ATLL

1. Leucemia/linfoma de
células T del adulto.
MR1 Yesenia Huerta Collado

2. INTRODUCCIÓN
 Linfoma de células T asociado a infección HTLV-1 (+).
 Áreas endémicas: Japón, Islas Caribe, Centroamérica, Sudamérica, África
intertropical, Este Medio.
 Edad común de inicio en Sud america: promedio 40 años
 Riesgo estimado de ATL siendo portador: 6-7% en Varones, 2-3% mujeres.
 Alta carga viral >4 copias/100 mononucleares SP es factor de riesgo
independiente.
 Rutas de transmisión: vertical, lactancia, sexual y sanguínea.
 Se asocia a infección con Strongyloides estercoralis y dermatitis infectiva

7. Maria C. Diumenjoa.The burden of non-Hodgkin lymphoma in Central and South America. Cancer Epidemiology 44S (2016) S168–S177

8. PATOGENESIS
 El HTLV-1 es un retrovirus que
codifica 3 proteínas estructurales:
Gag, Pol y Env.
 Pol codifica las funciones de la
transcriptasa inversa, la proteasa y
la integrasa.
 Gag proporciona al virión
proteínas básicas
 Env se utiliza a efectos de
infectividad viral.
 Además,el genoma del HTLV-1
tiene una región pX que codifica
proteínas reguladoras como Tax y
Rex

9. BIOLOGIA MOLECULAR HTLV-1
 PROTEINA TAX
 Media la persistencia viral y desarrollo de la enfermedad
 Potencial oncogénico
 Vias de señalización celular (NF-kb)
 Interfiere con los checkpoints e inhibe la reparación del
DNA
 Modulacion del RNA mensajero.
 Rpta transitoria.
 Altamente inmunogenica

11. FORMAS DE PRESENTACIÓN CLÍNICA

13. Formas de presentación clínica: Aguda
 The most common presentation of ATL
 60 percent of cases
 poor prognosis with survival measured in months to a year despite aggressive treatment
 A high peripheral blood white blood cell count is common due to the
presence of circulating lymphocytes with highly abnormal
convoluted nuclei
 Bone marrow involvement is observed in 5 to 35 percent of cases.
 Lymphadenopathy is seen in almost all cases.
 Involvement of the liver and spleen is present in approximately 16
and 22 percent, respectively.
 40 to 50 percent will have hypercalcemia with or without lytic bone
lesions at presentation and an additional third will develop
hypercalcemia at some point during the course of their disease.
Raro:
 Interstitial pulmonary infiltrates, which may be due to
pneumocystis jirovecii pneumonia
 Central nervous system involvement with mass lesions on imaging

15. Formas de presentación clínica: Linfomatosa
 Approximately 20% of cases
 Is characterized by prominent
lymphadenopathy without blood involvement.
 Patients frequently have an elevated LDH
level
 Can have hypercalcemia.
 Prognosis is poor with a survival similar to that
of patients with the acute varian.

16. Formas de presentación Clínica:
Smoldering
 The smoldering variant is least common, accounting for approximately 10
percent of cases.
 These patients are often asymptomatic except for skin and/or pulmonary
lesions.
 They have normal blood lymphocyte counts with <5 percent circulating
neoplastic cells and normal calcium levels.
 Median survival without treatment is approximately three years

17. Formas de presentación clínica: Crónica
 La variante crónica suele presentarse con erupciones cutáneas exfoliativas, leucocitosis
menos prominente con linfocitosis absoluta, linfadenopatía de carácter leve e
hipercalcemia
 CRONICA FAVORABLE: sin factor de mal pronóstico
 CRONICA NO FAVORABLES: con al menos 1 factor de mal pronostico
FACTORES PRONOSTICO:
Poor prognostic factors include three factors:
 including serum LDH > upper limit of normal (ULN)
 serum blood urea nitrogen > ULN
 serum albumin < lower limit of normal.

19. Viruses 2015, Recent Advances in Therapeutic Approaches for Adult T-cell
Leukemia/Lymphoma

20. Otros hallazgos Clínicos
 lesiones cutáneas se dan en el 43-72% de todas las variantes clínicas de la LLCTA debido a la
invasión directa de células malignas en la piel, resultando en diferentes tipos de erupciones.
Se han descrito 6 tipos de erupciones:
 nodulotumorales (38,7%)
 en placa (26,9%9
 multipapulares (19,3%)
 en parche (6,7%)
 eritrodérmicas (4,2%)
 purpúricas (4,2%)
 Las erupciones cutáneas no son exclusivas y suelen ser crónicas, indoloras o prurítica
 el tronco se ve comprometido enel 10% de los casos, el tronco y las extremidades en el 25%,y,
solo, la cabeza, el cuello, o las extremidades en el 5%

21. Histología
 Histología revela 3 patrones distintos de infiltración:
 Perivascular
 nodular
 difuso.
 El epidermotropismo y los microabscesos de Pautrier son una característica frecuente.
 Expresan marcadores de células T maduras:
 CD2, CD5, CD25 (fuerte y uniforme), CD29, CD45RO, TCR y HLA-DR.
 También suelen expresar CD4+ y CD8-
 Nódulos linfáticos comprometidos suelen exhibir compromiso difuso, principalmente con
expansión paracortical

23. INMUNOHISTOQUIMICA
CD4 (+) CD25(+)
Arch Pathol Lab Med—Vol 138, February 2014

24. El frotis de sangre periférica
 presencia de blastos a modo
de «células en forma de flor”:
son linfocitos de tamaño medio-grande
con núcleos con forma de pétalos y un
patrón de cromatina áspera, CD4+ y
CD25+
 Suelen confundirse con sombras de
Gumprecht.

26. Citometría de flujo
 Malignidad de células T reguladoras/células Th2 con
expresión de alta frecuencia de CD3/CD4/CD25/CCR4
y FoxP3 en casi la mitad de las células.

27. SMOLDERING
CRONICO
AGUDA
LINFOMATOSA
 Watchful waiting
 Antiviral therapy : AZT/IFN
 Skin directed therapy :
topical steroid,
 ultraviolet, surgery,
radiation
No favorable
Favorable
 Clinical trial
 Zidovudine and interferon
 Chemotherapy
 Clinical trial
 Chemotherapy

28. SMOLDERING
CRONICO
AGUDA
LINFOMATOSA
 Watchful waiting
 Antiviral therapy : AZT/IFN
 Skin directed therapy :
topical steroid,
 ultraviolet, surgery,
radiation
No favorable
Favorable
 Clinical trial
 Zidovudine and interferon
 Chemotherapy
 Clinical trial
 Chemotherapy
QT
 VCAP-AMP-VECP (JAPON)
CHOP14, CHOP21,
mEPOCH and ATL-G-CSF

29. SMOLDERING
CRONICO
AGUDA
LINFOMATOSA
 Watchful waiting
 Antiviral therapy : AZT/IFN
 Skin directed therapy :
topical steroid,
 ultraviolet, surgery,
radiation
No favorable
Favorable
 Clinical trial
 Zidovudine and interferon
 Chemotherapy
 Clinical trial
 Chemotherapy

30. SMOLDERING
CRONICO
AGUDA
LINFOMATOSA
 Watchful waiting
 Antiviral therapy :
AZT/IFN
 Skin directed therapy :
topical steroid,
 ultraviolet, surgery,
radiation
No favorable
Favorable
 Clinical trial
 Zidovudine and interferon
 Chemotherapy
 Clinical trial
 Chemotherapy
Responders
Non-responders
zidovudine and
interferon
Chemotherapy
Best supportive care
Responders
Non-responders
allogeneic
hematopoietic cell
transplant
prior therapy
 Clinical trial
 Best supportive care
 Alternate therapy

31. Japanese Cancer Association. 2015. Recent Advances in Treatment of ATL.

33. J Clin Oncol. 2019 Mar 10;37(8):677-687

34. CONSENSUS STATEMENTS
1. HTLV-1 serology should be undertaken in cases of T-cell
lymphoma and PTCL, particularly in HTLV-1 endemic
regions.
2. Active monitoring is not appropriate for PCT-ATL, and
intensive treatment should be considered
Previosly Report :
PRIMARY CUTANEOUS
TUMORAL (PCT) ATL
Included within
SMOLDERING
PCT-ATL is distinct cutaneous lesions tumors that grow
rapidly
histology shows large, atypical cells with a high
proliferative index
WITHOUT
leukemic,
lymph node
considered a poor prognostic
*defining
cutaneous tumoral
type is difficult

35. CONSENSUS STATEMENT
1. Prophylactic CNS therapy should be considered for all
patients with aggressive ATL
 10 – 20% of patients with aggressive ATL will experience CNS
progression.
 Thus, even in patients without a CNS lesion, it is important to
incorporate
CNS prophylaxis.
 Previous retrospective analysis that revealed that more than one
half of relapses that occurred at a new site after chemotherapy
occurred in the CNS