OK, we're going to switch gears a little bit and do rapid fire hemo-onc emergencies. For those of you taking the ABIM boards, this will be about 6% of the blueprint. There's a laundry list of hemo-onc emergencies. We're just going to deal with the high points. The recorded lecture, which is a 30-minute, 35-minute lecture, will expand on some of the things that we're going to talk about. So we had a test question on tumor lysis syndrome. This is the most common oncological metabolic emergency. So you got it familiar. It's guaranteed there'll be a question. Very commonly in situations where you have high-grade liquid tumors, but you can also see this with solid tumors that are treated with either checkpoint inhibitors or heavy-duty chemotherapy agents. The classic features for TLS are elevated uric acid, potassium, phosphorus, and then you have hypocalcemia as well. There are many risk factors, including volume depletion and pre-existing hyperuricemia. Classification of TLS is laboratory and clinical. Laboratory, you can see the parameters there. Clinical, usually the laboratory abnormality, is associated with either cardiovascular, CNS, like seizures, or acute kidney injury. So this is one of the questions that I brought up. I'm going to expand a little bit why Respirocase was the choice. So the treatment of tumor lysis syndrome is first aggressive fluid hydration, maintaining a high urine output. So these are patients that require 200, 250 cc's an hour of fluid. You've got to correct the electrolytes, potassium, phosphorus, et cetera. Loop diuretics can be considered if you want to augment urine output, but they have not been shown to change mortality. Alkalinization, previously done. We used to do it, but not anymore, as I mentioned in the question and answer, that that increases phosphate and precipitation in the tubules of the kidney. Allopurinol is a synthase oxidase inhibitor, blocks uric acid. This is typically given 48 hours before you start somebody on cytotoxic chemotherapy. The problem with allopurinol, it only takes care of already existing elevated uric acid. Doesn't really prevent further uric acid production, and that's why it's been replaced by rasburicase. Now it's more soluble in terms of how it degrades uric acid into allantoin, which is more soluble than uric acid, so easier to eliminate. It's superior to allopurinol. The one thing about a test question of rasburicase, it can have a serious side effect of hemolysis, and you have to screen patients for G6PD deficiency before you give rasburicase. Otherwise, you're gonna create a situation of hemolysis in these patients. Hemodialysis, or CBBH, will only be indicated if you have a clear indication, life-threatening hyperkalemia that doesn't respond to medical measures, or elevated phosphorus that's life-threatening. Patient is in volume overload, severe acidosis. You have to have a clear reason to be doing dialysis, or CRT, as your first step. Malignancy-associated hypercalcemia, another one that's very testable. Patients can be neurologically impaired. They may have signs of polyuria, acute kidney injury, prolonged QT, interval, bradycardia. High calcium levels are generally levels of over 14. You can have three types or mechanisms. You can either get hypercalcemia from malignancy by secretion of parathyroid hormone-related protein, or PTHP, or you can have hypercalcemia from bone destruction, or extra PTH-mediated reasons. Here's a test practice question for you. A 70-year-old man, nausea, vomiting, lethargy, diffuse bone pain, his somnolent. You can see his blood pressure there. He's slightly tachycardic, decreased skin turgor, dry mucous membranes. He has a calcium level of 16, an albumin of 3.8, elevated creatinine of 2.5. Which of the following is the most appropriate for initial management? Solidronic acid, isotonic saline and calcitonin, isotonic saline and furosemide, or denosumab? What's the correct answer? Correct answer is B. Again, just like with tumor lysis, we always want to pursue IV hydration for most of these metabolic derangements in patients that have metabolic abnormalities related to hemo-oncology etiologies. So we'll go over the management of hypercalcemia. Again, volume expansion is key to maintain a high urine output. Loop diuretics are not routinely recommended. They're only reserved for patients with hypercalcemia who are volume-overloaded. Calcitonin can be used. It doesn't act right away. You can see the dose there. Biphosphonates, I think, are currently the mainstay of treatment, particularly for those patients who have PTH-related or bone destruction that causes hypercalcemia. Solidronic acid, or Zometa, is favored over pomidronate in patients with malignancy-associated hypercalcemia, but keep in mind, this can be also potentially nephrotoxic and cause ATN, angiomarrow sclerosis. Corticosteroids, again, work very well for those with malignancy-associated hypercalcemia that's mediated by ectopic PTH release. Hydrocortisone is commonly used, followed by a short prednisone taper. Dinosumab is a relatively recent medication that's been approved, particularly for refractory malignancy-associated hypercalcemia. These are generally offered to patients who are not responding pretty well to solidronic acid or other therapies that you've already been given, or biphosphonates cannot be given because the patients have acute kidney injury. It's not renally excreted, and there's no need to dose adjust. Switching over to spinal cord compression, again, very common in patients with cancer, particularly lung, breast, and prostate. Thoracic vertebrae is commonly involved. Patients can have back pain, tenderness, and motor weakness. Pain control and preservation of neurologic function is essential in treatment. Generally, it's corticosteroids, surgical decompression with our neurosurgical colleagues if the patient is a neurosurgical candidate, and of course, radiation therapy as well. SVC syndrome, again, very testable. These are commonly seen in patients with malignancy, particularly lung and lymphomas. Patients have significant venous congestion of their neck, their face. They can be stridorous, have a cough, or even hoarseness of their voice. Chest X-ray or CT scan usually gives this away because of the widening of the mediastinum. There are many things in the treatment of SVC syndrome that you need to know, from elevation of the head of the bed to airway stabilization to, if there is related to a clot, maybe lysing the clot, avoiding overhydration, and of course, radiotherapy and chemotherapy in select cases. Cardiac tamponade is another very important emergency that may occur in patients with metastatic lung and breast cancer, as well as lymphomas. You all know the signs and symptoms from hypotension, elevated jugular venous pressure, distant heart sounds, the so-called VEC triad. ECG voltages are typically low. You may have electrical alternance, as shown in the ECG on the top right. Transthoracic echocardiogram is, of course, the imaging modality of choice. And you look for classic signs of tamponade, which you all know. Echocardiogram-directed pericardiocentesis, catheter drainage of the pericardium, or creating a pericardial window. And in some cases, pericardial sclerosis with diatepa may be indicated, as well, in patients with recurring effusion and tamponade physiology. Malignant airway obstruction, very common in patients with primary lung cancer. You can have external compression of the airway from tumor or enlarged lymph nodes. Dyspnea is typically worse at night and while lying supine. Patients can be presenting with wheezing or stridor, particularly if it's a central airway obstruction. And treatment, as you know, is rigid bronchoscopy with possibility of stenting. And that's not possible. Radiotherapy or chemotherapy may be given, as well. Turning over to some hematologic emergencies, you need to know about hyperleukocytosis and leukostasis. Here, the white count is typically over 50, over 100,000. This is common. So an elevated white cell count in this range of 50 to 100 is what we call hyperleukocytosis. Leukostasis is having a very high white count and having a symptomatic problem related to it. And that can typically be a crisis and that could lead to respiratory distress, respiratory failure. Another very testable item is that if you have a very, very high white count, you could have the phenomenon of a spuriously low PaO2. That's a so-called leukocyte larceny phenomenon. So in those patients, you should be checking your pulse oximeter reading for your SAT. That's gonna be more reliable rather than relying on a PaO2 from a blood gas because the high white count, the white cells are basically eating up all the oxygen. So it comes back spuriously low. So that's a question that might certainly come up. Treatment for high white counts and leukostasis is leukophoresis and cytoreduction, initially with hydroxyurea, and then followed by more intensive chemotherapy depending on the malignancy type. And one study in Europe showed that in patients with leukostasis, in a patient with AML who had ALI, ARDS phenomenon, the use of dexamethasone was proven to be safe and effective. Hyperviscosity syndrome, another important heme malignancy. This can be seen in patients with multiple myeloma or wildestrom macroglobulinemia. Neurologic ocular bleeding and constitutional symptoms are common. And this is one syndrome where plasmapheresis is usually the initial mainstay of treatment. You need to avoid transfusing patients because you're gonna promote more hyperviscosity and that can be a problem. And of course, treating the underlying malignancy with chemotherapy and in patients in need of plebotomy, that could be useful as well. HLH, we've all seen HLH. This is a life-threatening inflammatory syndrome. It can occur in patients that get CAR T-cell therapy or patients undergoing bone marrow transplant associated with GVHD. It's high mortality. There is the HLH diagnostic criteria. You just need five of these eight criteria. So patients can be febrile, spenomegaly. Two of three cell lines are usually down. Triglycerides are high, ferritin's very high. And then there's specific tests like soluble IR2 receptor, which is a very specific test for HLH. Commonly, it's gonna be very, very high in patients with HLH. Management is supportive because these patients are pancytopenic. You need to give them transfusion. Many patients will have an infectious reason as well that might trigger the HLH besides the malignancy. Blood pressure control in patients that have high blood pressure, steroids. And then you have more specific treatments like imipalumab, which is an inhibitor of interferon gamma, which is a very significant cytokine that is elevated in patients with HLH. So this is an approved drug that works a lot in pediatric and adult HLH cases. And then you have other treatments. Some of them we use in COVID like nikenra, roxolitinib, varicitinib, xiltoximab. And cytosorb is a strategy of extracorporeal removal of cytokines. Finally, checkpoint inhibitors are very commonly used now. We've shifted away from traditional chemotherapy for solid tumors and now using more and more checkpoint inhibitors. So you need to know pneumonitis, cardiovascular, pulmonary, and neurologic toxicities can be very common. So they might give you a case of pneumonitis and tell you this is a patient that got a checkpoint inhibitor, whether it's PEMBRO for lung cancer or melanoma. You need to know that pneumonitis can be a serious complication. Practice question for you, 50-year-old male, hypertensive, smoker, metastatic renal cell. He starts a combination of two checkpoint inhibitors, NEVO and IPI every two weeks. He's now in single drug NEVO and he comes to the hospital. I can see the presentation of altered mental status, fatigue, refractory hypotension. You can see the lab data. The sodium is low. Hemoglobin is 7.8 low. He's got a platelets of 102 creatinine, elevated at 1.5, beyond elevated 50. In addition to fluids and vasopressors, which of the following interventions should be initiated in this patient? So this is talking about a checkpoint-related toxicity that you should try to be familiar with. And the correct answer here is hydrocortisone. So this patient has adrenal insufficiency from the checkpoint inhibitor, which can produce this syndrome. So these are basically the different types of management scheme that we try to use. Corticosteroids remain the mainstay. You have other agents in patients that are refractory. The steroids then you might use infliximab. Finally, CAR T-cell therapy. These are the five syndromes that you can get with CAR T-cell. Cytokine release syndrome. You've probably seen this already. Very common in patients that get CAR T-cell products, particularly those with high disease burden and those that get fludarabine-based chemotherapy before the CAR T infusion. Symptoms usually are fever, hypoxia, hypotension. These are the grading that's standardized already. Treatments, supportive, treat the fever, work the patient up for sepsis. Patients with grade two, three, and four have to be in the ICU. We give them an IL-6 receptor inhibitor, intoxicatelucimab. In patients that are getting hypotensive, more hypoxic, we add steroids in increasing doses. And in refractory cases, in patients that don't respond to steroids or need further therapy, then we use anakinra as well as siltoximab as your other choices. Neurotoxicity is the other biggie. Again, related to impaired permeability of the blood-brain barrier. This will kind of overlap with CRS. So the CRS can occur, let's say, three to five days and then shortly after that, or sometimes in the middle of the CRS, you can get severe neurotoxicity. Again, there are certain laboratory markers. The patients generally have word problem difficulty. They can be confused. They can be frankly encephalopathic. Cytokine levels are high. Treatments generally are gonna be supportive. We do an EEG to rule out seizures. We do CT scan, MRI, LP. We try to make sure that we give them also high-dose thiamine for the encephalopathy. Seizure prophylaxis. We don't give TOSI unless there's concurrent CRS. TOSI does not cross the blood-brain barrier. It will not treat neurotoxicity. Steroids are the mainstay of treatment for neurotoxicity. And of course, in sick patients with grade three or four, many will require intubation and mechanical ventilation for airway protection. And for those that exhibit, unfortunately exhibit cerebral edema, this can be fatal in that scenario. We use steroids and all the other measures to try to lower ICP. So the key points, very quickly, oncologic emergencies. There's a slew of them. For TLS, fluids, resveracase are your go-to. For hypercalcemia, fluid by phosphonates, calcitonin, and steroids. For spinal cord compression, pain control, and steroids. For hyperviscosity syndromes, plasmophoresis. For HLH transfusion, steroids, imipalumab. For checkpoint inhibitor toxicity, it's steroids, steroids, steroids. And TOSI-Lucimab for CRS. And steroids for CAR-T neurotoxicity. And that's all I have. Thank you very much.

hematologic emergencies

oncologic emergencies

tumor lysis syndrome

hypercalcemia management

checkpoint inhibitors