scholarly journals Influence of Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphism on High-Dose Methotrexate-Related Toxicities in Pediatric Non-Hodgkin Lymphoma Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Suying Lu ◽  
Xiaoqin Zhu ◽  
Wei Li ◽  
Huimou Chen ◽  
Dalei Zhou ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Oral Mucositis ◽  
Methylenetetrahydrofolate Reductase ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Mutant Genotype ◽  
Non Hodgkin Lymphoma ◽  
Dose Methotrexate

PurposeThis retrospective study aimed to investigate the relationships between the methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C and high-dose methotrexate (HD-MTX)-related toxicities in pediatric non-Hodgkin lymphoma (NHL) patients.Patients and MethodsWe reviewed the medical records of 93 NHL patients aged under 18 years who received HD-MTX therapy at the dose of 5 g/m2 with 24-h infusion at Sun Yat-sen University Cancer Center between 2014 and 2019.ResultsThere were 61 males and 32 females, with a median age of 8.8 years (0.9–15.8 years). The tumor types included lymphoblastic lymphoma (n = 38), Burkitt’s lymphoma (n = 31), anaplastic large cell lymphoma (n = 18), diffuse large B-cell lymphoma (n = 6). Overall, 355 courses of HD-MTX therapy were prescribed. All patients were rescued with calcium folinate 12 h after the end of MTX infusion. We found that plasma MTX levels > 0.2 μmol/L at 48 h post-infusion increased the risk of developing oral mucositis (2.4% VS. 9.5%, P = 0.018). Also, patients carrying the C677T and T677T genotypes had tendencies to be more susceptible to oral mucositis (P = 0.034). Patients harboring mutant 677T allele were more likely to develop leucopenia (38.5 vs. 50.3%, P = 0.025) and thrombocytopenia (22.0 vs. 32.4%, P = 0.028). For polymorphism A1298C, the mutant genotype played a protective role in vomiting (11.1 vs. 4.3%, P = 0.018) but increased the risk of anemia (23.8 vs. 41.7%, P < 0.001) and leucopenia (38.1 vs. 50.3%, P = 0.021).ConclusionChildhood NHL patients harboring C677T genotype were more vulnerable to oral mucositis, leucopenia, and thrombocytopenia, while those with A1298C genotype were at a decreased risk of vomiting and more likely to develop anemia and leucopenia.

scholarly journals Impact of High-Dose Methotrexate on the Outcome of Patients with Diffuse Large B-Cell Lymphoma and Skeletal Involvement

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2945
Author(s):  
Mélanie Mercier ◽  
Corentin Orvain ◽  
Laurianne Drieu La Rochelle ◽  
Tony Marchand ◽  
Christopher Nunes Gomes ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Skeletal Involvement ◽  
Large B Cell Lymphoma ◽  
Dose Methotrexate ◽  
The Impact ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL) with extra nodal skeletal involvement is rare. It is currently unclear whether these lymphomas should be treated in the same manner as those without skeletal involvement. We retrospectively analyzed the impact of combining high-dose methotrexate (HD-MTX) with an anthracycline-based regimen and rituximab as first-line treatment in a cohort of 93 patients with DLBCL and skeletal involvement with long follow-up. Fifty patients (54%) received upfront HD-MTX for prophylaxis of CNS recurrence (high IPI score and/or epidural involvement) or because of skeletal involvement. After adjusting for age, ECOG, high LDH levels, and type of skeletal involvement, HD-MTX was associated with an improved PFS and OS (HR: 0.2, 95% CI: 0.1–0.3, p < 0.001 and HR: 0.1, 95% CI: 0.04–0.3, p < 0.001, respectively). Patients who received HD-MTX had significantly better 5-year PFS and OS (77% vs. 39%, p <0.001 and 83 vs. 58%, p < 0.001). Radiotherapy was associated with an improved 5-year PFS (74 vs. 48%, p = 0.02), whereas 5-year OS was not significantly different (79% vs. 66%, p = 0.09). A landmark analysis showed that autologous stem cell transplantation was not associated with improved PFS or OS. The combination of high-dose methotrexate and an anthracycline-based immunochemotherapy is associated with an improved outcome in patients with DLBCL and skeletal involvement and should be confirmed in prospective trials.

A Phase II Clinical Study of Rituximab and High-Dose Biweekly THP-COP (Pirarubicin, Cyclophosphamide, Vincristine and Predonisolone) with G-CSF for Non-Hodgkin Lymphoma: Results of a Multicentric Study of NMLSG (Niigata Malignant Lymphoma Study Group).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4734-4734
Author(s):  
Jun Takizawa ◽  
Sadao Aoki ◽  
Kazue Takai ◽  
Tohri Kurasaki ◽  
Keiichiro Honma ◽  
...  
Keyword(s):  
Clinical Study ◽  
T Cell ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Histological Subtypes ◽  
Non Hodgkin Lymphoma

Abstract Introduction CHOP chemotherapy has been accepted as the standard treatment for patients with non-Hodgkin lymphoma (NHL), but in some histological or clinical subtypes the results are not satisfactory. We have shown the efficacy and safety of high-dose biweekly THP-COP with G-CSF support (HDBW-TCOP(G)) for NHL. In this regimen, we choose pirarubicin in stead of doxorubicin because it was proven high efficacy against NHL and the lower toxicity than doxorubicin. Recently, the combination of rituximab and standard CHOP has been shown to have a synergistic effect for NHL. We performed a phase II multicentric clinical study to assessed the feasibility and toxicity of the combination chemotherapy of rituximab and HDBW-TCOP(G) (HDBW-R-TCOP(G)) compared with those of HDBW-TCOP(G). Patients and methods Between August 1998 and December 2004, Forty-one Japanese patients with previously untreated NHL from whom informed consent was obtained were included in this study. Median age was 45 (range 19–63) years. There were 19 males and 22 females. According to WHO-classification diagnoses, histological subtypes included follicular lymphoma (FL) 15(37%); nodal marginal zone B-cell lymphoma (NMZBCL) 2(5%); mantle cell lymphoma (MCL) 3(7%); anaplastic large cell lymphoma (ALCL) 1(2%), diffuse large B-cell lymphoma (DLBCL) 18(44%); peripheral T-cell lymphoma (PTCL) 1(2%), angioimmunoblastic T-cell lymphoma (AILT) 1(2%). Of 41 patients, one patient was stage 1, stage 2, 11 stage 3 and 16 stage 4. International prognostic index (IPI) included L 6; LI 22; HI 7; H 6. HDBW-TCOP(G) consisted of pirarubicin 70 mg/m2 on day 1; cyclophosphamide 1000 mg/m2 on day 1; vincristine 1.4 mg/m2 on day 1; predonisolone 50 mg/m2 orally from day 1 to 5; lenograstim 2.0 μg/kg/day from day 3. Fifteen patients who enrolled after rituximab was approved in Japan received therapy combined HDBW-TCOP(G) with rituximab 375mg/ m2 on day -2 (HDBW-R-TCOP(G)). Six cycles were administered at intervals of two weeks. Results Of the 41 patients treated, 32 (78.0%) achieved a complete remission (CR) and nine (22.0%) achieved a partial remission (PR), for an overall response rate of 100%. After median follow-up of 36 months (range 2.9– 81.8), progression free survival (PFS) and overall survival (OS) were 68.2% and 97.5%, respectively. PFS was 90.9% for HDBW-R-TCOP(G), and 69.5% for HDBW-TCOP(G), but no significant differences was found among two regimen. There was no significant difference in the PFS and OS between aggressive and indolent histological subtypes. 76% of patients developed Grade4 leukopenia (according to NCI criteria) but no patients experienced febrile neutropenia. 15% of patients developed G4 anemia and 17% of patients G4 thrombocytopenia. Other adverse effects were minimal. Conclusion Both HDBW-TCOP(G) and HDBW-R-TCOP(G) are feasible for NHL with acceptable toxicity. The excellent result suggests they are effective for aggressive NHL patients with poor prognostic factors and advanced stage indolent NHL.

Utilization of ‘Rainy Day’ Autologous Peripheral Blood Stem Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4913-4913
Author(s):  
Dominic Wall ◽  
Alexander Yallouridis ◽  
Peter Gambell ◽  
Ritchie David ◽  
Prince Miles
Keyword(s):  
Myeloid Leukaemia ◽  
Hodgkin Lymphoma ◽  
Peripheral Blood ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Common Disease ◽  
High Dose ◽  
Peripheral Blood Stem Cells ◽  
Non Hodgkin Lymphoma ◽  
L 14

Abstract High-Dose myeloablative therapy in conjunction with Autologous Peripheral Blood Stem Cell (APBSC) transplantation is an effective first line treatment in patients with haematological malignancies including Multiple Myeloma (MM) and Non-Hodgkin Lymphoma (NHL). With sufficient resources, APBSC’s can be harvested in patients during remission or consolidation treatment for subsequent transplantation if required (‘Rainy Day’ Collection). We investigated the eventual transplantation of ‘Rainy Day’ collections at our centre to assess the utilization of this strategy. We defined ‘Rainy Day’ collections as those that were not intended to be used as part of initial therapy and in general, patients were not planned to be transplanted within the 12 months following harvest. For collections that were transplanted within 12 months following harvest, ‘Rainy Day’ collections were differentiated based on the utilization intent at time of collection. Any collections infused within 3 months following harvest were excluded from the analysis. Over a 6 year period, we collected APBSC’s from 365 patients with the intent of ‘Rainy Day’ storage. Primary disease indications included NHL (45%, n=166), MM (12%, n=44), Acute Myeloid Leukaemia (AML) (8%, n=29) and Chronic Myeloid Leukaemia (CML) (7%, n=25). To date, 23% (n=84) of these ‘Rainy Day’ collections have been subsequently infused. NHL has been the most common disease requiring Rainy Day collections and has resulted in 41 subsequent transplants (24% utilization) with a median time between collection and infusion of 1.74 years (SD =1.60). Mean days until platelets > 20x109/L=15 (SD=7.0) and days until ANC > 0.5x106/L=10 (SD=1.7). Follicular Non-Hodgkin Lymphoma (fNHL) has accounted for the majority of NHL transplants (37%, 5/15), with 5 of 15 patients exhibiting transformation of fNHL into Diffuse Large B-Cell Lymphoma and an average time between collection and infusion of 2.07 years (SD 2.01). Peripheral T-Cell Lymphoma (T-NHL) has contributed to 15% (n=6/41) of transplanted NHL ‘Rainy Day’ collections with a mean time between collection and infusion being shorter at 1.53 years (SD=0.97). 23% of MM patients (n=44/202) have had APBSC’s collected for potential ‘Rainy Day’ utilization compared with 53% of NHL (n=166/309), 86% of AML (n=29/34) and 100% of CML (25/25). MM has shown to have the highest ‘Rainy Day’ APBSC utilisation with 55% (n=23/44) of patients resulting in transplantation. The average time between collection and infusion has been 2.79 years (SD=1.65) with mean days until platelets > 20x109/L=14 (SD =6.9) and days until ANC > 0.5x106/L=10 (SD=1.7). We conclude that it is clinically feasible and safe to perform ‘Rainy Day’ collections although more stringent criteria would result in a more efficient use of this resource intensive strategy.

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