Transcript File
A 19-YO Woman with Huge Mediastinal Mass
She had history of chronic cough and night sweat for 1 month. She had no swelling of face nor upper extremities.
Left axillary and left lower cervival lymph node were palpated afterward.
Chest film showed large mediastinal mass.
CT chest and abdomen A large lobulated anterior mediastinal mass (4.5x10x6.5 cm) involving prevascular space of superior mediastinum and surrounding SVC, brachiocephalic vessels, ascending aorta, aortic arch MPA, left main pulmonary artery without obstruction. Multiple small paraaortic LN above IMA origin Atelectasis and obstructive pneumonia at lingular segment of LUL and bronchopneumonia at aterior segment of LUL
CT Image of Neck and Chest
Pretreatment FDG-PET/CT Image
Echocardiography
Good LV contraction, LVEF 65.1%, no LA dilatation, no significant valvular dysfunction No abnormal wall motion. No intracardiac shunt, no intracardiac mass, normal pericardium, no pericardial effusion
Lymph Node Tissue Diagnosis
Lymph node biopsy
, left cervical group Diffuse large B-cell lymphoma , anaplastic variant Some resembling Hodgkin or Reed-Sternberg cells Lymphoma cells mark distinctly with CD20, not CD3 or EMA. Some mark with CD30
Bone marrow biopsy
Negative for lymphoma cells High LDH 1037 U/L (N 225-450), ECOG 2
Diffuse Large B-cell Lymphoma: At Least Three Disease
Cell of origin Oncogenic Mechanisms Clinical outcome Germinal Center B Cell-like (GCB DLBCL) Germinal center Translocation • C-rel amplification Favorable 59% 5-yr survival Activated B Cell-like (ABC DLBCL) ? Post-germinal Center B cell Constitutive activation Of NF-kB Poor 30% 5-yr survival Primary Mediastinal B Cell Lymphoma (PMBL) ? Thymic B cell Chr. 9q24 Amplification PDL2 Favorable 64% 5-yr survival
Primary Mediastinal B-Cell Lymphoma (PMBL)
Large cells with polymorphic nuclei that have an abundant rim of clear cytoplasm. Fibrosis commonly results in compartmentalization of the neoplastic cells Immunophenotyping demonstrates the presence of B cell antigens in all cases (CD19, CD20, CD22 and CD79a). Bcl-2 is expressed in 80% of cases, CD10 is infrequently expressed and CD21 is negative. Surface immunoglobulin (sIg) expression is absent, CD30 staining is common, but weak. In contrast to HL, the transcription factors PAX5, BOB.1, Oct-2 and PU.1 are always expressed and CD15 is negative.
Haematologica 2008;93:1364-71.
Comparison of DLBCL and PMLBCL
Median age (years) Nodal/extranodal presentation Sex distribution (M:F) Stage I-II/III-IV Bulky disease
DLBCL
55 65%/35% 1:1 40%/60% 30%
PMLBCL
35 0%/100% 1:4 80%/20% 60%-70%
PMBL vs HL vs MGZL Dunleavy K, et al. Gray zone lymphoma; better treated like Hodgkin lymphoma or mediastinal large B-cell lymphoma. Curr Hematol Malig Rep 2012;7:241-7.
Diagnosis and Treatment
Diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma stage III BX IPI = 3 (LDH, stage, ECOG); Bulky Treatment R-CHOP-21 x 8 cycles After CR, autologous stem cell transplantation was done without prior radiotherapy
Interim PET after 2
nd
R-CHOP
A
soft tissue density mass
lymphadenopathy at left anterosuperior mediastinum,
4.5x6.0
cm at prevascular, paraaortic, AP window, lower paratracheal to left hilar region; no cervical
No FDG avidity
at soft tissue density mass.
Mild FDG avidity at left hilar node
tumor) (residual
CT whole body after 4
th
R-CHOP
Decreased size of soft tissue mass
mediastinum, effusion
3.7x1.9x3
at anterior cm. No pericardial Decreased size of multiple lymph nodes at left gastric, EG junction, paraaortic, aortocaval, celiac region
PET/CT after 8
th
R-CHOP
No pathological size of lymph nodes in head and neck regions, normal orbits and paranasal sinuses No pulmonary mass or nodule. An ill-defined isodensity mass in anterosuperior mediastinum (5x2.8 cm) occupying in prevascular space, paraaortic and AP window No demonstrable mass or cyst or fluid in abdominal and pelvic cavity No demonstrable bony destruction IMP: complete response, no active lymphoma
Haematologica 2008;93:1364-71.
The recommended first-line therapy is chemotherapy and radiotherapy (grade B). An anthracycline-based chemotherapy with CHOP, MACOP-B or VACOP-B is recommended (grade B) Patients with an inadequate early response should be candidates for early intensification with high-dose chemotherapy (grade C) Patients with refractory or relapsed disease should undergo rescue programs including intensive, non-cross-resistant debulking treatment followed, in chemosensitive patients, by high-dose chemotherapy and ABMT (grade B).
Overall survival by chemotherapy subtype in the IELSG study of 426 patients with primary mediastinal large B-cell lymphoma (PMBL)
100% 80 60 40 20 P < .0001
3 HDS/ABMT, n = 44 rd generation regimens, n = 277 426 pts CHOP, n = 105 0 2 4 6 8 10 Haematologica 2002;87:1258-126 12 14 16 18 years
The Therapeutic Outcome with the Inclusion of Radiation Therapy
Chemotherapy subgroup Patients who achieved CR after CHT
First-generation Third generation High-dose 50/105 (49%) 142/277 (51%) 23/44 (53%)
Conversions to CR among patients who received RT while in PR
14/21 (67%) 76/90 (84%)
Global CR after chemotherapy and RT
64/105 (61%) 218/277 (79%) 10/13 (77%) 33/44 (75%) Overall 215/426 (51%) 100/124 (81%) 315/426 (74%)
Haematologica 2002;87:1258-64.
Multivariate analysis of poor prognostic factors influence OS
Increasing age Male sex Poor performance status Advanced stage Induction chemotherapy P-value 0.0002
0.02
0.001
0.004
0.0002
Exp (B) 1.02
1.49
0.51
0.57
0.49
95% Cl 1.01-1.03
1.05-2.12
0.34-0.77
0.39-0.83
0.34-0.71
R-CHOP
RT vs
CHOP RT
Vassilakopoulos TP, et al. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone with or without radiotherapy in primary mediastinal large B-cell lymphoma: the emerging standard of care. The Oncologist 2012;17:139-49.
R-CHOP
RT vs
CHOP RT
Vassilakopoulos TP, et al. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone with or without radiotherapy in primary mediastinal large B-cell lymphoma: the emerging standard of care. The Oncologist 2012;17:139-49.
Comparative Outcome of 76 PMBL with R-CHOP RT and 45 Historical Control with CHOP RT
Vassilakopoulos TP, et al. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone with or without radiotherapy in primary mediastinal large B-cell lymphoma: the emerging standard of care. The Oncologist 2012;17:139-49.
Leuk Lymphoma 2012; early online:1-7,
All Patients Early Stage Patients
Leuk Lymphoma 2012; early online:1-7,
Front-line ASCT in PMBL
OS PFS DFS Rodriguez J, et al. Primary mediastinal large cell lymphoma (PMBL): frontline treatment with autologous stem cell transplantation (ASCT). The GEL-TAMO experience. Hematol Oncol 2008;26:171-8.
A 30-YR Female with Bilateral Cervical Lymphadenopathy
She had chronic intermittent fever with night sweats for 3 months. Bilateral enlarged cervical lymph nodes were palpated.
Physical examination revealed moderate anemia without jaundice, bilateral cervical and supraclavicular lymphadenopathy , and palpable splenomegaly .
Cervical lymph node biopsy revealed
classical Hodgkin lymphoma, nodular sclerosis
type.
CT whole body
Multiple matted LN at bilateral supraclavicular regions, right upper paratracheal, paraesophageal, subcarina, intraabdominal cavity, bilateral iliac regions
Hepatomegaly and splenomegaly with multiple splenic lymphoma nodules
Initial Laboratory Results
CBC :
Hb 8.6
g/dl, WBC 4880/mm 3 15,
L 6
, M 2), platelet 295,000/mm 3 (N 75, band ESR 75 mm/h LDH 964 U/L (N 225-450 U/L)
Albumin 3.2
g/dl, Ca 8.5 mg/dl Bone marrow study Multifocal marrow necrosis with diffuse myelofibrosis with abnormal medium to large mononuclear cells marked with CD30+, CD20-, CD3-, ALK-, CD15-
Diagnosis
Classical Hodgkin ’s lymphoma, nodular sclerosis Stage IV BS Advanced Stage with 4 risk factors Hb < 10.5 g/dl Stage IV Albumin < 4 g/dl Lymphocyte < 8%
Treatment group Limited stage Intermediate stage Advanced stage EORTC/GELA
CS I-II without risk factors (supradiaphragmatic) CS I II with ≥1 risk factors (supradiaphragmatic) CS III-IV
GHSG
CS I-II without risk factors CS I, IIA with ≥1 risk factors CS IIB with risk factors C/D, but not A/B CS IIB with risk factors A/B, CS III/IV
Risk factors
A large mediastinal mass B age ≥50 years C elevated ESR >50 mm/h without B symptoms; >30 mm/h with B symptoms D ≥4 nodal areas GHSG, German Hodgkin Study Group A large mediastinal mass (>1/3 maximum horizontal chest diameter) B extranodal disease C elevated ESR D ≥3 nodal areas EORTC, European Organisation for Research and Treatment of Cancer GELA, Groupe d ’Etude des Lymphomes de l’adulte
Advanced Stage HL
Associated with failure rate 30-40% with anthracycline polychemotherapy Treatment Evaluation of regimens comprising multi-agent chemotherapy Multiple consolidative strategies Improved disease control
Higher Intensive regimens to increase efficacy
BEACOPP -based regimen (GHSG) standard BEACOPP Escalated BEACOPP BEACOPP-14 > 2000 patients treated: esc BEACOPP CR: >90% (RT: 15-65%) FFTF: 82-88%, 4-10 yr follow up
OS: 86-90%, 4-10 yr follow up
MDS/AML: 0.9%
Significant more hematological and infectious toxicity, secondary leukemia/MDS, infertility
Hodgkin Lymphoma Advanced Stages
1.0
0.8
BEACOPP escalated BEACOPP base C/ABVD 0.6
0.4
0.2
No treatment (1940) Only alkylating agents (1965) 0.0
0 1 2 3 4 5 6 7 Overall Survival (y) 8 9 10
Other intensive regimen Standford V regimen and RT to any bulky disease Consolidation treatment Consolidation RT Patient with poor risk or residual lesions Less toxic than ASCT Supported by EORTC (MOPP/ABV cases IFRT) in PR Not recommended in PET-CR patients (GELA H89, GHSG H15) Autologous stem cell transplant (ASCT) Only in very high risk patient Not recommended in 1 st CR patient
Risk Adapted Treatment
Assessing chemosensitivity by interim PET Prognostic value of PET after 2 cycles of chemotherapy (PET2) PET2 – negative better FFS High negative predictive value for disease progression Low positive predictive value Ongoing trial 2xABVD PET2+ BEACOPP-14 or EB; PET2 ABVD or ABV (UK RATHL) 2xEB PET2+ 6xEB rituximab; PET2 (GHSG HD18) 2x vs 6xEB
Gallamini A, et al. Early interim 2-[18F] Fluoro-2-deoxy-D-glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage Hodgkin ’s lymphoma: a report from a joint Italian-Danish study.
JCO 2007;25(24):3746-52.
BEACOPPesc vs
ABVD
in advanced HL
3 Italian cooperative group Michelangelo Foundation The Gruppo Italiano di Terapie Innovative nei Linfomi (GITIL) The Intergruppo Italiano Linfomi (IIL) Unfavorable and advanced HL patients (331 patients) 6x ABVD 4x BEACOPPesc / 4x BEACOPPstd For CR and VGPR pt 30 G IFRT For Viviani S, et al. NEJM 2011;365(3):203-12. Better initial control in BEACOPP No difference in long-term clinical outcome Viviani S, et al. NEJM 2011;365(3):203-12. ABVD 4 published trials (2868 adult patients) GHSG HD9 and HD14 from Germany HD2000 and GSM-HD from Italy PFS significantly longer for escBEACOPP OS, not statistically significant More toxicity in escBEACOPP than ABVD Hematological, infection, AML/MDS No differences in 2 nd cancer, TRM or infertility 16-60 adult patients with unfavorable/ advanced HL benefited from escBEACOPP for PFS, no difference in OS Bauer K, et al. Cochrane Database of Systematic Reviews 2011, Issue 8. Bauer K, et al. Cochrane Database of Systematic Reviews 2011, Issue 8. The patient was treated with ABVD x4 CT whole body after 4x ABVD Much improvement of multiple lymph nodes and masses Small cervical, surpraclavicular nodes < 1 cm No mediastinal mass Multiple paraaortic node 1-1.7 cm Normal live and spleen No pelvic mass, no ascites Before After ABVDx4 Much improvement after 4 cycles of ABVD Another 2 cycles of ABVD was added PET/CT after completion of 6 th done ABVD was No hypermetabolic or enlarged lymph node in neck, chest and intraabdominal regions and no abnormal uptake in the bony structure that indicated no evidence of active lymphoma Suggestive of hypermetabolic intramural myoma at posterior fundus Thank You for Your Attentionesc BEACOPP vs
in early unfavorable and advanced stage HL
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