NCCN Guidelines® Insights: Systemic Mastocytosis, Version 3.2024.

Mastocytosis is a heterogeneous group of disorders comprising cutaneous mastocytosis, systemic mastocytosis, and mast cell sarcoma. It is associated with a variety of symptoms related to the release of mast cell mediators and mast cell tissue infiltration. Referral to specialized centers with expertise in the management of mastocytosis and multidisciplinary collaboration with subspecialists (eg, allergists for the management of anaphylaxis and drug hypersensitivities, anesthesiologists for invasive procedures or surgery, high-risk obstetrician for pregnancy) is recommended. The NCCN Guidelines for Systemic Mastocytosis provide evidence- and consensus-based recommendations for the diagnosis and comprehensive care of patients with systemic mastocytosis. The multidisciplinary panel of experts convenes at least once a year to review requested changes to the guidelines from both internal and external entities as well as to discuss data on existing and new therapies. These NCCN Guidelines Insights focus on some of the recent updates to the guidelines.

Acetabular Labral Reconstruction Does Not Demonstrate Superior Biomechanical Properties Compared to Labral Repair or Intact Native Labrum but Is Superior to Labral Excision: A Systematic Review of Cadaveric Studies.

PURPOSE: To systematically review and compare biomechanical properties of labral reconstruction to labral repair, intact native labrum, and labral excision in cadaveric studies. METHODS: A search of the PubMed and Embase databases was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and checklist. Cadaveric studies focused on hip biomechanics related to intact labrum, labral repair, labral reconstruction, labral augmentation, and labral excision were included. Investigated parameters included biomechanical data measures, such as distraction force, distance to suction seal rupture, peak negative pressure, contact area, and fluid efflux. Review articles, duplicates, technique reports, case reports, opinion articles, articles written in a language other than English, clinical studies focusing on patient-reported outcomes, studies performed in animals, and articles with no abstract available were also excluded. RESULTS: Fourteen cadaveric biomechanical studies were included that compared labral reconstruction to labral repair (4 studies), labral reconstruction to labral excision (4 studies); and evaluation of distractive force of the labrum (3 studies), the distance to suction seal rupture (3 studies), fluid dynamics (2 studies), displacement at peak force (1 study), and stability ratio (1 study). Data pooling was not performed because of methodological heterogenicity of the studies. Labral reconstruction did not outperform labral repair in restoring the hip suction seal or any other biomechanical property. Labral repair significantly prevented greater fluid efflux when compared to labral reconstruction. Labral repair and reconstruction improved the distractive stability of the hip fluid seal from the labral tear and labral excision stage, respectively. Furthermore, labral reconstruction demonstrated to have better biomechanical properties than labral excision. CONCLUSIONS: In cadaveric studies, labral repair or intact native labrum was biomechanically more superior than labral reconstruction; however, labral reconstruction can restore acetabular labral biomechanical properties and was biomechanically superior to labral excision. CLINICAL RELEVANCE: In cadaveric models, labral repair outperforms segmental labral reconstruction in preserving the hip suction seal; nonetheless, segmental labral reconstruction biomechanically outperforms labral excision at time 0.

Defining the Percent Thresholds for Achieving the Maximum Outcome Improvement of the Modified Harris Hip Score, the Non-Arthritic Hip Score, the Hip Outcome Score-Sports Subscale, the Visual Analog Scale for Pain, and the International Hip Outcome Tool-12 in Revision Hip Arthroscopy at Minimum 2-Year Follow-Up.

PURPOSE: To determine the respective percent thresholds for achieving the maximal outcome improvement (MOI) for the modified Harris Hip Score (mHHS), the Non-Arthritic Hip Score (NAHS), the Hip Outcome Score-Sports Subscale (HOS-SSS), the visual analog scale (VAS) for pain, and the International Hip Outcome Tool-12 (iHOT-12) that were associated with satisfaction following revision hip arthroscopy, and to identify predictors for achieving the MOI. METHODS: An anchor question was provided to patients who underwent revision hip arthroscopy between April 2017 and July 2020. Patients were included for the final analysis if they answered the anchor question and had minimum 2-year follow-up. Receiver operating characteristic analysis was used to determine the thresholds for the percentage of the MOI predictive of satisfaction. A P-value of < .05 was considered significant. RESULTS: In total, 318 patients underwent revision hip arthroscopy. Of those patients, 292 (91.8%) had minimum 2-year follow-up. Of this cohort, 68 answered the anchor question, with 49 (72.1%) female and 19 (27.9%) male patients. The mean age, and body mass index time were 32.9 ± 13 years and 25.4 ± 5.1, respectively. It was determined that 42.1%, 50%, 48.1%, 50%, and 50% of MOI were the thresholds for maximal predictability of satisfaction for mHHS, NAHS, HOS-SS, VAS for pain, and the iHOT-12, respectively. The presence of unaddressed subspine impingement was a significant predictor for achieving the MOI threshold for the VAS (odds ratio 1.40; 95% confidence interval 1.00-1.95; P = 0.0273). CONCLUSIONS: Following revision hip arthroscopy, the percent thresholds for achieving the MOI at a minimum 2-year follow-up for the mHHS, NAHS, HOS-SS, VAS for pain, and iHOT-12 were 42.1%, 50%, 48.1%, 50%, and 50.9%, respectively. Addressing residual subspine impingement was identified as significant positive predictor for achieving the MOI. LEVEL OF EVIDENCE: Level IV, case-series.

Increased TIM-3 and galectin-9 serum levels in patients with advanced systemic mastocytosis.

BACKGROUND: Systemic mastocytosis is characterized by expansion of clonal mast cells in various tissues. Several biomarkers with diagnostic and therapeutic potential have recently been characterized in mastocytosis, such as the serum marker tryptase and the immune checkpoint molecule PD-L1. OBJECTIVE: We aimed to investigate whether serum levels of other checkpoint molecules are altered in systemic mastocytosis and whether these proteins are expressed in mastocytosis infiltrates in the bone marrow. METHODS: Levels of different checkpoint molecules were analyzed in serum of patients with different categories of systemic mastocytosis and healthy controls and correlated to disease severity. Bone marrow biopsies from patients with systemic mastocytosis were stained to confirm expression. RESULTS: Serum levels of TIM-3 and galectin-9 were increased in systemic mastocytosis, particularly in advanced subtypes, compared with healthy controls. TIM-3 and galectin-9 levels were also found to correlate with other biomarkers of systemic mastocytosis, such as serum tryptase and KIT D816V variant allele frequency in the peripheral blood. Moreover, we observed expression of TIM-3 and galectin-9 in mastocytosis infiltrates in bone marrow. CONCLUSIONS: Together, our results demonstrate for the first time that serum levels of TIM-3 and galectin-9 are increased in advanced systemic mastocytosis. Moreover, TIM-3 and galectin-9 are expressed in bone marrow infiltrates in mastocytosis. These findings provide a rationale for exploring TIM-3 and galectin-9 as diagnostic markers and eventually therapeutic targets in systemic mastocytosis, particularly in advanced forms.

Triple-Negative Primary Myelofibrosis: A Bone Marrow Pathology Group Study.

Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm driven by canonical gene mutations in JAK2, CALR, or MPL in >80% of the cases. PMF that lacks these canonical alterations is termed triple-negative PMF (TN-PMF). The pathologic and genetic characteristics of TN-PMF compared with those of conventional PMF with canonical driver mutations (DM-PMF) have not been well studied. We aimed to identify clinicopathologic and molecular genetic differences between patients with TN-PMF (n = 56) and DM-PMF (n = 89), all of whom fulfilled the 2016 World Health Organization diagnostic criteria for PMF. Compared with the control group, patients in the TN-PMF group were more likely to have thrombocytopenia and less likely to have organomegaly. The bone marrow in patients with TN-PMF showed fewer granulocytic elements and more frequent dyserythropoiesis. Cytogenetic analysis showed a higher incidence of trisomy 8. Targeted next-generation sequencing revealed a lower frequency of ASXL1 mutations but enrichment of ASXL1/SRSF2 comutations. Our findings demonstrated several clinicopathologic and molecular differences between TN-PMF and DM-PMF. These findings, particularly the observed mutation profile characterized by a higher frequency of ASXL1 and SRSF2 comutation, suggest that at least a subset of TN-PMF may be pathogenetically different from DM-PMF, with potential prognostic implications.

STAT5B mutations in myeloid neoplasms differ by disease subtypes but characterize a subset of chronic myeloid neoplasms with eosinophilia and/or basophilia.

STAT5B has been reported as a recurrent mutation in myeloid neoplasms (MNs) with eosinophilia, but the overall frequency and importance across a spectrum of MNs are largely unknown. We conducted a multicenter study on a series of 82 MNs with STAT5B mutations detected by next-generation sequencing. The estimated frequency of STAT5B mutation in MNs was low.

Proposed refined diagnostic criteria and classification of eosinophil disorders and related syndromes.

Eosinophilia and eosinophil activation are recurrent features in various reactive states and certain hematologic malignancies. In patients with hypereosinophilia (HE), HE-induced organ damage is often encountered and may lead to the diagnosis of a hypereosinophilic syndrome (HES). A number of known mechanisms and etiologies contribute to the development of HE and HES. Based on these etiologies and the origin of eosinophils, HE and HES are divided into primary forms where eosinophils are clonal cells, reactive forms where an underlying reactive or neoplastic condition is detected and eosinophils are considered to be "non-clonal" cells, and idiopathic HE and HES in which neither a clonal nor a reactive underlying pathology is detected. Since 2012, this classification and the related criteria have been widely accepted and regarded as standard. However, during the past few years, new developments in the field and an increasing number of markers and targets have created a need to update these criteria and the classification of HE and HES. To address this challenge, a Working Conference on eosinophil disorders was organized in 2021. In this conference, a panel of experts representing the relevant fields, including allergy, dermatology, hematology, immunology, laboratory medicine, and pathology, met and discussed new markers and concepts as well as refinements in definitions, criteria and classifications of HE and HES. The outcomes of this conference are presented in this article and should assist in the diagnosis and management of patients with HE and HES in daily practice and in the preparation and conduct of clinical trials.

Patient-Reported Outcomes Improve at 2-Year Minimum Follow-Up After Hip Arthroscopy for Femoroacetabular Impingement Syndrome: A Systematic Review.

PURPOSE: To provide an updated review of recent literature on postoperative outcomes following hip arthroscopy for femoroacetabular impingement syndrome (FAIS), focusing on larger-population studies with a minimum 2-year follow-up published within the last 5 years. METHODS: A literature search of the PubMed, Ovid Medline, Web of Science, and Cochrane databases was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles were screened for clinical studies published from 2017 to 2022 with greater than 100 patients and minimum 2-year follow-up. Exclusion criteria included failure to report postoperative patient-reported outcomes (PROs), no preoperative radiographic measurements, and surgery for pathology other than FAIS. Data collection included study characteristics, patient demographics, radiographic findings, intraoperative findings, procedures performed, postoperative PROs, and subsequent surgeries. RESULTS: Nine studies met inclusion criteria. Mean or median patient ages ranged from 32.3 to 41 years, with 4 studies reporting on greater than 50% female patients. Mean preoperative lateral center edge angles and alpha angles ranged from 30.2° to 37° and from 56.2° to 71°, respectively. Labral repairs (range 69.7%-100%) were performed more commonly than debridements (range 0%-26.3%). All studies demonstrated improved PROs at most recent follow-up. Seven studies reported mean or median modified Harris Hip Scores, with preoperative and postoperative values that ranged from 53.1 to 80 and from 67.4 to 100, respectively. Revision hip arthroscopies and conversions to hip arthroplasty ranged from 0.8% to 11.6% and from 0% to 34%, respectively. CONCLUSIONS: All included studies found improvements in PROs after hip arthroscopy for FAIS at a minimum of 2-year follow-up. Conversion to total hip arthroplasty is most common in older patients at minimum 10-year follow-up. LEVEL OF EVIDENCE: Level IV, systematic review of Level I through IV studies.

Orthobiologics as an adjunct in treatment of femoroacetabular impingement syndrome: cell-based therapies facilitate improved postoperative outcomes in the setting of acetabular chondral lesions-a systematic review.

PURPOSE: To evaluate studies utilizing orthobiologics in the management of femoroacetabular impingement syndrome (FAIS) to (1) assess the indications for usage, and (2) analyze patient-reported outcome measures (PROM) following treatment. It was hypothesized that orthobiologics would (1) be utilized for symptomatic FAIS in the setting of labral or chondral pathology, and (2) improve PROM at most recent follow-up. METHODS: The Pubmed, Ovid Medline, Cochrane, and Web of Science databases were searched for clinical studies evaluating orthobiologics [hyaluronic acid (HA), platelet-rich plasma (PRP), or cell-based therapy (CBT) for treatment of FAIS. Exclusion criteria included orthobiologics used in conjunction with cartilage transfer or scaffolding procedures and a primary indication other than FAIS. Data collection included patient demographics, indications, and baseline and most recent PROM. RESULTS: Eleven studies (one level I, four level II, four level III, and two level IV evidence) met inclusion criteria, consisting of 440 patients with mean ages ranging from 32.8 to 47 years. All 11 studies demonstrated an improvement in PROM from baseline to most-recent follow-up. Four studies administered PRP either intraoperatively or the day after surgery as an adjunct to labral repair. CBT was used intraoperatively in the setting of acetabular chondral lesions (three studies) and labral repair (one study). When comparing to a control group at most recent follow-up, three PRP cohorts demonstrated similar PROM (n.s.), while one PRP group exhibited worse visual analog pain scores (2.5 vs. 3.4, p = 0.005) and modified Harris Hip Scores (mHHS) (82.6 vs. 78.7, p = 0.049). The four CBT studies reported favorable results compared to a control group, with a significantly higher mHHS at most recent follow-up or mean improvement from baseline in Hip Outcome Score-Activities of Daily Living (p < 0.05). Three studies reported on HA, which was utilized exclusively in the nonoperative setting. CONCLUSIONS: Intraoperative PRP and CBT have been commonly reported in the setting of hip arthroscopy for labral repairs and acetabular chondral lesions, respectively. The CBT cohorts demonstrated more favorable PROM at most recent follow-up when compared to a control group, though these results should be interpreted with caution due to heterogeneity of orthobiologic preparations. LEVEL OF EVIDENCE: IV.

Myelodysplastic/myeloproliferative neoplasms-unclassifiable with isolated isochromosome 17q represents a distinct clinico-biologic subset: a multi-institutional collaborative study from the Bone Marrow Pathology Group.

Classification of myeloid neoplasms with isolated isochromosome i(17q) [17p deletion with inherent monoallelic TP53 loss plus 17q duplication] is controversial. Most cases fall within the WHO unclassifiable myelodysplastic/myeloproliferative neoplasms (MDS/MPN-U) category. The uniformly dismal outcomes warrant better understanding of this entity. We undertook a multi-institutional retrospective study of 92 adult MDS/MPN-U cases from eight institutions. Twenty-nine (32%) patients had isolated i(17q) [MDS/MPN-i(17q)]. Compared to MDS/MPN without i(17q), MDS/MPN-i(17q) patients were significantly younger, had lower platelet and absolute neutrophil counts, and higher frequency of splenomegaly and circulating blasts. MDS/MPN-i(17q) cases showed frequent bilobed neutrophils (75% vs. 23%; P = 0.03), hypolobated megakaryocytes (62% vs. 20%; P = 0.06), and a higher frequency of SETBP1 (69% vs. 5%; P = 0.002) and SRSF2 (63% vs. 5%; P = 0.006) mutations that were frequently co-existent (44% vs. 0%; P = 0.01). TP53 mutations were rare. The mutation profile of MDS/MPN-U-i(17q) was similar to other myeloid neoplasms with i(17q) including atypical chronic myeloid leukemia, chronic myelomonocytic leukemia, myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis, myelodysplastic syndrome and acute myeloid leukemia, with frequent concomitant SETBP1/SRSF2 mutations observed across all the diagnostic entities. Over a median follow-up of 52 months, patients with MDS/MPN-i(17q) showed a shorter median overall survival (11 vs. 28 months; P < 0.001). The presence of i(17q) retained independent poor prognostic value in multivariable Cox-regression analysis [HR 3.686 (1.17-11.6); P = 0.026] along with splenomegaly. We suggest that MDS/MPN-i(17q) warrants recognition as a distinct subtype within the MDS/MPN-U category based on its unique clinico-biologic features and uniformly poor prognosis.

New developments in diagnosis, prognostication, and treatment of advanced systemic mastocytosis.

Systemic mastocytosis (SM) has greatly benefited from the broad application of precision medicine techniques to hematolymphoid neoplasms. Sensitive detection of the recurrent KIT D816V mutation and use of next-generation sequencing (NGS) panels to profile the genetic landscape of SM variants have been critical adjuncts to the diagnosis and subclassification of SM, and development of clinical-molecular prognostic scoring systems. Multilineage KIT involvement and multimutated clones are characteristic of advanced SM (advSM), especially SM with an associated hematologic neoplasm (AHN). A major challenge is how to integrate conventional markers of mast cell disease burden (percentage of bone marrow mast cell infiltration and serum tryptase levels) with molecular data (serial monitoring of both KIT D816V variant allele frequency and NGS panels) to lend more diagnostic and prognostic clarity to the heterogeneous clinical presentations and natural histories of advSM. The approval of the multikinase/KIT inhibitor midostaurin has validated the paradigm of KIT inhibition in advSM, and the efficacy and safety of second-generation agents, such as the switch-control inhibitor ripretinib (DCC-2618) and the D816V-selective inhibitor avapritinib (BLU-285) are being further defined in ongoing clinical trials. Looking forward, perhaps the most fruitful marriage of the advances in molecular genetics and treatment will be the design of adaptive basket trials that combine histopathology and genetic profiling to individualize treatment approaches for patients with diverse AHNs and relapsed/refractory SM.

Myeloproliferative Neoplasms, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

The classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) consist of myelofibrosis, polycythemia vera, and essential thrombocythemia and are a heterogeneous group of clonal blood disorders characterized by an overproduction of blood cells. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for MPN were developed as a result of meetings convened by a multidisciplinary panel with expertise in MPN, with the goal of providing recommendations for the management of MPN in adults. The Guidelines include recommendations for the diagnostic workup, risk stratification, treatment, and supportive care strategies for the management of myelofibrosis, polycythemia vera, and essential thrombocythemia. Assessment of symptoms at baseline and monitoring of symptom status during the course of treatment is recommended for all patients. This article focuses on the recommendations as outlined in the NCCN Guidelines for the diagnosis of MPN and the risk stratification, management, and supportive care relevant to MF.

Proceedings from the Inaugural American Initiative in Mast Cell Diseases (AIM) Investigator Conference.

The American Initiative in Mast Cell Diseases (AIM) held its inaugural investigator conference at Stanford University School of Medicine in May 2019. The overarching goal of this meeting was to establish a Pan-American organization of physicians and scientists with multidisciplinary expertise in mast cell disease. To serve this unmet need, AIM envisions a network where basic, translational, and clinical researchers could establish collaborations with both academia and biopharma to support the development of new diagnostic methods, enhanced understanding of the biology of mast cells in human health and disease, and the testing of novel therapies. In these AIM proceedings, we highlight selected topics relevant to mast cell biology and provide updates regarding the recently described hereditary alpha-tryptasemia. In addition, we discuss the evaluation and treatment of mast cell activation (syndromes), allergy and anaphylaxis in mast cell disorders, and the clinical and biologic heterogeneity of the more indolent forms of mastocytosis. Because mast cell disorders are relatively rare, AIM hopes to achieve a coordination of scientific efforts not only in the Americas but also in Europe by collaborating with the well-established European Competence Network on Mastocytosis.

Knowledge and perceptions of adverse childhood experiences (ACEs) among prelicensure nursing students.

OBJECTIVES: Adverse childhood experiences (ACEs) impact health outcomes in adulthood. Positive childhood experiences (PCEs) are associated with resiliency and improved mental and physical health outcomes. There is often a lack of content on ACEs in nursing education. The purpose of this project was to determine the knowledge and perceptions of ACEs and PCEs among prelicensure nursing students. METHODS: A mixed-method pilot study was implanted. Prelicensure nursing students received didactic instruction on ACEs and PCEs and completed online, anonymous ten-item pre- and post-surveys about knowledge on ACEs and PCEs. RESULTS: A positive percent change was observed with all ten statements from pre- to post-surveys. Six themes emerged from qualitative analysis, revealing the importance and benefits of education on ACEs and PCEs. CONCLUSIONS: This study shows that nursing students valued education regarding ACEs, were willing to incorporate their knowledge of ACEs into their practice, and discovered they might have been exposed to ACEs themselves. Implications for International Audience: All nursing programs must include content on ACEs and PCEs to prepare better nurses to care for patients.

Resilience and GRIT among undergraduate nursing students during the COVID 19 pandemic.

OBJECTIVES: Grit and resilience are related but separate concepts. Grit is a long-term commitment toward goals, and it impacts student success and academic achievement. Resilience is the ability of students to recover from stress. Both are important factors in nursing students. METHODS: This descriptive study included surveys measuring demographics, grit, and resilience among two cohorts of senior nursing students in their last semester and explored challenges and difficulties experienced during the COVID-19 pandemic. RESULTS: The mean grit score for all students was 4.0 (0.52) and the mean resilience score was 3.63 (0.73). Directed content analysis of the ten open-ended survey questions revealed three themes: Impact on Education, Personal Impact, and Coping Mechanisms. CONCLUSIONS: Grit and resilience are important factors that can contribute to success in nursing programs and as graduate nurses in the healthcare settings.

Clinical, immunophenotypic and genomic findings of NK lymphoblastic leukemia: a study from the Bone Marrow Pathology Group.

Natural killer (NK) cells are lymphocytes of the native immune system that play a pivotal role in host defense and immune surveillance. While the conceptual view of NK-neoplasms is evolving, little is known about the rare NK lymphoblastic leukemia (NK-LL), which remains as a provisional entity in the 2016 WHO Classification. The goal of this study is to characterize NK-LL cases and compare with other CD56 co-expressing acute leukemias. We identified 105 cases, diagnosed as NK-LL (6), CD56+ acute undifferentiated leukemia (AUL) (6), CD56+ T-lymphoblastic leukemia (T-LL) (51), and CD56+ acute myeloid leukemia (AML) (42). Compared to AUL patients, NK-LL patients were significantly younger (p = 0.021) and presented with higher white blood cell (WBC) (p = 0.037) and platelet counts (p = 0.041). Flow cytometry showed more frequent expression of cytoplasmic CD3 (cCD3, p = 0.064) and CD33, (p = 0.065), while HLA-DR was significantly absent from NK-LL (p = 0.035) compared to AUL. Compared to T-ALL, NK-LL cases showed less frequent cCD3 (p = 0.002), CD4 (p = 0.051), and CD10 expression (p = 0.06). The frequency of abnormal karyotypes was similar between NK-LL, AUL, and T-ALL. The mutational profile differed in four leukemia groups, with a significance enrichment of NOTCH1 (p = 0.002), ETV6 (p = 0.002) and JAK3 (p = 0.02) mutations in NK-LL as compared to AML. As compared to T-ALL, NK-LL cases showed a higher number of total mutations (p = 0.04) and significantly more frequent ETV6 mutations (p = 0.004). Clinical outcome data showed differences in overall survival between all four groups (p = 0.0175), but no difference in event free survival (p = 0.246). In this largest study to date, we find that that NK-LL shows clinical presentation, immunophenotypic and molecular characteristics distinct from AUL, T-ALL, and AML. Our findings suggest NK-LL is a distinct acute leukemia entity and should be considered in the clinical diagnosis of acute leukemias of ambiguous lineage.

Chronic myeloid neoplasms harboring concomitant mutations in myeloproliferative neoplasm driver genes (JAK2/MPL/CALR) and SF3B1.

JAK2, CALR, and MPL are myeloproliferative neoplasm (MPN)-driver mutations, whereas SF3B1 is strongly associated with ring sideroblasts (RS) in myelodysplastic syndrome (MDS). Concomitant mutations of SF3B1 and MPN-driver mutations out of the context of MDS/MPN with RS and thrombocytosis (MDS/MPN-RS-T) are not well-studied. From the cases (<5% blasts) tested by NGS panels interrogating at least 42 myeloid neoplasm-related genes, we identified 18 MDS/MPN-RS-T, 42 MPN, 10 MDS, and 6 MDS/MPN-U cases with an SF3B1 and an MPN-driver mutation. Using a 10% VAF difference to define "SF3B1-dominant," "MPN-mutation dominant," and "no dominance," the majority of MDS/MPN-RS-T clustered in "SF3B1-dominant" and "no dominance" regions. Aside from parameters as thrombocytosis and ≥15% RS required for RS-T, MDS also differed in frequent neutropenia, multilineage dysplasia, and notably more cases with <10% VAF of MPN-driver mutations (60%, p = 0.0346); MPN differed in more frequent splenomegaly, myelofibrosis, and higher VAF of "MPN-driver mutations." "Gray zone" cases with features overlapping MDS/MPN-RS-T were observed in over one-thirds of non-RS-T cases. This study shows that concomitant SF3B1 and MPN-driver mutations can be observed in MDS, MPN, and MDS/MPN-U, each showing overlapping but also distinctively different clinicopathological features. Clonal hierarchy, cytogenetic abnormalities, and additional somatic mutations may in part contribute to different disease phenotypes, which may help in the classification of "gray zone" cases.

Bone marrow necrosis in pediatric malignancies: 10-Year retrospective review and review of literature.

Bone marrow necrosis (BMN) is a rare pathologic finding, but when encountered is most often associated with malignancy. In adults, its presence correlates with an inferior prognosis, however in children the prognostic implication is unclear. We performed a retrospective review of 3,760 bone marrow specimens in patients ≤18 years over a 10-year period. BMN was identified in less than 1% of specimens and only in patients with leukemia, lymphoma, or neuroblastoma. BMN contributed to a delay in diagnosis; however, advanced medical imaging may serve as a tool to localize nonnecrotic areas for bone marrow sampling, facilitating an expedited diagnosis.

Midostaurin improves quality of life and mediator-related symptoms in advanced systemic mastocytosis.

BACKGROUND: Advanced systemic mastocytosis (advSM) is characterized by presence of the KIT D816V mutation and pathologic accumulation of neoplastic mast cells (MCs) in various tissues, leading to severe symptoms and organ damage (eg, cytopenias, liver dysfunction, portal hypertension, malabsorption, and weight loss). Treatment with midostaurin, an orally active multikinase/KIT inhibitor now approved for advSM in the United States and the European Union, resulted in a high rate of response accompanied by reduced MC infiltration of the bone marrow and lowered serum tryptase level. OBJECTIVE: We aimed to determine whether midostaurin improves health-related quality of life (QOL) and MC mediator-related symptoms in patients with advSM. METHODS: In 116 patients with systemic mastocytosis (89 patients with advSM fulfilling the strict inclusion criteria of the D2201 study [ClinicalTrials.gov identifier NCT00782067]), QOL and symptom burden were assessed during treatment with midostaurin by using the 12-Item Short-Form Health Survey (SF-12) and the Memorial Symptom Assessment Scale patient-reported questionnaires, respectively. MC mediator-related symptoms were evaluated by using a specific physician-reported questionnaire. RESULTS: Over the first 6 cycles of treatment with midostaurin (ie, 6 months), patients experienced significant improvements in total SF-12 and Memorial Symptom Assessment Scale scores, as well as in subscores of each instrument. These improvements were durable during 36 months of follow-up. Similarly, we found substantial improvements (67%-100%) in all MC mediator-related symptoms. CONCLUSION: QOL and MC mediator-related symptoms significantly improve with midostaurin treatment in patients with advSM (ClinicalTrials.gov identifier, NCT00782067).

Myeloid/Lymphoid Neoplasms with Eosinophilia and TK Fusion Genes, Version 3.2021, NCCN Clinical Practice Guidelines in Oncology.

Eosinophilic disorders and related syndromes represent a heterogeneous group of neoplastic and nonneoplastic conditions, characterized by more eosinophils in the peripheral blood, and may involve eosinophil-induced organ damage. In the WHO classification of myeloid and lymphoid neoplasms, eosinophilic disorders characterized by dysregulated tyrosine kinase (TK) fusion genes are recognized as a new category termed, myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB or FGFR1 or with PCM1-JAK2. In addition to these aforementioned TK fusion genes, rearrangements involving FLT3 and ABL1 genes have also been described. These new NCCN Guidelines include recommendations for the diagnosis, staging, and treatment of any one of the myeloid/lymphoid neoplasms with eosinophilia (MLN-Eo) and a TK fusion gene included in the 2017 WHO Classification, as well as MLN-Eo and a FLT3 or ABL1 rearrangement.