Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is a recently recognized highly aggressive malignant proliferation of plasmacytoid dendritic-cell (PDC) precursors which consistently express CD4, CD56 and CD123. Mortality is high despite transplant and the response to treatment is poor, except for preliminary results with conjugated anti-CD123. Clinically, cutaneous involvement is the most common feature with or without the presence of initial bone marrow infiltration, however patients may present with bone marrow-only disease. BPDCN is underdiagnosed, and can be confused with several entities, including acute myeloid leukemia. We describe our experience with 7 cases of BPDCN, their clinical and pathological presentation, and describe possible misdiagnosis and the antibodies that may help in corroborating BPDCN. See table for clinical characteristics at diagnosis. Diagnosis of BPDCN must take into account clinical, morphological and immunohistochemical analysis (IHC), since these tumors variably express markers that may be shared with other neoplasias including CD56 and TCL-1. When IHC is not categorical for BPDCN, the WHO recommends reporting the cases as AML of ambiguous lineage. The typical IHC includes CD4, CD43, CD45RA, CD56, CD123, TCL1, CLA and CD68. The absence of CD56 does not exclude the diagnosis. Markers shared with other hematological tumors include: CD7, CD33, CD2,CD36 and CD38 and TdT. Thus differential diagnosis should be done primarily with A) Skin infiltration by acute myeloid leukemia (myeloperoxidase +, 7- lysozyme +, CD34 +, CD117 +/-) B) Skin Infiltration by T / NK extra nodal lymphoma ( CD8 , cytotoxic cytoplasmic granules [CCG] , granzyme B, perforin, TIA1 and EBER) C) cutaneous peripheral T lymphoma ( +/- CD8, CD2 +/-, +/- CD5, CD7 +/- and variably positive CCG´s). D) Other histiocytic and dendritic cell-neoplasms may also be considered in the differential diagnosis however the histological appearance is usually characteristic. BPDCN is a poorly known entity that should be suspected by both clinician and pathologist in order to make a correct diagnosis. Table Table. Disclosures No relevant conflicts of interest to declare.

IntroductionClindamycin is used to treat various bacterial infections, but its administration can cause anaphylaxis, liver reactions, pseudomembranous colitis, and peripheral blood cytopenias (anemia, neutropenia, and thrombocytopenia), alone or in combination. We report the case of a patient with a recurrent infection of the tonsils who received clindamycin. Pancytopenia, a previously unreported hematological disorder related to clindamycin use, was observed in conjunction with the infection and clindamycin treatment.Case presentationOne month prior to hospitalization, a 22-year-old man of Hispanic origin had a tonsillar infection and cough and began to have anal pain. These conditions became exacerbated three weeks later, coinciding with a new tonsillar infection, frequent nonproductive cough, and febrile syndrome. He received clindamycin for four days prior to his admission, without improvement. While hospitalized, he was found to have fever, tonsillar abscess, hemorrhoid thrombosis, and anal fissure; the latter was immediately resected under general anesthesia. Before surgery, our patient’s blood count showed intense leukoneutropenia and mild thrombocytopenia that increased 12 hours later, along with the establishment of anemia. A bone marrow study showed decreased cell content, micromegakaryocytes, and an interruption of the differentiation of granulocytes and erythroblasts. Post-surgery, our patient received metronidazole, meropenem, and amikacin along with acetaminophen, ketoprofen, omeprazole, and pegfilgrastim, with resulting clinical and hematological improvement.ConclusionOur experience with this patient establishes that well-documented clinical cases should be the basis for identifying and publicizing unknown or uncommon undesirable effects of drugs. We report that, in some individuals, clindamycin can cause pancytopenia, a complication that in our patient’s case was caused by direct injury of his hematopoietic tissue.

Background: Mexico and Central America have a high incidence of acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYA). Chemotherapy with Hyper-CVAD has been widely used with poor outcomes, with a 3-year overall survival (OS) of 25.7% in this group of age. In low-and middle-income countries (LMIC), limitations in supportive care such as low access to neutrophil stimulant agents, antifungal prophylaxis and limited intensive care access, may increase treatment-related mortality. On the other hand, reports suggest that specific high-risk subgroups may be more frequent in Hispanic patients from Mexico and Central America. We hypothesize that the use of a less-myeloablative regimen, based on L-asparaginase could overcome the bad outcomes previously reported. Methods We modified the original CALGB 10403 based on local drug-access. We include patients with newly diagnosed Philadelphia-negative B- or T-cell ALL between 14-49 years from 4 centers in Mexico and one in Guatemala. We modified the regimen as following: replaced pegaspargase by E. Coli asparaginase, thioguanine by 6-mercapatopurine and incorporate rituximab 375mg/m2 for 6 doses in CD20 positive patients. After the first interim analysis (October 2019), we replaced the prednisone by dexamethasone during induction. Minimal residual disease (MRD) was assessed by flow cytometry after induction and after first consolidation. We considered high-risk karyotype if MLL-rearrangements, complex or hypodiploid and high-white blood cell count (WBC) if >30 x10 3/mcL for B-ALL or >100 x10 3/mcL for T-ALL. The main objective was to evaluate OS and as secondary objectives to evaluate complete response (CR) rate, relapse-free survival (RFS) and to assess the safety of this regimen. Results From January 2017 to December 2020, 95 patients have been enrolled with a median age of 23 years (range 14-49). One third (34.6%) had overweight and 11.7% were obese. The majority (92.6%) had a B-cell ALL and a normal karyotype (81.2%). The median WBC was 18.4 x10 3/mcL (0.2-427.7) and 40.9% had a high-WBC. During induction, adverse events (AE) included grade 3/4 elevated bilirubin (21.1%), transaminases (14.7%), hyperglycemia (14.7%), hypofibrinogenemia (44.2%), thrombosis (10.5%), hypersensitivity (2.2%) and pancreatitis (2.1%). During consolidation, AE included grade 3/4 hepatic toxicity (18.9%), hypertriglyceridemia (14.8%), thrombosis (5.3%) and pancreatitis (2.1%). Neutropenic fever occurred in 55.8% during induction (grade 4: 31.5%), and in 32.9% during consolidation (grade 4/5: 5.3%). A dose adjustment due to AE was required in 22.1% during induction and in 23.2% during consolidation. The induction related-mortality (IRM) rate was 7.4% The CR rate was 87.8%. After-induction, MRD was <0.01% in 39.1%, 0.01-0.1% in 39.1% and > 0.1% in 24.6%. Post-consolidation MRD was only measured in 43 patients and was <0.01% in 37.2%. During follow-up, 26.7% relapsed: 62.5% bone marrow (BM) relapses, 25.0% central nervous system (CNS) relapses and 12.5% CNS + BM relapses. Eight patients (8.4%) received an allogeneic-stem cell transplant (HSCT) as consolidation. The 2-year OS was 72.1%. The post-induction MRD <0.1% was associated with a better OS (figure 1A) (HR: 0.17 (95%CI: 0.06-0.55), p=0.003) and a high-WBC with an inferior OS (figure 1B) (HR: 4.13 (95%CI: 1.68-10.14), p=0.002). The 2-year RFS was 65.2%. The post-induction MRD <0.1% was associate with a better RFS (figure 1C) (HR: 0.19 (95%CI: 0.07-0.50), p=0.001) and a high-WBC and overweight / obesity with an inferior RFS (HR: 4.08 (95%CI: 1.71-9.73), p=0.001 and 2.50 (95%CI: 1.06-5.86), p=0.036 respectively) (figure 1D). Conclusions: The adoption of modified CALGB10403 regimen in Central America based on local resources is feasible. It is associated with a significant improvement in the OS and decrease in IRM when compared with previous reports. Despite a very high-rate of hepatic and metabolic toxicities, these were manageable. As reported by other groups, MRD, high-WBC and overweight/obesity are associated with poor outcomes. Despite being encouraging results, a significant number of patients persist with positive MRD and the main cause of dead is disease progression. Access to cellular therapies, and BiTes is cost restricted in LMIC. Hence, we should generate strategies to intensify treatment in MRD positive patients and expand transplant access to overcome outcomes. Figure 1 Figure 1. Disclosures Rangel-Patiño: Bristol: Consultancy; Abbvie: Speakers Bureau. Ceniceros: Amgen: Speakers Bureau. Espinosa: Amgen: Speakers Bureau; Janssen: Consultancy; Pfizer: Consultancy. Amador: Abbvie: Consultancy, Speakers Bureau; Bristol: Consultancy. Cabrero Garcia: Takeda: Speakers Bureau; Abbvie: Speakers Bureau; Roche: Speakers Bureau; Janssen: Speakers Bureau; Astellas: Consultancy; BD: Speakers Bureau. Inclan-Alarcon: Janssen: Speakers Bureau; Boehringer: Speakers Bureau. Neme Yunes: Janssen: Consultancy, Speakers Bureau; Bristol: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Bristol: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Abbvie: Speakers Bureau. Meillon-García: Amgen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Roche: Speakers Bureau; Astellas: Consultancy. Apodaca: Sanofi: Consultancy; Asofarma: Consultancy, Speakers Bureau; Abbvie: Speakers Bureau. Demichelis: Bristol/Celgene: Consultancy, Speakers Bureau; Astellas: Consultancy; Gilead: Consultancy; ASH: Research Funding; Abbvie: Consultancy, Speakers Bureau; AMGEN: Consultancy, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau; Jazz: Consultancy.

Introduction: "Philadelphia like" ALL has been related to poor prognosis. CRLF2 over-expression (cytokine receptor like factor-2) has been found in up to 50% of patients with Philadelphia-like ALL and its expression can be measured by Flow Cytometry (FC). CRLF2 over-expression is more common in Hispanic population (45-68%) however, there is no current recommendation in using it as a prognostic marker. Objectives: Find the prevalence of CRLF2 overexpression measured by FC, in adult Mexican patients with treatment-naïve ALL Describe the outcomes of the patients who over-expressed CRLF2 by Complete Response (CR), Minimal Residual Disease (MRD), Leukemia-Free Survivale (LFS) and Overall Survival (OS). Methodology: This is a retrospective cohort study in adults with newly diagnosed ALL from two reference centers in Mexico City. We measured CRLF2 expression by FC in fresh bone marrow samples from treatment-naïve patients at one location; to define over-expression, samples were first analyzed by two different experts who grouped the cases in over-expression or no overexpression using Mean Fluorescence Intensity (MFI) between two populations, blasts and controls (normal B cells). Outcomes were compared using chi-square test for binary variables and log-rank test for time-to-event variables with a p value <0.05 as significant. Results: From April 2018 to January 2020 46 patients with treatment-naïve B-cell ALL were evaluable; the median age was 29.5 years, 38 (82.6%) were Adolescents and Young Adults (AYA), 22 (47.8%) had leukocytosis, 15 (53.5%) of the evaluable karyotypes, were assigned to high-risk group. The median time of follow-up was 24.5 months and 19 (41.3%) patients were positive for CRLF2-overexpression. For the follow-up cohort all of the patients were evaluable for outcomes. CNS disease was detectable in 11(24.5%) patients which was higher in CRLF2-overexpresed patients (15.5% vs 8.9%, p=0.015). We found no difference in Complete Remission (CR) in CRLF2 status but a high tendency for R/R (Relapse/Refractory) disease (83.3% in CRLF2-overexpression vs 60% in CRLF2 negative group; p=0.09) and dead (63.2% in CRLF2-overexpression vs 37% in CRLF2 negative group; p=0.07). MRD1, 2 and 3 (1=after induction, 2= week 16 and 3= before maintenance) was significantly worse in patients with CRLF2 overexpression (1=15.8% vs 58.3%, p<0.01; 2=7.1% vs 52.6%, p<0.01; 3=0% vs 55.6%, p<0.05). Overall Survival was significantly worse in patients with CRLF2 overexpression (Median Not Reached vs 11.05 months; p=0.04) (Figure 1); Disease-Free Survival (DFS) had a tendency towards worse outcome in patients with CRLF2 overexpression (18.48 vs 5.82 months, p=0.07) (Figure 2). Conclusion: Survival in patients who have CRLF2 overexpression is significantly worse when measured by FC, this might be related to early high-risk markers as MRD. CRLF2 overexpression in this hispanic sample was higher (41%) than other reports. CRLF2 measured as a prognostic factor by FC needs to be further considered due to the high availability of this technique across Latin-America. Figure 1 Figure 1. Disclosures Rangel-Patiño: Abbvie: Speakers Bureau; Bristol: Consultancy. Espinosa: Pfizer: Consultancy; Amgen: Speakers Bureau; Janssen: Consultancy. Demichelis: Novartis: Consultancy, Research Funding, Speakers Bureau; Gilead: Consultancy; Bristol/Celgene: Consultancy, Speakers Bureau; Jazz: Consultancy; ASH: Research Funding; Astellas: Consultancy; AMGEN: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau.

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