Today in our Jacobs afternoon conference, Dr. Tiffany Tanaka gave a very practical, case-based talk on how to read peripheral blood smears as well as common findings for platelets and leukocytes. She gave a primer on hematopoietic lineages and differentiation, how to read a peripheral smear systematically, and some common, high-yield findings that are often tested on boards. Special thanks to her for helping to teach not one, but two conferences today!!
Today we discussed a case of thrombocytopenia with our expert discussant hematologist oncologist Dr. Tanaka. We discussed a case in which a patient with CLL developed severe thrombocytopenia. We discussed ruling out pseudothrombocytopenia when evaluating thrombocytopenia. This is caused by the anticoagulant EDTA in the blood collection tube and can be fixed by using a tube with citrate or heparin. We then broke down thrombocytopenia causes into three main buckets underproduction, splenic sequestration and peripheral destruction. The final diagnosis for our patient was immune mediated platelet destruction secondary to CLL.
September is Sickle Cell Awareness Month and this morning Alex Sykes, one of our awesome R2s, presented a case of a 26-year old man with homozygous sickle cell disease who presented with acute hip pain. We were lucky to have the patient’s hematologist, UCSD’s Dr. Srila Gopal, join us as an expert discussant. We covered the various genetic variants of sickle cell spectrum as we reviewed the patient’s electrophoresis (note that the reason he has any Hb A is due to prior transfusions!) and discussed environmental triggers of vaso-occlusive crises (VOCs). We then covered the why behind the use of hydroxyurea in patient with sickle cell disease and learned about exciting new therapies that are being implemented and researched. Finally, we covered the pathophysiology of vaso-occlusive crisis before learning that our patient’s pain was due to an infarct of the right acetabulum. Many thanks to Dr. Gopal for sharing her vast wisdom with us.
Today our fantastic hematologic malignancy expert, Dr. Asimakopoulos, walked us through an interesting case of amyloidosis! We discussed the fine details of what exactly SPEP, UPEP, and Immunofixation are, and how they are useful in the workup of patients with infiltrative protein disease. We also reviewed the most common types of amyloidosis: AL (light chain), AA (chronic inflammatory), and how to distinguish these patients both clinically and with laboratory data. Thank you Dr. Asimakopoulos!
This afternoon, Kimberly Kreitinger presented the case of a female in her 50s with a history of metastatic colorectal cancer. The patient has had a course involving treatment for the past 4 years with FOLFOX + Avastin, which was stopped due to HTN, FOLFOX + cetuximab, SBRT to lung and liver lesions, then targeted therapy with trastuzumab and pertuzumab, though demonstrated disease progression. The patient was then considered for immune checkpoint inhibitor therapy with Pembrolizumab, a PD-1 inhibitor.
We discussed the tested indications for the use of ICIs in the treatment of metastatic colorectal cancer. Notably, multiple trials have demonstrated efficacy in prolonging progression free survival and improving overall survival in patients with metastatic CRC, but in patients demonstrated to have either mismatch repair deficiency (MMR-D) or high degrees of microsatellite instability (MSI-H). These trials demonstrated the effectiveness of Pembrolizumab (PD-1 inhibitor), Ipilimumab (a CTLA-4 inhibitor), or the combination of Ipilimumab and nivolumab (PD-1 inhibitor). The rationale behind the use of ICIs in these patients is that those with defective MMR are felt to be prone to indels or frameshift mutations, which may confer increased immunogenicity due to epitope formation.
The patient was found on genomic testing to have microsatellite stability, though demonstrated intermediate levels of tumor mutational burden (TMB) and high levels of Tumor infiltrating lymphocytes (TILs), which may have favorable prognostic profiles with regard to response rates to ICI therapy–active research performed by investigators here at UCSD! Much of this data is preliminary, though provides us with a glimpse of advanced therapies for patients whose disease has progressed beyond standard systemic chemotherapeutic options. Thank you to Dr. Sacco for her expert input and Kim Kreitinger for a great case presentation.
Go RS, Winters JL, Kay NE. How I treat autoimmune hemolytic anemia. Blood. 2017 Jun 1;129(22):2971-2979.
Today Dr. Susan Seav presented a case of bloody diarrhea in a young male. The combination of elevated bilirubin, anemia, and reticulocytes on his blood smear raised concern for underlying autoimmune hemolytic anemia, and the patient was diagnosed with WAIHA secondary to lupus. Up to 10% of patients with WAIHA are DAT/Coombs negative, as with this patient. For more on WAIHA classification and serology, see the figure above from the referenced 2017 Blood review article on the subject. Many thanks to Dr. Fotis Asimakopoulos for serving as our expert discussant!
Today at the VA, Dr. Ken Winter presented a fascinating case of an otherwise healthy middle-aged man who presented with sub-acute right-upper extremity swelling, neck swelling, and dysphonia. After learning about his smoking history and seeing both upper extremity, neck, and facial swelling on exam, the team astutely recognized that our patient was experiencing SVC syndrome! We then took some time to discuss different aspects and key points about SVC syndrome (see below). Ultimately, our patient had a biopsy that demonstrated SCLC and he was started on inpatient chemotherapy. He was discharged after resolution of his symptoms with plans to further follow-up in oncology clinic!
Take Away Points:
1. SVC syndrome is a clinical diagnosis and is associated most strongly with lung cancer and non-Hodgkin lymphomas.
2. Severity grading drives your management for SVC syndrome: for grades 1-2, initial biopsy is key! Reserve upfront interventions for grades 3-4.
3. Although SVC syndrome is an oncologic emergency, it is rarely life-threatening and does not change the overall prognosis for your patient.
Congratulations to our second round of HollyWould teams! We tackled VTE treatment in malignancy, and produced four videos for the UCSD video archive that cover the core trials in the field. The big take away this time surrounds adherence. In our previous sessions, we discussed that LMWH adherence was lower in the DOAC trials. While this might mean the LMWH effect was reduced, it also reminds us that adherence often depends on delivery method. Patients would rather take a pill than inject themselves, and pills that don’t require blood work and monitoring are preferred. The best medication may be the one your patient actually takes! Looking toward the future, the question about preventive anticoagulation for high risk VTE malignancies remains; cancers with high Khorana scores such as pancreatic cancer may be candidates for anticoagulation even before VTE’s are identified.
- Better DOAC adherence likely reflects patient preference for pills over injections
- The jury is still out on preventive anticoagulation — perhaps a future journal club is in order.
- Speaking of the jury, the winning team this week used a Law and Order theme to great effect. Be on the lookout for the upcoming video archive links!
This week, Diego Vargas presented the case of a middle aged man who had presented with rectal pain, hematochezia, fevers and chills. He was found to have metastatic rectal adenocarcinoma, complicated by local abscess and fistula formation, and was septic. The patient was stabilized with several courses of broad spectrum antibiotics and referred to our medical center for further evaluation of his cancer. Upon initial work up, CT chest/abdomen/pelvis revealed liver metastases as well as intraabdominal and intrathoracic lymph node involvement. Moreover, the case was complicated with a worsening AKI, findings of hyperuricemia to 11, hyperkalemia, and mild hyperphosphatemia, raising suspicion for potential spontaneous tumor lysis syndrome.
We discussed TLS in more detail and the types of malignancy that are most likely to have TLS as a consequence of treatment–primarily liquid hematologic malignancies were the most likely etiologies (acute leukemias/lymphomas, burkitt’s lymphoma, etc). More rarely, solid tumors can also present with TLS following treatment–these tumor types have been mainly described in case reports–breast cancer, SCLC, and widely metastatic colon cancer. Spontaneous TLS is not commonly seen in solid tumors.
We also discussed the Cairo-Bishop criteria for Tumor Lysis Syndrome, which include both laboratory and Clinical criteria as a tool to help establish TLS in the right clinical setting. It is important to note that these criteria apply primarily for cases either <3 days or >7 days following treatment, which may be chemotherapy or radiation.
Ultimately, the it was felt that while the patient’s tumor had metastasized the ultimate tumor burden and the fact that it was a solid tumor was an unlikely cause of the patient’s multiple electrolyte abnormalities and renal dysfunction, but rather it was more likely that an AKI was the causative etiology to explain the former. Thank you Diego for a great, live case and we appreciate Dr. Husain’s expert input!
- Hematologic malignancies are much more likely to cause tumor lysis syndrome following initiation of chemotherapy. Solid tumors, unless with aggressive SCLC, breast cancer or metastatic colon ca, are much less likely to have TLS as a consequence of treatment.
- Spontaneous tumor lysis can occur in tumors with very high cell turnover–most commonly aggressive acute leukemias and lymphomas.
- The Cairo-Bishop criteria may help with the identification and recognition of TLS if clinical suspicion is high.
Today Dan S. Kaufman MD, PhD, Director of UCSD’s Cell Therapy Program gave us a fascinating talk on the recent advancements in targeted cancer therapy.
Dr. Kaufman began by describing the methodology to derive mature cells from pluripotent stem cells and the implications for cancer therapy. He then went through typical options for cancer treatment, with the antibody and cell-based therapies being most recently introduced.
Dr. Kaufman then informed us that in regards to cell based therapies, the only FDA approved therapy is CAR-T cells for certain B and T cell lymphomas. He notes they are working to expand their application to solid tumors, but there are challenges including antigen escape, toxicity concerns, manufacturing limitations.
Dr. Kaufman then emphasizes that the goal of cellular immunotherapy is to make cells as easy to use as a drug. This can be done by making them 1) targeted 2) standardized 3) off-the-shelf.
NK cells can be used to meet the key goals of cellular cancer therapy because they do not need to be patient matched, can function as allogenic cells and can be regulated by a repertoire of activating and inhibitory receptors. There are ongoing trials presently and they have shown to be most effective against refractory AML. He went over a few studies showing its efficacy in mouse models for treating leukemia. They have been promising because no evidence of GVHD or other toxicities.
He then went over some strategies he’s identified to improve tumor targeting regarding to genetic modifications he can make to the cells. Dr. Kaufman proceeded to share the results of a number of completed studies that have highlighted their efficacy.
He ended by informing us about how this translational medicine is making it to the bedside via a number of active trials. Here at UCSD patients with refractory cancers (with or without concomitant treatment of checkpoint inhibitors) are now getting NK cells through a phase 1 trial with Fate therapeutics.
Thank you Dr. Kaufman for such a thought-provoking lecture!