Autologous Stem-Cell Transplantation for Primary Central Nervous System Lymphoma: Systematic Review and Meta-analysis

Alnahhas, Iyad; Jawish, Mohammad; Alsawas, Mouaz; Zukas, Alicia M.; Prokop, Larry J.; Murad, M. Hassan; Malkin, Mark G.

doi:10.1016/j.clml.2018.11.018

Cited by 31 publications

(21 citation statements)

References 59 publications

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“…Based on this results and various single arm studies [34][35][36]38] HCT-ASCT has been established as a widely used treatment approach in PCNSL patients up to the age of 65 to 70 years. These findings are supported by the results of a systemic review and meta-analysis including 43 studies and reporting outcome data of mainly thiotepa-based HCT-ASCT as consolidating or salvage treatment in PCNSL patients with a median age range between 42 and 68.5 years [102]. Alnahhas et al reported an overall response rate of 94% after consolidative HCT-ASCT with respective two-year OS and PFS rates of 86% and 70%.…”

Section: Discussionmentioning

confidence: 64%

“…The rationale for HCT-ACST in PCNSL is the delivery of blood-brain-barrier penetrating agents in several-fold higher concentrations, which cannot be achieved with conventionally dosed therapy [78,101]. During the past years, 2 RCTs [32,33] have established HCT-ASCT in PCNSL patients up to the age of 65 to 70 years as a widely used treatment approach in younger PCNSL patients [30,60,102]. The RCT by Ferreri et al included patients up to the age of 65 years or between 65 and 70 years in case of a good PS (ECOG PS ≤ 2) and provided subgroup analyses for those 2 age groups.…”

Section: Discussionmentioning

confidence: 99%

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Treatment Regimens for Immunocompetent Elderly Patients with Primary Central Nervous System Lymphoma: A Scoping Review

Schorb

Isbell

Illerhaus

et al. 2021

Cancers

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Background: Most patients diagnosed with primary central nervous system lymphoma (PCNSL) are older than 60 years. Despite promising treatment options for younger patients, prognosis for the elderly remains poor and efficacy of available treatment options is limited. Materials and Methods: We conducted a scoping review to identify and summarize the current study pool available evaluating different types and combinations of (immuno) chemotherapy with a special focus on HCT-ASCT in elderly PCNSL. Relevant studies were identified through systematic searches in the bibliographic databases Medline, Web of Science, Cochrane Library and ScienceDirect (last search conducted in September 2020). For ongoing studies, we searched ClinicalTrials.gov, the German study register and the WHO registry. Results: In total, we identified six randomized controlled trials (RCT) with 1.346 patients, 26 prospective (with 1.366 patients) and 24 retrospective studies (with 2.629 patients). Of these, only six studies (one completed and one ongoing RCT (with 447 patients), one completed and one ongoing prospective single arm study (with 65 patients), and two retrospective single arm studies (with 122 patients)) evaluated HCT-ASCT. Patient relevant outcomes such as progression-free and overall survival and (neuro-)toxicity were adequately considered across almost all studies. The current study pool is, however, not conclusive in terms of the most effective treatment options for elderly. Main limitations were (very) small sample sizes and heterogeneous patient populations in terms of age ranges (particularly in RCTs) limiting the applicability of the results to the target population (elderly). Conclusions: Although it has been shown that HCT-ASCT is probably a feasible and effective treatment option, this approach has never been investigated within a RCT including a wide range of elderly patients. A RCT comparing conventional (immuno) chemotherapy with HCT-ASCT is crucial to evaluate benefit and harms in an un-biased manner to eventually provide older PCNSL patients with the most effective treatment.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Treatment Regimens for Immunocompetent Elderly Patients with Primary Central Nervous System Lymphoma: A Scoping Review

Schorb

Isbell

Illerhaus

et al. 2021

Cancers

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“…44 A meta-analysis of HDC/ASCT for PCNSL found carmustine/thiotepa to be the conditioning regimen with the lowest risk of TRM, but the TBC regimen to have numerically superior PFS and OS rates. 45 Neurotoxicity appears to be less common with HDC/ASCT than with WBRT consolidation. We report a rate of 27.1% for reversible neurotoxicity, most commonly consisting of delirium and rarely seizure (4.2%).…”

Section: Discussionmentioning

confidence: 99%

Durable Survival Outcomes in Primary and Secondary Central Nervous System Lymphoma After High-dose Chemotherapy and Autologous Stem Cell Transplantation Using a Thiotepa, Busulfan, and Cyclophosphamide Conditioning Regimen

Young

Gaut

Kimaiyo

et al. 2020

Clinical Lymphoma Myeloma and Leukemia

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MicroAbstractWe retrospectively analyzed 48 CNS lymphoma patients who received HDC/ASCT using TBC conditioning. We found a 2-year PFS and OS rate of 80.5% and 80.1%, respectively. Toxicities included nausea/vomiting, diarrhea, mucositis, and febrile neutropenia. Treatment-related mortality was 8.3% in the first 100 days post-transplant. This data supports the use of consolidative ASCT in PCNSL and secondary CNS lymphoma patients.

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“…Although no formal comparison of conditioning regimens has been conducted to date, historical results gathered after using the BEAM regimen [carmustine (BCUY), etoposide, cytarabine, and melphalan] were disappointing, with a modest treatment response rate and a 2-year OS rate of 60% [11]. According to the meta-analysis by Alnahhas et al, BCNU/TT carried the lowest risk of TRM and an equivalent response rate to that of TBC, while TBC achieved a lower relapse rate and numerically superior OS and PFS rates [23]. A recent investigation by Omuro et al found that the 2-year PFS and OS rates in their study population were both 81% with a median follow-up period of 45 months [16].…”

Section: Discussionmentioning

confidence: 99%

R-MPV Followed by High-dose Chemotherapy With Thiotepa-based and Autologous Stem Cell Transplantation for Newly Diagnosed Primary Central Nervous System Lymphoma: A Single-center Experience

Lee

Paik

Suh

et al. 2020

Preprint

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BackgroundHigh-dose chemotherapy followed by autologous stem-cell transplantation (HDC–ASCT) as a consolidation treatment is a promising approach in eligible patients with newly diagnosed primary central nervous system lymphoma (PCNSL). This study sought to assess the safety and efficacy of initial methotrexate-based chemotherapy followed by consolidation HDC-ASCT with a thiotepa-based conditioning regimen in patients with newly diagnosed PCNSL. MethodsIn this retrospective analysis, 22 patients with newly diagnosed PCNSL received chemotherapy with rituximab, methotrexate, procarbazine, and vincristine (R-MPV). Those who showed a complete or partial response subsequently received consolidation HDC-ASCT with a thiotepa-based conditioning regimen and no radiotherapy. ResultsCharacteristics of the PCNSL patients included a median age of 57 years (range: 49–67 years), Eastern Cooperative Oncology Group performance status of grade 2 or more in 9.1%, elevated lactate dehydrogenase level in 26.3%, and involvement of multiple lesions in 72.1%. About 82% of patients received six cycles of induction chemotherapy, which was well-tolerated with excellent disease control. The rate of confirmed/or unconfirmed complete response increased from 45.5% in the interim to 81.8% before HDC-ASCT. With a median follow-up of 19.6 months (range: 7.5–56.5 months), the 2-year progression-free survival and overall survival estimates were 84% and 88%, respectively. There were no treatment-related deaths. Grade 3 toxicity was recorded in 90.9% after HDC-ASCT, and the most common grade 3 adverse event was febrile neutropenia without sepsis. ConclusionsThe discussed treatment approach appears feasible in patients with newly diagnosed PCNSL, yielding encouraging results.

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Autologous Stem-Cell Transplantation for Primary Central Nervous System Lymphoma: Systematic Review and Meta-analysis

Cited by 31 publications

References 59 publications

Treatment Regimens for Immunocompetent Elderly Patients with Primary Central Nervous System Lymphoma: A Scoping Review

Treatment Regimens for Immunocompetent Elderly Patients with Primary Central Nervous System Lymphoma: A Scoping Review

Durable Survival Outcomes in Primary and Secondary Central Nervous System Lymphoma After High-dose Chemotherapy and Autologous Stem Cell Transplantation Using a Thiotepa, Busulfan, and Cyclophosphamide Conditioning Regimen

R-MPV Followed by High-dose Chemotherapy With Thiotepa-based and Autologous Stem Cell Transplantation for Newly Diagnosed Primary Central Nervous System Lymphoma: A Single-center Experience

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