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1. Expectations and outcomes of varying treatment strategies for CML presenting during pregnancy.

Author

Robertson, H. F., Milojkovic, D., Butt, N., Byrne, J., Claudiani, S., Copland, M., Gallipoli, P., Innes, A. J., Knight, K., Mahdi, A. J., Parker, J., Virchis, A., and Apperley, J. F.

Subjects
*CHRONIC myeloid leukemia, *PROTEIN-tyrosine kinase inhibitors, *FETAL abnormalities, *LEUKAPHERESIS, *PREGNANCY
Abstract

Summary: Diagnosing chronic myeloid leukaemia (CML) during pregnancy is rare. Tyrosine kinase inhibitors (TKIs) have traditionally been contraindicated owing to their teratogenicity. Management decisions should consider the risks to mother and foetus of uncontrolled disease and teratogenic medications. Further cases are required to build upon the paucity of current literature. We report 22 cases of CML diagnosed during pregnancy from 2002 to date. Twenty‐one pregnancies resulted in healthy babies and one patient miscarried. Some patients remained untreated throughout pregnancy but the majority received one or both of interferon‐α and leucapheresis. One patient was started on imatinib at Week 26, and one on hydroxycarbamide in the third trimester. We report haematological parameters during pregnancy to provide clinicians with realistic expectations of management. There were no fetal abnormalities related to treatment during pregnancy. Seventeen patients achieved at least major molecular response on first‐line TKI. A diagnosis of CML during pregnancy can be managed without significant consequences for mother or child. Leucapheresis and interferon‐α are generally safe throughout pregnancy. Despite having been avoided previously, there is growing evidence that certain TKIs may be used in particular circumstances during the later stages of pregnancy. Future work should aim to further elucidate this safety profile. [ABSTRACT FROM AUTHOR]

Published
2024
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2. FISH-negative BCR::ABL1-positive e19a2 chronic myeloid leukaemia: the most cryptic of insertions

Author

May, P, Reid, A, Robinson, M, Khorashad, J, Milojkovic, D, Claudiani, S, Genomics England Research Consortium, Willis, F, Apperley, J, and Innes, A

Abstract

Background: Chronic myeloid leukaemia (CML) is one of the most well characterised human malignancies. Most patients have a cytogenetically visible translocation between chromosomes 9 and 22 which generates the pathognomonic BCR::ABL1 fusion gene. The derivative chromosome 22 (‘Philadelphia’ or Ph chromosome) usually harbours the fusion gene encoding a constitutively active ABL1 kinase domain. A small subset of patients have no detectable translocation. Historically, these ‘Philadelphia chromosome negative’ patients caused diagnostic confusion between CML and other myeloproliferative neoplasms; it is now well established that the BCR::ABL1 fusion gene can be generated via submicroscopic intrachromosomal insertion of ABL1 sequence into BCR, or, more rarely, of BCR into ABL1. The fusion genes arising from cryptic insertions are not detectable via G-banded chromosome analysis [karyotype] but can nevertheless always be detected using fluorescence in situ hybridisation (FISH) and/or qualitative reverse transcriptase PCR. Case presentation: A 43-year-old female presented with suspected CML in 2007; however, contemporaneous gold standard laboratory investigations, G-banded chromosome analysis and FISH, were both negative. The reverse transcriptase quantitative PCR (RT-qPCR) assay available at the time, which was capable of detecting the common BCR::ABL1 transcripts (e13a2/e14a2), was also negative. Upon review in 2009, the newly recommended reverse transcriptase multiplex PCR (capable of detecting all BCR::ABL1 transcripts including the atypical ones) subsequently detected an e19a2 fusion. The patient then responded to tyrosine kinase inhibitor therapy. In contrast, FISH studies of both samples with three commercially available probes remained consistently negative. Retrospective whole genome sequencing, undertaken as part of the 100,000 Genomes Project, has now revealed that the patient’s BCR::ABL1 fusion gene arose via a uniquely small insertion of 122kb ABL sequences into BCR. Conclusions: We present a patient with suspected chronic myeloid leukaemia whose genetic investigations were originally negative at the time of diagnosis despite the use of contemporaneous gold standard methods. This is the first report of a FISH-negative, BCR::ABL1 positive CML which demonstrates that, even after sixty years of research into one of the most well understood human malignancies, whole genome sequencing can yield novel diagnostic findings in CML.

Published
2023

4. Persistence of Drug-Resistant Leukemic Stem Cells and Impaired NK Cell Immunity in CML Patients Depend on MIR300 Antiproliferative and PP2A-Activating Functions

Author

Silvestri, G, Trotta, R, Stramucci, L, Ellis, J, Harb, J, Neviani, P, Wang, S, Eisfeld, A, Walker, C, Zhang, B, Srutova, K, Gambacorti-Passerini, C, Pineda, G, Jamieson, C, Stagno, F, Vigneri, P, Nteliopoulos, G, May, P, Reid, A, Garzon, R, Roy, D, Moutuou, M, Guimond, M, Hokland, P, Deininger, M, Fitzgerald, G, Harman, C, Dazzi, F, Milojkovic, D, Apperley, J, Marcucci, G, Qi, J, Polakova, K, Zou, Y, Fan, X, Baer, M, Calabretta, B, Perrotti, D, Silvestri G., Trotta R., Stramucci L., Ellis J. J., Harb J. G., Neviani P., Wang S., Eisfeld A. -K., Walker C. J., Zhang B., Srutova K., Gambacorti-Passerini C., Pineda G., Jamieson C. H. M., Stagno F., Vigneri P., Nteliopoulos G., May P. C., Reid A. G., Garzon R., Roy D. -C., Moutuou M. M., Guimond M., Hokland P., Deininger M. W., Fitzgerald G., Harman C., Dazzi F., Milojkovic D., Apperley J. F., Marcucci G., Qi J., Polakova K. M., Zou Y., Fan X., Baer M. R., Calabretta B., Perrotti D., Silvestri, G, Trotta, R, Stramucci, L, Ellis, J, Harb, J, Neviani, P, Wang, S, Eisfeld, A, Walker, C, Zhang, B, Srutova, K, Gambacorti-Passerini, C, Pineda, G, Jamieson, C, Stagno, F, Vigneri, P, Nteliopoulos, G, May, P, Reid, A, Garzon, R, Roy, D, Moutuou, M, Guimond, M, Hokland, P, Deininger, M, Fitzgerald, G, Harman, C, Dazzi, F, Milojkovic, D, Apperley, J, Marcucci, G, Qi, J, Polakova, K, Zou, Y, Fan, X, Baer, M, Calabretta, B, Perrotti, D, Silvestri G., Trotta R., Stramucci L., Ellis J. J., Harb J. G., Neviani P., Wang S., Eisfeld A. -K., Walker C. J., Zhang B., Srutova K., Gambacorti-Passerini C., Pineda G., Jamieson C. H. M., Stagno F., Vigneri P., Nteliopoulos G., May P. C., Reid A. G., Garzon R., Roy D. -C., Moutuou M. M., Guimond M., Hokland P., Deininger M. W., Fitzgerald G., Harman C., Dazzi F., Milojkovic D., Apperley J. F., Marcucci G., Qi J., Polakova K. M., Zou Y., Fan X., Baer M. R., Calabretta B., and Perrotti D.

Abstract

Persistence of drug-resistant quiescent leukemic stem cells (LSC) and impaired natural killer (NK) cell immune response account for relapse of chronic myelogenous leukemia (CML). Inactivation of protein phosphatase 2A (PP2A) is essential for CML-quiescent LSC survival and NK cell antitumor activity. Here we show that MIR300 has antiproliferative and PP2A-activating functions that are dose dependently differentially induced by CCND2/CDK6 and SET inhibition, respectively. MIR300 is upregulated in CML LSCs and NK cells by bone marrow microenvironment (BMM) signals to induce quiescence and impair immune response, respectively. Conversely, BCR-ABL1 downregulates MIR300 in CML progenitors to prevent growth arrest and PP2A-mediated apoptosis. Quiescent LSCs escape apoptosis by upregulating TUG1 long noncoding RNA that uncouples and limits MIR300 function to cytostasis. Genetic and pharmacologic MIR300 modulation and/or PP2A-activating drug treatment restore NK cell activity, inhibit BMM-induced growth arrest, and selectively trigger LSC apoptosis in vitro and in patient-derived xenografts; hence, the importance of MIR300 and PP2A activity for CML development and therapy. SIGNIFICANCE: Tumor-naïve microenvironment–induced MIR300 is the only tumor suppressor miRNA that induces CML LSC quiescence while inhibiting NK cell antitumor immune response, and CML LSC/ progenitor cell apoptosis through its anti-proliferative and PP2A-activating functions, respectively. Thus, the importance of MIR300 and PP2A-activating drugs for formation/survival and eradication of drug-resistant CML LSCs, respectively.

Published
2020

5. A retrospective observational research study to describe the real-world use of bosutinib in patients with chronic myeloid leukemia in the United Kingdom and the Netherlands

Author

Claudiani, S., Janssen, J., Byrne, J., Smith, G., Blijlevens, N.M., Raghavan, M., Smith, M., Clark, R.E., McLain-Smith, S., Carter, A.M., Milojkovic, D., Apperley, J.F., Claudiani, S., Janssen, J., Byrne, J., Smith, G., Blijlevens, N.M., Raghavan, M., Smith, M., Clark, R.E., McLain-Smith, S., Carter, A.M., Milojkovic, D., and Apperley, J.F.

Abstract

Contains fulltext : 251599.pdf (Publisher’s version ) (Open Access), OBJECTIVES: To describe the real-world effectiveness and safety of bosutinib in patients with chronic myeloid leukemia (CML). METHODS: This was a multi-center, retrospective, non-interventional chart review study conducted in 10 hospitals in the United Kingdom and the Netherlands. RESULTS: Eighty-seven patients were included. Bosutinib was the third-line tyrosine kinase inhibitor (TKI) in 33 (38%) and fourth-line in 44 (51%) patients. Median treatment duration was 15.6 months. Among 84 patients in chronic phase (CP) at baseline, 26 (31%) switched to bosutinib due to resistance and 57 (68%) due to intolerance to prior TKIs. Cumulative complete cytogenetic and major molecular response rates in CP patients were 67% and 55%, respectively. After a median follow-up of 21.5 months, nine (11%) patients in CP died; estimated overall survival rates at 1 and 2 years postbosutinib initiation were 95% and 91%, respectively. Overall, 33/87 (38%) patients discontinued bosutinib due to either lack of efficacy/disease progression (17%), adverse events (14%), death (2%), or other reasons (5%). Eighty-two (94%) patients experienced ≥1 adverse event possibly related to bosutinib, most commonly diarrhea (52%). CONCLUSIONS: Bosutinib used in routine clinical practice in heavily pretreated patients with CML is an effective treatment for patients in CP and is generally tolerable.

Published
2022

6. Bosutinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia: final results from the BFORE trial

Author

Brümmendorf, T, Cortes, J, Milojkovic, D, Gambacorti-Passerini, C, Clark, R, le Coutre, P, Garcia-Gutierrez, V, Chuah, C, Kota, V, Lipton, J, Rousselot, P, Mauro, M, Hochhaus, A, Hurtado Monroy, R, Leip, E, Purcell, S, Yver, A, Viqueira, A, Deininger, M, Brümmendorf, Tim H, Cortes, Jorge E, Milojkovic, Dragana, Gambacorti-Passerini, Carlo, Clark, Richard E, le Coutre, Philipp, Garcia-Gutierrez, Valentin, Chuah, Charles, Kota, Vamsi, Lipton, Jeffrey H, Rousselot, Philippe, Mauro, Michael J, Hochhaus, Andreas, Hurtado Monroy, Rafael, Leip, Eric, Purcell, Simon, Yver, Anne, Viqueira, Andrea, Deininger, Michael W, Brümmendorf, T, Cortes, J, Milojkovic, D, Gambacorti-Passerini, C, Clark, R, le Coutre, P, Garcia-Gutierrez, V, Chuah, C, Kota, V, Lipton, J, Rousselot, P, Mauro, M, Hochhaus, A, Hurtado Monroy, R, Leip, E, Purcell, S, Yver, A, Viqueira, A, Deininger, M, Brümmendorf, Tim H, Cortes, Jorge E, Milojkovic, Dragana, Gambacorti-Passerini, Carlo, Clark, Richard E, le Coutre, Philipp, Garcia-Gutierrez, Valentin, Chuah, Charles, Kota, Vamsi, Lipton, Jeffrey H, Rousselot, Philippe, Mauro, Michael J, Hochhaus, Andreas, Hurtado Monroy, Rafael, Leip, Eric, Purcell, Simon, Yver, Anne, Viqueira, Andrea, and Deininger, Michael W

Abstract

This analysis from the multicenter, open-label, phase 3 BFORE trial reports efficacy and safety of bosutinib in patients with newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML) after five years’ follow-up. Patients were randomized to 400-mg once-daily bosutinib (n = 268) or imatinib (n = 268; three untreated). At study completion, 59.7% of bosutinib- and 58.1% of imatinib-treated patients remained on study treatment. Median duration of treatment and time on study was 55 months in both groups. Cumulative major molecular response (MMR) rate by 5 years was higher with bosutinib versus imatinib (73.9% vs. 64.6%; odds ratio, 1.57 [95% CI, 1.08–2.28]), as were cumulative MR4 (58.2% vs. 48.1%; 1.50 [1.07–2.12]) and MR4.5 (47.4% vs. 36.6%; 1.57 [1.11–2.22]) rates. Superior MR with bosutinib versus imatinib was consistent across Sokal risk groups, with greatest benefit seen in patients with high risk. Treatment-emergent adverse events (TEAEs) were consistent with 12-month data. After 5 years of follow-up there was an increase in the incidence of cardiac, effusion, renal, and vascular TEAEs in bosutinib- and imatinib-treated patients, but overall, no new safety signals were identified. These final results support 400-mg once-daily bosutinib as standard-of-care in patients with newly diagnosed CP CML.

Published
2022

7. P713: REAL-WORLD MANAGEMENT OF PATIENTS WITH CHRONIC MYELOID LEUKAEMIA (CML): FIRST ANALYSIS FROM THE UK NATIONAL REGISTRY FOR CML

Author

Nesr, G., primary, Szydlo, R., additional, Braithwaite, B., additional, Frackelton, S., additional, Mathew, P., additional, Hashmi, M., additional, Fernando, F., additional, Innes, A., additional, Claudiani, S., additional, Khan, A., additional, Rao, A., additional, Foroni, L., additional, Milojkovic, D., additional, Apperley, J. F., additional, and Clark, R. E., additional

Published
2022
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9. P706: ASCIMINIB USE IN CML: THE UK EXPERIENCE

Author

Innes, A., primary, Orovboni, V., additional, Claudiani, S., additional, Fernando, F., additional, Khan, A., additional, Byrne, J., additional, Gallipoli, P., additional, Copland, M., additional, Horne, G., additional, Arnold, C., additional, Collins, A., additional, Cunningham, N., additional, Danga, A., additional, Frewin, R., additional, Garland, P., additional, Hannah, G., additional, Hassan, S., additional, Makkuni, S., additional, Rothwell, K., additional, Foroni, L., additional, Hayden, C., additional, Apperley, J., additional, and Milojkovic, D., additional

Published
2022
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13. Patient-reported outcomes in the phase 3 BFORE trial of bosutinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia

Author

Cortes, J, Gambacorti-Passerini, C, Deininger, M, Mauro, M, Chuah, C, Kim, D, Milojkovic, D, le Coutre, P, Garcia-Gutierrez, V, Crescenzo, R, Mamolo, C, Reisman, A, Hochhaus, A, Brummendorf, T, Cortes J. E., Gambacorti-Passerini C., Deininger M. W., Mauro M. J., Chuah C., Kim D. -W., Milojkovic D., le Coutre P., Garcia-Gutierrez V., Crescenzo R., Mamolo C., Reisman A., Hochhaus A., Brummendorf T. H., Cortes, J, Gambacorti-Passerini, C, Deininger, M, Mauro, M, Chuah, C, Kim, D, Milojkovic, D, le Coutre, P, Garcia-Gutierrez, V, Crescenzo, R, Mamolo, C, Reisman, A, Hochhaus, A, Brummendorf, T, Cortes J. E., Gambacorti-Passerini C., Deininger M. W., Mauro M. J., Chuah C., Kim D. -W., Milojkovic D., le Coutre P., Garcia-Gutierrez V., Crescenzo R., Mamolo C., Reisman A., Hochhaus A., and Brummendorf T. H.

Abstract

Background: In the phase 3 BFORE trial (NCT02130557), treatment with bosutinib resulted in a significantly higher major molecular response rate at 12 months versus imatinib in the modified intent-to-treat (mITT) population of patients with newly diagnosed chronic phase chronic myeloid leukemia (CP CML). Assessment of patient-reported outcomes (PROs) was an exploratory objective. Methods: Patients with newly diagnosed CP CML were randomized 1:1 to receive once-daily bosutinib 400 mg or imatinib 400 mg as first-line therapy. Patients completed the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leu) and EuroQoL-5 Dimensions (EQ-5D) questionnaires at baseline, every 3 months for the first 24 months of treatment, every 6 months thereafter, and at treatment completion. We report PRO results at month 12 in the mITT population (bosutinib: n = 246; imatinib: n = 241). Results: Mean FACT-Leu combined and subscale scores were similar at baseline in the bosutinib and imatinib arms; at month 12, all scores demonstrated improvement or maintenance of health-related quality of life (HRQoL) in both treatment arms. Repeated-measures mixed-effects models showed no significant difference between bosutinib and imatinib for any FACT-Leu score. Functional health status, as measured by EQ-5D, also demonstrated improvement or maintenance with bosutinib and imatinib at month 12. Conclusions: Similar improvements in PROs compared with baseline were seen after 12 months of treatment with first-line bosutinib or imatinib in the BFORE trial. Newly diagnosed patients with CP CML receiving bosutinib or imatinib can preserve or improve HRQoL during treatment, although clinical efficacy was superior with bosutinib

Published
2019

17. SIGNIFICANCE OF ACHIEVING SECOND CHRONIC PHASE PRIOR TO ALLOGENEIC STEM CELL TRANSPLANT FOLLOWING TYROSINE KINASE INHIBITOR THERAPY: A RETROSPECTIVE STUDY FROM THE CHRONIC MALIGNANCY WORKING PARTY OF THE EUROPEAN GROUP FOR BLOOD AND MARROW TRANSPLANTATION: PH-P099

Author

Milojkovic, D., Szydlo, R., Hoek, J., Beelen, D., Hamladji, R., Kyrcz-Krzemien, S., Bacigalupo, A., Niederwieser, D., Tischer, J., Schwerdtfeger, R., Volin, L., Gurman, G., Greinix, H., Chalandon, Y., Kroeger, N., and Olavarria, E.

Published
2014

18. PROGNOSTIC SIGNIFICANCE OF EBMT SCORE FOR CHRONIC MYELOID LEUKAEMIA PATIENTS IN THE ERA OF TYROSINE KINASE INHIBITOR THERAPY: A RETROSPECTIVE STUDY FROM THE CHRONIC MALIGNANCY WORKING PARTY OF THE EUROPEAN GROUP FOR BLOOD AND MARROW TRANSPLANTATION (EBMT): PH-O064

Author

Milojkovic, D., Szydlo, R., Hoek, J., Beelen, D., Hamladji, R., Kyrcz-Krzemien, S., Bacigalupo, A., Niederwieser, D., Tischer, J., Schwerdtfeger, R., Volin, L., Gurman, G., Greinix, H., Chalandon, Y., Kroeger, N., and Olavarria, E.

Published
2014

20. Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a position statement and new risk assessment tools from the Cardio-Oncology Study Group of the Heart Failure Association of the European Society of Cardiology in collaboration with the International Cardio-Oncology Society

Author

Lyon, A.R. Dent, S. Stanway, S. Earl, H. Brezden-Masley, C. Cohen-Solal, A. Tocchetti, C.G. Moslehi, J.J. Groarke, J.D. Bergler-Klein, J. Khoo, V. Tan, L.L. Anker, M.S. von Haehling, S. Maack, C. Pudil, R. Barac, A. Thavendiranathan, P. Ky, B. Neilan, T.G. Belenkov, Y. Rosen, S.D. Iakobishvili, Z. Sverdlov, A.L. Hajjar, L.A. Macedo, A.V.S. Manisty, C. Ciardiello, F. Farmakis, D. de Boer, R.A. Skouri, H. Suter, T.M. Cardinale, D. Witteles, R.M. Fradley, M.G. Herrmann, J. Cornell, R.F. Wechelaker, A. Mauro, M.J. Milojkovic, D. de Lavallade, H. Ruschitzka, F. Coats, A.J.S. Seferovic, P.M. Chioncel, O. Thum, T. Bauersachs, J. Andres, M.S. Wright, D.J. López-Fernández, T. Plummer, C. Lenihan, D.

Abstract

This position statement from the Heart Failure Association of the European Society of Cardiology Cardio-Oncology Study Group in collaboration with the International Cardio-Oncology Society presents practical, easy-to-use and evidence-based risk stratification tools for oncologists, haemato-oncologists and cardiologists to use in their clinical practice to risk stratify oncology patients prior to receiving cancer therapies known to cause heart failure or other serious cardiovascular toxicities. Baseline risk stratification proformas are presented for oncology patients prior to receiving the following cancer therapies: anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor inhibitors, second and third generation multi-targeted kinase inhibitors for chronic myeloid leukaemia targeting BCR-ABL, multiple myeloma therapies (proteasome inhibitors and immunomodulatory drugs), RAF and MEK inhibitors or androgen deprivation therapies. Applying these risk stratification proformas will allow clinicians to stratify cancer patients into low, medium, high and very high risk of cardiovascular complications prior to starting treatment, with the aim of improving personalised approaches to minimise the risk of cardiovascular toxicity from cancer therapies. © 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Published
2020

21. Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a position statement and new risk assessment tools from theCardio-OncologyStudyGroup of theHeartFailureAssociation of theEuropeanSociety ofCardiology in collaboration with theInternationalCardio-OncologySociety

Author

Lyon, AR, Dent, S, Stanway, S, Earl, H, Brezden-Masley, C, Cohen-Solal, A, Tocchetti, CG, Moslehi, JJ, Groarke, JD, Bergler-Klein, J, Khoo, V, Tan, LL, Anker, MS, von Haehling, S, Maack, C, Pudil, R, Barac, A, Thavendiranathan, P, Ky, B, Neilan, TG, Belenkov, Y, Rosen, SD, Iakobishvili, Z, Sverdlov, AL, Hajjar, LA, Macedo, AVS, Manisty, C, Ciardiello, F, Farmakis, D, de Boer, RA, Skouri, H, Suter, TM, Cardinale, D, Witteles, RM, Fradley, MG, Herrmann, J, Cornell, RF, Wechelaker, A, Mauro, MJ, Milojkovic, D, de Lavallade, H, Ruschitzka, F, Coats, AJS, Seferovic, PM, Chioncel, O, Thum, T, Bauersachs, J, Andres, MS, Wright, DJ, Lopez-Fernandez, T, Plummer, C, Lenihan, D, Lyon, AR, Dent, S, Stanway, S, Earl, H, Brezden-Masley, C, Cohen-Solal, A, Tocchetti, CG, Moslehi, JJ, Groarke, JD, Bergler-Klein, J, Khoo, V, Tan, LL, Anker, MS, von Haehling, S, Maack, C, Pudil, R, Barac, A, Thavendiranathan, P, Ky, B, Neilan, TG, Belenkov, Y, Rosen, SD, Iakobishvili, Z, Sverdlov, AL, Hajjar, LA, Macedo, AVS, Manisty, C, Ciardiello, F, Farmakis, D, de Boer, RA, Skouri, H, Suter, TM, Cardinale, D, Witteles, RM, Fradley, MG, Herrmann, J, Cornell, RF, Wechelaker, A, Mauro, MJ, Milojkovic, D, de Lavallade, H, Ruschitzka, F, Coats, AJS, Seferovic, PM, Chioncel, O, Thum, T, Bauersachs, J, Andres, MS, Wright, DJ, Lopez-Fernandez, T, Plummer, C, and Lenihan, D

Abstract

This position statement from the Heart Failure Association of the European Society of Cardiology Cardio-Oncology Study Group in collaboration with the International Cardio-Oncology Society presents practical, easy-to-use and evidence-based risk stratification tools for oncologists, haemato-oncologists and cardiologists to use in their clinical practice to risk stratify oncology patients prior to receiving cancer therapies known to cause heart failure or other serious cardiovascular toxicities. Baseline risk stratification proformas are presented for oncology patients prior to receiving the following cancer therapies: anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor inhibitors, second and third generation multi-targeted kinase inhibitors for chronic myeloid leukaemia targeting BCR-ABL, multiple myeloma therapies (proteasome inhibitors and immunomodulatory drugs), RAF and MEK inhibitors or androgen deprivation therapies. Applying these risk stratification proformas will allow clinicians to stratify cancer patients into low, medium, high and very high risk of cardiovascular complications prior to starting treatment, with the aim of improving personalised approaches to minimise the risk of cardiovascular toxicity from cancer therapies.

Published
2020

26. A randomised phase II trial of hydroxychloroquine and imatinib versus imatinib alone for patients with chronic myeloid leukaemia in major cytogenetic response with residual disease

Author

Horne, G. A., primary, Stobo, J., additional, Kelly, C., additional, Mukhopadhyay, A., additional, Latif, A. L., additional, Dixon-Hughes, J., additional, McMahon, L., additional, Cony-Makhoul, P., additional, Byrne, J., additional, Smith, G., additional, Koschmieder, S., additional, BrÜmmendorf, T. H., additional, Schafhausen, P., additional, Gallipoli, P., additional, Thomson, F., additional, Cong, W., additional, Clark, R. E., additional, Milojkovic, D., additional, Helgason, G. V., additional, Foroni, L., additional, Nicolini, F. E., additional, Holyoake, T. L., additional, and Copland, M., additional

Published
2020
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31. Safety and efficacy of bosutinib in fourth-line therapy of chronic myeloid leukemia patients

Author

García-Gutiérrez V, Milojkovic D, Hernandez-Boluda JC, Claudiani S, Martin Mateos ML, Casado-Montero LF, González G, Jimenez-Velasco A, Boque C, Martinez-Trillos A, Vázquez IM, Payer ÁR, Senín A, Amustio Díez E, García AB, Carrascosa GB, Ortí G, Ruiz BC, Fernández MÁ, Del Carmen García Garay M, Giraldo P, Guinea JM, De Las Heras Rodríguez N, Hernán N, Pérez AI, Piris-Villaespesa M, Lorenzo JLL, Martí-Tutusaus JMM, Vallansot RO, Ortega Rivas F, Puerta JM, Ramirez MJ, Romero E, Romo A, Rosell A, Saavedra SS, Sebrango A, Tallon J, Valencia S, Portero A, Steegmann JL, and Grupo Español de Leucemia Mieloide Crónica (GELMC)

Published
2019

36. PS1182 REAL WORLD TYROSINE KINASE INHIBITOR TREATMENT PATHWAYS, MONITORING PATTERNS AND RESPONSES COMPARED WITH ELN RECOMMENDATIONS IN CHRONIC MYELOID LEUKAEMIA: FINAL ANALYSIS OF THE UK TARGET CML STUDY

Author

Milojkovic, D., primary, Cross, N.C., additional, Ali, S., additional, Byrne, J.L., additional, Campbell, G., additional, Dignan, F.L., additional, Fildes, L., additional, McMullin, M.-F., additional, Neelakantan, P., additional, Sivakumaran, M., additional, Wandroo, F., additional, Willis, F., additional, Ryan, J., additional, Clark, R.E., additional, and Mead, A., additional

Published
2019
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37. S1626 INCOMPLETE COUNT RECOVERY IN PATIENTS WITH COMPLETE REMISSION PRIOR TO ALLOGENEIC HCT FOR AML IS ASSOCIATED WITH A HIGH NON-RELAPSE MORTALITY WITHOUT AN INCREASED RELAPSE RISK

Author

Innes, A., primary, Wooley, P., additional, Szydlo, R., additional, Lozano, S., additional, Fernando, F., additional, Bansal, D., additional, Palanicawandar, R., additional, Milojkovic, D., additional, May, P., additional, Nadal-Melsio, E., additional, Yebra-Fernandez, E., additional, Olavarria, E., additional, Apperley, J., additional, and Pavlu, J., additional

Published
2019
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38. Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: Results from the randomized BFORE trial

Author

Cortes, J, Gambacorti Passerini, C, Deininger, M, Mauro, M, Chuah, C, Kim, D, Dyagil, I, Glushko, N, Milojkovic, D, Le Coutre, P, Garcia-Gutierrez, V, Reilly, L, Jeynes-Ellis, A, Leip, E, Bardy-Bouxin, N, Hochhaus, A, Brümmendorf, T, Cortes, JE, Deininger, MW, Mauro, MJ, Chuah, Charles, Kim, DW, Brümmendorf, TH, Cortes, J, Gambacorti Passerini, C, Deininger, M, Mauro, M, Chuah, C, Kim, D, Dyagil, I, Glushko, N, Milojkovic, D, Le Coutre, P, Garcia-Gutierrez, V, Reilly, L, Jeynes-Ellis, A, Leip, E, Bardy-Bouxin, N, Hochhaus, A, Brümmendorf, T, Cortes, JE, Deininger, MW, Mauro, MJ, Chuah, Charles, Kim, DW, and Brümmendorf, TH

Abstract

Purpose Bosutinib is a potent dual SRC/ABL kinase inhibitor approved for adults with Philadelphia chromosome–positive chronic myeloid leukemia (CML) resistant and /or intolerant to prior therapy. We assessed the efficacy and safety of bosutinib versus imatinib for first-line treatment of chronic-phase CML. Methods In this ongoing, multinational, phase III study, 536 patients with newly diagnosed chronic-phase CML were randomly assigned 1:1 to receive 400 mg of bosutinib once daily (n = 268) or imatinib (n = 268). Per protocol, efficacy was assessed in patients who were Philadelphia chromosome–positive with typical (e13a2/e14a2) transcripts (bosutinib, n = 246; imatinib, n = 241). Patients with Philadelphia chromosome–negative–/BCR-ABL1–positive status and those with unknown Philadelphia chromosome status and/or atypical BCR-ABL1 transcript type were excluded from this population. Results The major molecular response (MMR) rate at 12 months (primary end point) was significantly higher with bosutinib versus imatinib (47.2% v 36.9%, respectively; P = .02), as was complete cytogenetic response (CCyR) rate by 12 months (77.2% v 66.4%, respectively; P = .0075). Cumulative incidence was favorable with bosutinib (MMR: hazard ratio, 1.34; P = .0173; CCyR: hazard ratio, 1.38; P, .001), with earlier response times. Four patients (1.6%) receiving bosutinib and six patients (2.5%) receiving imatinib experienced disease progression to accelerated/blast phase. Among treated patients, 22.0% of patients receiving bosutinib and 26.8% of patients receiving imatinib discontinued treatment, most commonly for drug-related toxicity (12.7% and 8.7%, respectively). Grade $ 3 diarrhea (7.8% v 0.8%) and increased ALT (19.0% v 1.5%) and AST (9.7% v 1.9%) levels were more common with bosutinib. Cardiac and vascular toxicities were uncommon. Conclusion Patients who received bosutinib had significantly higher rates of MMR and CCyR and achieved responses faster than those who received imatinib. Co

Published
2018

39. European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia

Author

Steegmann, J. L., Baccarani, M., Breccia, M., Casado, L. F., Garcia-Gutierrez, V., Hochhaus, A., Kim, D-W, Kim, T. D., Khoury, H. J., Le Coutre, P., Mayer, J., Milojkovic, D., Porkka, Kimmo, Rea, D., Rosti, G., Saussele, S., Hehlmann, R., Clark, R. E., Clinicum, Department of Medicine, Hematologian yksikkö, and Department of Oncology

Subjects
DIAGNOSED CHRONIC-PHASE, DASATINIB 100 MG, PULMONARY ARTERIAL-HYPERTENSION, PATIENTS RECEIVING IMATINIB, CHRONIC MYELOGENOUS LEUKEMIA, CHROMOSOME-POSITIVE LEUKEMIAS, 3122 Cancers, IMATINIB MESYLATE THERAPY, TYROSINE-KINASE INHIBITOR, ACUTE-RENAL-FAILURE, ACUTE LYMPHOBLASTIC-LEUKEMIA
Abstract

Most reports on chronic myeloid leukaemia (CML) treatment with tyrosine kinase inhibitors (TKIs) focus on efficacy, particularly on molecular response and outcome. In contrast, adverse events (AEs) are often reported as infrequent, minor, tolerable and manageable, but they are increasingly important as therapy is potentially lifelong and multiple TKIs are available. For this reason, the European LeukemiaNet panel for CML management recommendations presents an exhaustive and critical summary of AEs emerging during CML treatment, to assist their understanding, management and prevention. There are five major conclusions. First, the main purpose of CML treatment is the antileukemic effect. Suboptimal management of AEs must not compromise this first objective. Second, most patients will have AEs, usually early, mostly mild to moderate, and which will resolve spontaneously or are easily controlled by simple means. Third, reduction or interruption of treatment must only be done if optimal management of the AE cannot be accomplished in other ways, and frequent monitoring is needed to detect resolution of the AE as early as possible. Fourth, attention must be given to comorbidities and drug interactions, and to new events unrelated to TKIs that are inevitable during such a prolonged treatment. Fifth, some TKI-related AEs have emerged which were not predicted or detected in earlier studies, maybe because of suboptimal attention to or absence from the preclinical data. Overall, imatinib has demonstrated a good long-term safety profile, though recent findings suggest underestimation of symptom severity by physicians. Second and third generation TKIs have shown higher response rates, but have been associated with unexpected problems, some of which could be irreversible. We hope these recommendations will help to minimise adverse events, and we believe that an optimal management of them will be rewarded by better TKI compliance and thus better CML outcomes, together with better quality of life.

Published
2016

41. Development of acute graft-versus-host disease post allogeneic stem cell transplantation results in significant episodes of recurrent and prolonged hospitalisations which are with associated a significant economic burden to stem cell transplant units

Author

Innes, A, Apperley, J, Allwood, Z, Altaf, S, Chaidos, A, Kanfer, E, Kirschke, S, Milojkovic, D, MacDonald, D, Pavlu, J, Rahemtulla, A, Slade, D, Szydlo, R, Olavarria, E, Gabriel, I, Imperial College Trust, and Imperial College Healthcare NHS Trust- BRC Funding

Subjects
Transplantation, Science & Technology, Oncology, Immunology, Biophysics, 1103 Clinical Sciences, Hematology, Life Sciences & Biomedicine
Published
2016

42. Donor Lymphocyte Infusions for Chronic Myeloid Leukemia Relapsing after Allogeneic Stem Cell Transplantation: May We Predict Graft-versus-Leukemia Without Graft-versus-Host Disease?

Author

Radujkovic, A., Guglielmi, C., Bergantini, S., Iacobelli, S., Biezen, A. van, Milojkovic, D., Gratwohl, A., Schattenberg, A.V.M.B., Verdonck, L.F., Niederwieser, D.W., Witte, T.J. de, Kroger, N., and Olavarria, E.

Subjects
Oncology, Male, Transplantation Conditioning, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], Lymphocyte, allogeneic stem cell transplantation, chronic myeloid leukemia, donor lymphocyte infusions, graft-versus-host disease, Graft-versus-leukemia, Relapse, Adolescent, Adult, Child, Child, Preschool, Chromosome Aberrations, Chronic Disease, Female, Graft vs Host Disease, Hematopoietic Stem Cell Transplantation, Humans, Immunosuppressive Agents, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Middle Aged, Myeloablative Agonists, Prognosis, Recurrence, Retrospective Studies, Sex Factors, Siblings, Survival Analysis, Transplantation, Homologous, Unrelated Donors, Graft vs Leukemia Effect, Lymphocyte Transfusion, Hematology, Transplantation, Disease, Graft-versus-host disease, hemic and lymphatic diseases, Chronic, Leukemia, Chronic myeloid leukemia, Myeloid leukemia, medicine.anatomical_structure, Stem cell, Homologous, medicine.medical_specialty, Human leukocyte antigen, Settore MED/01 - Statistica Medica, Internal medicine, medicine, Preschool, business.industry, medicine.disease, Allogeneic stem cell transplantation, Donor lymphocyte infusions, Immunology, BCR-ABL Positive, business, Myelogenous
Abstract

Item does not contain fulltext Donor lymphocyte infusions (DLI) are an effective treatment for relapsed chronic myeloid leukemia (CML) after allogeneic stem cell transplantation (alloSCT). Leukemia resistance and secondary graft-versus-host disease (GVHD) are major obstacles to success with DLI. The aim of this study was to identify pre-DLI factors associated with prolonged survival in remission without secondary GVHD. We retrospectively analyzed 500 patients treated with DLI for CML relapse (16% molecular, 30% cytogenetic, and 54% hematological) after alloSCT. The overall probabilities of failure- and secondary GVHD-free survival (FGFS) were 29% and 27% at 5 and 10 years after DLI, respectively. The type of relapse was the major factor influencing FGFS (40% for molecular and/or cytogenetic relapse and 20% for hematological relapse at 5 years, P < .001). Chronic GVHD before DLI and an interval /= 50 x 10(6)/kg, donor-recipient sex mismatch, and chronic GVHD before DLI. FGFS was 0%, 17%, 33%, to 37% in patients with 3, 2, 1, and 0 adverse features, respectively. The probability of survival in remission without secondary GVHD was highest (>50% at 5 years) when DLI were given beyond 1 year from alloSCT for molecular and/or cytogenetic CML relapse that was not preceded by chronic GVHD.

Published
2015

43. European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia

Author

University of Helsinki, Clinicum, Steegmann, J. L., Baccarani, M., Breccia, M., Casado, L. F., Garcia-Gutierrez, V., Hochhaus, A., Kim, D-W, Kim, T. D., Khoury, H. J., Le Coutre, P., Mayer, J., Milojkovic, D., Porkka, Kimmo, Rea, D., Rosti, G., Saussele, S., Hehlmann, R., Clark, R. E., University of Helsinki, Clinicum, Steegmann, J. L., Baccarani, M., Breccia, M., Casado, L. F., Garcia-Gutierrez, V., Hochhaus, A., Kim, D-W, Kim, T. D., Khoury, H. J., Le Coutre, P., Mayer, J., Milojkovic, D., Porkka, Kimmo, Rea, D., Rosti, G., Saussele, S., Hehlmann, R., and Clark, R. E.

Abstract

Most reports on chronic myeloid leukaemia (CML) treatment with tyrosine kinase inhibitors (TKIs) focus on efficacy, particularly on molecular response and outcome. In contrast, adverse events (AEs) are often reported as infrequent, minor, tolerable and manageable, but they are increasingly important as therapy is potentially lifelong and multiple TKIs are available. For this reason, the European LeukemiaNet panel for CML management recommendations presents an exhaustive and critical summary of AEs emerging during CML treatment, to assist their understanding, management and prevention. There are five major conclusions. First, the main purpose of CML treatment is the antileukemic effect. Suboptimal management of AEs must not compromise this first objective. Second, most patients will have AEs, usually early, mostly mild to moderate, and which will resolve spontaneously or are easily controlled by simple means. Third, reduction or interruption of treatment must only be done if optimal management of the AE cannot be accomplished in other ways, and frequent monitoring is needed to detect resolution of the AE as early as possible. Fourth, attention must be given to comorbidities and drug interactions, and to new events unrelated to TKIs that are inevitable during such a prolonged treatment. Fifth, some TKI-related AEs have emerged which were not predicted or detected in earlier studies, maybe because of suboptimal attention to or absence from the preclinical data. Overall, imatinib has demonstrated a good long-term safety profile, though recent findings suggest underestimation of symptom severity by physicians. Second and third generation TKIs have shown higher response rates, but have been associated with unexpected problems, some of which could be irreversible. We hope these recommendations will help to minimise adverse events, and we believe that an optimal management of them will be rewarded by better TKI compliance and thus better CML outcomes, together with better q

Published
2016

44. Flipped classroom: The novel learning environment for medical students

Author

Pejin Irina, Oroz Sara, Milojković Đorđe, Milić Nikola, Milić Nataša, and Rajović Nina

Subjects
flipped classroom, students, medicine, Medicine
Abstract

Introduction: The ongoing pandemic caused by Coronavirus has strongly initiated digital developments and closed in-person classes in higher education. In order to achieve remote high-quality online delivery, the learning method "flipped classroom" has been introduced to both students and teachers. The flipped classroom represents a type of blended learning aiming to increase students' engagement by preparing materials for learning at home and having faceto-face problem-solving during class time. Aim: To assess attitudes and perceptions of medical undergraduate students toward flipped classroom method of learning. Material and methods: This was a cross-sectional study conducted among undergraduate students attending Faculty of Medicine University of Belgrade during January 2022, using online questionnaire. The questionnaire used in this study consisted of 34 questions and was divided among six main sections: demographics, overall attitudes, communication, independence in learning, preparedness and motivation, and creative thinking and collaborative work. Results: A total of 60 medical students were included in the study. Two thirds of the students were female (75,0%), with the mean age of 23,48 ± 1,53 years. Most of the respondents were fifthand sixth-year students. The results of this study revealed that significant differences in perceptions of the students toward flipped classroom method of learning between gender and age group were found. Female and younger students had more positive attitudes toward flipped classroom than male and older students. Conclusion: Flipped classroom method of learning suits the demands of medical students at a university level, advancing their problem-solving skills and higher-order thinking. Bearing in mind that younger students had positive perceptions and attitudes toward flipped classroom method of learning, curriculum designers and educators should adjust the lessons and teaching methods strategies to students' preferences in order to help them to gain their full academic potential.

Published
2022

45. Circulating purine compounds, uric acid, and xanthine oxidase/dehydrogenase relationship in essential hypertension and end stage renal disease

Author

Dušan Sokolović, Tatjana Jevtovic-Stoimenov, Tatjana Cvetkovic, Radmila Pavlovic, Boris Djindjic, Milojkovic D Bobana, Marina Deljanin-Ilic, Sonja Radenkovic, Stevan Ilic, Milojkovic Boban, Dijana Stojanovic, and Gordana Kocic

Subjects
Purine, Adenosine monophosphate, Male, medicine.medical_specialty, Xanthine Oxidase, Xanthine Dehydrogenase, Blood Pressure, Critical Care and Intensive Care Medicine, Essential hypertension, End stage renal disease, chemistry.chemical_compound, Adenosine Triphosphate, Renal Dialysis, Internal medicine, Medicine, Humans, Urea, Xanthine oxidase, business.industry, Adenine Nucleotides, General Medicine, medicine.disease, Adenosine Monophosphate, Uric Acid, Adenosine Diphosphate, Adenosine diphosphate, Endocrinology, chemistry, Xanthine dehydrogenase, Nephrology, Creatinine, Hypertension, Disease Progression, Uric acid, Kidney Failure, Chronic, Female, Essential Hypertension, business
Abstract

Purine nucleotide liberation and their metabolic rate of interconversion may be important in the development of hypertension and its renal consequences. In the present study, blood triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) breakdown pathway was evaluated in relation to uric acid concentration and xanthine dehydrogenase/xanthine oxidase (XDH/XO) in patients with essential hypertension, patients with chronic renal diseases on dialysis, and control individuals. The pattern of nucleotide catabolism was significantly shifted toward catabolic compounds, including ADP, AMP, and uric acid in patients on dialysis program. A significant fall of ATP was more expressed in a group of patients on dialysis program, compared with the control value (p

Published
2014

46. European LeukemiaNet recommendations for the management and avoidance of adverse events of treatment in chronic myeloid leukaemia

Author

Steegmann, J L, primary, Baccarani, M, additional, Breccia, M, additional, Casado, L F, additional, García-Gutiérrez, V, additional, Hochhaus, A, additional, Kim, D-W, additional, Kim, T D, additional, Khoury, H J, additional, Le Coutre, P, additional, Mayer, J, additional, Milojkovic, D, additional, Porkka, K, additional, Rea, D, additional, Rosti, G, additional, Saussele, S, additional, Hehlmann, R, additional, and Clark, R E, additional

Published
2016
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49. Circulating purine compounds, uric acid, and xanthine oxidase/dehydrogenase relationship in essential hypertension and end stage renal disease

Author

Boban, Milojkovic, primary, Kocic, Gordana, additional, Radenkovic, Sonja, additional, Pavlovic, Radmila, additional, Cvetkovic, Tatjana, additional, Deljanin-Ilic, Marina, additional, Ilic, Stevan, additional, Bobana, Milojkovic D., additional, Djindjic, Boris, additional, Stojanovic, Dijana, additional, Sokolovic, Dusan, additional, and Jevtovic-Stoimenov, Tatjana, additional

Published
2014
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50. The price of drugs for chronic myeloid leukemia (CML) is a reflection of the unsustainable prices of cancer drugs: From the perspective of a large group of CML experts

Author

Abboud, C, Berman, E, Cohen, A, Cortes, J, Deangelo, D, Deininger, M, Devine, S, Druker, B, Fathi, A, Jabbour, E, Jagasia, M, Kantarjian, H, Khoury, J, Laneuville, P, Larson, R, Lipton, J, Moore, J, Mughal, T, O'Brien, S, Pinilla-Ibarz, J, Quintas-Cardama, A, Radich, J, Reddy, V, Schiffer, C, Shah, N, Shami, P, Silver, R, Snyder, D, Stone, R, Talpaz, M, Tefferi, A, Van Etten, R, Wetzler, M, Abruzzese, E, Apperley, J, Breccia, M, Byrne, J, Cervantes, F, Chelysheva, E, Clark, R, De Lavallade, H, Dyagil, I, Gambacorti-Passerini, C, Goldman, J, Haznedaroglu, I, Hjorth-Hansen, H, Holyoake, T, Huntly, B, Le Coutre, P, Lomaia, E, Mahon, F, Marin-Costa, D, Martinelli, G, Mayer, J, Milojkovic, D, Olavarria, E, Porkka, K, Richter, J, Rousselot, P, Saglio, G, Saydam, G, Stentoft, J, Turkina, A, Vigneri, P, Zaritskey, A, Aguayo, A, Ayala, M, Bendit, I, Bengio, R, Best, C, Bullorsky, E, Cervera, E, Desouza, C, Fanilla, E, Gomez-Almaguer, D, Hamerschlak, N, Lopez, J, Magarinos, A, Meillon, L, Milone, J, Moiraghi, B, Pasquini, R, Pavlovsky, C, Ruiz-Arguelles, G, Spector, N, Arthur, C, Browett, P, Grigg, A, Jianda, H, Huang, X, Hughes, T, Jiang, Q, Jootar, S, Kim, D, Malhotra, H, Malhotra, P, Matsumura, I, Melo, J, Ohnishi, K, Ohno, R, Saikia, T, Schwarer, A, Takahashi, N, Tam, C, Tauchi, T, Usuki, K, Wang, J, Abdel-Rahman, F, Aljurf, M, Bazarba-Chi, A, Yehuda, D, Chaudhri, N, Durosinmi, M, Kamel, H, Louw, V, Matti, B, Nagler, A, Raanani, P, Salem, Z, Abboud, Camille, Berman, Ellin, Cohen, Adam, Cortes, Jorge, DeAngelo, Daniel, Deininger, Michael, Devine, Steven, Druker, Brian, Fathi, Amir, Jabbour, Elias, Jagasia, Madan, Kantarjian, Hagop, Khoury, Jean, Laneuville, Pierre, Larson, Richard, Lipton, Jeffrey, Moore, Joseph O., Mughal, Tariq, O'Brien, Susan, Pinilla-Ibarz, Javier, Quintas-Cardama, Alfonso, Radich, Jerald, Reddy, Vishnu, Schiffer, Charles, Shah, Neil, Shami, Paul, Silver, Richard T., Snyder, David, Stone, Richard, Talpaz, Moshe, Tefferi, Ayalew, Van Etten, Richard A., Wetzler, Meir, Abruzzese, Elisabetta, Apperley, Jane, Breccia, Massimo, Byrne, Jenny, Cervantes, Francisco, Chelysheva, Ekaterina, Clark, R. E., De Lavallade, Hugues, Dyagil, Iryna, Gambacorti-Passerini, Carlo, Goldman, John, Haznedaroglu, Ibrahim, Hjorth-Hansen, Henrik, Holyoake, Tessa, Huntly, Brian, Le Coutre, Philipp, Lomaia, Elza, Mahon, Francois-Xavier, Marin-Costa, David, Martinelli, Giovanni, Mayer, Jiri, Milojkovic, Dragana, Olavarria, Eduardo, Porkka, Kimmo, Richter, Johan, Rousselot, Philippe, Saglio, Giuseppe, Saydam, Guray, Stentoft, Jesper, Turkina, Anna, Vigneri, Paolo, Zaritskey, Andrey, Aguayo, Alvaro, Ayala, Manuel, Bendit, Israel, Bengio, Raquel Maria, Best, Carlos, Bullorsky, Eduardo, Cervera, Eduardo, Desouza, Carmino, Fanilla, Ernesto, Gomez-Almaguer, David, Hamerschlak, Nelson, Lopez, Jose, Magarinos, Alicia, Meillon, Luis, Milone, Jorge, Moiraghi, Beatriz, Pasquini, Ricardo, Pavlovsky, Carolina, Ruiz-Arguelles, Guillermo J., Spector, Nelson, Arthur, Christopher, Browett, Peter, Grigg, Andrew, Hu, Jianda, Huang, Xiao-jun, Hughes, Tim, Jiang, Qian, Jootar, Saengsuree, Kim, Dong-Wook, Malhotra, Hemant, Malhotra, Pankaj, Matsumura, Itaru, Melo, Junia, Ohnishi, Kazunori, Ohno, Ryuzo, Saikia, Tapan, Schwarer, Anthony P., Takahashi, Naoto, Tam, Constantine, Tauchi, Tetsuzo, Usuki, Kensuke, Wang, Jianxiang, Abdel-Rahman, Fawzi, Aljurf, Mahmoud Deeb Saeed, Bazarba-Chi, Ali, Yehuda, Dina Ben, Chaudhri, Naeem, Durosinmi, Muheez, Kamel, Hossam, Louw, Vernon, Matti, Bassam Francis, Nagler, Arnon, Raanani, Pia, Salem, Ziad, Abboud, C, Berman, E, Cohen, A, Cortes, J, Deangelo, D, Deininger, M, Devine, S, Druker, B, Fathi, A, Jabbour, E, Jagasia, M, Kantarjian, H, Khoury, J, Laneuville, P, Larson, R, Lipton, J, Moore, J, Mughal, T, O'Brien, S, Pinilla-Ibarz, J, Quintas-Cardama, A, Radich, J, Reddy, V, Schiffer, C, Shah, N, Shami, P, Silver, R, Snyder, D, Stone, R, Talpaz, M, Tefferi, A, Van Etten, R, Wetzler, M, Abruzzese, E, Apperley, J, Breccia, M, Byrne, J, Cervantes, F, Chelysheva, E, Clark, R, De Lavallade, H, Dyagil, I, Gambacorti-Passerini, C, Goldman, J, Haznedaroglu, I, Hjorth-Hansen, H, Holyoake, T, Huntly, B, Le Coutre, P, Lomaia, E, Mahon, F, Marin-Costa, D, Martinelli, G, Mayer, J, Milojkovic, D, Olavarria, E, Porkka, K, Richter, J, Rousselot, P, Saglio, G, Saydam, G, Stentoft, J, Turkina, A, Vigneri, P, Zaritskey, A, Aguayo, A, Ayala, M, Bendit, I, Bengio, R, Best, C, Bullorsky, E, Cervera, E, Desouza, C, Fanilla, E, Gomez-Almaguer, D, Hamerschlak, N, Lopez, J, Magarinos, A, Meillon, L, Milone, J, Moiraghi, B, Pasquini, R, Pavlovsky, C, Ruiz-Arguelles, G, Spector, N, Arthur, C, Browett, P, Grigg, A, Jianda, H, Huang, X, Hughes, T, Jiang, Q, Jootar, S, Kim, D, Malhotra, H, Malhotra, P, Matsumura, I, Melo, J, Ohnishi, K, Ohno, R, Saikia, T, Schwarer, A, Takahashi, N, Tam, C, Tauchi, T, Usuki, K, Wang, J, Abdel-Rahman, F, Aljurf, M, Bazarba-Chi, A, Yehuda, D, Chaudhri, N, Durosinmi, M, Kamel, H, Louw, V, Matti, B, Nagler, A, Raanani, P, Salem, Z, Abboud, Camille, Berman, Ellin, Cohen, Adam, Cortes, Jorge, DeAngelo, Daniel, Deininger, Michael, Devine, Steven, Druker, Brian, Fathi, Amir, Jabbour, Elias, Jagasia, Madan, Kantarjian, Hagop, Khoury, Jean, Laneuville, Pierre, Larson, Richard, Lipton, Jeffrey, Moore, Joseph O., Mughal, Tariq, O'Brien, Susan, Pinilla-Ibarz, Javier, Quintas-Cardama, Alfonso, Radich, Jerald, Reddy, Vishnu, Schiffer, Charles, Shah, Neil, Shami, Paul, Silver, Richard T., Snyder, David, Stone, Richard, Talpaz, Moshe, Tefferi, Ayalew, Van Etten, Richard A., Wetzler, Meir, Abruzzese, Elisabetta, Apperley, Jane, Breccia, Massimo, Byrne, Jenny, Cervantes, Francisco, Chelysheva, Ekaterina, Clark, R. E., De Lavallade, Hugues, Dyagil, Iryna, Gambacorti-Passerini, Carlo, Goldman, John, Haznedaroglu, Ibrahim, Hjorth-Hansen, Henrik, Holyoake, Tessa, Huntly, Brian, Le Coutre, Philipp, Lomaia, Elza, Mahon, Francois-Xavier, Marin-Costa, David, Martinelli, Giovanni, Mayer, Jiri, Milojkovic, Dragana, Olavarria, Eduardo, Porkka, Kimmo, Richter, Johan, Rousselot, Philippe, Saglio, Giuseppe, Saydam, Guray, Stentoft, Jesper, Turkina, Anna, Vigneri, Paolo, Zaritskey, Andrey, Aguayo, Alvaro, Ayala, Manuel, Bendit, Israel, Bengio, Raquel Maria, Best, Carlos, Bullorsky, Eduardo, Cervera, Eduardo, Desouza, Carmino, Fanilla, Ernesto, Gomez-Almaguer, David, Hamerschlak, Nelson, Lopez, Jose, Magarinos, Alicia, Meillon, Luis, Milone, Jorge, Moiraghi, Beatriz, Pasquini, Ricardo, Pavlovsky, Carolina, Ruiz-Arguelles, Guillermo J., Spector, Nelson, Arthur, Christopher, Browett, Peter, Grigg, Andrew, Hu, Jianda, Huang, Xiao-jun, Hughes, Tim, Jiang, Qian, Jootar, Saengsuree, Kim, Dong-Wook, Malhotra, Hemant, Malhotra, Pankaj, Matsumura, Itaru, Melo, Junia, Ohnishi, Kazunori, Ohno, Ryuzo, Saikia, Tapan, Schwarer, Anthony P., Takahashi, Naoto, Tam, Constantine, Tauchi, Tetsuzo, Usuki, Kensuke, Wang, Jianxiang, Abdel-Rahman, Fawzi, Aljurf, Mahmoud Deeb Saeed, Bazarba-Chi, Ali, Yehuda, Dina Ben, Chaudhri, Naeem, Durosinmi, Muheez, Kamel, Hossam, Louw, Vernon, Matti, Bassam Francis, Nagler, Arnon, Raanani, Pia, and Salem, Ziad

Abstract

As a group of more than 100 experts in chronic myeloid leukemia (CML), we draw attention to the high prices of cancer drugs, with the particular focus on the prices of approved tyrosine kinase inhibitors for the treatment of CML. This editorial addresses the multiple factors involved in cancer drug pricing and their impact on individual patients and health care policies, and argues for the need to (1) lower the prices of cancer drugs to allow more patients to afford them and (2) maintain sound long-term health care policies.

Published
2013

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