Treatment of Hematologic Malignancies

Transcript

00:00 --> 00:02Support for Yale Cancer Answers
00:02 --> 00:04comes from AstraZeneca, dedicated
00:05 --> 00:07to advancing options and providing
00:07 --> 00:10hope for people living with cancer.
00:10 --> 00:14More information at astrazeneca-us.com.
00:14 --> 00:16Welcome to Yale Cancer Answers with
00:16 --> 00:18your host doctor Anees Chagpar.
00:18 --> 00:20Yale Cancer Answers features the
00:20 --> 00:23latest information on cancer care by
00:23 --> 00:24welcoming oncologists and specialists
00:24 --> 00:27who are on the forefront of the
00:27 --> 00:29battle to fight cancer. This week,
00:29 --> 00:31it's a conversation about Hematologic
00:31 --> 00:33malignancies with Doctor Francesca Montanari.
00:33 --> 00:35Doctor Montanari is an assistant
00:35 --> 00:36professor of clinical medicine and
00:37 --> 00:39hematology at the Yale School of Medicine,
00:39 --> 00:41where Doctor Chagpar is a
00:41 --> 00:43professor of surgical oncology.
00:43 --> 00:43Francesca, can we
00:43 --> 00:46start off by you telling
00:46 --> 00:48us a little bit about Hematologic
00:48 --> 00:50malignancies, what they are,
00:50 --> 00:54how common they are, and how people who have
00:54 --> 00:57a hematological malignancy can present?
00:57 --> 00:59Hematological malignancies
00:59 --> 01:02include all types of blood cancers.
01:02 --> 01:06So these are cancers that can affect the
01:06 --> 01:10bone marrow where the blood cells are made,
01:10 --> 01:13blood cells, lymph nodes and other
01:13 --> 01:16parts of the lymphatic system and
01:16 --> 01:18typical hematological malignancies
01:18 --> 01:21or blood cancers are leukemias,
01:21 --> 01:22lymphomas, Myelomas,
01:22 --> 01:26and others that are rare, such as
01:26 --> 01:28myelodysplastic and Myeloproliferative disorders,
01:28 --> 01:31and these diseases represent less
01:31 --> 01:34than 10% of all the cancers,
01:34 --> 01:36and there are approximately 1.8
01:36 --> 01:39million new cases of cancer per year
01:39 --> 01:42in the United States and approximately
01:42 --> 01:45180,000 cases of blood cancers.
01:45 --> 01:47So every 3 minutes,
01:47 --> 01:50one person in the US is diagnosed
01:50 --> 01:53with one of these diseases.
01:53 --> 01:56Approximately half of the blood
01:56 --> 01:58cancers are lymphomas which account
01:58 --> 02:01for 86,000 cases per year.
02:01 --> 02:04They are further divided in Hodgkin
02:04 --> 02:05and non Hodgkin,
02:05 --> 02:08which are the most common
02:08 --> 02:10and then Hodgkin is
02:10 --> 02:13classified into over 60 distinct subtypes.
02:13 --> 02:16So as you can imagine,
02:16 --> 02:19numbers tend to become very very small
02:19 --> 02:23for the most rare of these subtypes.
02:27 --> 02:29Leukemia is approximately 60,000 cases
02:29 --> 02:33per year and less than 10% are myelomas,
02:33 --> 02:35so symptoms and manifestation
02:35 --> 02:37of these diseases can vary.
02:37 --> 02:40There is a very wide range of
02:40 --> 02:43symptoms that can be associated
02:43 --> 02:46with any of these blood cancers,
02:46 --> 02:48which depends on the specific
02:48 --> 02:50disease and the localization.
02:50 --> 02:51For instance,
02:51 --> 02:53lymphoma can present with the so-called
02:53 --> 02:56constitutional symptoms,
02:56 --> 02:58which are very
02:58 --> 03:00specific, fever, chills,
03:00 --> 03:02night sweats,
03:02 --> 03:05unintentional weight loss.
03:05 --> 03:08But there are a lot of other
03:08 --> 03:10symptoms which depend on the specific
03:10 --> 03:12localization of the disease.
03:12 --> 03:13For instance,
03:13 --> 03:15there are lymphomas that like to
03:15 --> 03:17affect the gastrointestinal tract,
03:17 --> 03:19and they cause gastrointestinal disturbances.
03:19 --> 03:21Other lymphoma can involve the
03:21 --> 03:24eye or the structures around the
03:24 --> 03:26eye causing trouble with vision,
03:26 --> 03:29or they can affect the skin.
03:29 --> 03:31And as you can imagine,
03:31 --> 03:34depending upon the organ that is involved,
03:34 --> 03:37you can have very different symptoms.
03:37 --> 03:39Leukemia tends to present with
03:39 --> 03:41symptoms related to the bone marrow
03:41 --> 03:44involvement and the cytopenias such
03:44 --> 03:46as fatigue from the anemia,
03:46 --> 03:48bleeding from low platelets,
03:48 --> 03:51infection from low blood white cell
03:51 --> 03:53count and multiple myeloma also
03:53 --> 03:55can present with fatigue from anemia,
03:55 --> 03:57infection and bone pain.
03:57 --> 04:01But bone pain is a more distinct
04:01 --> 04:03sign of a multiple myeloma as
04:03 --> 04:06it involves the bone structure and
04:06 --> 04:08can cause pathological fractures.
04:08 --> 04:11Lethargy and other gastrointestinal
04:11 --> 04:13symptoms related to the hypercalcemia
04:13 --> 04:16also can be present at presentation.
04:17 --> 04:20That seems like just an amazing
04:20 --> 04:23potpourri of symptoms and
04:23 --> 04:26sites that these blood cancers
04:26 --> 04:29can harbor in so how
04:29 --> 04:32do patients find out that they have
04:32 --> 04:35one of these hematologic malignancies?
04:35 --> 04:39It seems like they can be
04:39 --> 04:43anywhere from your bone marrow to your eyes,
04:43 --> 04:44to your gastrointestinal tract,
04:44 --> 04:47and the symptoms can be completely
04:47 --> 04:50nonspecific, like a little bit of
04:50 --> 04:53fatigue to having visual loss
04:53 --> 04:55or gastrointestinal problems.
04:55 --> 05:01So how is the diagnosis actually made?
05:06 --> 05:09It depends on the various scenarios.
05:11 --> 05:13Some of these blood cancers
05:13 --> 05:16tend to be
05:16 --> 05:19very slow growing and might be picked up
05:19 --> 05:20incidentally,
05:20 --> 05:22just performing some routine blood
05:22 --> 05:25work by the primary care physician
05:25 --> 05:28on occasion of the well being visit.
05:28 --> 05:32So finding a new presence of
05:32 --> 05:34increased protein in the blood
05:34 --> 05:37might raise the suspicion of myeloma
05:37 --> 05:41and determine additional
05:41 --> 05:43testing that eventually lead
05:43 --> 05:46to the diagnosis and in other
05:46 --> 05:50cases the symptoms can be more
05:50 --> 05:52prominent and therefore as part
05:52 --> 05:56of the initial investigation by
05:56 --> 05:59the primary care physician,
05:59 --> 06:01certain signs and symptoms
06:01 --> 06:04might be detected that raise a
06:04 --> 06:06flag for this condition,
06:06 --> 06:07and further evaluation
06:07 --> 06:09include imaging studies and
06:09 --> 06:12more in depth blood work
06:12 --> 06:15and eventually valuation by a blood
06:15 --> 06:18cancer specialist and so once that
06:18 --> 06:22happens, once they come to
06:22 --> 06:26you as a blood cancer specialist,
06:26 --> 06:29what's the next thing that happens?
06:29 --> 06:31So typically we
06:31 --> 06:34do really need to run a
06:34 --> 06:36little bit more of a work up,
06:36 --> 06:39and that includes imaging studies,
06:39 --> 06:43which can be anything from MRI or CT scan,
06:43 --> 06:46even a newer form of CAT scan
06:46 --> 06:50that is called PET Scan where we
06:50 --> 06:54use glucose to track down in the
06:54 --> 06:57body where there is an increase in
06:57 --> 06:59the metabolic activity that may
06:59 --> 07:03reveal the presence of a cancer.
07:03 --> 07:05And ultimately the diagnosis
07:05 --> 07:08is made through a pathology,
07:08 --> 07:13so we would need a tissue sample either
07:13 --> 07:19from a lymph node or from the bone marrow.
07:19 --> 07:23Or sometimes a blood sample is
07:23 --> 07:26sufficient where we do run specific
07:26 --> 07:30tests to detect these diseases and
07:30 --> 07:34once we have a pathological confirmation
07:34 --> 07:37then other tests might be warranted
07:37 --> 07:41depending on the nature of the disease
07:41 --> 07:45and typically this test helps us with
07:45 --> 07:48prognostication and with staging.
07:49 --> 07:51Let's talk about that.
07:51 --> 07:53How do we determine prognosis?
07:53 --> 07:55And in general, what is the
07:55 --> 07:57prognosis of these hematological
07:57 --> 07:58malignancies, understanding,
07:58 --> 08:01however, that this is a
08:01 --> 08:03varied group of diseases that
08:03 --> 08:06are lumped into this basket term.
08:07 --> 08:11Right, so there is a lot of variability
08:11 --> 08:15in the behavior of these diseases,
08:15 --> 08:19and as we have improved our knowledge
08:19 --> 08:23in the biology and mechanism
08:23 --> 08:26that drives these diseases,
08:26 --> 08:31we have a very complex way to
08:31 --> 08:35assess prognosis and prognosis
08:35 --> 08:40typically depends on very general
08:40 --> 08:42information
08:42 --> 08:45such as the burden of
08:45 --> 08:47disease at presentation, and
08:47 --> 08:49the performance status of the
08:49 --> 08:53patient plays a big role and
08:53 --> 08:56the presence of comorbidities or
08:56 --> 08:59end organ damage from the disease,
08:59 --> 09:05and then there are other markers that we
09:05 --> 09:09gather from the pathology evaluation
09:09 --> 09:12and from the genetic makeup through
09:12 --> 09:16molecular studies and based on each
09:16 --> 09:19disease as a specific list of
09:19 --> 09:22features that we pay attention to
09:22 --> 09:25when we determine the risk
09:25 --> 09:26stratification and ultimately
09:26 --> 09:29based on all this information,
09:29 --> 09:32we determine what is the
09:32 --> 09:34best treatment approach.
09:35 --> 09:39What is the treatment
09:39 --> 09:41approach for these cancers
09:41 --> 09:42in general?
09:42 --> 09:46The type of approach is very variable.
09:46 --> 09:51So first of all, the most important
09:51 --> 09:55point that I'd like to make is that,
09:55 --> 09:58as I mentioned, the behavior of
09:58 --> 10:01blood cancer is very variable.
10:01 --> 10:04There are blood cancers that are
10:04 --> 10:06very indolent and slow growing.
10:06 --> 10:09And we don't necessarily start
10:09 --> 10:11treatment upon diagnosis.
10:11 --> 10:14These diseases are considered
10:14 --> 10:17generally not curable, but very,
10:17 --> 10:19very manageable and treatable
10:19 --> 10:21with certain drugs.
10:21 --> 10:26And the most important thing upon
10:26 --> 10:30diagnosis is determining if a patient
10:30 --> 10:34requires treatment or can be watched.
10:34 --> 10:36We call that
10:36 --> 10:38watchful monitoring,
10:38 --> 10:41and once there is an indication
10:41 --> 10:43when therapy is warranted,
10:43 --> 10:48then the decision of which kind of therapy
10:48 --> 10:53depends on the specific type of disease,
10:53 --> 10:55the staging of the disease,
10:55 --> 10:57and the predicted behavior,
10:57 --> 11:00which is usually based on the genetic
11:00 --> 11:03makeup of the specific blood cancer.
11:03 --> 11:05Another important factor that
11:05 --> 11:07helps the decision about the best
11:07 --> 11:10strategy is based on patients
11:10 --> 11:12characteristics such as the age,
11:12 --> 11:13the performance status,
11:13 --> 11:15the presence of medical conditions
11:15 --> 11:17which might have an impact
11:17 --> 11:19on the tolerability of the
11:19 --> 11:22treatment and if transplant,
11:22 --> 11:25if bone marrow transplant can be
11:25 --> 11:26used for that
11:26 --> 11:27specific patient,
11:27 --> 11:30as part of the treatment strategy.
11:30 --> 11:33Another factor that is very important is
11:33 --> 11:35a patients preference now that
11:35 --> 11:37we have multiple therapy options
11:37 --> 11:39which offer similar results
11:39 --> 11:42in the long term but differ in
11:42 --> 11:44terms of administration
11:44 --> 11:47modality and side effects profile.
11:47 --> 11:49Patient preference might play a
11:49 --> 11:52big role in the final decision.
11:55 --> 11:58During the past year there is another
11:58 --> 12:01factor that has played
12:01 --> 12:05a big role in our decision making,
12:05 --> 12:07which has been the COVID pandemic.
12:07 --> 12:10So having an aggressive blood cancer
12:10 --> 12:13that requires treatment and has not
12:13 --> 12:16had any variation.
12:16 --> 12:18But because of the presence of the COVID pandemic,
12:18 --> 12:21for those diseases that are
12:21 --> 12:23more indolent and not immediately
12:23 --> 12:25life threatening,
12:25 --> 12:28we have been shifted away from
12:28 --> 12:30using certain drugs or certain
12:30 --> 12:34strategies to maintain the disease in
12:34 --> 12:38remission for longer period of time.
12:38 --> 12:40Unless there was an overall survival
12:40 --> 12:43benefit in order to minimize the
12:43 --> 12:45risks of increasing the severity and
12:45 --> 12:48mortality from the infection.
12:50 --> 12:53There's a few points there that you
12:53 --> 12:56mentioned that I want to pick up
12:56 --> 12:59on and the first is that some of
12:59 --> 13:01these diseases are fairly indolent
13:01 --> 13:04and may not require treatment.
13:04 --> 13:05This kind of expectant
13:05 --> 13:07watchful waiting approach.
13:07 --> 13:09How do you determine whether
13:09 --> 13:11that's the case for patients,
13:11 --> 13:13particularly when you mentioned that
13:13 --> 13:16many of these cancers are not quote
13:16 --> 13:19curable but they are manageable?
13:19 --> 13:22And do patients get some anxiety over
13:22 --> 13:26the idea that they may have a cancer
13:26 --> 13:29that were simply watching?
13:29 --> 13:32It's very important to have that
13:32 --> 13:35clear communication with the patient
13:35 --> 13:37that initiating treatment earlier
13:37 --> 13:41for this kind of cancer does not
13:41 --> 13:43necessarily translate in a prolongation
13:43 --> 13:46of their life expectancy and the
13:46 --> 13:50goal of the treatment in their case
13:50 --> 13:52is to minimize the toxicity related
13:52 --> 13:56to the use of certain agents and
13:56 --> 13:59maximizing the effect in terms of
13:59 --> 14:03allowing them to live their normal life
14:03 --> 14:06without having any side effects from
14:06 --> 14:09either the treatment or the disease.
14:10 --> 14:12So important to
14:12 --> 14:13have good communication.
14:13 --> 14:16We're going to learn a
14:16 --> 14:17lot more about hematological
14:17 --> 14:20malignancies right after we take a
14:20 --> 14:22short break for a medical minute.
14:22 --> 14:25Please stay tuned to learn more with
14:25 --> 14:26my guest Doctor
14:26 --> 14:28Francesca Montanari.
14:28 --> 14:30Support for Yale Cancer Answers comes from
14:30 --> 14:32AstraZeneca, working to eliminate
14:32 --> 14:34cancer as a cause of death.
14:34 --> 14:37Learn more at astrazeneca-us.com.
14:37 --> 14:39This is a medical minute
14:39 --> 14:41about head and neck cancers,
14:41 --> 14:43although the percentage of oral
14:43 --> 14:45and head and neck cancer patients
14:45 --> 14:48in the United States is only about
14:48 --> 14:505% of all diagnosed cancers,
14:50 --> 14:52there are challenging side effects
14:52 --> 14:53associated with these types
14:53 --> 14:55of cancer and their treatment.
14:55 --> 14:57Clinical trials are currently
14:57 --> 14:59underway to test innovative new
14:59 --> 15:00treatments for head and neck cancers,
15:00 --> 15:02and in many cases less radical
15:02 --> 15:05surgeries are able to preserve nerves,
15:05 --> 15:07arteries and muscles in the neck,
15:07 --> 15:09enabling patients to move, speak,
15:09 --> 15:12breathe and eat normally after surgery.
15:12 --> 15:14More information is available
15:14 --> 15:15at yalecancercenter.org.
15:15 --> 15:18You're listening to Connecticut Public Radio.
15:19 --> 15:21Welcome back to Yale Cancer Answers.
15:21 --> 15:24This is doctor Anees Chagpar
15:24 --> 15:26and I'm joined tonight by my
15:26 --> 15:28guest doctor Francesca Montanari.
15:28 --> 15:31We're talking about the care of patients
15:31 --> 15:32with hematologic malignacies and
15:32 --> 15:34Francesca right before the break we
15:34 --> 15:37were talking about the fact that these
15:37 --> 15:39hematologic malignancies are so varied,
15:39 --> 15:42varied in terms of where they present,
15:42 --> 15:45some being in the bone marrow,
15:45 --> 15:47some being in the lymph nodes,
15:47 --> 15:50some being organs like
15:50 --> 15:53eyes and GI track and bone and other
15:53 --> 15:56places, they are varied in terms of
15:56 --> 15:58their clinical presentation and the
15:58 --> 16:01symptoms that they cause
16:01 --> 16:03in terms of their clinical course.
16:03 --> 16:06Some being very indolent and slow
16:06 --> 16:08growing such that they wouldn't even
16:08 --> 16:10warrant necessarily treatment and
16:10 --> 16:12others being far more aggressive.
16:12 --> 16:15Can you tell us a little bit
16:15 --> 16:17more about the cancers,
16:17 --> 16:18specifically what you treat?
16:18 --> 16:20Is there a certain type of
16:21 --> 16:23these hematologic malignancies
16:23 --> 16:24that you specialize in?
16:25 --> 16:29Yes, so in terms of blood cancer
16:29 --> 16:32my research interest has
16:32 --> 16:36always been on the lymphoma side.
16:36 --> 16:39So lymphomas by themselves
16:39 --> 16:41constitute the
16:42 --> 16:45biggest part of the blood cancer.
16:45 --> 16:46They are approximately half
16:46 --> 16:49of all the blood cancers,
16:49 --> 16:52but they are very diverse themselves
16:52 --> 16:56and we do typically
16:56 --> 17:00divide them into big categories,
17:00 --> 17:02Hodgkin and non Hodgkin,
17:02 --> 17:05and then furthermore into
17:05 --> 17:08aggressive and indolent in the
17:08 --> 17:11non Hodgkin lymphoma type and
17:11 --> 17:14so the focus of my research
17:14 --> 17:17has been in trying to better
17:17 --> 17:21understand the biology of the more
17:21 --> 17:25rare of these lymphoma types.
17:25 --> 17:28And based on the insights in the
17:28 --> 17:32biology to develop new treatment
17:32 --> 17:34strategies that are targeted
17:34 --> 17:38for these less known subtypes.
17:38 --> 17:39In particular,
17:39 --> 17:42the focus of my research over
17:42 --> 17:47the past decade or so has been on
17:47 --> 17:49posttransplant lymphoproliferative disorders,
17:49 --> 17:52which are a rare lymphomas that arise
17:52 --> 17:56as potentially life threatening complication
17:56 --> 17:58of solid organ transplant.
17:58 --> 18:02These are lymphomas that arise in the
18:02 --> 18:05setting of reactivation of infection
18:05 --> 18:08due to the immunosuppressive treatment
18:08 --> 18:11or due to the chronic dysregulation
18:11 --> 18:15of the immune system in the setting
18:15 --> 18:16of chronic immunosuppression,
18:16 --> 18:17and historically,
18:17 --> 18:21the prognosis of these lymphomas have
18:21 --> 18:24been very poor because of inability
18:24 --> 18:27to deliver full dose treatment.
18:27 --> 18:29And due to the frailty and
18:29 --> 18:32risk of infectious complication
18:32 --> 18:36that this patients experience with a
18:36 --> 18:38regular conventional chemotherapy,
18:38 --> 18:41the risk of dying of infection
18:41 --> 18:44during treatment in this population
18:44 --> 18:47has been estimated around 30%,
18:47 --> 18:49which is extraordinarily high and
18:49 --> 18:53in order to try to minimize the
18:53 --> 18:56complication from the treatment,
18:56 --> 18:58I developed the
18:58 --> 19:02risk stratified treatment adapted
19:02 --> 19:07strategies which are based essentially on
19:07 --> 19:08induction phase
19:08 --> 19:11where we do
19:11 --> 19:13not use cytotoxic chemotherapy but
19:13 --> 19:16more a targeted antibody approach.
19:16 --> 19:20And then we do reserve escalation
19:20 --> 19:22to chemotherapy only to patients
19:22 --> 19:26that do not achieve a full response
19:26 --> 19:29on the least invasive treatment.
19:29 --> 19:33And with these strategies we have
19:33 --> 19:35been able to
19:35 --> 19:37limit the use of cytotoxic agent
19:37 --> 19:41to less than half of the patient
19:41 --> 19:43population that we do treat.
19:43 --> 19:46Another area
19:46 --> 19:48where I've been conducting
19:48 --> 19:50research is in T cell lymphoma.
19:51 --> 19:53Those are also very rare lymphomas.
19:53 --> 19:57They are much rarer than the B cell
19:57 --> 19:59lymphoma which are the most common
19:59 --> 20:02non Hodgkin lymphoma out there
20:02 --> 20:04and unfortunately historically we
20:04 --> 20:06have been using
20:06 --> 20:08a treatment
20:08 --> 20:10that has been extrapolated from
20:10 --> 20:12the B cell counterparts,
20:12 --> 20:16so not really specific to these
20:16 --> 20:19subtypes of lymphomas and the
20:19 --> 20:22results are not as optimal as in
20:22 --> 20:24the B cell counterpart's.
20:24 --> 20:27Over the past few years,
20:27 --> 20:304 new drugs have been approved in
20:30 --> 20:32the space for this, specifically
20:32 --> 20:35for T cell lymphoma and one of
20:35 --> 20:38the challenges that we have now
20:38 --> 20:39are trying to identify
20:39 --> 20:42what is the best sequencing of this
20:42 --> 20:45agent and what is the best way to
20:45 --> 20:47combine them to improve the outcome
20:47 --> 20:50of patients with additional malignancies.
20:51 --> 20:54It sounds like in both of those
20:54 --> 20:56scenarios the overarching theme
20:56 --> 20:58is really personalizing treatment
20:58 --> 21:01to the patients individual disease,
21:01 --> 21:05so I wanted to just take a step back
21:05 --> 21:08and talk a little bit more about
21:08 --> 21:11the intricacies of each of these.
21:11 --> 21:14So with regards to the post transplant
21:14 --> 21:16lymphoma, help us to understand
21:16 --> 21:19again how these lymphomas occur,
21:19 --> 21:21'cause certainly there are listeners
21:21 --> 21:25who may have gone through a solid organ
21:25 --> 21:28transplant or may know someone who has and
21:28 --> 21:32these patients are on immunosuppressives.
21:32 --> 21:34So does that immunosuppressive
21:34 --> 21:36therapy automatically increase
21:36 --> 21:38their risk of lymphoma?
21:38 --> 21:42And is there anything that they can do to
21:42 --> 21:46reduce their risk of developing lymphoma
21:46 --> 21:47in that setting?
21:47 --> 21:50That's a really good question,
21:50 --> 21:54so we do after the transplant patient
21:54 --> 21:56received different immunosuppressive
21:56 --> 21:59treatment which are related to the different
21:59 --> 22:03kind of transplant that they have received.
22:03 --> 22:04For transplant,
22:04 --> 22:06such as intestinal transplant,
22:06 --> 22:08multi visceral transplant,
22:08 --> 22:11immunosuppressive treatment is much tougher
22:11 --> 22:15and much deeper than a patient that
22:15 --> 22:19for instance receives renal transplant where
22:19 --> 22:21immunosuppresant treatment required
22:21 --> 22:24for the recipient to accept the graft is much less.
22:33 --> 22:35And the reason we do see as a
22:35 --> 22:38consequence of the immune suppression
22:38 --> 22:40reactivation of common infection,
22:40 --> 22:41and most important,
22:41 --> 22:43is the Epstein Barr virus,
22:43 --> 22:46which is the virus that causes mononucleosis.
22:46 --> 22:49Most of the adult population has been
22:49 --> 22:52exposed by adulthood to the virus,
22:52 --> 22:55and the virus is dormant in
22:55 --> 22:58a silent state in our body,
22:58 --> 23:01and is kept at bay by our immune system.
23:01 --> 23:03So conditions such as immunosupression where
23:04 --> 23:07our immune system defenses are lowered
23:07 --> 23:11allow the virus to thrive again
23:11 --> 23:14and replicate and
23:14 --> 23:16this particular kind of virus,
23:16 --> 23:20in the absence of an immune system
23:20 --> 23:25that fights it and keeps it at bay,
23:25 --> 23:29is able to transform the blood
23:29 --> 23:32cells into lymphoma cells so
23:32 --> 23:34typically in the first year
23:34 --> 23:35after the transplant,
23:35 --> 23:39most of the lymphoma that we do
23:39 --> 23:42see are related to Epstein Barr
23:42 --> 23:44reactivation in the
23:44 --> 23:47setting of the immune suppression,
23:47 --> 23:49the lymphoma that arise after one
23:49 --> 23:53year still can be
23:53 --> 23:55linked to the Epstein Barr virus,
23:55 --> 23:58but approximately half of them happen
23:58 --> 24:01without a reactivation of Epstein virus,
24:01 --> 24:04and they do not hardwire the genetic
24:04 --> 24:07material of the virus and are
24:07 --> 24:09thought to arise in the setting
24:09 --> 24:12of a chronic immune dysregulation
24:12 --> 24:16due to the longstanding immunosuppression.
24:16 --> 24:18Is there anything that
24:18 --> 24:21people can do to limit that
24:21 --> 24:23reactivation of Epstein Barr virus?
24:23 --> 24:26You mentioned that most adults have
24:26 --> 24:28already experienced Epstein Barr virus,
24:28 --> 24:31and so should have some degree
24:31 --> 24:34of natural immunity to the virus,
24:34 --> 24:35although they're on immunosuppresants.
24:35 --> 24:39So has anybody looked at ways that
24:39 --> 24:41people who are on immunosuppresants
24:41 --> 24:43can prevent that reactivation?
24:43 --> 24:46That is a really good question, and
24:46 --> 24:48indeed,
24:48 --> 24:52a part of these
24:52 --> 24:56strategies in the period after transplant
24:56 --> 24:58include close monitoring of the
24:58 --> 25:02EBV presence in the blood.
25:02 --> 25:05So after a solid organ transplant,
25:05 --> 25:09depending on the kind of solid
25:09 --> 25:12organ transplant there are
25:12 --> 25:14algorithms
25:14 --> 25:18and there is a monitoring of the
25:18 --> 25:22EBV which is done
25:22 --> 25:26in certain cases twice a month.
25:26 --> 25:28Other cases once a month,
25:28 --> 25:32depending on the nature of the
25:32 --> 25:33immunosuppression and preemptive
25:33 --> 25:35strategies to intervene.
25:37 --> 25:40Treating the EBV before the lymphoma
25:40 --> 25:43appears has been attempted,
25:43 --> 25:46but the results are not optimal
25:46 --> 25:50because there is a lot of variation in
25:50 --> 25:54the levels of EBV that is noted
25:54 --> 25:57in patients post transplant and not
25:57 --> 25:59everybody that experience a reactivation
25:59 --> 26:04of the virus end up developing a
26:04 --> 26:07lymphoma and therefore there is not
26:07 --> 26:10good guidance out there regarding
26:10 --> 26:12who to treat preemptively
26:12 --> 26:15and who to observe.
26:15 --> 26:19When I was at Columbia University prior
26:19 --> 26:23to joining the group here at Yale
26:23 --> 26:28I was leading the effort to come up with
26:28 --> 26:33with guidelines to help clinician in the
26:33 --> 26:37solid organ transplant team to troubleshoot
26:37 --> 26:39these problems,
26:39 --> 26:43meaning want to check the EBV
26:43 --> 26:46at what intervals and what
26:46 --> 26:50is the threshold of the
26:50 --> 26:54virus to consider potentially
26:54 --> 26:57leading to a lymphoma and when
26:57 --> 27:00to utilize treatment to reduce
27:00 --> 27:04that virus level and it is still a
27:04 --> 27:08discussion and a work in progress.
27:09 --> 27:11And do we know what factors
27:11 --> 27:14kind of trigger that EBV
27:14 --> 27:16to turn into a lymphoma?
27:16 --> 27:18Because potentially that's another
27:18 --> 27:21place to intervene in thinking about
27:21 --> 27:24is there a way to
27:24 --> 27:28potentially mitigate that transformation.
27:28 --> 27:30That is an excellent
27:30 --> 27:32question, and unfortunately the reason
27:32 --> 27:37why EBV can turner in vitro
27:37 --> 27:39into malignant cells is because
27:39 --> 27:42one side triggers
27:42 --> 27:45the proliferation of these cells and
27:45 --> 27:48the other side blocks an important
27:48 --> 27:51mechanism that is called apoptosis,
27:51 --> 27:55by which the cells die but alone is
27:55 --> 27:59not able to induce lymphoma in vivo.
27:59 --> 28:03And the thought is that there are,
28:03 --> 28:08like in all the other kinds of cancer,
28:08 --> 28:11a multi step process where the
28:11 --> 28:14cells progressively gain additional
28:14 --> 28:16mutation and overtime
28:16 --> 28:19the addition of this mutation together
28:19 --> 28:24sort of cause the transformation into cancer,
28:27 --> 28:30but we are not able in 2021 to predict
28:30 --> 28:33which mutation and when these
28:33 --> 28:35mutations are acquired.
28:36 --> 28:38Doctor Francesca Montanari is assistant
28:38 --> 28:40professor of clinical medicine and
28:40 --> 28:42hematology at the Yale School of Medicine.
28:42 --> 28:44If you have questions,
28:44 --> 28:45the address is canceranswers@yale.edu
28:45 --> 28:47and past editions of the program
28:47 --> 28:49are available in audio and written
28:49 --> 28:51form at yalecancercenter.org.
28:51 --> 28:54We hope you'll join us next week to
28:54 --> 28:57learn more about the fight against
28:57 --> 29:00cancer here on Connecticut Public Radio.

Download Audio Download Transcript

Information

May 23, 2021

Yale Cancer Center

visit: http://www.yalecancercenter.org

email: canceranswers@yale.edu

call: 203-785-4095

6623

To Cite

DCA Citation Guide