Relation of cellular drug resistance to long-term clinical outcome in childhood acute lymphoblastic leukaemia
The clinical relevance of cellular drug resistance in children with acute lymphoblastic leukaemia (ALL) is unknown. The relation between in-vitro sensitivity to chemotherapeutic drugs at initial diagnosis and long-term clinical outcome was investigated in 44 children with ALL. The short-term MTT ass...
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| Veröffentlicht in: | The Lancet (British edition) 1991-08, Vol.338 (8764), p.399-403 |
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| creator | Pieters, R. Huismans, D.R. Loonen, A.H. Veerman, A.J.P. Hahlen, K. van der Does-van den Berg, A. Wering, E.R. |
| description | The clinical relevance of cellular drug resistance in children with acute lymphoblastic leukaemia (ALL) is unknown. The relation between in-vitro sensitivity to chemotherapeutic drugs at initial diagnosis and long-term clinical outcome was investigated in 44 children with ALL. The short-term MTT assay was used to assess sensitivity to prednisolone, vincristine, colaspase (asparaginase), daunorubicin, and thioguanine (instead of mercaptopurine which is unstable in vitro). For vincristine and colaspase there was no difference in outcome (probability of continuous complete remission) between sensitive and resistant patients. However, the probability of continuous complete remission was significantly lower in patients with resistant cells than in those with sensitive cells for thioguanine (p |
| doi_str_mv | 10.1016/0140-6736(91)91029-T |
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The relation between in-vitro sensitivity to chemotherapeutic drugs at initial diagnosis and long-term clinical outcome was investigated in 44 children with ALL. The short-term MTT assay was used to assess sensitivity to prednisolone, vincristine, colaspase (asparaginase), daunorubicin, and thioguanine (instead of mercaptopurine which is unstable in vitro). For vincristine and colaspase there was no difference in outcome (probability of continuous complete remission) between sensitive and resistant patients. However, the probability of continuous complete remission was significantly lower in patients with resistant cells than in those with sensitive cells for thioguanine (p<0·01), daunorubicin (p<0·02), and prednisolone (p<0·05). For prednisolone there was a significant worsening of the prognosis (p<0·05) from the extremely sensitive patients through an intermediate group to the most resistant group. The prognostic significance of cellular drug resistance was independent of white-blood-cell count, age, sex, and hepatosplenomegaly. Leukaemic cells from boys were more resistant to thioguanine than those from girls. Thus, the short-term highly efficient MTT assay can help to predict long-term response to chemotherapy in childhood ALL.</description><identifier>ISSN: 0140-6736</identifier><identifier>EISSN: 1474-547X</identifier><identifier>DOI: 10.1016/0140-6736(91)91029-T</identifier><identifier>PMID: 1678081</identifier><identifier>CODEN: LANCAO</identifier><language>eng</language><publisher>London: Elsevier Ltd</publisher><subject>6-Mercaptopurine ; Acute lymphoblastic leukemia ; Antineoplastic agents ; Antineoplastic Agents - pharmacology ; Asparaginase ; Asparaginase - pharmacology ; Biological and medical sciences ; Chemotherapy ; Chi-Square Distribution ; Child ; Children ; Children & youth ; Coloring Agents ; Daunorubicin ; Daunorubicin - pharmacology ; Drug Resistance ; Drug Screening Assays, Antitumor ; Female ; Girls ; Humans ; Leukemia ; Male ; Medical research ; Medical sciences ; Patients ; Pharmacology. Drug treatments ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality ; Prednisolone ; Prednisolone - pharmacology ; Prognosis ; Remission ; Remission Induction ; Sensitivity analysis ; Tetrazolium Salts ; Thiazoles ; Thioguanine ; Thioguanine - pharmacology ; Tumor Cells, Cultured - drug effects ; Vincristine ; Vincristine - pharmacology</subject><ispartof>The Lancet (British edition), 1991-08, Vol.338 (8764), p.399-403</ispartof><rights>1991</rights><rights>1992 INIST-CNRS</rights><rights>Copyright Lancet Ltd. Aug 17, 1991</rights><rights>Copyright Elsevier Limited Aug 17, 1991</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c492t-57cef2737866294a89c4f1846d74163e317894d1babfe2bbb7da34a048f837fb3</citedby><cites>FETCH-LOGICAL-c492t-57cef2737866294a89c4f1846d74163e317894d1babfe2bbb7da34a048f837fb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/0140-6736(91)91029-T$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27928,27929,45999</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4955368$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1678081$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pieters, R.</creatorcontrib><creatorcontrib>Huismans, D.R.</creatorcontrib><creatorcontrib>Loonen, A.H.</creatorcontrib><creatorcontrib>Veerman, A.J.P.</creatorcontrib><creatorcontrib>Hahlen, K.</creatorcontrib><creatorcontrib>van der Does-van den Berg, A.</creatorcontrib><creatorcontrib>Wering, E.R.</creatorcontrib><title>Relation of cellular drug resistance to long-term clinical outcome in childhood acute lymphoblastic leukaemia</title><title>The Lancet (British edition)</title><addtitle>Lancet</addtitle><description>The clinical relevance of cellular drug resistance in children with acute lymphoblastic leukaemia (ALL) is unknown. The relation between in-vitro sensitivity to chemotherapeutic drugs at initial diagnosis and long-term clinical outcome was investigated in 44 children with ALL. The short-term MTT assay was used to assess sensitivity to prednisolone, vincristine, colaspase (asparaginase), daunorubicin, and thioguanine (instead of mercaptopurine which is unstable in vitro). For vincristine and colaspase there was no difference in outcome (probability of continuous complete remission) between sensitive and resistant patients. However, the probability of continuous complete remission was significantly lower in patients with resistant cells than in those with sensitive cells for thioguanine (p<0·01), daunorubicin (p<0·02), and prednisolone (p<0·05). For prednisolone there was a significant worsening of the prognosis (p<0·05) from the extremely sensitive patients through an intermediate group to the most resistant group. The prognostic significance of cellular drug resistance was independent of white-blood-cell count, age, sex, and hepatosplenomegaly. Leukaemic cells from boys were more resistant to thioguanine than those from girls. Thus, the short-term highly efficient MTT assay can help to predict long-term response to chemotherapy in childhood ALL.</description><subject>6-Mercaptopurine</subject><subject>Acute lymphoblastic leukemia</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Asparaginase</subject><subject>Asparaginase - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Chemotherapy</subject><subject>Chi-Square Distribution</subject><subject>Child</subject><subject>Children</subject><subject>Children & youth</subject><subject>Coloring Agents</subject><subject>Daunorubicin</subject><subject>Daunorubicin - pharmacology</subject><subject>Drug Resistance</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Female</subject><subject>Girls</subject><subject>Humans</subject><subject>Leukemia</subject><subject>Male</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Patients</subject><subject>Pharmacology. Drug treatments</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality</subject><subject>Prednisolone</subject><subject>Prednisolone - pharmacology</subject><subject>Prognosis</subject><subject>Remission</subject><subject>Remission Induction</subject><subject>Sensitivity analysis</subject><subject>Tetrazolium Salts</subject><subject>Thiazoles</subject><subject>Thioguanine</subject><subject>Thioguanine - pharmacology</subject><subject>Tumor Cells, Cultured - drug effects</subject><subject>Vincristine</subject><subject>Vincristine - pharmacology</subject><issn>0140-6736</issn><issn>1474-547X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUuLFDEQgIMo67r6DxSCiuihNdWdzuMiyOILFgQZwVtIp6t3sqY7s0la2H9vxhlWEPRQ1KG-KqrqI-QxsNfAQLxhwFkjZCdeanilgbW62dwhp8Alb3ouv98lp7fIffIg5yvGGBesPyEnIKRiCk7J_BWDLT4uNE7UYQhrsImOab2kCbPPxS4OaYk0xOWyKZhm6oJfvLOBxrW4OCP1C3VbH8ZtjCO1bi1Iw82828Yh2Fy8owHXHxZnbx-Se5MNGR8d8xn59uH95vxTc_Hl4-fzdxeN47otTS8dTq3spBKi1dwq7fgEiotRchAddiCV5iMMdpiwHYZBjrbjlnE1qU5OQ3dGXhzm7lK8XjEXM_u8v84uGNdsFJMdA80r-Owv8Cquaam7mRa4Fr2sUamn_6JAa8YUV1AhfoBcijknnMwu-dmmGwPM7IWZvQ2zt2E0mN_CzKa2PTnOXocZxz9NB0O1_vxYt7k-fUpViM-3GNd93wlVsbcHDOtbf3pMJjuP1d3oE7pixuj_v8cvT1CxuQ</recordid><startdate>19910817</startdate><enddate>19910817</enddate><creator>Pieters, R.</creator><creator>Huismans, D.R.</creator><creator>Loonen, A.H.</creator><creator>Veerman, A.J.P.</creator><creator>Hahlen, K.</creator><creator>van der Does-van den Berg, A.</creator><creator>Wering, E.R.</creator><general>Elsevier Ltd</general><general>Lancet</general><general>Elsevier Limited</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QP</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>ASE</scope><scope>C1K</scope><scope>FPQ</scope><scope>H94</scope><scope>K6X</scope><scope>K9.</scope><scope>KB~</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>7X8</scope></search><sort><creationdate>19910817</creationdate><title>Relation of cellular drug resistance to long-term clinical outcome in childhood acute lymphoblastic leukaemia</title><author>Pieters, R. ; Huismans, D.R. ; Loonen, A.H. ; Veerman, A.J.P. ; Hahlen, K. ; van der Does-van den Berg, A. ; Wering, E.R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c492t-57cef2737866294a89c4f1846d74163e317894d1babfe2bbb7da34a048f837fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>6-Mercaptopurine</topic><topic>Acute lymphoblastic leukemia</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Asparaginase</topic><topic>Asparaginase - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Chemotherapy</topic><topic>Chi-Square Distribution</topic><topic>Child</topic><topic>Children</topic><topic>Children & youth</topic><topic>Coloring Agents</topic><topic>Daunorubicin</topic><topic>Daunorubicin - pharmacology</topic><topic>Drug Resistance</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Female</topic><topic>Girls</topic><topic>Humans</topic><topic>Leukemia</topic><topic>Male</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Patients</topic><topic>Pharmacology. Drug treatments</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality</topic><topic>Prednisolone</topic><topic>Prednisolone - pharmacology</topic><topic>Prognosis</topic><topic>Remission</topic><topic>Remission Induction</topic><topic>Sensitivity analysis</topic><topic>Tetrazolium Salts</topic><topic>Thiazoles</topic><topic>Thioguanine</topic><topic>Thioguanine - pharmacology</topic><topic>Tumor Cells, Cultured - drug effects</topic><topic>Vincristine</topic><topic>Vincristine - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pieters, R.</creatorcontrib><creatorcontrib>Huismans, D.R.</creatorcontrib><creatorcontrib>Loonen, A.H.</creatorcontrib><creatorcontrib>Veerman, A.J.P.</creatorcontrib><creatorcontrib>Hahlen, K.</creatorcontrib><creatorcontrib>van der Does-van den Berg, A.</creatorcontrib><creatorcontrib>Wering, E.R.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>British Nursing Index</collection><collection>Environmental Sciences and Pollution Management</collection><collection>British Nursing Index (BNI) (1985 to Present)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>British Nursing Index</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Newsstand Professional</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>The Lancet (British edition)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pieters, R.</au><au>Huismans, D.R.</au><au>Loonen, A.H.</au><au>Veerman, A.J.P.</au><au>Hahlen, K.</au><au>van der Does-van den Berg, A.</au><au>Wering, E.R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Relation of cellular drug resistance to long-term clinical outcome in childhood acute lymphoblastic leukaemia</atitle><jtitle>The Lancet (British edition)</jtitle><addtitle>Lancet</addtitle><date>1991-08-17</date><risdate>1991</risdate><volume>338</volume><issue>8764</issue><spage>399</spage><epage>403</epage><pages>399-403</pages><issn>0140-6736</issn><eissn>1474-547X</eissn><coden>LANCAO</coden><abstract>The clinical relevance of cellular drug resistance in children with acute lymphoblastic leukaemia (ALL) is unknown. The relation between in-vitro sensitivity to chemotherapeutic drugs at initial diagnosis and long-term clinical outcome was investigated in 44 children with ALL. The short-term MTT assay was used to assess sensitivity to prednisolone, vincristine, colaspase (asparaginase), daunorubicin, and thioguanine (instead of mercaptopurine which is unstable in vitro). For vincristine and colaspase there was no difference in outcome (probability of continuous complete remission) between sensitive and resistant patients. However, the probability of continuous complete remission was significantly lower in patients with resistant cells than in those with sensitive cells for thioguanine (p<0·01), daunorubicin (p<0·02), and prednisolone (p<0·05). For prednisolone there was a significant worsening of the prognosis (p<0·05) from the extremely sensitive patients through an intermediate group to the most resistant group. The prognostic significance of cellular drug resistance was independent of white-blood-cell count, age, sex, and hepatosplenomegaly. Leukaemic cells from boys were more resistant to thioguanine than those from girls. Thus, the short-term highly efficient MTT assay can help to predict long-term response to chemotherapy in childhood ALL.</abstract><cop>London</cop><pub>Elsevier Ltd</pub><pmid>1678081</pmid><doi>10.1016/0140-6736(91)91029-T</doi><tpages>5</tpages></addata></record> |
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| ispartof | The Lancet (British edition), 1991-08, Vol.338 (8764), p.399-403 |
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| subjects | 6-Mercaptopurine Acute lymphoblastic leukemia Antineoplastic agents Antineoplastic Agents - pharmacology Asparaginase Asparaginase - pharmacology Biological and medical sciences Chemotherapy Chi-Square Distribution Child Children Children & youth Coloring Agents Daunorubicin Daunorubicin - pharmacology Drug Resistance Drug Screening Assays, Antitumor Female Girls Humans Leukemia Male Medical research Medical sciences Patients Pharmacology. Drug treatments Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality Prednisolone Prednisolone - pharmacology Prognosis Remission Remission Induction Sensitivity analysis Tetrazolium Salts Thiazoles Thioguanine Thioguanine - pharmacology Tumor Cells, Cultured - drug effects Vincristine Vincristine - pharmacology |
| title | Relation of cellular drug resistance to long-term clinical outcome in childhood acute lymphoblastic leukaemia |
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