Successful treatment of meningeal leukemia using systemic high-dose cytosine arabinoside.

Frick, Jacob; Ritch, Paul S.; Hansen, Richard M.; Anderson, Tom

doi:10.1200/jco.1984.2.5.365

Cited by 69 publications

(13 citation statements)

References 18 publications

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“…22 Moreover, administration of HDCA can maintain therapeutic concentrations of CA even in the cerebrospinal fluid. 23 These pharmacokinetic and pharmacodynamic features of HDCA may explain the reduction of relapse and the prognostic improvement in our study.…”

Section: Discussionsupporting

confidence: 53%

Efficiency of high-dose cytarabine added to CY/TBI in cord blood transplantation for myeloid malignancy

Arai

Takeda

Aoki

et al. 2015

Blood

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Key Points• HDCA plus CY/TBI improved overall survival relative to CY/TBI in CBT for myeloid malignancy.• HDCA suppressed relapse but did not increase the incidence of severe adverse events or nonrelapse mortality.Cord blood transplantation (CBT) is an effective therapeutic option for adults with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) after the conventional cyclophosphamide and total body irradiation (CY/TBI) regimen, but posttransplant relapse is still of high importance. High-dose cytarabine (HDCA) can be added to CY/TBI for an intensified regimen; however, its additional effects have not yet been completely elucidated. Therefore, we conducted a cohort study to compare the prognosis of HDCA/ CY/TBI (n 5 617) and CY/TBI (n 5 312) in CBT for AML/MDS, using a Japanese transplant registry database. The median age was 40 years, and 86.2% of the patients had AML; highrisk disease was observed in 56.2% of the patients. The median follow-up period after CBT was approximately 3.5 years. Overall survival was significantly superior in the HDCA/CY/ TBI group (adjusted hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.45-0.69; P < .01), and tumor-related mortality was lower (HR, 0.50; P < .01). The incidence of grade II to IV acute graft-vs-host disease (aGVHD) and chronic GVHD was significantly higher in the HDCA/CY/TBI group (HR, 1.33 and 2.30, respectively), but not grade III to IV aGVHD. Incidence of infectious episodes showed no significant difference. Nonrelapse mortality was not increased by the addition of HDCA. Higher-dose CA (12 rather than 8 g/m 2 ) was more effective, particularly in patients at high-risk for disease. This study is the first to show the superiority of HDCA/CY/TBI to CY/TBI in CBT for AML/MDS. A large-scale prospective study is warranted to establish new conditioning regimens including HDCA administration. (Blood. 2015;126(3):415-422)

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Section: Discussionsupporting

confidence: 53%

Efficiency of high-dose cytarabine added to CY/TBI in cord blood transplantation for myeloid malignancy

Arai

Takeda

Aoki

et al. 2015

Blood

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“…The high frequency of leptomeningeal relapse observed in our study suggests that a high-dose cytarabine-containing regimen might be employed as cytoreductive chemotherapy before DLI, reducing the likelihood of relapse at this site by increasing the level of drug in the cerebrospinal fluid. 46 Alternatively, intrathecal chemotherapy using methotrexate or cytarabine could be considered for the same purpose. The effectiveness of these therapeutic approaches for reducing leptomeningeal relapse after Chemo-DLI should be evaluated in future studies.…”

Section: Figurementioning

confidence: 99%

Treatment of relapsed acute myeloid leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF-primed donor leukocyte infusion: a high incidence of isolated extramedullary relapse

et al. 2004

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For patients with acute myeloid leukemia (AML) relapsed after allogeneic bone marrow transplantation (BMT), donor leukocyte infusion (DLI) as sole therapy has very limited efficacy. We tested the effects of cytoreductive chemotherapy, followed immediately by G-CSF-primed DLI (chemotherapy followed by DLI, Chemo-DLI), in 16 AML patients who relapsed after allogeneic BMT. In all, 10 of these patients achieved complete remission (CR), four of whom remain alive in CR at a median follow-up of 1488 days after DLI. The 2-year overall survival (OS) for the entire cohort was 31%. The 1-year OS for patients with post-BMT remission of 6 months or longer was 55%, compared with 0% for patients with post-BMT remission of less than 6 months, making post-BMT remission duration the only significant prognostic factor for OS (P ¼ 0.015). These findings suggest that Chemo-DLI could induce durable remissions in a proportion of relapsed AML patients with relatively long post-BMT remission duration. All five patients who relapsed after achieving CR with Chemo-DLI relapsed at extramedullary sites in the presence of continuous bone marrow remission, suggesting uneven graft-versus-leukemia effects in different parts of the body. Although our data should be interpreted cautiously considering the limited number of patients, isolated extramedullary relapse seems to be common after Chemo-DLI.

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“…Systemic chemotherapy for neoplastic meningitis often fails because of poor CSF penetration of nearly all chemotherapeutic agents and difficulty in achieving a significant intra-CSF drug exposure interval [32][33][34][35][36][37][38][39][40][41][42][43]. Exceptions include systemic high-dose intravenous methotrexate, cytarabine, and thiotepa, all of which result in cytotoxic CSF levels and have been used successfully to treat neoplastic meningitis (Table 1).…”

Section: Systemic Therapymentioning

confidence: 99%

“…Several approaches for systemic cytarabine administration have been used. A regimen of 3 g/m 2 administered every 12 hours demonstrated activity in patients with meningeal leukemia [35], and 72-hour continuous intravenous infusion of doses greater than or equal to 4 g/m 2 achieved cytotoxic CSF cytarabine concentrations [36]. High-dose systemic cytarabine administration is associated with significant toxicity, with severe myelosuppression nearly universal.…”

Section: Cytarabinementioning

confidence: 99%

Systemic chemotherapy, intrathecal chemotherapy, and symptom management in the treatment of leptomeningeal metastasis

Berg

Chamberlain

2003

Curr Oncol Rep

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Metastasis to the leptomeninges occurs in many common cancers, including leukemia; lung, breast, and gastrointestinal cancers; and tumors of the brain. By way of the flow of cerebrospinal fluid, leptomeningeal metastasis spreads throughout the neuraxis. Consequently, therapy for leptomeningeal metastasis must be directed to the entire central nervous system (CNS). Treatment often consists of involved-field radiotherapy, systemic chemotherapy, and intrathecal chemotherapy. However, because meningeal spread occurs most often in advanced disease, treatment is mainly palliative, except in childhood leukemia, where durable remission has been reported. This article outlines the role of systemic and intrathecal chemotherapy in patients with leptomeningeal metastases. Strategies for symptom management in these patients are also described.

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Successful treatment of meningeal leukemia using systemic high-dose cytosine arabinoside.

Cited by 69 publications

References 18 publications

Efficiency of high-dose cytarabine added to CY/TBI in cord blood transplantation for myeloid malignancy

Efficiency of high-dose cytarabine added to CY/TBI in cord blood transplantation for myeloid malignancy

Treatment of relapsed acute myeloid leukemia after allogeneic bone marrow transplantation with chemotherapy followed by G-CSF-primed donor leukocyte infusion: a high incidence of isolated extramedullary relapse

Systemic chemotherapy, intrathecal chemotherapy, and symptom management in the treatment of leptomeningeal metastasis

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