lunes, 8 de agosto de 2016

Leucemia mieloide aguda en adultos (PDQ®)—Versión para profesionales de salud - National Cancer Institute

Leucemia mieloide aguda en adultos (PDQ®)—Versión para profesionales de salud - National Cancer Institute



Instituto Nacional Del Cáncer

Leucemia mieloide aguda en adultos: Tratamiento (PDQ®)–Versión para profesionales de salud

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Información general sobre la leucemia mieloide aguda en adultos

Incidencia y mortalidad

Cálculo del número de casos nuevos y defunciones por leucemia mieloide aguda (LMA) en Estados Unidos en 2016:[1]
  • Casos nuevos: 19.950.
  • Defunciones: 10.430.

Pronóstico y supervivencia

Los adelantos en el tratamiento de la LMA (también llamada leucemia mielógena aguda, leucemia no linfocítica aguda o LNLA) han dado lugar a tasas de remisión completa sustancialmente mejores.[2] El tratamiento deberá ser lo suficientemente intensivo como para lograr una remisión completa, ya que la remisión parcial no ofrece beneficios sustanciales de supervivencia. Aproximadamente, de 60 a 70% de los adultos con LMA se puede esperar que logren un estado de remisión completa después del tratamiento apropiado de inducción. Se puede esperar que más de 25% de los adultos con LMA (cerca de 45% de los que logran remisión completa) sobrevivan 3 años o más y es posible que se curen. Las tasas de remisión de LMA en adultos están inversamente relacionadas con la edad, con una tasa esperada de remisión de más de 65% para los pacientes menores de 60 años de edad. Existen datos que indican que una vez que se logra, la duración de la remisión puede ser más corta entre los pacientes de edad más avanzada. Parece que la mayor morbilidad y mortalidad durante la inducción está directamente relacionada con la edad. Otros factores pronósticos adversos son la complicación del sistema nervioso central con leucemia, infección sistémica al momento del diagnóstico, recuento elevado de leucocitos (>100.000/mm3), LMA inducida por tratamiento y antecedentes de síndrome mielodisplásico o un trastorno hematológico previo. Los pacientes de leucemias que expresan el antígeno CD34 de células progenitoras o la glicoproteína P (producto de genMDR1) tienen un resultado inferior.[3-5] La LMA relacionada con una duplicación interna en tándem del gen FLT3 (FLT3/mutación ITD) tiene un resultado inferior atribuido a una mayor tasa de recaída.[6,7]

Análisis citogenético

El análisis citogenético proporciona una de las pruebas más sólidas disponibles para el pronóstico, prediciendo así resultados tanto de la inducción a remisión como el tratamiento posremisión, según se ve en el estudio del Southwest Oncology Group (SWOG) y el Eastern Cooperative Oncology Group (ECOG) (E-3489).[8] Las anomalías citogenéticas que indican un pronóstico bueno son la t(8;21), inv(16) o t(16;16) y t(15;17). Las características citogenéticas normales presagian una LMA de riesgo regular. Los pacientes con LMA que se caracteriza por supresiones de los grupos grandes o monosomías de cromosomas 5 o 7; por translocaciones o inversiones de cromosoma 3, t(6;9), t(9;22); o por anomalías de cromosoma 11q23 tienen pronósticos particularmente precarios con quimioterapia. Estos subgrupos citogenéticos según se ve en el ensayo del Medical Research Council (MRC) (MRC-LEUK-AML11), predicen el resultado clínico en pacientes de edad avanzada con LMA al igual en pacientes jóvenes.[9] Los genes de fusión formados en t(8;21) e inv(16) pueden ser detectados por reacción en cadena de polimerasa relacionada con la transcriptasa inversa (RCP-TI) o hibridación por fluorescencia in situ (HFIS) la cual indicará la presencia de estas alteraciones genéticas en algunos pacientes en quienes la citogenética estándar era técnicamente inadecuada. RCP-TI no parece identificar un número significativo de pacientes con genes de fusión de pronóstico favorable con características citogenéticas normales.[10]

Pronóstico y clasificación de la Organización Mundial de la Salud

La clasificación de la LMA ha sido revisada por un grupo de patólogos y de médicos clínicos, patrocinados por la Organización Mundial de la Salud (OMS).[11] Si bien se conservaron los elementos de la clasificación franco-americano-británica (es decir, morfología, fenotipo inmune, citogenética y características clínicas), la clasificación de la OMS incorpora hallazgos más recientes sobre la genética y las características clínicas de la LMA en un intento por definir entidades que son biológicamente homogéneas y relevantes para el pronóstico y el tratamiento.[11-13] Cada criterio tiene implicaciones para el pronóstico y el tratamiento pero, para los fines prácticos, el tratamiento antileucémico es similar para todos los subtipos.
Un seguimiento a largo plazo de 30 pacientes que tenían LMA en remisión por al menos 10 años, ha mostrado un 13% de incidencia de tumores secundarios. De 31 mujeres con supervivencia prolongada de LMA o leucemia linfoblástica aguda menores de 40 años de edad, 26 recuperaron la menstruación normal al cabo del tratamiento. Entre los 36 hijos vivos de las supervivientes, se presentaron dos problemas congénitos.[14]
Distinguir la LMA de la leucemia linfocítica aguda tiene consecuencias terapéuticas importantes. Las tinciones histoquímicas y las determinaciones del antígeno de la superficie celular ayudan a diferenciarlas.

Sumarios relacionados

Otros sumarios del PDQ que contiene información relacionada con la leucemia mieloide aguda son los siguientes:
Bibliografía
  1. American Cancer Society: Cancer Facts and Figures 2016. Atlanta, Ga: American Cancer Society, 2016. Available online. Last accessed July 11, 2016.
  2. American Cancer Society: Cancer Facts and Figures 2014. Atlanta, Ga: American Cancer Society, 2014. Available online. Last accessed July 11, 2016.
  3. Myint H, Lucie NP: The prognostic significance of the CD34 antigen in acute myeloid leukaemia. Leuk Lymphoma 7 (5-6): 425-9, 1992. [PUBMED Abstract]
  4. Geller RB, Zahurak M, Hurwitz CA, et al.: Prognostic importance of immunophenotyping in adults with acute myelocytic leukaemia: the significance of the stem-cell glycoprotein CD34 (My10) Br J Haematol 76 (3): 340-7, 1990. [PUBMED Abstract]
  5. Campos L, Guyotat D, Archimbaud E, et al.: Clinical significance of multidrug resistance P-glycoprotein expression on acute nonlymphoblastic leukemia cells at diagnosis. Blood 79 (2): 473-6, 1992. [PUBMED Abstract]
  6. Kottaridis PD, Gale RE, Frew ME, et al.: The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood 98 (6): 1752-9, 2001. [PUBMED Abstract]
  7. Yanada M, Matsuo K, Suzuki T, et al.: Prognostic significance of FLT3 internal tandem duplication and tyrosine kinase domain mutations for acute myeloid leukemia: a meta-analysis. Leukemia 19 (8): 1345-9, 2005. [PUBMED Abstract]
  8. Slovak ML, Kopecky KJ, Cassileth PA, et al.: Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group Study. Blood 96 (13): 4075-83, 2000. [PUBMED Abstract]
  9. Grimwade D, Walker H, Harrison G, et al.: The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood 98 (5): 1312-20, 2001. [PUBMED Abstract]
  10. Mrózek K, Prior TW, Edwards C, et al.: Comparison of cytogenetic and molecular genetic detection of t(8;21) and inv(16) in a prospective series of adults with de novo acute myeloid leukemia: a Cancer and Leukemia Group B Study. J Clin Oncol 19 (9): 2482-92, 2001. [PUBMED Abstract]
  11. Brunning RD, Matutes E, Harris NL, et al.: Acute myeloid leukaemia: introduction. In: Jaffe ES, Harris NL, Stein H, et al., eds.: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press, 2001. World Health Organization Classification of Tumours, 3, pp 77-80.
  12. Bennett JM, Catovsky D, Daniel MT, et al.: Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group. Br J Haematol 33 (4): 451-8, 1976. [PUBMED Abstract]
  13. Cheson BD, Cassileth PA, Head DR, et al.: Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia. J Clin Oncol 8 (5): 813-9, 1990. [PUBMED Abstract]
  14. Micallef IN, Rohatiner AZ, Carter M, et al.: Long-term outcome of patients surviving for more than ten years following treatment for acute leukaemia. Br J Haematol 113 (2): 443-5, 2001. [PUBMED Abstract]
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Clasificación de la leucemia mieloide aguda en adultos










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

National Cancer Institute

Adult Acute Myeloid Leukemia Treatment (PDQ®)–Health Professional Version



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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]
  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]
Next section >
Stage Information for CLL
  • Updated: August 3, 2016
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