Unraveling Lymphoid Malignancies: Leukaemia and Lymphoma Explained with Dr. Joanna Czerwinski

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Lymphoid malignancies is a topic which encompasses lymphocytic leukaemia and lymphoma and represents a diverse group of blood cancers originating from lymphocytes, a type of white blood cell crucial to our immune system.

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These conditions range from slow-growing, often indolent forms to rapidly progressive diseases.

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Understanding these malignancies is vital for any healthcare professional, as they can present in various clinical settings, from routine check-ups to emergency admissions.

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Whether you're a GP managing initial presentations or a medical student aiming to understand the fundamentals of lymphocytic leukaemia and lymphoma, today's episode is essential.

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Today, we're here to break down this complex area with an interview with Dr Joanna Czerwinski, a haematologist specialising in this area.

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Welcome to Aussie Med Ed.

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Good day and welcome to Aussie Med Ed, the Australian medical education podcast designed with a pragmatic approach to medical conditions by interviewing specialists in the medical field.

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I'm Gavin Nimon, an orthopaedic surgeon based in Adelaide, and I'm broadcasting from Kaurna land.

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I'd like to start the podcast by acknowledging the traditional owners of the land on which this podcast is produced, the Kaurna people, and pay my respects to the elders, both past, present and emerging.

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Well, it's my pleasure now to introduce Jo Czerwinski, a haematologist who works at Flinders Public Hospital, who specialises in haematological malignancies and other haematological conditions.

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Jo, thanks very much for coming on.

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Aussie Med Ed.

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How do you go through in your mind how you divide up these haematological malignancies?

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I used to think of them as leukaemias versus lymphomas, but I understand you go through lymphoid versus myeloid type conditions as a way of considering them.

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Thanks, Gavin, for having me.

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So yes, I often divide them into lymphoid and myeloid conditions, because hematological malignancies begin from the hematologic stem cell, which is at the top end of the rung, and these divide into two types of stem cells the rung, and these divide into two types of stem cells the lymphoid stem cell and the myeloid stem cell.

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From the lymphoid stem cell you generate B cells, t cells and natural killer cells they're the different subcategories of lymphoid cells and from the myeloid stem cell you have the red cells, all of the different granulocytes and the platelets, and as we go through the different types of malignancies, I will be able to show where these malignancies have generated along those development lines.

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Excellent.

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So I understand the lymphoid ones were the ones we're going to talk about today.

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They're also the ones that are actually involved in development of lymphomas as well, which is a different type of condition as opposed to leukemias.

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How do you consider leukemias versus lymphomas and how do they vary for the medical student?

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Yeah, so leukemia comes from the Latin word of leuc, which is white cell, and aemia, meaning in the blood system.

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So leukemias are just the cancer is in the blood system, whereas a lymphoma is in the lymphatic system.

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So you often find it in lymph nodes as well as the spleen and the liver, which are part of that lymphatic.

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The conditions can overlap when it comes to the bone marrow.

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Right, and I understand.

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You can't get myeloid cells in lymphomas.

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It's purely from the lymphoid type cells.

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That's correct, although the bone marrow microenvironment let's call it has both types of cells, so you can have changes to the myeloid component with lymphoid conditions.

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So in your experience, how often do these conditions present in everyday practice?

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I'm curious because they seem quite rare in general practice, but I'd like to get a sense of what to look out for.

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From my experiences speaking with different GPs, it seems to be that each GP may see two or three cases in their patient cohort, so it's not very common from a GP perspective.

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It's very common from my perspective, though.

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The most common ones that we'll be speaking about today is chronic lymphocytic leukemia, as that's one of the most common lymphoid conditions that we see.

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Although I understand the acute lymphocytic leukemia is actually the commonest cancer in the young children.

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So acute lymphoblastic leukemia is an aggressive form of lymphoid cancer and it has a bimodal development, that in children and that in much older adults as well.

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Well, why don't you talk about first of all how they may present, initially, and then talk about how you classify them down into those different areas?

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Yeah, sure.

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So leukemias and lymphomas can present with very few symptoms to begin with, especially if they're chronic versions of disease states.

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So chronic lymphocytic leukemia, for instance, can present, incidentally, just through a blood count, where the patient has gone to their GP just for a regular checkup.

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But when these conditions become more aggressive, they start to present with what we term constitutional symptoms, and this includes dramatic weight loss where the patient is not dieting.

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It can include fevers and night sweats, and the night sweats are drenching where they have to change their pajamas or their bedsheets.

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And it can come with severe fatigue where they're essentially bed bound or couch bound for majority of the day.

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Other ways in which patients can present is recurrent infections which they can't get over and they need multiple rounds of antibiotics, and they can sometimes present with cytopenic complications of anemia needing transfusion thrombocytopenia, where they come out in a petechial rash or excessive bleeding and bruising.

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And, as we mentioned, rash or excessive bleeding and bruising and, as we mentioned, infections where they have low white blood cell counts Excellent.

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From what I can understand in my reading, the simple blood test to see a complete blood picture can often pick up the diagnosis straight off.

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Yeah, very often when lymphoid condition spills out into the bloodstream, it can be seen by a simple blood test and a blood film analysis.

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So the laboratories will look at a drop of blood under a microscope and can see the normal lymphoid cells as well as the abnormal forms.

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Okay.

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So I'm interested in how you approach the classification once you've got the initial findings.

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What guides your decision-making when identifying the specific type of lymphoid malignancy?

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Hmm.

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So for the lymphoid conditions, acute lymphoblastic leukemia is sort of the prototype of acute illness.

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It usually presents within only a couple of weeks from development to full-blown symptoms, and usually the acute lymphoblastic leukemias will present with a pancytopenia, so low red cells, low neutrophil counts, low platelet counts, and they may have lymphoblasts in their circulation.

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That's how the diagnosis is made.

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To further go along, obviously this is a bone marrow malignancy and it is a leukemia.

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So it's spilt out into the blood system.

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So oftentimes you can get a diagnosis by complete blood examination and flow cytometry which tells us the clone of that cell.

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Now to go into a bit more of the classification when we look at the lymphoid stem cell and how it generates into more mature cells, we think about it as where that cell is in its natural state.

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So the lymphoid stem cell is where acute lymphoblastic leukemia originates from.

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It is a mutation in that stem cell.

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Once the stem cell goes through its normal development and exits from the bone marrow, then you have your mantle cell lymphomas and some variations of chronic lymphocytic leukemia, before that lymphoid cell then enters the lymph node to start its development and its training, as it were.

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And in the lymph node is where you get a whole bunch of the different types of lymphomas.

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Now there's more than 80 different types of lymphoma and they're classified into B-cell lymphomas and T-cell lymphomas and they range in aggressiveness from indolent to more aggressive lymphoma types.

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And then, once the lymphoid cell has undergone its training and left the lymph node back into circulation, you then have other forms of chronic lymphocytic leukemia and you also have plasma cell myeloma and other plasma cell disorders, because the end differentiating lymphoid cell is a plasma cell which is capable of producing antibodies.

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So, to get back to your earlier question about how I would undergo investigations, they all start with a CBE, they all have a blood film and they all have flow cytometry from peripheral blood, because even some lymphomas they can spill out of the lymphatic system and into the blood where we can easily pick them up through flow cytometry.

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What's the importance for classifying them?

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If they all present with a similar way and they all can cause anemia and infections, why is it so important to classify them into these different subgroups?

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I guess because the treatment is very different amongst the different subtypes of lymphoid disorders.

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So how I would treat an acute leukemia versus a chronic leukemia, versus a B-cell lymphoma versus a T-cell lymphoma.

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And the stages between acute and chronic are really how quickly they present.

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In that sense it's a crude way of thinking about it.

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Yes, so anything acute or aggressive has usually been there for a very short period of time before a patient presents, whereas a chronic indolent process can be there for many months to even years before a patient is aware of their condition.

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What's the cause of the aplastic type effect that you get from leukemias and lymphomas?

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In that sense, why does that sense?

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Why does that occur?

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So, if we think about the bone marrow being a production factory for red cells, white cells and platelets, if you have an acute leukemia event, usually the lymphoblasts in this scenario will crowd out the bone marrow, leaving very little space left over for normal cells to be created.

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So oftentimes it's because of, say, 80% of the bone marrow is filled up with blasts and that only leaves 20% left over for normal myeloid cells, which is why you get the aplastic appearances.

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Okay.

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So I'm curious about this staging how do you determine the stage of condition after you've classified it, and what role does that play in treatment planning?

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So the leukaemias are staged differently for the acute and the chronic lymphoid leukemias.

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So acute leukemia, we would do molecular or genetic testing from their bone marrow to determine whether they're aggressive, intermediate or low risk genetics and that will then define whether they go ahead with a bone marrow transplant in their course of treatment.

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For the chronic lymphocytic leukemias there is what are called Rye and Binet staging systems and they are based on how many cytopenias the patient has, how many lymph node areas are increased by palpation and whether they have hepatosplenomegaly.

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And so most patients that I see are actually stage zero from those systems, meaning that the only syndrome they have is their lymphocytosis.

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They have otherwise normal blood counts, they don't have enlarged lymph nodes and their liver and spleen is normal.

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So those are the staging systems for the leukemias.

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For the lymphomas it is by Ann Arbor staging systems, which is usually through CT guidance or PET guidance, depending on the lymphoma type.

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So stage one is one group of lymph nodes, say in the cervical area.

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Stage two would be two separate areas of lymph nodes but on the same side of the diaphragm.

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Stage three is that it's crossed both sides of the diaphragm but it's still within the lymph node areas.

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And stage four is if it's invaded into other organs, such as bone marrow, spleen and other organs like kidneys, for instance.

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So those are the staging systems for lymphoma and finally, for myeloma, there is the revised international staging system, which is based off of a few different markers like albumin, ldh, the genetics and the beta-2 microglobulin.

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What's the cause of these conditions?

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Is it because there's such a high turnover of these blood cells that they've got a greater chance of causing malignancy or a genetic transmutation?

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Or does it all relate to a congenital cause?

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Or is it some sort of exposure cause that causes them?

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Most of these conditions are diagnosed above the age of 50.

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So I like to think of them as wear and tear conditions where the body has undergone, say, 60 years of life and along with that it is acquired mutations.

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There are some circumstances where there are inherited disorders, so particularly where we mentioned acute lymphoblastic leukemia in children.

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So, particularly where we mentioned acute lymphoblastic leukemia in children, there are certain circumstances where it's related to a genetic mutation when they were born.

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Okay, I understand, Down syndrome is actually a higher risk of it as well.

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Is that correct?

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Yes, absolutely so.

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It is one of the causes of inherited acute lymphoblastic leukemia.

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So, jo, are there any other exposure causes that can lead to these conditions as well?

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Is there anything you might see as an adult hematologist that can be related to this condition?

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Certainly, if patients have received chemotherapy or radiotherapy for other conditions, say breast cancer for instance, then there is an increased risk of developing lymphomas and leukemias in general.

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The same thing goes for some of the immunotherapies, for instance methotrexate, used commonly for rheumatoid arthritis.

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There is an increased incidence of lymphomas following methotrexate use.

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In general, there is a tendency with autoimmune and inflammatory conditions to have a higher incidence of lymphoma and there is also exposure risks.

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I've also read that smoking might be a factor as well.

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Is that a big factor or is that only a slight association?

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It's a slight association.

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It's not as strong as, for instance, lung cancer or head and neck cancers.

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So, once you've got a diagnosis and you've classified it and you've gone through the staging, what are the treatment options?

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If we start with, say, the acute episode, what's the sort of thoughts that go through the process of actually treating such a condition?

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So for acute lymphoblastic leukemia the treatment is often many months of chemotherapy.

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The treatment is often many months of chemotherapy, usually in the hospital for majority of that time, as the induction chemotherapies are multi-drug, multi-day therapies and they're often quite sick in hospital needing to manage their febrile neutropenias, manage their toxicities from their chemotherapies.

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Many of the acute lymphoblastic leukemia patients will undergo an allogeneic stem cell transplant as part of their therapy and that can be considered sort of their consolidation treatment.

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And some patients following an allogeneic transplant or following their induction chemotherapy will also have what we call maintenance therapies.

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Patients following an allogeneic transplant or following their induction chemotherapy will also have what we call maintenance therapies.

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So the acute lymphoblastic leukemias are very different from the lymphoma in terms of the intensity of management.

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If we think about diffuse large B-cell lymphoma and follicular lymphoma as the two prototype lymphomas in B-cell malignancies, diffuse large B-cell lymphoma is RCHOP gold standard and that's the first-line therapy and that's delivered one day every three weeks for a total of six rounds and most patients will go into remission from just that course of chemotherapy.

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But there are some patients which will be resistant and will need to undertake an autologous stem cell transplant in their future.

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Follicular lymphoma is a much more indolent lymphoma and not all patients will need to undertake treatment straight away.

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And you'll often see a lot of this watch and wait program that hematologists prescribe.

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But if a follicular lymphoma is needing treatment it is because it is symptomatic and causing that patient harm.

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So for those indolent lymphomas, we only treat when the lymphoma is causing an actual problem to the patient.

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Right.

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So that's different to the acute lymphoblastic leukemia where they're more aggressive type treatment.

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In that scenario these lymphomas do they occur in children as well, or are they more in the adult age group?

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There are some Burkitt lymphomas and follicular lymphomas that can occur in teenagers.

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Usually they are again older populations, but diffuse large b-cell lymphoma can occur, you know, from 30 years onwards as well so we've got a acute lymphocytic leukemias occurring, the young children which have a quite aggressive treatment of chemotherapy and I believe it has quite a high success rate in treating, in cure.

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They involve an induction, a consolidation and a maintenance type of treatment.

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Is that correct?

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Yep, then we have our lymphoma group.

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What age group do the lymphomas did you say they occur in?

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Some types of lymphoma can occur in teenage years, but most lymphomas will occur above the age of 40 or 50.

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Okay, and they're divided up into various forms of non-Hodgkin's lymphomas or Hodgkin's lymphomas.

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The ones you were mentioning before are non-Hodgkin's lymphoma styles.

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Is that correct?

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That's right, yes, and what determines the difference between a non-Hodgkin and a Hodgkin's is the presence of a type of cell.

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Is that the way it goes?

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So they're called Hodgkin cells or Reed-Sternberg cells.

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You may have heard that in reference in a textbook, but they're very large cells that have a particular histological feature when they're looked at under a microscope.

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Is that the one with the two nuclei, or something?

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in memory they look like owl's eyes.

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So the non-Hodgkin lymphomas involve these large type of B-cell lymphomas?

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You said there's 60 various forms of it.

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Is that correct?

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80 different forms across B-cell non-Hodgkin lymphomas, and then there's also the T-cell non-Hodgkin lymphomas as well.

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Right NK cells also included in this group.

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Yeah, they're called natural killer cells.

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They're very uncommon.

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Lymphomas and leukemias, and they predominantly present, and leukemias, and they predominantly present as leukemias.

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Okay, so either B cell or T cell, predominantly B cells, and they present in the older age group.

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If they actually get missed and are picked up late, I've read somewhere they can present with bowel obstructions or with respiratory distress from collections around the lungs.

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Is that correct or is that?

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A pretty rare finding nowadays.

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I mean, it's not rare to me but it will be rare to the general population.

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So some types of aggressive lymphomas like Burkitt's and diffuse large B-cell lymphoma, we've been able to pick them up as stage 1 disease, but in the bowel.

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We've been able to pick them up as stage 1 disease, but in the bowel.

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And there is this theory that if patients have pre-existing Crohn's disease or ulcerative colitis or they've had some other immunodeficiency that it can occur in the bowel as the primary site.

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These are still treated the same way as if they occurred in the lymph nodes, though there is also presentations in the lungs.

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So superior vena cava obstructive syndromes can often present with shortness of breath and chest tightness, and the Hodgkin lymphomas in particular can present with mediastinal masses With the difference between non-Hodgkin lymphomas in particular can present with mediastinal masses, With the difference between non-Hodgkin's and Hodgkin-style lymphomas.

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is there Hodgkin-style?

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Is there only one type or are there various sub-forms of Hodgkin's as well?

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There are five different forms of Hodgkin's.

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Most of them are under what we call the classical Hodgkin presentations and the description.

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Differences between them is how they appear under the microscope from their histology samples.

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The one that's a bit different is the nodular lymphocyte predominant Hodgkin's lymphoma, because this is treated more like your B-cell lymphomas, like DLBCL, for instance.

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DL.

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What does that stand for then?

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Diffuse Large B-Cell Lymphoma.

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Sorry.

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And the Hodgkins?

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Have they got a worse or better prognosis than the non-Hodgkins?

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Generally very good prognosis.

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So especially this also has a bimodal presentation in the population.

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So we can see 20-year-olds with 80 year olds with them, and how well you do and how your prognosis is is based a bit on your fitness.

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So a young person with Hodgkin's lymphoma 90% cure rate with standard treatments.

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An older person with Hodgkin's because they can't have the standard chemotherapies at their ages they are less survived, but still reasonable prognosis and the actual percentage of people with Hodgkin's versus non-Hodgkin's is a significantly greater number of non-Hodgkin's or Hodgkin's.

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Non-Hodgkin's is certainly much more common.

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Once the diagnosis is confirmed, how do you start mapping out the treatment plan?

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What are the main factors that guide your choice of treatment?

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So often, what can help with a referral to a hematologist is by having the basic complete blood examination and full biochemistry with the LDH, as well as, if there is a lump that is easily accessible to biopsy.

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A core biopsy is going to give us a world of information, because that can already start subtyping what type of lymphoma it is, how aggressive it is and how soon does it need treatment.

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And how soon does it need treatment?

00:23:13.858 --> 00:23:21.320
And often what I encourage GPs to write on their referral is whether this patient has constitutional symptoms or not, because that's going to dictate how quickly I need to see the patient as well.

00:23:21.320 --> 00:23:27.883
There are certain other tests that can be helpful, so flow cytometry from peripheral blood.

00:23:27.883 --> 00:23:34.580
But even if that's negative, that doesn't exclude the probability of a lymphoma or leukemia.

00:23:36.204 --> 00:23:42.065
So flow cytometry is that where the blood is passed through a tube and a computer analyzes the type of cells they are.

00:23:42.065 --> 00:23:43.347
Or is that how it works?

00:23:43.795 --> 00:23:45.678
Yeah, roughly so.

00:23:45.678 --> 00:24:00.647
The blood is pulled through a machine in single file and a laser is pointed at these cells and with all the refracting light from it it gives off a certain cell signature.

00:24:00.647 --> 00:24:04.746
And what we're looking for is a clone of B cells.

00:24:04.746 --> 00:24:13.250
So, for instance, in chronic lymphocytic leukemia B cells will express CD20 and CD19.

00:24:13.250 --> 00:24:15.021
That's part of being a B cell.

00:24:15.021 --> 00:24:28.640
And chronic lymphocytic leukemia will have another marker called CD5, which will be positive and CD10 will be negative, and that begins sort of the clonality of that cell and that begins sort of the clonality of that cell.

00:24:28.640 --> 00:24:40.615
What defines a clone of a cell is whether they're expressing a certain light chain no-transcript.

00:24:40.215 --> 00:24:42.002
You mentioned also getting a core biopsy.

00:24:42.002 --> 00:24:48.404
Is that saying that a GP just takes out a needle and puts it into a lump, or is it done by ultrasound guidance or CT guidance?

00:24:48.404 --> 00:24:50.462
How is it actually physically done?

00:24:51.435 --> 00:24:58.345
So I recommend that GPs refer off to a radiology company for an ultrasound-guided core biopsy.

00:24:59.236 --> 00:25:02.705
We also mentioned passing was the bone marrow biopsies as well.

00:25:02.705 --> 00:25:04.060
How are they actually physically done?

00:25:04.060 --> 00:25:06.323
Is that something that needs an admission to a hospital and an anaesthetic?

00:25:06.994 --> 00:25:10.201
So in South Australia we do them under sedation.

00:25:10.201 --> 00:25:12.946
So it is like a day procedure.

00:25:12.946 --> 00:25:21.599
A patient will come in fasted and they'll have the anaesthetic team performing the sedation and a hematology team performing the actual bone marrow.

00:25:21.599 --> 00:25:32.788
The procedure itself is only a 15 minute procedure and involves taking a blood sample and a bone sample from the posterior superior iliac spine.

00:25:33.755 --> 00:25:40.383
Excellent, and one question that came to mind also is when I was doing this reading as a surgeon, I felt sort of left out of the process.

00:25:40.383 --> 00:25:43.423
It doesn't sound like often surgery is required in these conditions.

00:25:43.855 --> 00:25:47.266
There certainly is circumstances where we need to involve a surgeon.

00:25:47.266 --> 00:25:57.744
So where we mentioned Hodgkin's lymphoma before, hodgkin's cells aren't actually not that popular in the actual core biopsy specimens.

00:25:57.744 --> 00:26:07.318
So sometimes a core biopsy will be performed and the specimen quality is quite good, but it still misses out on those key Reed-Sternberg cells.

00:26:07.318 --> 00:26:16.267
So often we will refer to surgeons to perform an excisional lymph node biopsy where the whole lymph node is then sent away for analysis.

00:26:16.267 --> 00:26:24.500
Similarly I need a cardiothoracic surgeon for the mediastinal lymph nodes if that's the only area of disease.

00:26:24.500 --> 00:26:27.595
Sometimes, you know, colorectal surgeons are needed for the mediastinal lymph nodes if that's the only area of disease.

00:26:27.595 --> 00:26:33.079
Sometimes, you know, colorectal surgeons are needed for the bowel specimens because they've come in with obstruction or perforation.

00:26:33.079 --> 00:26:43.224
And sometimes I need even orthopedic or neurosurgeons for the vertebral lesions that may present.

00:26:44.387 --> 00:26:48.440
Excellent, all right, so we've got our biopsies.

00:26:48.440 --> 00:26:52.478
We're going to talk about our treatment plans then, and they obviously vary depending on all the different classifications.

00:26:52.478 --> 00:26:56.146
What are the main headings for treatment options for treating these conditions?

00:26:57.496 --> 00:27:10.736
So the stock standard would be chemotherapy, and that's quite common for the aggressive forms of cancers and usually it's a protocol of several cycles.

00:27:10.736 --> 00:27:17.881
Many of the protocols involve hair loss, nausea, vomiting the usual side effects from chemotherapy.

00:27:17.881 --> 00:27:25.906
But over the last decade or so we've developed quite a lot of different alternative treatment options.

00:27:25.906 --> 00:27:41.977
So R-CHOP, being the sort of prototype, involves rituximab, which is what the R stands for and that's a monoclonal antibody.

00:27:41.977 --> 00:27:57.960
So it is actually targeting CD20, which we mentioned before, and so any of the B-cell malignancies that express CD20 can be targeted with rituximab and certainly for some of the more indolent lymphomas you can use rituximab by itself without chemotherapy.

00:27:57.960 --> 00:28:02.945
So chemotherapy, monoclonal antibodies.

00:28:02.945 --> 00:28:07.775
There are also immunotherapies or targeted treatments as well.

00:28:08.415 --> 00:28:17.656
So chronic lymphocytic leukemia has emerged as quite a popular disease to try and avoid chemotherapy.

00:28:17.656 --> 00:28:24.859
We know that chemotherapy works, but chemotherapy is quite a slog for patients and has long-term side effects.

00:28:24.859 --> 00:28:33.108
So there has been quite a focus over the last decade in trying to transform the treatment algorithm for patients.

00:28:33.108 --> 00:28:51.606
So there's these targeted agents which are called Bruton, tyrosine kinase inhibitors or BTK inhibitors, which is actually targeting an area of the B-cell receptor to turn off proliferation and to turn off adhesion factors.

00:28:51.606 --> 00:29:03.490
So the three BTKs which I use quite often are ibrutinib, acalabrutinib and zanubrutinib.

00:29:03.490 --> 00:29:05.462
You'll notice that all of them end in nib.

00:29:07.816 --> 00:29:09.137
So these three agents.

00:29:09.137 --> 00:29:30.803
They act on CLL by releasing all of them from the lymphatic system, from the bone marrow system, so that stops the adhesion to those areas, and then they stop proliferation, so they make these cells inert and the body eventually destroys them just from it being in circulation.

00:29:30.803 --> 00:29:44.703
So it's quite a common treatment and it is being expanded into other areas, so Waldenstrom's macroglobulinemia, which is another form of lymphoma and mantle cell lymphoma.

00:29:44.703 --> 00:29:50.490
We now are able to use these BTK inhibitors in those diseases as well.

00:29:53.521 --> 00:30:01.048
Amazing, I keep getting this common theme that keeps occurring when we talk about cancers on these podcasts is actually the importance of the patient's immunity themselves, their natural immunity.

00:30:01.695 --> 00:30:09.759
It is certainly something that I discuss, with all of my new diagnoses of any form of cancer, with my patients.

00:30:09.759 --> 00:30:15.058
Lymphoid malignancies are a particular kettle of fish that we need to discuss.

00:30:15.058 --> 00:30:21.337
So it doesn't make a difference whether it's a B-cell malignancy or a T-cell malignancy.

00:30:21.337 --> 00:30:25.865
There is damage to the immune system talking to itself.

00:30:25.865 --> 00:30:47.291
So B cells and T cells the normal approach to infection to foreign bodies is the B cell will present antigens to the T cell and the T cell will then destroy those antigens and associated pathogens.

00:30:47.291 --> 00:30:55.215
And this is a broken system when you've got a malignancy from either the B cell or the T cell side.

00:30:55.215 --> 00:31:08.404
So one thing that I often talk to with patients is that, regardless of their lymphoid malignancy, they are now considered immunocompromised and there are three things that I can do for that patient.

00:31:08.404 --> 00:31:23.561
I can test their immunoglobulin levels and if the immunoglobulin G level is low, there is replacement available in the form of intravenous or subcutaneous immunoglobulins.

00:31:23.582 --> 00:31:40.486
There is the system of needing to have easy access to antibiotics and antivirals because they're more likely to suffer with infections at a more severe degree than a patient with a normal immune system, and there is vaccinations.

00:31:41.327 --> 00:31:50.943
So we do not give any live vaccines because there is a great risk that the patient will actually develop the disease that the vaccination was intended for.

00:31:50.943 --> 00:32:06.188
But I tell all of my patients to be up to date with the influenza vaccine, covid vaccine, the latest shingles vaccine, which is called shingrix, and then the pneumococcal or pneumovax vaccine.

00:32:06.188 --> 00:32:12.028
So that's one part of the immune system that is in a way broken.

00:32:12.028 --> 00:32:29.544
The other part of the immune system that is also broken is what's called tumor surveillance, so that same B cell presenting antigen to T cells that presents tumor antigens as well in the normal healthy individual and that system is again broken.

00:32:29.544 --> 00:32:37.083
So any patient with any of these lymphoid malignancies has an increased risk of a second malignancy occurring.

00:32:37.083 --> 00:32:44.061
So I tell patients you know, be up to date with your age, appropriate malignancy screening.

00:32:44.061 --> 00:32:52.486
So that's bowel cancer, prostate cancer, breast cancer, cervical cancer, and must not forget about skin cancers.

00:32:53.375 --> 00:33:00.343
You talked about the use of chemotherapy as well, but then chemotherapy can also be associated with the cause of leukemias and lymphomas as well.

00:33:00.343 --> 00:33:05.202
So can the actual drugs you use to treat the leukemias cause a cancer too, in that sense?

00:33:05.775 --> 00:33:07.479
Yeah, absolutely so.

00:33:07.479 --> 00:33:45.367
Once a patient has undergone chemotherapy, and regardless of if they've achieved a cure or remission, I do tell them that it is important to keep up to date with their normal malignancy checks, but also to have a blood test every year just a complete blood examination and biochemistry because we have found some patients have had chemotherapy and it's damaged their bone marrow in other ways, and so we can often see myelodysplastic syndrome and acute myeloid leukemia developing as a result of prior chemotherapy.

00:33:46.016 --> 00:33:49.645
Well, actually we mentioned targeted therapy and use of monoclonal antibodies.

00:33:49.645 --> 00:33:57.304
Is that like a tablet you can just get over the counter, or is it specifically produced for one individual patient and they have to have a genetic testing to actually produce it?

00:33:57.304 --> 00:33:58.580
How do these medications work?

00:33:59.516 --> 00:34:08.262
So the monoclonal antibodies are infusions and so long as the patient has a CD20 malignancy we can apply for it.

00:34:08.262 --> 00:34:21.041
It is dosed based on their body surface area, so their height and weight are taken into account For the targeted treatments like the BTK inhibitors that I mentioned.

00:34:21.041 --> 00:34:34.615
That is an authority script that only a hematologist can apply for, but it is the same dosing regardless of the patient indication and regardless of the patient weight.

00:34:35.577 --> 00:34:41.349
So the immune therapy, then the actual targets, are actually a common form of therapy.

00:34:41.349 --> 00:34:41.755
It's not.

00:34:41.755 --> 00:34:48.429
I always had this idea that you might take the patient's blood, work out what the immune response would be and target that particular individual.

00:34:49.255 --> 00:34:49.757
I would hope.

00:34:49.757 --> 00:34:55.621
I would hope that that will be the case in the future, where we have more tailored approaches to patients.

00:34:55.621 --> 00:35:01.400
At the moment, we're using the genetic tests predominantly to give us the risk profile of the patient.

00:35:01.400 --> 00:35:12.548
So if they're high risk, I know that they may not respond to chemotherapies and I would more likely use the targeted treatments or immunotherapy approach.

00:35:12.548 --> 00:35:24.726
And similarly, if they're low risk, that gives me prognostic information and tells me that it could be a while away before this patient needs treatment, and that's a good thing.

00:35:25.414 --> 00:35:36.802
Jo, when we're talking to a lot of other physicians about the treatment of different malignancies or even just conditions in general, another common thing that comes up is the use of multidisciplinary teams involved with treatment of patients.

00:35:36.802 --> 00:35:42.702
Jo, do you tend to use an MDT as a part of your process, or is it more of an individualised type approach?

00:35:43.364 --> 00:35:44.106
No, absolutely.

00:35:44.106 --> 00:35:47.284
We definitely utilise multidisciplinary teams.

00:35:47.284 --> 00:35:56.646
For Flinders, we do have an established lymphoma MDT, and so in these groups we have several hematologists.

00:35:56.646 --> 00:36:06.847
We have the radiation oncologists who can provide their input in whether radiation can be delivered safely in this patient.

00:36:06.847 --> 00:36:20.626
We've got the anatomical pathologists which are presenting the histology specimens, and we have the radiologists who present the CT scan and PET scan and MRI findings.

00:36:20.626 --> 00:36:28.938
So with all this information together we can establish a treatment plan that is agreed to by the consensus group.

00:36:28.938 --> 00:36:47.956
We also have other types of MDTs where we involve our allied health colleagues, because oftentimes having a cancer diagnosis is very stressful for a patient and involves financial and legal matters as well as how is this patient going to be cared for?

00:36:47.956 --> 00:36:52.483
Do they need additional OT or PT input?

00:36:52.483 --> 00:36:58.737
And we also involve palliative care, as that can be.

00:36:58.737 --> 00:37:02.762
One of the treatment options is supportive cares.

00:37:02.762 --> 00:37:14.398
We also involve our infectious diseases colleagues in a weekly meeting because many times, especially in the hospital setting, our patients have come in with infectious complications.

00:37:15.041 --> 00:37:17.407
So it really is quite an extensive group we've got there.

00:37:17.407 --> 00:37:23.918
When others were reading about CLL as well, almost it sounded a bit like prostate cancer, in that it's actually a lot of.

00:37:23.918 --> 00:37:32.425
It can be quite indolent and longstanding and that generally there'll be a large number of proportions of the community might have it without even knowing it and might not even have symptoms of it.

00:37:32.425 --> 00:37:34.099
Is that the way of thinking about CLL?

00:37:34.099 --> 00:37:35.664
It can be as low as grade as that.

00:37:36.175 --> 00:37:52.088
More than 90% of my patients are found incidentally and they go on to Lymphoma Australia and the various private Facebook groups and they find that you know, neighbors, friends they have CLL as well.

00:37:52.088 --> 00:38:04.601
It's only 10% of my patients that need treatment and those 10% usually need second and third-line treatments some way down the line.

00:38:04.601 --> 00:38:09.641
Usually need second and third line treatments some way down the line.

00:38:09.641 --> 00:38:12.572
But if a patient has had CLL for a decade, that bodes well that they will never require treatment.

00:38:13.155 --> 00:38:20.041
Obviously, we mentioned the ALL definitely requires treatment, and the lymphomas almost invariably would require treatment as well.

00:38:20.041 --> 00:38:21.184
Would that not be the case?

00:38:22.135 --> 00:38:25.045
Most of the lymphomas will require treatment at some point.

00:38:25.045 --> 00:38:32.804
For some of the subtypes that are indolent, like the follicular lymphoma, marginal zone lymphoma is usually indolent as well.

00:38:32.804 --> 00:38:44.226
Many of them can undergo watch and wait, and that could be the case for a few years, before the lymphoma progresses enough that it requires treatment at that stage.

00:38:45.014 --> 00:38:46.983
So, jo, where do you think things are heading for the future?

00:38:46.983 --> 00:38:48.862
Obviously it's been a lot of advances.

00:38:48.862 --> 00:38:56.362
Will AI have a lot of input into this area down the track, and is there other areas or new advances coming out, new medications or new approaches?

00:38:57.775 --> 00:39:09.782
Certainly there's a lot of work in the genetic side of things, where the more information we are gleaning from a patient's genomic status, the more we can tailor our approach.

00:39:09.922 --> 00:39:14.797
So, for instance, in CLL there are the BTK inhibitors that I mentioned.

00:39:15.257 --> 00:39:42.184
There are also another class of drug called the BCL inhibitors, like venetoclax, and which one you start off with may be differentiated by what genetic status that patient has, and certainly you can develop resistances to those protein markers and you would not want to treat a patient with a BCL2 inhibitor if they've got a BCL2 mutation, if they've got a BCL2 mutation.

00:39:43.465 --> 00:40:20.889
The other side of things, where the future holds, there's a lot of input and research into CAR-T therapies, which is chimeric antigen receptor T cell therapies, and this is in a way a form of a transplant, where you take a patient's T cells, you send it away for engineering and manufacturing to make that T cell smarter and target the lymphoma or the leukemia, and then you re-infuse the T cells back into the patient and so you're retraining the immune system to target that tumor and kill it.

00:40:20.889 --> 00:40:38.737
The other form of treatment that is emerging quite strongly is bite therapies, which are bispecific T-cell engagers and again you're harnessing the T-cells to target the B-cell malignancies.

00:40:38.737 --> 00:40:45.128
Now, these technologies that I've both mentioned are against B-cell malignancies.

00:40:45.128 --> 00:40:53.644
We don't have that kind of technology against T-cells as yet, but that is something for the future with further research.

00:40:54.065 --> 00:40:54.467
Brilliant.

00:40:54.467 --> 00:40:57.041
Well, it's been fantastic hearing about this area.

00:40:57.041 --> 00:40:59.402
It's actually massive.

00:40:59.402 --> 00:41:04.465
In preparation for this podcast today, you might have heard me mention my reading.

00:41:04.465 --> 00:41:07.726
I have had to do a lot of reading as a general orthopedic surgeon.

00:41:07.726 --> 00:41:14.807
I didn't know much about it and it's great hearing about these different areas and the great treatment you're offering these patients.

00:41:14.807 --> 00:41:16.380
So thank you very much, joe, for coming on.

00:41:16.380 --> 00:41:18.048
Aussie med ed been brilliant.

00:41:18.048 --> 00:41:24.226
I'd like to get you back at some stage to talk about the myeloid dysplasias and lignancies, and it it's great to have you here today.

00:41:24.226 --> 00:41:25.148
So thank you very much.

00:41:25.614 --> 00:41:27.802
Thank you for having me and looking forward to the future.

00:41:28.403 --> 00:41:28.894
Brilliant Well.

00:41:28.894 --> 00:41:30.963
Thank you very much, Dr Jo Czerwinski.

00:41:30.963 --> 00:41:32.000
Thank you very much for coming on.

00:41:32.000 --> 00:41:34.704
A specialist haematologist at the Flinders Public Hospital.

00:41:34.704 --> 00:41:40.519
I'd like to remind you that all the information presented today is just one opinion and that there are numerous ways of treating all medical conditions.

00:41:40.519 --> 00:41:44.346
Therefore, you should always seek advice from your health professionals in the area in which you live.

00:41:44.346 --> 00:41:52.967
Also, if you have any concerns about the information raised today, please speak to your GP or seek assistance from health organisations such as Lifeline in Australia.

00:41:52.967 --> 00:41:55.766
Thank you very much for listening to our podcast today.

00:41:55.766 --> 00:42:01.976
I'd like to remind you that the information provided is just general advice and may vary depending on the region in which you are practising or being treated.

00:42:01.976 --> 00:42:07.126
If you have any concerns or questions about what we've discussed, you should seek advice from your general practitioner.

00:42:07.126 --> 00:42:12.398
I'd like to thank you very much for listening to our podcast and please subscribe to the podcast for the next episode.

00:42:12.398 --> 00:42:14.253
Until then, please stay safe.