miércoles, 10 de agosto de 2016

Leucemia linfocítica crónica (PDQ®)—Versión para profesionales de salud - National Cancer Institute

Leucemia linfocítica crónica (PDQ®)—Versión para profesionales de salud - National Cancer Institute

National Cancer Institute



Instituto Nacional Del Cáncer

Leucemia linfocítica crónica: Tratamiento (PDQ®)–Versión para profesionales de salud



SECCIONES



Información general sobre la leucemia linfocítica crónica

Incidencia y mortalidad

Cálculo del número de casos nuevos y defunciones por leucemia linfocítica crónica (LLC) en los Estados Unidos en 2016:[1]
  • Casos nuevos: 18.960.
  • Defunciones: 4.660.
La LLC consiste en un trastorno de linfocitos morfológicamente maduros pero inmunológicamente menos maduros, y se manifiesta por la acumulación progresiva de estas células en la sangre, médula ósea y tejido linfático.[2] En este trastorno, el recuento de linfocitos en la sangre generalmente es mayor o igual a 5.000/mm3 con un inmunofenotipo característico (células B positivas CD5 y CD23).[3,4] En la medida en que los análisis se convirtieron en instrumentos más sensibles para detectar células similares a las monoclonales B-LLC en la sangre periférica, los investigadores han detectado una linfocitosis monoclonal de células B (LMB) en 3% de los adultos mayores de 40 años y en 6% de aquellos mayores de 60 años.[5] Este diagnóstico y detección temprana podría indicar falsamente una mejoría en la supervivencia del grupo y podría de manera innecesaria ocasionar preocupación o resultar en una terapia en aquellos pacientes que hubieran permanecido sin ser diagnosticados durante su vida, circunstancia esta conocida en la literatura médica como sobrediagnóstico o pseudoenfermedad.[6,7]
En dos series determinadas con más de 900 pacientes a los que se les dio un seguimiento prospectivo durante una mediana de 5 a 7 años, la LLC manifiesta que requirió de quimioterapia se presentó en el 7% de los pacientes.[5,8] En un análisis de una base de datos con información de hasta 77 meses antes del diagnóstico, casi todos los pacientes con un diagnóstico de LLC presentaron clones de células B prediagnósticos que fueron identificados en la sangre periférica cuando estuvieron disponibles.[4,9]
En aquellos pacientes con LLC evolutiva, el tratamiento con dosis convencionales de quimioterapia no es curativo; determinados pacientes que han sido tratados mediante trasplante de células madre alogénicas, han logrado sobrevivir de manera prolongada sin episodios de enfermedad.[10-14] El tratamiento antileucémico es generalmente innecesario al principio de la enfermedad cuando no hay complicaciones.[15] La mediana de supervivencia en todos los pacientes oscila entre 8 a 12 años, esto acorde a datos de ensayos anteriores desde los años 70 incluyendo los 90.[15,16] Hay sin embargo, una gran variación en cuanto a la supervivencia en sentido individual, que va de varios meses a una esperanza de vida normal. El tratamiento debe ser personalizado con base en el comportamiento clínico de la enfermedad.[17]
Según se encontró en un informe, la LLC se presenta principalmente en pacientes de mediana edad y ancianos, con una mayor frecuencia en los decenios sucesivos de la vida.[18] El curso clínico de esta enfermedad evoluciona de una linfocitosis poco activa sin otra enfermedad evidente a un estado que presenta aumento generalizado de volumen linfático con pancitopenia concomitante. Complicaciones de pancitopenia, incluyendo hemorragia e infección, son una causa principal de muerte en estos pacientes.[19] Anomalías inmunológicas, incluyendo anemia hemolítica con prueba de Coombs positiva, trombocitopenia inmunitaria y concentraciones reducidas de inmunoglobulinas pueden complicar el manejo de LLC.[20] Los factores de pronóstico que podrían ayudar a pronosticar el desenlace clínico incluyen el subgrupo citogenético, estado mutacional de inmunoglobulina, ZAP-70 y CD38.[2,21-29] (Para mayor información, consultar la sección sobre Factores pronósticos en la sección de este sumario Información sobre los estadios de la leucemia linfocítica crónica). Los pacientes que presentan linfoma no Hodgkin de multiplicación rápida de grado alto, generalmente linfoma difuso de células B grandes denominado transformación de Richter, tienen un pronóstico precario.[30] En los pacientes con LLC se ve un aumento en el riesgo de presentar otras neoplasias, aun antes del tratamiento.[31] En un análisis poblacional de casi dos millones de pacientes con cáncer de la base de datos National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) se indica que, en aquellos pacientes con LLC preexistente que después presentaron cáncer colorrectal y de mama, la supervivencia específica de cáncer es significativamente más baja (cociente de riesgos instantáneos [CRI], 1,46; P < 0,001 para el cáncer colorrectal y CRI 1,41; P = 0,005 para el cáncer de mama) que la supervivencia específica por cáncer en los pacientes de cáncer colorrectal y de mama sin antecedentes de LLC; después de ajustar por edad, sexo, raza y estadio de la enfermedad y excluir las muertes relacionadas con LLC.[32]
La confusión con otras enfermedades se puede evitar con la determinación de los marcadores celulares de superficie. Los linfocitos de la LLC coexpresan los antígenos CD19 y CD20 de las células B junto con el antígeno CD5 de las células T.[33] Esta coexpresión sólo sucede en otra entidad clínica, el linfoma de células de manto. Las células B de la LLC expresan concentraciones relativamente bajas de inmunoglobulina de superficie de membrana (comparadas con las células B normales de la sangre periférica) y una sola cadena ligera (κ o λ).[15] La LLC se diagnostica por un incremento absoluto de linfocitosis, infiltración de la médula ósea o ambos, junto con las características de morfología e inmunofenotipo, lo que confirma la población clonal característica.
El diagnóstico diferencial debe excluir la leucemia de células pilosas y la macroglobulinemia de Waldenström (para mayor información, consultar el sumario del PDQ sobre el Tratamiento de la leucemia de células pilosas y Tratamiento del linfoma no Hodgkin en adultos). La macroglobulinemia de Waldenström tiene una evolución natural y opciones terapéuticas similares a las de la LLC, con la excepción del síndrome de hiperviscosidad relacionado con la macroglobulinemia como resultado de una concentración alta de inmunoglobulina M. La leucemia prolinfocítica (LPL) es una entidad poco común que se caracteriza por un número excesivo de prolinfocitos en la sangre con un fenotipo típico que es positivo para CD19, CD20, e inmunoglobulina de superficie de membrana y negativo para CD5. Estos pacientes presentan esplenomegalia y una respuesta precaria a quimioterapia de dosis alta o baja.[15,34]
La cladribina (2-clorodeoxiadenosina) parece ser un agente activo (60% de remisión completa) para pacientes con leucemia prolinfocítica de células B.[35][Grado de comprobación: 3iiiDiv] El alemtuzumab (campath-1H), un anticuerpo monoclonal humanizado anti-CD52, fue utilizado por 76 pacientes con leucemia prolinfocítica de células T después de no haber respondido ante la quimioterapia previa (usualmente pentostatina o cladribina) quienes lograron 51% de tasa de respuesta (intervalo de confianza 95%, 40–63%) y una mediana de tiempo hasta la evolución de 4,5 meses (con un intervalo , 0,1–45,4 meses).[36][Grado de comprobación: 3iiiDiv] Estas tasas de respuesta han sido confirmadas por otros investigadores.[37] Los pacientes con LLC que muestran transformación prolinfocitoide mantienen el fenotipo clásico de LLC y tienen un pronóstico más precario que los pacientes con LPL.
La leucemia de linfocitos granulares grandes (LLG) se caracteriza por linfocitosis con un inmunofenotipo de linfocitos citotóxicos naturales (CD2, CD16 y CD56) o un inmunofenotipo de células T (CD2, CD3 y CD8).[38-40] Estos pacientes presentan con frecuencia neutrocitopenia y antecedentes de artritis reumatoide. La evolución natural es poco activa, marcada frecuentemente por anemia y esplenomegalia. Esta afección parece corresponder al espectro clínico del síndrome de Felty.[41] Un dato genético característico que se presenta en casi 50% de los pacientes con LLG de células T se trata de mutaciones en el transductor de señales y activador del gen de la transcripción 3 (STAT 3).[42] La terapia incluye dosis bajas de ciclofosfamida o metotrexato orales, ciclosporina y el tratamiento de las infecciones bacterianas adquiridas durante la neutrocitopenia grave.[38,40,43,44]

Sumarios relacionados

Otros sumarios del PDQ que contienen información sobre la LLC son:
Bibliografía
  1. American Cancer Society: Cancer Facts and Figures 2016. Atlanta, Ga: American Cancer Society, 2016. Available online. Last accessed July 11, 2016.
  2. Dighiero G, Hamblin TJ: Chronic lymphocytic leukaemia. Lancet 371 (9617): 1017-29, 2008. [PUBMED Abstract]
  3. Hallek M, Cheson BD, Catovsky D, et al.: Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 111 (12): 5446-56, 2008. [PUBMED Abstract]
  4. Shanafelt TD, Kay NE, Jenkins G, et al.: B-cell count and survival: differentiating chronic lymphocytic leukemia from monoclonal B-cell lymphocytosis based on clinical outcome. Blood 113 (18): 4188-96, 2009. [PUBMED Abstract]
  5. Rawstron AC, Bennett FL, O'Connor SJ, et al.: Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia. N Engl J Med 359 (6): 575-83, 2008. [PUBMED Abstract]
  6. Dighiero G: Monoclonal B-cell lymphocytosis--a frequent premalignant condition. N Engl J Med 359 (6): 638-40, 2008. [PUBMED Abstract]
  7. Fazi C, Scarfò L, Pecciarini L, et al.: General population low-count CLL-like MBL persists over time without clinical progression, although carrying the same cytogenetic abnormalities of CLL. Blood 118 (25): 6618-25, 2011. [PUBMED Abstract]
  8. Shanafelt TD, Kay NE, Rabe KG, et al.: Brief report: natural history of individuals with clinically recognized monoclonal B-cell lymphocytosis compared with patients with Rai 0 chronic lymphocytic leukemia. J Clin Oncol 27 (24): 3959-63, 2009. [PUBMED Abstract]
  9. Landgren O, Albitar M, Ma W, et al.: B-cell clones as early markers for chronic lymphocytic leukemia. N Engl J Med 360 (7): 659-67, 2009. [PUBMED Abstract]
  10. Ritgen M, Stilgenbauer S, von Neuhoff N, et al.: Graft-versus-leukemia activity may overcome therapeutic resistance of chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene status: implications of minimal residual disease measurement with quantitative PCR. Blood 104 (8): 2600-2, 2004. [PUBMED Abstract]
  11. Moreno C, Villamor N, Colomer D, et al.: Allogeneic stem-cell transplantation may overcome the adverse prognosis of unmutated VH gene in patients with chronic lymphocytic leukemia. J Clin Oncol 23 (15): 3433-8, 2005. [PUBMED Abstract]
  12. Khouri IF, Keating MJ, Saliba RM, et al.: Long-term follow-up of patients with CLL treated with allogeneic hematopoietic transplantation. Cytotherapy 4 (3): 217-21, 2002. [PUBMED Abstract]
  13. Doney KC, Chauncey T, Appelbaum FR, et al.: Allogeneic related donor hematopoietic stem cell transplantation for treatment of chronic lymphocytic leukemia. Bone Marrow Transplant 29 (10): 817-23, 2002. [PUBMED Abstract]
  14. Pavletic SZ, Khouri IF, Haagenson M, et al.: Unrelated donor marrow transplantation for B-cell chronic lymphocytic leukemia after using myeloablative conditioning: results from the Center for International Blood and Marrow Transplant research. J Clin Oncol 23 (24): 5788-94, 2005. [PUBMED Abstract]
  15. Rozman C, Montserrat E: Chronic lymphocytic leukemia. N Engl J Med 333 (16): 1052-7, 1995. [PUBMED Abstract]
  16. Wierda WG, O'Brien S, Wang X, et al.: Prognostic nomogram and index for overall survival in previously untreated patients with chronic lymphocytic leukemia. Blood 109 (11): 4679-85, 2007. [PUBMED Abstract]
  17. Montserrat E: CLL therapy: progress at last! Blood 105 (1): 2-3, 2005.
  18. Catovsky D, Fooks J, Richards S: Prognostic factors in chronic lymphocytic leukaemia: the importance of age, sex and response to treatment in survival. A report from the MRC CLL 1 trial. MRC Working Party on Leukaemia in Adults. Br J Haematol 72 (2): 141-9, 1989. [PUBMED Abstract]
  19. Anaissie EJ, Kontoyiannis DP, O'Brien S, et al.: Infections in patients with chronic lymphocytic leukemia treated with fludarabine. Ann Intern Med 129 (7): 559-66, 1998. [PUBMED Abstract]
  20. Mauro FR, Foa R, Cerretti R, et al.: Autoimmune hemolytic anemia in chronic lymphocytic leukemia: clinical, therapeutic, and prognostic features. Blood 95 (9): 2786-92, 2000. [PUBMED Abstract]
  21. Döhner H, Stilgenbauer S, Benner A, et al.: Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 343 (26): 1910-6, 2000. [PUBMED Abstract]
  22. Hamblin TJ, Davis Z, Gardiner A, et al.: Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood 94 (6): 1848-54, 1999. [PUBMED Abstract]
  23. Damle RN, Wasil T, Fais F, et al.: Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood 94 (6): 1840-7, 1999. [PUBMED Abstract]
  24. Rosenwald A, Alizadeh AA, Widhopf G, et al.: Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia. J Exp Med 194 (11): 1639-47, 2001. [PUBMED Abstract]
  25. Klein U, Tu Y, Stolovitzky GA, et al.: Gene expression profiling of B cell chronic lymphocytic leukemia reveals a homogeneous phenotype related to memory B cells. J Exp Med 194 (11): 1625-38, 2001. [PUBMED Abstract]
  26. Orchard JA, Ibbotson RE, Davis Z, et al.: ZAP-70 expression and prognosis in chronic lymphocytic leukaemia. Lancet 363 (9403): 105-11, 2004. [PUBMED Abstract]
  27. Rassenti LZ, Huynh L, Toy TL, et al.: ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. N Engl J Med 351 (9): 893-901, 2004. [PUBMED Abstract]
  28. Kröber A, Bloehdorn J, Hafner S, et al.: Additional genetic high-risk features such as 11q deletion, 17p deletion, and V3-21 usage characterize discordance of ZAP-70 and VH mutation status in chronic lymphocytic leukemia. J Clin Oncol 24 (6): 969-75, 2006. [PUBMED Abstract]
  29. Byrd JC, Gribben JG, Peterson BL, et al.: Select high-risk genetic features predict earlier progression following chemoimmunotherapy with fludarabine and rituximab in chronic lymphocytic leukemia: justification for risk-adapted therapy. J Clin Oncol 24 (3): 437-43, 2006. [PUBMED Abstract]
  30. Tsimberidou AM, Keating MJ: Richter syndrome: biology, incidence, and therapeutic strategies. Cancer 103 (2): 216-28, 2005. [PUBMED Abstract]
  31. Tsimberidou AM, Wen S, McLaughlin P, et al.: Other malignancies in chronic lymphocytic leukemia/small lymphocytic lymphoma. J Clin Oncol 27 (6): 904-10, 2009. [PUBMED Abstract]
  32. Solomon BM, Rabe KG, Slager SL, et al.: Overall and cancer-specific survival of patients with breast, colon, kidney, and lung cancers with and without chronic lymphocytic leukemia: a SEER population-based study. J Clin Oncol 31 (7): 930-7, 2013. [PUBMED Abstract]
  33. DiGiuseppe JA, Borowitz MJ: Clinical utility of flow cytometry in the chronic lymphoid leukemias. Semin Oncol 25 (1): 6-10, 1998. [PUBMED Abstract]
  34. Melo JV, Catovsky D, Galton DA: The relationship between chronic lymphocytic leukaemia and prolymphocytic leukaemia. I. Clinical and laboratory features of 300 patients and characterization of an intermediate group. Br J Haematol 63 (2): 377-87, 1986. [PUBMED Abstract]
  35. Saven A, Lee T, Schlutz M, et al.: Major activity of cladribine in patients with de novo B-cell prolymphocytic leukemia. J Clin Oncol 15 (1): 37-43, 1997. [PUBMED Abstract]
  36. Keating MJ, Cazin B, Coutré S, et al.: Campath-1H treatment of T-cell prolymphocytic leukemia in patients for whom at least one prior chemotherapy regimen has failed. J Clin Oncol 20 (1): 205-13, 2002. [PUBMED Abstract]
  37. Dearden CE, Matutes E, Catovsky D: Alemtuzumab in T-cell malignancies. Med Oncol 19 (Suppl): S27-32, 2002. [PUBMED Abstract]
  38. Sokol L, Loughran TP Jr: Large granular lymphocyte leukemia. Oncologist 11 (3): 263-73, 2006. [PUBMED Abstract]
  39. Semenzato G, Zambello R, Starkebaum G, et al.: The lymphoproliferative disease of granular lymphocytes: updated criteria for diagnosis. Blood 89 (1): 256-60, 1997. [PUBMED Abstract]
  40. Lamy T, Loughran TP Jr: How I treat LGL leukemia. Blood 117 (10): 2764-74, 2011. [PUBMED Abstract]
  41. Bowman SJ, Sivakumaran M, Snowden N, et al.: The large granular lymphocyte syndrome with rheumatoid arthritis. Immunogenetic evidence for a broader definition of Felty's syndrome. Arthritis Rheum 37 (9): 1326-30, 1994. [PUBMED Abstract]
  42. Koskela HL, Eldfors S, Ellonen P, et al.: Somatic STAT3 mutations in large granular lymphocytic leukemia. N Engl J Med 366 (20): 1905-13, 2012. [PUBMED Abstract]
  43. Loughran TP Jr, Kidd PG, Starkebaum G: Treatment of large granular lymphocyte leukemia with oral low-dose methotrexate. Blood 84 (7): 2164-70, 1994. [PUBMED Abstract]
  44. Dhodapkar MV, Li CY, Lust JA, et al.: Clinical spectrum of clonal proliferations of T-large granular lymphocytes: a T-cell clonopathy of undetermined significance? Blood 84 (5): 1620-7, 1994. [PUBMED Abstract]
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Información sobre los estadios de la leucemia linfocítica crónica
  • Actualización: 5 de febrero de 2016








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

National Cancer Institute



National Cancer Institute

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





SECTIONS





General Information About Chronic Lymphocytic Leukemia (CLL)

Incidence and Mortality

Estimated new cases and deaths from CLL in the United States in 2016:[1]
  • New cases: 18,960.
  • Deaths: 4,660.
CLL is a disorder of morphologically mature but immunologically less mature lymphocytes and is manifested by progressive accumulation of these cells in the blood, bone marrow, and lymphatic tissues.[2] In this disorder, lymphocyte counts in the blood are usually greater than or equal to 5,000/mm3 with a characteristic immunophenotype (CD5- and CD23-positive B cells).[3,4] As assays have become more sensitive for detecting monoclonal B-CLL–like cells in peripheral blood, researchers have detected a monoclonal B-cell lymphocytosis (MBL) in 3% of adults older than 40 years and 6% in adults older than 60 years.[5] Such early detection and diagnosis may falsely suggest improved survival for the group and may unnecessarily worry or result in therapy for some patients who would have remained undiagnosed in their lifetime, a circumstance known in the literature as overdiagnosis or pseudodisease.[6,7]
In two selected series of more than 900 patients followed prospectively for a median of 5 to 7 years, overt CLL requiring chemotherapy occurred in 7% of patients.[5,8] In a database analysis and for up to 77 months before diagnosis, almost all patients with a diagnosis of CLL had prediagnostic B-cell clones that were identified in peripheral blood when available.[4,9]
For patients with progressing CLL, treatment with conventional doses of chemotherapy is not curative; selected patients treated with allogeneic stem cell transplantation have achieved prolonged disease-free survival.[10-14] Antileukemic therapy is frequently unnecessary in uncomplicated early disease.[15] The median survival for all patients ranges from 8 to 12 years in older trials with data from the 1970s through the 1990s.[15,16] There is, however, a large variation in survival among individual patients, ranging from several months to a normal life expectancy. Treatment must be individualized based on the clinical behavior of the disease.[17]
As found in one report, CLL occurs primarily in middle-aged and elderly adults, with increasing frequency in successive decades of life.[18] The clinical course of this disease progresses from an indolent lymphocytosis without other evident disease to one of generalized lymphatic enlargement with concomitant pancytopenia. Complications of pancytopenia, including hemorrhage and infection, represent a major cause of death in these patients.[19] Immunological aberrations, including Coombs-positive hemolytic anemia, immune thrombocytopenia, and depressed immunoglobulin levels may all complicate the management of CLL.[20] Prognostic factors that may help predict clinical outcome include cytogenetic subgroup, immunoglobulin mutational status, ZAP-70, and CD38.[2,21-29] (Refer to the Prognostic Factors section in the Stage Information for Chronic Lymphocytic Leukemia section of this summary for more information.) Patients who develop an aggressive high-grade non-Hodgkin lymphoma, usually diffuse large B-cell lymphoma and termed a Richter transformation, have a poor prognosis.[30] Patients with CLL are also at increased risk for other malignancies, even before therapy.[31] A population-based analysis of almost 2 million cancer patients in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database suggests that cancer-specific survival for patients with preexisting CLL who subsequently develop colorectal and breast cancer is significantly lower (hazard ratio [HR], 1.46; P < .001 for colorectal cancer and HR, 1.41; P = .005 for breast cancer) than cancer-specific survival for patients with colorectal and breast cancer who do not have antecedent CLL, after adjusting for age, sex, race, and disease stage, and excluding CLL-related deaths.[32]
Confusion with other diseases may be avoided by determination of cell surface markers. CLL lymphocytes coexpress the B-cell antigens CD19 and CD20 along with the T-cell antigen CD5.[33] This coexpression only occurs in one other disease entity, mantle cell lymphoma. CLL B cells express relatively low levels of surface-membrane immunoglobulin (compared with normal peripheral blood B cells) and a single light chain (kappa or lambda).[15] CLL is diagnosed by an absolute increase in lymphocytosis and/or bone marrow infiltration coupled with the characteristic features of morphology and immunophenotype, which confirm the characteristic clonal population.
The differential diagnosis must exclude hairy cell leukemia and Waldenström macroglobulinemia. (Refer to the PDQ summaries on Hairy Cell Leukemia and Adult Non-Hodgkin Lymphoma Treatment for more information.) Waldenström macroglobulinemia has a natural history and therapeutic options similar to CLL, with the exception of hyperviscosity syndrome associated with macroglobulinemia as a result of elevated immunoglobulin M. Prolymphocytic leukemia (PLL) is a rare entity characterized by excessive prolymphocytes in the blood with a typical phenotype that is positive for CD19, CD20, and surface-membrane immunoglobulin and negative for CD5. These patients demonstrate splenomegaly and poor response to low-dose or high-dose chemotherapy.[15,34]
Cladribine (2-chlorodeoxyadenosine) appears to be an active agent (60% complete remission rate) for patients with de novo B-cell prolymphocytic leukemia.[35][Level of evidence: 3iiiDiv] Alemtuzumab (campath-1H), an anti-CD52 humanized monoclonal antibody, has been used for 76 patients with T-cell prolymphocytic leukemia after failure of prior chemotherapy (usually pentostatin or cladribine) with a 51% response rate (95% confidence interval, 40%–63%) and median time to progression of 4.5 months (range, 0.1–45.4 months).[36][Level of evidence: 3iiiDiv] These response rates have been confirmed by other investigators.[37] Patients with CLL who show prolymphocytoid transformation maintain the classic CLL phenotype and have a worse prognosis than PLL patients.
Large granular lymphocyte (LGL) leukemia is characterized by lymphocytosis with a natural killer cell immunophenotype (CD2, CD16, and CD56) or a T-cell immunophenotype (CD2, CD3, and CD8).[38-40] These patients often have neutropenia and a history of rheumatoid arthritis. The natural history is indolent, often marked by anemia and splenomegaly. This condition appears to fit into the clinical spectrum of Felty syndrome.[41] A characteristic genetic finding in almost 50% of the patients with T-cell LGL involves mutations in the signal transducer and activator of the transcription 3 gene (STAT 3).[42] Therapy includes low doses of oral cyclophosphamide or methotrexate, cyclosporine, and treatment of the bacterial infections acquired during severe neutropenia.[38,40,43,44]

Related Summaries

Other PDQ summaries containing information about CLL include the following:
References
  1. American Cancer Society: Cancer Facts and Figures 2016. Atlanta, Ga: American Cancer Society, 2016. Available online. Last accessed July 11, 2016.
  2. Dighiero G, Hamblin TJ: Chronic lymphocytic leukaemia. Lancet 371 (9617): 1017-29, 2008. [PUBMED Abstract]
  3. Hallek M, Cheson BD, Catovsky D, et al.: Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 111 (12): 5446-56, 2008. [PUBMED Abstract]
  4. Shanafelt TD, Kay NE, Jenkins G, et al.: B-cell count and survival: differentiating chronic lymphocytic leukemia from monoclonal B-cell lymphocytosis based on clinical outcome. Blood 113 (18): 4188-96, 2009. [PUBMED Abstract]
  5. Rawstron AC, Bennett FL, O'Connor SJ, et al.: Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia. N Engl J Med 359 (6): 575-83, 2008. [PUBMED Abstract]
  6. Dighiero G: Monoclonal B-cell lymphocytosis--a frequent premalignant condition. N Engl J Med 359 (6): 638-40, 2008. [PUBMED Abstract]
  7. Fazi C, Scarfò L, Pecciarini L, et al.: General population low-count CLL-like MBL persists over time without clinical progression, although carrying the same cytogenetic abnormalities of CLL. Blood 118 (25): 6618-25, 2011. [PUBMED Abstract]
  8. Shanafelt TD, Kay NE, Rabe KG, et al.: Brief report: natural history of individuals with clinically recognized monoclonal B-cell lymphocytosis compared with patients with Rai 0 chronic lymphocytic leukemia. J Clin Oncol 27 (24): 3959-63, 2009. [PUBMED Abstract]
  9. Landgren O, Albitar M, Ma W, et al.: B-cell clones as early markers for chronic lymphocytic leukemia. N Engl J Med 360 (7): 659-67, 2009. [PUBMED Abstract]
  10. Ritgen M, Stilgenbauer S, von Neuhoff N, et al.: Graft-versus-leukemia activity may overcome therapeutic resistance of chronic lymphocytic leukemia with unmutated immunoglobulin variable heavy-chain gene status: implications of minimal residual disease measurement with quantitative PCR. Blood 104 (8): 2600-2, 2004. [PUBMED Abstract]
  11. Moreno C, Villamor N, Colomer D, et al.: Allogeneic stem-cell transplantation may overcome the adverse prognosis of unmutated VH gene in patients with chronic lymphocytic leukemia. J Clin Oncol 23 (15): 3433-8, 2005. [PUBMED Abstract]
  12. Khouri IF, Keating MJ, Saliba RM, et al.: Long-term follow-up of patients with CLL treated with allogeneic hematopoietic transplantation. Cytotherapy 4 (3): 217-21, 2002. [PUBMED Abstract]
  13. Doney KC, Chauncey T, Appelbaum FR, et al.: Allogeneic related donor hematopoietic stem cell transplantation for treatment of chronic lymphocytic leukemia. Bone Marrow Transplant 29 (10): 817-23, 2002. [PUBMED Abstract]
  14. Pavletic SZ, Khouri IF, Haagenson M, et al.: Unrelated donor marrow transplantation for B-cell chronic lymphocytic leukemia after using myeloablative conditioning: results from the Center for International Blood and Marrow Transplant research. J Clin Oncol 23 (24): 5788-94, 2005. [PUBMED Abstract]
  15. Rozman C, Montserrat E: Chronic lymphocytic leukemia. N Engl J Med 333 (16): 1052-7, 1995. [PUBMED Abstract]
  16. Wierda WG, O'Brien S, Wang X, et al.: Prognostic nomogram and index for overall survival in previously untreated patients with chronic lymphocytic leukemia. Blood 109 (11): 4679-85, 2007. [PUBMED Abstract]
  17. Montserrat E: CLL therapy: progress at last! Blood 105 (1): 2-3, 2005.
  18. Catovsky D, Fooks J, Richards S: Prognostic factors in chronic lymphocytic leukaemia: the importance of age, sex and response to treatment in survival. A report from the MRC CLL 1 trial. MRC Working Party on Leukaemia in Adults. Br J Haematol 72 (2): 141-9, 1989. [PUBMED Abstract]
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Stage Information for CLL
  • Updated: August 3, 2016
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