Table of contents :
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oncogene |
B1 cells
chronic
lymphocytic
leukemia (B-CLL)![]() |
t(14;15)(q32;q13) |
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MALT lymphoma | t(11;18)(q21;q21) |
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precursor B
cell
acute lymphoid
leukemia![]() |
t(9;22)(q34;q11) or variant t(4;11)(q21;q23) BCR/ABL AF4, ALLI |
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precursor acute lymphoid leukemia | t(9;22) t(1;19) t(17;19) t(5;14) BCR, ABL E2A, PBX HLF, E2A IL3, IG |
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mantle cell
lymphoma (MCL)![]() |
t(11;14)(q13;q32) | BCL-1, IgH |
follicular
lymphoma (FL)![]() |
t(14;18)(q32;q21) | BCL-2, IgH |
diffuse
large B-cell lymphoma
(DLBCL)![]() |
t(3;-)(q27;-) a t(17;-)(p13;-) |
BCL-6 p53 |
Burkitt's
lymphoma (BL)![]() |
t(8;-)(q24;-) (numerous sites of translocation may be involved with these genes) | C-MYC |
CD30+ anaplastic large cell lymphoma | t(2;5)(p23;q35) | ALK |
lymphoplasmacytoid lymphoma | t(9;14)(p13;q32) | - |
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B1 cells
chronic
lymphocytic
leukemia (B-CLL)![]() |
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mantle cell
lymphoma (MCL)![]() |
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extranodal marginal
zone
B-cell
lymphoma (MZL)![]() |
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follicular
lymphoma (FL)![]() |
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diffuse
large B-cell lymphoma
(DLBCL)![]() |
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55 |
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Burkitt's
lymphoma (BL)![]() |
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89 |
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precursor T cell lymphoblastic lymphoma![]() |
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64 |
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anaplastic large T/null cell lymphoma |
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69 |
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peripheral T cell non-Hodgkin's lymphoma |
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55 |
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6 |
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11a | 11b |
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13 | 14 | 15 | 16 |
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24 |
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27 | 28 |
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34 |
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45RA | 45RO |
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54 |
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57 | 68 |
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72 | 74 | w75 | 79a |
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103 |
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154 |
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typical B-CLL![]() |
+ | + | - (1-2% +ref1, ref2, ref3, ref4, ref5, ref6, ref7) | - | + | - | + | weak | - (rarely +ref) | + | weak | + | - | bad px | + | 18% (atypical CLL and trisomy 12)ref; truncated | Iglow IgLdim |
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atypical B-CLL![]() |
- | -ref | + (< 0.5%)ref | + | high | high | high | - | +ref | +ref | IgL high | |||||||||||||||||||||||||||||||||||||||||
T-CLL | - (rarely +) | ++ | ++ | - (+ in 5%) | - (+) | +/- | ++ | - | - | - | - | - | - | - | TdT-, sIg- HLA-DR- | |||||||||||||||||||||||||||||||||||||
B-PLL![]() |
30% | - | + | + | + | + | + | - | - | Ig high | ||||||||||||||||||||||||||||||||||||||||||
T-PLL | -/+ | ++ | + | ++ | ++ | ++ | -/+ | - | - | - | - | - | - | +/- | TdT-, sIg-, HLA-DR -/+ | |||||||||||||||||||||||||||||||||||||
ATL | - | ++ | ++(-) | ++ | ++ | ++ | - | - | - | - | - | ++ | + | +/- | TdT-, sIg-, HLA-DR+ | |||||||||||||||||||||||||||||||||||||
SS![]() |
++ | ++ | ++ | ++ | ++ | ++ | - (rarely +) | - | - | - | - | - | - | - | TdT-, sIg-, HLA-DR- | |||||||||||||||||||||||||||||||||||||
WM![]() |
5% | 3% | 81% | 100% | 100% | 38% | 33% | 61% | 71% | - | 48% | 100%ref | 85% | cIg+, IgMhi | ||||||||||||||||||||||||||||||||||||||
MM![]() |
+/- | 9% | + | +/- | ++ | +/- | 9% | 5%ref | + | 72% | 18% | + | + | HM1.24 SP17 MUC1 sIg- cIghi |
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SMZL![]() |
- | - (+ in 20%) | - | - (+ in SLVL) | - | + | + | + | -/+ | + | - | + | - | - | - | +/- | - | - | + | + | - | - | -/+ | + | -/+ | + | + | - | high IgM low IgD L chain+ MIB1low cyclin D1- p53- Bcl-2+ Bcl-6- Ln3+, Kib3-/+, TRAP-/+, p27-/+, CXCR3+, IRTA-1+, BSAP+, IRF4-, E2F-1- |
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HCL![]() |
- | - | + | + | + | + | - | + | - | + | - | - | +ref | + | B-ly-7+, sIg+, cIg+ | |||||||||||||||||||||||||||||||||||||
MALT![]() |
- | - | - | + | + | + | + | - | - | + | - | +ref | ||||||||||||||||||||||||||||||||||||||||
IPSID![]() |
- | - | + | + | + | + | - | - | + | |||||||||||||||||||||||||||||||||||||||||||
NMZL![]() |
- | - | - | + | + | + | + | - | - | + | - | |||||||||||||||||||||||||||||||||||||||||
FL![]() |
- | + | - | + | + | -/+ | + | -/+ | - | - | + | AlkP+
centrocytes; AlkP- centroblasts. Blc-6+ |
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MCL![]() |
86%ref (rarely -ref) | - (rarely +ref) | + | + | + | + | + | - (rarely + ref1, ref2) | - | 62%ref | 60%ref1, ref2 | BCL-6 (5%), cyclin D1+(95%), IgLbright, IgD (62%), IgM (100%)ref | ||||||||||||||||||||||||||||||||||||||||
DLBCL![]() |
-/+ | 50% | + | + | + | -/+ | + | - | 50% | +/- | 75%ref | 50% | + | HLA-DR 50% | ||||||||||||||||||||||||||||||||||||||
ALBCL![]() |
+ | + | + | + | ||||||||||||||||||||||||||||||||||||||||||||||||
MLBCL![]() |
+/- | - | + | + | + | + | +/- | |||||||||||||||||||||||||||||||||||||||||||||
EATCL![]() |
+ | - | - | + | - | + | + | + | TcR- cyTcRb+, HLA-DR-ßF1- | |||||||||||||||||||||||||||||||||||||||||||
BL![]() |
- | +/- | + | + | eBL | + | - | + | - | 75%ref | Ig+/- | |||||||||||||||||||||||||||||||||||||||||
B-ALL![]() |
+ref | |||||||||||||||||||||||||||||||||||||||||||||||||||
T-ALL![]() |
-ref | |||||||||||||||||||||||||||||||||||||||||||||||||||
AITL![]() |
+ | + (sometimes - but cyCD3+ref) | + | +ref | - | TcR+ | ||||||||||||||||||||||||||||||||||||||||||||||
ALTCL![]() |
-ref | |||||||||||||||||||||||||||||||||||||||||||||||||||
PTCL-NOS![]() |
-ref | |||||||||||||||||||||||||||||||||||||||||||||||||||
HL![]() |
-ref | |||||||||||||||||||||||||||||||||||||||||||||||||||
AML![]() |
-ref | |||||||||||||||||||||||||||||||||||||||||||||||||||
APL![]() |
- | + | + | - | + | - | + |
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NK-cell antigens | - | + | + (some populations lack NK-cell antigens ) |
cytoplasmic CD3 (e chain) | + | + | +/- |
surface CD3 | + | + | - |
CD4, CD8 | CD8+>>>CD4+ | CD8+>CD4-8->>CD4+ | CD4-8+/- |
TCRaß, gd (TCR gene rearrangement and protein expression) | + | + | - |
cytotoxic granules | + | + | + |
killing mechanism | MHC restricted | non-MHC restricted | non-MHC restricted |
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hepatosplenic | CD4-8->CD8+ | + | + (most cases have a non-activated phenotype (TIA-1+, granzyme B-, perforin-)) | -/+ | - | gd > ab |
subcutaneous panniculitis-like T-cell lymphoma (SCPTCL) | CD8+>CD4-8->CD4+ | -/+ | + | -/+ | - | ab > gd |
anaplastic large cell lymphoma (ALCL), primary cutaneous | CD4+>CD4-8->CD8+ | -/+ | +/- | + | - (based on nodal cases) | ab > gd |
nasal/nasal type NK/T-cell | CD8+>CD4-8- | + | + | +/- | + | NK > gd > ab |
aggressive NK-cell leukemia | CD8+,CD4-8- | + | + | NT | -/+ | NK,T cell |
intestinal | CD4-8->CD8+>CD4+ | -/+ | + | +/- | ab > gd >>NK | |
blastic NK-cell lymphoma/leukemia | CD4 | + | + | NT | - | NK |
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marrow involvement | ++ | ++ (the number of blasts may be small and involvement patchy compared to other leukemias) | ++ (13-41% of AML overall are CD56+) |
skin disease | ++ | - | < 10% |
lymph node involvement | + | ++ | ++ |
hepatosplenomegaly | 15% | + | < 10% |
EBV | - | +/- | - |
cytoplasmic granules | +/- | + | - |
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Spainref | 174 | 95 (55) | 30 (17) | 22 (13) | 4 (8) | 13 (7) | ALCL had the best survival (65 mo median); the others were in 20-25 mo range with the in testinal as the predominant rare subtype at only 4 mos. | |
Franceref | 288 | 160 (55) | 60 (21) | 68 (24) | - | - | 5 yr OS for T-ALCL was 64% compared to 53% for DLBCL and 35% for other PTCL | |
Italyref | 167 | 78 (47) | 62 (37) | 19 (11) | 2 (1) | 6 (4) | ALCL had a better DFS (66% vs 38%, p=0.0001) than the remaining PTCL | |
USAref (Arrowsmith ER, Greer JP, Stein RS, et al. Peripheral t-cell lymphomas: A clinicopathological study of 94 unselected patients using the Revised European American Lymphoma (REAL) classification. J Clin Oncol. 1998;17:50a) | 78 | 53 (68) | 8 (10) | 7 (9) | 9 (12) | 1 (1) | IPI correlated with 5 yr OS: 76% low, 32% low- intermediate, 28% high-intermediate, 9% high risk | |
92 | 28 (30) | 40 (43) | 13 (14) | - | 11 (12) | OS was 49% and PFS was 22% at 5 yr. ALCL had best prognosis (58% OS, 40% PFS) compared to other subtypes | ||
Korearef | 125 | 53 (42) | 5 (4) | 5 (4) | 59 (47) | 3 (2) | Angiocentric were primarily nasal/nasopharyngeal origin. PTCL, NOS, had a worse survival compared to DLBCL. | |
Japan (Lymphoma Study Group of Japanese Pathologists. The World Health Organization classification of malignant lymphomas in Japan: incidence of recently recognized entities. Pathol Internat. 2000:50:696:702) | Kyushu | 265 | 83 (27) | 22 (6) | 38 (10) | 28 (8) | 3 (1) | ATLL accounted for 181 (52%) in Kyushu and 47 (15%) in other areas, for a combined 238 cases in Japan |
Other | 315 | 130 (41) | 27 (9) | 39 (12) | 55 (17) | 17 (5) |
study | total no. pts | PTCL subtype (n) | first remission or relapsed/refractory (n) | EFS/PFS | OS | comments |
Rodriguezref | 115 | PTCLUS (80) | first remission (37) | 79% (5 y) | 80 % (5 y) | ALK status unknown; median age 31 for primary transplant |
ALCL (25) | auto | |||||
AILT (6) | ||||||
other (2) | relapsed/refractory (78) | 79% (5 y) | 80% (5 y) | No patient salvaged with refractory disease | ||
auto | 39% (5 y) | 45% (5 y) | ||||
Jagasiaref | 28 | PTCLUS (6) | relapsed/refractory | 50% (3 y) | 43% (6 y) | Outcome analyses combined auto and allo transplants superior outcome to other PTCLs and DLBCL |
ALCL (11) | auto (23) | |||||
allo (5) | Non-ALCL 38% (3 y) | Non-ALCL 47% (3 y) | ||||
ALK positive (7) | ||||||
ALK negative (4) | ||||||
CUTALCL (5) | ||||||
AILT (3) | ALK ALCL | ALK+ ALCL 100% (3 y) | ALK+ ALCL 100% (3 y) | |||
NK/T (3) | ALK- ALCL 0% (3 y) | ALK- ALCL 50% (3 y) | ||||
Blystadref | 40 | PTCLUS(20) | first remission (17) | 48% (3 y) | 58% (3 y) | Outcome analyses combined first remission and relapsed groups ALK status unknown |
ALCL (14) | auto | |||||
AILT (2) | non-ALCL 44% (3 y) | |||||
ETTL (2) | relapsed (23) | ALCL 79% (3 y) | ||||
NK/T (2) | auto | |||||
Songref | 36 | PTCLUS (20) | relapsed/refractory | 37% (3 y) | 48% (3 y) | ALCL (ALK status unknown) xxx to improve outcome compared with PTCLUS and DLBCL |
ALCL (9) | auto | |||||
AILT (2) | PTCLUS 23% (3 y) | PTCLUS 35% (3 y) | ||||
NK/T (4) | ||||||
ETTL (1) | ALCL 67% (3 y) | ALCL 78% (3 y) | ||||
Corradiniref | 17 | PTCLUS (9) | relapsed/refractory | 64% (3 y) | 81% (3 y) | Many had late relapses |
ALK- ALCL (4) | RIC allo | |||||
AILT (4) | Unknown whether primary CUTALCL were included |
agents | target | PTCL (n) | clinical studies |
nucleoside analogs | |||
gemcitabine![]() |
nucleoside analog; non-specific DNA synthesis inhibition | PTCL (10) | 60% ORRref |
araG | |||
506U78 (nelarabine)-pro-drug | nucleoside analog; selective toxicity for T cells | PTCL (8) | Phase II ORR 14% (Czuczman MS, Porcu P,
Johnson J, Niedzwiecki
D, Canellos G, Cheson BD. CALGB 59901: Results of a
phase II study of
506U78
in CTCL and PTCL [abstract]. Blood
2004;104(11):2486a) Toxicity: 2 early deaths |
immunotoxin | |||
denileukin
difitox![]() |
IL-2 receptor | PTCL (14) | Phase II ORR 50% (Dang NH, Pro B, Hagemeister FB, et al. Interim analysis of a phase II study of denileukin diftitox (Ontak) for relapsed/refractory T-cell non-Hodkin’s lympoma [abstract]. Blood. 2004;104(11):2641a) |
histone deaceylase Inhibitors | |||
depsipeptide | Histone de-acetylation | PTCL (19) | Phase II ORR 26% (Piekarz RL, Frye R, Turner M, et al. Responses and molecular markers in patients with peripheral t-cell lymphoma treated on a phase II trial of depsipeptide, FK228. Proc ASCO. 2005;24:3061a) |
immunotherapy | |||
anti-CD25
mAbs![]() |
CD25 | ATLL (18) | Phase I/II ORR 56%ref |
alemtuzumab![]() |
CD52 | PTCL (14) | Pilot ORR 36%ref
Toxicity: CMV reactivation 43%; 36% TRM-study closed early |
alemtuzumab![]() ![]() ![]() ![]() |
CD52 | PTCL except ALK+ ALCL (23) included untreated patients | Pilot ORR 61% (Weidmann E, Hess G,
Krause
SW, et al. Combination
chemo-immunotherapy using alemtuzumab, fludarabine,
cyclophosphamide
and
doxorubicin is an effective first-line regimen in
peripheral T-cell
lymphoma
[abstract]. Blood. 2004;104(11):2640a) Toxicity: 81% grade III/IV leukopenia; 56% CMV reactivation |
SGN30![]() |
CD30 | ALCL (5) | SGN30 phase II OR 33% (Forero-Torres A,
Bernstein S, Gopal
A, et al. SGN-30 (anti-CD30 monoclonal antibody) is
active and well
tolerated
in patients with refractory or recurrent systemic
anaplastic large cell
lymphoma [abstract]. Blood. 2004;104(11):2637a) Toxicity: well tolerated |
MDX-060![]() |
CD30 | ALCL (6) | MDX-060 ORR 33% Toxicity: no MTDref |
5F11![]() |
CD30 | CD30+ ALCL | 5F11 phase I study ongoing in CD30+ lymphomas |
KM2760![]() |
CCR4 | ATLL CCR4+ PTCLs | preclinical studies ongoingref |
group | CR | PR | PD |
NCI of Canada Clinical Trials Group | Disappearance of all disease No symptoms Must last 4 weeks or "unconfirmed CR" |
>= 50% decrease in SPD No increase or new lesion Assessable disease stable or decreased Must last 4 weeks or "unconfirmed" |
Increase by 25% in longest diameter New lesion Assessable disease progression |
Cancer and Leukemia Group B | Disappearance of all disease No symptoms Biopsy suspicious residual nodes Must last 4 weeks by physical examination With residual abnormality:Mediastinal or abdominal mass persists for two cycles after > 50% decrease |
> 50% decrease in SPD of all lesions No new
lesions Disappearance of symptoms > 30% decrease in liver below right costal margin Normal liver function tests |
> 25% increase in sum of the products of the greatest
diameters (SPD)
of any lesion compared with study baseline New lesion |
Eastern Cooperative Oncology Group | If Ga scan was positive, now must be negative
Disappearance
of all
disease (normal nodes <= 1 x 1
cm;
nodes > 1 x 1
biopsied or
observed x
3 months) Normal liver/spleen; biopsy if was positive
Negative
unilateral
bone marrow Must last >= 4 weeks |
>= 50% decrease in SPD Liver decrease by 50%
(PE) Spleen <= 5 cm below left costal margin must become normal Spleen > 5 cm decrease by 50% Must last >= 4 weeks |
Increase by > 25% in sum of the products of the greatest diameters (SPD) or new lesion (relapse: new disease after CR or PD after PR) |
European Organization for Research and Treatment of Cancer/Dutch Hemato-Oncology Group | Disappearance of all disease Normal labs, x-rays, bone
marrow Persistent nodes biopsied or considered CR Must last 4 weeks |
>= 50% decrease in SPD of all lesions, no new lesions
No symptoms No increase >= 25% in any lesion (a) with positive bone marrow (> or < 20%), (b) with negative bone marrow Must last 4 weeks |
>= 25% increase in sum of the products of the
greatest
diameters (SPD)
of >= one lesion New lesion |
Group d'Etude des Lymphomes de l'Adulte | Disappearance of all lesions (No palpable nodes, no mass
> 1 cm in
diameter on CT, no bone marrow involvement) Normal performance status (PS) Disappearance of initial biologic abnormalities |
Regression of initial tumor mass (nodal, extranodal) by
> 50% or Disappearance of all lesions but persistent bone marrow involvement with normal PS and disappearance of initial biologic abnormalities |
ND |
Uncertain CR: Persistence for 4 months of palpable node
or
mass on
CT that has regressed >= 75% but not disappeared.
Biopsy of accessible masses recommended. CT-guided needle biopsy if > 5 cm in thoracic of mediastinum Normal bone marrow, normal PS, no symptoms Disappearance of initial biologic abnormalities |
ND | ND | |
Southwest Oncology Group | Disappearance of all disease No new lesions Normal markers, laboratory values If restaging is required, separate path response is defined Lasts >= 6 weeks |
>= 50% decrease in SPD of all lesions No new lesions No progression of assessable disease Lasts >= 6 weeks |
50% increase or 10 cm2 (whichever is smaller)
in
sum of
the products of the greatest diameters (SPD) over
baseline, worse
assessable
disease New lesion Failure to return, death/worsening Not worse assessable |
response category | physical examination | lymph node | lymph node masses | bone marrow |
CR | normal | normal | normal | normal |
CRu | normal | normal | normal | indeterminate |
normal | normal | > 75% decrease | normal or indeterminate | |
PR | normal | normal | normal | positive |
normal | >= 50% decrease | >= 50% decrease | irrelevant | |
decrease in liver/spleen | >= 50% decrease | >= 50% decrease | irrelevant | |
relapse/progression | enlarging liver/spleen; new sites | new or increased | new or increased | reappearance |
end point | response category | definition | point of measurement |
overall survival (OS) | all patients | death from any cause | entry onto trial |
event-free survival (EFS) | all patients (under circumstances where presentation of EFS is more appropriate for responders only, this point should be clearly stated) | failure or death from any cause | entry onto trial |
progression-free survival (PFS) | all patients | disease progression or death from NHL | entry onto trial |
disease-free survival (DFS) | CR, CRu | time to relapse (TTR) | first documentation of response |
response duration | CR, CRu, PR | time to relapse or progression | first documentation of response |
time to next treatment | all patients | time when new treatment is needed | entry onto trial |
cause-specific death | all patients | death related to NHL | death |
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