Mantle cell lymphoma
Mantle cell lymphoma
Steven the GOUILL1, 2, 3, 4
Dousset2, 3
Thomas Gastinne1, 2
David Brousseau3
Pierre Peterlin1
Sara Touzeau1
Catherine
Pellt-Deceunynck3
Mike Amiot3
Anne Moreau5
1 CHU of Nantes,
Clinical Hematology Service,
Nantes
France
2 CHU de Nantes,
Clinical Research Unit in
Oncohaematology
Nantes
France
3 Oncology Research Centre
Nantes/Angers,
Team 10,
Inserm UMR 892,
Nantes
France
4 CHU de Nantes,
Clinical Investigation Centre in
Oncology (CI2C),
Nantes
France
<steven.legouill@chu-nantes.fr>
5 CHU de Nantes,
Pathology service,
Nantes
France
Summary. Mantle cell lymphoma (LCM) is a pathology that does not
Represents only 5 to 8% of non-Hodgkin malignant lymphomas. The LCM is characterized
By the presence of reciprocal translocation between chromosomes 11
and 14 (11; 14) (q13; q32). This induces an increase in the expression of the
Cyclin D1, resulting in the deregulation of the cell cycle. To date, the LCM is
Considered an incurable pathology, but the life expectancy of patients has been
Almost doubled over the last decade, and is currently around 5 years old.
In this review, we present the clinical and biological characteristics of the
LCM, and then we approach therapeutic management on the front line. The
New therapeutic options are also discussed. The progress made in recent
Years, both fundamentally and therapeutically, have altered our approach to
Of the disease, and other major advances are to be expected in the years to
Come.
Key words: Mantle cell lymphoma, review
Abstract. Mantle cell lymphoma (MCL) is a B-cell malignancy that accounts
Approximately for 5 to 8% of Hodgkin's lymphomas. The hallmark of MCL is the
Presence of the T (11; 14) that is responsible forover expression of protein cyclin D1
and cell cycle dysregulation. The expected overall survival from time of diagnosis
has doubled in less than a decade and is around 5 years. However, despite
Major advances regarding our understanding of MCL physiopathology and treatment,
MCL remains an incurable disease. Herein, we summarize the morphology
and immunophenotype of MCL cells and clinical features at diagnosis. Frontlines
Strategies are presented and novel treatment options are discussed.
Key words: Mantle cell lymphoma, review
Epidemiology
Mantle cell lymphoma
(LCM) is an uncommon pathology
In malignant lymphomas
No hodgkiniens (LMNH), cases of
LCM approximately 5 to 8% of
patients. The LCM is preferentially
a pathology of topics beyond
60 years with a median age of 68.
In a study published in Cancer,
Zhou and al. report an impact
of 0.07 cases per 100,000 people
below 50 years [1]. The impact
increases gradually with age,
reaching 1.96 cases per 100,000
inhabitants for the age group 60 -.
69 then 2.78 case beyond
80. More recently, hotel led
an epidemiological study from
three French of the hemopathies records
(Lower Normandy, Gironde and)
Gold Coast), there are 213 cases
on the 2002-2006 period a
impact of 0.72 case
per 100,000 in France. On
the basis of these studies, it is however
difficult to know with certainty
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Tires´ has: '
S. the Gouill
DOI:10.1684/HMA.2011.0638
Haematology, vol. 17, n '' o 5, September-October 2011
To quote this article: the Gouill S, Michael C, Gastinne T, Brousseau C, Peterlin P, Touzeau C, Pellat-Deceunynck C, Amiot M, Moreau A. Lymphoma in
cells of the mantle. Hematology 2011 ''; 17 (5): 322-30 doi:10.1684/hma.2011.0638
Journal Identification = HMA Article Identification = 0638 Date: November 22, 2011 Time: 1:41 pm
If the impact of the LCM is or is not on the rise. If
According to the study of Zhou et al, it would seem
that there is a slight increase in the impact.
One of the peculiarities of the LCM is also to present an imbalance
of the sex ratio since two thirds of patients are
men. An imbalance that remains to this day without explanation.
Factors predisposing to the occurrence of MCL are
also not well known.
Pathophysiology
The malignant cell is a cell B CD5 +
classically not mutated after the area of the mantle [2].
The absence of IgVH mutation is the rule for more than 80%
patients. In other cases, the question of a stimulus
antigenic inducing the oncogenic phenomenon is
would pose.
The field of cytogenetics, the characteristic of the LCM is the
presence of the translocation (11; 14)(q13;q32) to
complaints that it is not restricted to the LCM. The t (11; 14) is
responsible for the increase in the level of expression of
the protein cyclin D1. This protein causes the phosphatising
RB bringing cells (via the E2F1 protein)
tumor in the cycle cell (figure 1).
If the occurrence of this translocation is considered
the initial oncogenic event, there are the LCM without
t (11; 14). These are then the D2 or D3 tetracyclines which are
involved. Whether cyclin D1, D2 or D3, the effect
deleterious on the cell cycle is the same, with an entry
unregulated tumor cells in phase S, resulting
M p27
G1
G2
S
CDK4
E2F1
RB
RB
P P
E2F1
+
Cyclin D1
T (11; 14)
Cyclin E
CDK2
P21
SKP2 p16
p53
Cycle
cell phone
Figure 1. The t(11;14)-induced changes in the cell cycle.
both chromosomal and genomic instability, which
promotes the occurrence of additional oncogeniques events.
Tumor cell will thus accumulate many
abnormalities affecting the cell cycle but also the way
repair of DNA, the apoptotic mechanism or
again the way p53. Initiated by the cell cycle abnormalities,
the LCM is enriched so quickly other anomalies
[3].
These peculiarities confer on the LCM expression profile
Gene feature that will distinguish it from other types
Lymphoma as the marginal zone Lymphoma,.
the LLC and the lymphoma follicular, as well as other syndromes
lymphoproliferatifs in general [4, 5]. Anomalies
affecting the ways of proliferation are especially
marked in the LCM in the other hemopathies
mature B-lymphoid (constitutive activation of the path
PI3k/AKT affecting mTOR and phosphatising of protein
4E-BP1 and p70 - S6K, for example).
The existence of a translocation (11; 14) is therefore not an event
unique and still less enough for oncogenic
trigger the occurrence of MCL. The t (11; 14) is also not
more specific to the LCM, and cyclin D1 can be replaced
by cyclin D2 or D3. We start now
to grasp the complexities of this pathology, including the whole
process oncogenic remains largely
obscure. Thus, Jares and Campos had initially declined
a linear oncogenic process starting from the appearance
t(11;14) and resulting in a form of LCM blast,.
the most advanced form of the disease (figure 2). The existence
a ganglionic, more indolent form most often
mutated, brought to redesign the evolution of Pathology
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Naïve B cell
Classic LCM LCM form blast
ATM
CHK2
Karyotype
complex
INK4A/CDK4
RB1/ARF/MDM2
p53
No mutated IgVH proliferation
+ SOX11
> 90%
< 10%
No ganglionic LCM
IgVH hypermuté
SOX - 11
Indolent evolution
t (11; 14)
Cyclin D1
LCM
in-situ del 17 p
Stimulation
antigenic?
Figure 2. Proposal of oncogenic model Jares et al. and Campo et al.
in a different way and to consider both oncogenic processes
separate (figure 2). But it is a simple track,
and the question is not settled.
Diagnosis
Histopathology and cytological characteristics
of the pathology are described in the classification
WHO 2008 [6]. The diagnosis rests on a biopsy of
tumour tissue.
At the cytological level, described a classic with shape
a tumor cell cytoplasm sometimes heterogeneous size
abundant, little CrossMatch and a kernel more often
irregular to loose chromatin. Morphological variants
are also described, including blast shape or form
Pleomorphic, who are recognized as more aggressive in
Clinic.
Tumor proliferation can present an architecture
Nodular or diffuse. At the phenotypic level, the cell
polyposis expresses CD20, the CD19, the CD24 and
the CD5. However, the cell does not express the CD23
Neither the CD10. The BCL-2 protein is expressed, but not the
protein BCL-6. There is an expression of an immunoglobulin
membrane frequently isotype M.
Sometimes, D. The light chain is often lambda. He
is important to quantify the proliferation in the help index
the Ki-67 antibody, which can be extremely variable
in the tumor tissue of one patient to another.
The percentage of Ki - 67 + cells especially has a value
prognostic [7].
Diagnosis begins with search,
within the sample, a proliferation of lymphoid cells
which morphology can be compatible with a
LCM or one of the variants. The Immunohistochemistry study allows
to confirm the diagnosis by showing the expression of the
CD20 (sometimes low) CD5 and cyclin D1, as well
that the lack of expression of the CD23 and the CD10. In case
unusual immunophenotype, it is important to confirm
the diagnosis by looking for the presence of the translocation
t (11; 14) by FISH technique.
A few tracks are being explored to facilitate the
diagnosis in cases of doubt. He thus found a
expression of the 20 CD in the LCM, but not in others
lymphopathies B. In the same way, the presence of the
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Sox-11 protein at the nuclear level would sign the presence
of MCL [8, 9]. These two markers are not validated and
are not required to establish the diagnosis.
Clinical presentation to diagnosis
At diagnosis, the general State of the patient is most often
kept with a performance higher than 1 status in
less than 20% of cases. Symptoms B are found
in 30% of patients. The ganglionic achievement is found
in more than 80% of the cases with strong masses for
20% of the patients. The bone marrow is overrun in 70 to
90% of the cases. The frequency of attacks extraganglionnaires
explains that 80% of cases of LCM are classified in stage IV
to the diagnosis. Splenomegaly is present in half
patients. Digestive is common: about
60% of the cases when it is searched systematically
by endoscopy techniques. In the case of symptomatology
digestive, it is necessary to carry out these investigations
digestive. Digestive signs affect around 30% of
patients. On the other hand, the achievement of the central nervous system
is rare at diagnosis (less than 5% of patients)
and may be more common in the forms blast.
It would be the bone damage and impairment
skin.
The biological assessment at diagnosis found
a hyperlymphocytose for 20 to 50% of patients. In
the absence of hyperlymphocytose, the presence of a population
tumor circulating is, however, detectable in more
50% of patients. Anemia classically macrocytic
normocytic and aregenerative is present in 40 to
50% of the cases. It remains the most often moderate, just as
thrombocytopenia. The LDH and 2-microglobulin increased
For more than half of patients. The presence of a
Monoclonal immunoglobulin in the serum, of a hypogammaglobulinaemia
or a positive Coombs test
is noted that in less than 10% of patients. So it's
most often the hyperlymphocytose which is put forward in
initial biological balance.
In the forms of LCM no ganglion, it is found
What a hyperlymphocytose and isolated splenomegaly.
Some few studies have looked at these forms of
LCM (significantly less than 10% of cases) which would seem to
develop from B cells mutated, not having any
complex but with t(11;14) karyotype. The LCM, sometimes called
'indolent', would evolve according to a clinical
less aggressive mode. The lack of expression of the protein
Sox - 11 would characterize these indolent lymphomas [10].
At the time of diagnosis, review biological and iconographic
is no different from other lymphomas and must
have a scanner and biopsy osteomedullaire. The
question the relevance of the pet in the LCM is to
define.
Therapeutic support
Once diagnosed, treatment is required. The case of LCM
No ganglionic (still need to know characterize them with
certainty) can discuss a forbearance/monitoring
with consultations closer.
Treatment of the topic young
The CHOP or the Vadchloraminophene type polychimiotherapies,
based on anthracyclines, allow
complete remission rates (RC) lying around
30%, with figures of overall response of the order of
70 to 80%. This type of chemotherapy, without rituximab, has
been widely used from the end of the 1990s at the beginning
2000s. Over this period, the median survival of
patients was less than 3 years. The combination of rituximab, contribution
the aracytine and the autologous transplant helped improve
very significantly these results.
The contribution of rituximab which, for some, was still under
questions about its ultimate impact on survival, not
more can be discussed. In 2005, Lenz and al. have published the
results of a randomized study comparing CHOP to his
Association to rituximab (CHOP-R) on the first line at
122 patients [11]. The percentage of RC was 34% in
R-CHOP arm compared with only 7% in the CHOP arm.
The authors show that the addition of rituximab delay the
relapse, without causing a benefit in survival
overall (SG). In 2008, Davis (Abstract 581, ASH 2008),.
for him GELA, compared two studies of phase II completed
successively and including a same alternative treatment.
CHOP then DHAP, one with rituximab and the other without.
For patients who receive rituximab, the median of
(HSE) event-free survival is 83 months, it is that
51 months for patients who have not received of rituximab
[12]. breadsticks, for the GOELAMS, also compared a treatment
VAD-clinical type to the same association
with the rituximab [13]. The study demonstrates an advantage, to
the limit of the significance (p = 0,054), in terms of SG,
for the R-VAD-clinical arm. Relapse, Forspointner
and al. It also shows that an arm R - FCM is greater than
a FCM arm [14]. Finally, the meta-analysis conducted by Schulz
and al. confirms the gain in terms of the combination SG
chemotherapy more rituximab [15]. End of the controversy. He
need of rituximab in the treatment of MCL.
The other major contribution in the treatment of first line
young subjects has been the early introduction of the aracytine,
and this from the first line of treatment. Team
M.D. Anderson had published the results of a study conducted
in 45 patients treated by hyper-CVAD [16]. It comes
of a combination chemotherapy combining the aracytine with strong
dose of cyclophosphamide, an anthracycline more
methotrexate. The percentage of RC was 40% for
a 93% overall response rate. In the experience of the
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GELA, the percentage of RC was only 7% after four
cures of CHOP and it was 84% after four courses of
[12: 17] DHAP. A similar approach, proposed by Geisler
et al. reported a percentage of RC of 54.4% [18].
The most convincing evidence of the importance of the aracytine
from the first line of treatment recently were made
by the European MCL Network, that compared chemotherapy
Type R-CHOP then autograft to chemotherapy
alternative R-CHOP/R-DHAP followed as an autograft
[19]. the results of the study (n = 399) show the superiority
a strategy of induction alternating R-DHAP/R-CHOP.
Before autograft, 59% of the patients are in RC/RCu in
arm consisting of the aracytine, against 41 percent in the arm
R - CHOP (p = 0.0004). The advantage in response continues
After autograft with an extension of the duration of the
always answer for the arm R-CHOP/R-DHAP. With
the current decline in the study, it is not found of difference
in overall survival.
Finally, these last 10 years saw also the introduction
autograft in first line. To date, only one
randomized study has shown the superiority of approach
therapy including chemotherapy autograft
conventional. In this study, six cures chop followed
maintenance by interferon were compared with
the followed CHOP of an autologous transplant [20, 21]. The updating of
the study confirms the gain in survival without progression (SSP) and
SG for arm autograft. The median of SG
is 7 years for the arm autograft against 5.3 years in
the CHOP arm more interferon (p = 0.03). Several studies,
prospective or retrospective, have confirmed the very good
RC percentages obtained after autograft (usually
greater than 80%). The use in the first line to
autograft so lets extend the SSP - that is,at 3 years, between 50 and 70%, with an SG of the order of 80%
3 years and 60% at 5 years. If the autograft in first line
is the recommendation on treatment for subjects
the younger, the nature of the packaging of the autograft
remains a topic of discussion. In the study of the European
MCL Network presented at the ASH 2010, packaging
was different depending on the arm of randomization, but
the two used packaging included an irradiation
body total (ICT) (ICT-cytoxan for arm R-CHOP
and ICT-aracytine-melphalan in the R-R-CHOP/DHAP arm).
Several retrospective studies have raised the question of the
place of ICT. In the end, whether in the retrospective study
the EBMT or SFGM-TC, ICT seems
not to make profit from packaging
based on the chemotherapy, such as the BEAM [22, 23]. The study
the EBMT registry would see a place for
ICT in the subgroup of patients with partial response
before autograft, advantage not found in the study of the
SFGM-TC. The trend is to encourage packaging
without ICT, which will decrease the incidence of mucositis and the
long-term complications.
In younger subjects, it emerges now a
first treatment line that must recommend
: chemotherapy consisting of the aracytine and
the rituximab then an autograft.
Treatment of the elderly
For patients unable to receive treatment
intensive, it will turn to the polychimiotherapies without
autograft. Naturally, the R-CHOP and its variants
are the most used. Regarding the hyper-CVAD more
rituximab and its different variants, they are difficult to
applicable to the subjects aged and fragile.
Recently, the European Group has conducted a prospective study
phase III comparing R-CHOP and FCR in induction
[24]. after induction, the study involved a second randomization
between maintenance versus rituximab
interferon. The first issue of the study, the
induction (R-CHOP or FCR), R-CHOP shows higher
the FCR with 88% of response against 77 percent, and higher
also in median survival (49 months compared to 37 months,
(p = 0.046). So, the subject too fragile to receive
an autograft, the FCR cannot be recommended. About
the second issue of the study, a maintenance by
rituximab (an injection every 2 months until progression)
the group in response to R-CHOP brings a
longer response time and a SG to 3 years of 85%,
which is significantly higher than the survival of the interferon arm
(70%). We can always speculate about the absence of benefit
maintenance for patients of the FCR arm or on
the absence of an arms control without maintenance. However, this
study and analysis of subgroup on patients
by R-CHOP, and in response, demonstrate an advantage in
SG, maintained by rituximab with curves of
survival still never reached in this pathology and for
This type of patient. All this positions so the maintenance
rituximab after R-CHOP as a reference.
The question for these patients is now if the
R - CHOP is the best Induction chemotherapy, and
If a chemotherapeutic agents including the aracytine could not
do better. This issue will not fail to supply the
future studies like the question of maintenance.
Perspectives and issues
Therapeutic prospects
The new molecules
Temsirolimus is currently the only molecule having
the AMM in the treatment of the LCM. Temsirolimus is a
selective and specific protein mTOR inhibitor generating
a blockage in the phase G1 of tumor cells. The
phase II published by Witzig et al. demonstrated the effectiveness of
the molecule in the LCM [25]. In phase III, Hess and al. have
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then demonstrated the superiority of temsirolimus PHC by
report to a treatment left to the choice of the investigator
[26]. in this study, temsirolimus brought a lengthening
the duration of the SSP, but no advantage in
terms of SG. The median time to progression was
4.8 months in arm temsirolimus against 1.9 months in the
arms control. Temsirolimus, associated with rituximab, has recently
was appraised in a study of phase II [27]. The
studies are now underway, combining of temsirolimus in
other molecules.
Monotherapy, the velcade has also demonstrated its effectiveness.
Fischer et al. in 2006, reported a study of
155 patients in relapse treated with velcade monotherapy.
The response rate was 33% to 8% of RC/RCu. The
median time to progression was 6.2 months [28].
The velcade has also been tried in association with different
polychimiotherapies. A study of phase III comparing RCHOP
in velcade-CAP (CHOP without oncovin) in first
processing line is currently underway. The velcade has
also been associated to of the aracytine, and a study of phase
III comparing strong aracytine dose with or without velcade is
expected for this year. Lenalidomide is without doubt
the other promising molecule in the LCM [29]. As of 2008,.
Wirnick and al. related experience of 15 patients
treated with lenalidomide [30]. The study showed 2 RC for a
overall response rate of 53% with a median
response of 13.7 months. Regarding the bendamustine,.
It is also in the LCM that this molecule appears
Active [31]. Thus, the study of Rummel et al, which compared
R - bendamustine (BR) to R-CHOP in indolent lymphomas
on the front line had also included patients
LCM. The median age of these patients was 70 years of age and
the duration of SSP in the arm BR was higher than
in the arms of R-CHOP (p = 0,0146). Also include the GA101,
new anti-CD20 humanised, which positions itself as a
interesting molecule. In the longer term, other molecules
like the CAL-101, the HDAC, the radio-immunotherapy, the
immunotoxins, the new antibody monoclonal or bispecifiques
or inhibiting BTK could come
enrich the therapeutic arsenal.
Place of the Allograft
For the younger subjects who received first
line an intensive approach, it seems legitimate to discuss
use of the Allograft. Several retrospective studies
have been published. There is likely a graft versus effect
LCM, although the results of these studies are sometimes
contradictory. In 1999, the team of MD Anderson reported
16 cases of Allograft in patients in relapse or
refractory [32]. It was Allografts to conditioning
myeloablative. With a median follow-up of 24 months, the SG to 3 years
was 55%. The authors concluded there was an effect
graft against LCM based on three observations:
-obtaining of complete remission occurred concomitantly
at the outbreak of the graft against
the host;
-conversion of a positive residual disease in one
negative residual disease after Allograft;
-the fact that the only patient with relapsed was defeated in
transplant.
There were three arguments more than three real
evidence. The observation of Sohn and al. appears more convincing
[33]. the authors describe the occurrence of a RC
post-Allograft after injections of donor lymphocytes.
Other indirect evidence for the existence of an effect
graft against the LCM was brought by the increase
the risk of relapse in packaging comprising
alemtuzumab, which lead to a lymphocyte depletion
T and therefore an abolition of the effect plugin against the
LCM [34]. Of course, there is no formal evidence
the existence of an effect plugin against the LCM, but these beams
observations converge in this sense. Allograft
so is a valid therapeutic approach, you need to know
discuss. The use of Allograft after a conditioning
myeloablative became exceptional. The first experiences
of Allograft in the LCM with this type of procedure
gave rise to too important toxicities. Experience
MD Anderson earns a rate of mortality by toxicity
of the order of 31% in patients aged from about
50 years [35]. The comments published in recent years
were all retrospective studies using one
non-myeloablative conditioning. The first study
by the EBMT, reported by Robinson et al. in 2002, was
particularly disappointing, since the SG was that of
12.8% at 2 years and that all patients had relapsed.
[36]. in an update made in 2006 the registry of
the EBMT, Robinson and al. report more optimistic figures
[37]. on the 180 patients, the SG at 5 years is 31%
with an ESCO by 25%. In 2010, Cook et al. reported
the experience of the British centres [38]. To 5 years.
the SG is 37%, but it rises to 60% at 3 years for
RC patients at the time of the Allograft with an ESCO
which is 14% at 5 years. The monocentric experience
the MD Anderson describes an SG to 45% for 3 years
SSE 33%. There are so many studies, mainly
registry or monocentric, all studies studies
retrospectives, which, although sometimes contradictory, show
only some patients relapse after several lines of treatment
get the RC extended after Allograft; them
relapses are important.
The questions of prognostic factors
The IPI and FLIPI score classics have been widely applied
with more or less of success in the LCM. In what
concerns the FLIPI, it seems unsuited to this pathology.
The results of the IPI are sometimes contradictory study
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to another and to another chemotherapy. A new score
has recently been proposed: MIPI [39]. Quite complicated
to be calculated, taking into account the PS, the age, the LDH and the
number of leukocytes, the MIPI score separates patients in
three groups: an intermediate group, a group with low
risk and a high risk group. Several studies have applied
with success the score MIPI. The percentage of cells
+ Ki67 would better distinguish indolent forms
of more aggressive forms; It has therefore been created a MIPI including
the Ki67. Rosenwald and al. proposed a gene signature
predictive of survival, impossible to apply in routine
[4]. the signature is based on the genes involved mainly
in proliferation. To this day, and perhaps a little
If nothing else, the MIPI seems to be gradually
as the score prognostic of the LCM. The PET scanner could
also be used for prognostic purposes [40].
The issue of residual disease
The level of detectable disease end of treatment, but
also at intermediate points, is one of the big questions
topical in the LCM. Whether through technology
Cytometry flow or by the PCR technique from the
blood or spinal cord sampling, it became possible
to detect extremely low levels (of the order of 10-4 to)
(10 - 5) of disease. The PCR will search for the presence of the rearrangement
IGH/CCND1 and cytometry, the presence of
cells with a phenotype of LCM. With the chemotherapy
more effective and improved detection techniques.
We can truly talk about measurement of residual disease
(MRD) in the LCM. In a study published in
Blood, Pott showed that the quantitative measurement of the disease
residual PCR techniques after autograft
was highly predictive of the duration of remission [41].
The most recent study of the European Group confirms the weight
of the DSM in pre - and post-autogreffe. The Nordic study
MCL2 also showed similar results. For all that, he
There is currently no consensus about
the technique used to quantify residual disease
or times when it must be evaluated (before autograft
or after? After two, four or six priests?).
According to
the studies of the European MCL Network, about 50% of
patients reach an undetectable disease threshold at the end of
patient treatment in RC molecular. Regarding the
predictive value of a molecular RC, it would seem that the
marrow is more informative than the blood.
With the emergence of maintenance strategies, the question
assessment of the DSM is all the more important
that it might be possible to use a treatment
preemptive clinical relapse by the MRD level or
yet to adapt the treatment according to the level of the response
Molecular. Ladetto, in 2006, showed that the injection
the rituximab in molecular relapse patients allowed
to lower the MRD below the detection threshold
[42]. a preemptive treatment has also been applied to some
patients from the Nordic study MCL-2. Ninety-two
informative patients by nested-PCR techniques have
thus followed [43]. If detectable residual disease.
patients received an infusion of rituximab. The study
shows that about two thirds of patients with a threshold
detectable residual disease responded, lowered
their level of disease below the threshold of detection and
have not relapsed.
We see through these studies that the place of the follow-up of the
DSM is expected to significantly change management
therapy of patients and time of a therapeutic strategy
adapted to the DSM seems far away.
Conclusion
Although uncommon, the LCM is a heterogeneity
clinical and biological makes this disease particularly
interesting. The progress made during these 10
years have largely altered the natural evolution
of pathology. The median duration of survival, initially of
3 years, is now estimated to be about 5 or 6 years. Of
new molecules have emerged, which allow for
high hopes for the years to come (temsirolimus,
Revlimid, bendamustine, Velcade®...). Finally, therapeutic choices
may need to be changed according to the
level of the MRD.
Thanks. S. the Gouill is supported by INCa and the Region
Country of the Loire.
Conflict of interest: No.
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