Primary Lymphosarcoma of the Larynx in a Child

1978 ◽  
Vol 87 (5_suppl) ◽  
pp. 20-24 ◽  
Author(s):  
Seymour R. Cohen ◽  
Benjamin H. Landing ◽  
Stephen Feig ◽  
William J. Byrne ◽  
Hart Isaacs
Keyword(s):  
Bone Marrow ◽  
Cranial Irradiation ◽  
Intrathecal Methotrexate ◽  
Local Irradiation ◽  
Suspected Sepsis ◽  
Bone Marrow Depression ◽  
Cns Prophylaxis ◽  
History Of ◽  
Caucasian Female ◽  
Gastrointestinal Ulceration

A 4 7/12-year-old Caucasian female with a history of “croup-like symptoms” and persistent airway obstruction, was found to have a primary lymphosarcoma by biopsy at the time of laryngoscopy and bronchoscopy. No metastatic disease was found. After an induction course of vincristine, prednisone and local irradiation, she received CNS prophylaxis with intrathecal methotrexate and cranial irradiation. Maintenance therapy, administered over a 2¾ year period, consisted of cyclophosphamide, methotrexate, and 6-mercaptopurine. Excluding the diagnostic evaluation, she was hospitalized only once for the management of suspected sepsis, gastrointestinal ulceration and severe bone marrow depression. Since discontinuing treatment 27 months ago, she has remained free of disease.

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.

Successful therapy of convoluted T-lymphoblastic lymphoma in the adult

Blood ◽  
1983 ◽  
Vol 61 (1) ◽  
pp. 92-98
Author(s):  
AM Levine ◽  
SJ Forman ◽  
PR Meyer ◽  
SC Koehler ◽  
H Liebman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Median Survival ◽  
Bone Marrow Involvement ◽  
Cranial Irradiation ◽  
Lymphoblastic Lymphoma ◽  
Intrathecal Methotrexate ◽  
Induction Phase ◽  
Relapse Free Survival ◽  
Free Survival ◽  
T Lymphoblastic Lymphoma

Fifteen adult patients with biopsy-proven convoluted T-lymphoblastic lymphoma were treated with an aggressive regimen, modified from the LSA2-L2 protocol used for childhood lymphoma. The treatment schema consisted of induction phase, including cyclophosphamide, vincristine, prednisone, adriamycin, and 2000 rads to mediastinum, as well as intrathecal methotrexate. Consolidation phase included cytosine arabinoside, 6-thioguanine, L-asparaginase, and CCNU, along with cranial irradiation and further intrathecal methotrexate. Maintenance consisted of cyclical chemotherapy and intrathecal methotrexate, continuing for a total of 3 yr. Median age in the group was 25 yr (range 16–73). There were 8 males and 7 females. At diagnosis, 9 patients had mediastinal involvement, and 9 had bone marrow involvement. Five of these demonstrated malignant cells in the peripheral blood. Complete clinical response was attained in 11 patients. Three patients achieved partial response. Four complete responders have relapsed, 1 in the central nervous system at 6 mo. and 1 in nodal sites at 3 mo, 1 in multiple sites at 24 mo. and 1 in bone marrow at 42 mo while off all chemotherapy for 6 mos. At this time, median survival of all patients is 28.3 mo. and median relapse-free survival is 21 mo. The median survival for complete responders in excess of 71 mo. while the median relapse-free survival for this group is 41 mo.

Long-term evaluation of a CNS prophylaxis trial--treatment comparisons and outcome after CNS relapse in childhood ALL: a report from the Childrens Cancer Study Group.

1987 ◽  
Vol 5 (10) ◽  
pp. 1646-1654 ◽  
Author(s):  
J A Ortega ◽  
M E Nesbit ◽  
H N Sather ◽  
L L Robison ◽  
G J D'Angio ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Current Status ◽  
Intrathecal Methotrexate ◽  
Childhood All ◽  
Cns Disease ◽  
Cns Prophylaxis ◽  
Cns Relapse ◽  
Significant Difference

The current status of children with acute lymphoblastic leukemia (ALL) who had developed CNS disease while being treated on protocol CCG-101 was investigated. Seven hundred thirty-six eligible patients were entered into the study between June 1972 and July 1974. All children who were greater than 18 months of age were eligible for randomization to a CNS prophylaxis trial for which one regimen gave only a short course of intrathecal methotrexate (IT MTX) as prophylaxis. All other regimens included radiation therapy as prophylaxis. Current follow-up (median, greater than 10 years) shows no significant difference by standard life-table analysis for ultimate survival, although a substantial excess of CNS episodes occurred on the IT MTX regimen. Of the 675 patients who completed induction therapy and achieved remission in the study, 100 (14.8%) developed CNS disease as the first evidence of relapse. Fifty-five of these 100 had no subsequent CNS episodes. Only 17 of these 55 patients are surviving without further relapses since the CNS episode. The median time to isolated CNS relapse was 457 days. Time to the initial CNS relapse was found to be the most important factor for predicting outcome. Thirty-five of the 55 patients with isolated relapse subsequently relapsed in the bone marrow, and of these, 32 have died. Twenty patients of the 100 with CNS disease as the first evidence of relapse developed two episodes of CNS involvement and 17 of these 20 patients subsequently relapsed in the bone marrow; only one patient survived. Twenty-five patients of the 100 have shown a pattern of chronic CNS disease with multiple CNS relapses. The overall disease-free survival for the 100 patients who developed one or more relapse was only 16%. These data demonstrate that the occurrence of a CNS relapse is an indicator of poor subsequent outcome. Comparison of results of groups receiving different CNS prophylaxis required careful consideration of the entire pattern of relapses and mortality.

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.

Intermediate Dose Intravenous Methotrexate (MTX) Dramatically Reduces the Risk of Secondary Central Nervous System (CNS) Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3442-3442
Author(s):  
Ephraim P. Hochberg ◽  
Peter Hammerman ◽  
Tak Takvorian ◽  
Christiana Toomey ◽  
James Michaelson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Bone Marrow ◽  
Intrathecal Methotrexate ◽  
Cns Lymphoma ◽  
High Dose ◽  
Expected Number ◽  
Cns Prophylaxis ◽  
Extranodal Site ◽  
Dose Methotrexate ◽  
Intermediate Dose

Abstract Secondary CNS lymphoma (SCNSL) is a rare complication of diffuse large B cell non-Hodgkins lymphoma (DLBCL) which is almost universally fatal. Several groups have analyzed risk factors for the development of SCNSL and published risk estimates for both individual anatomic sites of DLBCL as well as combinations of clinical risk factors. Although the rates of SCNSL for all DLBCL patients range from 2.5% to 5% subgroups can be identified with risks as high as 33%. High risk scenarios where CNS prophylaxis is most commonly offered include either a combination of an elevated LDH and more than one extranodal site of disease, or disease involving the bone marrow, testicle, sinus, orbit, or a para-spinal location. The type of prophylaxis used varies widely from intrathecal to high-dose intravenous methotrexate as well as intrathecal use of cytarabine. Despite the advances made in the systemic therapy of DLBCL there is very limited data on the efficacy of these chemopreventive regimens in SCNSL. We undertook a retrospective review at our institution of all patients with DLBCL treated with inpatient intermediate dose methotrexate (3.5 grams per meter squared) followed by leucovorin rescue between 2002 and 2006 for CNS prophylaxis. We found 37 patients. Of 15 patients initially evaluated with diagnostic lumbar punctures (LP), no patient had a positive CSF cytology. The median age of the patients was 59 (26–79). The average IPI was 3. All patients were tested for HIV and 3 were found to be positive. The indications for CNS prophylaxis were primarily an elevated LDH and more than 1 extranodal site of disease (20) but also included patients with bone marrow (9), testicular (3), orbital (5), para-spinal (2) and sinus (6) involvement, with 6 patients having more than one site of involvement. All patients received an anthracycline containing chemotherapy regimen with curative intent. Thirty-six patients received rituximab. Patients received a median of 6 cycles of systemic chemotherapy and 3 courses of MTX given on day 15 of alternating cycles (usually 2, 4 and 6). In addition 2 patients received a single dose of 12 mg of intrathecal methotrexate at the time of their initial LP and 5 patients received intrathecal liposomal cytarabine. We calculated the expected number of cases of SCNSL using the estimates from van Besien et al. Blood ‘98, Hollender et al. Ann Onc ‘02, and Boehme et al. Ann Onc ‘06 as appropriate depending on the sites of disease for each patient. For this population the expected number of cases of SCNSL was 7.98 and the observed number of cases was 1 (p=.002 two-sided binomial probability). In this population of 37 patients with an elevated risk of SCNSL, the use of intravenous intermediate dose methotrexate substantially reduced their risk of this fatal complication.

scholarly journals Successful therapy of convoluted T-lymphoblastic lymphoma in the adult

Blood ◽  
1983 ◽  
Vol 61 (1) ◽  
pp. 92-98 ◽  
Author(s):  
AM Levine ◽  
SJ Forman ◽  
PR Meyer ◽  
SC Koehler ◽  
H Liebman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Median Survival ◽  
Bone Marrow Involvement ◽  
Cranial Irradiation ◽  
Lymphoblastic Lymphoma ◽  
Intrathecal Methotrexate ◽  
Induction Phase ◽  
Relapse Free Survival ◽  
Free Survival ◽  
T Lymphoblastic Lymphoma

Abstract Fifteen adult patients with biopsy-proven convoluted T-lymphoblastic lymphoma were treated with an aggressive regimen, modified from the LSA2-L2 protocol used for childhood lymphoma. The treatment schema consisted of induction phase, including cyclophosphamide, vincristine, prednisone, adriamycin, and 2000 rads to mediastinum, as well as intrathecal methotrexate. Consolidation phase included cytosine arabinoside, 6-thioguanine, L-asparaginase, and CCNU, along with cranial irradiation and further intrathecal methotrexate. Maintenance consisted of cyclical chemotherapy and intrathecal methotrexate, continuing for a total of 3 yr. Median age in the group was 25 yr (range 16–73). There were 8 males and 7 females. At diagnosis, 9 patients had mediastinal involvement, and 9 had bone marrow involvement. Five of these demonstrated malignant cells in the peripheral blood. Complete clinical response was attained in 11 patients. Three patients achieved partial response. Four complete responders have relapsed, 1 in the central nervous system at 6 mo. and 1 in nodal sites at 3 mo, 1 in multiple sites at 24 mo. and 1 in bone marrow at 42 mo while off all chemotherapy for 6 mos. At this time, median survival of all patients is 28.3 mo. and median relapse-free survival is 21 mo. The median survival for complete responders in excess of 71 mo. while the median relapse-free survival for this group is 41 mo.

5-Fluorouracil toxicosis in cats and dogs

2019 ◽  
Vol 24 (6) ◽  
pp. 288-292
Author(s):  
Nicola Bates
Keyword(s):  
Bone Marrow ◽  
Companion Animals ◽  
Skin Lesions ◽  
Therapeutic Window ◽  
Bone Marrow Depression ◽  
Malignant Skin ◽  
Neurological Effects ◽  
And Control ◽  
Supportive Management ◽  
Gastrointestinal Ulceration

5-Fluorouracil is an antineoplastic drug with a narrow therapeutic window. Pets are commonly exposed to the cream used for pre-malignant and malignant skin lesions in humans. 5-Fluorouracil poisoning is characterised by severe gastrointestinal (vomiting; diarrhoea; and gastrointestinal ulceration and haemorrhage) and neurological effects (ataxia, tremors and convulsions), and from 4–7 days bone marrow depression. Progression of signs can be rapid and control of neurological effects can be refractory to treatment. There is no specific antidote suitable for companion animals with 5-fluorouracil toxicosis, and aggressive supportive management is required. Filgrastim (a human granulocyte colony stimulating factor) can be used in the management of severe bone marrow depression, but prognosis is generally poor in dogs and cats with pronounced signs from 5-fluorouracil poisoning.

scholarly journals Impact of Intrathecal Triple Therapy Versus Intrathecal Methotrexate on Disease-Free Survival for High-Risk B-Lymphoblastic Leukemia: Children’s Oncology Group Study AALL1131

2020 ◽  
Vol 38 (23) ◽  
pp. 2628-2638
Author(s):  
Wanda L. Salzer ◽  
Michael J. Burke ◽  
Meenakshi Devidas ◽  
Yunfeng Dai ◽  
Kristina K. Hardy ◽  
...  
Keyword(s):  
Bone Marrow ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Intrathecal Methotrexate ◽  
Oncology Group ◽  
Free Survival ◽  
Oncology Group Study ◽  
Cns Prophylaxis ◽  
Disease Free

PURPOSE The high-risk stratum of Children’s Oncology Group Study AALL1131 was designed to test the hypothesis that postinduction CNS prophylaxis with intrathecal triple therapy (ITT) including methotrexate, hydrocortisone, and cytarabine would improve the postinduction 5-year disease-free survival (DFS) compared with intrathecal methotrexate (IT MTX), when given on a modified augmented Berlin-Frankfurt-Münster backbone. PATIENTS AND METHODS Children with newly diagnosed National Cancer Institute (NCI) high-risk B-cell acute lymphoblastic leukemia (HR B-ALL) or NCI standard-risk B-ALL with defined minimal residual disease thresholds during induction were randomly assigned to receive postinduction IT MTX or ITT. Patients with CNS3-status disease were not eligible. Postinduction IT therapy was given for a total of 21 to 26 doses. Neurocognitive assessments were performed during therapy and during 1 year off therapy. RESULTS Random assignment was closed to accrual in March 2018 after a futility boundary had been crossed, concluding that ITT could not be shown to be superior to IT MTX. The 5-year postinduction DFS and overall survival rates (± SE) of children randomly assigned to IT MTX versus ITT were 93.2% ± 2.1% v 90.6% ± 2.3% ( P = .85), and 96.3% ± 1.5% v 96.7% ± 1.4% ( P = .77), respectively. There were no differences in the cumulative incidence of isolated bone marrow relapse, isolated CNS relapse, or combined bone marrow and CNS relapse rates, or in toxicities observed for patients receiving IT MTX compared with ITT. There were no significant differences in neurocognitive outcomes for patients receiving IT MTX compared with ITT. CONCLUSION Postinduction CNS prophylaxis with ITT did not improve 5-year DFS for children with HR B-ALL. The standard of care for CNS prophylaxis for children with B-ALL and no overt CNS involvement remains IT MTX.

A prospective comparison of neuropsychologic performance of children surviving leukemia who received 18-Gy, 24-Gy, or no cranial irradiation.

1991 ◽  
Vol 9 (8) ◽  
pp. 1348-1356 ◽  
Author(s):  
R K Mulhern ◽  
D Fairclough ◽  
J Ochs
Keyword(s):  
Lymphoblastic Leukemia ◽  
Cranial Irradiation ◽  
Intrathecal Methotrexate ◽  
Specific Method ◽  
Significant Deterioration ◽  
Cns Prophylaxis ◽  
Prospective Comparison ◽  
Increased Risk ◽  
Patients At Risk ◽  
Clinically Significant

To compare the late neuropsychologic toxicities of CNS prophylaxis for childhood acute lymphoblastic leukemia (ALL), longitudinal assessments were performed on three groups of patients: those who received repeated courses of moderate-dose (1 g/m2) intravenous (IV) and intrathecal methotrexate (IT MTX) without cranial irradiation (MTX group, n = 26), those who received IT MTX and 18 Gy cranial irradiation (18-Gy group, n = 23), and those who received IT MTX and 24 Gy cranial irradiation (24-Gy group, n = 28). All patients were free of CNS leukemia at diagnosis and had remained in continuous, complete remission 5 to 11 years (median, 7.4 years) following CNS prophylaxis. An analysis of serial intelligence quotient (IQ), achievement, and neuropsychologic studies revealed no significant influence of either age at CNS prophylaxis or CNS prophylaxis group on any neuropsychologic outcome measure. After adjusting for changes in IQ test versions that were necessitated by advancing patient age, no statistically significant declines in Verbal, Performance, or Full Scale IQs were noted for the three CNS treatment groups. However, comparisons of group means masked declines in individual children; 22% to 30% of children exhibited a clinically significant deterioration (greater than or equal to 15 points) in uncorrected IQ values over the study period. Female sex was associated with an increased risk of deterioration in Verbal IQ, but we were unable to identify risk factors associated with other declines in intellect and achievement. The inability to reliably predict individual patients at risk for clinically significant neuropsychologic toxicities on the basis of age at diagnosis or specific method of CNS prophylaxis suggests that other etiologic factors must be explored as the basis for these changes, such as ecologic factors and chemotherapy during the continuation phase of treatment.

The importance of an isolated central nervous system relapse in children with acute lymphoblastic leukemia.

1985 ◽  
Vol 3 (6) ◽  
pp. 776-781 ◽  
Author(s):  
S L George ◽  
J J Ochs ◽  
A M Mauer ◽  
J V Simone
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Fold Increase ◽  
Cranial Irradiation ◽  
Preventive Therapy ◽  
Intrathecal Methotrexate ◽  
Central Nervous System Relapse ◽  
Cns Prophylaxis ◽  
Cns Relapse ◽  
Therapy Studies

We assessed the influence of an initial isolated meningeal relapse on treatment outcome in 839 children with acute lymphoblastic leukemia (ALL) who were admitted to St Jude Children's Research Hospital (Memphis) from mid-1967 through mid-1979. The patients were entered in a series of five clinical trials (Total Therapy Studies V through IX), each designed to test one or more modifications of treatment for ALL. Two groups were compared: 699 children who received CNS prophylaxis (2,400-rad craniospinal irradiation or 2,400-rad cranial irradiation plus intrathecal methotrexate) v 56 who did not. Our results, obtained with a time-dependent covariate model and a matching technique, indicate a 2 to 3.5-fold increase in the risk of hematologic relapse or death among patients who experienced an isolated CNS relapse compared with similar patients (matched for leukocyte count and length of complete remission) who remained free of CNS involvement. Of the 107 children with an initial isolated CNS relapse, 89 (83%) have died or have had a subsequent relapse. There was no detectable difference in the rate of hematologic relapse or death after a CNS relapse between patients who had received preventive therapy and those who had not. We conclude that CNS prophylaxis is important both for the prevention of initial CNS leukemia and for reducing the risk of hematologic relapse or death subsequent to a CNS relapse.

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