Impact of front line relative dose intensity for methotrexate and comorbidities in immunocompetent elderly patients with primary central nervous system lymphoma
Jonathan FarhiKamel LaribiCorentin OrvainJean‐François HamelMélanie MercierAurélien Sutra Del GalyAline ClavertMarie‐Christine RousseletAline SchmidtMathilde HunaultMarie‐Pierre Moles‐Moreau
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Keywords:
Univariate analysis
Performance status
Idarubicin
Mitoxantrone
Induction chemotherapy
Regimen
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Summary. The optimal dose of cytarabine for induction chemotherapy is unknown. Most studies have utilized doses of 100–200 mg/m 2 /d, although higher doses have been proposed to increase the concentration of the active metabolite ara‐CTP within leukaemia cells. To address this question 101 adults with newly diagnosed acute myeloid leukaemia were randomized to receive treatment with daunorubicin and either conventional‐dose cytarabine (200 mg/m 2 /d by continuous infusion) or an intermediate‐dose of cytarabine (500 mg/m 2 every 12 h). 36/51 (71%) patients assigned to conventional‐dose cytarabine achieved complete remission compared to 37/50 (74%) who achieved remission with intermediate‐dose cytarabine (P = 0.9). Patient age significantly affected remission rate. 8/17 patients age >60 assigned to conventional‐dose cytarabine and 10/17 assigned to intermediate‐dose cytarabine achieved complete remission compared to 27/33 patients under age 60 assigned to the conventional dose and 28/34 patients assigned to the intermediate dose arm (P=0.004). Actuarial 4‐year disease‐free survival for patients assigned to conventional‐dose cytarabine was 20.16% versus 28.17% for patients assigned to intermediate‐dose cytarabine (P=0–9). We conclude that intermediate dose cytarabine did not substantially improve results of induction chemotherapy for acute myeloid leukaemia.
Induction chemotherapy
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To the Editor.—
In answer to Dr. Auerbach's letter concerning maintenance dosage of methotrexate, I certainly agree that methotrexate should not be maintained when conventional therapy will control the psoriasis. In our article, we pointed out that methotrexate was to be used only in severe cases of psoriasis which were unresponsive to conventional methods of therapy. Certainly, I would agree that methotrexate should be withdrawn as quickly as possible, but clinically this is often impossible. Many patients with severe psoriasis will flare in two to three weeks if their methotrexate is suddenly stopped. We have even seen some cases of rebound with more severe psoriasis as is seen after oral corticosteroid therapy. Our approach has been to maintain the patient on methotrexate 25 mg/week, orally, until their psoriasis is cleared. We then will gradually reduce this dose of methotrexate and attempt to withdraw the drug especially during the summer monthsClearance
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Fifty five patients of extensive psoriasis were treated with oral weekly methotrexate. All patients responded promptly to methotrexate therapy. Relapse was observed after variable periods following stoppage of methotrexate. Safety, efficacy, maintenance dose, relapse and long term effects of methotrexate in psorasis are discussed.
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저자들은 융모성질환의 화학치료에 있어서 methotrexate 치료도중 문제가 될 수 있는 약제의 독성을 줄이고, 내성을 방지하기 위하여 leucovorin rescue를 주는 적절한 시기 및 용량을 결정하고자 methotrexate 포화검사를 시행하여 다음과 같은 결론을 얻었다. 1. Methotrexate혈중치는 methotrexate의 정맥내 주사후 30분에 최고 농도에 달하며, 그 반감기는 5.04±2.05 시간이었다. 2. Methotrexate정맥내 주사후 24시간후와 28시간후에 30mg이 folic acid를 줄때 혈중 methotrexate 평균농도는 24시간후에 50μmole/liter였고, 48시간후에 0.32μmole/liter이었다. 3. Methotrexate치료중 약제의 독성과 반감기를 비교해 본 결과 반감기가 평균보다 긴 경우 그 약제의 독성이 강한 것으로 보이나 통계적인 유효성은 없는 것으로 나타났다. Methotrexate 치료중 약제의 족성과 methotrexate 정맥주사후 48시간의 methotrexate 혈중치를 비교해 본 결과 간독성에 있어서는 유의한 차이가 없으나, 혈액학적 독성에 있어서는 methotrexate 혈중치가 평균보다 높은군이 낮은군에 비해 강한 독성이 나타났다. 이상과 같이 저자들은 methotrexate의 항암화학 요법에 있어서 강한 약제의 독성을 나타낼 가능성이 있는 환자를 알아내는데에 methotrexate 포화검사가 유용하게 쓰일 수 있으며, 약제의 독성을 나타낼 가능성이 큰 환자에 있어서는 methotrexate 혈중농도를 측정하여야 그에 따른 leucovorin rescue를 시행하여야 한다고 결론지었다.
Antifolate
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Objective To investigate the effect of mifepristone in combination with methotrexate for the medical treatment of ectopic pregnancy. Methods All patients with ectopic pregnancy for medical management were analysed retrospectively.Treatment consisted of methotrexate injected intramuscularly and 400 mg of mifepristone, administered orally,compared with a previous group who received only methotrexate alone.Results Success rate was 85% in combination group. Success rate was similar with that in methotrexate alone group.The time until Serum (3- hCG resolution in combination group was(22.64±6.77)d versus(27.22±6.11)d in methotrexate alone group( P 0.05). Conclusion The success rate of mifepristone in combination with methotrexate was similar to that of methotrexate alone. The time until Serum (3 - hCG resolution in combination group was shorter than that in methotrexate alone group.
Medical treatment
Abortifacient
Combination therapy
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We report the first case of primary central nervous system lymphoma (PCNSL) developing in a patient with rheumatoid arthritis (RA) undergoing low-dose methotrexate therapy (LD-MTX). The characteristic clinical management and course in our experience of the present case illustrate the important points about PCNSL in methotrexate-associated lymphoproliferative disorders (MTX-LPD). The number of cases of MTX-LPD in RA patients may increase in the future, since current treatment strategies for RA recommend starting MTX use in early stage RA, and recent insights have tended to show an increase with higher doses.
Lymphoproliferative Disorders
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The main initial and evolutive variables of 133 patients with large-cell lymphoma treated with adriamycin-containing regimens were evaluated for prognostic significance. At the time of analysis, 66 patients had died with the median survival of the series being 48.9 months. Variables associated with poor prognosis in the univariate study were: lymphoma of immunoblastic subtype, advanced Ann Arbor stage, presence of B-symptoms, poor performance status, bulky disease (≥10cm), involvement of two or more extranodal sites, bone marrow infiltration, and high serum LDH levels. In the multivariate analysis, Ann Arbor stage (p < 0.001), bulky disease (p = 0.004), performance status (p = 0.018), and histologic subtype (p = 0.021) retained their prognostic value. After excluding those patients with localized disease (stage I), the Ann Arbor staging system lost prognostic significance in favor of bone marrow infiltration (p = 0.009) and serum LDH (p < 0.001). However, when response to treatment was included in the regression model, it proved to be the most important prognostic factor (p < 0.001), followed by serum LDH (p = 0.004). On the other hand, when the analysis was restricted to complete responders, serum LDH at diagnosis was the only parameter useful to predict survival (p = 0.008). Finally, five recently proposed prognostic classifications were useful to separate different risk-groups of patients when applied to the series.
Univariate analysis
B symptoms
Performance status
International Prognostic Index
Univariate
Prognostic variable
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