Impact of age, obesity, and renal impairment on outcomes after autologous stem cell transplantation for patients with newly diagnosed multiple myeloma.

INTRODUCTION: There remains a need to determine whether certain subgroups of newly diagnosed multiple myeloma (NDMM) derive the same benefit from high-dose chemotherapy-autologous stem cell transplant (HDT-ASCT). We describe our institutional experience highlighting the impact of age, obesity, and renal impairment on outcomes after HDT-ASCT for patients with NDMM in a real-world setting. METHODS: A total of 449 consecutive patients were included in this retrospective analysis. RESULTS: No difference in median progression free survival or overall survival was seen for patients with age > 65, body mass index (BMI) > 30 kg/m2, or estimated glomerular filtration rate < 60 mL/min/1.73 m2 when compared to those without these characteristics. From a safety standpoint, there were no differences in the incidence of transplant-related mortality or secondary malignancy among subgroups. CONCLUSION: For patients with NDMM undergoing HDT-ASCT, there is no difference in outcomes based on age, BMI, or renal function, and the presence of one or more of these factors should not preclude patients from HDT-ASCT.

Impact of race and ethnicity on outcomes after autologous stem cell transplantation for patients with newly diagnosed multiple myeloma.

Non-Hispanic Black patients are disproportionally affected by multiple myeloma (MM) and whether efficacy outcomes after autologous stem cell transplant (ASCT) differ by race and ethnicity remains an area of active investigation. This study included 449 patients enriched with a large proportion of non-Hispanic Black patients and sought to highlight the impact of race and ethnicity on outcomes after HDT-ASCT for patients with newly diagnosed MM. We found induction chemotherapy followed by high-dose therapy-ASCT and maintenance chemotherapy is associated with long-term PFS and OS, regardless of race or ethnicity.

Stem Cell Mobilization for Multiple Myeloma Patients Receiving Daratumumab-Based Induction Therapy: A Real- World Experience.

For patients with newly diagnosed multiple myeloma (MM) undergoing high-dose chemotherapy and autologous stem cell transplantation (HDT-ASCT), hematopoietic stem cell mobilization can be affected by induction chemotherapy. In clinical trials, the addition of daratumumab (dara) to a triplet backbone lowered hematopoietic stem cell yield, necessitating the administration of plerixafor to achieve the desired yield for ASCT. Here we describe our experience of stem cell mobilization and collection after dara-based and non-dara-based induction regimens. This single-center retrospective analysis included patients with newly diagnosed MM who had received induction chemotherapy and were candidates for upfront HDT-ASCT. Based on the induction regimen used, patients were divided into 2 groups, RVd (lenalidomide, bortezomib, and dexamethasone) and DRVd (RVd with the addition of dara). Based on our institutional practice, patients received pegylated growth colony-stimulating factor (G-CSF) on day -3 (at 0900 hours) in combination with plerixafor on day -1 (at 2300 hours) as a preemptive mobilization strategy. Patients continued apheresis for 1 to 3 days until the goal dose of hematopoietic stem cells was collected (2.5 × 106 cells/kg for one ASCT and 5.0 × 106 cells/kg for 2 ASCTs). Patients with a suboptimal stem cell yield on day 1 received additional doses of plerixafor with or without G-CSF. A total of 101 patients with newly diagnosed MM who underwent mobilization between July 2021 and June 2022 were analyzed. The median patient age was 61 years (range, 36 to 80 years), and 51.5% of the cohort was female. Patients received a median of 5 (range, 2 to 12) cycles of induction chemotherapy, with a median of 4 (range, 2 to 12) cycles of DRVd and 6 (range, 3 to 12) cycles of RVd. The median number of CD34+ cells collected in the DRVd and the RVd groups was 6.54 × 106/kg and 6.78 × 106/kg, respectively. Target CD34+ stem cells were collected in a median of 1 day (range, 1 to 4 day) in each group. On average, more patients in the DRVd group compared to the RVd group received additional doses of plerixafor (51% versus 43%) and additional doses of GCSF (19% versus 14%) to achieve the target stem cell yield. There were no mobilization failures or grade 3+ mobilization-related adverse events reported in either group. The addition of daratumumab to the RVd induction regimen did not lead to any clinically significant differences in stem cell yield or number of collection days, provided that the patient received preemptive G-CSF and plerixafor. Patients with suboptimal collection on day 1 were able to collect adequate stem cells with additional doses of plerixafor with or without G-CSF.

Impact of Cytogenetic Abnormalities, Induction and Maintenance Regimens on Outcomes After High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Patients With Newly Diagnosed Multiple Myeloma: A Decade-Long Real-World Experience.

Background: High-dose chemotherapy and autologous stem cell transplant (HDT-ASCT) has become a standard of care for transplant eligible newly diagnosed multiple myeloma (NDMM) patients. While cytogenetic abnormalities have been shown to affect outcomes after HDT-ASCT in clinical trials, these trials often exclude or underrepresent elderly patients with comorbidities and those belonging to ethnic minorities. We describe our institutional experience highlighting the impact of high-risk cytogenetic abnormalities (HRCAs) on outcomes after HDT-ASCT for NDMM patients. Methods: A total of 449 patients with NDMM who underwent HDT-ASCT between February 2012 and August 2022 were included in this retrospective analysis. HRCAs included the presence of one or more of: deletion 17p, t(14;16), t(4;14), and amplification 1q. Survival analyses, including progression-free survival (PFS) and overall survival (OS), were performed using Kaplan-Meier estimator. Results: With a median follow-up of 29 (1 - 128) months for the entire patient population, the best overall response rate for the patients with HRCAs was lower compared to those with standard risk cytogenetics (90% vs. 96%; P = 0.01). Patients with HRCAs had an inferior PFS compared to patients with standard-risk cytogenetics (29 vs. 58 months; P < 0.001) without a difference in OS (70 months vs. not reached; P = 0.13). Conclusions: In a multivariable analysis adjusting for factors including age, race, and comorbidities, HRCAs, non-lenalidomide-based maintenance, non-proteasome inhibitor-based maintenance, and age greater than 65 were associated with inferior PFS. Amongst these factors, only non-lenalidomide-based maintenance was associated with inferior OS.

Successfully treated acute adult T-cell leukemia with haploidentical stem cell transplantation.

Adult T-cell leukemia-lymphoma caused by human T-lymphotropic virus type 1 is a rare and aggressive tumor with high morbidity and mortality. Historically it has been treated with chemotherapy, but more recent studies suggest improvement in survival with the combination of chemotherapy and stem cell transplantation. Our case study reports a middle-aged African American woman with no other risk factors diagnosed with the acute form of adult T-cell leukemia-lymphoma and in remission after completing chemotherapy and a haploidentical stem cell transplantation.

Anti-cancer Drugs Associated Atrial Fibrillation-An Analysis of Real-World Pharmacovigilance Data.

Background: Several anti-cancer drugs have been linked to new onset atrial fibrillation (AF) but the true association of these drugs with AF is unknown. The FDA Adverse Event Reporting System (FAERS), a publicly available pharmacovigilance mechanism provided by the FDA, collects adverse event reports from the United States and other countries, thus providing real-world data. Objectives: To identify anti-cancer drugs associated with AF using the FAERS database. Methods: The FAERS database was searched for all drugs reporting AF as an adverse event (AE). The top 30 anti-cancer drugs reporting AF cases were shortlisted and analyzed. Proportional reporting ratio (PRR) was used to measure disproportionality in reporting of adverse events for these drugs. Results: When analyzed for AF as a percentage of all reported AE for a particular drug, Ibrutinib had the highest percentage (5.3%) followed distantly by venetoclax (1.6%), bortezomib (1.6%), carfilzomib (1.5%), and nilotinib (1.4%). The percentage of cardiac AE attributable to AF was also highest for ibrutinib (41.5%), followed by venetoclax (28.4%), pomalidomide (23.9%), bortezomib (18.2%), and lenalidomide (18.2%). Drugs with the highest PRR for AF included ibrutinib (5.96, 95% CI= 5.70-6.23), bortezomib (1.65, 95% CI = 1.52-1.79), venetoclax (1.65, 95% CI = 1.46-1.85), carfilzomib (1.53, 95% CI = 1.33-1.77), and nilotinib (1.46, 95% CI = 1.31-1.63). Conclusions: While newer anti-cancer drugs have improved the prognosis in cancer patients, it is important to identify any arrhythmias they may cause early on to prevent increased morbidity and mortality. Prospective studies are needed to better understand the true incidence of new onset AF associated with anti-cancer drugs.

A Case of Aplastic Anemia and Colon Cancer With Underlying Spliceosome Mutation: Is It an Incidental Finding or a Novel Association?

Alternative splicing is an epigenetic mechanism that plays a role in the development and function of antigen-specific lymphocytes. One such is the zinc-finger-RNA-binding-motif-and-serine/arginine-rich-2 (ZRSR2), which is clinically implicated in myelodysplastic syndrome and leukemia. Here, we present a case of a young male with myriad autoimmune conditions and adenocarcinoma of the colon in the setting of ZRSR2 mutation. A 28-year-old male with common variable immunodeficiency disease, atopic dermatitis, autoimmune gastroenteropathy, inflammatory polyarthropathy, primary bone marrow failure, colon cancer, and family history of Lynch syndrome was admitted to our hospital for an acute flare of autoimmune enteropathy secondary to subtherapeutic tacrolimus levels. He initially developed pancytopenia at the age of 26 years. Workup for HIV, hepatitis, cytomegalovirus, human-herpesvirus 6, parvovirus was negative. Partial thromboplastin time (PTT), international normalized ratio (INR), d-dimer, ferritin, iron profile, antinuclear antibodies (ANA) screen was unremarkable. Direct, indirect, and super-combs antibodies were undetectable. Chromosomal study for Fanconi-related chromosomal breakage and telomerase gene panel was negative. Flow cytometry did not reveal an abnormal clone. Bone marrow biopsy showed markedly hypocellular marrow with reduced trilineage hematopoiesis and 1% blasts with normal cytogenetics, immunohistochemistry, fluorescence in situ hybridization (FISH), and negative for myelodysplastic syndrome and paroxysmal nocturnal hemoglobinuria (PNH). Cincinnati inherited children's bone marrow transplant (BMT) panel was negative. He was diagnosed with aplastic anemia and was treated with antithymocyte globulin, cyclosporine, prednisone, and currently tacrolimus. At the age of 26 years, he was diagnosed with colon cancer. Immunohistochemistry was positive for MLH1, but the confirmatory genetic testing for Lynch syndrome was negative. He underwent total proctocolectomy and ileostomy and is currently in remission. Next-generation sequencing of bone marrow revealed a germline homozygous ZRSR2 mutation.  ZRSR2 spliceosome mutations are more common in males as it's an X-linked gene. They are seen in myelodysplastic syndrome, leukemia, increased autoimmune phenomenon, and 35 cases of colon cancer associated with this mutation are reported. In the setting of aplastic anemia and lynch negative colon cancer, we suspect our patient could have aplastic anemia due to an autoimmune phenomenon, underlying common variable immunodeficiency disease (CVID), or the new ZRSR2 mutation could be playing a role. Further studies and research is warranted to determine its true association with the disease entities. The underlying contributing factor is ZRSR2 mutation.

Myosin Heavy Chain 9 (MYH9)-Related Congenital Macrothrombocytopenia.

Myosin heavy chain 9 (MYH9)-related hereditary macrothrombocytopenia is caused by mutation of the MYH9 gene encoding the heavy chain A of non-muscle myosin of class II. We present a case that emphasizes the importance of awareness of rare disorders which could potentially avoid over-investigation, especially in benign conditions. A 72-year-old Caucasian female presented for preoperative evaluation for cataract extraction. She was noted to have thrombocytopenia of 30 K/uL along with elevated creatinine. She denied any acute symptoms except for a prolonged history of easy bruising. Physical exam revealed bruising over the extremities. Upon further questioning, she was previously investigated for thrombocytopenia and had multiple diagnostic as well as therapeutic interventions including bone marrow biopsies, steroids, intravenous immunoglobulins with no improvement. Her family history is consistent with low platelet counts for at least three generations. Peripheral blood smear showed large platelets, normal red and white blood cells with Döhle bodies. Further genetic testing revealed an inherited MYH9 mutation which is autosomal dominant. MYH9-related disorders are characterized by macrothrombocytopenia, often associated with glomerulonephritis, sensorineural deafness, cataracts, and cytoplasmic inclusion bodies within leukocytes. Management is mainly conservative and directed towards the prevention of iron deficiency anemia in young females. The use of desmopressin, in combination with tranexamic acid, is recommended in a perioperative setting. Our case emphasizes the importance of history-taking skills that could potentially minimize further diagnostic or therapeutic interventions in this benign genetic disorder.

Paradoxical Arthralgia Secondary to Anti-Tumor-Necrosis-Factor Alpha Therapy in Crohn's Disease.

The current treatment of choice for polyarthralgia in Crohn's disease consists of disease-modifying agents and anti-inflammatory therapy, such as anti-tumor-necrosis-factor alpha inhibitors like infliximab. However, here we report the case of a patient with longstanding Crohn's disease, who developed polyarthritis after receiving only one dose of infliximab. A 57-year-old male with a past medical history of Crohn's disease and stage 1 colon cancer was admitted to our hospital with complaints of polyarticular polyarthralgia, stiffness, and restriction of movements at the joints that started one day prior to admission. It initially began in bilateral wrists, impairing him to hold objects, then spread to bilateral ankles, causing him to fall, and finally affected his jaw, leading to inability to chew or articulate. He received the first dose of infliximab infusion 10 days prior to admission. Labs revealed elevated anti-infliximab antibody levels with low infliximab drug levels. He was treated with steroids, azathioprine, and non-steroidal anti-inflammatory drugs with discontinuation of infliximab. On follow-up, he was initiated on vedolizumab for maintenance of Crohn's disease and did not develop similar complaints again. Our patient had neither had pre-medication antibodies and positive anti-nuclear antibody, nor received the medication for a long duration as proposed in various studies. He developed severe symptoms affecting the majority of axial skeleton from face to feet just after receiving one dose of infliximab. This suggests that further studies in regard to pathophysiological mechanisms and the dose and duration in correlation to symptoms need to be performed for a better understanding of this disease entity.

Do the 2013 United States Preventive Services Task Force guidelines for lung cancer screening fail high-risk African American smokers? An institutional retrospective observational cohort study.

BACKGROUND: Lung cancer cause nearly 1.76 million deaths worldwide in 2018. In 2011, the National-Lung-Cancer-Screening-Trial showed 20% relative risk reduction with LDCT and subsequently led to the current USPSTF screening guidelines. However, the predominant focus on elderly, Caucasian questions its generalizability to communities with young, African Americans such as our institution. Hence, the objective of our study is to investigate the need to modify the current screening guidelines at our institution by assessing the applicability of newer individual risk-based prediction models for LDCT screening. METHODS: This is a retrospective observational cohort study of newly diagnosed lung cancer patients at LSU Health Sciences Center Shreveport from 2011 to 2015. One-third of the patients did not meet the current USPSTF screening guidelines. We categorized them into high-risk (groups1 and 2), moderate-risk, and low-risk according to 2018 NCCN Lung Cancer Screening Guidelines Version 1.2020. The high-risk groups were differentiated using the Tammemagi lung cancer risk calculator. RESULTS: Among those who did not meet the screening guidelines, nearly 50% were African American, 95% with known smoking history, and 80% diagnosed at advanced stage at the time of diagnosis. After employing the Tammemagi Risk based calculator, 12.5% were categorized into high-risk group 2, who are also eligible for annual LDCT. CONCLUSION: The current USPSTF guidelines have failed in our population consisting of young African American smokers, questioning the health disparity in medicine. By employing individual risk-based prediction models, we could potentially identify tailored high-risk populations leading to appropriate use of LDCT screening.