methotrexate IV

Dexamethasone (DXM) was used in average-risk 2 (AR2) T-ALL and B-ALL during induction, 10 and 6 mg/m2/day, respectively. Leucovorin rescue was delayed to 42 h instead of 36 h after initiation of high-dose methotrexate, and a postconsolidation MRD time point was added to stratify patients...The HR was 2.15 (99% CI: 0.67-6.85) for very low-risk but 0.34 (99% CI: 0.13-0.89) for AR2. The particularly favorable results observed in the T-ALLs and AR2 subgroups suggest the benefit of using DXM in specific patient groups and highlight the importance of risk stratification.

Our series reinforces the poor prognosis of advanced stage HGBCL with less intensive regimens such as R-CHOP. In contrast to several other series, MYC/BCL6-R are associated with inferior OS in our cohort, which may be secondary to a higher frequency of CNS relapse despite similar administration of CNS prophylaxis. Indeed, there was no clear impact of CNS prophylaxis/IT-chemotherapy as relapses were distributed equally between those who did or did not receive prophylaxis.

HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis, and early application of gene sequencing is beneficial for evaluating prognosis.

P2, N=16, Recruiting, Wake Forest University Health Sciences | Trial completion date: Jan 2025 --> Jan 2027 | Trial primary completion date: Oct 2024 --> Mar 2025

A chemotherapy regimen includes a combination of high-dose Methotrexate (MTX), doxorubicin, and cisplatin...CUR and MTX combined determined a β-Catenin decrease and a trend toward reducing NF-kB and matrix metalloproteinases (MMP-2 and MMP-9). Our findings suggest CUR as a support to OS treatment, improving outcomes and reducing the adverse effects of current therapies.

P2, N=30, Not yet recruiting, Sun Yat-sen University

This strategy, partly adopted in the ongoing SIOPE protocol,confirmed improved EFS and OS over previously reported outcomes in all high-risk categories;SHH tumors appeared the most aggressive.

The developed method was useful for therapeutic drug monitoring of MTX and suitable for assessing the risks and benefits of chemotherapy in patients with primary central nervous system lymphoma. Intravenous mannitol did not increase MTX concentration in the CSF of patients.

This is the first reported case of isolated optic nerve involvement with a durable response to chemotherapy. This case emphasizes the importance of considering malignancy and maintaining a low threshold for optic nerve biopsy in patients with atypical cases of severe steroid-refractory vision loss with enhancement or enlargement of the optic nerve on MRI. Standard chemotherapy regimens for PCNSL can potentially achieve a curative response in these patients.

P3, N=340, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Oct 2024 --> Apr 2025

Whole-exome sequencing revealed a higher prevalence of RTK-RAS and PI3K pathway mutations in the durable clinical benefit group, while a greater frequency of Notch and Hippo pathway mutations in the no durable benefit group. These findings suggest the SMTR regimen is highly efficacious and tolerable for newly diagnosed PCNSL, warranting further investigation.

The patient received whole-brain radiotherapy following the failure of high-dose methotrexate...This is the first report of DH-PCNSL where identical gene rearrangements were confirmed in both the resected CNS tumor and BM tissue. Patients with DH-PCNSL require careful follow-up because they may be at a potential risk of BM infiltration, which may be undetectable by FDG-PET, particularly early in the disease course.

P1, N=12, Active, not recruiting, OHSU Knight Cancer Institute | Recruiting --> Active, not recruiting

These results suggest that hypocitrullinaemia following HDMTX increases the risk of BSI, confirming previous observations from more intensive treatments. Moreover, these data indicate that the patients' vulnerability to mucositis and inflammatory toxicity after chemotherapy varies with treatment protocol.

Gene and molecular profiling studies may provide new therapeutic strategies, especially the BCR/TLR/IL-1R/NF-κB signaling pathway in IVLBCL. Here, we treated the hemophagocytic IVLBCL CNS-involved patient with the Bruton tyrosine kinase inhibitor (BTKi) to block NF-κB pathway, and indicated that the second-generation BTKi zanubrutinib-based treatment was feasible and efficient.

P=N/A, N=34, Recruiting, Tanta University | Not yet recruiting --> Recruiting

P=N/A, N=34, Not yet recruiting, Tanta University

P2, N=20, Recruiting, First Affiliated Hospital of Zhejiang University

She was diagnosed with intravascular large B-cell lymphoma (IVLBCL) and went into remission of the skin manifestations after seven courses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) and four courses of intravenous high-dose methotrexate (HD MTX). From a review of the literature, we found that generalized telangiectasia is a remarkable manifestation of intravascular lymphoma, and the differential diagnosis of intravascular lymphoma and panniculitis or vasculitis is very important. When the diagnosis is confusing, multiple skin biopsies are useful.

P1/2, N=18, Active, not recruiting, Charite University, Berlin, Germany | Recruiting --> Active, not recruiting | Trial completion date: Apr 2025 --> Dec 2024 | Trial primary completion date: Aug 2024 --> Dec 2024

She was treated with 6 cycles of R-hyperCVAD/MA (R = rituximab, C = cyclophosphamide, V = vincristine, A = cytarabine, D = dexamethasone, M = methotrexate) and intrathecal chemotherapy (IT CT)...Primary DLBCL of the breast with rearrangement of MYC and BCL2 and tdt expression is an aggressive disease not very well studied that needs to be treated with an intensive CT and CNS prophylaxis. Stem cell transplant could be given after first remission.

Among these, variations in SLCO1B1 have the most significant and consistent impact on methotrexate clearance. These implicated variants may contribute to the precision and tailoring of HD-MTX treatment in pediatric ALL patients.

P2, N=16, Recruiting, Wake Forest University Health Sciences | Trial completion date: Sep 2024 --> Jan 2025 | Trial primary completion date: Jun 2024 --> Oct 2024

P2, N=40, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting | Trial completion date: Oct 2027 --> Nov 2030 | Initiation date: Jun 2024 --> Sep 2024 | Trial primary completion date: Oct 2027 --> Nov 2030

Among them, L-arginine, homocysteine, and betaine were significantly upregulated, suggesting their possible association with cardiac tissue injury. Overall, we provided evidence for using untargeted metabolomics to identify novel metabolites associated with HDMTX cardiac toxicity.

P2, N=17, Active, not recruiting, University of Washington | Recruiting --> Active, not recruiting

Our results suggest that despite an objective response, the persistence of detectable e-IL-10 is associated with a high risk of early relapse in PCNSL. A closer follow-up of such patients is warranted.

Induction therapy consistedof methotrexate, vincristine, procarbazine (MVP) with (40...1%) rituximab (R-MVP)... We observed a significant proportion of "high-risk" PCNSL characterized by dismal prognosis and tumorupregulation of immune checkpoints TIGIT and HAVCR2, supporting immune evasion as a disease mechanism. This represents a potential avenue for integrating immunotherapy into existing treatment regimens.

P=N/A, N=1000, Recruiting, Protherics Medicines Development Limited | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Aug 2024

P2, N=137, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Sep 2024 --> Mar 2024

P1, N=32, Suspended, National Cancer Institute (NCI) | Trial completion date: May 2024 --> May 2025 | Trial primary completion date: May 2024 --> May 2025

P3, N=70, Completed, Children's Oncology Group | Active, not recruiting --> Completed | Trial completion date: Aug 2024 --> Mar 2024

P3, N=340, Active, not recruiting, Boehringer Ingelheim | Trial completion date: May 2024 --> Aug 2024

P2, N=68, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

This comprehensive review aids researchers and clinicians in early identification of HDMTX toxicity risk factors. By understanding the multifaceted risk factors associated with hematologic malignancies, personalized treatment approaches can be tailored to optimize therapeutic outcomes.

In conclusion, the findings indicate that roflumilast may have a potential therapeutic benefit in treating rats with MTX-induced liver toxicity by mitigating its effects. The aim of this study is to investigate the potential protective effects of roflumilast against MTX-induced liver toxicity in Wistar rats.

GGH mutation was mainly concerned with anemia. Pharmacogenetic testing are recommended to optimize MTX therapy.

P4, N=250, Active, not recruiting, Nationwide Children's Hospital | Recruiting --> Active, not recruiting

P2, N=40, Not yet recruiting, City of Hope Medical Center | Initiation date: Jan 2024 --> Jun 2024

P2, N=16, Recruiting, Wake Forest University Health Sciences | Trial primary completion date: Feb 2024 --> Jun 2024

P1, N=32, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

P2, N=37, Completed, Roswell Park Cancer Institute | Active, not recruiting --> Completed