Hello, welcome to the session about the malignancies of the hemopoietic system. You heard both Dr. Porter being interviewed about various leukemias. Could you please tell me how frequently you see patients with leukemia in your practice? So, mindful that we are in a hospital setting. We do see quite a few patients with, that have been already diagnosed with leukemia. Some of them are before they are going to have a transplant, either a bone marrow or stem cell transplant. They will ask us to make sure that there is no significant acute dental alveolar infection before the immune system is really wiped out, in order for the transplant to take over. But we do see patients also acutely, if after they've had significant chemotherapy which we would say is myeloablative that which destroys some of the bone marrow cells. Most of those patients will develop some level of mucositis and some level of pain that's an inflammation or an ulceration in the mucus. So, let's start first with the diagnosis. How instrumental can the dentist or an oral medicine specialist be in the diagnosis of blood malignancies such as leukemia? So, occasionally, the oral cavity is the first sign of patients that are neutropenic for instance, they may get aphthous-like ulcers, canker sores, that may be the first sign that there may be something askew in the patient's bone marrow. Occasionally, I think most of us that practice in a hospital will relate a story where bleeding is the first sign and oral bleeding. The scenario as it goes, is that someone had their teeth cleaned two days ago or a day ago and they continue to bleed. And upon further investigation, it's not because there was anything locally but because their leukemia or their blood malignancy, led to a decrease in the amounts of platelets and therefore the increased amount of bleeding that we see orally. So, in order not to alarm unduly, patients in dental practice, the patient comes and sees me and says that their gums bleed. What other additional factors will lead me to believe there may be a potential of blood malignancy? I think time. I mean, it's quite common people with gum disease that they have bleeding gums but their gums don't bleed for 10, 15, 20 minutes or let alone hours. I think that, that's the key. I think if your gums are bleeding for a much longer period of time, that needs get investigated. Patients also may present with the associated signs and symptoms related to oral bleeding. So, patients often complain of persistent fever which is usually of unknown origin. So that may be associated with evidence of leukemia in the oral cavity. In addition, patients may develop blood spots or petechiae, as we call them inside the oral cavity or even on their skin as well. So these are some of the other things to look for that may lead the clinician to think about perhaps a leukemia-related diagnosis. Once again, I think it comes down to the medical history. I think it's incumbent upon the dental practitioner to take an adequate medical history and ask about things like fatigue, like frequent colds, like excessive bleeding, like if they've noticed any skin abnormalities. Those things are very important in terms of framing the entire picture. So, as usual in these discussions, oral complications can result both from the disease and from the treatment of the disease. So, why don't we start first from the disease itself? What type of oral complications can be caused by blood malignancies? So, the most common is you can get oral ulcers relating to often low white blood counts or something called neutropenia, you can get bleeding. As was mentioned in various types of leukemias, there could be a thrombocytopenia or a low-platelet count. You can see in a small subset of patients that have leukemia, actual leukemic infiltration of the gum tissue in certain types of myeloid, acute myeloid leukemia. So, acute myelogenous leukemias in certain subtypes of those, you can see a leukemic infiltrate. And then there's certain other stigmata that have been associated with malignancies as mentioned a little earlier, Dr. Stoopler, where you get little red spots or petechiae which could be suggestive of a low-platelet count. In addition, patients may also complain of burning of their tongue which may be attributed to balding, which could be a sign of anemia that's often related to leukemic diagnoses. And so, patients may have generalized redness to their tissues and generalized redness or a balding pattern to the top of their tongue, which could also be indicative of what we're talking about today. And another thing, sometimes you can see and we didn't spend much time speaking to this, but your cavity could be an area where someone might experience a lymphoma, where there will be actual altered tissue in the oral cavity in which lymphoma is diagnosed. I see. Could you now please discuss some of the more common complications associated with treatment of leukemia which may involve chemotherapy and other modalities? Sure. So, there are several complications that could arise in the oral cavity from treatment of leukemia. Most prominently is something called mucositis, which is an inflammation of the lining of the mouth and oral tissues, which can be severely debilitating. In fact, it can be a rate-limiting step in the overall treatment of leukemia because patients experience such severe symptoms such as pain, discomfort, it affects the way that they can eat and their intake. And so, this is something that we see quite often as a common complication from leukemia treatment. In addition, patients who have undergone allogeneic stem cell transplant have a higher risk of developing a condition called graft versus host disease which is a mucosal disorder that looks very similar to something like lichen planus, where patients develop either acutely or chronically after they've received their allogeneic stem cell transplant which again can cause ulceration, burning, bleeding inside the oral cavity and it may be very difficult to manage chronically. And of course, you always have to remember that if somebody's immune system is debilitated because of very strong chemotherapy, they are much more susceptible to oral viral infections, recurrent herpetic infections inside the mouth, as well as fungal infections, both superficial fungal infections like candidiasis. But even deep fungal infections, if they've been neutropenic or if they've been profoundly leukopenic for a any length of time, it becomes a concern. And, how do you treat these conditions? Well, in terms of the infections, they're treated with standard medications. Many of these medications are given intravenously during the time that the patient is in the hospital, whether it be an anti-fungal medication or whether it be an anti-viral medication. In terms of some of the other conditions as was mentioned by Dr. Stoopler. Graft versus host disease, often, it's done in conjunction with the patient's oncologist because graft versus host disease is one of those conditions that could have serious repercussions for the patient because it doesn't only affect the oral cavity, but it affects the entire GI system, as well as the skin. And so what an oral oncologist will do is they might turn up the immunosuppression, which sounds somewhat counterintuitive, but once that graft has ungrafted, it views the body as foreign. So if you turn up the immunosuppression, you're turning off of the graft to go against or fight the host. Now, there's also something I believe Dr. Porter spoke of and that's graft versus leukemia effect, in which it has a very positive response in destroying any residual leukemic cells. But those are the main ways of taking care of patients. In terms of mucositis, I know we spoke a little bit about mucositis earlier, there are a variety of agents that can be used. First line usually is topical therapy, topical anesthetics are used on a very routine basis. But this is an indication where opioids are of use and there are analgesic protocols, particularly for patients of mucositis, where it is indicated for pain control to use opioids, and so we spoke about that earlier and in another context. But it's very common to see patients who are using opioids if they're outpatients. Inpatients use a device called a PCA or a Patient Controlled Analgesic machine which they can deliver opioid medication on a timed basis. One of the things I failed to mention earlier is also salivary gland disease is seen. So you will have patients that are undergoing chemotherapy or have undergone chemotherapy in preparation for a bone marrow transplant, and then after that treatment, they develop severe dry mouth. And that, coupled with mucositis or coupled with some type of viral infection or yeast infection, becomes very very painful and problematic for patients. So we also try and keep the patients hydrated and their mouth moist as best we can. Perhaps since we're talking about hematopoietic diseases, we should also mention multiple myeloma. I know that this disease is often treated with by bisphosphonates. Could you tell us a little bit what are some of the problems associated in overcoming with this treatment. Yes certainly. I think one thing I would like to mention and Eric will remember this, we've shared a number of patients with multiple myeloma. There is a secondary problem with patients with multiple myeloma. That is, they can get a condition known as secondary amyloidosis. And secondary amyloidosis there is a significant oral manifestation. Patients would come in complaining of a thickened tongue. We shared a case, a while back, in which the thickness of the tongue was so strong that it moved teeth out of the way. And that was an oral manifestation. In addition, one parry oral manifestation is something called Pinched Purpura that can be seen just underneath the eyelids. Again a clinical manifestation of amyloidosis in the setting of somebody with multiple myeloma. But in terms of the bisphosphonate maybe you want to cover them. Sure. So multiple myeloma. One of the major risks involved with the condition is that it can cause lytic lesions of the bone. And so, bisphosphonates are a class of medication that can be used to prevent these lesions from occurring in the bone and to maintain bone integrity as best as possible. The issue that we as dental providers face when patients are on bisphosphonates, particularly intravenous bisphosphonates as such in the multiple myeloma population, is that it has been associated strongly with a condition called Medication Related Osteonecrosis of the Jaw or MRONJ. MRONJ is characterized differently according to different classifications as proposed by the current guidelines from The American Academy of Oral Maxillofacial Surgeons or The American Association of Oral and Maxillofacial Surgeons. There are different stages depending on the different clinical phenomena that are associated with it but, in its most extreme form, patients develop necrosis of their bone which can spontaneously exfoliate or come off. It can create a nidus of infection which can be very severe and cause significant oral pain. So it can be a problem that is difficult to manage. And it can even continue after the patient is in significant remission from their multiple myeloma. Once the bone has been exposed to these chemicals, particularly the bisphosphonates particularly the I.V. nitrogen containing bisphosphonates, it is something where there is significant risk of this osteonecrosis for years if not decades. So does the general dentist practitioner needs to take precaution on patients who report taking these medications? Yes. I think there's no question that the dentist needs to understand these medications. By and large most of the patients that are taking these medications is not for metastatic cancer treatment or treatment of multiple myeloma. Although it's a significant population. Most of these medications are being used for patients with osteopenia and osteoporosis. Those patients tend to have less of an incidence of these types of necrotic areas of the bone. Dentists, before a patient is placed on these medications and sometimes with cancer therapy, you don't have the luxury of time. But if you do want to eliminate any infection prior to being started on these medications. Then you need to also be mindful of early diagnosis of somebody that could have necrosis of the bone and you would want to manage that appropriately. Often it's managed by an maxillofacial surgeon. I think the dentist also is going to play a significant role in explaining patient risk, to understanding that those patients that have had I.V. medications are at a greater risk of having a complication from an extraction, from an infected tooth, or even from implant placement. So I think it's incumbent upon the dentist to discuss these issues, without worrying patients, but give them the understanding and the statistics regarding the risk of being on these medicines. The only thing I was going to add was dentists should consider that there is risk although it's much lower than with I.V. medications with people who use oral bisphosphonates. There is still risk and I think it's important to have that frank discussion and perhaps even using an informed consent prior to surgical procedures. Well good. Thank you for this enlightened conversation.
