Post cytotoxic myeloid neoplasms signify a heterogenous pool of poorly understood hematologic neoplasms with unfortunate survival and ineffective therapies. There is a lack of consensus on prognostic indicators, primarily due to the heterogenous disease spectrum encompassing different pathological, cytogenomic and original disease variables. This retrospective, single-center study over 10 years duration on MN-pCT cases diagnosed at NCCCR, a member of Hamad Medical Corporation. The study aimed to analyze clinicopathologic and cytogenomic characteristics, identify key prognostic predictors, and assess their impact on mortality through univariate and multivariate analyses. We identified 42 MN-pCT patients, noting a 31.7

Levodopa/carbidopa remains the gold standard for treating Parkinson disease (PD), but chronic pulsatile administration contributes to motor complications. This Phase 1 study used a new immediate-release (IR) formulation of carbidopa/levodopa 25/100 mg that is functionally scored for easy and precise splitting to evaluate the effects on levodopa plasma variability when smaller doses are taken more frequently. These functionally scored tablets were shown to be bioequivalent to carbidopa/levodopa 25-/100-mg IR generic reference tablets. Twenty-two healthy volunteers received a whole tablet every 4 hours versus half of the tablet every 2 hours. Plasma levodopa fluctuations were significantly reduced with half-tablets dosed every 2 hours, with a 44% reduction in peaks (P < .0001). While drug exposure did not differ, parameters that underlie motor response variations, including mean peak-to-trough difference and variance, were 51% and 56% less, respectively, with more frequent dosing (both P <= .0024). Safety and tolerability of both regimens were similar. In conclusion, more frequent administration of half-tablets of the new functionally scored IR formulation safely provided more constant levodopa levels than whole tablets dosed less often. This tablet technology could facilitate the benefits of more physiologic dopamine replenishment in patients with PD, particularly those with reduced manual dexterity.

Background: A new recombinant activated factor VII, eptacog beta (SEVENFACT®, rFVIIa-jncw) has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of bleeding events (BEs) in individuals >12 years of age with hemophilia A or B (HAB) with inhibitors. In the eptacog beta phase III trial (Wang, Haemophilia, 2017), 87% of BEs were successfully treated using two different dosing regimens within 12 hours of bleeding onset. In two studies looking at the safety of eptacog beta Ducore, Haemophilia, 2017), a total of 11 treatment-emergent adverse events (TEAEs) were reported in 42 participants, all mild and transitory. To date, no studies designed to assess safety of treatment of breakthrough BEs in people on emicizumab with eptacog beta have been performed.

Surgical procedures in persons with haemophilia A or B with inhibitors (PwHABI) require the use of bypassing agents (BPA) and carry a high risk of complications. Historically, only two BPAs have been available; these are reported to have variable responses.

Introduction Haemophilia patients with inhibitors often require a bypassing agent (BPA) for bleeding episode management. Eptacog beta (EB) is a new FDA-approved recombinant activated human factor VII BPA for the treatment and control of bleeding in haemophilia A or B patients with inhibitors (>= 12 years of age). We describe here the EB safety profile from the three prospective Phase 3 clinical trials performed to date. Aim To assess EB safety, immunogenicity and thrombotic potential in children and adults who received EB for treatment of bleeding and perioperative care. Methods Using a randomized crossover design, 27 subjects in PERSEPT 1 (12-54 years) and 25 subjects in PERSEPT 2 (1-11 years) treated bleeding episodes with 75 or 225 mu g/kg EB initially followed by 75 mu g/kg dosing at predefined intervals as determined by clinical response. Twelve PERSEPT 3 subjects (2-56 years) received an initial preoperative infusion of 75 mu g/kg (minor procedures) or 200 mu g/kg EB (major surgeries) with subsequent 75 mu g/kg doses administered intraoperatively and post-operatively as indicated. Descriptive statistics were used for data analyses. Results Sixty subjects who received 3388 EB doses in three trials were evaluated. EB was well tolerated, with no allergic, hypersensitivity, anaphylactic or thrombotic events reported and no neutralizing anti-EB antibodies detected. A death occurred during PERSEPT 3 and was determined to be unlikely related to EB treatment by the data monitoring committee. Conclusion Results from all three Phase 3 trials establish an excellent safety profile of EB in haemophilia A or B patients with inhibitors for treatment of bleeding and perioperative use.

Abstract Introduction Following treatment with a bypassing agent, parents or caregivers often face difficulties in determining bleeding episode (BE) resolution in children with hemophilia A or B and inhibitors (CwHABI), potentially contributing to a longer treatment duration in children as compared to adults (Valentino et al, Haemophilia 2012; 18:554-60. Gruppo et al, Haemophilia 2013; 19:524-32). Eptacog beta is a new recombinant activated human factor VII proven to be safe and effective for the treatment and control of BEs in patients with hemophilia A or B with inhibitors (≥12 years of age). The pivotal phase 3 trial (PERSEPT 1; NCT02020369) included subjects from ages 12 to <18 years, in addition to adult subjects. A subsequent phase 3 trial (PERSEPT 2; NCT02448680) further examined the safety and efficacy of eptacog beta for bleed treatment in CwHABI <12 years of age. Within this population, we hypothesized that caregivers could better ascertain treatment success in older children, which would manifest as increasing eptacog beta efficacy measurements and tighter 95% confidence intervals (CIs) with increasing subject age. We explored this question by analyzing BE treatment success in three age subgroups within PERSEPT 1 and PERSEPT 2. Aims The study objective is to evaluate and compare the clinical response to eptacog beta for BEs in CwHABI at 12 and 24 hours after initial dose of eptacog beta in 3 pediatric age subgroups (<6 years, 6 to <12 years, and 12 to <18 years). Methods PERSEPT 1 and PERSEPT 2 were prospective, global, open-label trials of eptacog beta using two initial dose regimens (IDRs) of 75 and 225 µg/kg in a randomized, non-blinded, crossover design. Subjects received initial doses of 75 or 225 µg/kg eptacog beta followed by 75 µg/kg dosing at predefined intervals (determined by clinical response) to treat BEs (Figure 1). Treatment success for mild or moderate BEs was defined as obtaining a hemostasis evaluation of "excellent" or "good" with no use of additional eptacog beta, alternative hemostatic agents or blood products, and no increase in pain following the first "excellent" or "good" assessment. Evaluations were provided by the parent/caregiver in conjunction with the study participant when possible, depending upon subject age and verbal capacity. Written informed consent from the participants' parents/legal guardians were obtained at enrollment. Results Thirty subjects were assessed (25 from PERSEPT 2 [13 subjects, 0 to <6 years; 12 subjects, 6 to <12 years] and 5 from PERSEPT 1 [ages 12 to <18 years]). These subjects experienced 628 mild/moderate BEs. No subject was receiving emicizumab prophylaxis. Nearly all BEs in every pediatric age subgroup were successfully treated by 24 hours after initial eptacog beta infusion (Figure 2). At 12 hours, BE treatment success proportions in the 0 to <6 year, 6 to <12 year, and 12 to <18 year subgroups for the 75 µg/kg IDR were 58%, 72%, and 93%, respectively. Corresponding treatment success proportions for the 225 µg/kg IDR in the 0 to <6 year, 6 to <12 year, and 12 to <18 year subgroups were 58%, 63%, and 89%, respectively. The increased treatment success proportions seen for the 12 to <18 year subgroup over those seen for the 0 to <6 year and 6 to <12 year subgroups were statistically significant for both IDRs (p < 0.05; Figure 2). Differences in treatment success between the 0 to <6 year and 6 to <12-year subgroups were not statistically significant for either IDR. Treatment success point estimates at 12 hours in the 0 to <6 years age group showed the widest CIs among the various subgroups (Figure 2). Conclusions Eptacog beta treatment of BEs in this pediatric population yielded remarkable (>95%) treatment success proportions in both IDRs by 24 hours after initial eptacog beta infusion of 75 or 225 µg/kg. Differing age group pharmacokinetics could contribute to the observed increase in treatment efficacy at 12 hours with increasing subject age. In addition, when taken together with the wide CIs associated with treatment success point estimates at 12 hours for the 0 to <6 year subgroup, these results are consistent with well-known challenges that drive pediatric dosing of bypassing agents: chiefly, that of caregivers experiencing uncertainty with regard to BE resolution in young children. The high efficacy and narrow 95% CIs seen at 24 hours further indicate that caregivers had achieved clarity regarding BE resolution by the 24-hour timepoint. Figure 1 Figure 1. Disclosures Young: Apcintex, BioMarin, Genentech/Roche, Grifols, Novo Nordisk, Pfizer, Rani, Sanofi Genzyme, Spark, Takeda, and UniQure: Consultancy; Genentech/Roche, Grifols, and Takeda: Research Funding. Pipe: Catalyst Biosciences: Consultancy; CSL Behring: Consultancy; HEMA Biologics: Consultancy; Freeline: Consultancy, Other: Clinical trial investigator; Novo Nordisk: Consultancy; Pfizer: Consultancy; Roche/Genentech: Consultancy, Other; Sangamo Therapeutics: Consultancy; Sanofi: Consultancy, Other; Takeda: Consultancy; Spark Therapeutics: Consultancy; uniQure: Consultancy, Other; Regeneron/ Intellia: Consultancy; Genventiv: Consultancy; Grifols: Consultancy; Biomarin: Consultancy, Other: Clinical trial investigator; Bayer: Consultancy; ASC Therapeutics: Consultancy; Apcintex: Consultancy; Octapharma: Consultancy; Shire: Consultancy. Carcao: Bayer, Bioverativ/Sanofi, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche, and Shire/Takeda: Research Funding; Bayer, Bioverativ/Sanofi, CSL Behring, Grifols, LFB, Novo Nordisk, Pfizer, Roche, and Shire/Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Castaman: Uniqure: Honoraria; Bayer: Honoraria; Sobi: Honoraria; CSL Behring: Honoraria; Novo Nordisk: Honoraria; Kedrion: Honoraria; LFB: Honoraria; Grifols: Honoraria; Werfen: Honoraria; Biomarin: Honoraria; Sanofi: Honoraria; F Hoffmann-La Roche Ltd: Honoraria. Davis: Genentech, Spark Therapeutics, BioMarin, Bayer: Consultancy; Takeda, Sanofi: Honoraria; Genentech, Sanofi, Novo Nordisk: Membership on an entity's Board of Directors or advisory committees. Ducore: Octapharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; HEMA Biologics: Consultancy, Honoraria; Bayer: Consultancy, Honoraria, Speakers Bureau; Shire: Consultancy, Honoraria. Dunn: Sanofi, Takeda, Freeline, BioMarin, ATHN, Novo Nordisk: Research Funding; Genentech, Kedrion, CSL Behring, BioMarin: Consultancy; UniQure, CSL Behring, World Federation of Hemophilia USA: Membership on an entity's Board of Directors or advisory committees; Roche/Genentech: Honoraria. Journeycake: HEMA Biologics: Honoraria; LFB: Honoraria. Khan: Genentech, Octapharma, BioMarin, CSL Behring, HEMA Biologics, Kedrion, and Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Mahlangu: Bayer, Biogen, BioMarin, CSL, Novo Nordisk, Sobi, Roche, and UniQure: Research Funding; Amgen, Bayer, Biotest, Biogen, Baxalta, CSL Behring, Catalyst Biosciences, Novo Nordisk, Roche, and Spark: Membership on an entity's Board of Directors or advisory committees; Alnylam, Bayer, Biotest, Biogen, Novo Nordisk, Pfizer, Sobi, Shire, Roche, ISTH, and WFH: Speakers Bureau. Meeks: Sangamo Therapeutics: Consultancy; Spark Therapeutics: Consultancy; National Hemophilia Foundation: Research Funding; Pfizer: Consultancy; Sanofi: Consultancy; CSL Behring: Consultancy; Genentech: Consultancy; Takeda: Consultancy; Hemophilia of Georgia: Research Funding; National Institutes of Health: Research Funding. Négrier: UniQure: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Biomarin: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche-Chugai: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi-Sobi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Spark: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Recht: Foundation for Women and Girls with Blood Disorders, Partners in Bleeding Disorders: Speakers Bureau; uniQure: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy; Octapharma: Consultancy; Novo Nordisk: Consultancy; Kedrion: Consultancy; Hema Biologics: Consultancy; Genentech: Consultancy; CSL Behring: Consultancy; Catalyst Biosciences: Consultancy; American Thrombosis and Hemostasis Network: Current Employment; Oregon Health & Science University: Current Employment. Chrisentery-Singleton: Biomarin: Speakers Bureau; Spark: Consultancy, Research Funding; Takeda: Consultancy, Speakers Bureau; Kedrion: Consultancy; Octapharma: Consultancy; Pfizer: Consultancy, Research Funding, Speakers Bureau; Sanofi: Consultancy; Hema Biologics: Consultancy; Grifols: Consultancy; CSL Behring: Consultancy, Speakers Bureau; Genentech: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy, Speakers Bureau. Stasyshyn: CSL Behring: Consultancy, Research Funding; Novo Nordisk: Consultancy, Research Funding, Speakers Bureau; Octapharma: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Takeda: Consultancy, Research Funding, Speakers Bureau; Grifols: Consultancy, Speakers Bureau; Shire: Consultancy. Wang: Octapharma: Other; Pfizer/Spark: Other: clinical trial investigator; uniQure: Consultancy, Other: Clinical trial investigator; Hema Biologics: Consultancy, Other: Clinical trial investigator; Takeda: Consultancy, Other: Clinical trial investigator; Genentech: Consultancy, Other: Clinical trial investigator; Novo Nordisk: Consultancy, Other: Clinical trial investigator; CSL Behring: Consultancy, Other: Clinical trial investigator; Bioverativ: Consultancy, Other: Clinical trial investigator; Bayer: Consultancy, Other: Clinical trial investigator; BioMarin: Consultancy, Other: Clinical trial investigator. Windyga: Alnylam Pharmaceuticals: Research Funding; Novo Nordisk: Research Funding, Speakers Bureau; Octapharma: Research Funding, Speakers Bureau; Rigel: Research Funding; Roche: Research Funding, Speakers Bureau; Sanofi/Genzyme: Research Funding, Speakers Bureau; Shire/takeda: Research Funding, Speakers Bureau; Sobi: Research Funding, Speakers Bureau; Alexion: Speakers Bureau; CSL Behring: Speakers Bureau; Werfen: Speakers Bureau. Alexander: HEMA Biologics: Consultancy, Ended employment in the past 24 months. Al-Sabbagh: LFB: Current Employment. Bonzo: LFB: Current Employment. Macie: HEMA Biologics: Current Employment. Mitchell: HEMA Biologics: Consultancy, Current Employment. Wilkinson: GLOVAL, LLC: Consultancy. Shapiro: Genentech: Other: Advisory board fees, Research Funding, Speakers Bureau; Glover Blood Therapeutics: Research Funding; Kedrion Biopharma: Research Funding; Daiichi Sankyo: Research Funding; Bioverativ (a Sanofi company): Other: Advisory board fees, Research Funding; Takeda: Research Funding; Novo Nordisk: Other: Advisory board fees, Research Funding, Speakers Bureau; Octapharma: Research Funding; OPKO: Research Funding; Sangamo: Other: Advisory board fees, Research Funding; Prometric BioTherapeutics: Research Funding; Pfizer: Research Funding; Sigilon Therapeutics: Other: Advisory board fees, Research Funding; Novartis: Research Funding; BioMarin: Research Funding; Agios: Research Funding.

Gamma-delta (γδ) T-cell lymphomas are very rare and aggressive neoplasms. We describe here a challenging case of γδ T-cell neoplasm composed of γδ mature T-cells and γδ precursor T-cells with marked eosinophilia that is inapplicable to the current 2016 World Health Organization (WHO) classification. A 3-year-old female child who was presented with fever and marked leukocytosis. Peripheral blood smear showed marked lymphocytosis, marked eosinophilia, neutrophilia, monocytosis, and 5% circulating blasts. CT scan showed anterior mediastinal mass, lymphadenopathy, and hepatosplenomegaly. The patient underwent a bone marrow examination and a biopsy taken from the mediastinal mass. Peripheral blood and bone marrow findings were consistent with a γδ T-cell neoplasm with increased blasts and eosinophilia. The patient was sequentially treated with imatinib (tyrosine kinase inhibitor), acute lymphoblastic leukemia protocol (BFM 2009) then shifted to lymphoma protocol (LMP 96). In conclusion, we report a unique rare case of γδ T-cell neoplasm with a combination of mature and immature γδ T-cells and eosinophilia that is inapplicable to the current 2016 WHO classifications. This case raises a challenging concept of a mature T-cell lymphoma arising in an immature T-cell neoplasm. It also highlights the need to target all neoplastic components to eradicate the disease.

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.

Lymphoid enhancer‐binding factor 1 (LEF‐1) overexpression has been recently remarkably reported in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and has shown utility in distinguishing CLL/SLL from other B‐cell lymphomas. CLL has a well‐defined immunophenotype, yet, some cases of CLL demonstrate atypical morphology/ phenotype reflected by low Matutes score (atypical CLL). Till date, LEF1 expression has not been systematically studied in cases of CLL with atypical features.

Introduction Joint bleeding events (BEs) have cumulative, irreversible and debilitating consequences for persons with hemophilia A or B with inhibitors (PwHABI) due to synovitis and joint iron deposition. To limit the long-term consequences of bleeding into joints, early bleed resolution is a primary treatment goal. Eptacog beta (Sevenfact®, HEMA Biologics and LFB) is a new bypassing agent indicated for the treatment and control of BEs in adults and adolescents with hemophilia A or B with inhibitors. In a prospective, randomized, cross-over, phase 3 clinical trial (PERSEPT 1, NCT#02020369) in the first 24 hours following bleed onset, eptacog beta demonstrated dose-dependent improvements in successful clinical response with 2 initial dose regimens (IDRs) (75 µg/kg IDR: 75 µg/kg q3h; and 225 µg/kg IDR: 225 µg/kg followed by 75 µg/kg q3h after 9 hours if necessary; Figure 1). 91% of all mild or moderate BEs achieved hemostatic efficacy at 12 hours (225 µg/kg IDR), as did 82% at 12 hours in the 75 µg/kg IDR. The majority (85%) of mild/moderate BEs treated in PERSEPT 1 were joint BEs. Aims A subset analysis of mild or moderate joint BE data from the PERSEPT 1 trial was performed to investigate the effect of 2 IDRs on clinical response at 3, 9, 12 and 24 hours on joint BEs in PwHABI. IRB approval and informed consent were obtained. Methods At enrollment, male PwHABI (n=27) were randomized to receive BE treatment on either the 75 µg/kg IDR or the 225 µg/kg IDR (Figure 1) for the first 3 months of treatment; subjects were crossed over to the alternate IDR every 3 months. The 12-hour composite endpoint subset analysis for joint BEs used the same success criteria that were used for the primary efficacy endpoint (for all BEs at 12 hours) in PERSEPT 1. Hemostatic efficacy at all other intermediate timepoints and at 24 hours was assessed using a 4-point evaluation scale (an excellent or good evaluation being considered hemostatic efficacy, and moderate or poor being considered a lack of hemostatic efficacy.) BE treatment continued until bleeding ceased as determined by the subject or physician to discontinue treatment. Results A subset of 396 mild/moderate joint BEs were analyzed. The proportion of successfully treated BEs (composite endpoint) at 12 hours was 91.5% [95% CI: 83.4%, 99.6%] on the 225 µg/kg IDR and 80.6% [95% CI: 69.6%, 91.6%] on the 75 µg/kg IDR. At 9 hours, the proportion of BEs with hemostatic efficacy (using the 4-point evaluation scale) from the first dose in the 225 µg/kg IDR was 86.5%; 3- and 24-hour data are shown in Table 1. Conclusions The joint BE success proportion following a first dose in the 225µg/kg IDR at 3 hours was 85.2%; joint BEs treated by the 75µg/kg IDR demonstrated a 26.4% 3-hour success proportion. These success proportions demonstrate a dose-dependent onset of action; this effect on efficacy was also observed in the 12- and 24-hour data. At 9 hours, sustained hemostatic efficacy from a single 225 µg/kg dose was observed (86.5%). Overall, both initial dose regimens showed successful resolution of joint BEs with early hemostatic success proportions. Further, the onset of action data supports the concept that a larger initial thrombin burst may result in an earlier effective clot that drives earlier bleed resolution. Further observations of this type are needed to understand the role of rFVIIa in hemostatic clot formation. Disclosures Hermans: Bayer: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Shire, a Takeda company: Consultancy, Research Funding, Speakers Bureau; Sobi: Consultancy, Research Funding, Speakers Bureau; Biogen: Consultancy, Speakers Bureau; CAF-DCF: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; LFB: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Octapharma: Consultancy, Speakers Bureau; Kedrion: Speakers Bureau; EAHAD: Other; WFH: Other. Ducore:Octapharma: Consultancy; Bayer: Consultancy, Honoraria, Speakers Bureau; HEMA Biologics: Consultancy, Honoraria. Escobar:Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; National Hemophilia Foundation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Young:BioMarin, Freeline, Genentech/Roche, Grifols, Kedrion, Novo Nordisk, Sanofi Genzyme, Spark, Takeda, and UniQure: Honoraria; Bayer, CSL Behring, Freeline, UniQure: Consultancy; Genentech/Roche, Grifols, and Takeda: Research Funding. Wang:Bayer: Honoraria; Takeda: Honoraria; Genentech: Honoraria; Biomarin: Honoraria; CSL Behring: Honoraria; Bioverativ Inc: Honoraria. Quon:Shire/Takeda: Speakers Bureau; Octapharma: Honoraria; Biomarin: Honoraria, Speakers Bureau; Genentech, Inc./F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; Novo Nordisk: Honoraria, Speakers Bureau; Bayer: Honoraria; Orthopaedic Institute for Children: Current Employment; Bioverativ/Sanofi: Honoraria, Speakers Bureau. Alexander:HEMA Biologics, LLC: Current Employment, Patents & Royalties: No royalties or benefits. Mitchell:HEMA Biologics: Consultancy. Al-Sabbagh:LFB: Current Employment. Bonzo:International Association for Statistical Computing: Other; International Statistics Institute: Other; American Statistical Association: Other; LFB USA, Inc.: Current Employment.

Pleural effusion is a rare presentation of plasma cell myeloma, occurring in around 6% of patients during the course of their disease, most commonly as a consequence of a concurrent disease process like heart failure secondary to amyloid deposition. Direct infiltration of the pleural fluid by malignant cells leading to myelomatous pleural effusion is a rare mechanism occurring in less than 1% of patients with plasma cell myeloma, and it is associated with a worse prognosis. There are few case reports of myelomatous pleural effusion as an initial presentation of multiple myeloma. Pleural fluid infiltration by monoclonal plasma cells in the absence of an underlying plasma cell myeloma was not reported before in the literature. Tuberculosis is a known cause of polyclonal gammaglobulinemia, however few case reports described the coexistence of monoclonal gammopathy of undetermined significance and tuberculosis. Here we present an interesting case of pleural fluid infiltration by an abnormal looking clonal plasma cells associated with active pulmonary tuberculosis and parapneumonic effusion in a patient with a background of acute myeloid leukemia. Interestingly, the clonal plasma cell proliferation was confined to the pleural fluid without any evidence of an underlying plasma cell neoplasms (including monoclonal gammopathy of undetermined significance and plasmacytomas). Since our patient had an underlying meyloid neoplasm, we though about the possibility of secondary malignancy. However, in almost all patients with coexisting myeloid and plasma cell neoplasms, myeloid neoplasms developed following chemotherapeutic treatment of plasma cell neoplasms not the other way around. Given that, one must conclude localized extramedullary (pleural) plasma cell proliferation probably represents a transient reactive process to pulmonary tuberculosis which is an extremely rare phenomenon and not described before.

Objective: Unusual clinical courseBackground: 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.

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).

Introduction Eptacog beta [Sevenfact®, coagulation factor VIIa (recombinant)-jncw] (HEMA Biologics and LFB) is a human rFVIIa variant indicated for the treatment and control of bleeding events (BEs) in adults and adolescents with hemophilia A or B with inhibitors. Eptacog beta has not yet been approved for perioperative management; therefore, a phase 3 trial (PERSEPT 3, NCT02548143) was initiated to evaluate the safety and efficacy of eptacog beta for the prevention of excessive bleeding and achievement of hemostasis in persons with hemophilia A or B with inhibitors (PwHABI) undergoing elective surgery or other invasive procedures. Aims To determine the perioperative safety and efficacy of eptacog beta in major and minor elective procedures in PwHABI. Methods PERSEPT 3 was a global, multicenter, single-arm, phase 3 trial that enrolled male PwHABI who required elective minor or major procedures. IRB approval was obtained, and all subjects provided informed consent. Immediately prior to the start of the procedure, subjects undergoing minor invasive procedures were administered an initial dose of 75 µg/kg eptacog beta and those undergoing major invasive procedures were administered an initial dose of 200 µg/kg eptacog beta. Additional eptacog beta (75 µg/kg) was administered during the procedure and post-operatively (Table 1). Hemostatic efficacy was assessed using a 4-point evaluation scale during the procedure, immediately following the procedure, at regular post-operative intervals, and 48 hours following the last dose of eptacog beta (hemostatic evaluations were recorded as excellent, good, moderate and poor). The primary efficacy endpoint was the percentage of good and excellent responses (ie, successes) at 48 (±4) h following the final dose of eptacog beta and was based upon the investigators' integrated assessment; taking into consideration the investigators' intraoperative hemostatic assessment; the number of postoperative bleeding events and interventions, and blood transfusions; and the amount of eptacog beta used. Results Twelve male subjects (age 2-56 years; median 20 years) were enrolled at 8 sites in 5 countries; all subjects had severe hemophilia A with inhibitors. Six minor procedures [circumcision (3) and tooth extraction (3)] and 6 major procedures (left transtibial amputation, hip replacement, orthopedic knee surgery, amputation of the left leg, left knee joint endoprosthesis removal, and left ankle achilloplasty) were evaluated. The primary efficacy endpoint is shown in Table 2: the success proportion was 67% for major procedures and 100% for minor procedures. The intraoperative efficacy of eptacog beta was rated as good or excellent in all 12 procedures (100% success); mean estimated actual intraoperative blood loss was lower than the mean maximum predicted blood loss for a patient without a bleeding disorder undergoing the same procedure. Efficacy 24 hours following procedure completion was rated as good or excellent in all procedures where data were reported (major, 4/4; minor, 6/6). One subject (major procedure) was withdrawn from the study due to an adverse event (postprocedural hematoma); this subject subsequently received aPCC and NSAIDs and experienced blood loss anemia and GI hemorrhage. One subject (minor procedure) withdrew consent. Other nontreatment-related adverse events included postoperative anemia, post-procedural hemorrhage, procedural pain, wound secretion and hemorrhage. No allergic, hypersensitivity, or anaphylactic events were reported; no anti-eptacog beta antibodies were observed; and no thromboembolic events occurred. Conclusions This controlled study demonstrated the efficacy and safety of 2 different dose regimens of eptacog beta in minor and major elective procedures. The intraoperative hemostatic efficacy of eptacog beta was rated as good or excellent in all major and minor procedures, and the success proportion 48h following the final dose (primary efficacy endpoint) was 82% overall. The breadth of procedures examined (ranging from circumcision and tooth extraction to amputation and hip replacement), low mean blood loss, and high intraoperative efficacy suggests that eptacog beta may be successfully utilized in a variety of minor and major procedures. This study provides useful perioperative data for providers who manage congenital hemophilia A or B patients with inhibitors. Disclosures Escobar: National Hemophilia Foundation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees. Quon:Genentech, Inc./F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; Novo Nordisk: Honoraria, Speakers Bureau; Shire/Takeda: Speakers Bureau; Octapharma: Honoraria; Bayer: Honoraria; Biomarin: Honoraria, Speakers Bureau; Orthopaedic Institute for Children: Current Employment; Bioverativ/Sanofi: Honoraria, Speakers Bureau. Leissinger:Bayer: Consultancy; CSL Behring: Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy; HEMA Biologics: Consultancy; Takeda: Consultancy; Uniqure: Consultancy; Kedrion: Consultancy; Spark: Consultancy. Luck:Orthopaedic Institute for Children: Research Funding; National Hemophilia Foundaton: Honoraria, Speakers Bureau; Board of Trustees, Orthopaedic Institute for Children: Membership on an entity's Board of Directors or advisory committees. Al-Sabbagh:LFB: Current Employment. Bonzo:LFB USA, Inc.: Current Employment; American Statistical Association: Other; International Statistics Institute: Other; International Association for Statistical Computing: Other. Mitchell:HEMA Biologics: Consultancy. Alexander:HEMA Biologics, LLC: Current Employment, Patents & Royalties: No royalties or benefits. Hermans:Bayer: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Shire, a Takeda company: Consultancy, Research Funding, Speakers Bureau; Sobi: Consultancy, Research Funding, Speakers Bureau; Biogen: Consultancy, Speakers Bureau; CAF-DCF: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; LFB: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Octapharma: Consultancy, Speakers Bureau; Kedrion: Speakers Bureau; EAHAD: Other; WFH: Other. OffLabel Disclosure: SEVENFACT(R) [eptacog beta, coagulation factor VIIa (recombinant)-jncw] is a human rFVIIa variant indicated for the treatment and control of bleeding events (BEs) in adults and adolescents with hemophilia A or B with inhibitors. Eptacog beta is not yet indicated for perioperative management

Introduction: Different cytotoxic agents have been implicated in development of therapy related myeloid neoplasm (t-MN). These include alkylating agents, topoisomerase II inhibitors, antimetabolites, and ionizing field radiation given to large field including active bone marrow (BM) (Swerdlow, 2016). This report highlight the impact of local field radiotherapy on BM through discussing few patients diagnosed in our center who showed profound BM hypocellularity or developed t-MN following exposure to local field radiotherapy without chemotherapy. Local field Radiotherapy as a causative agent for t-MN: A result of retrospective study performed in our center through (2012-2018), a total of 20 patients of t-MN out of 232 total AML patients (8.6%) were detected. Two patients out of 20 (10%) in our cohort had developed t-MN following exposure to local field radiotherapy. Patient (1): 50-year old Asian male diagnosed as Vocal cord tumor, received local field radiotherapy for 2 months with no chemotherapy. 15.8 months later, he presented to with two days history of gum bleeding associated with pancytopenia (WBCx10^3/µl:2.3, Hb g/dl:6.7, Platelets x10^3/µl:100). Peripheral blood smear showed infiltration with many leukaemic promyelocytes and diagnosed as Acute promyelocytic leukemia (APL). The diagnosis was confirmed by BM examination and detection of PML RARA classic rearrangement fusion indicating PML/RARA, t(15;17) in 88.5% cells. Reticulin stain shows increased reticulin fibrosis (1-2/ 3). The patient was stratified as intermediate risk and started on ATRA followed by PETHEMA protocol with complete remission. Patient (2): A 62-year old Egyptian lady with background of hepatitis C and previous stroke, diagnosed as Endometrioid Endometrial Cancer FIGO grade I. The patient received Brachytherapy 21 Gy dose to vaginal vault, in 3 fractions (7 Gy each) without complications. 22 months later, she developed progressive neutropenia and diagnosed as high grade myelodysplastic syndrome (MDS-EB-2) with complex karyotype and P53 somatic mutation, managed by palliative therapy. Discussion: Generally laryngeal cancers radiotherapy is directed to confined area and secondary cancers are more common in the area of close proximity to radiation field. Brachytherapy is a limited source of radiation placed into a cylinder and inserted within the prostate or the vagina for treatment of cancer prostate or endometrial carcinoma respectively. Compared to external radiotherapy (RT), the limited field radiotherapy (including external beam RT and brachytherapy), the doses received by BM is very low and hence the risk of secondary leukaemia is expected to be significantly lower. Although local field RT appears to be associated with a small increase in the incidence of solid cancers, only a few studies have evaluated the risk of developing myeloid malignancies after limited field radiotherapy. Numerous cases of (t-APL) have been reported in the literature mostly following TOPO isomerase II inhibitors. However, up to our knowledge no previous reports of t-MN with recurrent genetic translocations (including t-APL) following local field radiotherapy. Local field radiotherapy induced bone marrow suppression: Two male patients with previous history of cancer prostate and limited field radiotherapy. BM examination for both patients revealed profound hypocellularity (<5-5%) with suppressed trilineage hematopoiesis. Patient (3): A 66 year-old male diagnosed as cancer prostate, subjected to radical prostatectomy, followed by salvage radiotherapy. Two months later, the patient was referred for persistent cytopenia (WBC 2.9 x10^3/uL, Hemoglobin 12.8 gm/dL and platelets (92 x10^3/uL). Follow-up revealed persistent thrombocytopenia. No follow-up BM was performed. Patient (4): A 73-year old male patient with previous history of marginal zone lymphoma and cancer prostate treated by brachytherapy. He underwent BM examination for lymphoma staging. Discussion: For patients who have received adjuvant, salvage or radical RT, a significant portion of the pelvic BM receives a substantial dose of RT. To our knowledge, there are no significant published data assessing the impact of limited field radiotherapy on BM particularly radiation induced BM suppression. Larger studies are required in order to accurately assess the actual effect of local field radiotherapy on hematopoiesis and its genetic profiling. Disclosures No relevant conflicts of interest to declare.

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.

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.

Chronic Myeloid Leukemia (CML) is a clonal myeloproliferative neoplasm (MPN) characterized by the presence of a reciprocal translocation between the long arms of chromosomes 9 and 22, t(9;22)(q34:q11), resulting in fusion of the break point cluster region (BCR) with the ABL gene, which forms an oncogene, the transcript of which is an oncoprotein with a tyrosine kinase function. In the great majority of CML; BCR/ABL1 is cytogenetically visualized as t(9;22); giving rise to the Ph chromosome, harboring the chimeric gene. Cryptic or masked translocations occur in 2-10% patients with no evidence for the BCR/ABL rearrangement by conventional cytogenetics but are positive by Fluorescence in Situ Hybridization (FISH) and/or reverse transcriptase polymerase chain reaction (RT-PCR). These patients are described as Philadelphia negative (Ph negative) BCR/ABL1- positive CML with the chimeric gene present on the derivative chromosome 22, as in most CML cases, or alternatively on the derivative 9 in rare occasions. In the majority of cases, CML is diagnosed in the chronic phase; it is less frequently diagnosed in accelerated crises, and occasionally, its initial presentation is as acute leukemia. The prevalence of extramedullary blast phase (BP) has been reported to be 7-17% in patients with BP. Surprisingly, no extra-medullary blast crises of B- lymphoid lineage have been reported before among cases of CML as the initial presentation. We report an adult male diagnosed as CML- chronic phase when he was shortly presented with treatment-naive extramedullary B-lymphoid blast crises involving multiple lymph nodes, with no features of acceleration or blast crises in the peripheral blood (PB) and bone marrow (BM). In addition the patient had variant/cryptic Philadelphia translocation. This is the first report of CML, on the best of our knowledge, with extramedullary B-lymphoid blast phase, as initial presentation, that showed a cryptic Ph translocation.