Hook, C. Christopher

SummaryInstitutional database search (1999–2020) for acute myeloid leukaemia (AML) identified 109 cases of myeloid sarcoma (MS), of which 19 were isolated and presented de novo. The latter displayed longer survival (median 78 months), compared to MS with synchronous intramedullary AML (n = 32; median 16 months) and de novo AML without MS (n = 729; median 22 months; P = 0·13). However, the difference in survival was no longer apparent after accounting for bone marrow cytogenetic risk status (P = 0·67). Treatment‐induced MS tumour resolution was not affected by the presence of intramedullary disease (P = 0·61). The current study clarifies the prognosis of de novo isolated MS, in the context of AML.

AbstractIntroductionHemostatic prophylaxis (HP) is recommended for patients with bleeding disorders (PWBD) before invasive procedures. However, evidence‐based guidelines are needed to determine optimal HP strategies.AimTo determine outcomes of HP for PWBD undergoing colonoscopy.MethodsWe undertook a retrospective cohort study of HP and outcomes of colonoscopy procedures performed between 9 November 1993 and 13 February 2018 for PWBD who received care in the Mayo Clinic Comprehensive Hemophilia Treatment Center.ResultsDuring the study period, 73 PWBD (58 with milder phenotypes: haemophilia, von Willebrand disease [subtypes 1 and 2; II, VII and XI deficiency]) underwent 141 procedures. Preprocedural HP was given to 61%, and interventions were performed in 47%. Of the 39% without preprocedural HP, postprocedural HP was given for 11%. One major (0.7%; 6 days postprocedure despite HP) and 10 minor (7%) bleeding complications occurred, which tended to be in patients with severe disease and/or after excision of larger polyps. There was no significant difference in the rate of bleeding complications with or without preprocedural HP (8.1% vs 5.5%, respectively; P = .74, Fisher's exact test).ConclusionThe low bleeding rates in our cohort suggest that preprocedure HP may be withheld for patients with mild bleeding disorders who undergo colonoscopy with a low likelihood of requiring an intervention or who require only low‐risk intervention. This strategy may be best used in experienced centres, provided optimal local hemostasis measures are undertaken and postprocedural HP is rapidly available if high‐risk intervention is required. Further studies are needed to determine optimal evidence‐based HP strategies for PWBD undergoing colonoscopy.

Abstract Background: The combination of MPD and amyloidosis is rare, and this patient population's clinical outcome is not well studied. Methods: Pts with a MPD and amyloidosis were identified via an clinical note search engine that searches through the electronic medical records of patients seen at Mayo Clinic Rochester, Jacksonville, and Scottsdale between 1990 and 2016. Terms used included amyloid or amyloidosis, chronic myelogenous leukemia or CML, essential thrombocytopenia or ET, and polycythemia vera or PV. Demographic and clinical data were abstracted from the medical record. Pts with both disorders were analyzed and their mortality rates along with median time to death were calculated. Prevalences at the Mayo Clinic were calculated for the years 2014 and 2015. Results: Twenty-three pts diagnosed with both a MPD and amyloidosis were identified. Thirteen (56.5%) were male, 10 (43%) were female. Eleven (47.8%) were initially diagnosed at the Mayo Clinic. Types of amyloidosis were as follows: Eleven (47%) had immunoglobulin light-chain (AL), four had localized (17%), two (8.7%) had wild-type transthyretin (ATTR), one (4.3%) had mutant ATTR, and five (21.8%) were unknown. Types of MPD were as follows: Seven (30%) had polycythemia vera (PV), seven (30%) had chronic myelogenous leukemia (CML), five (22%) had myelofibrosis, and four (17%) had essential thrombocytosis (ET). Fifteen (65%) were initially diagnosed with a MPD. Median time to last follow-up from second diagnosis was 1.7 years, and median time to death following second diagnosis was 1.4 years. The mortality rate was 87% in the total population. The median time to death for AL and PV was 2.7 years, AL and CML 1.0 years, and AL and ET 1.17 years. Myelofibrosis did not occur with AL. The most common combination was AL and PV, which accounted for five (22%) of the cases. Treatment regimens for the patients with AL were varied. Multiple drugs were combined with dexamethasone including melphalan, velcade, pomalidomide, lenalidomide, doxorubicin, and revlimid. Cyclophosphamide, bortezomib, and dexamethasone (CyBorD) were used in two cases. The mean time to diagnosis of amyloidosis from symptom onset was 10.3 months. Prevalences of AL and a MPD in 2014 and 2015 at the Mayo Clinic were 2.8% and 1.5%, respectively. Conclusions: The mortality rate for the combined diagnoses is high. The most common combination of diagnoses was that of AL and PV, which was associated with a mean time to death of 2.7 years. Disclosures Al-Kali: Celgene: Research Funding; Onconova Therapeutics, Inc.: Research Funding.

Abstract Introduction: Gardner-Diamond Syndrome (GDS), also known as psychogenic purpura, is a rare disorder characterized by unexplained recurrent painful bruising typically arising after physical and/or psycho-emotional stress. Classically ecchymoses (ecch) spontaneously appear and are associated with a prodrome of warmth and pain at the ecch sites. Prior GDS reports are limited to single cases or small series. Aims:To characterize presentation, natural history, management and long term outcomes (LTO) of GDS. Methods: In this retrospective study, after IRB approval, patients (pt) with GDS, encountered between 1976 and 2016, were identified from within Mayo Clinic Rochester clinical databases. Medical records of consenting pts were reviewed. Results: 75 females (ages 16-69 years (yr)) and 2 males (46-65 yr) met our study criteria. Pt presented 3.2 yrs (range 0-27) after onset of initial symptoms (sym). 52 pt (67.5%) had an antecedent history of physical abuse (n=2), trauma (n=12), an emotional event (n=13), surgery (n=11), or infection (n=3). Prodromal sensations prior to appearance of ecch in 55 pts (71.4%) were described as itching (n=15), burning (n=19), stinging (n=11), and/or pain (n=44). Other localized sym after appearance of ecch included swelling (n=46) and pain (n=67). Maximum size of ecch ranged from >0 and ≤5 cm (n=26), ≥6 and ≤ 10 cm (n=14), and >10 cm (n=13) and not described in 24 pts Systemic sym at time of ecch, reported in 49 pts, included malaise (n=26), myalgia (n=21), headaches (n=19), fevers (n=15), and abdominal pain (n=10). 50 (65%) of pts' lesions were isolated to arms and legs, while 27 (35%) had trunk and head involvement in addition to extremity involvement. Ecch duration varied: 0-7 days (n=14), 1 week-1 month (n=31), or >1 month (n=5) and not described in 27 pts. Complete blood count was normal (nl) in 84% (64/76) of pts tested; anemia was the most common abnormality. PT, APTT, VWF, and Factor XIII screen were nl in 100% (67/67), 98.4% (63/64), 97.9% (46/47), and 100 % (30/30) of pts respectively. Platelet aggregation studies were nl in 83% (25/30) with abnormalities attributed to drug effect. Bleeding (bld) scores (ISTH BAT), calculated with exclusion of cutaneous (cut) manifestations in scoring, were: 0 (n=48), 1 (n=12), 2 (n=9), 4 (n=2), 5-6 (n=2), 7 (n=2), and 9 (n=2). 21 pts had testing with subcut injections of autologous red cells (SCIAR) with 9 positive and 2 equivocal. 28 pts had skin biopsies with the most common finding being subcut hemorrhages. 45 pts (58.4%) underwent psychiatric (psych) evaluations and 7 (15%) pts were found not to have a psych dx. 42 pts had a psych dx including depression (n=23), hysterical personality (n=8), anxiety (n=2), personality disorder (n=2), psych other (n=7). Of these pts, 4 did not undergo further psych eval given prior dx. 42 pts had a history of a neurological dx including headaches (n=34), paresthesias (n=10), and seizures (n=7). Additional pharmacological treatments (pharmt) were recommended for 30 pts: antidepressants (n=4), antihistamines (n=13), anti-inflammatory/immunosuppressants (n=11), or hormonal (n=2) medications. 47 pts were treated with observation and/or counseling alone to address psychological stressors. 28 pts had follow-up (fu) at least 1 yr (1 to 34 yrs) after the initial visit. 13 of these pts had no mention of recurrence during fu while 15 pts had continued recurrence. Of those with recurrence, 7 pts continued to seek fu for GDS. Conclusion: In this large clinical cohort of GDS pts we confirm and expand on known clinical findings of GDS. Majority of pts had fairly benign disease (dz) manifestations; however, in a subset, a negative impact on pt quality of life was noted due mainly to persistent/recurrent pain. Refractory dz was mostly associated with ongoing/ recurrent stressors. The relatively low bld scores, together with laboratory assessments, support that GDS is primarily a dermal rather than a systemic bld diathesis. SCIAR did not provide additional value in dx. CBC, PT, APTT & VWF testing should be performed, and platelet testing considered, to rule out other hemostatic dz. Addressing stressors was the most effective treatment for pts, however pharmt was given for refractory dz. Though our study provides new insights regarding dx, therapy and LTO, future work investigating the pathophysiology leading to the hemostatic abnormalities in GDS would be valuable. Disclosures No relevant conflicts of interest to declare.

Abstract Background Congenital/hereditary qualitative platelet disorders (CQPD) can be classified by platelet count (eg, normal or decreased) and platelet size as well as by functional defect. Based on mean platelet volume (MPV), congenital thrombocytopenias (CT) are classified as macro-thrombocytopenias (eg, Bernard-Soulier syndrome [BSS], MYH-9 [myosin heavy chain 9, non-muscle]-associated thrombocytopenias, gray platelet syndrome [GPS], etc.); microthrombocytopenias (eg, Wiskott-Aldrich syndrome and variants); and those with normal platelet size. CQPDs with normal platelet count include Glanzmann thrombasthenia (GT), dense granule storage pool disorders (DG-SPD) including Hermansky-Pudlak syndrome (HPS), platelet secretion disorders and many others. Diagnosis has relied on platelet counting and sizing, blood smear light microscopy, platelet aggregation (agg) and platelet function analyzer (PFA-100) studies. Platelet transmission electron microscopy (PTEM) and flow cytometry can provide supplementary information and molecular analysis is also evolving. The objective of this study was to determine the roles of platelet transmission electron microscopy (PTEM) and flow cytometry in the diagnosis of CQPD and CT. Methods In this retrospective cohort study, after IRB approval, the electronic medical record system was queried for patients (pt) with a confirmed CQPD or CT seen at Mayo Clinic between 2000 and 2015. A detailed chart review was undertaken. Results 54 pt (64% female) met our study criteria; median age was 32 years (range 1 day to 81 years). 18/54 (33%) pt had macrothrombocytopenia: BSS 4 (7%); MYH-9 10 (19%); gray platelet syndrome 4 (7%). 36/54 (66%) had normal MPV: Glanzmann thrombasthenia 6 (11%); storage pool disorders including DG-SPD 10 (19%) and HPS 2 (3%), mild alpha granule deficiency 3 (6%) and York platelet syndrome 4 (7%); platelet secretion disorders 4 (7%); ANKRD26 mutation 3 (6%); congenital amegakaryocytic thrombocytopenia 1 (2%); GATA-1 mutation 1 (2%); RUNX-1 mutation 1 (2%); and Jacobsen syndrome 1 (2%). 44 pt (81%) had a positive bleeding history: epistaxis 52%, cutaneous bleeding 57%, gastrointestinal bleeding 21% and menorrhagia 54%; 10 pt (19%) had a negative bleeding history. Results of standard and esoteric platelet testing are summarized in Table 1. Diagnosis in the 10 pt with glycoprotein deficiency (BSS or GT) was established by agg; flow cytometry was confirmatory but not necessary. Of the 23 pt with SPD, 5 had a negative bleeding history; 4 pt had normal agg and PFA-100 and were diagnosed exclusively by PTEM. In this group, the abnormalities on platelet aggregation and PFA were variable and PTEM allowed for a better definition of the specific abnormalities. For MYH-9 patients, PTEM confirmed leukocyte inclusions that had already been identified on light microscopy. PTEM was the only diagnostic modality able to identify the abnormality in York platelet syndrome. In 5/54 (9%) genetic testing was necessary for diagnosis (GATA-1, ANKRD26 and RUNX-1) Conclusion In this cohort, standard platelet assays established the diagnosis in the large majority of CQPD and CT. PTEM was essential for confirmation in DG-SPD, mild alpha granule deficiency and York platelet syndrome and useful in combination with molecular testing to establish a diagnosis in selected cases. Guidance on selection of patients for such specialized testing requires further study. Table 1. Results of standard and esoteric platelet testing for 54 patients with congenital qualitative platelet disorders and/or thrombocytopenia Disorder n (%) Platelet aggregation PFA PTEM Flow cytometry Confirmation by genetics Done Abnormal Done Abnormal Done Abnormal Done Abnormal Glanzmann thrombasthenia 6 (11) 6 6 5 5 1 0 3 3 0 Bernard-Soulier syndrome & variants 4 (7) 4 4 4 4 3 0 4 4 0 MYH-9 related disorders 10 (19) 7 2 8 3 5 5 4 2 5 Dense granule deficiency and HPS 12 (22) 12 8 12 8 12 12 4 0 0 Alpha granule deficiency* 7 (13) 7 4 7 6 7 7 4 4 1 York platelet syndrome 4 (7) 1 0 1 1 4 4 1 1 0 TXA2 or PG synthesis/receptor defect 4 (7) 4 4 4 3 3 0 3 0 0 CATM 1 (2) 0 - 0 - 0 - 0 - 1 ANKRD26 3 (6) 3 3 3 2 3 3 3 3 3 GATA-1 1 (2) 0 - 1 1 1 1 1 1 1 RUNX-1 1 (2) 1 0 1 1 0 - 0 - 1 Jacobsen syndrome 1 (2) 1 0 1 1 1 1 1 0 1 MYH-9: myosin heavy chain 9, non-muscle (MHY-9) associated thrombocytopenia, HPS: Hermansky-Pudlak Syndrome, TXA2: thromboxane A2, PG: prostaglandin CATM: congenital amegakaryocytic thrombocytopenia. * Includes gray platelet syndrome Disclosures Pardanani: Stemline: Research Funding.

AbstractObjectivesDescribe the clinical presentation, treatment, and outcomes of postsurgical thrombotic microangiopathy (TMA).MethodsIn this retrospective study, records of individuals diagnosed with TMA developing within 30 days of a surgical procedure at Mayo Clinic from 2000 to 2016 were reviewed. Available literature regarding postsurgical TMA was comparatively reviewed.ResultsTwenty patients were diagnosed with TMA developing within 30 (median 6.5, range (1‐28)) days) following a procedure. Preceding procedures included orthopedic (n = 4), vascular (n = 4), abdominal (n = 8), thoracic (n = 2), and other (n = 2). Review of the literature identified 65 patients with postsurgical TMA and cardiovascular procedures were the most common preceding surgery. The majority of patients in the current cohort and literature were treated with therapeutic plasma exchange (TPE). Among the evaluable patients in the current cohort, 100% demonstrated response to TPE; however, 25% required the addition of other therapy including eculizumab to maintain a response 80% of patients in the literature demonstrated a response to TPE.ConclusionsAlthough rare, early recognition and treatment of postsurgical TMA can lead to good outcomes. More research is necessary to determine the underlying pathophysiology and optimal treatment for postsurgical TMA.