caso clínico linfoma t periférico - abhh eventos · caso clínico linfoma t periférico ....
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Caso clínico Linfoma T periférico
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Clinical case • 57-year-old, male. The clinical picture began 1 year ago, initially with generalized
arthralgias. Three months later he observed right cervical lymph node enlargement.
Although serology for Rheumatoid Arthritis was negative, radiologic and MRI images
were suggestive. He received oral metothrexate for 6 months. PS=0.
• Physical examination: Bilateral cervical lymph node enlargement (2 cm) and right
axillar lymph node 3 cm in diameter. Thoracic and abdominal CAT scans: anterior
mediastinal and pretracheal lymph node enlargement (1-2 cm). Para-aortic, splenic
hilar, hepatic hilar, celiac, common iliac and inguinal lymph node enlargement (>
diameter 3 cm).
• Bone marrow biopsy: normal
• LDH= normal. Hb=12 g/dl, Ht=37%, 3500 leucocytes (54% neutrophils, 26%
lymphocytes),
125 000 platelets. HIV and HCV negative.
• Histopathology of the axillary lymph node : Peripheral T cell lymphoma, NOS
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Histopathologic findings
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CD3 CD4
CD5 CD8
Immunohistochemical findings
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% of Total Cases Diffuse Large B-cell
Follicular Lymphoma
Marginal zone B-celllymphoma, MALT Peripheral T-celllymphomasCLL/SLL
Mantle Cell Lymphoma
Mediastinal Large B-cell LymphomaAnaplastic Large CellLymphoma/T-nullBurkitt
Incidence of Common Lymphoma Subtypes
30% DLBCL
25% Follicular 8%
MALT
7% CLL/SLL
85%
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Brazil (Rio de Janeiro) 20/145 13,8
Armitage, Ann Oncol 2004
Milito, JBPML, 2002
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PTCL-NOS
Mature T-cell lymphomas
Defined entities
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International T cell lymphoma project. JCO 2008
77%
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Peripheral T-cell lymphoma, NOS
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Peripheral T-cell lymphoma, NOS
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Ki67
Peripheral T-cell lymphoma, NOS
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Ballester et al, Oncogene, 2006
Biologic and morphologic heterogeneity suggests the existence of more
than one lymphoma in the PTCL-NOS category, to
be identified
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Angioimmunoblastic T-cell lymphoma
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Angioimmunoblastic T-cell lymphoma
Pattern 1 Hyperplastic follicles and
paracortical expansion
Pattern 3 Classical morphology
Pattern 2
Atrophic follicles and paracortical expansion
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Angioimmunoblastic T-cell lymphoma
CD21 CD3
CXCL3 CD79a + EBER CD10
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CD30
EMA
ALK1
Anaplastic Large Cell Lymphoma
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Log Rank Test: p<0.001
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
Years 0 1 2 3 4 5 6 7 8 9
Large Cell Lymphomas: Overall Survival Su
rviv
al
Anaplastic Large T-Cell
Diffuse Large B-Cell
Burkitt-like
Peripheral T-Cell
Armitage et al, 1997
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ALK-negative ALCL Has been controversial as to whether this is A variant of ALCL or related to PTCL, NOS
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Anaplastic Large-cell Lymphoma, ALK- (provisional category)
• Morphology: – Identical to ALK+ ALCL – Large cells with abundant
cytoplasm, cohesive growth, horseshoe-shaped nuclei (“hallmark cells”)
• Immunophenotype: – CD30+ strong, diffuse – No B-cell antigens (Pax5-) – ALK-
• Clinical: – Adult (med 60y) – Prognosis intermediate between
ALK+ and PTCL-NOS
CD30
CD30
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ALK + x ALK -
• ALK + occurs in younger age group • ALK + has improved prognosis over ALK negative
ALCL • ALK negative ALCL shows overlap with some PTCL,
NOS, but in general shows a plateau in survival curve, in contrast to most PTCL
• ALK negative ALCL included in WHO 2008 as entity distinct from ALK+ or PTCL NOS (provisional)
Anaplastic Large Cell Lymphoma
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Diagnosis CENSOR FAIL TOTAL MEDIAN
Anaplastic large cell lymphoma, ALK- 31 40 71 1.53 Anaplastic large cell lymphoma, ALK+ 45 33 78 10.4
p=0.015
Failure-free Survival Pr
opor
tion
0.0
0.1
0.2
0.3 0.4
0.5
0.6
0.7
0.8
0.9 1.0
Time 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
ALCL ALK+ vs. ALCL ALK -
5 y 60% vs 36%
ALK -
ALK +
Savage 2008
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Diagnosis CENSOR FAIL TOTAL MEDIAN ALCL ALK neg 31 40 71 1.53
PTCL-U 72 258 330a 0.91
p=0.012
Failure-free Survival ALK neg ALCL vs PTCL-U
Prop
ortio
n
0.0
0.1
0.2
0.3 0.4
0.5
0.6
0.7
0.8
0.9 1.0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Time
Savage 2008
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Adult T-cell leukaemia/lymphoma
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CD30
Adult T-cell leukaemia/lymphoma
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Leucemia/linfoma de célula T do adulto no Rio de Janeiro. Correlação clínico-patológica de 10 casos.
J Bras Patol, v.36, p.45 - 53, 2000.
Principais achados
– Forma aguda (6), linfomatosa (3) e crônica (1) – Gânglio (9), medula (5) e pele (4) – Estrongiloidíase (2), escabiose (2) – HPV, pneumocistose, herpes zoster, criptococose – Malacoplaquia pulmonar
MILITO C, MORAIS JC, LOUREIRO M, PULCHERI W, NUCCI M, SPECTOR N
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Treatment
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Distribuição dos subtipos
ILSG UFRJ n=1403 n=145
LDGC 30,6% 29,7% Folicular 22,1% 20,0% Linfócitos peqs 6,7% 5,5% Manto 6,0% 5,5% Mediastinal B 2,4% 2,8% Anaplásico 2,4% 4,1% Burkitt < 1% 6,2% T-periférico 7,0% 13,8% Anaplásico 2,4% 4,1%
International Lymphoma Study Group. Blood, Vol 89, No 11 (June 1), 1997: pp 3909-3918 Milito C, Morais JC, Spector N. J Bras Patol 2002
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Cancer 2007;109:1146–51.
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Vose J et al. International T-cell lymphoma project. J Clin Oncol 2008
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Treatment of PTCL-NOS
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Standard treatment
• CHOP • Benefit of anthracyclines?
International T cell lymphoma project. JCO 2008
PTCL-NOS AILT
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Is there an R-CHOP for PTCLs? • Alemtuzumab (anti-CD52, Campath®)
– n=24 – CR 50%, FFS < 48% – Infectious deaths > 10%
• Denileukin-diftitox (IL-2, Ontak®)
– n=49 – CR 75%, FFS 41% – Early discontinuation in 20/49, 7 due to adverse
events (anaphylaxis, pneumonitis, cardiac arrest, rhabdomyolysis)
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ASCT as consolidation in PTCL
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• 83 patients in CR or PR after CHOP x 6 • 55 underwent ASCT (TBI+CY) • Reasons for exclusion
– Progressive disease 24 – Patient request 2 – Treatment related mortality 1
Reimer, JCO, Jan 2009
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Reimer, JCO, Jan 2009
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Reimer, JCO, Jan 2009
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ASCT
• Does ASCT improve results or is it only selecting younger patients with chemosensitive disease?
• Primary non-responders are not eligible
• Moderately better than CHOP (?) – Selection
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Phase II trial of RIC-AlloSCT
• Relapsed/refractory PTCL/AITL/ALCL • N=17 (previous ASCT=8) • Median age 41 (23-60) • Median FUP 28 months
Corradini, JCO 2004
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• French registry • Retrospective study • 77 pts submitted to Allo-ASCT
– PTCL-NOS=27 – ALCL=27 – AILT=11 – Age 16-58
Allo-SCT
LeGouill S et al
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63%
5-year overall survival
Transplant-related mortality
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Drugs being studied for PTCL • Inibidores de HiDAC
– Vorinostat (Zolinza®) e romidepsin (Istodax®) • Análogos de purinas
– Fludarabina, cladribina e pentostatina – Gemcitabina, forodesina e clofarabina
• Anticorpos – Alemtuzumab (CD52) – Zanolimumab (CD4) – Siplizumab (CD2) – Bevacizumab (anti-VEGF, Avastin®) – cardiotoxicidade com
CHOP • Inibidor de proteossomo
– Bortezomibe Howard R. New dug therapies in PTCL. 2011
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JCO, 2011
N=111 pts previamente muito tratados
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Angioimmunoblastic T cell lymphoma
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Pacientes idosos ou assintomáticos
• “Watch and wait” (pode involuir espontaneamente)
• Corticóides
• Interferon
• MTX em dose baixa + corticóide
• Cladribina
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Blood 2008
5y OS = 30%
IPI não estratifica
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This study shows that HDT and ASCT offers the possibility of long-term disease-free
survival to patients with AITL. Early transplantation is necessary to achieve
optimal results.
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• Ciclosporina • Rituximab • Bevacizumab (anti-VEGF, Avastin®)
• Mini-allo
Linfoma T angioimunoblástico Tratamentos experimentais
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Linfoma anaplásico de grandes células
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ALCL
ALK + ALK -
60-80% 20-40%
Mais jovens Idade mediana = 34 anos
SG em 5 anos = 70% SG em 5 anos = 49%
Menos jovens Idade mediana = 60 anos
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ALCL ALK +
• Localizado: 4 CHOP + IFRT
• Avançado: 6-8 CHOP
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• Deve ser abordado como um linfoma T
periférico
ALCL ALK -
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Doença recaída
• brentuximab vedotin • FDA: “approved for the treatment of
patients with systemic anaplastic large cell lymphoma (ALCL) after failure of at least one prior multi-agent chemotherapy regimen.”