Randomized trial of radiation-free central nervous system prophylaxis comparing intrathecal triple therapy with liposomal cytarabine in acute lymphoblastic leukemia

Bassan, Renato; Masciulli, Arianna; Intermesoli, Tamara; Audisio, Ernesta; Rossi, Giuseppe; Pogliani, Enrico Maria; Cassibba, Vincenzo; Mattei, Daniele; Romani, Claudio; Cortelezzi, Agostino; Corti, Consuelo; Scattolin, Anna Maria; Spinelli, Orietta; Tosi, Manuela; Parolini, Margherita; Marmont, Filippo; Borlenghi, Erika; Fumagalli, Monica; Cortelazzo, Sergio; Gallamini, Andrea; Marfisi, Rosa Maria; Oldani, Elena

doi:10.3324/haematol.2014.123273

Cited by 27 publications

(18 citation statements)

References 28 publications

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“…In fact, in our series we observed only a 34% of AEs, mostly grade 1–2. This compares favourably to other recent series that present a 60% of AEs without dexamethasone arm vs 44.4% in dexamethasone arm[21]. Other studies also reported a high rate of AEs (63.1% to 79.2%) after ITLC administration[18,19,24].…”

Section: Discussionsupporting

confidence: 79%

Analysis of the role of intratecal liposomal cytarabine in the prophylaxis and treatment of central nervous system lymphomatosis: The Balearic Lymphoma Group experience

et al. 2017

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Central nervous system (CNS) lymphomatosis is a fatal complication of aggressive non-Hodgkin lymphoma (NHL). In lymphoblastic or Burkitt lymphoma, without specific CNS prophylaxis the risk of CNS relapse is 20–30%. DLBCL has a lower risk of relapse (around 5%) but several factors increase its incidence. There is no consensus or trials to conclude which is the best CNS prophylaxis. Best results seem to be associated with the use of intravenous (iv) high-dose methotrexate (HDMTX) but with a significant toxicity. Other options are the administration of intrathecal (IT) MTX, cytarabine or liposomal cytarabine (ITLC). Our aim is to analyze the experience of the centers of the Balearic Lymphoma Group (BLG) about the toxicity and efficacy of ITLC in the prophylaxis and therapy of CNS lymphomatosis. We retrospectively reviewed cases from 2005 to 2015 (n = 58) treated with ITLC. Our toxicity results were: 33% headache, 20% neurological deficits, 11% nausea, 9% dizziness, 4% vomiting, 4% fever, 2% transient blindness and 2% photophobia. In the prophylactic cohort (n = 26) with a median follow-up of 55 months (17–81) only 3 CNS relapses (11%) were observed (testicular DLBCL, Burkitt and plasmablastic lymphoma, with a cumulative incidence of 8%, 14% and 20% respectively). In the treatment cohort (n = 32), CSF complete clearance was obtained in 77% cases. Median OS was 6 months (0–16). Death causes were lymphoma progression (19 patients, 79%), treatment toxicity (2 patients) and non-related (3 patients, 12%). Toxicity profile was good especially when concomitant dexamethasone was administered. In the prophylactic cohort the incidence of CNS relapse in DLBCL group was similar to previously reported for HDMTX and much better than IT MTX. A high number of ITLC injections was associated with better rates of CSF clearance, clinical responses, PFS and lower relapses. Survival is still poor in CNS lymphomatosis and new therapeutic approaches are still needed.

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Section: Discussionsupporting

confidence: 79%

Analysis of the role of intratecal liposomal cytarabine in the prophylaxis and treatment of central nervous system lymphomatosis: The Balearic Lymphoma Group experience

et al. 2017

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“…However, CNS relapse rates were consistently low (1.2–3%), suggesting that even in adult patients radiotherapy could be safely omitted when intrathecal prophylaxis is associated with systemic HD‐MTX and cytarabine. A very effective radiation‐free prophylaxis combining MTX 5 g/m 2 with intrathecal liposome‐associated cytarabine was recently reported in adult ALL (CNS relapse 0% in T‐ALL) .…”

Section: Cns Prophylaxismentioning

confidence: 99%

Lymphoblastic lymphoma: an updated review on biology, diagnosis, and treatment

Bassan

Maino

Cortelazzo

2016

European J of Haematology

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Lymphoblastic lymphoma is a rare aggressive neoplasm of T-/B-precursors resembling acute lymphoblastic leukemia, with no or limited bone marrow involvement (<25%), that develops more frequently in children and young adults and is typically characterized by a grossly enlarged mediastinum, and whose diagnostic hallmark is the expression of a T-/B-precursor cell immunophenotype, the T-cell subset accounting for 90% of all cases. The adoption of pediatric-derived, intensive lymphoblastic leukemia-like protocols led to significantly improved results, with survival rates of about 70% and 90% in adults and children, respectively. Adequate central nervous system prophylaxis and mediastinal irradiation contributed to the therapeutic success; however, the role of radiation therapy is debated due to toxicity concerns and the excellent results obtained with radiation-free programs especially in pediatric patients. With these modern schedules, localized radiotherapy and/or hematopoietic stem cell transplants could be generally omitted, and considered only for high-risk patients identified through postinduction computed tomography/positronemission tomography scans, minimal residual disease analysis, and new genetics and genomics. New clinical studies will have to confirm the value of these assays for risk-oriented therapy, while further therapeutic progress is expected from the introduction of new drugs and targeting agents.

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“…While the last study (NCT01044966) was terminated due to lack of adequate patient enrollment into trial, four studies were available for acute lymphoblastic leukemia. One was suspended (due to sterility problems in DepoCyt production), one was terminated (due to lack of adequate patient enrollment into trial), one was defined as 'unknown' (the principal investigator did not report necessary info or update the file), and only one (NCT00795756) had results which have been published in Haematologica [87]. This last study compared intrathecal DepoCyt with triple intrathecal therapy (TIT) (Methotrexate 12.5 mg + Cytarabine 50 mg + Prednisolone 40 mg injected intrathecally).…”

Section: Preclinical Data and Researchmentioning

confidence: 99%

Liposomal Cytarabine as Cancer Therapy: From Chemistry to Medicine

et al. 2019

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Cancer is the second leading cause of death worldwide. The main modality to fight against cancer is surgery, radiotherapy, and chemotherapy, and more recently targeted therapy, gene therapy and immunotherapy, which play important roles in treating cancer patients. In the last decades, chemotherapy has been well developed. Nonetheless, administration of the drug is not always successful, as limited drug dosage can reach the tumor cells.. In this context, the possibility to use an encapsulated anti-cancer drug may potentially solve the problem. Liposomal cytarabine is a formulation with pronounced effectiveness in lymphomatous meningitis and reduced cardiotoxicity if compared to liposomal anthracyclines. Thus, the future liposomal cytarabine use could be extended to other diseases given its reduction in cytotoxic side effects compared to the free formulation. This review summarizes the chemistry and biology of liposomal cytarabine, with exploration of its clinical implications.

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Randomized trial of radiation-free central nervous system prophylaxis comparing intrathecal triple therapy with liposomal cytarabine in acute lymphoblastic leukemia

Cited by 27 publications

References 28 publications

Analysis of the role of intratecal liposomal cytarabine in the prophylaxis and treatment of central nervous system lymphomatosis: The Balearic Lymphoma Group experience

Analysis of the role of intratecal liposomal cytarabine in the prophylaxis and treatment of central nervous system lymphomatosis: The Balearic Lymphoma Group experience

Lymphoblastic lymphoma: an updated review on biology, diagnosis, and treatment

Liposomal Cytarabine as Cancer Therapy: From Chemistry to Medicine

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