International multicenter retrospective analysis of thiotepa-based autologous stem cell transplantation for secondary central nervous system lymphoma

Khwaja, Jahanzaib; Kirkwood, Amy A.; Isbell, Lisa K; Steffanoni, Sara; Goradia, Harshita; Pospiech, Lisa; Fail, Thomas; Nicholson, Emma; Fletcher, Kate; Linton, Kim; Parsons, Katrina; Elmusharaf, Nagah; Eccersley, Lydia; Eyre, Toby A.; Chaganti, Sridhar; Smith, Jeffrey A.; Thakrar, Nisha; Kutilina, Alexandra; Calimeri, Teresa; Martínez‐Calle, Nicolás; El‐Sharkawi, Dima; Osborne, Wendy; Illerhaus, Gerald; Fox, Christopher P.; Ferreri, Andrés J.M.; Schorb, Elisabeth; Cwynarski, Kate

doi:10.3324/haematol.2022.281640

Cited by 14 publications

(14 citation statements)

References 16 publications

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“…The largest series of 134 SCNSL patients undergoing thiotepa-based ASCT reported 3-year overall and progression-free survival rates of 71.6% (95% CI: 61.9%-not reached) and 61.1% (95% CI: 52.2-68.9%), respectively. 56 One-hundred-day non-relapse mortality was 3% and the cumulative incidence at 1 and 3 years was 8.4% (95% CI: 4.7-14.6). The risk factors determining progression after SCNSL were similar to those prior to ASCT.…”

Section: Treatment Approach For Secondary Central Nervous System Lymp...mentioning

confidence: 91%

“… 55 Most patients relapse early and are therefore resistant to primary therapy in both compartments. The minority are chemo-responsive, but those who undergo ASCT have better outcomes (3-year progression-free survival 40%) 56 so this should be the treatment goal. Systemic treatment options include RICE and RDHAP (rituximab, cytarabine, cisplatin and dexamethasone) ( Figure 2 ).…”

Section: Treatment Approach For Secondary Central Nervous System Lymp...mentioning

confidence: 99%

“…Patients who relapsed after ASCT had poor outcomes and time to relapse after ASCT predicted overall survival. 56 …”

Section: Treatment Approach For Secondary Central Nervous System Lymp...mentioning

confidence: 99%

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Prevention and management of secondary central nervous system lymphoma

et al. 2022

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Secondary central nervous system (CNS) lymphoma (SCNSL) is defined by the involvement of the CNS, either at the time of initial diagnosis of systemic lymphoma, or in the setting of relapse, either isolated or with synchronous systemic disease. The risk of CNS involvement in patients with diffuse large B-cell lymphoma is approximately 5%, however, certain clinical and biological features have been associated with a risk of up to 15%. There has been growing interest in improving the definition of patients at increased risk of CNS relapse, as well as identifying effective prophylactic strategies to prevent it. SCNSL often occurs within months of initial lymphoma diagnosis, suggesting presence of occult disease at diagnosis in many cases. The differing presentations of SCNSL present a therapeutic challenge of control of both systemic disease and CNS disease, which uniquely requires agents that penetrate the blood brain barrier. Outcomes are generally poor with a median overall survival of approximately 6 months in retrospective series, particularly those presenting with SCNSL after prior therapy. Prospective studies of intensive chemotherapies containing high-dose methotrexate (HD-MTX), followed by haematopoietic stem cell transplantation have shown the most favourable outcomes, especially for patients receiving thiotepa-based conditioning regimens. However, a proportion of patients will not respond to induction therapies or subsequently relapse, indicating the need for more effective treatment strategies. In this review we focus on the identification of high-risk patients, prophylaxis strategies and recent treatment approaches for SCNSL. The incorporation of novel agents to immunochemotherapy deserves further study in prospective trials.

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Section: Treatment Approach For Secondary Central Nervous System Lymp...mentioning

confidence: 91%

Section: Treatment Approach For Secondary Central Nervous System Lymp...mentioning

confidence: 99%

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Prevention and management of secondary central nervous system lymphoma

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“…The best survival outcomes are for patients with SCNSL who undergo ASCT consolidation 19 . A retrospective study of 134 patients undergoing ASCT (38% TN, 62% R/R) reported a 2‐year PFS of 61%, far exceeding expected outcomes for all patients with SCNSL 32 ; ASCT consolidation is now widely used and routinely incorporated in prospective SCNSL trials (Table 1).…”

Section: Consolidation Autologous Stem Cell Transplantation In Scnslmentioning

confidence: 99%

“…The MARIETTA trial reported a 14% 2‐year PFS for 28 patients with RC‐SCNSL, consistent with other studies of this population. Whilst previous studies report significantly improved outcomes (46% 2‐year PFS) for responding patients receiving consolidation TT‐based ASCT, 32 the majority of patients in MARIETTA did not proceed to ASCT despite an overall response rate (ORR) of 46% 19 . Fitness for intensive treatment, anticipated benefit and patient wishes must be taken into consideration; palliative approaches may be more appropriate for many patients (Figure 2).…”

Section: Treatment Approaches For Scnslmentioning

confidence: 99%

Management of secondary central nervous system lymphoma

et al. 2022

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CNS lymphoma (CNSL) is associated with inferior outcomes, which may be attributed to several factors: poor CNS penetrance of chemotherapeutics, including RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone), 1 impaired neurocognitive function and patient performance status (PS) contributing to increased treatment toxicity, 2,3 and recurrent genetic aberrations conferring treatment resistance. [4][5][6] The rarity and heterogeneity of SCNSL also limits the evidence base for treatment recommendations, with poor outcomes potentially attributable at least in part to lack of optimised treatment protocols.This good practice paper focuses on diffuse large B-cell lymphoma (DLBCL), the most common SCNSL subtype. It covers diagnostic and therapeutic aspects of care for the three SCNSL scenarios and multiply relapsed SCNSL. Treatment recommendations are framed by patient fitness and treatment intent.

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Management of primary and secondary CNS lymphoma

Khwaja

Cwynarski

2023

Hematological Oncology

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Central nervous system (CNS) lymphoma has traditionally had very poor outcomes however advances in management have seen dramatic improvements and long‐term survival of patients. In primary CNS lymphoma there are now randomised trial data to inform practice, however secondary CNS lymphoma has a lack of randomised trial data and CNS prophylaxis remains a contentious area. We describe treatment strategies in these aggressive disorders. Dynamic assessment of patient fitness and frailty is key throughout treatment alongside delivery of CNS‐bioavailable therapy and enrolment in clinical trials. Intensive high‐dose methotrexate‐containing induction followed by autologous stem cell transplantation is preferred for patients who are fit. Less intensive chemoimmunotherapy, whole brain radiotherapy and novel therapies may be reserved for patients unfit or chemoresistant. It is essential to better define patients at increased risk of CNS relapse, as well as effective prophylactic strategies to prevent it. Future prospective studies incorporating novel agents are key.

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International multicenter retrospective analysis of thiotepa-based autologous stem cell transplantation for secondary central nervous system lymphoma

Abstract: Not available.

Cited by 14 publications

References 16 publications

Prevention and management of secondary central nervous system lymphoma

Prevention and management of secondary central nervous system lymphoma

Management of secondary central nervous system lymphoma

Management of primary and secondary CNS lymphoma

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