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The use of novel small molecule inhibitors alone or in combination with anti-CD20 monoclonal antibodies for chronic lymphocytic leukemia (CLL) has raised a number of questions on efficacy, tolerability, long-term treatment adherence in patients with heterogeneous clinical features. To fill this gap, we designed a study focusing on treatment sequencing in patients with CLL in order to (i) compare the outcome of patients treated with chemoimmunotherapy (CIT) combinations in first-line versus those receiving Bruton's tyrosine kinase inhibitors (BTKi); (ii) characterize the efficacy and tolerability of venetoclax-based regimens; (ii) understand the impact of treatment sequencing when it comes to chemo-free options including venetoclax after BTKi and vice versa. Data from consecutive sets of patients diagnosed with CLL between 2000-2020 attended at 77 institutions affiliated with ERIC were collected and analyzed. Collected variables included: demographics, clinical stage at diagnosis, IGHV gene somatic hypermutation status; cytogenetic status for chromosomes 11q, 13q 17p and 12 determined by fluorescence in situ hybridization; TP53 gene mutation status; treatment; treatment response; discontinuation; reason for discontinuation; death. We included 9173 patients with a diagnosis of CLL who received at least one line of treatment. The median age at diagnosis was 67 years with a male:female ratio of 1.9. The median follow-up was 78 months (IQR, 48-120 months). Regarding novel targeted agents, 1860/9173 (20.2%) patients had received at least one line of treatment with BTKi (ibrutinib, n=1788; acalabrutinib, n=72) over the disease course; 631/9173 (6.9%) with venetoclax; and, 447/9173 (4.9%) with the PI3K inhibitor idelalisib. Seventy-nine patients were treated with both BTKi and venetoclax (59 BTKi followed by BCL2i, 20 vice versa). At last follow-up, 5870/9173 patients (64.0%) were alive, 3229/9173 (35.2%) died and 74/9173 (0.8%) were lost to follow-up. Patients treated with BTKi in first-line were enriched for TP53 aberrations [del(17p) 27.6%, TP53 mutation 26.3%] and unmutated IGHV genes (69%) and obtained an ORR of 87.7%. Of these, 136 (26.3%) discontinued treatment after a median of 1.2 years (0.07-5.98); main reasons of discontinuation were toxicity (40.5%) and failure (26.2%). Among 631 patients treated with venetoclax at any line, 100 (15.8%) received BCL2 +/- anti-CD20 as first-line; 170 (26.9%) as second line (125 previously treated with CIT, 27 with BTKi); and, 361 as third or subsequent line. ORR ranged between 71.5% (≥3 lines) with 30.5% CR/CRi to 90.3% (first-line) with 68.1% CR/CRi. Treatment discontinuation was due to toxicity in 28.6% of patients treated in the first-line, and 17.6% and 21.8% of patients treated in second and third-or-higher-line, respectively. Disease progression led to treatment discontinuation in 14.3%, 20.6% and 33.6% in first, second and third-or-higher line, respectively. CIT was used as front-line treatment in 5465 patients (59.6%). Of these, 2070 (37.9%) and 1018 (18.6%) patients received a second and third line of treatment, respectively. The great majority (865/1086 cases, 79.7%) of patients who received a second line before 2014 were retreated with CIT, most commonly Bendamustine-Rituximab (284/1086, 26.1%) and Fludarabine-Cyclophosphamide-Rituximab (252/1086, 23.2%); alemtuzumab monotherapy was used in 55/1086 (5%) of patients. After 2014, 415/984 patients (42.1%) were retreated with BTKi; 93 (9.5%) with venetoclax; 70 (7.2%) with idelalisib; 50 (5%) with Alemtuzumab monotherapy, and 315 (32%) with CIT. Similarly, in the third-or-higher line of treatment, most patients (86.3%) were retreated with CIT before 2014, while BTKi, BCL2i, and PI3Ki were mainly used after 2014 (in 43.1%, 15.7% and 14.7% of cases, respectively). Finally, our cohort included 1075 patients with TP53 aberrations. The ORR of patients receiving BTKis (n=171) as first-line of treatment was 86.5% (22.2 CR+64.3 PR), while the ORR with venetoclax +/- anti-CD20 (n=15) was 91% (45.5% CR+45.5 PR). Patients treated with CIT (n=694) had an ORR of 68.7% (28.3% CR+40.4% PR). In conclusion, in a large international study we provide real world data regarding the selection and sequencing of treatment in CLL, charting a major shift in treatment patterns before and after the introduction of novel trargeted agents and confirming their efficacy even in high-risk CLL. Disclosures Scarfo: Janssen: Honoraria, Other: Travel grants; Astra Zeneca: Honoraria; Abbvie: Honoraria. Iacoboni: BMS/Celgene, Gilead, Novartis, Janssen, Roche: Honoraria. Collado: Abbvie,: Other: pharmaceutical Company, Research Funding; Janssen: Other: Pharmaceutical Company, Research Funding. Galimberti: AbbVie, Janssen: Honoraria, Other: Travel grants; Incyte: Speakers Bureau. García-Serra: AbbVie: Other: Educational grands; Janssen: Other: Educational grants; Novartis: Other: Educational grants. Gozzetti: Janssen: Honoraria; AbbVie: Honoraria. Hatzimichael: Amgen, Roche, Genesis, Novartis, Bristol Mayer Squibb, Celgene, Pfizer: Consultancy; Abbvie, Amgen, Bristol Mayer Squibb, MSD, Gilead, Janssen Cilag, Genesis Pharma, Roche, Takeda: Honoraria. Herishanu: AbbVie: Honoraria, Research Funding; Janssen: Honoraria; Roche: Honoraria; Medison: Honoraria. Jaksic: Roche, Oktal-Pharma/Celtrion, Sandoz: Consultancy, Honoraria. Kater: Janssen, AstraZeneca: Other: Ad Board, steering committee, Research Funding; Abbvie: Honoraria, Other: Ad Board, Research Funding; BMS, Roche/Genentech: Other: Ad Board, , Research Funding; Genmab, LAVA: Other: Ad Board, Steering Committee. Kotsianidis: Astellas: Other: NONE, Research Funding, Speakers Bureau; Genesis: Consultancy, Other: NONE; Janssen Hellas: Consultancy, Other: NONE, Speakers Bureau; Bristol Hellas: Consultancy, Other: NONE, Research Funding, Speakers Bureau; Novartis Hellas: Consultancy, Other: NONE, Research Funding, Speakers Bureau; Abbvie: Consultancy, Other: NONE, Research Funding, Speakers Bureau. Kreitman: NIH: Patents & Royalties: Moxetumomab Pasudotox; Genentech: Research Funding; Teva: Research Funding; AstraZeneca/MedImmune: Research Funding; Innate: Research Funding; GSK/Novartis: Research Funding; Array BioPharma/Pfizer: Research Funding. Laribi: BeiGene: Other: Personal Fees; Jansen: Research Funding; Novartis: Other: Personal Fees, Research Funding; Astellas Phama, Inc.: Other: Personal Fees; AstraZeneca: Other: Personal Fees; Le Mans Hospital: Research Funding; Takeda: Other: Personal Fees, Research Funding; AbbVie: Other: Personal Fees, Research Funding; IQONE: Other: Personal Fees. Lopez-Garcia: Roche: Other: Speaker Honoraria, Travel and accommodation grants; Novonordisk: Other: Speaker Honoraria; Fresenius: Other: Speaker Honoraria; Celgene: Other: Speaker Honoraria; Abbvie: Other: Speaker Honoraria, Advisor, Travel and accommodation grants; Janssen: Other: Speaker Honoraria, Advisor, Travel and accommodation grants, Research Funding. Milosevic: Roche: Honoraria; Abbvie,: Honoraria; Janssen: Honoraria; Sandoz: Honoraria. Reda: Beigene: Consultancy; Astra Zeneca: Consultancy; Abbvie: Consultancy; Janssen: Consultancy. Ruchlemer: AbbVie: Consultancy, Honoraria, Research Funding. Šimkovič: Janssen, Gilead, Roche, AstraZeneca, and AbbVie: Other: consultancy fees, advisory board participation fees, travel grants, and honoraria; University Hospital Hradec Kralove: Current Employment; AbbVie: Consultancy, Current equity holder in publicly-traded company, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Merck: Current equity holder in publicly-traded company; Eli Lilly: Current equity holder in publicly-traded company; J&J: Current equity holder in publicly-traded company; Gilead: Other: Travel, Accommodations, Expenses. Špaček: AbbVie, AstraZeneca, Gilead, Janssen, and Roche: Honoraria. Tadmor: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Visentin: Italfarmaco and Gilead: Speakers Bureau. Vassilakopoulos: AstraZeneca: Honoraria; Amgen: Honoraria, Research Funding; Pfizer: Research Funding; Dr. Reddy's: Research Funding; Novartis: Consultancy, Honoraria; GlaxoSmithKline: Honoraria, Other: Travel; Merck: Honoraria, Research Funding; Integris: Honoraria; Roche: Consultancy, Honoraria, Other: Travel; Genesis Pharma: Consultancy, Honoraria, Other: Travel; Takeda: Consultancy, Honoraria, Other: Travel, Research Funding; AbbVie: Consultancy, Honoraria; Karyopharm: Research Funding. Vitale: Janssen: Honoraria. Yáñez: Gilead-Kite, Janssen, AbbVie, AstraZeneca, Beigene, Roche, Pfizer, Jazz, BMS, and Merck: Other: Advisory board participation fees ; Janssen, AbbVie, AstraZeneca, Gilead-Kite, Roche, Pfizer, and Merck: Speakers Bureau. Antic: AbbVie, Janssen, and Roche: Honoraria. Coscia: Janssen: Honoraria, Other, Research Funding; Gilead: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria, Other. Cuneo: AstraZeneca: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau. Gaidano: Beigene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astrazeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Guièze: Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Astrazeneca: Consultancy, Honoraria. Laurenti: AstraZeneca: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Research Funding; Roche: Honoraria, Research Funding; Gilead: Honoraria; Janssen: Consultancy, Honoraria; BeiGene: Honoraria. Murru: Abbvie: Consultancy, Honoraria, Other: travel and accommodation; Janssen: Consultancy, Honoraria. Sportoletti: AstraZeneca: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria. Tam: Beigene: Research Funding; Janssen: Research Funding; Abbvie: Research Funding; Loxo: Honoraria; Beigene: Honoraria; Janssen: Honoraria; Abbvie: Honoraria. Trněný: Amgen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Gilead Sciences: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses; Celgene: Consultancy; 1st Faculty of Medicine, Charles University, General Hospital in Prague: Current Employment; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Portola: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses. Bosch Albareda: Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria; Abbvie: Consultancy; AstraZeneca: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Kite: Honoraria; Sanofi: Honoraria; Lilly: Honoraria. Doubek: Janssen-Cilag, AbbVie, AstraZeneca, Amgen, Gilead, Novartis: Honoraria, Research Funding. Chatzidimitriou: Abbvie: Honoraria, Research Funding; Janssen: Honoraria, Research Funding. Ghia: AbbVie: Consultancy, Honoraria, Research Funding; Acerta/AstraZeneca: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; ArQule/MSD: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; Celgene/Juno/BMS: Consultancy, Honoraria; Gilead: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Sunesis: Research Funding. Stamatopoulos: AstraZeneca: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Janssen: Honoraria, Research Funding.

Lymphomas are presently categorized according to their origin from B or T lymphocytes. The co-expression of CD3 in B-cell lymphomas or CD20 in T-cell lymphomas has been rarely reported. Immature and less often mature lymphomas may incorporate the rearrangements of both B- and T-cell antigen receptor genes (dual genotype or bigenotype). Lymphoma cells with a sole genotype hardly concurrently express both B- and T-cell markers (biphenotypic lymphomas). We describe a 63-year-old female who was presented with obstructive jaundice and epigastric pain of 10 days. Initial CBC revealed 43x103/μL white blood cells, 11.2 g/dL hemoglobin, and 88x103/μL platelets. CT abdomen revealed hepatomegaly and suspected pancreatic mass with large retroperitoneal lymph nodal mass. Peripheral smear showed 56% lymphoid cells with blast morphology. The bone marrow (BM) aspirate smear was infiltrated by 83% immature-looking cells. BM biopsy showed interstitial to diffuse extensive infiltration by primitive-looking cells, positive for pan-B-cell antigens CD20, CD79, and PAX5 as well as the T-cell antigen CD4, CD5, CD3, while negative for all immaturity markers (CD34, TdT, and CD1a). In situ hybridization for Epstein-Barr virus (EBV)-encoded small RNA (EBER) was negative. Flow cytometry on BM aspirate showed an abnormal population (50%) expressing the B-cell antigens (CD19, CD20, CD79, CD22) and CD10, and showed lambda light chain restriction as well as the T-cell antigens cCD3 and CD4 with partial CD5. The analysis showed, also, another abnormal population of lambda restricted monotypic B cells (8%) with dimmer CD45 (blast gate) and showed the same immunophenotype (expressing the B-cell antigens), but negative for CD10, cCD3, CD5, and CD4. Conventional cytogenetic revealed complex karyotype. Molecular studies revealed rearrangements of the immunoglobulin heavy chain region consistent with a clonal B-cell population. TCR gene rearrangement analysis was equivocal concerning clonality but was not conclusive for clonal T-cell disease. Our final diagnosis was peripheral blood and BM involvement by EBV-negative high-grade lymphoid neoplasm (in leukemic phase with blast morphology) and an ambiguous immunophenotype with a differential diagnosis that may include the rare entity of bigenotypic lymphoma or an unusual case of high-grade B-cell lymphoma with aberrant expression of T-cell markers (biphenotypic lymphomas).

Polycythemia Vera (PV) is a clonal myeloproliferative disease characterized by an erythroid dominant trilineage proliferation of hematopoietic precursor cells. Acute coronary syndrome is known to occur in patients with PV. However, there are very rare reported cases of myocardial infarction upon the initial presentation of PV. We present such a case of a 37 years old male, with no known cardiovascular risk factors, who had an initial presentation of NSTEMI treated with drug eluting stent (DES). Later investigations revealed a diagnosis of Polycythemia Vera. Treatment strategies for MI in cases of myeloproliferative disease lacking clear guidance, further studies are needed in this matter.

Background. Mast cell leukaemia is a unique disease among hematopoietic neoplasms, being one of the rarest leukaemia subtypes. In addition, its prompt diagnosis is usually challenging. This is due to its heterogeneity in clinical presentations and cytomorphological and immunophenotypical features together with potential associations with other hematologic neoplasms which can complicate the condition and delay accurate diagnosis. To the best of our knowledge, this is the first case report of CD4-positive mast cell leukaemia. Case Presentation. A 39-year-old male presented with acute onset of fever, abdominal pain, and generalized body aches of two-week duration. Peripheral blood smear showed circulating blasts (13%) with coarsely basophilic granulation. Bone marrow (BM) aspirate showed extensive infiltration with immature mast cells of blast-like morphology with trilineage dysplasia and evident hemophagocytic activity exhibited by histiocytes and neoplastic mast cells. BM biopsy was diffusely infiltrated with many atypical mast cells positive for CD45, CD117, mast cell tryptase, CD25, and CD4 with partial positivity for CD7 and CD30. Cytogenetics showed an abnormal karyotype: 47, XY, +1947, XY, +19[13]/46, XY[9]. Molecular analysis revealed a KIT D816V mutation consistent with a diagnosis of systemic mastocytosis, mast cell leukaemia. Conclusion. The expression of T-cell associated markers by abnormal mast cells is well documented; however, CD4 and CD7 expression have not previously been described in association with mast cell leukaemia. Coexpression of CD2, CD4, CD7, and CD30 by the mast cells particularly in skin lesions may provoke misinterpretation as a cutaneous T-cell neoplasm. To the best of our knowledge, this is the first report of CD4-positive mast cell leukaemia. Moreover, hemophagocytic mast cell leukaemia is a very rare morphologic variant, and possible correlation between this finding and expression of CD4 by neoplastic mast cells is a topic for further investigation.

This is a report of a very rare case of marginal zone lymphoma in a 15-years old male with Ataxia Telangiectasia. Besides being a rare diagnosis within the pediatric age group, this case exhibited a true challenge not only from diagnostic point of view but also regarding management plans. Marginal zone lymphoma is an indolent disease in which transformation is extremely rare particularly the pediatric subtype. However, there isn't enough data regarding marginal zone lymphoma in a sitting of immunodeficiency conditions had been published so far. The case described here showed some features pointing to more aggressive disease with massive bone marrow involvement and areas of focal transformation unlike the subtle pattern of infiltration that is usually seen in cases of marginal zone lymphoma. Another interesting finding in our case is the presence of a clone of CD4/CD8 double positive T-cells of moderate size (12%) with restricted expansion of Vb1 region. The significance of this clone is uncertain as it could be a transient reactive clone or a pre-malignant one. Keywords: Ataxia telangiectasia, Marginal zone lymphoma, Low grade lymphoma

Introduction: In the era of routine use of positron emission tomography/computed tomography (PET/CT) for staging, it is not yet clear whether PET/CT can replace bone marrow biopsy for the assessment of bone marrow involvement in large B-cell lymphoma. Objectives: To compare the clinical utility of bone marrow biopsy and PET/CT scanning in the staging of large B-cell lymphoma. Methods: This was a retrospective analysis of all patients who presented to single center over a 4-year period with large B-cell lymphoma who had concurrent PET/CT and bone marrow biopsy performed in the assessment and staging of the lymphoma. Results: Out of 89 patients, 24 had bone marrow involvement either by PET/CT, by bone marrow biopsy, or by both. Bone marrow biopsy identified 12 patients (sensitivity 50%, specificity 100%, negative predictive value 84%), whereas PET/CT identified 23 patients (sensitivity 96%, specificity 100%, negative predictive value 98%). No patients were upstaged by the bone marrow biopsy result, and no patients had their treatment plan changed based on the bone marrow biopsy result. Conclusion: The results show that PET-CT is more sensitive and has better negative predictive value than bone marrow biopsy. This suggests that PET-CT could replace bone marrow biopsy in detecting bone marrow involvement for staging of large B-cell lymphoma.

T-cell large granular lymphocytic leukemia is characterized by clonal expansion of a CD3+/CD57+ subpopulation, which are typically CD8+ positive cytotoxic T- cells, and can only be diagnosed if there is a persistent, greater than 6 months, elevation of LGL in the blood (usually 2–20 × 109/L), in the absence of an identifiable cause. T-LGLL has been associated with reactive conditions such as autoimmune diseases and viral infections and has also been reported in association with hematologic and non-hematologic malignancies. We report a case of asymptomatic CD4/CD8 double-positive T-LGLL. Flow cytometry on peripheral blood revealed a subpopulation of CD4/CD8 double-positive T cells expressing CD57 and cTIA. Clonality was established by flow cytometric analysis of T-cell receptor V(â) region repertoire which showed that >70% of the cells failed to express any of the tested V(â) regions. Clonality was further confirmed by PCR with the detection of clonal TCR beta and TCR gamma gene rearrangements. Six months later, she presented with persistent lower back pain and diagnosed with IgG kappa multiple myeloma. CD4/CD8 double-positive T-large granular leukemia is the first case reported in the literature. This rare phenotype is either underreported or a truly rare clinical entity. More studies are warranted to characterize the pathogenesis and clinical characteristics of this group of patients and to further assess the relationship between multiple myeloma and T-LGLL as a cause-and-effect relationship or simply related to the time at which diagnosis has been made.

The current study retrospectively evaluated cytogenetic profiles, various prognostic factors, and survival outcomes in 128 acute myeloid leukemia (AML) patients (14 ≤ age ≤ 70 years) admitted to the National Center for Cancer Care and Research (NCCCR), Hamad Medical Corporation, Doha, Qatar, between January 2010 and December 2016. The median age at diagnosis was 43 years, and 80% were less than 60 years old; 75% of patients were male. Cytogenetic analysis was integrated into the World Health Organization 2008 classification and showed that the percentages of normal and abnormal karyotypes were similar, accounting for 48.4% of each group of patients. The AML risk stratification based on cytogenetic analysis resulted in the following distribution: 18% in the favorable risk group, 57% in the intermediate-risk group, 24% in the unfavorable risk group, and 1% unknown. Only 88 patients received therapy with curative intent; 67% achieved complete remission, increasing to 81% after inductions 1 and 2. The median overall survival (OS) and disease-free survival (DFS) in AML patients were 26.6 and 19.5 months, respectively. The 3-year OS and DFS were 40 and 36%, respectively. Prognostic factors including age, gender, white blood cell count, and risk stratification were not significantly associated with treatment outcomes, whereas response to treatment vs. failure was significantly associated with the outcome (p = 0.01). The current study supports the importance of cytogenetics as a useful tool in diagnosis, prognosis, and risk assessment in AML treatment.

Patient: Male, 71-year-old Final Diagnosis: Chronic lymphocytic leukemia • small lymphocytic lymphoma Symptoms: Subcutaneous indurations • subcutaneous mass Medication:— Clinical Procedure: Skin biopsy Specialty: Hematology Objective: Unusual clinical course Background: Most patients with chronic lymphocytic leukemia (CLL) are asymptomatic at diagnosis, but 10% present with B symptoms. Most patients have palpable lymphadenopathy, while 20–50% of the patients have hepatosplenomegaly. Cutaneous infiltrations in patients with CLL can be localized or generalized in the form of erythematous papules, plaques, nodules and, ulceration, which is uncommon. Case Report: We present the case of a 71-year-old man diagnosed with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with atypical immunophenotype and increased prolymphocytes (CLL/PLL), which was treated initially after white blood counts (WBC) doubling with Bendamustine and Rituximab for 6 cycles, and achieved complete remission. The patient relapsed after 6 months of completion of treatment, with multiple large sub-cutaneous masses, proved to be infiltration with the same atypical CLL/SLL on tissue biopsy, with pathologic features indicating disease progression. The lack of similar reported cases, and the aggressiveness of the tumor clinically and histopathologically, resulted in the decision to treat with Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone (R-CHOP) as a case of aggressive lymphoma, with complete remission clinically and radiologically. Conclusions: We present a rare case of subcutaneous extramedullary masses of atypical CLL/SLL. The high proliferation index (Ki-67) and the increase of large cells are suggestive of aggressive progression of the disease; however, no frank features of Richter’s transformation were noted. Based on this and because of the unusual aggressive-looking skin masses, the panel decided to treat the patient with R-CHOP. The impact of this presentation on the prognosis of the disease is not clear. To date, our patient has responded well to treatment with R-CHOP, with complete remission of the subcutaneous masses and on PET scan, but further follow-up is needed.

Patient: Male, 22-year-old Final Diagnosis: Anaplastic plasma cell myeloma Symptoms: Bone pain Medication:— Clinical Procedure: BM examination Specialty: Hematology Objective: Unusual clinical course Background: Plasma cell myeloma is a neoplastic plasma cell disorder that usually presents after the fifth decade of life; it is rarely described in younger population especially under 30 years of age. However, there are conflicting reports in the literature about the clinical behavior and overall survival in younger age groups. In approximately 2% of plasma cell myeloma, the morphology of the neoplastic cells is highly pleomorphic, quite anaplastic, and may resemble metastatic tumor cells. While this poses a challenge for morphological interpretation during diagnosis, it has been demonstrated that bone marrow morphologic features (including diffuse sheet growth pattern, immature cell morphology and high mitotic index) significantly correlates with high risk disease. Moreover, there is limited description available about the morphology of the neoplastic cells when correlating the age at presentation with the clinical outcome/biological behavior; hence, the need to report and collect such cases. Case Report: We report a case of plasma cell myeloma in a 22-year-old male who presented with non-specific clinical features and posed a diagnostic challenge during clinical, radiological, and laboratory examination. The pathology specimens showed anaplastic morphology. Unfortunately, after diagnosis, despite treatment with brotezomib, his disease had an aggressive clinical course and he passed away 4 months after diagnosis. Conclusions: Although plasma cell myeloma is rare in patients younger than 30 years, it must be considered in the differential diagnosis and investigated properly especially in patients with clinical suspicion of a metastatic non-hematological tumor. The anaplastic variant in a young patient is a diagnostic challenge and is associated with bizarre morphology, aggressive presentation, adverse cytogenetics, resistance to chemotherapy, and poor, short-term, survival.

Patient: Male, 57-year-old Final Diagnosis: CLL/SLL and MCL composit lymphoma Symptoms: Abdominal pain Medication:— Clinical Procedure: BM examination Specialty: Hematology Objective: Rare co-existance of disease or pathology Background: Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL) both have a common origin arising from mature CD5+ B-lymphocytes. Their distinction is crucial since MCL is a considerably more aggressive disease. Composite lymphoma consisting of CLL/SLL and MCL has been rarely reported. This type of composite lymphoma may be under-diagnosed as the 2 neoplasms have many features in common, both morphologically and immunophenotypically. Case Report: We report the case of a 57-year-old male patient who presented with a 4-month history of recurrent abdominal pain and distention with hepatosplenomegaly. Peripheral blood showed a high leukocytes count (46.7×103/uL) with marked lymphocytosis of 35.0×103/uL, mostly small mature-looking, with some showing nuclear irregularities, with approximately 3% prolymphocytes. Immunophenotyping by flow cytometry and immunohistochemistry revealed 2 immunophenotypically distinct abnormal CD5+monotypic B-cell populations. Fluorescence in situ hybridization (FISH) on peripheral blood demonstrated IGH/CCND1 rearrangement consistent with t(11;14) in 65% of cells analyzed. Accordingly, based on compilation of findings from morphology, flow cytometry, immunohistochemistry, and FISH, A diagnosis of composite lymphoma consisting of MCL; small cell variant and CLL/SLL was concluded. Conclusions: We describe a case of composite lymphoma of MCL (small cell variant) and CLL/SLL that emphasizes the crucial role of the multiparametric approach, including vigilant cyto-histopathologic examination, immunophenotyping by flow cytometry and immunohistochemistry, as well as genetic testing, to achieve the correct diagnosis.

Background Among several groups of clinicians and hematopathologists a conflict of opinion has been repeatedly expressed concerning the validity of bone marrow (BM) features characterizing myeloproliferative neoplasms (MPNs). In this regard, controversy is mainly focused on the distinction between essential thrombocythemia (ET) and pre-fibrotic/early primary myelofibrosis (pre-PMF) Although other groups confirmed the characteristic BM features and emphasized the clinical impact to discriminate both MPN subtypes the existence of pre-PMF has been questioned, including clinical usefulness and particularly reproducibility of the corresponding diagnostic guidelines. In this context, it has been criticized that the MPN classification proposed by the World Health Organization (WHO), updated in 2008 and revised in 2016,was focused on BM morphology as the gold standard of diagnosis. The current standard for follow-up of these patients is based on pathological markers (peripheral blood counts and/ bone marrow histomorphology) and molecular markers. Bone marrow examination is the gold standard method to assess the disease's extent; it offers detailed information about cellularity, the morphology of each lineage, the degree of fibrosis, and the transformation and dysplastic features. However, many patients are reluctant to go for this invasive technique which precludes precise disease activity assessment at the desirable frequencies. A non-invasive technique that can offer reliable prognostic and predictive information about the disease is lacking. The objective of this study is to explore the diagnostic value of FLT-PET in malignant hematopoiesis of Pre-PMF and ET. The potential to use FLT-PET metrics to differentiate between Pre-PMF and ET is assessed Methods A total of 13 patients (mean age of 43.23 ± 14.42 years, 7 males and 6 females) with Essential Thrombocythemia (ET) and/or Prefibrotic myelofibrosis were included in this study. One male subject was excluded due to an inconclusive diagnosis. The study was approved by the institutional review board. Written informed consents were obtained from all subjects. Each subject underwent FLT PET imaging as well as bone marrow examination (gold standard) and all were tested for JAK2v617F , CALR and MPL . Semi-quantitative (SUVmax and SUVmean) measurements of FLT uptake in the liver, spleen and Lumbar spine, SUVmean, as well as the Total Lesion Glycolysis (TLG) of the Lspine were performed. Results from the two patient cohorts were compared using = Kruskal-Wallis statistical test. A P-value of Discussion: Pre-PMF and ET exhibited different features of bone marrow; however, this is not always easy to judge objectively, making pathologists' distinction often suboptimal. And in another scenario, bone marrow which is mandated for diagnosis, cannot be obtained due to technical issues or patient-related factors. In the 2016 revised classification,pre-PMF was recognized as a separate entity, distinct from ET. Thrombosis and hemorrhage represent two of the main causes of morbidity and mortality in patients with ET. Incidence of arterial and venous thrombosis prior to diagnosis revealed no significant differences (23% /20 and 9/8%) in WHO-defined ET compared with pre-PMF; thrombotic complications were also similar during the follow-thrombosis is not significantly different, whereas bleeding is more frequent in pre-PMF.From clinical prespective it is important to differentiate between the two categories. Results The differences in FLT SUVmax and SUVmean measurements in the three organs (liver, spleen, and LSpine) between the ET and Pre-PMF patients were not statistically significant (P>0.05). In contrast, TLG measurements in the LSpine were statistically different (P=0.013), and therefore, compared to gold standard bone marrow results, TLG can separate ET and Pre-PMF patients. Conclusion TLG of the Lumbar Spine in FLT PET images is a potential quantitative parameter to discriminate between ET and PRE-PMF patients Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction Blood cancers are collectively common and strikingly heterogeneous diseases both clinically and molecularly. According to the WHO taxonomy, there are over 100 distinct myeloid and lymphoid neoplasms. Genomic profiling of blood cancers has been applied in a somewhat ad hoc fashion using diverse sequencing approaches including the use of targeted panels, whole exome sequencing, whole genome sequencing, RNA sequencing, etc. The lack of data uniformity has made it difficult to comprehensively understand the clinical and molecular spectrum within and across diseases. Systematic genomic approaches can address the central challenges in the diagnosis and treatment of blood cancers. For the diagnosis of blood cancers, the incorporation of genomics could greatly enhance the accuracy and speed of clinical diagnostics. Genomics could also inform their pathology classification. However, these applications must be preceded by a clear understanding of the particular genetic aberrations and expression profiles that unite and distinguish different leukemias and lymphomas. Therapeutic development can also be aided by genomic approaches through identification of new targets and establishing the relevance of existing targets and treatments. Targeted therapies including those directed at specific surface markers (e.g. CD19, CD30 and CD123) or molecular targets (e.g. BCR-ABL fusions, IDH1 mutations and EZH2 mutations) are rarely restricted to a single disease, with most occurring in multiple blood cancers. A systematic understanding of the presence or overlap of these targets within or across blood cancers would significantly expand the therapeutic possibilities and better enable the use of existing therapies in both common and rare cancers. However, such therapeutic possibilities need to be established through a rigorous, data-driven approach. We initiated the Atlas of Blood Cancers Genomes (ABCG) project to systematically elucidate the molecular basis of all leukemias and lymphomas by building upon advances in genomic technologies, our capabilities for data analysis and economies of scale. Using a uniform approach to systematically profile all blood cancers through DNA and RNA sequencing at the whole exome/whole transcriptome level, we aim to link genomic events with clinical outcomes, disease categories and subcategories, thereby providing a complete molecular blueprint of blood cancers. Methods/Results The ABCG project consists of collaborators from 25 institutions around the world who have collectively contributed samples from 10,481 patients comprising every type of blood cancer in the current WHO classification. The samples include thousands of myeloid leukemias and mature B cell lymphomas, hundreds of Hodgkin lymphoma and plasma cell myeloma, as well as every rare type of hematologic malignancy (along with case-matched normal tissue). All cases were de-identified and their associated pathology and detailed clinical information entered into a purpose-built web-based system that included disease-specific data templates. All cases were subjected to centralized pathology review and clinical data review by experienced hematopathologists and oncologists. All 10,481cases are being sequenced at the DNA and RNA level, and are being profiled to define the genetic alterations and expression changes that are characteristic of each disease. Analysis will include translocations, copy number alterations, and viral status. These molecular features will be examined in conjunction with genetic events, pathologic factors, and the clinical features. We have already generated results for ALK-negative anaplastic large B cell lymphoma and primary mediastinal B cell lymphomas (N=210). These data demonstrate novel subgroup and molecular discoveries that are enabled by integrative DNA and RNA sequencing analysis and the examination of molecular features across different diseases as well as within individual entities. In addition, other disease entities and the collective data will be presented in the meeting. Conclusion The ABCG project will comprehensively study the genetic and clinicopathological features of all blood cancers using systematic genomic approaches. We anticipate our data, approaches and results will serve as a lasting resource for the molecular classification and therapeutic development for leukemias and lymphomas. Disclosures McKinney: Novartis: Research Funding; Nordic Nanovector: Research Funding; Molecular Templates: Consultancy, Research Funding; Kite/Gilead: Honoraria, Speakers Bureau; Incyte: Research Funding; Genetech: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy; Celgene: Consultancy, Research Funding; BTG: Consultancy; Beigene: Research Funding; ADC Therapeutics: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy; Verastem: Consultancy. Behdad: Lilly: Speakers Bureau; Roche/Foundation Medicine: Speakers Bureau; Thermo Fisher: Speakers Bureau.

Introduction: Primary mediastinal large B-cell lymphoma (PMBL) is a rare non-Hodgkin lymphoma subtype that occurs predominantly in young adults, with an overall favorable prognosis. The cell of origin is presumed to be thymic medullary B-cells and the gene expression profile of PMBL is similar to classic Hodgkin lymphoma. Recent studies have begun unravelling the genomic alterations underlying PMBL. Frequent, recurrent mutations (e.g. B2M, TNFAIP3, SOCS1, STAT6, GNA13) have been reported, but most of the studies have analyzed a small number of cases. To gain further insights into disease biology, we recruited 63 cases of PMBL as part of the Atlas of Blood Cancer Genomes (ABC-G) initiative, a consortium consisting of 25 institutions. Methods: Formalin-fixed paraffin-embedded (FFPE) biopsies and clinical data were collected. All cases were subjected to centralized review by an experienced panel of hematopathologists to ensure accurate diagnosis. Whole-exome DNA and RNA sequencing was performed using the Illumina platform and the DNA and RNA reads aligned to the GRCh38 genome and transcriptome respectively. Exonic variants were filtered using a set of paired normal samples and population-based databases to identify putative driver mutations, which were then aggregated at the gene level. Mutational analysis was performed on 56 samples that passed quality filtering and expression analysis on 45 samples. RNAseq data was normalized using DESeq2. Results: The cohort included samples from 16 males and 24 females, with a median age of 33 years (range 16 - 72) at the time of diagnosis. The majority of patients were treated with R-CHOP (47%) or R-EPOCH (43%), with 93% of patients surviving through the end of follow-up (median follow-up: 60.1 months). Besides the known recurrent mutations involving the JAK-STAT (STAT6 -21%, SOCS1 - 26%), NFKB (TNFAIP3 - 27%, NFKB1A - 7%), immune escape (B2M - 20%, LTB - 11%, IRF8 - 9%, IRF4 -9%), and chromatin modification (ZNF217 - 16%, CREBBP - 11%, KMT2D -11%) pathways , we discovered recurrent somatic variants in novel candidate driver genes in this disease, including NOTCH4 (7%), DICER1 (11%), MCL1 (7%), amongst others. EZH2, EP300, and XPO1 mutations were not detected. CIITA mutations and fusions were observed in 14% and 11% of cases, respectively, with novel partner genes (IGHA2, IGHG1, CDC6) detected in 67% of the fusion positive cases. Copy number alterations included gains at 2p16.1 (REL - 20%) and 9p24.2 (JAK2/PDL1/PDL2 - 24%), as well as loci not previously implicated in PMBL, 8q24.3 and 9q34.3 (each in 20%). Of note, CIITA alterations and 9p24 gains were virtually mutually exclusive, highlighting diverse mechanisms of immune escape in this entity. The transcriptomes of cases harboring CIITA alterations demonstrated differential enrichment of genes involved in protein glycosylation. The PMBLs in our series showed significant enrichment of the reported PMBL genetic classifier score, compared to nodal diffuse large B cell lymphoma (DLBCL) (p=0.0003). Finally, the gene expression profile of thymic B cells was more similar to that of PMBL than nodal DLBCL (p=0.0144). Conclusions: Our study, representing one of the largest comprehensive genomic and transcriptomic analyses of PMBL, expands the mutational landscape of PMBL, provides evidence for biologically distinct disease subsets and suggests an origin of PMBLs from thymic B-cells. Disclosures Hsi: AbbVie: Research Funding; Eli Lilly: Research Funding; Cytomx: Honoraria; Seattle Genetics: Honoraria. McKinney: BTG: Consultancy; Celgene: Consultancy, Research Funding; Epizyme: Consultancy; Genetech: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Kite/Gilead: Honoraria, Speakers Bureau; Molecular Templates: Consultancy, Research Funding; Nordic Nanovector: Research Funding; Novartis: Research Funding; Pharmacyclics: Consultancy; Verastem: Consultancy; Beigene: Research Funding; ADC Therapeutics: Consultancy, Speakers Bureau. Jaye: Stemline Therapeutics: Honoraria. Cohen: Genentech, Takeda, BMS/Celgene, BioInvent, LAM, Astra Zeneca, Novartis, Loxo/Lilly: Research Funding; Janssen, Adaptive, Aptitude Health, BeiGene, Cellectar, Adicet, Loxo/Lilly, AStra ZenecaKite/Gilead: Consultancy. Behdad: Lilly: Speakers Bureau; Roche/Foundation Medicine: Speakers Bureau; Thermo Fisher: Speakers Bureau. Dave: Data Driven Bioscience: Current equity holder in publicly-traded company.

Background Plasma cell neoplasms can show aberrant expression of different lineage-related antigens; however, co-expression of T-cell-associated markers on malignant plasma cells is extremely rare. Material and methods This report describes clinicopathologic characteristics of three myeloma patients with emergent plasmablastic morphology and aberrant acquisition of T-cell-associated markers diagnosed in our center. An extensive literature search for similar cases was conducted, and the relevant pathologic, clinical, and prognostic characteristics were summarized. Results A total of 22 cases of plasma cell neoplasm (including the three cases reported here) showed aberrant co-expression of T-cell markers. We found an evident association between aberrant expression of T-cell markers on malignant plasma cells and extramedullary involvement, aggressive morphologic features, high proliferative index ki67 >90%, aggressive clinical course, an adverse outcome, and short survival. Discussion & Conclusion Due to the rarity of this aberrant phenotype and scarcity of the published data, the precise causative mechanism and its clinical implications have not yet been elucidated.

Background Rare factors (F) deficiencies are defined as deficiencies of factors other than F VIII or IX. They are inherited as autosomal recessive with a prevalence that varies between 1:500,000 to 1:2000,000.FI deficiency includes Afibrinogenemia, Hypofibrinogenemia and Dysfibrinogenemia. While most patients with dysfibrinogenemia don't bleed patients with afibrinogenemia can present with life threatening bleeding. FII deficiency can be acquired or inherited. the most frequent severe symptoms are muscle hematomas and hemarthrosis. With FV deficiency some patients may be asymptomatic while children with severe deficiency can present with CNS bleeding. Patients with low FV should also get their FVIII checked to rule out combined (F5F8) deficiency which is a separate rare coagulation disorder that results from a mutation in a protein that transfers both factors from the cell to the blood stream. Symptoms are generally mild and it rarely causes hematomas or hemarthrosis. FVII deficiency is the most common autosomal recessive coagulation disorder (1:500,000). The severity of symptoms is reported to be poorly correlated with the plasma levels. FX deficiency can present with serious bleeding manifestations. Options for treatment include fresh frozen plasma (FFP) or prothrombin concentrate. FXI deficiency (Hemophilia C) unlike F8 and F9 doesn't cause joint or muscle bleeding. Hemophilia C is the second most common bleeding disorder affecting women following Von Willebrand disease. The most common presentation of FXII deficiency is asymptomatic prolongation of aPTT. Deficiency of this factor carries a more thrombotic risk rather than bleeding because it plays a bigger role in initiation of fibrinolysis compare to its contribution to the coagulation cascade. Most patients with FXIII deficiency experience symptoms from birth often bleeding from the umbilical cord stump and bleeding symptoms tend to continue throughout life. Methodology Data was collected from hematology outpatients' clinics from January 2018 to June 2020. Patients above 18 years with rare factor deficiencies.were included in the study,We excluded FVIII and IX as it is less rare and there are specific guidelines for these patients.Data included were demographics, the factor deficient, level, surgical history and others. Results The total number is 29 patients. The mean age is 34 years (18-77). There is female predominance with 69 %. 65 % of the patients were Qataris and 36% from other nationalities. The most deficient factor is FI 41%, followed by FVII 20 %, then FXII and XIII. Interestingly we found one rare case of combined F5F8 deficiency in a Lebanese lady. Family history was positive in 41 % of cases, almost in all the cases of Fibrinogen deficiency. All the cases of Hypofibrinogenemia came from one qatari Tribe. 38 % of the patients had history of bleeding, while 80 % had surgical procedures. 55% received replacement therapy for bleeding or before procedures. Due to the history of transfusions we checked for HIV, HBV and HCV status and we found only one case with HCV. Conclusion Some factor deficiencies pose a challenge in hematology clinics due its rarity and lack of guidelines. Mild deficiency can be discovered for the first time in adult life, during surgery, pregnancy or gynecological procedures. Therefore, females are more likely to be discovered than males. Abnormalities in coagulation should be considered before surgical procedures, which might require hematologist consultation. Educating patients and physicians will help in preparing these patients and initiation of protocols if needed. Figure Disclosures No relevant conflicts of interest to declare.

Introduction: Multiple myeloma (MM) is a plasma cell neoplasm characterized by the neoplastic proliferation of clonal plasma cells in the bone marrow, and often result in extensive bone destruction with osteolytic lesions, anemia, hypercalcemia and renal insufficiency. MM usually presents after the fifth decade of life and there are conflicting reports about the clinical features and overall survival in younger age group. Objective: We aim to study the clinical and laboratory features of newly diagnosed untreated Myeloma patients with age 50 years old and below and to describe the first line treatment protocols, overall survival (OS) and progression-free survival (PFS). Methods: A retrospective medical record review was conducted in all patients at age of 50 and below, who are diagnosed with MM and treated at the National Center for Cancer Care and Research (NCCCR) in Qatar between 2007 to 2019. Relevant clinical and pathological parameters were recorded and correlated with OS and PFS. The analysis was descriptive and exploratory in nature. OS and PFS were descriptively analyzed using the Kaplan-Meier method. Statistical analysis was performed with STATA version 12.0 (Statacorp, College Station, TX). Results: A total of 43 cases of MM at 50 years old and below were diagnosed in Qatar in the period between 2007 and 2019.The median age of all patients was 41 years (range, 22-50 years) with (2)5% of patients being younger than 30 years of age, 18(42%) between 30-39 years and 23(53%) between 40 and 50 years 7(16%) were Qatari citizen, there was obvious male predominance with 33 (77%) male and 10 (23%) female. The immunoglobulin (Ig) subtypes were IgG in 15(35%), IgA in 4(9%), free light chain in 18(42%), IgD in 3(7%) and others in 3(7%). At diagnosis,35 patients out of 41 (85%) had bone lesions (lytic lesion or vertebral compression fractures). Twenty patient (46.5%) had extramedullary plasmacytoma, including five patients (11.5%) presented with spinal cord compression. Anemia (with hemoglobin 11.0 mg/dL), and 11patients (26%) had renal dysfunction (serum creatinine > 2.0 mg/dL) with two patient required hemodialysis at diagnosis. Other laboratory tests revealed albumin < 3.5g/dL in 13(30%) and beta2 microglobulin ≥5.5mg/L in 14(33%). 80% of patients had bone marrow plasmacytosis more than 10%. In 8 patients (19.5%) the bone marrow plasma cells were less than 10% and the diagnosis was based on the presence of plasmacytoma. The data was not available in two patients. The proportion of patients at ISS stage III was 33%. Conventional chromosomal study was performed in 35 patients and chromosomal abnormalities were found in 25.7% (9 out of 35) of the patients. A diverse range of first-line treatments was used. 35 patients (72%) were given induction therapy with a Bortezomib (V)-based regimen (Bortezomib-Dexamethasone)(2) VTD(1), PAD(8), VCD(16), VRD(8) while 3 patients received CTD, 2 patients were given dexamethasone only, one patient received HPERCVAD and 2 patients didn't receive any therapy. 21(48%) of patients underwent autologous stem cell transplant (including 2 tandem), as upfront therapy and 7 patients had second transplant during relapse. The overall response rate (ORR) to first line therapy was 85%, with 46%, of patients having complete response (CR),26% having a very good partial response (VGPR) and partial response (PR) in 14 % while refractory and progressive disease was recorded in 14%. Response was not evaluated in 8 patients (18.5%) due to lack of data. The median follow-up of all patients was 27month, median overall survival (mOS) and Median progression-free (mPFS) were 67.4 and 36.5 month respectively. Conclusion: This is a single Centre preliminary data on MM in young patients, which showed that (MM) in younger age group had different clinical and biochemical pattern with high incidence of light chain myeloma and extramedullary involvements. This study will provide a platform for the design of future comparative studies for patients above and below 50 years in the Qatari population. Figure Disclosures No relevant conflicts of interest to declare.

Introduction Acute leukemias can be divided into acute myeloid leukemia and acute lymphoblastic leukemia. Common presentations of acute leukemia include fever, symptoms of anemia, bleeding, bone pain palpable Lymph nodes or spleen and symptoms due inflation or leukocystasis. Extramedullary mass is rare and can be of myeloid tissue and known as Chloroma or myeloid (granulocytic) sarcoma which one of the WHO classifications for acute myeloid leukemia. Common sites of occurrence are skin, sinuses, bone and other. It's rarely involve central nervous system. Spinal cord involvement usually manifest as epidural mass causing cord compression. Spinal epidural tumor with acute leukemia and myeloid sarcoma is rare and can be found in 3-9% in patients with leukemia. In this review we decide to review the cases of spinal cord compression caused by acute myeloid leukemia (including Chloroma) and acute lymphoblastic leukemia due to the significance of such presentation in addition to reports that Myeloid sarcoma of the spine has very poor prognosis Methodology: We have reviewed the literature using: PubMed, google scholar, Scopus for patient with spinal cord compression and acute leukemia. We used the search term and synonyms : : acute myeloid leukemia , acute myelocytic leukemia , acute monocytic leukemia , acute lymphoblastic leukemia , acute lymphoid leukemia, chloroma , myeloid sarcoma ,granulocytic sarcoma, spinal cord compression .We included adult patients above 18 years old only cases we exclude pediatrics cases and cases of chronic leukemia's and other myeloproliferative disorders as well as cases of central nervous system involvement other than spinal cord Results We gathered the information from 98 cases with general demographics, presentation, image modality, cytogenetics and molecular in addition to management and outcome. We have found mean age for the patients is 38 years old with male predominance with 70% of the cases. The most presenting symptom was back pain in around 75% of the cases. Neurological findings showed sensory loss and parapreresis in most of the documented cases. MRI was most performed modality of imaging 63% followed by Computed tomography(CT) 15 % and then myelogram 13 %, which is least used due to invasive nature and before the era of MRI. The most common affected site on spinal cord were thoracic followed by lumbar. Cytogenetics and molecular data was not reported in most of the cases. Patients were treated with either steroids or surgery or radiotherapy and or chemotherapy while few underwent bone marrow transplant, but the most common approach was surgery+ radiotherapy + chemotherapy combination. Steroids used in most of the cases especially in the cases of acute lymphoblastic leukemia and dexamethasone was the steroids of the choice mainly. The outcome of the patients were variable, 30 % were alive at the time of the reports 30 % died and 30 % between relapse and complete remission. Conclusions Acute leukemia can be presented as mass causing spinal cord compression which is very serious. There are is no standardized management of patients with acute leukemia who presented with spinal cord compression nether guidelines or steps to follow. Some reports speculated also specific morphology and cytogenetics association with predisposition to have Extramedullary mass, however there lack of reporting of such a valuable information. Large studies including all adjusted variables required to determine if spinal cord compression presentation can be an independent risk facto or not Effective diagnosis and prompt action should take place. Figure Disclosures No relevant conflicts of interest to declare.

Introduction: Plasma cell neoplasms can show aberrant expression of different lineages related antigens, but expression of T-cell associated markers, is exceedingly rare. Herein, we describe two patients with plasma cell Myeloma who relapsed with an aggressive disease with plasmablastic morphology, skin involvement, high Ki-67, complex karyotype (with abnormalities in chromosome 1) and interestingly both patients showed aberrant acquisition of single or multiple T-cell associated markers including CD4 and died shortly after last presentation. T-cell markers were not expressed at diagnosis. Multiple theories have been proposed to explain aberrant expression of T-cell markers on a terminally differentiated plasma cells. Due to rarity of this aberrant phenotype and scarcity of the published data, the precise causative mechanism and its clinical implications have not yet been elucidated. An extensive literature review for patients with similar findings was conducted and the relevant pathological, clinical and prognostic characteristics were summarised. Methodology: Herein we describe two patients with emergent plasmablastic morphology and aberrant acquisition of multiple T-cell markers (confirmed by both flow cytometry (FCM) and immunohistochemistry), diagnosed in national Centre for Cancer Care and Research in Qatar. In addition, we conducted a systematic literature review using PubMed, google scholar and Scopus for patients with plasma cell myeloma (PCM) and aberrant T-cell expression, using pre-defined search terms and synonyms. Results: Patients diagnosed in our centre: Case 1: A 47-year-old male presented with multiple subcutaneous swellings, skin biopsy showed plasma cell neoplasm (PCN). Serum protein electrophoresis showed two bands; IgD lambda and free lambda. The patient started on VRD followed autologous SCT. Two months later, he developed new skin nodules in the upper chest wall and right renal mass. BM at relapse, showed many pleomorphic myeloma cells with plasmablastic/ anaplastic morphology. FCM showed a large population of monotypic plasma cells expressing CD10 with aberrant expression of CD33, CD4 and CD7 (partial). By IHC: the plasma cells were positive for cMYC with aberrant expression of CD4 and CD7 (partial) and CD3 (minority of cells) with Lambda light chain restriction and negative for CD20, CD56 and CD117. KI-67 >90%. Karyotype: 47,X, Y,i(1)(q10) ,t(1;3)(p32;p13),+der(3)t(1;3)(p32;p13) ,add(4)(q35),der(8)t(8;15)(q24;q11.2) add(8)(p23),add(13)(q34),+20[20]. The patient started on second line treatment for two days, unfortunately, he progressively deteriorated and passed away. Case 2: 56-year-old male presented with solitary spinal plasmacytoma and PCM. The patient underwent local radiotherapy followed by Lenalidomide and dexamethasone for 12 cycles and achieved complete remission. 5 years later, the disease progressed with multifocal spinal lesions and right chest wall mass which was treated with Pomalidomide and Daratumumab but he progressed and developed as scalp mass lesion. BM was infiltrated by many myeloma cells with plasmablastic morphology. FCM showed a monotypic plasma cell with aberrant expression of CD4 and complex karyotype. New line of therapy include Elotuzumab-Pomalidomide-dexamethasone started and unfortunately the patient shortly succumb. Upon literature review: A total of 19 cases of PCNs (table 1) showed aberrant expression of T-cell associated markers (including the two cases reported here). 11 case at relapse & two at initial presentation. Anaplastic/plasmablastic morphology and extramedullary presentation were reported in 8/12 cases. 10/18 patients out showed aberrant expression of CD4. 9/11 cases had a very short survival. Conclusion: Here we discuss an interesting, yet a rare finding of aberrant acquisition of T-cell associated markers on PCM. This review emphasises the importance of recognising atypical and rare immunophenotypic aberrancies in PCN that could possibly lead to diagnostic pitfalls (particularly with extramedullary involvement) and provide important prognostic information. We conclude that there is an evident association between aberrant expression of T-cell associated markers on PCM and aggressive disease including plasmablastic morphology, high KI-67, extramedullary involvement and adverse outcome with short survival. Disclosures No relevant conflicts of interest to declare.

Chronic Myeloid Leukaemia can rarely present in essential Thrombocythaemia-like picture. Apart from the genetic defining marker (BCR-ABL fusion), these cases lack almost all typical features of CML. Here, we highlight the response of these patients to different therapeutic approaches and to emphasize that although the proliferation is solely limited to the platelets; this group of patients did not show any response except after initiation of Tyrosine kinase inhibitors which highpoints the essentiality of excluding CML by performing BCR/ABL-1 in all cases with features of myeloproliferative neoplasms in order to avoid delayed management and adverse outcome. Apparently, many hematologists have not been persuaded to always test for BCR/ABL-1 when there are no features suggesting CML. Unlike what was previously reported, upon literature review, we found no significant difference in disease prognosis in this group of patients compared to classic CML, provided TKI was started early in disease course.

Introduction Tuberculosis (TB) and is the leading infectious cause of death in adult's worldwide.TB can have a wide variety of presentations manifestation. Hematological manifestations of tuberculosis have different forms and one of the rare associated is TB with isolated thrombocytopenia. ITP is relatively common autoimmune bleeding disorder.. However, ITP is very rarely associated with TB with only a few cases reported. Isolated Thrombocytopenia in TB is multifactorial and could be explained by different mechanisms as follows Immune-mediated platelet destruction through antiplatelet antibodies as mycobacterium TB may share antibodies with platelets or platelet-associated immunoglobulin, Tuberculosis-induced hemophagocytosis, Defective platelet production due to bone marrow (BM) infiltration, Hypersplenism, intravascular coagulation, anti-tuberculous treatment (ATT) induced thrombocytopenia. Methodology We reviewed the literature using PubMed, google scholar and English language articles only. We have included all the reported cases of tuberculosis and immune thrombocytopenia if it is associations or initial presentations using the keyword: tuberculosis. Pulmonary tuberculosis, immune thrombocytopenia, Idiopathic thrombocytopenia purpura and we excluded drug induced thrombocytopenia. Our review identified forty-two cases in total, in our review Baseline and clinical characteristics are provided. Results Of the forty-two cases identified, more than one quarter of cases (n=12) were from India; the remainder of the reported cases from thirteen different countries. Gender was nearly equally distributed (males n= 21, females n=20, one case unknown); age ranged from 4 to 74 years. The most reported sites of TB as follows; lung (n=20), disseminated (n=8), lymph nodes (n=6), abdomen (n=4), mediastinum (n=2), spleen (n=1) and knee (n=1). Bone marrow aspiration and biopsy done in 27 cases, three of them (7%) found granuloma and 14 (32%) found to have normal to hyprecellular marrow with increased number of megakaryocytes. Of the forty-two cases, ITP was the first presentation of TB with or without typical TB symptoms and signs in more than three quarters of the cases (n=33), while ITP was discovered in TB patients in routine investigations without obvious bleeding symptoms or signs in only four cases. Hemorrhagic symptoms were reported in most of the cases (n=31), skin manifestations (petechiae/purpura/ecchymosis) being the most common (n=28). The therapeutic approach to TB-associated ITP showed significant heterogeneity with Anti tuberculous treatment and first- and/or second-line treatment for ITP given with or without platelets transfusion. Most of the cases (n=36) achieved full recovery with Anti-tuberculous treatment(ATT) and IVIG ± Steroids. Of the 42 cases, six cases were treated with blood and platelet transfusion for thrombocytopenia which did not normalize the platelet count as thrombocytopenia as expected as this is most likely an immune mediated phenomenon. Conclusion Unfortunately, there are no clear guidelines for management of TB-associated ITP and is anecdotal or observational at best. This highlights the importance of conducting prospective and standardized studies in the future. We found that Anti tuberculous treatment could have play pivotal role in management of ITP in TB Patients. Figure Disclosures No relevant conflicts of interest to declare.

No abstract, as A letter to the Editor.

Patient: Male, 28-year-old Final Diagnosis: Chronic myeloid leukaemia Symptoms: Splenomegaly Medication:— Clinical Procedure: Bone marrow biopsy Specialty: Hematology Objective: Rare co-existance of disease or pathology Background: Single or multiple cell line dysplasia is a characteristic feature of myelodysplastic syndrome. However, significant dysgranulopoiesis is not a feature of chronic myeloid leukemia (CML). Systemic mastocytosis (SM) with an associated hematologic neoplasm (SM-AHN) comprises 5% to 40% of cases of SM. All types of hematologic neoplasms have been previously reported, although CML has been rarely encountered. Case Report: A 28-year-old male presented with a 3-month-history of weight loss and massive splenomegaly. Peripheral blood revealed marked leukocytosis, shift to left with 13% blasts. There was evident dysgranulopoiesis that raised a provisional diagnosis of myelodysplastic/myeloproliferative neoplasm. Bone marrow (BM) examination revealed granulocytic hyperplasia with 10% blasts and significant dysgranulopoiesis. Unexpectedly, cyto-genetic analysis revealed t(9;22) with BCR/ABL1 rearrangement, diagnostic of chronic myeloid leukemia in an accelerated phase. The patient was started on dasatinib 100 mg upfront, however, he failed to respond, with increasing leukocytosis. Repeat BM examination showed persistence of the findings with 8% blasts. At this time, aggregates of mast cells with aberrant expression of CD25 were elicited, thus concluding the diagnosis of SM-AHN. The patient failed multiple lines of treatment (dasatinib, nilotinib, hydroxyurea, cytarabine subcutaneous, 6-mercaptopurine and interferon) and progressed to the blast phase a few months later. Conclusions: We report an unusual case of CML, presented with significant dysgranulopoiesis with an aggressive clinical course including SM uncovered during the disease course with subsequent transformation to the blast phase. The different biological behavior of this case underscores the need for studies on a larger number of cases to explore the significance of the aforementioned coexistent features.

Background: Combined factor V and factor VIII deficiency (F5F8D) is a rare autosomal recessive inherited coagulopathy. It has a higher prevalence in the Mediterranean region (1:100,000) compare to its prevalence in the general population which is estimated to be (1:1000,000). Case report: We report a 59 years old Lebanese lady who was referred from the general surgery clinic with an asymptomatic prolongation of prothrombin time (PT), international normalized ratio (INR) and activated partial thromboplastin time (aPTT) detected during preoperative work up for an elective umbilical hernia repair. The patient had history of bleeding following dental procedures since childhood as well as easy bruising with minimal trauma. Physical examination was unremarkable. haematological investigations were normal apart from the prolonged PT, INR and aPTT which were corrected following mixing studies. Factor assay revealed factor V level of 5.5% and factor VIII level of 11.9% with other factors within normal ranges confirming the diagnosis of combined F5F8D. Conclusion: Combined factor V and factor VIII deficiency should be suspected in patients with prolonged PT, INR and aPTT especially if they are of Mediterranean, Middle east or Arabic origin with a history of consanguineous marriages. Treatment is generally not indicated unless the patient has recurrent serious bleeding manifestations.

Background: Prolymphocytic leukemia (PLL) is a rare disease, accounting for < 2% of lymphoid leukemias [1].There are 2 quite different entities with distinct pathologic features and different therapeutic strategies, T-cell and B-cell [2]. T-PLL is more common [3]. Although termed ‘prolymphocytic,’ T-PLL is characterized by the proliferation of post-thymic T-lymphocytes. It is estimated that physicians will see a case of T-PLL every five to ten years [4]. Over the last 15 years, 3 cases of T-PLL were diagnosed in our center. We present here the latest case, with typical pathological findings. Case Report: A 63-year-old British gentleman, previously healthy with good performance, presented with fatigue for 6 – 8 weeks with puffiness of face and eyelids and weight loss of 5 kilograms. Physical exam showed periorbital edema and conjunctival injection (Figure 1), cervical lymphadenopathy, and hepatosplenomegaly. Initial complete blood count (CBC): white blood cells (WBCs) 331.9 x109/L (4.0 – 10.0), with 94% lymphocytes, hemoglobin (Hb) 119 gm/L (130 – 170), platelets (Plts) 128 x109/L (150 – 400). Lactate dehydrogenase 10.4 µkat/L (2.1 – 3.7), uric acid 537 µmol/L (210 – 420). Abdomen ultrasound showed markedly enlarged spleen (20.3 cm). The peripheral blood smear showed profound leukocytosis with 94% abnormal lymphoid cells. The cells were small to medium in size with high nucleo-cytoplasmic ratio, moderately condensed chromatin and almost all with prominent nucleolus. Substantial number of the cells show irregular nuclear contour with short indentation. The cytoplasm was basophilic agranular and many cells show irregular cytoplasmic protrusions (Figure 2). Flow cytometry on peripheral blood revealed one homogenous abnormal population positive for cluster of differentiation 45 (CD45) and express the pan T-cell markers (CD3, CD2, CD5 and CD7). All were positive for CD4, T-cell receptor (TCR) alpha/beta, CD43 and BCl2 with partial expression of CD38. These cells were negative for CD56, CD57, CD16, CD25, CD103, CD10, CD117, Terminal deoxynucleotidyl transferase (TdT), CD1a and CD34. (Figure3A) TCRVb region analysis by flow cytometry using IO Test Beta Mark TCR Repertoire kit (Beckman Coulter, Brea, CA, USA) using the panel of 24 monoclonal antibodies to TCR Vb families showed restricted expansion of region 13.1 in 99%. (Figure 3B) Bone marrow aspirate was remarkably hypercellular and extensively infiltrated with abnormal lymphoid cells comprising approximately 75% of total nucleated cells, morphologically similar to those seen in peripheral blood. The biopsy showed extensive diffuse infiltration with small to moderately sized lymphoid cells with prominent nuclear irregularity (Figure 4A&B). The immunophenotype was confirmed by immunohistochemistry and the cells were positive for CD3, CD5, CD7, CD2, CD4, BCL2 as well as for Zap70. BCL6 was uniformly negative. Based on the morphology and the immunophenotypic profile, a diagnosis of CD4+/CD8− T-prolymphocytic leukemia was made. FISH analysis revealed ATM deletion at 11q22 and TRA/D rearrangement in 93% of the cells analyzed and karyotype was complex with multiple numeric and structural abnormalities including inv(14)(q11.2q32); Karyotype: 43,XY,del(11)(q14),add(11)(p15),-13,inv(14)(q11.2q32),der(19)t(13;19)(q11;q13.4),-20,-22[7]/42,idem,-9,add(14)(p11.1),add(17)(p13)[23] After confirming the diagnosis of T-PLL the patient travelled back to his home country. He was started on treatment with alemtuzumab, then pentostatin was added in week 4, after 10 weeks of treatment he achieved complete remission. After that he received reduced intensity conditioned allogeneic stem cell transplant from a matched brother, complicated by mild acute graft versus host disease. Until the time of writing this report he was doing fine.

According to World Health Organization (WHO) classification (2008), B-cell neoplasms are classified into precursor B-cell or a mature B-cell phenotype and this classification was also kept in the latest WHO revision (2016). We are reporting a male patient in his fifties, with tonsillar swelling diagnosed as diffuse large B-cell lymphoma (DLBCL), germinal center. He received 6 cycles of RCHOP and showed complete metabolic response. Two months later, he presented with severe CNS symptoms. Flow cytometry on bone marrow (BM) showed infiltration by CD10-positive Kappa-restricted B-cells with loss of CD20 and CD19, and downregulation of CD79b. Moreover, the malignant population showed Tdt expression. BM Cytogenetics revealed t(8;14)(q24;q32) within a complex karyotype. Retrospectively, MYC and Tdt immunostains performed on original diagnostic tissue and came negative for Tdt and positive for MYC. It has been rarely reported that mature B-cell neoplasms present with features of immaturity; however the significance of Tdt acquisition during disease course was not addressed before. What is unique in this case is that the emerging disease has acquired an immaturity marker while retaining some features of the original mature clone. No definitive WHO category would adopt high-grade neoplasms that exhibit significant overlapping features between mature and immature phenotypes.

Systemic mastocytosis (SM) is a condition associated with clonal neoplastic proliferation of mast cells. In up to 40% of systemic mastocytosis cases, an associated clonal hematological disease of non-mast cell lineage, such as acute myeloid leukemia (AML), is diagnosed before, simultaneously with, or after the diagnosis of SM. Herein, we report a case of a 30-year-old man diagnosed with AML with inv(16) (p13;q22) CBFB:MYH11. Associated mastocytosis was not noted at diagnosis and was only detected in the bone marrow at time of remission after successful chemotherapy. The diagnosis of mastocytosis was based on the demonstration of a multifocal dense mast cell infiltrate in the marrow biopsy with aberrant immunophenotype, with coexpression of tryptase, CD117, and CD25. The mast cells showed atypical morphology mostly with irregular nuclear contour, bilobed or multilobed nuclei with cytoplasmic hypogranulation or irregular metachromatic granule distribution, and some cells with eccentric nucleus or spindle shape. Reexamination of the pretherapeutic bone marrow with immunostain for tryptase and CD25 revealed that mastocytosis was present from the start but masked by extensive blast proliferation. This case indicates that mast cell infiltrates are sometimes underappreciated at the original diagnosis of AML with inv(16) and that the concurrent diagnosis of SM with AML requires a high index of suspicion supported with comprehensive morphologic and immunohistochemical evaluation for a neoplastic mast cell proliferation.

Follicular Lymphoma (FL) is the most common indolent lymphoma derived from light zone germinal center B cells and characterized by a t(14;18) translocation resulting in upregulation of BCL2 in over 80% of cases. This translocation alone is not sufficient for tumorogenesis, and must be combined with additional genetic mutations to transform B cells. FL is incurable and the disease course can be highly varied, with survival ranging from a few months to decades following diagnosis and treatment with standard chemoimmunotherapy. The heterogeneity of FL poses major challenges to identifying the association of genetic alterations and clinical outcome. Current WHO guidelines recommend establishing grade for each FL case with grade 3 thought to be more aggressive than 1 and 2. The genetic basis and clinical implications of grade in FL are unclear. Recent sequencing studies have identified many genes found to be recurrently mutated in FL including KMT2D and CREBBP. However, the degree to which genetic alterations cooperate with each other or contribute to clinical outcome is unclear. Based on the observed mutational rates in follicular lymphoma, we estimated 900 cases were needed to comprehensively delineate the genetic alterations that underlie histologic grade and clinical outcome. Accordingly, we enrolled a cohort of 1042 patients with newly diagnosed FL. All treated patients received rituximab-containing standard regimens. To go beyond the identification of gene-coding events, we developed a very large panel of 110 Mbp covering exonic (~40Mbp) and non-exonic regions (~70Mbp) of interest to enable a wide range of genomic analysis including mutation calling in both coding and non-coding regions, rearrangement detection, viral identification, and copy number analysis. In addition to the whole exome, we extended coverage to include introns, promoters, and untranslated regions of all known driver genes in cancer. We included the entirety of the immunoglobulin loci, T-cell receptor loci and CD3 loci to detect clonotypes and rearrangements. We also included lymphoma-relevant long non-coding RNAs, microRNAs, enhancers, and breakpoint-prone regions. For viral detection, we targeted the genomes of eight cancer-related viruses: Epstein-Barr virus, human papillomavirus, human immunodeficiency virus, hepatitis B, hepatitis C, Kaposi's sarcoma-associated herpesvirus, human T-lymphotropic virus, and Merkel cell polyomavirus. In addition, to enable high resolution identification of copy number variation (CNV) calls, the entire genome was tiled with probes spaced 10kb apart. DNA and RNA were extracted from all tumors and their paired normal samples, prepared into DNA and RNA sequencing libraries and subjected to sequencing on the Illumina platform to a targeted coverage of 150X. Somatic events were identified and further filtered to identify driver events in both coding and non-coding regions. FLs demonstrated a significant degree of genetic heterogeneity with over 100 genes mutated with a frequency of at least 2%. Nearly 100% of FL cases had a mutation in at least one chromatin-modifying gene. The most frequently mutated genes in follicular lymphoma were KMT2D, BCL2, IGLL5 and CREBBP. In addition, we identified frequent mutations in SPEN, BIRC6 and SETD2. To our knowledge, this is the first description of alterations in these genes in FL. Transcriptome analysis indicated a strong correlation between BIRC6 mutations and the previously described immune response 2 signature that is associated with a poor prognosis. We further performed unbiased clustering of genetic alterations in these FL cases. We identified a cluster that was specifically enriched in BCL6 and TP53 alterations and was strongly associated with grade 3 FLs which are predicted to have poorer outcomes with low intensity therapies. We further examined the genetic profiles of 1001 DLBCLs in comparison to this cohort of FLs. Our data indicate a continuum of highly overlapping genetic alterations with DLBCL displaying more complex patterns that included alterations in MYC, TP53 and CDKN2A (mainly copy number losses), indicating shared pathogenetic mechanisms underlying FL and DLBCL, particularly those germinal center B cell origin. Disclosures Koff: Burroughs Wellcome Fund: Research Funding; V Foundation: Research Funding; Lymphoma Research Foundation: Research Funding; American Association for Cancer Research: Research Funding. Leppä:Roche: Honoraria, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees. Gang:ROCHE: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Hsi:Abbvie: Research Funding; Eli Lilly: Research Funding; Cleveland Clinic&Abbvie Biotherapeutics Inc: Patents & Royalties: US8,603,477 B2; Jazz: Consultancy. Flowers:AbbVie: Consultancy, Research Funding; Denovo Biopharma: Consultancy; BeiGene: Consultancy, Research Funding; Burroughs Wellcome Fund: Research Funding; Eastern Cooperative Oncology Group: Research Funding; National Cancer Institute: Research Funding; V Foundation: Research Funding; Optimum Rx: Consultancy; Millenium/Takeda: Research Funding; TG Therapeutics: Research Funding; Gilead: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Karyopharm: Consultancy; AstraZeneca: Consultancy; Pharmacyclics/Janssen: Consultancy, Research Funding; Spectrum: Consultancy; Bayer: Consultancy; Acerta: Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding. Neff:Enzyvant: Consultancy; EUSA Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fedoriw:Alexion Pharmaceuticals: Other: Consultant and Speaker. Reddy:Genentech: Research Funding; BMS: Consultancy, Research Funding; Celgene: Consultancy; KITE Pharma: Consultancy; Abbvie: Consultancy. Mason:Sysmex: Honoraria. Behdad:Loxo-Bayer: Membership on an entity's Board of Directors or advisory committees; Thermo Fisher: Membership on an entity's Board of Directors or advisory committees; Pfizer: Other: Speaker. Burton:Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dave:Data Driven Bioscience: Equity Ownership.

Introduction: Philadephia-negative Myeloproliferative neoplasms (MPNs) include polycythemia Vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). The diagnosis of MPNs and further sub classification are based mainly on WHO diagnostic criteria which rely on the presence of an evidence of single or multiple cell lineage proliferation reflected by elevated hemoglobin, and / leukocytosis and /thrombocytosis. In addition, to presence of certain pathologic features in the bone marrow (BM) including hypercellularity , panmyelosis, proliferation of megakaryocytes, the presence of atypical megakaryocytes and or increased marrow fibrosis. This is in addition to the presence of molecular genetic marker specific for MPN including JAK-2, MPL and CALR. Making a diagnosis of MPN in absence of the previously mentioned features is always challenging. Herein, we analyze the clinical, pathologic and molecular genetics features for five cases presented with splanchnic vein thrombosis and found to be positive for JAK-2 V617F. However, from the hematpathologic point of view, apart from JAK-2 positivity, none of these cases had fulfilled the WHO diagnostic criteria for MPNs. Although the BM specimens were reviewed by at least two experienced hematopathologists, it was so difficult to conclude the diagnosis and or do further sub classification into a specific MPN category. Objective: The aim of this report is to highpoint the difficulty in establishing the diagnosis within this group of patients based on the current WHO diagnostic criteria, to focus on BM pathologic features of this group of patients. Patients and Methods: The patients reported here were referred to our center presenting with portal vein, superior mesenteric or splenic vein thrombosis. Five adult female patients were recognized (2015 and 2019). The mean age at diagnosis is 40.8 years (27-56). None of these cases had an increase in peripheral blood counts except for patient (1) which had mild leukocytosis and thrombocytosis. All patients showed normocellular or slightly hypercellular BM. Slight erythroid predominance was reported in patient (2) and (4). Megakaryocytes were increased in all patients except for patient (2). Interestingly, megakaryocytes morphology was similar in all five patients as they showed anisocytosis with some degree of pleomorphism with predominant of large forms, no clustering and no abnormal topography was noted (figure 1 and 2). All patients showed no significant increase in reticulin fibrosis. Sub-classification into a specific MPN category cannot be performed in all patients. Next generation sequence had been used to analyze targeted regions in recurrently mutated genes in myeloid neoplasia. JAK-2V617F mutation was detected in all studied patients. In patient number (2) JAK-2 mutation was detected at a low level (4%), however, on follow-up, the mutation level increased in addition to detection of 3bp insertion/deletion in CALR gene resulting in a mutation other than type I or type II. table (1). Discussion: Splanchnic veins thrombosis (SVT) includes the portal vein thrombosis (PVT), mesenteric (MVT) splenic vein thrombosis, and the Budd Chiari syndrome (BCS). SVTs are rare events, estimated by 0.7 per 100,000 patients per year for PVT [Rajani et al. 2010]. In a laboratory setting, the diagnosis of latent MPN in patients with SVT is challenging due to absence of elevated blood counts, probably caused by portal hypertension and splenomegaly that result from SVT and MPN. However, the reason why this group of patients does not have overt features of myeloproliferation (particularly) the hypercellularity in the BM is not yet clear. It is possible that JAK-2 positivity induced venous thrombosis longer time before development of the full blown picture of MPN. However, follow-up BM studies for this group of patients might help in better characterization of the pathologic features of these patients. These patients are included in the MPN, unclassifiable subcategory in the current WHO classification. However, based on our findings and the previously published data it seems that these patients have distinctive clinical and pathological features that necessitate having them in a separate MPN entity that might have less strict diagnostic criteria that might include clinical symptoms especially venous thrombosis in large vessels. Separating this group of patients will help to study them thoroughly. Disclosures No relevant conflicts of interest to declare.

Introduction Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of NHL ~30% of newly diagnosed lymphoma cases. The International Prognostic Index (IPI) has been the primary clinical tool used to predict outcome for patients with large B-cell lymphomas (LBCL) and used in most clinical trials so far. This model identified five factors to predict DLBCL survival: age >60, elevated serum lactate dehydrogenase (LDH), ECOG performance status ≥2, Ann Arbor stage III or IV, and number of involved extranodal sites ≥2. This is a single center study aimed to study several clinicopathological characteristics of LBCL including: IPI parameters, double expressor status (DE) and patient's response at end of treatment by Positron emission tomography with 2-deoxy-2-[fluorine-18 ]fluoro- D-glucose integrated with computed tomography (18F-FDG PET/CT) (PET/CT scan). All relevant parameters were correlated to overall survival (OS) and event free survival (EFS). We found an excellent correlation between achievement of post treatment complete metabolic remission (CMR) by PET/CT and both OS and EFS while no statistically significant difference detected regarding OS or PFS among different IPI risk groups or in patients with DE phenotype compared to non-DE. Patient and Method: This is a 5- year mixed design study of adults with LBCLs. Baseline demographic, relevant laboratory data including LDH, pathological characteristics: cell origin of lymphoma, KI67 index, relevant immunohistochemical profile, DE status, achievement of CMR at end of treatment were correlated with OS and EFS at 2-years of diagnosis. Double expressor lymphomas (DELs) are defined by concomitant expression of MYC and BCL2 detected by IHC (cutoffs-40% MYC and 50% BCL2). Genetic double hit lymphomas (by FISH) were excluded. All patients in our cohort were treated with RCHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) plus Rituximab regimen and evaluated at end of treatment by PET/CT scan using the Deauville five-point scale with scores of 1-3 considered negative and scores 4-5 is positive. All residual lesions exhibiting equal or less intense uptake than the liver were reported as CMR. PET/CT was done six to eight weeks after completion of chemotherapy and 12 weeks after the completion of radiation therapy. Results: Our cohort was composed of 170 patients diagnosed as large B cell lymphoma, the EFS and OS curves demonstrate the excellent outcome in patients treated with R-CHOP. No statistically significant difference in OS or PFS among different IPI risk groups (1-2 versus 3-5) in our cohort. Disease stage and LDH level had affected EFS with statistically significant differences but not OS. Other individual IPI parameters showed no significant correlation OS or PFS. Although the difference in survival between the two groups (DE and non-DE) are not statistically significant, it was clinically significant with a difference in survival between the two groups of approximately 24 months. OS and EFS among patients with CMR found to be significantly longer compared to those who did not achieve CMR with a statically significant difference (p:< 0.05). CMR was noted to be higher among patients with favorable IPI (0 to 2) compared to patients with IPI values ranged between 3 - 5, however this difference was statistically insignificant (84.9 % vs 75.5%; P=0.178). The percentage of post treatment CMR was significantly higher among patients presented without extranodal disease compared to patients with extranodal involvement (94.1 % vs 74.1%; P=0.004). CMR was also significantly higher among patients presented with normal LDH compared to patients with high LDH (91.4 % vs 73.6%; P=0.009). The percentage of CMR was slightly higher among DE patients compared to non-DE patients , however this difference was statistically insignificant (83.3 % vs 79.6%; P=0.660). Conclusion While IPI is the most widely used prognostic predictor in LBCLs, there are limited data regarding the predictive value of post treatment PET/CT scans. We found that achievement of CMR at end of treatment was a very strong predictor of OS and PFS in our cohort compared to standard international prognostic parameters. To characterize the most important individual IPI parameters affected post treatment CMR and indirectly predicting OS and PFS, we found that extranodal involvement and LDH level were the most significant factors affecting CMR achievement. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Methemoglobinemia is a rare overlooked differential diagnosis in patients presented with cyanosis and dyspnea unrelated to cardiopulmonary causes. Our patient is 29 year old Indian non-smoker male, his story started 6 months prior to presentation to our center when he had generalized fatigue and discoloration of hands. He presented with persistent polycythemia with elevated hemoglobin level. The patient was misdiagnosed in another center as polycythemia and treated with Imatinib. The diagnosis of PV was revisited and ruled out in view of negative JAK2, normal erythropoietin level and absence of features of panmyelosis. Clinical cyanosis and lowoxygen saturation in the presence of normal arterial oxygen tension was highly suggestive of methemoglobinemia. Arterial blood gas revealed a methemoglobin level of 38% (normal: 0–1.5%). Cytochrome B5 reductase (Methemoglobin reductase B) was deficient at level of