Curability of Burkitt's lymphoma with high-dose cyclophosphamide-high-dose methotrexate therapy and intrathecal chemoprophylaxis.

1985 ◽  
Vol 3 (5) ◽  
pp. 627-636 ◽  
Author(s):  
M P Sullivan ◽  
I Ramirez
Keyword(s):  
Side Effects ◽  
Complete Remission ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
Disease Stage ◽  
Infusion Therapy ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
High Doses

Twenty-four children with Burkitt's lymphoma were treated beginning May 1976 with a regimen alternating high doses of cyclophosphamide and methotrexate in induction and consolidation; only high doses of methotrexate were used in the maintenance phase. Throughout therapy, which was planned for 54 weeks, intrathecal chemoprophylaxis using methotrexate, cytosine arabinoside, and hydrocortisone was coordinated with the high-dose methotrexate infusion therapy to provide CNS chemoprophylaxis that maintained therapeutic methotrexate spinal fluid levels (greater than 10(-6) mol/L) for approximately 60 hours. Twenty-two (92%) of the 24 children attained complete remission; two (8.3%) patients attained only partial remission, failing therapy. Two children died of infection while in complete remission; two children relapsed on therapy. Actual survival is 75%; the median follow-up time is 38+ months (range, 1 1/2+ to 84+ months). Relapses correlated with Murphy disease stage as follows: stage I--0/3, stage II--2/7, stage III--2/10, and stage IV--0/2. Serious side effects and toxicities of chemotherapy occurred in ten patients (metabolic disturbances after rapid tumor lysis, two; infectious and/or febrile episodes following cyclophosphamide therapy, three; methotrexate side effects, four; and complications of intrathecal therapy, one). Results of this therapy are similar to those of the best regimens that have been reported. Treatment has been adapted for use in Burkitt's lymphoma by the Pediatric Oncology Group; the responsiveness of other B cell lymphomas of childhood to this treatment is also being determined.

scholarly journals Reduced dose folinic acid rescue after rapid high-dose methotrexate clearance is not associated with increased toxicity in a pediatric cohort

2021 ◽  
Author(s):  
Riitta Niinimäki ◽  
Henri Aarnivala ◽  
Joanna Banerjee ◽  
Tytti Pokka ◽  
Kaisa Vepsäläinen ◽  
...  
Keyword(s):  
Folinic Acid ◽  
Lymphoblastic Leukemia ◽  
High Dose ◽  
Optimal Dosage ◽  
High Dose Methotrexate ◽  
Reduced Dose ◽  
Dose Methotrexate ◽  
Antileukemic Effect ◽  
Folinic Acid Rescue ◽  
High Doses

Abstract Purpose Low doses of folinic acid (FA) rescue after high-dose methotrexate (HD-MTX) have been associated with increased toxicity, whereas high doses may be related to a decreased antileukemic effect. The optimal dosage and duration of FA rescue remain controversial. This study was designed to investigate, whether a shorter duration of FA rescue in the setting of rapid HD-MTX clearance is associated with increased toxicity. Methods We reviewed the files of 44 children receiving a total of 350 HD-MTX courses during treatment for acute lymphoblastic leukemia according to the NOPHO ALL-2000 protocol. Following a 5 g/m2 HD-MTX infusion, pharmacokinetically guided FA rescue commenced at hour 42. As per local guidelines, the patients received only one or two 15 mg/m2 doses of FA in the case of rapid MTX clearance (serum MTX ≤ 0.2 μmol/L at hour 42 or hour 48, respectively). Data on MTX clearance, FA dosing, inpatient time, and toxicities were collected. Results Rapid MTX clearance was observed in 181 courses (51.7%). There was no difference in the steady-state MTX concentration, nephrotoxicity, hepatotoxicity, neutropenic fever, or neurotoxicity between courses followed by rapid MTX clearance and those without. One or two doses of FA after rapid MTX clearance resulted in a 7.8-h shorter inpatient time than if a minimum of three doses of FA would have been given. Conclusion A pharmacokinetically guided FA rescue of one or two 15 mg/m2 doses of FA following HD-MTX courses with rapid MTX clearance results in a shorter hospitalization without an increase in toxic effects.

scholarly journals PC3 - 130 A Meta-Analysis on the use of High-Dose Methotrexate Only Versus Combination Chemotherapy for the Treatment of Newly-Diagnosed Patients with Primary CNS Lymphoma

2016 ◽  
Vol 43 (S4) ◽  
pp. S20-S21
Author(s):  
M.C. Concepcion Sales
Keyword(s):  
Side Effects ◽  
Disease Progression ◽  
Combination Chemotherapy ◽  
Primary Cns Lymphoma ◽  
Complete Response ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cochrane Central Register ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

Primary CNS Lymphoma (PCNSL) is an unusual extranodal form of Non-Hodgkin’s Lymphoma with a locally aggressive course but a rare tendency to disseminate systemically. There are various modalities available for the treatment of PCNSL which include chemotherapy, radiotherapy, surgery and immunotherapy. The effectiveness of adding another anti-neoplastic agent to HD-MTX have been optimized in small scale studies yet the “ perfect combination” has yet to be elucidated Objectives: This study aims to 1) compare the response to treatment of monotherapy with high-dose Methotrexate (HD-MTX) versus HD-MTX and an additional anti-neoplastic agent by evaluating complete response, partial response, stable disease and disease progression and 2) to compare the hematologic and non-hematologic side effects among patients subjected to monotherapy vs combination chemotherapy. Methodology: Journals from Medline, EMBASE, Cochrane Central Register of Control Trials (CENTRAL) and other relevant websites (www.clinicaltrials.org) without any restrictions in the year, language and status of publication were searched. Literatures cited by eligible studies and systemic reviews were also checked to identify useful articles. The following Medical Subject Headings (MeSH) were used: ‘primary CNS lymphoma’, ‘treatment’, ‘chemotherapy’ and ‘randomized control trial’. Statistical analysis was performed using the RevMan software version 5.1. Odds ratio (OR) and 95 % confidence interval (95% CI) were used as summary statistics. Results and Conclusion: The use of high-dose methotrexate and another anti-neoplastic agent showed benefit in terms of achieving complete response and delaying disease progression among patients diagnosed with PCNSL. However, the risks of hematologic toxicities such as anemia, neutropenia, thrombocytopenia and infection was higher in patients treated with the combination chemotherapy. Significant non-hematologic side effects such as mucositis was also observed in patients receiving an add-on to high dose methotrexate.

HEMOSTATIC SIDE EFFECTS OF HIGH-DOSE METHOTREXATE IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA

2004 ◽  
Vol 21 (1) ◽  
pp. 77-83 ◽  
Author(s):  
Tunc Fisgin ◽  
Nese Yarali ◽  
Abdurrahman Kara ◽  
Ceyhun Bozkurt ◽  
Dilek Birgen ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Side Effects ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate

scholarly journals Effect of Age on High-Dose Methotrexate Infusion Therapy.

1996 ◽  
Vol 22 (1) ◽  
pp. 38-44
Author(s):  
HIROAKI IKEDA ◽  
KENJI KIHIRA ◽  
NAOHARU KUWATA ◽  
SHIGEAKI ARAI ◽  
YASUHIRO KIMURA ◽  
...  
Keyword(s):  
Infusion Therapy ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Effect Of Age

Rapid infusion of high-dose methotrexate resulting in enhanced penetration into cerebrospinal fluid and intensified tumor response in primary central nervous system lymphomas

1999 ◽  
Vol 91 (2) ◽  
pp. 221-230 ◽  
Author(s):  
Shoju Hiraga ◽  
Norio Arita ◽  
Takanori Ohnishi ◽  
Eiji Kohmura ◽  
Kazumi Yamamoto ◽  
...  
Keyword(s):  
Survival Time ◽  
Tumor Volume ◽  
Tumor Response ◽  
Infusion Therapy ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Rapid Infusion ◽  
Content Type ◽  
Dose Methotrexate ◽  
Fine Print

Object. Twenty-nine nonimmunocompromised patients with primary central nervous system (CNS) lymphoma were treated with high-dose methotrexate (MTX) therapy followed by irradiation. The authors investigated the correlation of infusion schedules with MTX penetration into cerebrospinal fluid (CSF), tumor response, and survival to develop a regimen that would lead to better clinical results.Methods. In this study, 100 mg/kg MTX was administered on either a rapid (3-hour) or regular (6-hour) infusion schedule for two or three cycles. Of 28 assessable patients, a complete or partial response was achieved in 15 (93.8%) of 16 who received rapid and in seven (58.3%) of 12 who received regular infusion therapy (p = 0.034). Rapid infusion significantly increased levels of MTX in the CSF (p < 0.001) and resulted in significant tumor volume reduction (p < 0.001). The mean tumor volume after the first, second, and third cycle of rapid infusion therapy was reduced to 34%, 14%, and 9%, respectively, of the initial volume, whereas the corresponding values were 54%, 42%, and 37% for regular infusion. The reduction between the second and third cycle was small and not significant for either schedule. Despite the longer median survival time in patients who underwent rapid MTX infusion and irradiation (> 60 compared with 20 months), the difference in survival was not significant (p = 0.147) because of the small number of patients enrolled. The median survival time was 39.3 months for all assessable patients who received high-dose MTX and radiation therapy, and the median relapse-free survival time was 35.2 months.Conclusions. Rapid infusion enhanced both MTX penetration into the CSF and tumor response and may improve patient survival. Administration of three or more cycles of therapy should be carefully weighed in terms of cytoreductive benefits.

scholarly journals Is R-CODOX-M/IVAC Inferior to Other Regimens in Burkitt’s Lymphoma: A Single Center Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5448-5448
Author(s):  
Erden Atilla ◽  
Ugur Sahin ◽  
Pinar Ataca ◽  
Atilla Uslu ◽  
Ekin Kircali ◽  
...  
Keyword(s):  
Overall Survival ◽  
Burkitt’S Lymphoma ◽  
Burkitt's Lymphoma ◽  
Disease Stage ◽  
Rank Test ◽  
Published Data ◽  
High Dose ◽  
Disease Characteristics ◽  
Log Rank Test ◽  
Lymphoma Risk

Abstract INTRODUCTION: Though widely used and accepted as a first line regimen, published data regarding R-CODOX-M/IVAC is very limited. Up to date only three prospective studies and one case series have been reported. Herein, we present our institution’s experience with the management of Burkitt’s lymphoma with a special emphasis on the R-CODOX-M/IVAC regimen. METHODS: The files and electronic records of 35 patients diagnosed with Burkitt’s lymphoma between January 2005 and June 2014 were retrospectively revised. RESULTS: The median age at diagnosis was 40 (21-86 years). Male patients constituted 71.4 (n=25). Stage IV disease was present in 60.6% (n=20), and stage I disease in 27.3% (n=9) of the patients. ECOG performance scoring was < 3 in 70.6% (n=24) and Burkitt’s lymphoma risk scoring (availability of complete surgical resection, stage, serum LDH and CNS involvement) > 2 in 58.6% (n=17). The distribution of patients to administered regimens were as follows: R-CODOX-M/IVAC 10 patients (28.6%), HyperCVAD 5 patients (14.3%), R-CHOP 9 patients (25.7%), R-CVP 2 patients (5.7%), CALGB 10002 1 patient (2.9%) and other regimens (high dose methotrexate, high dose cytarabine, vincristine-prednisolone, etc.) 8 patients (23.0%). Median overall survival (OS) was 23.5 (1-114) months and median progression free survival was 17.0 (0-114) months. Relapses occurred in 7 patients (20.0%), mortality in 12 patients (34.3). R-CODOX-M/IVAC group (n=10) was compared to other rituximab containing regimens (R-CHOP, R-CVP) (n=11) and HyperCVAD (n=5) and other rituximab-free regimens (n=9) with respect to patient and disease characteristics, DFS and OS. The disease stage, ECOG performance score and Burkitt’s lymphoma risk score were similar between the four groups (p=0.6, p=0.2 and p=0.2, respectively). However, median OS was 13 (1-42) months in R-CODOX-M/IVAC group and it was significantly lower than other regimens (p=0.04 log rank test). Median PFS was 13 (0-42) months and also lower compared to other regimens, however, the difference was not statistically significant (p=0,1 log rank test). CONCLUSIONS: Burkitt’s lymphoma is currently one of the most aggressive mature B- cell origin lymphomas and there is no consensus on the standard of care. CODOX-M/ IVAC is one of the most frequently used regimen. Adding rituximab is also known to prolong overall survival in this patient population. Though the sample sizes are too small and the drawbacks of the retrospective study design exist, the inferior OS and PFS observed in this study with R-CODOX-M within patients having similar disease characteristics should be taken into account. Further studies comparing the efficiency of currently used regimens are needed to reach a clear conclusion. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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