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Successful Use of High Dose Methotrexate in Treatment of Primary CNS Lymphoma Patients Without Access to Serum Methotrexate Levels Monitoring: Challenges and Outcome
Aims and Objectives High dose methotrexate (HDMTx) based chemotherapy forms the backbone of therapy for patients with Primary Central Nervous system Lymphoma (PCNSL). However, delivering HDMTx in resource constrained settings, especially without therapeutic drug monitoring, is difficult. We share ou...
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Published in: | Indian journal of hematology & blood transfusion 2022-01, Vol.38 (1), p.68-77 |
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creator | Singh, Charanpreet Jain, Arihant Takkar, Aastha Agarwal, Aniruddha Rohilla, Manish Lad, Deepesh Khadwal, Alka Basher, Rajender Radotra, B. D. Bal, Amanjit Das, Ashim Gupta, Vishali Lal, Vivek Varma, Subhash Malhotra, Pankaj Prakash, Gaurav |
description | Aims and Objectives
High dose methotrexate (HDMTx) based chemotherapy forms the backbone of therapy for patients with Primary Central Nervous system Lymphoma (PCNSL). However, delivering HDMTx in resource constrained settings, especially without therapeutic drug monitoring, is difficult. We share our experience of treatment of patients with PCNSL at our center over a 10-year period with local adaptations made to deliver HDMTx.
Materials and Methods
We retrospectively analysed the case records of patients diagnosed with a PCNSL over the course of 10 years from 2010 to 2020.
Results
Fifty-five patients received therapy for newly diagnosed PCNSL. Thirty-six patients received Modified De-Angelis protocol ± Rituximab with curative intent. Fourteen of these patients were unable to complete the protocol with the most common cause being development of methotrexate toxicity. Patients unable to complete the designated 5 cycles of HDMTx had a poorer PS and higher probability of having a high IELSG score at baseline. Nineteen patients were given non HDMTx based therapy either due to advanced age or poor performance status. Twenty-nine patients (52.7%) were able to achieve a complete response. The most common cause of mortality was relapse/progressive disease. The Median EFS and OS of the cohort was 29 months and 40 months respectively.
Conclusion
All attempts should be made to have therapeutic drug level monitoring for administration of HDMTX based therapy for the patients with PCNSL, more so in patients who have poor performance status and a high IELSG score. If it is imperative to give HDMTx without access to TDM facility then a possible risk of higher toxicity should be explained to all patients, beforehand |
doi_str_mv | 10.1007/s12288-021-01438-5 |
format | article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8804055</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2624218276</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-6b02ed904ee66243d6057cb0843e7987882cc85074adb789d19509d6892611a83</originalsourceid><addsrcrecordid>eNp9kctu2zAQRYWiQfNof6CLgkDXSocUKVJdFAjcRwI4TQAn6JKgpbHFQBIdkgqaD-p_lrbyaDZdkcTcOXOHN8veUzimAPJToIwplQOjOVBeqFy8yg6gkjwHzqvXuzvNuQC2nx2GcANQ0oKLN9l-ISgTkhYH2Z_FWNcYwmrsyHVA4lbk1K5b8tWlxznG1kWPv01EYgdy5dHEHoe4lV162xt_T2Y_F2R-329a1xtyaaJN9UB-2dQ6RnKyo5PoyAL92L9EzvEOu0DO3WCj83ZYfyaz1nQdDmsMxAwNuRhj7Xp8m-2tTBfw3cN5lF1__3Y1O83nFz_OZifzvOaSx7xcAsOmAo5YlowXTQlC1ktQvEBZKakUq2slQHLTLKWqGloJqJpSVayk1KjiKPsycTfjssemTqt40-nNtKp2xuqXlcG2eu3utFLAQYgE-PgA8O52xBD1jRv9kDxrlhwxqpgsk4pNqtq7EDyuniZQ0Nto9RStTtHqXbR6i_7wr7enlscsk6CYBGGz_Uv0z7P_g_0L7lqxeg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2624218276</pqid></control><display><type>article</type><title>Successful Use of High Dose Methotrexate in Treatment of Primary CNS Lymphoma Patients Without Access to Serum Methotrexate Levels Monitoring: Challenges and Outcome</title><source>Springer Nature</source><source>PubMed Central</source><creator>Singh, Charanpreet ; Jain, Arihant ; Takkar, Aastha ; Agarwal, Aniruddha ; Rohilla, Manish ; Lad, Deepesh ; Khadwal, Alka ; Basher, Rajender ; Radotra, B. D. ; Bal, Amanjit ; Das, Ashim ; Gupta, Vishali ; Lal, Vivek ; Varma, Subhash ; Malhotra, Pankaj ; Prakash, Gaurav</creator><creatorcontrib>Singh, Charanpreet ; Jain, Arihant ; Takkar, Aastha ; Agarwal, Aniruddha ; Rohilla, Manish ; Lad, Deepesh ; Khadwal, Alka ; Basher, Rajender ; Radotra, B. D. ; Bal, Amanjit ; Das, Ashim ; Gupta, Vishali ; Lal, Vivek ; Varma, Subhash ; Malhotra, Pankaj ; Prakash, Gaurav</creatorcontrib><description>Aims and Objectives
High dose methotrexate (HDMTx) based chemotherapy forms the backbone of therapy for patients with Primary Central Nervous system Lymphoma (PCNSL). However, delivering HDMTx in resource constrained settings, especially without therapeutic drug monitoring, is difficult. We share our experience of treatment of patients with PCNSL at our center over a 10-year period with local adaptations made to deliver HDMTx.
Materials and Methods
We retrospectively analysed the case records of patients diagnosed with a PCNSL over the course of 10 years from 2010 to 2020.
Results
Fifty-five patients received therapy for newly diagnosed PCNSL. Thirty-six patients received Modified De-Angelis protocol ± Rituximab with curative intent. Fourteen of these patients were unable to complete the protocol with the most common cause being development of methotrexate toxicity. Patients unable to complete the designated 5 cycles of HDMTx had a poorer PS and higher probability of having a high IELSG score at baseline. Nineteen patients were given non HDMTx based therapy either due to advanced age or poor performance status. Twenty-nine patients (52.7%) were able to achieve a complete response. The most common cause of mortality was relapse/progressive disease. The Median EFS and OS of the cohort was 29 months and 40 months respectively.
Conclusion
All attempts should be made to have therapeutic drug level monitoring for administration of HDMTX based therapy for the patients with PCNSL, more so in patients who have poor performance status and a high IELSG score. If it is imperative to give HDMTx without access to TDM facility then a possible risk of higher toxicity should be explained to all patients, beforehand</description><identifier>ISSN: 0971-4502</identifier><identifier>ISSN: 0974-0449</identifier><identifier>EISSN: 0974-0449</identifier><identifier>EISSN: 0971-4502</identifier><identifier>DOI: 10.1007/s12288-021-01438-5</identifier><identifier>PMID: 35125713</identifier><language>eng</language><publisher>New Delhi: Springer India</publisher><subject>Blood Transfusion Medicine ; Clinical outcomes ; Developing countries ; Drug dosages ; Hematology ; Human Genetics ; Immunotherapy ; LDCs ; Lymphoma ; Medicine ; Medicine & Public Health ; Methotrexate ; Monoclonal antibodies ; Nervous system ; Oncology ; Original ; Original Article ; Targeted cancer therapy ; Therapeutic drug monitoring</subject><ispartof>Indian journal of hematology & blood transfusion, 2022-01, Vol.38 (1), p.68-77</ispartof><rights>Indian Society of Hematology and Blood Transfusion 2021</rights><rights>Indian Society of Hematology and Blood Transfusion 2021.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-6b02ed904ee66243d6057cb0843e7987882cc85074adb789d19509d6892611a83</citedby><cites>FETCH-LOGICAL-c474t-6b02ed904ee66243d6057cb0843e7987882cc85074adb789d19509d6892611a83</cites><orcidid>0000-0003-4142-1592</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804055/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804055/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35125713$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Singh, Charanpreet</creatorcontrib><creatorcontrib>Jain, Arihant</creatorcontrib><creatorcontrib>Takkar, Aastha</creatorcontrib><creatorcontrib>Agarwal, Aniruddha</creatorcontrib><creatorcontrib>Rohilla, Manish</creatorcontrib><creatorcontrib>Lad, Deepesh</creatorcontrib><creatorcontrib>Khadwal, Alka</creatorcontrib><creatorcontrib>Basher, Rajender</creatorcontrib><creatorcontrib>Radotra, B. D.</creatorcontrib><creatorcontrib>Bal, Amanjit</creatorcontrib><creatorcontrib>Das, Ashim</creatorcontrib><creatorcontrib>Gupta, Vishali</creatorcontrib><creatorcontrib>Lal, Vivek</creatorcontrib><creatorcontrib>Varma, Subhash</creatorcontrib><creatorcontrib>Malhotra, Pankaj</creatorcontrib><creatorcontrib>Prakash, Gaurav</creatorcontrib><title>Successful Use of High Dose Methotrexate in Treatment of Primary CNS Lymphoma Patients Without Access to Serum Methotrexate Levels Monitoring: Challenges and Outcome</title><title>Indian journal of hematology & blood transfusion</title><addtitle>Indian J Hematol Blood Transfus</addtitle><addtitle>Indian J Hematol Blood Transfus</addtitle><description>Aims and Objectives
High dose methotrexate (HDMTx) based chemotherapy forms the backbone of therapy for patients with Primary Central Nervous system Lymphoma (PCNSL). However, delivering HDMTx in resource constrained settings, especially without therapeutic drug monitoring, is difficult. We share our experience of treatment of patients with PCNSL at our center over a 10-year period with local adaptations made to deliver HDMTx.
Materials and Methods
We retrospectively analysed the case records of patients diagnosed with a PCNSL over the course of 10 years from 2010 to 2020.
Results
Fifty-five patients received therapy for newly diagnosed PCNSL. Thirty-six patients received Modified De-Angelis protocol ± Rituximab with curative intent. Fourteen of these patients were unable to complete the protocol with the most common cause being development of methotrexate toxicity. Patients unable to complete the designated 5 cycles of HDMTx had a poorer PS and higher probability of having a high IELSG score at baseline. Nineteen patients were given non HDMTx based therapy either due to advanced age or poor performance status. Twenty-nine patients (52.7%) were able to achieve a complete response. The most common cause of mortality was relapse/progressive disease. The Median EFS and OS of the cohort was 29 months and 40 months respectively.
Conclusion
All attempts should be made to have therapeutic drug level monitoring for administration of HDMTX based therapy for the patients with PCNSL, more so in patients who have poor performance status and a high IELSG score. If it is imperative to give HDMTx without access to TDM facility then a possible risk of higher toxicity should be explained to all patients, beforehand</description><subject>Blood Transfusion Medicine</subject><subject>Clinical outcomes</subject><subject>Developing countries</subject><subject>Drug dosages</subject><subject>Hematology</subject><subject>Human Genetics</subject><subject>Immunotherapy</subject><subject>LDCs</subject><subject>Lymphoma</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Methotrexate</subject><subject>Monoclonal antibodies</subject><subject>Nervous system</subject><subject>Oncology</subject><subject>Original</subject><subject>Original Article</subject><subject>Targeted cancer therapy</subject><subject>Therapeutic drug monitoring</subject><issn>0971-4502</issn><issn>0974-0449</issn><issn>0974-0449</issn><issn>0971-4502</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp9kctu2zAQRYWiQfNof6CLgkDXSocUKVJdFAjcRwI4TQAn6JKgpbHFQBIdkgqaD-p_lrbyaDZdkcTcOXOHN8veUzimAPJToIwplQOjOVBeqFy8yg6gkjwHzqvXuzvNuQC2nx2GcANQ0oKLN9l-ISgTkhYH2Z_FWNcYwmrsyHVA4lbk1K5b8tWlxznG1kWPv01EYgdy5dHEHoe4lV162xt_T2Y_F2R-329a1xtyaaJN9UB-2dQ6RnKyo5PoyAL92L9EzvEOu0DO3WCj83ZYfyaz1nQdDmsMxAwNuRhj7Xp8m-2tTBfw3cN5lF1__3Y1O83nFz_OZifzvOaSx7xcAsOmAo5YlowXTQlC1ktQvEBZKakUq2slQHLTLKWqGloJqJpSVayk1KjiKPsycTfjssemTqt40-nNtKp2xuqXlcG2eu3utFLAQYgE-PgA8O52xBD1jRv9kDxrlhwxqpgsk4pNqtq7EDyuniZQ0Nto9RStTtHqXbR6i_7wr7enlscsk6CYBGGz_Uv0z7P_g_0L7lqxeg</recordid><startdate>20220101</startdate><enddate>20220101</enddate><creator>Singh, Charanpreet</creator><creator>Jain, Arihant</creator><creator>Takkar, Aastha</creator><creator>Agarwal, Aniruddha</creator><creator>Rohilla, Manish</creator><creator>Lad, Deepesh</creator><creator>Khadwal, Alka</creator><creator>Basher, Rajender</creator><creator>Radotra, B. D.</creator><creator>Bal, Amanjit</creator><creator>Das, Ashim</creator><creator>Gupta, Vishali</creator><creator>Lal, Vivek</creator><creator>Varma, Subhash</creator><creator>Malhotra, Pankaj</creator><creator>Prakash, Gaurav</creator><general>Springer India</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4142-1592</orcidid></search><sort><creationdate>20220101</creationdate><title>Successful Use of High Dose Methotrexate in Treatment of Primary CNS Lymphoma Patients Without Access to Serum Methotrexate Levels Monitoring: Challenges and Outcome</title><author>Singh, Charanpreet ; Jain, Arihant ; Takkar, Aastha ; Agarwal, Aniruddha ; Rohilla, Manish ; Lad, Deepesh ; Khadwal, Alka ; Basher, Rajender ; Radotra, B. D. ; Bal, Amanjit ; Das, Ashim ; Gupta, Vishali ; Lal, Vivek ; Varma, Subhash ; Malhotra, Pankaj ; Prakash, Gaurav</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-6b02ed904ee66243d6057cb0843e7987882cc85074adb789d19509d6892611a83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Blood Transfusion Medicine</topic><topic>Clinical outcomes</topic><topic>Developing countries</topic><topic>Drug dosages</topic><topic>Hematology</topic><topic>Human Genetics</topic><topic>Immunotherapy</topic><topic>LDCs</topic><topic>Lymphoma</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Methotrexate</topic><topic>Monoclonal antibodies</topic><topic>Nervous system</topic><topic>Oncology</topic><topic>Original</topic><topic>Original Article</topic><topic>Targeted cancer therapy</topic><topic>Therapeutic drug monitoring</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Singh, Charanpreet</creatorcontrib><creatorcontrib>Jain, Arihant</creatorcontrib><creatorcontrib>Takkar, Aastha</creatorcontrib><creatorcontrib>Agarwal, Aniruddha</creatorcontrib><creatorcontrib>Rohilla, Manish</creatorcontrib><creatorcontrib>Lad, Deepesh</creatorcontrib><creatorcontrib>Khadwal, Alka</creatorcontrib><creatorcontrib>Basher, Rajender</creatorcontrib><creatorcontrib>Radotra, B. D.</creatorcontrib><creatorcontrib>Bal, Amanjit</creatorcontrib><creatorcontrib>Das, Ashim</creatorcontrib><creatorcontrib>Gupta, Vishali</creatorcontrib><creatorcontrib>Lal, Vivek</creatorcontrib><creatorcontrib>Varma, Subhash</creatorcontrib><creatorcontrib>Malhotra, Pankaj</creatorcontrib><creatorcontrib>Prakash, Gaurav</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Indian journal of hematology & blood transfusion</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Singh, Charanpreet</au><au>Jain, Arihant</au><au>Takkar, Aastha</au><au>Agarwal, Aniruddha</au><au>Rohilla, Manish</au><au>Lad, Deepesh</au><au>Khadwal, Alka</au><au>Basher, Rajender</au><au>Radotra, B. D.</au><au>Bal, Amanjit</au><au>Das, Ashim</au><au>Gupta, Vishali</au><au>Lal, Vivek</au><au>Varma, Subhash</au><au>Malhotra, Pankaj</au><au>Prakash, Gaurav</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Successful Use of High Dose Methotrexate in Treatment of Primary CNS Lymphoma Patients Without Access to Serum Methotrexate Levels Monitoring: Challenges and Outcome</atitle><jtitle>Indian journal of hematology & blood transfusion</jtitle><stitle>Indian J Hematol Blood Transfus</stitle><addtitle>Indian J Hematol Blood Transfus</addtitle><date>2022-01-01</date><risdate>2022</risdate><volume>38</volume><issue>1</issue><spage>68</spage><epage>77</epage><pages>68-77</pages><issn>0971-4502</issn><issn>0974-0449</issn><eissn>0974-0449</eissn><eissn>0971-4502</eissn><abstract>Aims and Objectives
High dose methotrexate (HDMTx) based chemotherapy forms the backbone of therapy for patients with Primary Central Nervous system Lymphoma (PCNSL). However, delivering HDMTx in resource constrained settings, especially without therapeutic drug monitoring, is difficult. We share our experience of treatment of patients with PCNSL at our center over a 10-year period with local adaptations made to deliver HDMTx.
Materials and Methods
We retrospectively analysed the case records of patients diagnosed with a PCNSL over the course of 10 years from 2010 to 2020.
Results
Fifty-five patients received therapy for newly diagnosed PCNSL. Thirty-six patients received Modified De-Angelis protocol ± Rituximab with curative intent. Fourteen of these patients were unable to complete the protocol with the most common cause being development of methotrexate toxicity. Patients unable to complete the designated 5 cycles of HDMTx had a poorer PS and higher probability of having a high IELSG score at baseline. Nineteen patients were given non HDMTx based therapy either due to advanced age or poor performance status. Twenty-nine patients (52.7%) were able to achieve a complete response. The most common cause of mortality was relapse/progressive disease. The Median EFS and OS of the cohort was 29 months and 40 months respectively.
Conclusion
All attempts should be made to have therapeutic drug level monitoring for administration of HDMTX based therapy for the patients with PCNSL, more so in patients who have poor performance status and a high IELSG score. If it is imperative to give HDMTx without access to TDM facility then a possible risk of higher toxicity should be explained to all patients, beforehand</abstract><cop>New Delhi</cop><pub>Springer India</pub><pmid>35125713</pmid><doi>10.1007/s12288-021-01438-5</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-4142-1592</orcidid><oa>free_for_read</oa></addata></record> |
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source | Springer Nature; PubMed Central |
subjects | Blood Transfusion Medicine Clinical outcomes Developing countries Drug dosages Hematology Human Genetics Immunotherapy LDCs Lymphoma Medicine Medicine & Public Health Methotrexate Monoclonal antibodies Nervous system Oncology Original Original Article Targeted cancer therapy Therapeutic drug monitoring |
title | Successful Use of High Dose Methotrexate in Treatment of Primary CNS Lymphoma Patients Without Access to Serum Methotrexate Levels Monitoring: Challenges and Outcome |
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