WEBVTT 1 00:00:08.166 --> 00:00:10.566 Hello, my name is Taylor Jackson. 2 00:00:10.566 --> 00:00:14.400 I am, doctor here at the University of Utah 3 00:00:14.433 --> 00:00:20.000 in the pathology department, and, just as ways of introduction, 4 00:00:20.000 --> 00:00:25.300 before I went to medical school, I worked in laboratory science. 5 00:00:25.300 --> 00:00:30.833 I was in MLS, and I worked in that realm in a couple of different labs, 6 00:00:31.166 --> 00:00:34.633 in immunology, specifically for about nine years. 7 00:00:34.633 --> 00:00:39.100 And after doing that, I decided, well, if I'm want to do medicine, 8 00:00:39.100 --> 00:00:40.133 I better get after it. 9 00:00:40.133 --> 00:00:44.533 So I went to med school after that, and I'm currently in my last year 10 00:00:44.533 --> 00:00:48.933 of training here at the University of Utah for pathology residency. 11 00:00:50.166 --> 00:00:53.733 So today I'm going to talk about really kind of 12 00:00:54.733 --> 00:00:57.200 putting some of the laboratory 13 00:00:57.200 --> 00:01:00.200 testing involved in diagnosing 14 00:01:00.700 --> 00:01:03.700 myeloma and other plasma cell disgraces, 15 00:01:04.133 --> 00:01:07.766 and really putting that in the context of what we see clinically 16 00:01:07.766 --> 00:01:12.233 and how to use those results from testing 17 00:01:12.633 --> 00:01:15.333 and match them up with what we're seeing in the patient. 18 00:01:16.800 --> 00:01:18.333 This is 19 00:01:18.333 --> 00:01:21.866 something I've thought about a lot, especially when I was in the laboratory, 20 00:01:21.866 --> 00:01:25.100 and I would see, you know, weird results come across 21 00:01:25.100 --> 00:01:28.566 or you know, very what we think of as bad results. 22 00:01:29.000 --> 00:01:31.766 But without the context of what was going on clinically, 23 00:01:31.766 --> 00:01:34.766 it was hard to really know how these patients were doing. 24 00:01:34.866 --> 00:01:40.233 And if what I was seeing was real or if it was an artifact of something else. 25 00:01:40.233 --> 00:01:46.400 So I, I like, especially for my audience, who is maybe laboratory specific, 26 00:01:46.400 --> 00:01:50.466 I like to give them the clinical context of why we're doing 27 00:01:50.466 --> 00:01:53.466 the things we're doing. 28 00:01:55.866 --> 00:01:57.800 So here are some of my objectives. 29 00:01:57.800 --> 00:02:01.833 I'm mostly going to be talking about as PAP and ifI testing 30 00:02:01.833 --> 00:02:03.833 and the methods used there 31 00:02:03.833 --> 00:02:07.366 and how we put those together to generate an interpretation, 32 00:02:08.033 --> 00:02:13.100 also identifying the clinical context of when that testing is actually indicated 33 00:02:13.633 --> 00:02:16.100 and if there's any follow up testing that may be needed. 34 00:02:17.266 --> 00:02:19.333 Also, I want to talk a little bit 35 00:02:19.333 --> 00:02:23.433 about the potential interferences that can happen, 36 00:02:24.066 --> 00:02:26.766 for people who are undergoing 37 00:02:26.766 --> 00:02:31.233 treatment for these diseases and just review the treatment 38 00:02:31.233 --> 00:02:34.233 and management kind of what goes on after 39 00:02:34.300 --> 00:02:37.300 they receive a diagnosis. 40 00:02:37.900 --> 00:02:40.900 I have no disclosures. 41 00:02:41.500 --> 00:02:44.433 And then I just wanted to throw in a few helpful acronyms. 42 00:02:44.433 --> 00:02:46.000 I've already used a couple of them. 43 00:02:46.000 --> 00:02:50.233 So, as Pep refers to serum protein electrophoresis, 44 00:02:50.233 --> 00:02:56.400 you Pep for similarly urine protein electrophoresis, if he is for immuno 45 00:02:56.400 --> 00:03:01.333 fixation, electrophoresis and FLC stands for free light chains. 46 00:03:02.766 --> 00:03:05.766 So I'll be using all of these, 47 00:03:06.400 --> 00:03:07.366 fairly frequently. 48 00:03:07.366 --> 00:03:11.200 So just to give kind of, a baseline of what I'm talking about. 49 00:03:13.066 --> 00:03:14.433 So today 50 00:03:14.433 --> 00:03:18.100 I'll be talking about plasma cell, this craziness. 51 00:03:18.100 --> 00:03:22.300 And this is actually a group of different diseases that all relate 52 00:03:22.300 --> 00:03:27.333 back to the plasma cell and what happens when they become 53 00:03:28.066 --> 00:03:30.900 monoclonal and start producing, 54 00:03:30.900 --> 00:03:33.833 many, many clones of themselves and, 55 00:03:33.833 --> 00:03:37.033 ultimately causing symptoms and disease. 56 00:03:37.800 --> 00:03:41.966 So some of the, the main ones I'll talk about today include plasma cell myeloma. 57 00:03:42.466 --> 00:03:43.466 In the 58 00:03:44.666 --> 00:03:47.600 regular world, most people hear about this, 59 00:03:47.600 --> 00:03:50.600 and refer to it as multiple myeloma. 60 00:03:51.166 --> 00:03:54.133 I'll call that by both names. 61 00:03:54.133 --> 00:03:56.733 But in in the amateur pathology world, 62 00:03:56.733 --> 00:03:59.733 we refer to it as plasma cell myeloma. 63 00:04:01.000 --> 00:04:02.600 And then just running down 64 00:04:02.600 --> 00:04:06.200 some of these other, plasma cell disorders. 65 00:04:06.200 --> 00:04:10.366 So mGUS is a monoclonal come up the of undetermined significance. 66 00:04:10.733 --> 00:04:14.966 And you can think of it as kind of like the early signs of 67 00:04:16.400 --> 00:04:19.400 these plasma cell disgraces, 68 00:04:19.533 --> 00:04:24.266 also smoldering myeloma a little, further down the spectrum, getting towards 69 00:04:24.266 --> 00:04:27.500 worse disease one streams macro globule 70 00:04:27.500 --> 00:04:31.166 anemia is a related disease. 71 00:04:31.300 --> 00:04:35.500 But the symptoms and presentation of the patient 72 00:04:35.500 --> 00:04:39.633 will be different relative to other plasma cell myeloma. 73 00:04:40.866 --> 00:04:42.633 Solitary plasma cytometer. 74 00:04:42.633 --> 00:04:47.000 This is a collection of plasma cells, that, form a mass 75 00:04:47.000 --> 00:04:50.433 in the body and aren't necessarily in the liquid phase or in the blood. 76 00:04:51.633 --> 00:04:52.433 And then primary 77 00:04:52.433 --> 00:04:56.566 amyloidosis, refers to the amyloid deposits 78 00:04:56.566 --> 00:05:01.833 that can occur in patients with, any of these plasma cell disgraces. 79 00:05:03.000 --> 00:05:04.866 So there's a few others, but these are 80 00:05:04.866 --> 00:05:07.866 the main ones that I'll refer to and be talking about today. 81 00:05:09.733 --> 00:05:10.233 All right. 82 00:05:10.233 --> 00:05:11.500 So let's jump right in. 83 00:05:11.500 --> 00:05:14.400 I've got a couple of cases. 84 00:05:14.400 --> 00:05:16.266 So here's the first one. 85 00:05:16.266 --> 00:05:18.366 These are all real cases. 86 00:05:18.366 --> 00:05:21.166 And these are, from patients 87 00:05:21.166 --> 00:05:24.166 whose results I looked at myself. 88 00:05:24.500 --> 00:05:27.666 So first off, we have a 51 year old man. 89 00:05:28.733 --> 00:05:34.100 And he originally presented to the emergency department back in May of 2023. 90 00:05:34.533 --> 00:05:37.266 And this was brought on by, 91 00:05:37.266 --> 00:05:40.566 kind of worsening cognitive changes. 92 00:05:40.566 --> 00:05:45.800 So what that means is, over time, he had noticed he was getting more forgetful. 93 00:05:45.800 --> 00:05:48.800 He wasn't quite as efficient at doing, you know, his regular, 94 00:05:48.866 --> 00:05:51.233 regular daily activities. 95 00:05:51.233 --> 00:05:55.166 Specifically, he mentioned, you know, getting dressed or speaking, 96 00:05:55.233 --> 00:05:56.533 running errands. 97 00:05:56.533 --> 00:06:00.133 And he also had, some changes in balance. 98 00:06:00.133 --> 00:06:03.033 So you know, being unsure on his feet. 99 00:06:03.033 --> 00:06:06.033 And his wife had noticed some of these things as well. 100 00:06:06.433 --> 00:06:09.666 And originally, they didn't think much about it 101 00:06:09.666 --> 00:06:13.166 because you know, he didn't have much of a past medical history. 102 00:06:13.166 --> 00:06:17.733 He was pretty healthy guy otherwise hadn't really changed any medications. 103 00:06:17.733 --> 00:06:21.633 So those are some of the things we we want to rule out to make sure, 104 00:06:21.633 --> 00:06:23.700 you know, this is caused by something else. 105 00:06:23.700 --> 00:06:25.066 It's easily modifiable. 106 00:06:26.333 --> 00:06:27.333 He mentioned that 107 00:06:27.333 --> 00:06:31.233 he works as a mechanical engineer, and, you know, it's fairly demanding job. 108 00:06:31.233 --> 00:06:34.233 And that's, initially what his wife attributed to, 109 00:06:34.700 --> 00:06:38.433 these symptoms was it was just, you know, he was working a lot and, 110 00:06:39.133 --> 00:06:43.266 you know, thought he was getting tired and having some of these issues 111 00:06:43.266 --> 00:06:46.266 because you know, work was tough and 112 00:06:46.833 --> 00:06:48.333 so they didn't really do much about it. 113 00:06:48.333 --> 00:06:51.800 But, they, they noticed that, they, 114 00:06:51.800 --> 00:06:56.166 they went on a vacation and these symptoms really persisted. 115 00:06:56.166 --> 00:06:58.333 And even got worse during that vacation. 116 00:06:58.333 --> 00:07:03.066 So it was really after they got home from that vacation is when they came 117 00:07:03.066 --> 00:07:06.400 to the hospital and said, hey, we think there's something wrong there. 118 00:07:06.400 --> 00:07:09.400 This is this is weird. 119 00:07:09.766 --> 00:07:12.000 And again, just thinking 120 00:07:12.000 --> 00:07:16.600 kind of about the way we approach, patients in the clinic, wanted to see 121 00:07:16.600 --> 00:07:20.566 if there was any history of any sort of diseases or things 122 00:07:20.566 --> 00:07:22.466 that could point us in the right direction. 123 00:07:22.466 --> 00:07:24.033 We didn't have any of that. 124 00:07:24.033 --> 00:07:27.033 He didn't mention that he had lost quite a bit of weight. 125 00:07:27.233 --> 00:07:30.900 In a relatively short amount of time and, 126 00:07:31.100 --> 00:07:35.233 included about 15 pounds in the past two months. And, 127 00:07:36.433 --> 00:07:37.666 the follow up 128 00:07:37.666 --> 00:07:40.833 question that we always want to ask is, well, were you trying to lose weight? 129 00:07:41.833 --> 00:07:43.533 And if they are, that's something else. 130 00:07:43.533 --> 00:07:46.366 But if they're not trying and they're losing weight, that's concerning. 131 00:07:46.366 --> 00:07:49.366 So these these are kind of the things we think about, 132 00:07:49.433 --> 00:07:52.433 when we see the patient in the clinic. 133 00:07:52.933 --> 00:07:56.933 So with this story, we wanted to see, 134 00:07:58.233 --> 00:08:00.900 what was going on. 135 00:08:00.900 --> 00:08:04.900 So as part of the visit, the physician will do a clinical exam 136 00:08:05.366 --> 00:08:10.700 or a physical exam just to see if we can glean any information from that. 137 00:08:10.900 --> 00:08:13.000 That all came back normal. 138 00:08:13.000 --> 00:08:16.533 So we decided to order quite a few tests. 139 00:08:16.666 --> 00:08:19.133 And this is not infrequent. 140 00:08:19.133 --> 00:08:24.733 In the emergency department, especially where your differential is very broad. 141 00:08:25.033 --> 00:08:27.700 So you have to kind of start out broad. 142 00:08:27.700 --> 00:08:33.366 And then using testing, we can get more specific and narrow down our diagnosis. 143 00:08:35.566 --> 00:08:36.933 So kind of 144 00:08:36.933 --> 00:08:40.666 our broad testing that we started with was a CBC, 145 00:08:40.933 --> 00:08:43.866 CMP troponin. 146 00:08:43.866 --> 00:08:48.000 TSH, for thyroid function, urine analysis. 147 00:08:48.400 --> 00:08:53.566 He also got 12 lead EKG and, CT head imaging, 148 00:08:54.633 --> 00:08:56.100 and CT. 149 00:08:56.100 --> 00:08:59.733 So quite, quite a big workup, casting a broad net. 150 00:09:01.600 --> 00:09:04.600 So this is, it 151 00:09:04.833 --> 00:09:08.200 these are some of the results that we got back first. 152 00:09:08.800 --> 00:09:10.066 Just a quick glance. 153 00:09:10.066 --> 00:09:14.000 You can see there's a number of flags next to, quite a few of these values. 154 00:09:14.000 --> 00:09:19.166 So that, gets our suspicions up that, the, something's going on 155 00:09:19.833 --> 00:09:22.833 as if we weren't suspicious already. 156 00:09:24.200 --> 00:09:25.100 And then. 157 00:09:25.100 --> 00:09:30.800 So this is our CMP, number of chemistry tests, and then also our CBC, 158 00:09:31.166 --> 00:09:34.833 where we're evaluating, blood cells and, 159 00:09:35.500 --> 00:09:39.333 trying to get us pointed in the right direction. 160 00:09:41.133 --> 00:09:43.200 So I'm just going to highlight a few of these. 161 00:09:43.200 --> 00:09:46.100 You'll notice is sodium is, very low. 162 00:09:46.100 --> 00:09:48.900 And that's always concerning. 163 00:09:48.900 --> 00:09:50.766 Not really a specific finding. 164 00:09:50.766 --> 00:09:53.766 There's a number of things that can cause hyponatremia. 165 00:09:54.066 --> 00:09:57.300 But when we see it that low, that gets us concerned, 166 00:09:57.933 --> 00:09:59.433 for something that's going on. 167 00:09:59.433 --> 00:10:04.066 And it can also lead to other diseases, from having your sodium that low. 168 00:10:04.933 --> 00:10:08.933 His bun, Bun and creatinine were also elevated. 169 00:10:08.933 --> 00:10:14.433 So these are, two tests we look at for, kidney disease. 170 00:10:14.766 --> 00:10:18.333 So both of these being elevated indicate 171 00:10:18.333 --> 00:10:21.466 that there is something going on with the kidneys. 172 00:10:23.700 --> 00:10:25.233 And then we noticed 173 00:10:25.233 --> 00:10:30.300 that his total protein is elevated, significantly above the reference 174 00:10:30.300 --> 00:10:35.433 range and, above the limit of reporting for this assay. 175 00:10:36.333 --> 00:10:38.800 So putting all that together 176 00:10:38.800 --> 00:10:41.233 and then looking at his, hemoglobin 177 00:10:41.233 --> 00:10:44.733 and so evaluating the red cells, the both of those are 178 00:10:46.233 --> 00:10:48.866 pretty low. 179 00:10:48.866 --> 00:10:51.366 He's getting almost to the point where we would be 180 00:10:51.366 --> 00:10:54.366 considering, blood transfusion because it's low enough. 181 00:10:55.766 --> 00:10:56.500 All right. 182 00:10:56.500 --> 00:11:01.966 So moving forward, we had a few other tests 183 00:11:01.966 --> 00:11:06.533 that were still pending, as well as our imaging findings. 184 00:11:06.900 --> 00:11:10.233 So after performing the CBC, 185 00:11:10.233 --> 00:11:13.766 we wanted to break down the, white blood cell count. 186 00:11:14.233 --> 00:11:19.800 Just to see kind of what our ratios were or what sort of cells we were seeing. 187 00:11:19.800 --> 00:11:23.433 And most of these look, okay, you'll see lymphocytes 188 00:11:23.433 --> 00:11:26.366 or maybe slightly low, but that's a percentage. 189 00:11:26.366 --> 00:11:30.600 Really, when you see that, you also want to evaluate 190 00:11:30.600 --> 00:11:33.600 the absolute number, which I didn't put up here, but, 191 00:11:34.233 --> 00:11:37.400 this was the impression 192 00:11:37.400 --> 00:11:41.433 that was given by the radiologist from the CT head imaging. 193 00:11:41.866 --> 00:11:44.733 So no acute intracranial abnormality. 194 00:11:44.733 --> 00:11:46.166 So the brain looks okay. 195 00:11:46.166 --> 00:11:49.100 No intracranial hemorrhage or mass. 196 00:11:49.100 --> 00:11:49.833 Also good. 197 00:11:49.833 --> 00:11:52.833 Those are both acute and emergent situations. 198 00:11:53.200 --> 00:11:56.000 But the second line is important. 199 00:11:56.000 --> 00:11:59.733 So numerous lytic osseous lesions throughout the Calvary, skull base 200 00:11:59.733 --> 00:12:01.766 and upper cervical spine. 201 00:12:01.766 --> 00:12:04.233 So, what this looks like 202 00:12:04.233 --> 00:12:07.366 on imaging is kind of a, 203 00:12:08.733 --> 00:12:11.733 more cleared out space relative to the bone around it. 204 00:12:11.833 --> 00:12:14.466 And he had multiple of these present. 205 00:12:14.466 --> 00:12:18.466 So those are areas where the bone is being thinned out by some, 206 00:12:18.933 --> 00:12:21.433 some disease process. 207 00:12:21.433 --> 00:12:24.000 And the radiologists, when they see this, 208 00:12:24.000 --> 00:12:27.000 they'll give a differential diagnosis here. 209 00:12:27.033 --> 00:12:31.866 He stated, differential can include lytic metastasis. 210 00:12:31.866 --> 00:12:34.866 So you can think about things like prostate cancer. 211 00:12:35.200 --> 00:12:39.500 We'll often do this, multiple myeloma and lymphoma 212 00:12:40.000 --> 00:12:44.266 and then correlate with any history and consider an MRI. 213 00:12:45.200 --> 00:12:48.100 So MRI gives us a better look at the soft 214 00:12:48.100 --> 00:12:51.100 tissues and gives us some 215 00:12:52.033 --> 00:12:54.933 I won't say better resolution, but different 216 00:12:54.933 --> 00:12:58.100 look relative to our CT imaging. 217 00:12:58.100 --> 00:13:00.633 So we've got a number of findings here, 218 00:13:00.633 --> 00:13:04.033 thinking about we've got alterations on the CMP. 219 00:13:04.633 --> 00:13:07.833 The CBC is total protein is elevated, and now we've got, 220 00:13:08.233 --> 00:13:11.233 lytic lesions on imaging. 221 00:13:11.666 --> 00:13:14.600 So in the context of all these things, 222 00:13:14.600 --> 00:13:18.300 I'm sure the, physician in the emergency department 223 00:13:18.300 --> 00:13:22.533 was getting pointed towards a couple more specific diagnoses. 224 00:13:23.033 --> 00:13:26.366 And just for some of the other tests that, good order. 225 00:13:26.366 --> 00:13:30.033 There was a mild elevation in troponin, which may indicate 226 00:13:30.366 --> 00:13:31.900 you know, some strain on heart. 227 00:13:33.333 --> 00:13:36.333 All the other tests that were ordered were within normal range. 228 00:13:36.333 --> 00:13:40.666 So things like the TSH and the urinalysis all came back normal. 229 00:13:42.166 --> 00:13:45.633 So because of all these findings, 230 00:13:45.933 --> 00:13:49.366 he was admitted to the hospital, for additional workup. 231 00:13:52.300 --> 00:13:53.600 And just want to point out here 232 00:13:53.600 --> 00:13:57.633 that, you'll notice the plasma cell percentage is increased. 233 00:13:57.933 --> 00:13:59.900 But there's no reference range there. 234 00:13:59.900 --> 00:14:04.066 And that is because in normal, healthy individuals, 235 00:14:04.066 --> 00:14:09.666 we do not expect to see plasma cells circulating in the peripheral blood. 236 00:14:09.966 --> 00:14:12.600 So having any number there is concerning. 237 00:14:12.600 --> 00:14:15.866 But where he's got over 20%. 238 00:14:16.600 --> 00:14:21.766 And that is also, that that's going to piqued the interest of the physicians. 239 00:14:21.766 --> 00:14:24.766 Seeing him clinically. 240 00:14:25.033 --> 00:14:29.733 So here is the table for, when we're thinking about myeloma. 241 00:14:29.733 --> 00:14:34.200 And there's, a number of criteria that go into making that diagnosis, 242 00:14:34.200 --> 00:14:37.633 some of which we've already seen from the tests that have been ordered. 243 00:14:38.366 --> 00:14:41.900 And as I mentioned earlier, you can think of some of these things 244 00:14:41.900 --> 00:14:43.333 as kind of on a spectrum. 245 00:14:43.333 --> 00:14:47.200 So mGUS, monoclonal come up the undetermined significance 246 00:14:47.533 --> 00:14:51.433 kind of on the one end of the spectrum where all we're seeing 247 00:14:51.433 --> 00:14:55.233 is laboratory evidence of a, monoclonal process. 248 00:14:55.633 --> 00:14:59.166 But, the patient is a symptomatic and doesn't have the evidence 249 00:14:59.166 --> 00:15:01.000 of and organ damage. 250 00:15:01.000 --> 00:15:05.233 Smoldering myeloma a little further along the the spectrum 251 00:15:06.000 --> 00:15:10.066 where we've got laboratory evidence, but there's still 252 00:15:11.800 --> 00:15:13.733 no, clinical 253 00:15:13.733 --> 00:15:16.833 symptoms or, and organ damage being seen. 254 00:15:16.833 --> 00:15:21.400 And then multiple myeloma or plasma cell myeloma is when you've got 255 00:15:21.400 --> 00:15:26.000 all the criteria from smoldering or non mGUS, 256 00:15:26.733 --> 00:15:28.633 non mGUS, 257 00:15:28.633 --> 00:15:32.733 and then there is symptoms, evidence of and organ damage and some of these 258 00:15:32.733 --> 00:15:36.033 other findings that I'll get into a little later on in this talk. 259 00:15:39.533 --> 00:15:44.000 So I've talked a little bit about s PAP. 260 00:15:44.100 --> 00:15:45.733 So protein electrophoresis. 261 00:15:45.733 --> 00:15:49.833 So I wanted to just kind of break down real quick 262 00:15:49.833 --> 00:15:54.433 what we are expecting to see and what some of these things mean. 263 00:15:54.433 --> 00:15:59.533 So basically, this is a way to take someone's blood 264 00:15:59.533 --> 00:16:04.833 and evaluate all the different proteins that are circulating in the serum. 265 00:16:05.333 --> 00:16:11.433 So traditionally this was run on agarose or acetate gel. 266 00:16:11.733 --> 00:16:16.800 And an electric current was applied and based on the protein size and 267 00:16:17.733 --> 00:16:21.066 electrical charge, it would migrate through the gel 268 00:16:21.366 --> 00:16:24.500 and it would, make it would be stained 269 00:16:24.500 --> 00:16:27.966 and make a smear that looks similar to this, below the graph here. 270 00:16:28.333 --> 00:16:31.733 If you turned this smear, 90 degrees 271 00:16:32.233 --> 00:16:35.266 and, quantified it, you would get these peaks. 272 00:16:35.266 --> 00:16:38.633 So this is, this is a stone called normal. 273 00:16:38.733 --> 00:16:41.633 Serum protein electrophoresis. 274 00:16:41.633 --> 00:16:43.633 This is what we would expect to see. 275 00:16:43.633 --> 00:16:47.800 So you'll see albumin is a very large spike. 276 00:16:48.300 --> 00:16:52.700 This because it's the most abundant protein in, the serum. 277 00:16:53.133 --> 00:16:57.033 And it also migrates the farthest because it is also very small 278 00:16:57.033 --> 00:16:58.433 and negatively charged. 279 00:16:58.433 --> 00:17:01.533 So it moves easily through the gel towards the anode. 280 00:17:01.966 --> 00:17:05.666 And then you get other proteins of different sizes that will migrate 281 00:17:05.666 --> 00:17:07.433 to these different regions. 282 00:17:07.433 --> 00:17:12.000 There's a number of proteins present in the blood, and some of them get 283 00:17:12.000 --> 00:17:16.533 their names based on the different regions they migrate to. 284 00:17:16.533 --> 00:17:20.133 So for example, in the alpha one region, your 285 00:17:20.366 --> 00:17:23.400 is where alpha one lipoprotein will migrate. 286 00:17:23.966 --> 00:17:27.466 It's better known as HDL or good cholesterol. 287 00:17:28.166 --> 00:17:32.466 You also get, alpha one antitrypsin that migrates there, get alpha two 288 00:17:32.466 --> 00:17:37.033 macro globulin migrating to the alpha two region as well as have to globin. 289 00:17:37.600 --> 00:17:42.200 And then within the beta region, often now we can get a little better resolution 290 00:17:42.200 --> 00:17:45.200 where you'll actually see two peaks in the region. 291 00:17:45.400 --> 00:17:49.233 But you get proteins like transferrin and fibrinogen, as well 292 00:17:49.233 --> 00:17:52.933 as, C3 complement that will migrate to the beta region. 293 00:17:53.533 --> 00:17:55.600 And then down here in the gamma reach. 294 00:17:55.600 --> 00:18:00.900 And this is where we exit back to see, pretty much all of our immunoglobulins. 295 00:18:01.300 --> 00:18:04.166 And normally there should be a nice kind of, 296 00:18:04.166 --> 00:18:07.166 smooth, sloping, broad based hill. 297 00:18:07.566 --> 00:18:11.200 Our polyclonal peak, is how we think of that. 298 00:18:12.300 --> 00:18:13.966 As I said, 299 00:18:13.966 --> 00:18:16.966 this was traditionally done in gel. 300 00:18:17.100 --> 00:18:20.900 But these days it's performed by capillary electrophoresis. 301 00:18:20.900 --> 00:18:23.500 And I'll discuss that a little bit. 302 00:18:23.500 --> 00:18:26.500 As we go forward. 303 00:18:27.500 --> 00:18:31.366 So what we're looking for in cases of a plasma 304 00:18:31.366 --> 00:18:35.000 cell desecration is what we call a monoclonal protein spike. 305 00:18:35.366 --> 00:18:40.666 So if you compare these graphs to what, the, that last graph 306 00:18:40.666 --> 00:18:44.900 was where we had a nice, smooth, broad base hill in the gamma region. 307 00:18:45.333 --> 00:18:46.700 We're not seeing that here. 308 00:18:46.700 --> 00:18:49.666 We're seeing a nice big spike. 309 00:18:49.666 --> 00:18:54.466 Hence the name m spike is how we refer to these, 310 00:18:55.066 --> 00:18:58.100 and these are produced by, 311 00:18:59.100 --> 00:19:01.300 monoclonal plasma cells. 312 00:19:01.300 --> 00:19:04.300 So you can think of them as plasma cells that have, 313 00:19:05.133 --> 00:19:08.633 are starting to behave badly, and they just replicate. 314 00:19:08.633 --> 00:19:12.433 And because it's the same type of cell that's being cloned, 315 00:19:12.800 --> 00:19:15.800 they all produce the same type of immunoglobulin. 316 00:19:16.066 --> 00:19:18.933 And because it's just one type of immunoglobulin, 317 00:19:18.933 --> 00:19:21.333 they're all going to migrate to the same spot. 318 00:19:21.333 --> 00:19:24.833 That's why we get a big, spike in 319 00:19:24.833 --> 00:19:28.000 just this one area, because they're all roughly the same size, 320 00:19:28.266 --> 00:19:32.300 and the height of the spike correlates to the quantity. 321 00:19:32.966 --> 00:19:37.833 So albumin similarly, this is the normal finding creates this spike. 322 00:19:37.833 --> 00:19:40.400 But because albumin is that 323 00:19:40.400 --> 00:19:44.100 the same size and charge, they all migrate to the same spot. 324 00:19:46.666 --> 00:19:49.666 This one here in, 325 00:19:50.000 --> 00:19:53.100 graph A is very large. 326 00:19:53.266 --> 00:19:58.366 We always test the total protein, and then we can quantify the area 327 00:19:58.366 --> 00:20:04.100 under the craft to give us a total value, in grams per deciliter. 328 00:20:04.433 --> 00:20:08.433 So in this case, this one is over three grams per deciliter. 329 00:20:08.433 --> 00:20:11.333 That's pretty sizable. But they don't always have to be that big. 330 00:20:11.333 --> 00:20:15.000 You can have small ones as people are developing this disease. 331 00:20:15.333 --> 00:20:20.900 So for example in graph B the m spike is only 0.59g per deciliter. 332 00:20:21.733 --> 00:20:25.966 And you can see these spikes in almost all of the plasma cell disgraces. 333 00:20:26.300 --> 00:20:28.933 You'll see this in mGUS. 334 00:20:28.933 --> 00:20:32.800 That's when we see the spike, but no clinical symptoms. 335 00:20:33.433 --> 00:20:38.733 That's why it's called, monoclonal, gamma apathy of undetermined 336 00:20:38.733 --> 00:20:42.066 significance because we can see evidence that something's going on. 337 00:20:42.066 --> 00:20:45.066 But clinically, we don't see evidence. 338 00:20:45.366 --> 00:20:51.466 And then, just as I mentioned, you can see these in bone plasma cell 339 00:20:51.466 --> 00:20:55.533 myeloma, Walden streams, macro globular anemia and smoldering myeloma, as well. 340 00:20:57.633 --> 00:21:01.533 Most frequently, we will see them down in the gamma region. 341 00:21:01.533 --> 00:21:04.933 As I mentioned, this is where most of our immunoglobulins migrate. 342 00:21:06.333 --> 00:21:08.633 However, the 343 00:21:08.633 --> 00:21:12.066 these are a, neoplastic process. And 344 00:21:13.233 --> 00:21:15.733 cancer and neoplasms don't always read the textbook. 345 00:21:15.733 --> 00:21:20.833 So, personally, I have seen them migrating into this kind of beta gamma 346 00:21:20.833 --> 00:21:24.066 region up into the beta region and even, 347 00:21:24.066 --> 00:21:27.066 occasionally up into the Alpha two region. 348 00:21:27.466 --> 00:21:31.000 And but far and away, you 349 00:21:31.000 --> 00:21:34.000 mostly see them down in this gamma region. 350 00:21:35.500 --> 00:21:36.233 So as I mentioned, 351 00:21:36.233 --> 00:21:40.233 most of this testing is done via capillary electrophoresis. 352 00:21:40.233 --> 00:21:45.200 So instead of migrating everything through a gel, 353 00:21:45.733 --> 00:21:50.200 the sample is actually added to a buffer and placed on the instrument. 354 00:21:50.200 --> 00:21:53.300 And then the instrument, 355 00:21:53.300 --> 00:21:57.866 picks up the solution and migrates it through a capillary. 356 00:21:57.933 --> 00:21:59.433 So you can see, 357 00:22:00.500 --> 00:22:02.666 and out at one end cap out at the other. 358 00:22:02.666 --> 00:22:07.000 But the difference is there's your, electrical field force and then the, 359 00:22:07.300 --> 00:22:11.266 migration of the actual fluid through the capillary. 360 00:22:11.666 --> 00:22:15.133 So as that solution is being moved through the, 361 00:22:15.733 --> 00:22:18.733 proteins at the different sizes and charges will, 362 00:22:19.233 --> 00:22:22.500 migrate towards the edge of the capillary 363 00:22:22.500 --> 00:22:25.500 where there are detectors and based on, 364 00:22:25.833 --> 00:22:29.133 where those proteins are detected, 365 00:22:29.133 --> 00:22:33.933 a protein graph will be drawn as the migration is occurring. 366 00:22:34.500 --> 00:22:39.766 So what this looks like in the real world is you can actually watch these proteins 367 00:22:39.800 --> 00:22:45.433 or these graphs being drawn as the migration is happening again. 368 00:22:45.833 --> 00:22:49.533 The the separation is based on electrical charge 369 00:22:49.533 --> 00:22:52.533 and electro osmotic flow. 370 00:22:53.333 --> 00:22:54.666 And this is, 371 00:22:54.666 --> 00:22:59.733 this is done in most of the large reference labs, 372 00:22:59.733 --> 00:23:04.666 some of the smaller community labs may still perform these on a gel. 373 00:23:05.133 --> 00:23:08.633 But more and more, we're seeing them done by capillary electrophoresis, 374 00:23:08.633 --> 00:23:12.566 especially in labs with, high volume and high throughput. 375 00:23:14.366 --> 00:23:16.133 All right, so now that we've 376 00:23:16.133 --> 00:23:19.500 got a little bit of context, let's go back to our clinical case. 377 00:23:19.933 --> 00:23:24.600 So based on his findings you remember he was admitted to the hospital. 378 00:23:24.900 --> 00:23:29.333 And there was suspicion for a monoclonal 379 00:23:29.333 --> 00:23:33.500 come up the so one of the first things we do 380 00:23:33.500 --> 00:23:36.933 to evaluate for that is we order an S PAP and IFB. 381 00:23:36.933 --> 00:23:40.766 So serum protein electrophoresis and immuno fixation electrophoresis. 382 00:23:41.200 --> 00:23:44.233 And I'll speak about the difference and why we use these in conjunction. 383 00:23:45.333 --> 00:23:48.900 So the Pep again is we're generating that curve. 384 00:23:48.900 --> 00:23:52.933 We're evaluating for all the proteins within the blood. 385 00:23:53.900 --> 00:23:57.166 And then comparing that against the reference interval. 386 00:23:57.166 --> 00:24:01.300 So for our patient hey, you can see he was a little low in albumin, 387 00:24:01.300 --> 00:24:04.633 but he was elevated, in the gamma region. 388 00:24:04.633 --> 00:24:09.433 So already there's something interesting going on. But 389 00:24:10.400 --> 00:24:13.700 just based on this information, you can say it's necessary. 390 00:24:13.700 --> 00:24:16.700 And, spike, there's he could, you know, 391 00:24:16.700 --> 00:24:19.700 he could be sick and, just have a lot of, 392 00:24:19.866 --> 00:24:22.600 antibodies floating around, 393 00:24:22.600 --> 00:24:26.100 in which case you'd get a large, 394 00:24:26.100 --> 00:24:30.066 still broad based, curve in the gamma region. 395 00:24:30.433 --> 00:24:33.833 But we also did the, 396 00:24:35.300 --> 00:24:37.466 here's an image of the graph. 397 00:24:37.466 --> 00:24:40.466 You can see there's a large spike there. 398 00:24:41.300 --> 00:24:44.300 And this is how we interpreted it. So, 399 00:24:45.066 --> 00:24:48.066 looking at the values in the graph together, 400 00:24:48.466 --> 00:24:51.900 we reported a monoclonal spike in the gamma region, 401 00:24:52.466 --> 00:24:57.066 and then, we performed, the ifI to characterize, 402 00:24:57.633 --> 00:25:00.566 what type of, 403 00:25:00.566 --> 00:25:03.000 basically immunoglobulin 404 00:25:03.000 --> 00:25:06.000 is being produced here. 405 00:25:08.966 --> 00:25:10.966 And I'll get into the, 406 00:25:10.966 --> 00:25:14.766 the iffy side and what those gels look like, coming up, 407 00:25:15.466 --> 00:25:19.900 in addition to the ESP, and if we also perform 408 00:25:19.900 --> 00:25:24.400 quantitative immunoglobulins, as you can see in his case, 409 00:25:24.400 --> 00:25:30.466 the IgG was significantly higher above our upper limit of normal. 410 00:25:30.866 --> 00:25:34.166 And the IGA and IGA were both decreased. 411 00:25:34.400 --> 00:25:38.266 So the way I like to think about this is there's some process going on 412 00:25:38.266 --> 00:25:42.733 that's just producing lots and lots and lots of IgG, which leaves, 413 00:25:43.233 --> 00:25:48.433 less material available to produce IGA and items. 414 00:25:52.900 --> 00:25:55.900 And then in conjunction with this testing, 415 00:25:56.966 --> 00:25:59.666 it's also recommended to perform serum free light chains. 416 00:25:59.666 --> 00:26:02.666 So I'll get into, what this means. 417 00:26:02.733 --> 00:26:06.500 But just to note right now, his kappa free 418 00:26:06.833 --> 00:26:11.066 pre light chain was significantly elevated relative to his lambda. 419 00:26:11.066 --> 00:26:15.000 So normally these should be produced, relatively close 420 00:26:15.266 --> 00:26:19.900 to the same amount or maybe up to 2 to 1, ratio. 421 00:26:19.900 --> 00:26:23.766 But as you can see here, the ratio in his case is significantly elevated 422 00:26:23.766 --> 00:26:25.100 above the normal. 423 00:26:25.100 --> 00:26:29.500 So we're getting a lot more lambda being or kappa being produced 424 00:26:29.766 --> 00:26:32.766 as opposed to lambda. 425 00:26:34.533 --> 00:26:37.700 So here are a few images of normal 426 00:26:37.700 --> 00:26:40.966 ifI gel gels. 427 00:26:41.933 --> 00:26:43.100 Excuse me. 428 00:26:43.100 --> 00:26:49.233 And we do these to really characterize what those m spikes are. 429 00:26:49.233 --> 00:26:52.933 So we know the m spikes are being produced by, 430 00:26:53.533 --> 00:26:56.533 monoclonal, plasma cells. 431 00:26:56.933 --> 00:26:59.933 Plasma cells job is to produce antibodies. 432 00:27:00.433 --> 00:27:04.366 And as you may recall, there's different types of antibodies. 433 00:27:04.366 --> 00:27:08.133 Most frequently is IG followed by an IPA. 434 00:27:08.533 --> 00:27:10.266 There's also IGD and it. 435 00:27:11.233 --> 00:27:14.233 But we think about those in different contexts. 436 00:27:14.733 --> 00:27:18.800 But this is what a normal IFB gel should look like. 437 00:27:18.800 --> 00:27:22.000 So we use antiserum to block out, 438 00:27:22.433 --> 00:27:25.566 the other types 439 00:27:25.900 --> 00:27:28.600 so we can quantify, or evaluate, 440 00:27:28.600 --> 00:27:33.766 each individual, isotype as well as the 441 00:27:33.766 --> 00:27:37.266 free like chains or, excuse me, just the light chains. 442 00:27:37.633 --> 00:27:40.533 So we use an anti sera and then stain against that. 443 00:27:40.533 --> 00:27:42.200 And in a normal healthy person 444 00:27:42.200 --> 00:27:45.366 you should see kind of this broad based smear in each of these. 445 00:27:45.366 --> 00:27:49.133 That means there's many different types of IgG being produced. 446 00:27:49.633 --> 00:27:51.200 Which makes sense. 447 00:27:51.200 --> 00:27:53.700 The body needs to fight off a lot of different things. 448 00:27:53.700 --> 00:27:59.733 So it needs different antibodies that are specific to each separate thing. 449 00:27:59.733 --> 00:28:01.866 It's attempting to fight off. 450 00:28:03.100 --> 00:28:04.233 These are done, 451 00:28:04.233 --> 00:28:07.233 in a similar way to, 452 00:28:09.166 --> 00:28:12.200 The s pep in which these are performed on a gel 453 00:28:12.200 --> 00:28:15.200 and these are still performed on gel for the most part. 454 00:28:15.200 --> 00:28:19.533 And the patient serum is diluted 455 00:28:19.533 --> 00:28:25.266 and then placed on or placed into combs, which are then applied to the gel. 456 00:28:25.266 --> 00:28:28.000 That's why we get them in these nice bands. 457 00:28:28.000 --> 00:28:32.866 And then a, an electrical charge is run through the gel and you'll create, 458 00:28:33.266 --> 00:28:36.266 this separation, this, 459 00:28:36.833 --> 00:28:40.533 band on the far left of each of these gels 460 00:28:41.033 --> 00:28:44.600 correlates to the band we would see on an S pep. 461 00:28:44.600 --> 00:28:50.766 So this is just a, the anterior use here is, nonspecific. 462 00:28:50.766 --> 00:28:52.066 It's just against protein. 463 00:28:52.066 --> 00:28:55.066 So if you turned this on its side, quantify it, 464 00:28:55.066 --> 00:28:59.466 it would look just like, one of those, s Pep graphs. 465 00:29:02.100 --> 00:29:06.966 So, as I mentioned, we use this to characterize, 466 00:29:07.100 --> 00:29:09.566 both the heavy and light chains. 467 00:29:09.566 --> 00:29:12.566 When we detect, m spikes. 468 00:29:13.700 --> 00:29:15.300 Now, most of the time, 469 00:29:15.300 --> 00:29:19.733 when these, monoclonal proteins are being produced, 470 00:29:19.900 --> 00:29:24.433 the heavy chain will be produced 471 00:29:24.433 --> 00:29:27.433 in similar numbers to the light chain. 472 00:29:27.600 --> 00:29:32.166 I'll get into this a little bit later, but, all antibodies, 473 00:29:32.366 --> 00:29:36.333 are composed of two heavy chains and two 474 00:29:36.333 --> 00:29:40.300 light chains that are bound together by disulfide bonds. 475 00:29:42.433 --> 00:29:46.066 And they, they should be produced in similar numbers 476 00:29:46.066 --> 00:29:49.066 because they work as a unit. 477 00:29:49.233 --> 00:29:53.200 In these diseases, though, will sometimes see that the, light 478 00:29:53.200 --> 00:29:56.200 chains are overproduced relative to the heavy chain. 479 00:29:56.433 --> 00:29:57.633 And occasionally we'll see that 480 00:29:57.633 --> 00:30:00.633 only heavy chains are only light chains are being produced. 481 00:30:00.800 --> 00:30:04.800 And so using the if we can determine if there's a heavy chain 482 00:30:04.800 --> 00:30:09.166 with an associated light chain, or if there's only a heavy chain 483 00:30:09.166 --> 00:30:13.700 or only a light chain, and so we can get a better idea of what is being produced. 484 00:30:15.533 --> 00:30:19.033 Now we can also perform an IFC on urine. 485 00:30:20.033 --> 00:30:22.500 And that is what we do to, 486 00:30:22.500 --> 00:30:25.300 evaluate for excess free light chain. 487 00:30:25.300 --> 00:30:32.066 So when you've got too much protein in the serum, as it's filtered 488 00:30:32.066 --> 00:30:36.933 in the kidneys, those light chains can cause damage to the glomerular. 489 00:30:37.133 --> 00:30:40.066 And so you'll start to lose protein out in the urine. 490 00:30:40.066 --> 00:30:44.066 That's why we can test on urine and detect some of these, because they're losing, 491 00:30:44.466 --> 00:30:47.466 these proteins in their urine. 492 00:30:48.233 --> 00:30:51.233 So this is just to look at, 493 00:30:51.733 --> 00:30:54.733 and the Sabia instrument, which is one of the instruments 494 00:30:54.733 --> 00:30:58.366 used to generate, these IFB 495 00:30:58.533 --> 00:31:02.300 gels, you can see the little wells where the, 496 00:31:02.300 --> 00:31:07.800 patient, diluted sample is applied and then these are little combs. 497 00:31:07.800 --> 00:31:12.333 So the patient sample will wick through and that's applied onto the gel. 498 00:31:12.733 --> 00:31:14.333 So you can see the underlying gel. 499 00:31:14.333 --> 00:31:17.233 This is what it looks like before the migration happens. 500 00:31:19.166 --> 00:31:20.333 After 501 00:31:20.333 --> 00:31:24.733 it's done migrating it will be, stained and then dried. 502 00:31:24.733 --> 00:31:26.900 And so you can handle it. 503 00:31:26.900 --> 00:31:29.833 Look at it, 504 00:31:29.833 --> 00:31:32.200 look at it in conjunction with the, 505 00:31:32.200 --> 00:31:35.200 the ESP. 506 00:31:36.000 --> 00:31:37.166 All right. Jumping back. 507 00:31:37.166 --> 00:31:41.433 So now you can see what the if you look like for our patient 508 00:31:41.900 --> 00:31:45.000 instead of a nice, polish 509 00:31:45.033 --> 00:31:48.033 smear that we would hope to see. 510 00:31:48.266 --> 00:31:52.433 Instead, we see that there's a very strong band 511 00:31:52.533 --> 00:31:55.533 all migrating, in the gamma region. 512 00:31:55.633 --> 00:32:00.866 And, we can see that he's producing an IG 513 00:32:01.366 --> 00:32:04.666 heavy chain with an associated Kappa light chain. 514 00:32:04.666 --> 00:32:10.100 So, we presume they are associated because they are migrating 515 00:32:10.100 --> 00:32:12.166 at the same level. 516 00:32:12.166 --> 00:32:14.833 Occasionally you can see light 517 00:32:14.833 --> 00:32:19.533 chains at a different level, and then, you know that they're not associated 518 00:32:19.533 --> 00:32:24.133 with their heavy chain because they're not migrating at the same spot. 519 00:32:26.733 --> 00:32:27.033 All right. 520 00:32:27.033 --> 00:32:32.100 As I mentioned, this is just a quick review of our antibody structure. 521 00:32:32.533 --> 00:32:36.600 So you can see here you've got your heavy chains 522 00:32:37.200 --> 00:32:41.100 and there's two of them, and then your light chains are attached on the outside. 523 00:32:41.100 --> 00:32:45.700 And then your variable region are these domains at the end. 524 00:32:45.700 --> 00:32:49.566 And that is what gives specificity to their antigens. 525 00:32:50.700 --> 00:32:53.700 These are all, 526 00:32:53.766 --> 00:32:55.166 produced first by B cells. 527 00:32:55.166 --> 00:33:00.333 So the AGM specifically and then after the cells 528 00:33:00.333 --> 00:33:04.233 undergo isotype switching, and produce plasma cells, 529 00:33:05.800 --> 00:33:08.500 they'll start to produce these other isotype. 530 00:33:08.500 --> 00:33:12.433 So as I mentioned, GM and A are the most frequent 531 00:33:12.800 --> 00:33:15.800 followed by IGD and IgG. 532 00:33:16.600 --> 00:33:19.166 And what the heavy chain is really 533 00:33:19.166 --> 00:33:22.166 what determines the isotype. 534 00:33:23.466 --> 00:33:27.700 So you can see like the E has an extra segment here. 535 00:33:28.900 --> 00:33:31.233 And then the light chain portions 536 00:33:31.233 --> 00:33:34.233 are fairly similar across them. 537 00:33:38.633 --> 00:33:39.066 Okay. 538 00:33:39.066 --> 00:33:43.966 So I mentioned that we do testing in urine, and that, we, 539 00:33:44.600 --> 00:33:47.833 can perform urine if the reason we do this 540 00:33:47.866 --> 00:33:50.866 is we're looking for monoclonal proteins in the urine. 541 00:33:50.866 --> 00:33:54.900 And, when these monoclonal, light 542 00:33:54.900 --> 00:33:58.266 chains are referred to as Bence Jones protein. 543 00:33:58.833 --> 00:34:01.933 Again, this is caused by dysregulation of the heavy and light chains 544 00:34:02.200 --> 00:34:05.766 where the light chain, portions are overproduced. 545 00:34:06.700 --> 00:34:09.833 And these free floating light chains that are unbound to heavy 546 00:34:09.833 --> 00:34:13.566 chain, they can cause, damage to the kidney. 547 00:34:13.566 --> 00:34:16.400 And that's why we can detect them in the urine. 548 00:34:16.400 --> 00:34:19.000 In addition to the IFB, 549 00:34:19.000 --> 00:34:22.000 we can also perform urine protein electrophoresis. 550 00:34:22.000 --> 00:34:24.833 It works the same way as serum protein electrophoresis. 551 00:34:25.800 --> 00:34:31.500 And, this is included in the workup. 552 00:34:31.500 --> 00:34:36.566 So, for most, plasma cell disgraces, 553 00:34:37.233 --> 00:34:40.133 you may remember in our patient that he had, 554 00:34:40.133 --> 00:34:43.133 renal, 555 00:34:43.233 --> 00:34:44.433 injury going on. 556 00:34:44.433 --> 00:34:48.933 We saw that, based on his CMP, he had an elevated B1 and creatinine. 557 00:34:49.900 --> 00:34:54.600 So we detect Bence Jones proteins in about two thirds myeloma cases. 558 00:34:55.166 --> 00:34:57.433 So a fairly common. 559 00:34:57.433 --> 00:35:02.066 And the other thing that you'll find in the lab is that, 560 00:35:02.066 --> 00:35:07.700 the ratio of capital lambda free light chains, will also be to range. 561 00:35:07.700 --> 00:35:12.600 So, either significantly above the normal ratio, 562 00:35:12.600 --> 00:35:17.566 in which case it would be an excess of capillary chains or 563 00:35:17.566 --> 00:35:21.366 significantly below the normal range in which, 564 00:35:21.366 --> 00:35:25.233 that would mean a, an abundance of lambda three light chains. 565 00:35:26.066 --> 00:35:29.133 Important to know is that patients with underlying kidney 566 00:35:29.133 --> 00:35:32.233 disease from other causes have a slightly different range, 567 00:35:32.233 --> 00:35:36.533 because their kidneys don't function quite as well at baseline. 568 00:35:36.533 --> 00:35:40.466 So you have to look at these in context of their other diseases. 569 00:35:42.566 --> 00:35:43.033 Okay. 570 00:35:43.033 --> 00:35:47.966 So as I mentioned we can perform urine protein electrophoresis as well. 571 00:35:48.333 --> 00:35:53.266 So we did that on a 24 hour urine collection. 572 00:35:53.666 --> 00:35:56.300 You can see he's losing 573 00:35:56.300 --> 00:35:59.400 quite a bit of protein in the urine. 574 00:35:59.400 --> 00:36:02.400 Much, much, much higher than, normal. 575 00:36:02.966 --> 00:36:07.100 And you can also see, based on our testing, there's a large, 576 00:36:07.566 --> 00:36:10.433 m spike on the UPB 577 00:36:10.433 --> 00:36:14.700 and as well as bands in the, on the if you. 578 00:36:14.700 --> 00:36:17.133 So you can see the expected and G. 579 00:36:17.133 --> 00:36:18.733 Kappa band here. 580 00:36:18.733 --> 00:36:22.533 But then there's also, this large deposit or 581 00:36:22.966 --> 00:36:27.500 a large amount of free light chain that's unassociated with a heavy chain. 582 00:36:27.500 --> 00:36:30.500 So the this correlates to free kappa, 583 00:36:30.733 --> 00:36:33.233 light chains in his urine. 584 00:36:33.233 --> 00:36:35.700 And this is the interpretation that we gave for him. 585 00:36:35.700 --> 00:36:38.100 But there's a monoclonal spike in the beta region. 586 00:36:38.100 --> 00:36:42.400 And in this case that correlates to this large, 587 00:36:43.833 --> 00:36:45.400 collection of, 588 00:36:45.400 --> 00:36:48.400 free kappa light chains. 589 00:36:48.633 --> 00:36:53.300 And we mentioned that here, there's a heavy IgG heavy chain 590 00:36:53.300 --> 00:36:56.500 associated with capillary chain and excess monoclonal free 591 00:36:56.500 --> 00:36:59.500 kappa light chains. 592 00:36:59.866 --> 00:37:01.833 So just a quick discussion 593 00:37:01.833 --> 00:37:05.133 about how we, do this testing. 594 00:37:05.133 --> 00:37:10.666 So we use, instruments, that perform inflammatory. 595 00:37:10.933 --> 00:37:15.833 This is based on this is how we quantify the, 596 00:37:15.833 --> 00:37:19.300 different amounts of proteins, in the serum. 597 00:37:19.566 --> 00:37:22.333 So, for example, the light chains, they're added 598 00:37:22.333 --> 00:37:25.333 to a little cuvette and, 599 00:37:25.866 --> 00:37:29.333 with a buffer and produce, immune complexes. 600 00:37:29.333 --> 00:37:32.700 And then light is passed through that cuvette. 601 00:37:32.966 --> 00:37:35.133 And based on the way the light is scattered, 602 00:37:35.133 --> 00:37:38.366 we can quantify the amount of protein present. 603 00:37:38.933 --> 00:37:43.633 This method is used, to also quantitate other, 604 00:37:44.033 --> 00:37:48.500 the other immunoglobulins as well as other serum proteins. 605 00:37:49.566 --> 00:37:53.066 So it's important to distinguish 606 00:37:53.066 --> 00:37:57.633 this method from, turbid imagery, which is a different, 607 00:37:58.233 --> 00:38:02.533 test method that can be used to also quantify proteins. 608 00:38:02.533 --> 00:38:05.533 So in this case we're using scattered 609 00:38:06.000 --> 00:38:10.466 the light scatter to evaluate that versus turbid imagery. 610 00:38:10.866 --> 00:38:16.333 Similarly the patient serum is added to a cuvette, 611 00:38:16.633 --> 00:38:19.733 and generates these immune complexes. 612 00:38:19.733 --> 00:38:23.200 And then light is, transmitted through the solution. 613 00:38:23.200 --> 00:38:26.400 And based on the amount of light that is transmitted, 614 00:38:26.400 --> 00:38:30.100 it will, quantify the amount of protein present. 615 00:38:30.100 --> 00:38:33.766 So turban inventory is based on transmittance 616 00:38:34.000 --> 00:38:37.033 versus and inflammatory is based on light scatter. 617 00:38:37.400 --> 00:38:41.133 These are both methods that are used. 618 00:38:41.766 --> 00:38:45.466 To, to really quantify, 619 00:38:46.833 --> 00:38:50.500 the amount of protein of interest. 620 00:38:52.600 --> 00:38:54.800 So this is just a quick recap, 621 00:38:54.800 --> 00:38:58.000 of the different, test 622 00:38:58.566 --> 00:39:03.433 methods we've used in this gentleman's workup for his disease. 623 00:39:04.400 --> 00:39:05.133 And what we 624 00:39:05.133 --> 00:39:09.333 do in the laboratory is we take all these different results 625 00:39:09.333 --> 00:39:15.133 from these different methods, and we look at them in conjunction and in context 626 00:39:16.066 --> 00:39:19.833 and generate a, result interpretation 627 00:39:20.333 --> 00:39:23.333 based on all these findings. 628 00:39:26.433 --> 00:39:28.100 So I'll, I'll, 629 00:39:28.100 --> 00:39:33.066 get back to the resolution on, the first clinical case, 630 00:39:33.066 --> 00:39:37.166 but I just wanted to go through a second clinical case here 631 00:39:37.166 --> 00:39:40.366 just to give context, and differentiate. 632 00:39:40.833 --> 00:39:45.200 So this is a 46 year old male, with a history of type 633 00:39:45.200 --> 00:39:49.400 two diabetes for ten years and has stage four chronic kidney disease. 634 00:39:49.866 --> 00:39:52.433 So he was to the point where 635 00:39:52.433 --> 00:39:55.666 he was probably needing a kidney transplant. 636 00:39:55.666 --> 00:39:59.300 So in July of 2022, during his workup, 637 00:39:59.500 --> 00:40:02.300 for a potential transplant, 638 00:40:02.300 --> 00:40:07.366 they ordered a bunch of testing, to see if he was a good candidate. 639 00:40:07.366 --> 00:40:08.733 He didn't have any complaints. 640 00:40:08.733 --> 00:40:11.733 No symptoms, normal physical exam findings. 641 00:40:12.200 --> 00:40:16.000 And so, as part of this workup and aspect by biopsy and fruit, 642 00:40:16.266 --> 00:40:19.766 serum free light chains were ordered, as well as some of our, 643 00:40:19.866 --> 00:40:22.766 more, more, more common 644 00:40:22.766 --> 00:40:25.766 tests, including the, CPK and CMP. 645 00:40:25.766 --> 00:40:30.033 As you can see, mostly normal hemoglobin is a little bit low, 646 00:40:30.333 --> 00:40:33.733 not unexpected in the context of chronic kidney disease. 647 00:40:33.733 --> 00:40:38.200 And his CMP at that time was also normal, except for an elevated Bun. 648 00:40:38.200 --> 00:40:42.333 And regarding also to be expected in, chronic kidney disease. 649 00:40:43.733 --> 00:40:47.033 So the Pep and IEP were performed. 650 00:40:47.333 --> 00:40:51.233 As you can see here, the there was an increase in the gamma region. 651 00:40:51.566 --> 00:40:53.533 And we detected in him a spike. 652 00:40:53.533 --> 00:40:57.200 So maybe not as dramatic as in, 653 00:40:57.200 --> 00:41:01.766 our previous case, but still distinct, from the background. 654 00:41:01.766 --> 00:41:04.800 And then on the, if he, 655 00:41:05.800 --> 00:41:09.400 we see he was producing a G, 656 00:41:10.733 --> 00:41:13.333 heavy chain with associated Kappa light chain, 657 00:41:13.333 --> 00:41:16.566 I'll tell you that, this is the most common one that is seen. 658 00:41:16.833 --> 00:41:20.800 But you can also get monoclonal proteins, producing IGA 659 00:41:20.800 --> 00:41:24.333 or IGF, and in rare instances, IGD 660 00:41:24.600 --> 00:41:28.933 and in, in and extremely rare instances, 661 00:41:28.933 --> 00:41:31.933 an IgG E heavy chain. 662 00:41:32.933 --> 00:41:38.200 So we also tested for kappa Lambda free light chains. 663 00:41:38.200 --> 00:41:42.466 You can see both of them are elevated relative to normal. 664 00:41:42.466 --> 00:41:46.400 But the ratio is still within the normal range. 665 00:41:46.400 --> 00:41:50.866 So still being produced kind of in the right, 666 00:41:50.866 --> 00:41:54.700 amounts relative to each other, but but too many on both sides. 667 00:41:55.066 --> 00:41:57.133 And then is quantitative immunoglobulins. 668 00:41:57.133 --> 00:42:00.133 You'll see the IgG is also increased. 669 00:42:00.133 --> 00:42:03.666 This is not surprising given, 670 00:42:03.666 --> 00:42:07.533 that we've got a monoclonal IgG m spike. 671 00:42:10.300 --> 00:42:13.033 So I wanted to touch 672 00:42:13.033 --> 00:42:16.933 real quickly on how the clinicians think about myeloma. 673 00:42:16.933 --> 00:42:21.633 And these are some of the clinical things and laboratory tests that they are 674 00:42:21.633 --> 00:42:26.466 looking for to make a diagnosis of, plasma cell myeloma. 675 00:42:27.166 --> 00:42:31.400 And they use this mnemonic, slim Krabbe 676 00:42:31.733 --> 00:42:36.300 to, keep in mind all the things they need to look for. 677 00:42:36.300 --> 00:42:41.333 So if there are, serum or excuse me 678 00:42:41.333 --> 00:42:45.266 if there's, greater than 60 cent plasma cells in the bone marrow. 679 00:42:45.800 --> 00:42:50.033 This obviously you need a bone marrow biopsy to evaluate 680 00:42:50.333 --> 00:42:55.466 if the free light chain ratio is above 100 or less than 0.1. 681 00:42:56.066 --> 00:42:59.633 And if there is one or more focal lesions on MRI. 682 00:43:00.066 --> 00:43:03.700 So these are some laboratory findings, 683 00:43:04.000 --> 00:43:06.700 that we can use to meet, 684 00:43:06.700 --> 00:43:09.700 criteria for myeloma. 685 00:43:09.933 --> 00:43:12.533 And these are all taken in conjunction 686 00:43:12.533 --> 00:43:15.733 with if there is a monoclonal protein present, 687 00:43:17.700 --> 00:43:19.833 also from the laboratory, 688 00:43:19.833 --> 00:43:23.966 if there is, significantly increased calcium. 689 00:43:24.100 --> 00:43:27.100 So in this table, it gets a little more specific, 690 00:43:27.433 --> 00:43:30.033 if there's renal insufficiency, anemia 691 00:43:30.033 --> 00:43:34.500 or lytic bone lesions, important to note is 692 00:43:34.500 --> 00:43:38.300 there is a small percentage of patients who will have non secretory disease. 693 00:43:38.300 --> 00:43:40.666 So they won't have an N spike. 694 00:43:40.666 --> 00:43:44.366 But they may have some of these other findings. 695 00:43:46.766 --> 00:43:50.700 So this is just a look at that table again. 696 00:43:51.266 --> 00:43:58.833 So this is what we would expect to see in a bone marrow aspirate. 697 00:43:58.833 --> 00:44:01.833 So these are the plasma cells right here. 698 00:44:01.833 --> 00:44:05.266 So, for any of these plasma cell disgraces, 699 00:44:05.266 --> 00:44:09.600 we expect to see an increased number of plasma cells within the bone marrow. 700 00:44:11.100 --> 00:44:17.866 So this is just an image of what bone marrow should look like. 701 00:44:17.933 --> 00:44:23.800 You've got your marrow elements, with intervening fat within the marrow space. 702 00:44:23.800 --> 00:44:27.733 And then the this is just, the bone within that space. 703 00:44:29.733 --> 00:44:30.800 Normal bone marrow 704 00:44:30.800 --> 00:44:33.800 biopsy should show trial in lineage matapos. 705 00:44:34.000 --> 00:44:38.933 So, you know, mega curious sites, other red cells and white cells, 706 00:44:39.033 --> 00:44:43.700 as they are maturing, with normal mass fat intermixed. 707 00:44:44.100 --> 00:44:48.866 What you'll see in an abnormal biopsy is that, the 708 00:44:49.700 --> 00:44:53.933 cellular percentage of the marrow is increased, so there's less fat 709 00:44:54.266 --> 00:44:59.766 and there's, significantly more of one cell type. 710 00:44:59.766 --> 00:45:02.766 So in this case, it's plasma cells. 711 00:45:03.100 --> 00:45:06.100 If we detect greater than 60%, then we can make 712 00:45:06.333 --> 00:45:09.366 a diagnosis of plasma cell myeloma. 713 00:45:10.600 --> 00:45:15.333 Going back to our table, if we detect an M spike, 714 00:45:15.333 --> 00:45:20.133 but we don't see increased monoclonal protein above three grams, and, 715 00:45:21.033 --> 00:45:24.633 plasma cells in the bone marrow are still less than 10%. 716 00:45:25.000 --> 00:45:29.600 That is criteria for mGUS as well as there's no kind of, 717 00:45:29.633 --> 00:45:34.133 clinical symptoms going on, such as, you know, increased calcium, renal 718 00:45:34.133 --> 00:45:38.000 insufficiency, anemia or bone lesions, smoldering, 719 00:45:38.000 --> 00:45:41.500 myeloma is when there's an M spike 720 00:45:41.500 --> 00:45:44.966 that is greater than three grams per deciliter. 721 00:45:45.833 --> 00:45:49.600 Or the clonal, 722 00:45:49.600 --> 00:45:53.100 plasma cells in the marrow are between 10 and 60%. 723 00:45:53.633 --> 00:45:57.500 And again, if it's above 60%, that means criteria for myeloma. 724 00:45:58.133 --> 00:46:00.433 Or if there's evidence of and organ damage. 725 00:46:00.433 --> 00:46:03.700 And that's what we're evaluating with these Krab features. 726 00:46:03.700 --> 00:46:08.400 So the calcium renal insufficiency, anemia and lytic bone diseases. 727 00:46:10.766 --> 00:46:12.066 All right. 728 00:46:12.066 --> 00:46:15.066 So this is just a test algorithm 729 00:46:15.366 --> 00:46:18.700 that is used when thinking about myeloma. 730 00:46:19.766 --> 00:46:21.733 And you can see testing begins 731 00:46:21.733 --> 00:46:24.866 with the ESP, ifI and serum kappa 732 00:46:25.433 --> 00:46:28.433 and lambda free light chain ratios. 733 00:46:28.633 --> 00:46:32.433 You'll notice here that the exam is separate. 734 00:46:32.433 --> 00:46:36.600 So, I mentioned that Walden streams macro globulin anemia. 735 00:46:36.600 --> 00:46:40.400 What we expect to see is an exam, heavy chain 736 00:46:40.833 --> 00:46:43.833 producing, monoclonal protein. 737 00:46:43.900 --> 00:46:46.066 And the reason we break these out is, 738 00:46:46.066 --> 00:46:49.066 symptomatically, they appear different. 739 00:46:49.766 --> 00:46:51.766 From other myeloma patients. 740 00:46:51.766 --> 00:46:55.266 So they'll have, symptoms of hyper hyper viscosity. 741 00:46:55.633 --> 00:46:59.900 They can have, stroke like symptoms based on just, 742 00:46:59.900 --> 00:47:01.800 just all this protein in their blood, 743 00:47:01.800 --> 00:47:04.800 really making it more viscous so it doesn't flow as well. 744 00:47:06.033 --> 00:47:10.433 This is kind of the rest of that table that outlines criteria 745 00:47:10.433 --> 00:47:14.266 for some of these other, plasma cell disgraces. 746 00:47:14.266 --> 00:47:19.966 So you can have an mGUS where you've got a monoclonal protein, but still 747 00:47:19.966 --> 00:47:24.333 no evidence of, and or good damage, no evidence of hyper viscosity. 748 00:47:24.333 --> 00:47:27.166 And with that, not that you're a better spot to make. 749 00:47:27.166 --> 00:47:31.000 These are some of the things we typically see with, wild mushrooms, 750 00:47:31.000 --> 00:47:32.300 macro globulin, anemia. 751 00:47:33.666 --> 00:47:35.133 You can have a light chain 752 00:47:35.133 --> 00:47:39.233 only mGUS where we're only detecting, light chains. 753 00:47:39.666 --> 00:47:44.933 And then, as I mentioned at the beginning, a plasma cytometry is where there are 754 00:47:44.933 --> 00:47:48.300 monoclonal plasma cells being produced 755 00:47:48.300 --> 00:47:51.300 and forming a mass within the tissues. 756 00:47:52.933 --> 00:47:58.033 Briefly, I'll, go over this third case 757 00:47:58.033 --> 00:48:02.800 of a 63 year old female, also with type two diabetes, with neuropathy. 758 00:48:03.233 --> 00:48:07.533 And she was being worked out for poly arthritis, the SPF. 759 00:48:07.533 --> 00:48:10.333 She was ordered to as part of that workup. 760 00:48:10.333 --> 00:48:14.300 And because that what we, we detect it 761 00:48:14.300 --> 00:48:17.633 and and spike here she was referred to hematology. 762 00:48:19.433 --> 00:48:21.166 You can see from her CBC findings. 763 00:48:21.166 --> 00:48:22.433 White count looks okay. 764 00:48:22.433 --> 00:48:24.733 She's anemic. Platelets are okay. 765 00:48:24.733 --> 00:48:27.600 Her CMP was normal. 766 00:48:27.600 --> 00:48:30.466 So here are our findings from the ESP. 767 00:48:30.466 --> 00:48:34.533 And if you can see she's got an Em spike going on here. 768 00:48:34.866 --> 00:48:38.366 She also is producing a IgG, 769 00:48:38.633 --> 00:48:41.633 Kappa monoclonal protein. 770 00:48:42.066 --> 00:48:43.833 As I said, this is the most common one. 771 00:48:43.833 --> 00:48:46.833 That's why it's not surprising in all three of these cases. 772 00:48:46.966 --> 00:48:51.166 They were all producing this type of monoclonal protein. 773 00:48:52.100 --> 00:48:55.300 You can see, based on our quantitative immunoglobulins 774 00:48:55.300 --> 00:49:01.066 that, the IgG is again elevated the IGA and are decreased again. 775 00:49:02.233 --> 00:49:03.900 And then her serum free light chains, 776 00:49:03.900 --> 00:49:07.166 her kappa is significantly elevated relative to the lambda. 777 00:49:07.166 --> 00:49:10.166 Her ratio is above 100. 778 00:49:13.833 --> 00:49:16.566 So based on these, she, 779 00:49:16.566 --> 00:49:22.200 had a diagnosis of plasma cell myeloma and was started on therapy. 780 00:49:22.666 --> 00:49:26.633 And then part of her therapy included Darragh tumor Mab. 781 00:49:27.200 --> 00:49:32.233 So I want to mention this because, this is a monoclonal antibody 782 00:49:32.566 --> 00:49:36.500 that is, specific against cd38, 783 00:49:36.866 --> 00:49:41.866 antigens, which are a protein that are highly expressed on myeloma cells. 784 00:49:42.500 --> 00:49:45.933 And so they bind the myeloma cells and that, induces 785 00:49:45.933 --> 00:49:48.933 apoptosis, so kills the, 786 00:49:49.833 --> 00:49:51.933 monoclonal cells. 787 00:49:51.933 --> 00:49:56.300 The problem is, for patients on this therapy, 788 00:49:56.300 --> 00:49:59.433 it can interfere with the by a fee. 789 00:49:59.466 --> 00:50:02.466 So this is a monoclonal, 790 00:50:02.900 --> 00:50:04.533 protein. 791 00:50:04.533 --> 00:50:07.500 So that's what we're looking for on the ESP. 792 00:50:07.500 --> 00:50:11.633 And if so, when patients are on this therapy, 793 00:50:11.900 --> 00:50:16.966 we can see bands within on the, ISC that aren't, 794 00:50:17.966 --> 00:50:20.333 related 795 00:50:20.333 --> 00:50:23.466 to their known, monoclonal protein. 796 00:50:23.500 --> 00:50:26.500 So you'll see a band migrating at a different area 797 00:50:26.933 --> 00:50:29.933 then, their, their monoclonal protein. 798 00:50:30.633 --> 00:50:33.333 It also creates a challenge in the blood bank 799 00:50:33.333 --> 00:50:36.933 because antibody screens will, appear reactive. 800 00:50:37.433 --> 00:50:42.600 They can mitigate this by, treating the, the patient sample with DTT, 801 00:50:43.000 --> 00:50:45.933 which denatured CD 138, 802 00:50:45.933 --> 00:50:48.633 but that will destroy the kill antigen. 803 00:50:48.633 --> 00:50:53.566 So then they can't evaluate for whether the patient has an anti kill antibody. 804 00:50:53.566 --> 00:50:57.400 So they may require cal negative units. 805 00:50:57.466 --> 00:50:59.600 If they go to transfusion 806 00:50:59.600 --> 00:51:03.066 I just make mention of this to, to make the point that, 807 00:51:03.533 --> 00:51:07.566 we have a number of good therapies and more and more of these days 808 00:51:07.566 --> 00:51:12.366 we're seeing those therapies and, are monoclonal antibodies. 809 00:51:12.900 --> 00:51:13.666 And so 810 00:51:14.733 --> 00:51:16.933 in a vacuum, if we were testing in the lab, 811 00:51:16.933 --> 00:51:21.733 we could see a band on, ifI or in the, 812 00:51:22.233 --> 00:51:26.733 on the ESP, and we wouldn't know if that's from disease or from therapy. 813 00:51:26.733 --> 00:51:29.733 So having the clinical history is important. 814 00:51:31.300 --> 00:51:34.733 So just going back through our cases 815 00:51:35.466 --> 00:51:39.433 in case one he presented with hyponatremia hypercalcemia. 816 00:51:39.733 --> 00:51:40.933 He had renal disease 817 00:51:40.933 --> 00:51:44.466 based on an increase B and a creatinine and a high total protein. 818 00:51:44.966 --> 00:51:46.233 He was anemic. 819 00:51:46.233 --> 00:51:49.700 He had 21% plasma cells circulating in the blood. 820 00:51:50.133 --> 00:51:54.566 And his seat showed multiple lytic bone lesions. 821 00:51:54.933 --> 00:51:58.766 That's if you think back to our slim crab mnemonic. 822 00:51:59.066 --> 00:52:03.833 He's got calcium hypercalcemia, he's got renal insufficiency, he's got anemia, 823 00:52:03.833 --> 00:52:04.833 he's got bone lesions. 824 00:52:04.833 --> 00:52:08.100 So he's he's four for four for crab symptoms. 825 00:52:08.700 --> 00:52:11.700 And then based on his, testing, he, 826 00:52:11.933 --> 00:52:16.000 was diagnosed with plasma cell myeloma. 827 00:52:17.266 --> 00:52:19.533 And these are some of the tests we did 828 00:52:19.533 --> 00:52:22.533 to, reach that diagnosis. 829 00:52:23.166 --> 00:52:26.166 This is just a quick look at what we saw, 830 00:52:26.166 --> 00:52:29.166 on his testing again. 831 00:52:29.166 --> 00:52:31.366 So he's producing an IGT. 832 00:52:31.366 --> 00:52:34.366 Heavy chain, Kappa light chain. 833 00:52:37.933 --> 00:52:39.066 This is a look again 834 00:52:39.066 --> 00:52:42.333 at his urine protein, electrophoresis. 835 00:52:42.333 --> 00:52:46.533 And if he, So we see the same thing as well as increased, 836 00:52:46.633 --> 00:52:49.633 free capillary chains. 837 00:52:50.733 --> 00:52:56.033 So he received a diagnosis of 838 00:52:57.133 --> 00:52:58.833 plasma cell myeloma. 839 00:52:58.833 --> 00:53:04.466 I forgot to mention it, but in case two, he received a diagnosis of, smoldering 840 00:53:04.733 --> 00:53:07.833 myeloma based on the number 841 00:53:08.566 --> 00:53:11.700 of plasma cells in his bone marrow and the, 842 00:53:12.300 --> 00:53:15.300 the size of his ham spike. 843 00:53:18.633 --> 00:53:21.000 And then our third patient, 844 00:53:21.000 --> 00:53:24.233 also received a diagnosis of myeloma. 845 00:53:24.266 --> 00:53:27.466 But, in her case, she was undergoing therapy, 846 00:53:27.766 --> 00:53:30.733 so we needed to know that she was under tumor map. 847 00:53:30.733 --> 00:53:34.533 So I wanted to just give some updates to these cases, 848 00:53:35.733 --> 00:53:38.733 after they received their diagnosis. So. 849 00:53:38.733 --> 00:53:41.833 Case one, he was started on chemotherapy, 850 00:53:42.133 --> 00:53:46.833 for a few months, followed by hematopoietic stem cell transplant. 851 00:53:46.833 --> 00:53:49.833 And that occurred about six months after its diagnosis. 852 00:53:50.733 --> 00:53:52.233 And then his most recent bone marrow 853 00:53:52.233 --> 00:53:55.666 biopsy showed that he had normal cellular marrow. 854 00:53:56.000 --> 00:53:58.833 No monoclonal plasma cells were detected, 855 00:53:58.833 --> 00:54:02.833 and his minimal residual disease was negative by flow cytometry. 856 00:54:03.133 --> 00:54:06.333 So overall, he's looking great, seems to be doing well. 857 00:54:07.433 --> 00:54:11.933 The second case, this is our gentleman who was waiting for kidney transplant 858 00:54:12.466 --> 00:54:16.800 and was, received a diagnosis of smoldering myeloma. 859 00:54:17.100 --> 00:54:20.000 He's still awaiting his kidney transplant. 860 00:54:20.000 --> 00:54:24.466 But the good news is his, as pep. 861 00:54:24.466 --> 00:54:28.333 And if he and other testing has remained stable. 862 00:54:28.600 --> 00:54:28.933 Yeah. 863 00:54:28.933 --> 00:54:31.666 And he still has a stable, mild anemia. 864 00:54:31.666 --> 00:54:35.433 So, important to note that, patients 865 00:54:35.433 --> 00:54:39.233 who receive a diagnosis of mGUS or smoldering myeloma, 866 00:54:40.233 --> 00:54:40.866 that does not 867 00:54:40.866 --> 00:54:44.833 mean they will all progress to a full blown, multiple myeloma. 868 00:54:44.833 --> 00:54:48.400 Many of these patients remain at that same level. 869 00:54:48.400 --> 00:54:53.166 So we detect an Em spike in their blood, but they never have symptoms, 870 00:54:53.166 --> 00:54:57.733 and they never progressed to in dark and damage or the other criteria 871 00:54:58.233 --> 00:55:00.800 that would give, 872 00:55:00.800 --> 00:55:03.800 change their diagnosis to multiple myeloma. 873 00:55:04.033 --> 00:55:07.033 And so that's where, this gentleman is right now. 874 00:55:07.433 --> 00:55:11.500 And, hopefully, he can get his kidney transplant 875 00:55:11.500 --> 00:55:14.500 and get some of his underlying disease taken care of. 876 00:55:15.900 --> 00:55:18.866 The third case, this was Our Lady 877 00:55:18.866 --> 00:55:21.700 who was on dare tumor Mab therapy. 878 00:55:21.700 --> 00:55:25.533 She was changed to this therapy in October of 2023. 879 00:55:26.200 --> 00:55:29.700 More recently, she was hospitalized for pneumonia, 880 00:55:30.100 --> 00:55:33.600 and has continued to receive follow up testing, 881 00:55:33.600 --> 00:55:36.866 which includes, her most recent ESP, still 882 00:55:36.866 --> 00:55:40.133 showing her IgG Kappa m spike, 883 00:55:40.433 --> 00:55:44.400 but it had decreased to 0.65g per deciliter. 884 00:55:44.400 --> 00:55:47.733 And this is down from a high of greater 885 00:55:47.733 --> 00:55:50.733 than two grams per deciliter back in 2021. 886 00:55:50.833 --> 00:55:54.300 So it shows that, her therapy is working. 887 00:55:54.300 --> 00:55:58.733 It is decreasing, the number of monoclonal plasma cells, 888 00:55:59.066 --> 00:56:02.466 but they they are not completely gone away. 889 00:56:03.100 --> 00:56:05.766 And so, there is improvement. 890 00:56:05.766 --> 00:56:09.200 And she will continue to receive follow up testing. 891 00:56:11.533 --> 00:56:13.933 So after these patients have received 892 00:56:13.933 --> 00:56:19.466 a diagnosis of a plasma cell disgrace, follow up testing includes repeat testing. 893 00:56:20.100 --> 00:56:23.233 You can repeat the step to continue 894 00:56:23.233 --> 00:56:26.233 quantifying the M spike to see if therapy's working. 895 00:56:26.400 --> 00:56:29.400 You would expect the M spike to decrease. 896 00:56:29.700 --> 00:56:33.133 The current recommendations for those who are only diagnosed with, gas 897 00:56:33.133 --> 00:56:37.266 or smoldering myeloma is that they be retested after six months 898 00:56:37.600 --> 00:56:40.500 and then yearly after that for the low risk patients. 899 00:56:40.500 --> 00:56:43.233 So those are with the IGD type. 900 00:56:43.233 --> 00:56:47.200 The spike is still fairly low and they have a normal free light chain ratio. 901 00:56:48.033 --> 00:56:52.133 If they are going to progress, the risk is highest within the first year 902 00:56:52.133 --> 00:56:53.300 following diagnosis. 903 00:56:53.300 --> 00:56:56.866 If they make a past that, then their risk of progression decreases. 904 00:56:57.800 --> 00:57:01.266 And then followup testing can also be discontinued if, 905 00:57:01.333 --> 00:57:03.333 they have advanced age 906 00:57:03.333 --> 00:57:07.266 greater than 80 years, or if their life expectancy is five years. 907 00:57:10.066 --> 00:57:11.900 Here are some of my references. 908 00:57:11.900 --> 00:57:17.266 I appreciate, everyone who listened and, 909 00:57:18.500 --> 00:57:19.500 thank you very much. 910 00:57:19.500 --> 00:57:20.966 And that concludes my talk.