Go, Ronald S.

Introduction: There are discrepant definitions of both iron deficiency and anemia in pregnancy. It is recognized that iron requirements increase during pregnancy, particularly in the third trimester, and that deficiencies should be corrected to avoid adverse maternal-fetal outcomes. While low dose iron supplementation is recommended for all pregnant persons (ACOG Bulletin 233), dosing through prenatal vitamins varies widely. Additionally, despite the epidemic of iron deficiency in reproductive-age females globally and availability of high-value biomarkers (e.g., ferritin), current guidelines only recommend screening for iron deficiency during pregnancy in the presence of anemia. As anemia is the terminal manifestation of iron deficiency and reference ranges vary by organization, these guidelines and practices warrant further investigation and discussion. Methods: Retrospective review and analysis of the electronic health record at Mayo Clinic (Rochester, MN) was performed for obstetric deliveries between June 2022 and May 2023. Iron deficiency was defined as a ferritin <50 mcg/L and anemia was defined as a hemoglobin <11 g/dL. Results: A total of 2,141 unique deliveries were identified. The median age at delivery was 31 years old (range: 15 - 45) with 82% identifying as white. Anemia was documented in 42% (n=904) of pregnancies at least once throughout gestation, with an increasing frequency of 2% (n=43) in the first trimester, 11% (n=230) in the second trimester, 17% (n=361) in the third trimester, and 38% (n=803) from admission for delivery through the peri-partum period. There were five documented pRBC transfusions prior to admission for delivery; however, from admission for delivery through the peri-partum period, there were a total of 102 documented pRBC transfusions. In total, 15% (n=318) of pregnancies were screened for iron deficiency through ferritin testing. Ferritin levels were measured 415 times with 23% (n=96) occurring between the last menstrual period and 12 weeks gestational age (WGA), 24% (n=100) occurring between 13-27 WGA, 40% (n=164) occurring between 28-40 WGA, and 13% (n=55) occurring post-partum. Iron deficiency was found in 70% (n=67), 79% (n=79), 80% (n=164), and 78% (n=43) of measured ferritin levels, respectively. Despite the paucity of screening, prescriptions for oral iron increased throughout gestation with supplementation in pregnancy for 8% (n=170) prior to 12 WGA, 14% (n=290) for those 13-27 WGA, and 23% (n=489) for those 28-40 WGA. Similarly, intravenous iron infusions increased throughout gestation with supplementation in pregnancy for 0.3% (n=7) prior to 12 WGA, 0.7% (n=16) for those 13-27 WGA, and 4% (n=95) for those 28-40 WGA. Prenatal vitamins were documented in over 90% of pregnancies throughout gestation, although the majority were non-prescription and contained variable amounts of elemental iron. Conclusions: Iron deficiency in pregnancy is underrecognized and undertreated. It follows that the accuracy of current reference ranges for anemia in pregnancy are suspect without rigorous verification of replete iron stores in the reference population. Given potential implications for blood product utilization and prenatal care, additional studies are warranted to better characterize iron deficiency in pregnancy as well as clinical sequelae for both mothers and infants. Simultaneously, discussions are needed around current guidelines and recommendations for both screening and treating iron deficiency in pregnancy. Providers, institutions, and professional societies should pursue pragmatic quality improvement initiatives and equitable healthcare delivery efforts to optimize care for this vulnerable patient population at high risk of iron deficiency.

Background: AL amyloidosis is a potentially fatal plasma cell dyscrasia. In a randomized phase 3 study (Kastritis E et al, NEJM 2021;385:46-58), the addition of daratumumab to cyclophosphamide, bortezomib and dexamethasone (Dara-CyBorD) significantly improved hematological and organ responses, and prolonged event-free survival (EFS). There was no overall survival (OS) difference at a median follow-up of 11.4 months. Methods: A retrospective study of AL amyloidosis patients seen at our institution between January 2018 and December 2022 who received upfront Dara-CyBorD or CyBorD. We excluded patients who received other forms of upfront therapy (including modifications of the above regimens, such as bortezomib-dexamethasone or daratumumab-dexamethasone). We compared the hematologic and organ responses, EFS and OS between the two treatment groups. Hematologic response was assessed at 2 and 6 months from therapy initiation, while cardiac and renal responses at 6- and 12-month landmarks. In all response evaluations, we included responses up to autologous stem cell transplantation (ASCT) if used or second-line therapy for any reason. For EFS analysis, an event was defined as death of any cause, hematological progression, end-stage cardiac or renal failure, or need for subsequent anti-plasma cell therapy in the absence of hematological progression. OS was calculated from the time of treatment initiation to death or last follow-up. Results: Among 641 newly diagnosed patients seen at our center between 2018 and 2022, 361 patients (56%) were included on intention-to-treat analysis [Dara-CyBorD =147 (41% of the cohort); CyBorD=214 (59%)]. There was no difference in the baseline characteristics between the treatment groups, including age, sex, difference between involved and uninvolved light chains, bone marrow plasma cells percentage, NT-proBNP and 24-hour proteinuria. The 2-month hematologic complete response (hemCR; 15.3% vs 4.4%, P<0.001) and very good partial response or better (≥hemVGPR; 62.2% vs 32.5%, respectively; P<0.001) were higher with Dara-CyBorD compared to CyBorD. At 6 months, the hemCR and ≥hemVGPR were again in favor of the Dara-CyBorD group compared to CyBorD (32.0% vs 13.7%, and 72.8% vs 46.7%, respectively; P≤0.002). The 6- and 12-month cardiac response rate in the Dara-CyBorD and CyBorD groups were 40.2% vs 22.6% (P=0.01) and 44.1% vs 23.2%, respectively (P=0.006). Cardiac ≥VGPR at the 6- and 12-month landmarks were statistically higher with Dara-CyBorD compared to CyBorD and increased in both arms between 6 and 12 months [20.5 % vs 9.3% (P=0.03) and 34.3 % vs 20.0% (P=0.04), respectively]. The 6-month and 12-month renal response to first-line therapy were numerically higher with Dara-CyBorD compared to CyBorD but were not statistically significant (48% vs 31.3%, P=0.10; 54.1% vs 30.1%, P=0.05). The 6 month and 12 months, renal ≥VGPR were numerically higher with Dara-CyBorD compared to CyBorD, again without statistical significance (26% vs 19.6%, P=0.63; 35.7% vs 17.2%, P=0.11, respectively). Treatment with Dara-CyBorD was significantly associated with lower 6-month mortality rate compared to CyBorD (8.8% vs 16.3%, P=0.04). With a median follow-up of 43.3 months (30 vs 59.4 months for Dara-CyBorD vs CyBorD, respectively; P<0.001), the two-year EFS was superior in the Dara-CyBorD group compared to CyBorD (69.1% vs 30.3%, hazard ratio (HR) 0.36, 95% confidence interval (CI), 0.26 to 0.48, P<0.001). The 2-year OS was also statistically higher in the Dara-CyBorD group compared to CyBorD (82.0% vs 69.6%, HR 0.53, 95% CI, 0.36 to 0.79, P=0.003). 148 patients (40.9%) proceeded to second-line therapy with a median of 5.1 months from first line therapy. To adjust for difference in follow-up time between the two treatment groups, we analyzed the second line therapy utilization at the 12-month mark which was statistically higher with CyBorD compared to Dara-CyBorD (42.9% vs 14.9%, P<0.001). Also, at 12 months, a higher proportion of patients treated with CyBorD received ASCT compared to Dara-CyBorD (24.3% vs 13.6%, P= 0.01). Conclusions: In this cohort of newly diagnosed AL amyloidosis patients in a large referral center, we confirmed higher hematological and organ response rates with Dara-CyBorD compared to CyBorD. We have also demonstrated that these higher response rates translate into a survival advantage of Dara-CyBorD over CyBorD.

Background: The term classical hematology (CH), referring to a subspecialty focusing on non-cancer blood disorders, was officially adopted by the American Society of Hematology (ASH) in 2022. There is a perceived shortage of classical hematologists, although data are limited (Winter JN, Hematologist 2022). Prior studies have shown that <6% of hematology-oncology fellows pursue a practice subspecializing in CH after training (Todd RF, Blood 2004; Marshall Al, Blood Adv 2018). Moreover, mentorship is consistently cited as the most important factor guiding fellows' career decisions (Sharma D, Blood Adv 2019; Masselink LE, Blood Adv 2019). To help bridge the CH workforce gap, ASH has supported additional hematology-focused fellowship programs (HFFP) within select hematology-oncology fellowship programs. CH constitutes a large proportion of consults in US National Cancer Institute (NCI)-designated cancer centers (West CV, JCO Oncol Pract 2024). The goals of our study were: 1) to determine the proportion of adult hematologist-oncologists within NCI cancer centers who practice CH; and 2) to describe the physician characteristics of cancer centers with HFFP and compare these centers to those without HFFP. Methods: We included all NCI-designated cancer centers with a clinical program as of April 1, 2024. The only exception was St Jude Children's Hospital due to its pediatric focus. We obtained the practice profile of each internal medicine-trained adult hematologist-oncologist (henceforth, physician) as well as the availability of HFFP from the respective cancer center websites. We also searched the corresponding department of medicine and division of hematology at each affiliated academic institution to ensure inclusion of all physicians practicing CH. Each physician was classified into one of the following categories: classical hematologist (attending to only non-cancer conditions), general hematologist-oncologist (cancer and non-cancer conditions), and oncologist (cancer only). The number of hematology-oncology fellowship programs in the US was obtained from the Accreditation Council for Graduate Medical Education. Results: We included 64 NCI-designated cancer centers, 55 of which were considered as comprehensive cancer centers. There was a total of 4,616 physicians (3,891 oncologists [84.3%], 487 hematologists-oncologists [10.6%], and 238 classical hematologists [5.1%]). The median numbers of physicians, oncologists, general hematologist-oncologists, and classical hematologists per center were 55 (range, 16-275), 45 (range, 12-270), 5 (range, 0-48), and 3 (range, 0-13), respectively. The median proportions of classical hematologists and physicians practicing CH (general hematologist-oncologists plus classical hematologists) were 5.1% (range, 0-20.0) and 14.9% (range, 0-55.6%), respectively. There were 12 HFFP within NCI-designated cancer centers (18.8%). Most (11/12) centers with HFFP had >50 physicians (median 95 [range, 38-185]) and >5% classical hematologists (median 6% [range, 3.8-13.5%]); 11 centers with similar characteristics did not have HFFP. Centers with HFFP have significantly higher numbers of physicians (median 95.0 [range, 38-185] vs 49.5 [range, 16-275]; P=0.001) and classical hematologists (median 6.0 [range, 3-13] vs 2.0 [range, 0-11]; P<0.001) but similar proportions of classical hematologists (median 6.0% [range, 3.8-13.5] vs 4.5% [range, 0-20.0]; P=0.078) and physicians practicing CH (median 12.3% [range, 6.5-47.7] vs 15.7% [range, 0-55.6]; P=0.402) compared to those without HFFP. Conclusions: Among adult hematologist-oncologists at NCI-designated cancer centers, only 1 in 20 are classical hematologists, although 1 in 7 have CH as part of their practice. Within NCI-designated cancer centers, only 1 in 5 have an HFFP. These findings suggest that there is an opportunity for NCI-designated cancer centers to encourage and recruit physicians subspecializing in CH and a rationale to create additional HFFPs. These measures may help further alleviate CH workforce shortages and expand CH mentorship to meet the needs of an increasingly complex subspecialty within hematology.

Introduction: Traditional home-call, or the practice of holding a pager at home overnight to manage questions regarding patient care and direct patient calls, is a common component of hematology fellowship. Depending on the institution and training program, the frequency and expectations of home-call may vary. Home-call in fellowship is often performed overnight between two days of work without a “post-call” day to recover. As a field, medicine has entered the digital era, accompanied by changes in patient interactions and expectations involving after-hours calls. Little is known about modern non-digital interactions with patients such as after-hours calls in hematology practices and their effects on trainees. This project aims to evaluate the home-call pager burden and subjective experience in fellows. Methods: We analyzed Hematology Pager (HP) data from 7/1/19 - 4/14/23. The HPs for Mayo Clinic Rochester are covered by hematology fellows, including the weekend and after hours (6PM - 7AM) pagers. Those of interest were the Consults Pager (CP; covers new inpatient consults if discussion initiated outside of electronic order) and the Outpatient Pager (OP; covers direct patient calls as well as critical result communications for weekends and after-hours). The frequency of home-call varies based on each rotation but can require home-call up to 3-4 times per week with the expectation to occasionally present to the hospital overnight in the setting of a hematologic emergency. An optional survey was distributed to the fellowship in May 2024 with the intent to support trainee wellness and assess perceptions and attitudes toward the home-call experience. We allowed for free-text responses and used a 5-point Likert scale for structured responses. Results: The CP received a total of 5,304 pages during the analyzed period for a mean of 3.8 pages per day. Of those, 975 pages (18%) occurred after-hours and 1,250 (24%) during weekends. The OP received a total of 3,964 pages during the analyzed period, definitionally during weekends and/or after-hours, for a mean of 2.9 pages per day. The OP had the highest relative activity on weekends, which ranged from 1-18 calls per day. The survey captured 19/33 (58%) hematology/oncology fellows, which were comprised of 58% males and 42% females representing all levels of training with 42% PGY4s, 26% PGY5s, and 32% PGY6s. Over 85% felt that holding the HP was not an educational experience and that they did not learn about hematology while managing it. Moreover, 85% of respondents felt that they did not help patients get time-sensitive care when holding the HP. Only 5% felt that the majority of care provided through the HP required a Medical Degree and 32% agreed that the majority of calls were due to an acute clinical status change warranting immediate medical attention. If immediate medical attention was possibly required, 95% of fellows reported a recommendation of evaluation in the nearest emergency room. Over 85% of fellows felt that the HP affected other individuals (e.g., significant other) in their households. No respondents (0%) agreed that they could maintain their exercise schedule while holding the HP and only 16% reported no effect on their social life. Nearly all fellows reported not feeling well rested after a home call shift, regardless of whether the level of pager activity was low (≤2 calls), average (3-5 calls), or high (≥6 calls). Up to 95% of fellows reported feeling anxiety when holding the pagers. The free responses outlined concerns about sleep deprivation from call multiple times per week, the impact of home-call on learning, and the desire for a process that triaged patient calls at night that did not require physician resource utilization. Conclusions: Home-call is a long-standing tradition that gives hospital teams and patients access to specialty care after standard business hours. However, home-call can impact wellness, contribute to fatigue, and affect learning. To our knowledge, this is the first analysis evaluating call pager volumes and hematology fellows' perceptions and attitudes toward the home-call experience. Hematology is a dynamic field that requires empathy, critical thinking, and physician wellness to provide the best possible care to patients. In the digital era, the current structure of this long-standing tradition may warrant reevaluation and optimization to prioritize a system beneficial for both patient care and physician wellness.

Background: Erdheim-Chester disease (ECD) manifests as multi-organ infiltration of clonal histiocytes with mutations primarily in the mitogen-activated protein kinase (MAPK) pathway. The revised classification of histiocytosis (2016) categorizes ECD with typical bilateral, symmetric osteosclerosis of the lower extremity long bones as classical (C) and as non-classical (NC) if otherwise. The clinical and biological significance of this classification is unclear. This study compared the clinical and genotypic findings of the 2 subtypes within a large cohort of ECD patients. Methods: We included patients seen at our institution since 1990 meeting the following criteria: A) had an ECD diagnosis based on the revised criteria by Haroche J, et al. (Blood 2020;135:1311-1318); B) completed whole-body imaging studies including long bones of the legs. Classification as C-ECD required symmetric osteosclerosis of the distal femur and/or proximal tibia/fibula. Results: A total of 145 patients were enrolled, comprising a male-to-female ratio of 2:1 (66.2% male). C-ECD was diagnosed in 77.2% of cases, and NC-ECD in 22.8%. The median age at diagnosis was similar with 58.5 years (range, 18-82) in C-ECD and 55 years (range, 20-81) in NC-ECD, (p=0.65). The most frequently affected systems included skeletal (81.4%), renal (60.0%), vascular (45.5%), cardiac (40.0%), central nervous (38.6%), sinus (37.2%), pulmonary (36.6%), and adrenal (32.4%). The numbers of organs involved were significantly higher in C-ECD compared to NC-ECD (median 5 vs 3, p<0.01). Higher rates of skeletal (100% vs. 18.2%, p<0.01), adrenal gland (37.5% vs. 15.2%, p=0.02), and sinus (44.6% vs. 12.1%, p<0.01) involvement were observed in C-ECD. Arginine vasopressin deficiency (AVP-D) was exclusively observed in C-ECD (20.7% vs. 0%, p<0.01). NC-ECD had a higher rate of cardiac involvement (69.7% vs. 31.3%, p<0.01). No significant differences were found in other systems. The overall median time between onset of the first symptoms/signs to diagnosis was 15 months with no significant difference between C-ECD and NC-ECD (17.5 vs. 12 months, p=0.18). The median time to diagnosis of ECD in patients with AVP-D was 38.5 months, compared to 12 months without AVP-D (p=0.09). Genetic testing was conducted in 86.2% of patients and B-Raf proto-oncogene (BRAF) alterations were identified in 59.2% of the tested cases. BRAFV600E was more prevalent in C-ECD (61.3% vs. 21.9%, p<0.01), whereas non-V600 mutations were more commonly found in NC-ECD (12.5% vs. 1.1%, p<0.01). There was no significant difference in the frequency of BRAF fusions. NC-ECD patients exhibited a higher rate of MAP2K1 mutations (25.0% vs. 5.4%, p<0.01). Other frequently mutated genes included KRAS (4.0%), NRAS (2.4%), and CSF1R (2.4%), although no significant difference was observed in their frequency between C-ECD and NC-ECD. Testicular involvement appeared to be more common in patients with MAP2K1 mutations (23.1% vs. 8%, p=0.08). Two patients with pathogenic CSF1R mutations both had central nervous system (CNS) involvement. Among C-ECD patients, BRAFV600E conferred a higher rate of CNS involvement (50.9% vs. 25%, p=0.01). No significant difference was observed in NC-ECD patients (71.4% vs 36%, p=0.09). Among NC-ECD cases, MAP2K1 mutations conferred a reduced risk of cardiac involvement (37.5% vs. 79.2%, p=0.03) and no such difference was observed in patients with C-ECD (40% vs 34.1%, p=0.79). The median numbers of organs involved in patients with BRAF, MAP2K1, and KRAS/NRAS mutations were 5, 3, and 3, respectively, with no significant difference. Conclusions: C-ECD affects more organs and more frequently involves bones, adrenal glands, and sinuses. AVP-D was exclusively observed in C-ECD. Conversely, NC-ECD showed a higher prevalence of cardiac involvement. BRAFV600E was more commonly identified in C-ECD, whereas non-V600 mutations and MAP2K1 mutations were more prevalent in NC-ECD. Among C-ECD patients, BRAFV600E was correlated with a greater likelihood of CNS involvement. Conversely, NC-ECD patients with MAP2K1 mutations had a reduced risk of cardiac involvement. This study highlights the distinct clinical and molecular features of C-ECD and NC-ECD, underscoring the importance of subclassifying ECD into classical and non-classical forms. Further studies are needed to explore differences in the clinical outcomes between the 2 forms.

Background: Follicular dendritic cell sarcoma (FDCS) is a rare low- to intermediate-grade sarcoma, typically presenting as a slowly growing, painless mass composed of spindle-shaped cells in a whorled pattern. First described in 1986, FDCS has since been identified in several hundred cases. FDCS originates from mesenchymal dendritic cells and is distinct from other histiocytic neoplasms. Its management aligns more with soft tissue sarcomas. Epidemiologically, FDCS is exceedingly rare, constituting less than 0.4% of soft tissue sarcomas. Methods: With IRB approval, we identified patients with biopsy-proven FDCS treated at Mayo Clinic. Chart review extracted clinical characteristics, laboratory testing, treatment data, and clinical outcomes, compiled into Excel. Data analysis was performed through RStudios. Descriptive statistics of patient characteristics, such as gender and stage of disease, were summarized in tables. We compared overall survival (OS) through Kaplan Meier curves, stratifying patients into cohorts based on topics of interest, such as differences in survival in nodal vs. extranodal disease or differences in survival among different chemotherapy regimens. Results: Forty patients met the inclusion criteria, of biopsy proved FCDS. Median age at diagnosis was 57.7 years (SD 14). Men comprised 45% of patients. Locations of malignancy were abdomen and pelvis (32.5%), thoracic and pulmonary regions (32.5%), lymph nodes and neck (20.0%), musculoskeletal (2.5%), and other locations (12.5%). Primary therapies included surgical resection (42.5%), systemic chemotherapy (32.5%), no treatment (10.0%), radiation (2.5%), with data missing for 12.5% of cases. Concurrent or preceding Castleman's Disease was seen in 7.5% (3/40) of patients; one case preceded FCDS, and two were concurrent. Of these patients with Castleman's Disease, one was resected and the other two were not. Two cases were unicentric, and one was multicentric. First-line systemic chemotherapy was most often gemcitabine and docetaxel, with 9/40 patients receiving this regimen. Ifosfamide and doxorubicin were utilized in 3/40 patients. 2/4 patients had received doxorubicin alone. 2/4 patients had received CHOP. The response rate for patients with gemcitabine and docetaxel was complete response for 2/9 (22%) patients, partial response for 2/9 (22%), stable disease for 2/9 (22%), progressive disease for 1/9 (11%), and missing for 2/9 (22%), giving an overall response rate of 67%. For ifosfamide and doxorubicin, one patient had partial response (33%), another had stable disease (33%), and the last patient's data was missing (33%), adding up to a 66% overall response rate. For CHOP, one patient had progressive disease, and the other had partial response. For doxorubicin, both patients had stable disease. At a median follow-up of 29.5 months (IQR 9.2-75.2 months), the median OS was 160.68 months for the group with both nodal and extranodal disease versus 39.95 months for the extranodal disease-only group. The median OS of the nodal disease alone was not reached, with an estimated 2-year OS of 75%. To evaluate the impact of various primary therapies on outcomes in patients with advanced disease, we conducted a survival analysis by therapy used (no treatment, radiation, surgical resection, and systemic chemotherapy). Patients receiving no treatment had a median survival time of 28.9 months, while those treated with radiation had a median survival time of 19.3 months. Patients undergoing surgical resection had an undetermined median survival time, but notably, 80% were alive at the end of the time period analyzed in this study with a median follow-up time of 60.7 months. Those receiving systemic chemotherapy had a median survival time of 30.7 months. Conclusions: This project is one of the largest known single-center studies dedicated to FDCS. We show that the incidence of preceding or concurrent Castleman's Disease is relatively low. Gemcitabine and docetaxel was the most utilized chemotherapy regimen, but there weren't enough data to conclude if this regimen had a better response rate compared to others. Surgical resection of advanced disease is associated with superior outcomes. When systemic therapy is needed, the median survival was lower.

Background Absolute basophil count (ABC) might be increased in patients with myeloproliferative neoplasms and has been associated with poor prognosis in chronic myeloid leukemia (CML) and, possibly, primary myelofibrosis (PMF, Front. Oncol 2019;9:872). In a Mayo Clinic survey of 382 patients with BCR::ABL1-negative leukocytosis and ABC ≥0.09 x 109/L, 191 (50%) were associated with myeloid neoplasms, including 104 (27%) with CML, 23 (6%) essential thrombocythemia, 21 (6%) polycythemia vera (PV), and 18 (5%) PMF (AJH 2020;95:E216). Herein, we tapped into a well-characterized cohort of patients with PV, in order to describe the prevalence of basophilia, at specific ABC thresholds, and corresponding clinical, molecular, and prognostic correlates. Methods Study patients were retrospectively recruited from Mayo Clinic (USA) databases, after approval from IRB. Diagnostic criteria were according to the International Consensus Classification (Blood 2022;140:1200). Study inclusion criteria included the availability of information on ABC and absolute eosinophil count (AEC). Mayo Clinic institutional reference range for ABC was 0.01 to 0.08 x 109/L and for AEC 0.03 to 0.48 x 109/L. “Eosinophilia” was defined as an AEC of ≥0.6 x 109/L. Basophilia was evaluated both at an ABC of ≥0.1 x 109/L and ABC of ≥0.3 x 109/L, the latter representing 3 x the upper limit of the normal reference range. Cytogenetic information obtained within one year of diagnosis was available in 270 patients. Next-generation sequencing information collected before disease transformation was available in 99 patients. Conventional statistical methods were employed for comparisons of groups and survival analysis (JMP Pro 17.0.0 software SAS Institute, Cary, NC, USA). Results Information on ABC and AEC, obtained within one year of diagnosis, was available in 478 patients (median age 66 years; males 51%). Median values at presentation were 10.6 x 109/L for leukocyte count, 453 x 109/L platelet count, and 17.3 g/dL hemoglobin level. Presenting symptoms included palpable splenomegaly 24%, pruritus 31%, arterial thrombosis 12%, and venous thrombosis 17%. Median and range values for ABC and AEC were 0.12 x 109/L (0-3.2) and 0.27 x 109/L (0-6.5), respectively. ABC was ≥0.3 x 109/L in 80 (17%) patients and ≥0.1 x 109/L in 315 (66%). AEC was ≥0.6 x 109/L in 68 (14.6%) patients. ABC≥0.3 x 109/L was associated with AEC ≥0.6 x 109/L (p<0.01), leukocytosis (p<0.01), and palpable splenomegaly (p=0.02), but not platelet count, pruritus, smoking history, diabetes, or arterial or venous thrombosis; in multivariable analysis, the association with leukocytosis, but not that with splenomegaly, was confirmed. At a median follow-up of 5.7 years (range 0.03-32.8), 132 (28%) deaths, 17 (3.6%) leukemic and 40 (8.4%) fibrotic progressions were documented. Post-diagnosis events also included arterial (7%) and venous (9%) thrombosis. In univariate analysis, neither ABC (p=0.8, 0.7, and 0.96) nor AEC (p=0.7, 0.6, and 0.8), evaluated as continuous variables, affected overall (OS), leukemia-free (LFS), or myelofibrosis-free (MFFS) survival, respectively. Similarly, eosinophilia at AEC ≥0.6 x 109/L did not appear to influence OS (p=0.99), LFS (p=0.6) or MFFS (p=0.5). On the other hand, although basophilia at ABC≥0.3 x 109/L did not affect OS (p=0.27), it was significantly associated with inferior LFS (HR 6.5, 95% CI 2.3-18.0; p<0.01) and MFFS (HR 2.3, 95% CI 1.2-4.5; p=0.01); the corresponding p values for ABC≥0.1 x 109/L were 0.7, 0.1, and 0.17. The detrimental impact of basophilia (ABC≥0.3 x 109/L) on LFS was confirmed (P<0.01) with multivariable analysis that included other clinical variables, including leukocytosis (NS), platelet count (NS), basophil percentage (NS), age (p<0.01), and palpable splenomegaly (p<0.01). Results were similar during multivariable analysis for MFFS with palpable splenomegaly (p<0.01), ABC≥0.3 x 109/L (p=0.03), and age (p=0.05) sustaining independent predictive value. The number of informative cases was too small to evaluate prognostic interaction with mutations and karyotype. Conclusions: Basophilia in PV is associated with palpable splenomegaly and leukocytosis and independently predicts leukemic and myelofibrotic transformation. Additional studies are needed to confirm these observations and examine prognostic interaction with mutations and karyotype.

Introduction: Autoimmunity in Rosai-Dorfman disease (RDD) has been reported in several case reports and small case series. The recent consensus RDD guidelines even classify “immune-related RDD” as a distinct entity, but little is known about the prevalence and patterns of autoimmune conditions in this rare disease. We conducted this study to evaluate a large cohort of patients with RDD for concomitant autoimmunity. Methods: We conducted a retrospective review of cases diagnosed with RDD from five referral centers globally. Data pertaining to autoimmunity were captured in terms of serology and a clinical diagnosis of autoimmune disease (AID) and compared to previously reported prevalence of AID and autoimmunity in the general population and in patients with other lymphomas. Results: We included 157 patients diagnosed with RDD from 2003-2023. Median age at the time of RDD diagnosis was 48 years, IQR 35.5-60. This included 103 females (65.6%) and 54 male (34.4%). Racial distribution included 54 Black (34.4%), 52 White (33.1%), 40 Asian (25.5%), 7 Middle Eastern (4.5%) and 4 other (2.5%). 83 patients had multi-systemic disease (52.8%) and 74 had single organ involvement (47.2%). Most common organs involved were skin/subcutaneous tissue (78, 49.7%), lymph nodes (63, 40.1%), bone (54, 34.2%). Tissue next generation sequencing data was available for 100 patients (63.7 %) and showed KRAS mutation (19, 19 %), MAP2K/MEK (13, 13%), other mutations (27, 27 %), and no mutations (41, 41%). Mean ESR at diagnosis of RDD was 28.42 mm/Hr and mean CRP was 19.5 mg/L. In our cohort, 28 patients (17.8%) were diagnosed with an AID. 19 (67.8%) were diagnosed with the AID prior to the diagnosis of RDD. Most common AID was systemic lupus erythematosus (6, 21.4%), rheumatoid arthritis (5, 17.8%), autoimmune hemolytic anemia (3, 10.7%), polymyalgia rheumatica (2, 7.1%). AID was more common in female vs male (64.3% vs 35.7%, p 0.8) and were more commonly seen in patients with multisystem compared to single organ RDD (60.7% vs 39.3%, p 0.3). Mean ESR and CRP at the time of RDD diagnosis in patients with AID were 40.63 mm/Hr and 37.04 mg/L respectively. Autoimmune antibodies were tested in 90 patients (57.3%), of which 43 (47.8%) were positive for atleast one autoantibody which included 15 patients (16.7%) with AID and a positive autoantibody and 6 (6.6%) with AID and negative antibodies (p 0.01). Most common antibodies were ANA (29/83, 34.9%), 42.3% with a titer higher than 1:160. Other antibodies include RF (10/60, 16.67%), anti-neutrophilic cytoplasmic antibody (3/19, 15.8%), double stranded DNA (6/56, 10.7%). Positive Antibodies were more common in female compared to male patients (72% vs 23%, p 0.04) and in patients from China compared to North America (45.7% vs 22.6%, p 0.007). Autoantibody positivity was common in multi-system vs single organ RDD (53.5% vs 46.5%, p 0.9). Mean ESR and CRP in this group of patients were 34.54 mm/Hr and 23.93 mg/L respectively. Median duration of follow up for our cohort was 32 months (IQR 14-65). Five-year survival was 93.4%. There were a total 8 deaths reported in the cohort, none of which were in patients with underlying AID. In a multivariable analysis, AID was associated with race (odds ratio [OR] for Middle Eastern compared with Chinese, OR 7, p=0.02) but other factors like organ involvement, mutational status, sex and age at diagnosis were not significant. Conclusions: Our study reveals a high prevalence of autoimmunity in RDD, both in terms of AID (17.8 %) and positive autoantibodies (47.8 %), which is much higher than the general population rates of approximately 3% and 16% respectively, and higher than patients with non-Hodgkin lymphoma, 7.6% and 39%, respectively. There was a trend toward association of AID with multisystem RDD and among individuals from North America and Middle East compared to China, although auto-antibody positivity was more common in Chinese patients. Mean ESR and CRP at the time of diagnosis of RDD was higher in the patients who had AID. We did not find any statistically significant association between AID and autoantibody positivity with the underlying driver mutation. Nearly half of the patients with RDD who also had AID did not have a positive autoantibody, thereby implying the need of clinical evaluation for rheumatological symptoms rather than empiric serological testing. Overall, this study also highlights the need to explore the biological link between RDD and autoimmunity.

Background The American Society of Clinical Oncology (ASCO) launched the Diversity in Oncology initiative in 2017 to address the need for increased minority representation in the hematology-oncology workforce. A recent series of reports, titled “State of the Oncology Workforce in America,” published in JCO Oncology Practice in 2021 and 2022, focused on this issue. Notably, these reports did not include any data regarding the representation of Asian minorities in the field. Therefore, our objective was to assess the proportion of Asian professionals within the hematology-oncology workforce, encompassing both practitioners and trainees. Methods We conducted a comprehensive search for publicly available data regarding Asian representation among US hematology-oncology practitioners and trainees in both adult and pediatric fields. Our primary data sources included the 2020 US Census, the Association of American Medical Colleges, the Accreditation Council for Graduate Medical Education, and various professional societies. We defined practitioners to include hematologist-oncologists, gynecologic oncologists, radiation oncologists, surgical oncologists, hematopathologists, hematology-oncology nurse practitioners, hematology-oncology physician assistants, and nurses specializing in hematology-oncology. Trainees encompassed fellows and residents. Additionally, we gathered comparable data on the US population, medical students, adult internal medicine residents, gynecology residents, pediatric residents, pathology residents, surgery residents, nurses, nurse practitioners, and physician assistants. To provide a comprehensive overview of the hematology-oncology workforce, we utilized data from 2020 to 2022, and whenever possible, we collected longitudinal data on trainees over the years. Results As of 2020, Asians represented 6.2% of the US population. Among hematology-oncology physician practitioners, the percentage of Asian individuals ranges from 14.7% to 32.1%, including 32.1% of adult hematologist-oncologists, 20.4% of pediatric hematologist-oncologists, 25.9% of radiation oncologists, 14.7% of gynecologic oncologists, and 7.0% of hematology-oncology physician assistants. In the realm of physician trainees, Asian representation is between 17.9% and 35.3%, with 35.3% of adult hematology-oncology fellows, 20.0% of pediatric hematology-oncology fellows, 26.4% of radiation oncology residents, and 17.9% of gynecologic oncology fellows. Additionally, the proportion of Asian residents from which hematology-oncology fellows are drawn ranges from 14.9% to 35.9%. Specifically, 35.9% of internal medicine residents, 22.0% of pediatric residents, 14.9% of gynecology residents, 26.6% of pathology residents, and 19.2% of surgical residents are Asian. Furthermore, 26.7% of medical students identify as Asian. Notably, the proportions of Asian hematology-oncology trainees and medical students have remained relatively stable from 2005 to 2022. Data on hematopathologists, surgical oncologists, and non-physician practitioners are limited, although Asian representation among hematology-oncology physician assistants is 7.0% and among nurses is 7.2%. Conclusions Asians comprise a large segment of the hematology-oncology workforce in the US. While only 1 in 20 people in the US are Asians, between 1 in 3 and 1 in 5 hematology-oncology physician practitioners and trainees, are Asians. Data are limited for non-physician practitioners. Asian minority representation should be highlighted and considered as an example of success in diversity in hematology-oncology workforce. This framework should be embraced moving forward to continue advancing minority representation throughout the field of hematology-oncology.