{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:19:30Z","timestamp":1787019570394,"version":"build-2736575974"},"reference-count":47,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,3,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Imatinib is the mainstay of treatment of patients with chronic myeloid leukemia (CML) in Tanzania. Monitoring molecular response to therapy by real-time polymerase chain reaction at defined milestones is necessary for early detection of treatment failure. However, this assay is not routinely performed in Tanzania; therefore, the depth of molecular response among patients with CML is not known. A total of 158 patients with previously diagnosed CML who received imatinib treatment were recruited from January 2019 and followed up through October 2020 at Ocean Road Cancer Institute. Information was obtained at the time of diagnosis and follow-up. Blood samples were collected in EDTA tubes to measure the BCR\/ABL ratio on the Gene Xpert system for molecular response determination. The median age of the 158 adult patients was 45 years (range, 18-86). By reference to established treatment milestones, only 37 (23.4%) achieved optimal molecular response. Signs of advanced-stage disease, in particular the need for red cell transfusions before diagnosis (adjusted odds ratio [AOR], 3.4; 95% CI, 1.32-9.17) and cytopenias (AOR, 2.26; 95% CI, 1.03-4.96) necessitating drug interruptions were statistically validated predictors of treatment failure on multivariate, multinomial logistic regression. Patient survival at the 22-month follow-up was lowest, with 78.6% (95% CI, 69.4-85.4) in the failure-to-respond category and highest in patients achieving optimal response 97.0% (95% CI, 80.9-99.6). In summary, the majority of patients with CML treated with imatinib in Tanzania do not obtain deep molecular response. This outcome can be attributed to late diagnosis, the development of cytopenias requiring multiple drug interruptions, and poor adherence to treatment.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020002973","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T11:42:03Z","timestamp":1614944523000},"page":"1403-1411","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":25,"title":["Molecular response to imatinib in patients with chronic myeloid leukemia in Tanzania"],"prefix":"10.1182","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1513-0484","authenticated-orcid":false,"given":"Ahlam","family":"Nasser","sequence":"first","affiliation":[{"name":"Department of Hematology and Blood Transfusion, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6674-7487","authenticated-orcid":false,"given":"Ally","family":"Hussein","sequence":"additional","affiliation":[{"name":"Tanzania Field Epidemiology and Laboratory Training Program, Dar es Salaam, Tanzania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5154-7872","authenticated-orcid":false,"given":"Clara","family":"Chamba","sequence":"additional","affiliation":[{"name":"Department of Hematology and Blood Transfusion, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mbonea","family":"Yonazi","sequence":"additional","affiliation":[{"name":"Department of Hematology and Blood Transfusion, Muhimbili National Hospital, Dar es Salaam, Tanzania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemary","family":"Mushi","sequence":"additional","affiliation":[{"name":"Department of Oncology, Ocean Road Cancer Institute, Dar es Salaam, Tanzania; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3938-8490","authenticated-orcid":false,"given":"Anna","family":"Schuh","sequence":"additional","affiliation":[{"name":"Department of Hematology and Blood Transfusion, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania;"},{"name":"Department of Oncology, University of Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4663-8790","authenticated-orcid":false,"given":"Lucio","family":"Luzzatto","sequence":"additional","affiliation":[{"name":"Department of Hematology and Blood Transfusion, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2021,3,5]]},"reference":[{"issue":"3","key":"2021030516334752600_B1","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1056\/NEJM199907153410306","article-title":"The biology of chronic myeloid leukemia","volume":"341","author":"Faderl","year":"1999","journal-title":"N Engl J Med"},{"issue":"5405","key":"2021030516334752600_B2","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/243290a0","article-title":"Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining [letter]","volume":"243","author":"Rowley","year":"1973","journal-title":"Nature"},{"issue":"8","key":"2021030516334752600_B3","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1182\/blood-2008-03-144790","article-title":"Molecular biology of bcr-abl1-positive chronic myeloid leukemia","volume":"113","author":"Quint\u00e1s-Cardama","year":"2009","journal-title":"Blood"},{"issue":"7","key":"2021030516334752600_B4","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1182\/blood-2013-04-495598","article-title":"Tyrosine kinase inhibitor usage, treatment outcome, and prognostic scores in CML: report from the population-based Swedish CML registry","volume":"122","author":"H\u00f6glund","year":"2013","journal-title":"Blood"},{"issue":"24","key":"2021030516334752600_B5","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1200\/JCO.2015.66.2866","article-title":"Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population","volume":"34","author":"Bower","year":"2016","journal-title":"J Clin Oncol"},{"issue":"1","key":"2021030516334752600_B6","first-page":"186","article-title":"An optimized multiplex polymerase chain reaction (PCR) for detection of BCR-ABL fusion mRNAs in haematological disorders","volume":"8","author":"Cross","year":"1994","journal-title":"Leukemia"},{"issue":"1","key":"2021030516334752600_B7","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.blre.2005.01.008","article-title":"Molecular monitoring of BCR-ABL as a guide to clinical management in chronic myeloid leukaemia","volume":"20","author":"Hughes","year":"2006","journal-title":"Blood Rev"},{"issue":"6","key":"2021030516334752600_B8","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1182\/blood-2013-05-501569","article-title":"European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013","volume":"122","author":"Baccarani","year":"2013","journal-title":"Blood"},{"issue":"4","key":"2021030516334752600_B9","doi-asserted-by":"crossref","DOI":"10.4314\/thrb.v18i4.3","article-title":"Complete haematological response to imatinib in chronic myeloid leukaemia patients attending the Ocean Road Cancer Institute in Tanzania","volume":"18","author":"Tebuka","year":"2016","journal-title":"Tanzan J Health Res"},{"issue":"1","key":"2021030516334752600_B10","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1200\/JGO.2015.000570","article-title":"Novel Humanitarian Aid Program: The Glivec International Patient Assistance Program-Lessons Learned From Providing Access to Breakthrough Targeted Oncology Treatment in Low- and Middle-Income Countries","volume":"1","author":"Garcia-Gonzalez","year":"2015","journal-title":"J Glob Oncol"},{"key":"2021030516334752600_B11","doi-asserted-by":"crossref","first-page":"268921","DOI":"10.1155\/2010\/268921","article-title":"The effect of imatinib mesylate for newly diagnosed Philadelphia chromosome-positive, chronic-phase myeloid leukemia in sub-Saharan African patients: The experience of C\u00f4te d\u2019Ivoire","volume":"2010","author":"Koffi","year":"2010","journal-title":"Adv Hematol"},{"issue":"1","key":"2021030516334752600_B12","doi-asserted-by":"crossref","first-page":"e2017062","DOI":"10.4084\/mjhid.2017.062","article-title":"Outcome of frontline treatment with \u201cgeneric\u201d imatinib in adult patients with chronic myeloid leukemia in Algerian population: a multicenter study","volume":"9","author":"Entasoltan","year":"2017","journal-title":"Mediterr J Hematol Infect Dis"},{"issue":"10","key":"2021030516334752600_B13","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1007\/s00277-016-2745-4","article-title":"Pattern of chronic myeloid leukemia in the imatinib era in a Sub-Saharan African setting","volume":"95","author":"Faye","year":"2016","journal-title":"Ann Hematol"},{"issue":"20","key":"2021030516334752600_B14","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"issue":"4","key":"2021030516334752600_B15","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/s41375-020-0776-2","article-title":"European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia","volume":"34","author":"Hochhaus","year":"2020","journal-title":"Leukemia"},{"issue":"7","key":"2021030516334752600_B16","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1007\/s00432-017-2372-z","article-title":"Factors influencing adherence in CML and ways to improvement: Results of a patient-driven survey of 2546 patients in 63 countries","volume":"143","author":"Geissler","year":"2017","journal-title":"J Cancer Res Clin Oncol"},{"issue":"1","key":"2021030516334752600_B17","first-page":"1","article-title":"Adherence to imatinib in patients with chronic myeloid leukemia in the Congo","volume":"2","author":"Okouango","year":"2017","journal-title":"Austin Hematol"},{"key":"2021030516334752600_B18","author":"National Cancer Institute (US)","year":"2017"},{"issue":"5","key":"2021030516334752600_B19","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1182\/blood-2006-02-001495","article-title":"Survival advantage from imatinib compared with the combination interferon-\u03b1 plus cytarabine in chronic-phase chronic myelogenous leukemia: historical comparison between two phase 3 trials","volume":"108","author":"Roy","year":"2006","journal-title":"Blood"},{"issue":"23","key":"2021030516334752600_B20","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.1056\/NEJMoa062867","article-title":"Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia","volume":"355","author":"Druker","year":"2006","journal-title":"N Engl J Med"},{"issue":"9","key":"2021030516334752600_B21","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1056\/NEJMoa011573","article-title":"Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia","volume":"346","author":"Kantarjian","year":"2002","journal-title":"N Engl J Med"},{"issue":"6","key":"2021030516334752600_B22","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1038\/leu.2009.38","article-title":"Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia [published correction appears in Leukemia. 2010;24(5):1102]","volume":"23","author":"Hochhaus","year":"2009","journal-title":"Leukemia"},{"issue":"6","key":"2021030516334752600_B23","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1182\/blood.V86.6.2371.bloodjournal8662371","article-title":"Increase of bcr-abl chimeric mRNA expression in tumor cells of patients with chronic myeloid leukemia precedes disease progression","volume":"86","author":"Gaiger","year":"1995","journal-title":"Blood"},{"issue":"11","key":"2021030516334752600_B24","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1056\/NEJMoa022457","article-title":"Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia","volume":"348","author":"O\u2019Brien","year":"2003","journal-title":"N Engl J Med"},{"issue":"15","key":"2021030516334752600_B25","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1056\/NEJMoa030513","article-title":"Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia","volume":"349","author":"Hughes","year":"2003","journal-title":"N Engl J Med"},{"issue":"1","key":"2021030516334752600_B26","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1080\/16078454.2020.1765563","article-title":"Impact of anemia on the outcomes of chronic phase chronic myeloid leukemia in TKI era","volume":"25","author":"Liu","year":"2020","journal-title":"Hematology"},{"issue":"1","key":"2021030516334752600_B27","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1002\/cncr.11863","article-title":"The significance of myelosuppression during therapy with imatinib mesylate in patients with chronic myelogenous leukemia in chronic phase","volume":"100","author":"Sneed","year":"2004","journal-title":"Cancer"},{"issue":"2","key":"2021030516334752600_B28","doi-asserted-by":"crossref","first-page":"e2486","DOI":"10.1097\/MD.0000000000002486","article-title":"Combination of white blood cell count at presentation with molecular response at 3 months better predicts deep molecular responses to imatinib in newly diagnosed chronic-phase chronic myeloid leukemia patients","volume":"95","author":"Qin","year":"2016","journal-title":"Medicine"},{"key":"2021030516334752600_B29","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.exphem.2016.09.009","article-title":"Alterations in the bone marrow microenvironment may elicit defective hematopoiesis: a comparison of aplastic anemia, chronic myeloid leukemia, and normal bone marrow","volume":"45","author":"Park","year":"2017","journal-title":"Exp Hematol"},{"issue":"1","key":"2021030516334752600_B30","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s12288-010-0048-9","article-title":"Total Leukocyte Counts and the Requirement of Dose Reduction due to Cytopenias as Prognostic Indicators Affecting Response to Imatinib in Chronic Myeloid Leukemia","volume":"27","author":"Ashutosh","year":"2011","journal-title":"Indian J Hematol Blood Transfus"},{"issue":"8","key":"2021030516334752600_B31","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1038\/sj.leu.2402996","article-title":"Prognostic factors for patients with chronic myeloid leukaemia in chronic phase treated with imatinib mesylate after failure of interferon alfa","volume":"17","author":"Marin","year":"2003","journal-title":"Leukemia"},{"issue":"1","key":"2021030516334752600_B32","doi-asserted-by":"crossref","first-page":"30","DOI":"10.4103\/0976-500X.149141","article-title":"Adverse drug reactions of imatinib in patients with chronic myeloid leukemia: A single-center surveillance study","volume":"6","author":"Francis","year":"2015","journal-title":"J Pharmacol Pharmacother"},{"issue":"1","key":"2021030516334752600_B33","doi-asserted-by":"crossref","first-page":"e1000360","DOI":"10.1371\/journal.pgen.1000360","article-title":"Reduced neutrophil count in people of African descent is due to a regulatory variant in the Duffy antigen receptor for chemokines gene","volume":"5","author":"Reich","year":"2009","journal-title":"PLoS Genet"},{"issue":"10","key":"2021030516334752600_B34","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1200\/JCO.2009.24.3881","article-title":"Neutrophil count in African Americans: lowering the target cutoff to initiate or resume chemotherapy?","volume":"28","author":"Hsieh","year":"2010","journal-title":"J Clin Oncol"},{"issue":"3","key":"2021030516334752600_B35","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.beha.2009.06.001","article-title":"Management of drug toxicities in chronic myeloid leukaemia","volume":"22","author":"Mauro","year":"2009","journal-title":"Best Pract Res Clin Haematol"},{"issue":"1","key":"2021030516334752600_B36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00204-011-0729-7","article-title":"The safety profile of imatinib in CML and GIST: long-term considerations","volume":"86","author":"Thanopoulou","year":"2012","journal-title":"Arch Toxicol"},{"issue":"7","key":"2021030516334752600_B37","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1093\/jnci\/djr060","article-title":"Multicenter independent assessment of outcomes in chronic myeloid leukemia patients treated with imatinib","volume":"103","author":"Gambacorti-Passerini","year":"2011","journal-title":"J Natl Cancer Inst"},{"key":"2021030516334752600_B38","doi-asserted-by":"crossref","first-page":"18","DOI":"10.7812\/TPP\/18-033","article-title":"The unmet challenge of medication nonadherence","volume":"22","author":"Kleinsinger","year":"2018","journal-title":"Perm J"},{"issue":"8-9","key":"2021030516334752600_B39","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1177\/2040622317714966","article-title":"Evaluation of medication adherence in chronic disease at a federally qualified health center","volume":"8","author":"Oung","year":"2017","journal-title":"Ther Adv Chronic Dis"},{"issue":"4","key":"2021030516334752600_B40","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1590\/s1984-82502016000400001","article-title":"Adherence and\/or discontinuation of imatinib mesylate in patients with chronic myeloid leukemia","volume":"52","author":"Alves","year":"2016","journal-title":"Braz J Pharm Sci"},{"issue":"3","key":"2021030516334752600_B41","first-page":"174","article-title":"Adherence to treatment with imatinib in chronic myeloid leukemia: a study of the first decade of responses obtained at a Brazilian hospital","volume":"35","author":"Dos Reis","year":"2013","journal-title":"Rev Bras Hematol Hemoter"},{"issue":"14","key":"2021030516334752600_B42","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1200\/JCO.2009.26.3087","article-title":"Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieve complete cytogenetic responses on imatinib","volume":"28","author":"Marin","year":"2010","journal-title":"J Clin Oncol"},{"issue":"7","key":"2021030516334752600_B43","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.leukres.2012.01.021","article-title":"Adherence to oral tyrosine kinase inhibitor therapies in chronic myeloid leukemia","volume":"36","author":"Gater","year":"2012","journal-title":"Leuk Res"},{"issue":"3","key":"2021030516334752600_B44","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.japh.2017.01.004","article-title":"Medication adherence, molecular monitoring, and clinical outcomes in patients with chronic myelogenous leukemia in a large HMO","volume":"57","author":"Haque","year":"2017","journal-title":"J Am Pharm Assoc (2003)"},{"issue":"7","key":"2021030516334752600_B45","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.3109\/10428194.2012.745525","article-title":"Trends in chronic myeloid leukemia incidence and survival in the United States from 1975 to 2009","volume":"54","author":"Chen","year":"2013","journal-title":"Leuk Lymphoma"},{"issue":"9","key":"2021030516334752600_B46","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1182\/blood-2011-08-358135","article-title":"Improved survival in chronic myeloid leukemia since the introduction of imatinib therapy: a single-institution historical experience","volume":"119","author":"Kantarjian","year":"2012","journal-title":"Blood"},{"issue":"10","key":"2021030516334752600_B47","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1056\/NEJMoa1609324","article-title":"Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia","volume":"376","author":"Hochhaus","year":"2017","journal-title":"N Engl J Med"}],"container-title":["Blood Advances"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/5\/5\/1403\/1801841\/advancesadv2020002973.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/bloodadvances\/article-pdf\/5\/5\/1403\/1801841\/advancesadv2020002973.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:59:10Z","timestamp":1671497950000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/bloodadvances\/article\/5\/5\/1403\/475392\/Molecular-response-to-imatinib-in-patients-with"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,5]]},"references-count":47,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,3,9]]}},"URL":"https:\/\/doi.org\/10.1182\/bloodadvances.2020002973","relation":{},"ISSN":["2473-9529","2473-9537"],"issn-type":[{"value":"2473-9529","type":"print"},{"value":"2473-9537","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,5]]}}}