Chronic myelogenous leukemia medical therapy

Jump to navigation Jump to search

Chronic myelogenous leukemia Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Chronic myelogenous leukemia from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

Staging

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

CT

MRI

Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Chronic myelogenous leukemia medical therapy On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Chronic myelogenous leukemia medical therapy

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Chronic myelogenous leukemia medical therapy

CDC on Chronic myelogenous leukemia medical therapy

Chronic myelogenous leukemia medical therapy in the news

Blogs on Chronic myelogenous leukemia medical therapy

Directions to Hospitals Treating Chronic myelogenous leukemia

Risk calculators and risk factors for Chronic myelogenous leukemia medical therapy

Overview

Medical therapies for chronic myelogenous leukemia (CML) include tyrosine kinase inhibitors, chemotherapy, stem cell transplant, and/or biological therapy. Improved understanding of the nature of the BCR-ABL protein and its action as a tyrosine kinase, targeted therapies have been developed (the first of which was imatinib mesylate) which specifically inhibit the activity of theBCR-ABL protein. These tyrosine kinase inhibitors can induce complete remissions in chronic myelogenous leukemia, confirming the central importance of BCR-ABL as the cause of chronic myelogenous leukemia. In patients with blast phase CML, cytotoxic chemotherapy is usually indicated.

Medical Therapy

Chronic Phase

Targeted therapy: Targeted therapy is the primary treatment for most people with chronic myelogenous leukemia in the chronic phase:

These are tyrosine kinase inhibitors (TKIs) that can be used for initial treatment of CML.

Imatinib:

  • It is the primarily the standard first-line therapy for CML.
  • Imatinib is efficacious in chronic phase (CP) and is less expensive than other tyrosine kinase inhibitors (TKIs).
  • Compared with imatinib, second generation TKIs achieve faster responses, but all TKIs tend to accomplish effective long-term outcomes.
  • Imatinib is more effective than non-TKI medications (eg, interferon [IFN] alfa plus cytarabine) in this setting.

Dose of imatinib:

  • For patients with chronic phase, imatinib is started at 400 mg daily by mouth and is continued indefinitely for those who tolerate it and continue to respond by molecular and/or cytogenetic measures.[6]
  • More than 60 percent of patients can remain on imatinib for at least five years.

Side effects of imatinib:

Impact of imatinib on survival rate:

  • With a present follow-up of 5 years, the survival rate with imatinib is 87%. [8]
  • The estimated 5-year survival rate is 89%, and survival without transformation rate is 93%.
  • The impact of imatinib on survival rate in different phases of disease is presented in the following table.[9][10][11]
Survival Rates of Patients with CML treated with imatinib
Disease phase Imatinib daily dose (mg) Estimated survival rates at (X) years
Chronic Phase, newly diagnosed 400 89% (5)
Chronic phase, previously diagnosed 400 86% (4) 79% (5)
Accelerated phase 400 vs 600 44% (3) vs 66% (3)

53% (4)

Blastic phase 400-600 17% (2); 14-17% (2-3)

Resistance to imatinib:

  • Resistance to imatinib is defined as a failure to achieve complete hematologoic response at 3 months, a cytogenetic response at 6 months, or a major cytogenetic response at 12 months.[12][13]
  • Recent recommendations of definitions of resistance versus suboptimal response to imatinib have been proposed. [12]

Definition of sub optimal response

  • Lack of major molecular response may be considered as suboptimal response rather than failure as stated below in table :[11]
Criteria for failure to imatinib
Time on imatinib Response
Failure Suboptimal
3 Months No HR No CHR
6 Months No CHR

Ph+100%

Ph+ > 35%
12 Months Ph+>35% Ph+> 5%
18 months Ph+>5% No MMR < 3 months reduction of BCR-ABL/ABL
Any months Loss of CHR

Loss of cytogenetic response

Mutation

Clonal Evaluation

Loss of MMR

Mutation

HR: Hematologic response; CHR: Complete Hematologic response; MMR: Major molecular response.

  • Resistance to imatinib is often attributed to the emergence of clones expressing mutant forms of BCR-ABL, in which amino acid substitutions in the ABL kinase domain impair imatinib binding but retain kinase activity.[14][15][16][17]
  • Initial reports suggested these mutations to be present in up to 90% of patients failing imatinib therapy; recent studies suggested rates of 40%.[18]
  • Other proposed mechanisms of imatinib resistance include:[19][20]
  • In addition, leukemic stem cell quiescent and insensitive to imatinib may cause persistence of CML.
  • The estimated 4-year resistance rates are 20% in later chronic phaseand 70% to 90% in accelerated-blastic phases.

Dasatinib

  • Dasatinib is an oral, second generation TKI.
  • It is 350 times more potent than imatinib in vitro.[21][6] [22]
  • It also inhibits the Src family of kinases, which may be important in blunting critical cell signaling pathways.[23]
  • Though initially evaluated in patients in the salvage setting, it was later compared to imatinib in frontline CML to test the possibility that frontline use of the more potent TKIs might improve outcomes.
  • A five-year follow-up showed that dasatinib induced more rapid and deeper responses at early time points compared to imatinib.[24]
  • At 3 months, a higher proportion of patients treated with dasatinib achieved BCR-ABL1 transcripts
  • Transformations to CML-BP were fewer in patients treated with dasatinib versus imatinib (4.6% versus 7.3%).
  • However, the 5-year survival was similar with dasatinib and imatinib (91%, and 90%)
  • There is more toxicity experienced in the dasatinib arm (Grades 3 or 4 adverse events 58% with dasatinib and 35% imatinib), mostly hematologic toxicity.[25]
Summary of dasatinib results in CML post-imatinib failure
Disease No. Response
CHR Hematologic Cytogenic response
Chronic 387 90 00 51 40
Accelerated 175 34 59 34 25
Blastic Lymphoid 109 25 49 31 25
Blastic Myeloid 48 29 33 44 38
Ph+ALL 46 33 39 46 48

Dose of dasatinib:

  • 100 mg daily was found as effective as 140 mg daily, with a better safety profile.[26]

Side Effects of dasatinib:

  • There was no substantial difference in grade 3/4 toxicities by treatment schedule.
  • Thirty-five percent of patients required dose reductions, although the median dose for all patients at 12 months was 100 mg/day (range: 20 to 100).
  • Grade 3/4 toxicities included:
  • In addition, the safety profile was favorable; only one patient discontinued therapy (subdural hematoma unlikely related) and one patient had his dose reduced to 20 mg daily due to pleural effusion.
  • Such strategy will have a significant impact on our future practice.

Nilotinib:

  • Nilotinib is a structural analog of imatinib.
  • Its affinity for the ATP binding site on BCR-ABL1 is 30–50 times more in vitro.[27]
  • Like dasatinib, nilotinib initially demonstrated the ability to induce hematologic and cytogenetic responses in patients who had failed imatinib.[28]
  • The primary end point was the rate of major molecular response at 12 months.
  • This endpoint was achieved at statistically significantly higher rates for both doses of nilotinib compared with imatinib (44% and 43% versus 22%, P<.001).
Results of phase II nilotinib studies in CML post-imatinib failure
No. Treated Chronic Accelerated Blastic Ph+ALL
% CHR/HR 69/— 16/40 4/13 27/33
% Cytogenetic response 68 56 29 -
Complete 34 16 21 -
Partial 14 12 8 -

Bosutinib:

  • Bosutinib is an inhibitor of ABL and SRC kinases that is approved for initial treatment of CML in CP.[29]
  • When compared with imatinib in newly diagnosed CML, bosutinib produces faster and slightly superior response rates.
  • It is associated with more diarrhea and abnormal liver function tests.
  • When compared with imatinib, bosutinib resulted in faster cytogenetic responses but similar rates of CCyR at 12 and 24 months, and a higher rate of major molecular response at 12 months, but not at 24 months.[30]

Side Effects of bosutinib:

  • Bosutinib was associated with following:
  • The overall toxicity profile was improved compared to the BELA trial , which utilized a dose of 500 mg of bosutinib, and led to US Food and Drug Administration approval of 400 mg bosutinib as initial therapy for CP CML.
  • Compared with imatinib, bosutinib resulted in higher rates of MMRti and CCyR at 12 months, and achieved these milestones more quickly.[30]

Ponatinib:

  • Ponatinib is a third-generation TKI that is specifically effective in patients who have the T3 resistance mutation in BCR-ABL. The T315I mutation is characterized by the conversion of threonine to isoleucine at the 315th position. It is considered as a tyrosine kinase domain (TKD) mutation. Ponatinib is the only effective therapy for this mutation.[31]

Selection of initial TKI

  • The selection of a TKI for initial treatment of CML in chronic is determined by the following:
    • Prognostic score
    • Side effect profiles
    • Comorbid illnesses
    • Cost
  • The following suggestions for treatment of chronic phase CML are influenced by the CML risk score (eg, EUTOS, Euro [Hasford], or Sokal scores):

Low- or intermediate-risk CML

  • For most patients with low- or intermediate-risk chronic phase CML, it is advised that the treatment with any of the first or second generation TKIs (eg, imatinib, dasatinib, nilotinib, bosutinib).
    • In this setting, side effect profiles, comorbid illnesses, and cost are important factors to the choice of TKI.
  • Imatinib, which is available as a generic drug, is a reasonable choice for most patients and is preferred when cost is an important factor.
  • Second generation TKIs may be preferred by clinicians and/or patients who place a higher value on attaining a quicker response.
  • For patients with high-risk chronic phase CML, it is best to use second generation TKIs because, compared with imatinib, early molecular responses occur more frequent with second generation TKIs, and EMR is associated with improved survival in this setting.
  • Long-term follow-up of patients initially treated with imatinib suggests that more than half will remain on imatinib at five years; while some patients taking imatinib have persistent low-grade side effects (fatigue, arthralgias, and diarrhea), new toxicities have not emerged with longer follow-up.[32]
  • Patients on imatinib have excellent disease control and survival rates if clinicians monitor disease response and switch to a second generation TKI upon failure to meet a targeted response or with the development of drug intolerance.[34]
  • The prices of TKIs differ substantially and vary by country.[35]
  • In addition, the out-of-pocket expense for an individual depends upon their health care plan. Adherence is an independent predictor of response and is lower among patients with higher medication co-payments.[36]

Hematopoietic stem cell transplantation

  • Stem cell transplant may be offered for CML in the chronic phase.
  • It is sometimes used as a primary treatment option for younger people who have an HLA-matched donor.
  • It is a treatment option for some people who do not achieve a complete response or develop resistance to or relapse with imatinib.
  • A reduced intensity transplant may be an option for older people who may not tolerate a standard transplant.
  • Outcomes with HCT and tyrosine kinase inhibitors have not been directly compared in a well-designed trial.
  • However, based on historical comparisons, HCT is associated with increased morbidity and mortality, despite the possibility of cure.
  • Thus, allogeneic HCT is currently not offered as initial therapy, except in rare circumstances.
  • With HCT, the probability of survival can be predicted with reasonable accuracy using a scoring system devised by the European Group for Blood and Marrow Transplantation .[37]
  • The five-year overall survival rates for patients in the best risk groups ranged from 60 to 80 percent.
  • As an example, a prospective trial of HCT in patients in first chronic phase, most of whom had failed to respond to initial treatment with imatinib, reported a transplant-related mortality rate of 8 percent.[38]

Aims of therapy and monitoring the response:

  • The aim of initial therapy with a tyrosine kinase inhibitor is to achieve the milestones, which are optimal responses proposed by the European LeukemiaNet.[39]
    • At three months, BCR/ABL1 ≤10 % on the International Scale and/or Ph+ metaphase cells ≤35%
    • At six months, BCR/ABL1 <1 % and/or Ph+ 0
    • At 12 months, BCR/ABL1 ≤0.1 %
  • Failure to achieve these milestones should be confirmed with repeat studies before changes in therapy are initiated.
  • A decision to change therapy must also take into consideration the trends in these values over time.
  • Discontinuation of a TKI would be an option for only the approximately 15 to 20 percent of patients who achieve sustained non-detectable levels of BCR/ABL1 for at least two years; successful long-term discontinuation of therapy would be expected in less than 10 to 15 percent of newly diagnosed patients.[40]
  • For individuals who have had a deep molecular remission, about half will have evidence of molecular recurrence and progression within one year after discontinuing TKI therapy, since viable CML stem cells can remain in a quiescent state in the marrow.[41][42].
  • In general, the patients who are most likely to maintain a long treatment-free remission are those who have had the longest period of TKI treatment and have had undetectable transcript levels for years.

Biological therapy:

  • Biological therapy may be offered for chronic stage CML. Biological therapy can be used alone or in combination with chemotherapy.
  • The most common biological therapy used is interferon alfa (Intron A, Roferon A).
  • Interferon alfa may be used for people who cannot tolerate, or whose CML is resistant to, imatinib.
  • May be used in combination with interferon alfa
  • Busulfan (Myleran [oral], Busulfex [intravenous])

Accelerated Phase

  • Allogeneic transplant is preferred, but autologous transplant can also be done.
  • Clinicians usually prefer that the leukemia returns to the chronic phase or is controlled before the transplant.
  • A reduced-intensity transplant may be an option for older people who may not tolerate a standard transplant.
  • Targeted therapy
  • Targeted therapy with a tyrosine kinase inhibitor may be offered during the accelerated phase of CML. For those already taking targeted therapy, the dose may be increased. The types of targeted therapy used are:
  • Biological therapy
  • Chemotherapy may be offered for CML in the accelerated phase.
  • The types of chemotherapy used are:

Blast Phase

  • Targeted therapy[5]
  • Targeted therapy with a tyrosine kinase inhibitor may be offered for CML in the blast phase. For those already taking targeted therapy, the dose may be increased. The types of targeted therapy used are:
  • The most common drugs used when the leukemia cells appear like AML (myeloid blast crisis) include:
  • The most common drugs used when the leukemia cells look like ALL (lymphoid blast crisis) include the drugs listed above as well as:
  • Radiation therapy may be offered for blast phase CML for:

Relapsed or Refractory Chronic Myelogenous

  • Targeted therapy with a tyrosine kinase inhibitor may be offered for relapsed or refractory CML. For those already taking targeted therapy, the dose may be increased. The types of targeted therapy used are:

Supportive Therapy

  • Antibiotics and Antifungals
  • Blood products
  • Granulocyte colony-stimulating factors (G-CSF)

References

  1. ↑ National Cancer Institute. Physician Data Query Database 2015.http://www.cancer.gov/types/leukemia/hp/cml-treatment-pdq#section/_19
  2. ↑ Jabbour E, Kantarjian H (May 2014). "Chronic myeloid leukemia: 2014 update on diagnosis, monitoring, and management". Am. J. Hematol. 89 (5): 547–56. doi:10.1002/ajh.23691. PMID 24729196.
  3. ↑ Thompson PA, Kantarjian HM, Cortes JE (October 2015). "Diagnosis and Treatment of Chronic Myeloid Leukemia in 2015". Mayo Clin. Proc. 90 (10): 1440–54. doi:10.1016/j.mayocp.2015.08.010. PMC 5656269. PMID 26434969.
  4. ↑ Faderl S, Talpaz M, Estrov Z, Kantarjian HM (August 1999). "Chronic myelogenous leukemia: biology and therapy". Ann. Intern. Med. 131 (3): 207–19. PMID 10428738.
  5. ↑ 5.0 5.1 5.2 Canadian Cancer Society.2015.http://www.cancer.ca/en/cancer-information/cancer-type/leukemia-chronic-myelogenous-cml/treatment/chronic/?region=ab
  6. ↑ 6.0 6.1 O'Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, Cornelissen JJ, Fischer T, Hochhaus A, Hughes T, Lechner K, Nielsen JL, Rousselot P, Reiffers J, Saglio G, Shepherd J, Simonsson B, Gratwohl A, Goldman JM, Kantarjian H, Taylor K, Verhoef G, Bolton AE, Capdeville R, Druker BJ (March 2003). "Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia". N. Engl. J. Med. 348 (11): 994–1004. doi:10.1056/NEJMoa022457. PMID 12637609.
  7. ↑ Deininger MW, O'Brien SG, Ford JM, Druker BJ (April 2003). "Practical management of patients with chronic myeloid leukemia receiving imatinib". J. Clin. Oncol. 21 (8): 1637–47. doi:10.1200/JCO.2003.11.143. PMID 12668652.
  8. ↑ "Four Years of Follow-Up of 1027 Patients with Late Chronic Phase (L-CP), Accelerated Phase (AP), or Blast Crisis (BC) Chronic Myeloid Leukemia (CML) Treated with Imatinib in Three Large Phase II Trials. | Blood Journal".
  9. ↑ Kantarjian HM, Larson RA, Guilhot F, O'Brien SG, Mone M, Rudoltz M, Krahnke T, Cortes J, Druker BJ (February 2009). "Efficacy of imatinib dose escalation in patients with chronic myeloid leukemia in chronic phase". Cancer. 115 (3): 551–60. doi:10.1002/cncr.24066. PMC 4445370. PMID 19117345.
  10. ↑ Hochhaus A, Druker B, Sawyers C, Guilhot F, Schiffer CA, Cortes J, Niederwieser DW, Gambacorti-Passerini C, Gambacorti C, Stone RM, Goldman J, Fischer T, O'Brien SG, Reiffers JJ, Mone M, Krahnke T, Talpaz M, Kantarjian HM (February 2008). "Favorable long-term follow-up results over 6 years for response, survival, and safety with imatinib mesylate therapy in chronic-phase chronic myeloid leukemia after failure of interferon-alpha treatment". Blood. 111 (3): 1039–43. doi:10.1182/blood-2007-07-103523. PMID 17932248.
  11. ↑ 11.0 11.1 Druker, Brian J.; Guilhot, François; O'Brien, Stephen G.; Gathmann, Insa; Kantarjian, Hagop; Gattermann, Norbert; Deininger, Michael W.N.; Silver, Richard T.; Goldman, John M.; Stone, Richard M.; Cervantes, Francisco; Hochhaus, Andreas; Powell, Bayard L.; Gabrilove, Janice L.; Rousselot, Philippe; Reiffers, Josy; Cornelissen, Jan J.; Hughes, Timothy; Agis, Hermine; Fischer, Thomas; Verhoef, Gregor; Shepherd, John; Saglio, Giuseppe; Gratwohl, Alois; Nielsen, Johan L.; Radich, Jerald P.; Simonsson, Bengt; Taylor, Kerry; Baccarani, Michele; So, Charlene; Letvak, Laurie; Larson, Richard A. (2006). "Five-Year Follow-up of Patients Receiving Imatinib for Chronic Myeloid Leukemia". New England Journal of Medicine. 355 (23): 2408–2417. doi:10.1056/NEJMoa062867. ISSN 0028-4793.
  12. ↑ 12.0 12.1 Baccarani M, Saglio G, Goldman J, Hochhaus A, Simonsson B, Appelbaum F, Apperley J, Cervantes F, Cortes J, Deininger M, Gratwohl A, Guilhot F, Horowitz M, Hughes T, Kantarjian H, Larson R, Niederwieser D, Silver R, Hehlmann R (September 2006). "Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet". Blood. 108 (6): 1809–20. doi:10.1182/blood-2006-02-005686. PMID 16709930.
  13. ↑ Hochhaus A, La Rosée P (August 2004). "Imatinib therapy in chronic myelogenous leukemia: strategies to avoid and overcome resistance". Leukemia. 18 (8): 1321–31. doi:10.1038/sj.leu.2403426. PMID 15215876.
  14. ↑ Branford S, Rudzki Z, Walsh S, Parkinson I, Grigg A, Szer J, Taylor K, Herrmann R, Seymour JF, Arthur C, Joske D, Lynch K, Hughes T (July 2003). "Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis". Blood. 102 (1): 276–83. doi:10.1182/blood-2002-09-2896. PMID 12623848.
  15. ↑ Forrest DL, Jiang X, Eaves CJ, Smith CL (April 2008). "An approach to the management of chronic myeloid leukemia in British Columbia". Curr Oncol. 15 (2): 90–7. PMC 2365478. PMID 18454182.
  16. ↑ Soverini S, Martinelli G, Rosti G, Bassi S, Amabile M, Poerio A, Giannini B, Trabacchi E, Castagnetti F, Testoni N, Luatti S, de Vivo A, Cilloni D, Izzo B, Fava M, Abruzzese E, Alberti D, Pane F, Saglio G, Baccarani M (June 2005). "ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: a study by the GIMEMA Working Party on Chronic Myeloid Leukemia". J. Clin. Oncol. 23 (18): 4100–9. doi:10.1200/JCO.2005.05.531. PMID 15867198.
  17. ↑ Gorre, M. E. (2001). "Clinical Resistance to STI-571 Cancer Therapy Caused by BCR-ABL Gene Mutation or Amplification". Science. 293 (5531): 876–880. doi:10.1126/science.1062538. ISSN 0036-8075.
  18. ↑ Mahon FX, Deininger MW, Schultheis B, Chabrol J, Reiffers J, Goldman JM, Melo JV (August 2000). "Selection and characterization of BCR-ABL positive cell lines with differential sensitivity to the tyrosine kinase inhibitor STI571: diverse mechanisms of resistance". Blood. 96 (3): 1070–9. PMID 10910924.
  19. ↑ Raz A, Kloog Y, Perel E, Kenig-Wakshal R, Bose KS, Sarma RH, Fowler NO, McCall D, Chou TC, Holmes JC, Hanenson IB (September 1975). "Properties of solubilized prostaglandin synthetase from sheep vesicular glands". Life Sci. 17 (6): 951–8. PMID 571.
  20. ↑ Egan DN, Beppu L, Radich JP (January 2015). "Patients with Philadelphia-positive leukemia with BCR-ABL kinase mutations before allogeneic transplantation predominantly relapse with the same mutation". Biol. Blood Marrow Transplant. 21 (1): 184–9. doi:10.1016/j.bbmt.2014.09.012. PMC 4464836. PMID 25300870.
  21. ↑ Kantarjian H, O'Brien S, Cortes J, Giles F, Shan J, Rios MB, Faderl S, Verstovsek S, Garcia-Manero G, Wierda W, Kornblau S, Ferrajoli A, Keating M, Talpaz M (January 2004). "Survival advantage with imatinib mesylate therapy in chronic-phase chronic myelogenous ;eukemia (CML-CP) after IFN-alpha failure and in late CML-CP, comparison with historical controls". Clin. Cancer Res. 10 (1 Pt 1): 68–75. PMID 14734453.
  22. ↑ Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti-Passerini C, Niederwieser D, Resta D, Capdeville R, Zoellner U, Talpaz M, Druker B, Goldman J, O'Brien SG, Russell N, Fischer T, Ottmann O, Cony-Makhoul P, Facon T, Stone R, Miller C, Tallman M, Brown R, Schuster M, Loughran T, Gratwohl A, Mandelli F, Saglio G, Lazzarino M, Russo D, Baccarani M, Morra E (February 2002). "Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia". N. Engl. J. Med. 346 (9): 645–52. doi:10.1056/NEJMoa011573. PMID 11870241.
  23. ↑ Hughes TP, Kaeda J, Branford S, Rudzki Z, Hochhaus A, Hensley ML, Gathmann I, Bolton AE, van Hoomissen IC, Goldman JM, Radich JP (October 2003). "Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia". N. Engl. J. Med. 349 (15): 1423–32. doi:10.1056/NEJMoa030513. PMID 14534335.
  24. ↑ Roy L, Guilhot J, Krahnke T, Guerci-Bresler A, Druker BJ, Larson RA, O'Brien S, So C, Massimini G, Guilhot F (September 2006). "Survival advantage from imatinib compared with the combination interferon-alpha plus cytarabine in chronic-phase chronic myelogenous leukemia: historical comparison between two phase 3 trials". Blood. 108 (5): 1478–84. doi:10.1182/blood-2006-02-001495. PMID 16627756.
  25. ↑ Kantarjian HM, Talpaz M, O'Brien S, Jones D, Giles F, Garcia-Manero G, Faderl S, Ravandi F, Rios MB, Shan J, Cortes J (September 2006). "Survival benefit with imatinib mesylate versus interferon-alpha-based regimens in newly diagnosed chronic-phase chronic myelogenous leukemia". Blood. 108 (6): 1835–40. doi:10.1182/blood-2006-02-004325. PMID 16709931.
  26. ↑ Cortes J, Talpaz M, O'Brien S, Jones D, Luthra R, Shan J, Giles F, Faderl S, Verstovsek S, Garcia-Manero G, Rios MB, Kantarjian H (May 2005). "Molecular responses in patients with chronic myelogenous leukemia in chronic phase treated with imatinib mesylate". Clin. Cancer Res. 11 (9): 3425–32. doi:10.1158/1078-0432.CCR-04-2139. PMID 15867244.
  27. ↑ Weisberg E, Manley PW, Breitenstein W, Brüggen J, Cowan-Jacob SW, Ray A, Huntly B, Fabbro D, Fendrich G, Hall-Meyers E, Kung AL, Mestan J, Daley GQ, Callahan L, Catley L, Cavazza C, Azam M, Mohammed A, Neuberg D, Wright RD, Gilliland DG, Griffin JD (February 2005). "Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl". Cancer Cell. 7 (2): 129–41. doi:10.1016/j.ccr.2005.01.007. PMID 15710326.
  28. ↑ Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, Pasquini R, Clark RE, Hochhaus A, Hughes TP, Gallagher N, Hoenekopp A, Dong M, Haque A, Larson RA, Kantarjian HM (June 2010). "Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia". N. Engl. J. Med. 362 (24): 2251–9. doi:10.1056/NEJMoa0912614. PMID 20525993.
  29. ↑ Brümmendorf TH, Cortes JE, de Souza CA, Guilhot F, Duvillié L, Pavlov D, Gogat K, Countouriotis AM, Gambacorti-Passerini C (January 2015). "Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukaemia: results from the 24-month follow-up of the BELA trial". Br. J. Haematol. 168 (1): 69–81. doi:10.1111/bjh.13108. PMC 4274978. PMID 25196702.
  30. ↑ 30.0 30.1 Cortes JE, Gambacorti-Passerini C, Deininger MW, Mauro MJ, Chuah C, Kim DW, 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 TH (January 2018). "Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial". J. Clin. Oncol. 36 (3): 231–237. doi:10.1200/JCO.2017.74.7162. PMC 5966023. PMID 29091516.
  31. ↑ Parker WT, Yeung DT, Yeoman AL, Altamura HK, Jamison BA, Field CR; et al. (2016). "The impact of multiple low-level BCR-ABL1 mutations on response to ponatinib". Blood. 127 (15): 1870–80. doi:10.1182/blood-2015-09-666214. PMC 4832506. PMID 26773037.
  32. ↑ Gambacorti-Passerini C, Antolini L, Mahon FX, Guilhot F, Deininger M, Fava C, Nagler A, Della Casa CM, Morra E, Abruzzese E, D'Emilio A, Stagno F, le Coutre P, Hurtado-Monroy R, Santini V, Martino B, Pane F, Piccin A, Giraldo P, Assouline S, Durosinmi MA, Leeksma O, Pogliani EM, Puttini M, Jang E, Reiffers J, Piazza R, Valsecchi MG, Kim DW (April 2011). "Multicenter independent assessment of outcomes in chronic myeloid leukemia patients treated with imatinib". J. Natl. Cancer Inst. 103 (7): 553–61. doi:10.1093/jnci/djr060. PMID 21422402.
  33. ↑ Aichberger KJ, Herndlhofer S, Schernthaner GH, Schillinger M, Mitterbauer-Hohendanner G, Sillaber C, Valent P (July 2011). "Progressive peripheral arterial occlusive disease and other vascular events during nilotinib therapy in CML". Am. J. Hematol. 86 (7): 533–9. doi:10.1002/ajh.22037. PMID 21538470.
  34. ↑ Yeung DT, Osborn MP, White DL, Branford S, Braley J, Herschtal A, Kornhauser M, Issa S, Hiwase DK, Hertzberg M, Schwarer AP, Filshie R, Arthur CK, Kwan YL, Trotman J, Forsyth CJ, Taper J, Ross DM, Beresford J, Tam C, Mills AK, Grigg AP, Hughes TP (February 2015). "TIDEL-II: first-line use of imatinib in CML with early switch to nilotinib for failure to achieve time-dependent molecular targets". Blood. 125 (6): 915–23. doi:10.1182/blood-2014-07-590315. PMC 5161008. PMID 25519749.
  35. ↑ "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". Blood. 121 (22): 4439–42. May 2013. doi:10.1182/blood-2013-03-490003. PMC 4190613. PMID 23620577.
  36. ↑ Dusetzina SB, Winn AN, Abel GA, Huskamp HA, Keating NL (February 2014). "Cost sharing and adherence to tyrosine kinase inhibitors for patients with chronic myeloid leukemia". J. Clin. Oncol. 32 (4): 306–11. doi:10.1200/JCO.2013.52.9123. PMID 24366936.
  37. ↑ Gratwohl A, Hermans J, Goldman JM, Arcese W, Carreras E, Devergie A, Frassoni F, Gahrton G, Kolb HJ, Niederwieser D, Ruutu T, Vernant JP, de Witte T, Apperley J (October 1998). "Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation". Lancet. 352 (9134): 1087–92. PMID 9798583.
  38. ↑ Saussele S, Lauseker M, Gratwohl A, Beelen DW, Bunjes D, Schwerdtfeger R, Kolb HJ, Ho AD, Falge C, Holler E, Schlimok G, Zander AR, Arnold R, Kanz L, Dengler R, Haferlach C, Schlegelberger B, Pfirrmann M, Müller MC, Schnittger S, Leitner A, Pletsch N, Hochhaus A, Hasford J, Hehlmann R (March 2010). "Allogeneic hematopoietic stem cell transplantation (allo SCT) for chronic myeloid leukemia in the imatinib era: evaluation of its impact within a subgroup of the randomized German CML Study IV". Blood. 115 (10): 1880–5. doi:10.1182/blood-2009-08-237115. PMID 19965667.
  39. ↑ Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, Cervantes F, Clark RE, Cortes JE, Guilhot F, Hjorth-Hansen H, Hughes TP, Kantarjian HM, Kim DW, Larson RA, Lipton JH, Mahon FX, Martinelli G, Mayer J, Müller MC, Niederwieser D, Pane F, Radich JP, Rousselot P, Saglio G, Saußele S, Schiffer C, Silver R, Simonsson B, Steegmann JL, Goldman JM, Hehlmann R (August 2013). "European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013". Blood. 122 (6): 872–84. doi:10.1182/blood-2013-05-501569. PMC 4915804. PMID 23803709.
  40. ↑ Apperley JF (July 2013). "TWIST it but don't spin it". Blood. 122 (4): 470–1. doi:10.1182/blood-2013-06-506097. PMID 23886774.
  41. ↑ Michor F, Hughes TP, Iwasa Y, Branford S, Shah NP, Sawyers CL, Nowak MA (June 2005). "Dynamics of chronic myeloid leukaemia". Nature. 435 (7046): 1267–70. doi:10.1038/nature03669. PMID 15988530.
  42. ↑ Angstreich GR, Matsui W, Huff CA, Vala MS, Barber J, Hawkins AL, Griffin CA, Smith BD, Jones RJ (August 2005). "Effects of imatinib and interferon on primitive chronic myeloid leukaemia progenitors". Br. J. Haematol. 130 (3): 373–81. doi:10.1111/j.1365-2141.2005.05606.x. PMID 16042686.


Template:WikiDoc Sources

Retrieved from "https://www.wikidoc.org/index.php?title=Chronic_myelogenous_leukemia_medical_therapy&oldid=1743290"