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, Patricia A.; Gaut, Daria; Kimaiyo, Davis Kipkemboi; Grotts, Jonathan; Romero, Tahmineh; Chute, John P.; Schiller, Gary J.; Vos, Sven de; Eradat, Herbert; Timmerman, John M.

doi:10.1016/j.clml.2020.02.009

Cited by 14 publications

(7 citation statements)

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“…Recently, the usefulness of conditioning regimens, including thiotepa, has been reported for primary CNS lymphoma (CNSL) and secondary CNSL. 40,[42][43][44][45][46][47][48][49][50] While there are reports of zero cases of TRM when conditioning regimens with thiotepa are administered in primary CNSL, when administered in secondary CNSL, all studies report TRM in a small proportion of patients. Therefore, the effectiveness of performing auto-PBSCT at CR1 with a conditioning regimen that includes thiotepa for patients considered highly likely to have CNS recurrence at the initial onset has not been clearly demonstrated, but there is also no guarantee of safety.…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of high‐dose cytarabine MEAM therapy and other treatments for auto‐peripheral blood stem cell transplantation: A retrospective comparative study

Yui

Wakita

Nagata

et al. 2022

Asia-Pac J Clncl Oncology

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Aim The MEAM regimen consisting of ranimustine (MCNU), etoposide (ETP), cytarabine (Ara‐C), and melphalan (MEL) is widely used before auto‐peripheral blood stem cell transplantation (auto‐PBSCT) for malignant lymphoma in Japan. The MEAM regimen generally consists of 200–400 mg/m2 for 4 days, but we decided to increase the dosage of Ara‐C from the standard to 2 g/m2 for 2 days with the aim of increasing drug transferability to the central nervous system. We evaluate the safety and therapeutic efficacy of high‐dose Ara‐C MEAM therapy. Methods The high‐dose Ara‐C MEAM protocol consisted of MCNU 300 mg/m2 on day –7, ETP 200 mg/m2 on days –6, –5, –4, –3 and Ara‐C 2 g/m2 on day –4 –3, and MEL 140 mg/m2 on day –2. We retrospectively analyzed 37 cases of malignant lymphoma at our institution between May 2014 and July 2020. Results All patients got engraftment and there were no cases of treatment‐related mortality. In all cases, the 3‐year overall survival (OS) and progression‐free survival (PFS) after transplantation were 80.6% and 65.7%, respectively. Twenty‐one cases of diffuse large B‐cell lymphoma recurrence, for which there is proven usefulness of auto‐PBSCT, showed good results after transplantation, with the 3‐year OS and PFS after transplantation being 100% and 74.3%, respectively. Conclusion The safety and efficacy of high‐dose Ara‐C MEAM therapy were demonstrated, but the expected therapeutic effect on central nervous system lesions could not be fully evaluated owing to the small number of cases.

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Section: Discussionmentioning

confidence: 99%

Safety and efficacy of high‐dose cytarabine MEAM therapy and other treatments for auto‐peripheral blood stem cell transplantation: A retrospective comparative study

Yui

Wakita

Nagata

et al. 2022

Asia-Pac J Clncl Oncology

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“…High-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) has been investigated for post-remission consolidation and for relapsed disease, with promising results [ 11 , 12 , 24 , 25 , 26 , 27 , 28 ]. HD-MTX–based induction regimens, followed by ASCT, with various conditioning regimens, including BEAM (carmustine, etoposide, cytarabine, melphalan) [ 29 ], thiotepa, busulfan [ 30 , 31 ], TBC (thiotepa, busulfan, cyclophosphamide) [ 32 , 33 , 34 ] and thiotepa, carmustine [ 35 , 36 , 37 , 38 ] have been evaluated. The data thus far, however, have been limited to single-arm phase II-III trials, and several important questions remain, including the best candidates for such therapy, timing of its use, possible toxicities, and optimal conditioning regimen.…”

Section: Discussionmentioning

confidence: 99%

Ibrutinib Monotherapy as Bridge-to-Transplant for Relapsed/Refractory Primary Oculo-Cerebral Lymphoma

Deak-Mihaly

Iluta

Pașca

et al. 2021

JCM

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Introduction. Primary central nervous system lymphoma is an uncommon form of extranodal non-Hodgkin’s lymphoma, with increasing incidence, a relatively aggressive course and a poor 5-year survival. Because of its localization, the therapeutic compounds used in this disease must be able to pass through the blood-brain barrier. Chemotherapy regimens based on high-dose methotrexate are currently the standard of care for all patients who can tolerate such drugs. Autologous stem cell transplantation is indicated for malignant lymphomas in the relapsed/refractory setting. Methods. Three patients, with a median age of 60 years, range 53–64, were diagnosed with primary CNS lymphoma, and treated with ibrutinib monotherapy in the Department of Hematology, Ion Chiricuta Clinical Cancer Center, Cluj-Napoca, Romania, between September 2018 and November 2020 All the patients were relapsed–refractory following high-dose methotrexate chemotherapy. We present our experience using ibrutinib monotherapy-based treatment as a bridge-to-transplant option on a single-center case series and a review of the literature in this field. Results. Two of the patients were given ibrutinib as a second line therapy, both achieving complete remission and being eligible for an autologous stem cell transplantation. The third patient achieved a short remission using six cycles of systemic chemotherapy, but was started on ibrutinib monotherapy, with limited results. Conclusion. Our data is limited, and these results should be confirmed by multicentric clinical trials and should be regarded as a single-center case series, with all its limitations. Still, it brings forward a new therapeutic option for this rare subtype of malignant lymphomas, which if left untreated has a dismal prognosis.

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“…A retrospective study of 48 central nervous system lymphoma (CNSL) patients, who have received high-dose chemotherapy and ASCT using a TBC (thiotepa, busulfan, cyclophosphamide) conditioning regimen, showed that the 2-year PFS and OS were 80.5% and 80.1%, respectively (75). The 2-year PFS and OS for patients with PCNSL in CR1 were 95.2% and 95.2%, respectively.…”

Section: Autologous Stem-cell Transplantation (Asct)mentioning

confidence: 99%

Recent Progress on Primary Central Nervous System Lymphoma—From Bench to Bedside

Shao

et al. 2021

Front. Oncol.

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Primary central nervous system lymphoma (PCNSL) is a rare subtype of extra-nodal lymphoma. The high relapse rate of PCNSL remains a major challenge to the hematologists, even though patients exhibit high sensitivity to the methotrexate-based chemotherapeutic regimens. Recently, the advent of Bruton’s tyrosine kinase inhibitor (BTKi) and CAR T treatment has made more treatment options available to a proportion of patients. However, whether BTKi monotherapy should be given alone or in combination with conventional chemotherapy is still a clinical question. The status of CAR T therapy for PCNSLs also needs to be elucidated. In this review, we summarized the latest progress on the epidemiology, pathology, clinical manifestation, diagnosis, and treatment options for PCNSLs.

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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

Cited by 14 publications

References 50 publications

Safety and efficacy of high‐dose cytarabine MEAM therapy and other treatments for auto‐peripheral blood stem cell transplantation: A retrospective comparative study

Safety and efficacy of high‐dose cytarabine MEAM therapy and other treatments for auto‐peripheral blood stem cell transplantation: A retrospective comparative study

Ibrutinib Monotherapy as Bridge-to-Transplant for Relapsed/Refractory Primary Oculo-Cerebral Lymphoma

Recent Progress on Primary Central Nervous System Lymphoma—From Bench to Bedside

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