

PURPOSE To assess the effect of treatment intensification and that of extended intrathecal methotrexate substitution for cranial irradiation in intermediate-risk acute lymphoblastic leukemia (ALL) children treated with a Berlin-Frankfurt-Münster (BFM)-based intensive chemotherapy. PATIENTS Three hundred ninety-six children with non-B-ALL were enrolled onto the Associazione Italiana di Ematologia ed Oncologic Pediatrica (AIEOP) ALL 88 study. Standard risk (SR) included patients with low tumor burden (BFM risk index [RI], < 0.8); intermediate risk (IR) were patients with an RI > or = 0.8 but less than 1.2; and high risk (HR) were those with an RI > or = 1.2 or CNS involvement at diagnosis. The treatment schedule was a modified version of the ALL-BFM 86 study. CNS-directed treatment consisted of high-dose methotrexate (HD-MTX; 5 g/m2 for four courses) plus intrathecal methotrexate (IT-MTX; nine doses); IR patients additionally received extended IT-MTX (nine doses during continuation therapy); cranial irradiation was given only to HR patients. RESULTS Of the 375 (94.7%) children who achieved remission, 1.3% had an adverse event other than relapse. The estimated event-free survival (EFS) at 6 years was 66.6% (SE 2.4) overall; 80.7% (4.5) in the SR patients, 77.5% (3.9) in the IR patients, and 54.5% (3.7) in the HR patients. Relapse occurred in 107 children (27.0%). Isolated CNS relapse occurred in 20 children (5.0%): 5 (6.3%) in the SR group, 1 (0.8%) in the IR group, and 14 (7.1%) in the HR group. The estimated 6-year CNS leukemia-free survival was 94.6% (1.2) overall: 93.5% (2.8) in the SR group, 99.1% (0.9) in the IR group, and 92.3% (2.0) in the HR group. CONCLUSION Cranial irradiation may be omitted safely in IR ALL patients treated with BFM-based intensive chemotherapy when extended intrathecal chemotherapy is given. Because the CNS disease control was less complete in the SR group, these data challenge the effectiveness of HD-MTX for protection from CNS disease and support the protective role of extended intrathecal chemotherapy.

Download Full-text