Tratamiento de la leucemia mielógena crónica (PDQ®)–Versión para profesionales de salud

LEUCEMIA

SECCIONES

Información general sobre la leucemia mielógena crónica

Incidencia y mortalidad

Cálculo del número de casos nuevos y defunciones por leucemia mielógena crónica en los Estados Unidos en 2017:[1]

Casos nuevos: 8950.
Defunciones: 1080.

La leucemia mielógena crónica (LMC) forma parte de un grupo de enfermedades denominadas trastornos mieloproliferativos. Otras entidades relacionadas con esta enfermedad son las siguientes:

Policitemia vera.
Mielofibrosis.
Trombocitopenia esencial.

(Para obtener más información, consultar el sumario del PDQ Tratamiento de las neoplasias mieloproliferativas crónicas).

Características biológico moleculares y características citogenéticas de la leucemia mielógena crónica

La leucemia mielógena crónica (LMC) es un trastorno clonal que generalmente se diagnostica con facilidad porque las células leucémicas en más del 95 % de los pacientes presentan una anomalía citogenética característica, el cromosoma Filadelfia (Ph1).[2,3] El Ph1 resulta de una traslocación recíproca entre los brazos largos del cromosoma 9 y el 22 y se puede mostrar en todos los precursores hematopoyéticos.[4] Esta traslocación produce la transferencia del Abelson (ABL) en el oncogén del cromosoma 9 a un área en el cromosoma 22 denominada región de concurrencia de fracturas (BCR).[4] Esto a su vez da lugar a un gen fusionado de BCR/ABL y en la producción de una proteína tirosina cinasa anormal que puede estar relacionada con la mielopoyesis desordenada que se encuentra en la LMC. Además, estas técnicas moleculares pueden emplearse ahora para complementar los estudios de citogenética para detectar la presencia de la traslocación 9;22 en pacientes sin un Ph1 visible (Ph1-negativo).

Pronóstico y supervivencia

La leucemia mielógena crónica (LMC) de Ph1-negativo es una entidad mal definida que se distingue con menos claridad de otros síndromes mieloproliferativos. En general, los pacientes con LMC de Ph1-negativos tienen una respuesta más precaria al tratamiento y una supervivencia más corta que los pacientes Ph1-positivos.[5] Sin embargo, los pacientes Ph1-negativos que tienen el reordenamiento del gen BCR/ABL detectable por el análisis con la técnica Southern, tienen pronósticos equivalentes a los pacientes Ph1-positivos.[6,7]

Diagnóstico

Un pequeño subgrupo de pacientes tiene BCR/ABL detectable solamente por una reacción en cadena de la polimerasa con retrotranscriptasa (RCP-RT), la técnica más sensible con la que se cuenta en la actualidad. Los pacientes en los que es evidente el gen de fusión BCR/ABL por RCP-RT parecen idénticos a los pacientes con un cromosoma Ph1 clásico desde el punto de vista clínico y pronóstico; sin embargo, los pacientes que son negativos a BCR/ABL por RCP-RT tienen un curso clínico más consistente con la leucemia mielomonocítica crónica, una entidad clínica distinta relacionada con el síndrome mielodisplásico.[6,8,9] La hibridación fluorescente in situ de la traslocación de BCR/ABLpuede realizarse en el aspirado de la médula ósea o en la sangre periférica de pacientes con LMC.[10]

En el examen físico inicial de los pacientes, en el momento del diagnóstico de LMC, la esplenomegalia es el hallazgo más común que se encuentra.[10] El bazo puede ser enorme, ocupando la mayor parte del abdomen y convertirse en un problema clínico importante, o puede estar agrandado de forma mínima. En casi 10 % de los pacientes, el bazo ni es palpable ni está agrandado en la exploración esplénica.

La mediana de edad en los pacientes con LMC PH1-positivo es de 67 años.[11] Mientras que la mediana de la supervivencia era de 4 a 6 años, con el advenimiento de los tratamientos orales nuevos, se espera que la mediana de supervivencia se acerque a la esperanza de vida normal en la mayoría de los pacientes, aunque es demasiado pronto para aseverar esto de forma definitiva.

Bibliografía

American Cancer Society: Cancer Facts and Figures 2017. Atlanta, Ga: American Cancer Society, 2017. Available online Notificación de salida. Last accessed July 13, 2017.
Kurzrock R, Kantarjian HM, Druker BJ, et al.: Philadelphia chromosome-positive leukemias: from basic mechanisms to molecular therapeutics. Ann Intern Med 138 (10): 819-30, 2003. [PUBMED Abstract]
Goldman JM, Melo JV: Chronic myeloid leukemia--advances in biology and new approaches to treatment. N Engl J Med 349 (15): 1451-64, 2003. [PUBMED Abstract]
Deininger MW, Goldman JM, Melo JV: The molecular biology of chronic myeloid leukemia. Blood 96 (10): 3343-56, 2000. [PUBMED Abstract]
Onida F, Ball G, Kantarjian HM, et al.: Characteristics and outcome of patients with Philadelphia chromosome negative, bcr/abl negative chronic myelogenous leukemia. Cancer 95 (8): 1673-84, 2002. [PUBMED Abstract]
Martiat P, Michaux JL, Rodhain J: Philadelphia-negative (Ph-) chronic myeloid leukemia (CML): comparison with Ph+ CML and chronic myelomonocytic leukemia. The Groupe Français de Cytogénétique Hématologique. Blood 78 (1): 205-11, 1991. [PUBMED Abstract]
Cortes JE, Talpaz M, Beran M, et al.: Philadelphia chromosome-negative chronic myelogenous leukemia with rearrangement of the breakpoint cluster region. Long-term follow-up results. Cancer 75 (2): 464-70, 1995. [PUBMED Abstract]
Oscier DG: Atypical chronic myeloid leukaemia, a distinct clinical entity related to the myelodysplastic syndrome? Br J Haematol 92 (3): 582-6, 1996. [PUBMED Abstract]
Kurzrock R, Bueso-Ramos CE, Kantarjian H, et al.: BCR rearrangement-negative chronic myelogenous leukemia revisited. J Clin Oncol 19 (11): 2915-26, 2001. [PUBMED Abstract]
Jabbour E, Kantarjian H: Chronic myeloid leukemia: 2012 update on diagnosis, monitoring, and management. Am J Hematol 87 (11): 1037-45, 2012. [PUBMED Abstract]
Lee SJ, Anasetti C, Horowitz MM, et al.: Initial therapy for chronic myelogenous leukemia: playing the odds. J Clin Oncol 16 (9): 2897-903, 1998. [PUBMED Abstract]

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Información sobre los estadios de la leucemia mielógena crónica

Chronic Myelogenous Leukemia Treatment (PDQ®)—Health Professional Version - National Cancer Institute

Chronic Myelogenous Leukemia Treatment (PDQ®)–Health Professional Version

LEUKEMIA

SECTIONS

Changes to This Summary (07/14/2017)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Treatment Option Overview for Chronic Myelogenous Leukemia (CML)

Revised text to state that at 5 years, there was no difference in progression-free survival (PFS) or overall survival (OS). Added that progression to accelerated-phase CML or blast crisis occurred in 7% of patients on imatinib and in 5% of patients on dasatinib (cited Cortes et al. as reference 8).

Revised text to state that although one of these two studies showed statistically significant decreased rates of progression to accelerated or blastic phase, the 5- to 10-year follow-up period with nilotinib and dasatinib demonstrated a survival for these agents similar to that for imatinib.

Revised text to state that allogeneic bone marrow transplantation (BMT) or stem cell transplantation (SCT) has also been applied with curative intent. Added that long-term data beyond 10 years of therapy are available, and most long-term survivors show no evidence of the BCR/ABL translocation by any available test; however, some patients are not eligible for this approach because of age, comorbid conditions, or lack of a suitable donor. In addition, substantial morbidity and mortality result from allogeneic BMT or SCT; a 5% to 10% treatment-related mortality can be expected, depending on whether a donor is related and on the presence of mismatched antigens. Also added that in a prospective trial of 427 transplant-eligible, previously untreated patients, 166 patients were allocated to allogeneic SCT, and 261 patients were allocated to drug treatment; there was no difference in 10-year OS (cited Gratwohl et al. as reference 11 and level of evidence 3iiiA).

Added text to state that imatinib mesylate and the newer tyrosine kinase inhibitors, along with allogeneic SCT, have contributed to a life expectancy for a newly diagnosed patient in 2013 that is only 3 life-years fewer than that of the general population (cited Bower et al. as reference 15).

Chronic-Phase CML

Added text to state that at 5 years, there was no difference in PFS or OS. Revised text about the progression to accelerated-phase CML or blast crisis that occurred in 13 patients on imatinib and in 6 patients on dasatinib (cited Cortes et al. as reference 9).

Revised text to state that although one of these two studies showed statistically significant decreased rates of progression to accelerated- or blastic-phase CML, the 5- to 10-year follow-up period with nilotinib and dasatinib demonstrated a survival for these agents similar to that for imatinib.

Added text to state that a single-arm clinical trial using first-line imatinib with either selective imatinib intensification or selective switching to nilotinib resulted in a 3-year OS of 96% and transformation-free survival of 95%, with a confirmed major molecular response rate of 73% at 24 months (cited Yeung et al. as reference 27 and level of evidence 3iiiDiv). Also added that all patients started treatment with imatinib and were given 600 mg daily. Imatinib plasma trough levels that were under 1,000 ng/mL on day 22 prompted an increase of imatinib to 800 mg daily. Molecular targets were set, and failure to reach these targets prompted an increase of imatinib to 800 mg daily or a switch to nilotinib. The molecular target rates for BCR-ABL at 3, 6, or 12 months were given.

Added text to state that this strategy of employing front-line imatinib is an alternative to the immediate use of more-potent tyrosine kinase inhibitors, such as nilotinib and dasatinib.

Added text to answer the question of whether the newer tyrosine kinase inhibitors, dasatinib and nilotinib, should replace imatinib as front-line therapy by stating that randomized trials have failed to confirm OS differences. Also added that imatinib blood levels and timed molecular targets that informed of the need for increased doses of imatinib may make any clinical differences between nilotinib, dasatinib, and imatinib more about side effects than about efficacy.

Added text that reviewed several retrospective reports to answer the question of whether patients who obtain a complete molecular remission can discontinue therapy with tyrosine kinase inhibitors; provided three summarizations of the data (cited Hughes et al. as reference 30 and level of evidence 3iiiDiv).

Added text to state that the duration of remissions after a successful reinduction with a previous tyrosine kinase inhibitor or the depth of subsequent responses with reinduction of a previous tyrosine kinase inhibitor is not known; at this time, there are insufficient data to recommend routinely stopping tyrosine kinase inhibitors, even in this select group of patients.

This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.

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