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Acute myeloid leukemia (AML) has an aggressive course and a historically dismal prognosis. For many patients, hematopoietic stem cell transplantation (HSCT) represents the best option for cure, but access, utilization and health inequities on a global scale remain poorly elucidated.To describe patterns of global HSCT use in AML for a better understanding of global access, practices, and unmet needs internationally.Estimates of AML incident cases in 2016 were obtained from the Global Burden of Disease (GBD) 2019 study. HSCT activities were collected from 2009-2016 by the Worldwide Network for Blood and Marrow Transplantation (WBMT) through its member organizations. The primary endpoint was global and regional use (number of HSCT) and utilization of HSCT (number of HSCT/ number of incident cases) for AML. Secondary outcomes included trends from 2009 to 2016 in donor type, stem cell source and remission status at time of HSCT.Global AML incidence has steadily increased, from 102,000 (95% uncertainty interval (UI): 90,200-108,000) in 2009 to 118,000 (104,000-126,000) in 2016 (+16.2%). Over the same period, a +54.9% increase from 9,659 to 14,965 HSCT/year was observed globally, driven by an increase in allogeneic (+64.9%) with a reduction in autologous (-34.9%) HSCT. While the highest numbers of HSCT continue to be performed in high-resource regions, the largest increases were seen in resource-constrained regions [+94.6% in Africa/East Mediterranean Region (AFR/EMR); +34.7% in America-Nord Region (AMR-N)]. HSCT utilization was skewed towards high-resource regions [in 2016: AMR-N 18.4%, Europe (EUR) 17.9%, South-East Asia/Western Pacific Region (SEAR/WPR) 11.7%, America-South Region (AMR-S) 4.5% and AFR/EMR 2.8%]. For patients70 years of age, this difference in utilization was widened; AMR-N had the highest allogeneic utilization rate, increasing from 2009 to 2016 (30.6% to 39.9%) with continued low utilization observed in AFR/EMR (1.7% to 2.9%) and AMR-S (3.5% to 5.4%). Across all regions, total HSCT for AML in 1HSCT remains a central curative treatment modality in AML. Allogeneic HSCT for AML is rising globally but there are marked variations in regional utilization and practices, including types of graft source. Resource-constrained regions have the largest growth in HSCT use, but utilization rates remain low with a predilection for familial related donor sources and are typically offered in CR1. Further studies are necessary to elucidate the reasons, including economic factors, to understand and address these health inequalities and improve discrepancies in use of HSCT as a potentially curative treatment globally.

Introduction Allogeneic bone marrow transplantation (BMT) is a potentially curative treatment for many hematological diseases. However, lack of availability of specialized centers and high costs limit access to the procedure in low and middle income countries. Previous research has shown that Latin-American patients with hematological malignancies have worse outcomes when treated in public health systems compared to patients treated in the private setting. Healthcare in Mexico is provided by three systems: the private sector (financed by a private insurance or out of pocket), social security (government-run health systems) and a public system (partially funded by the government), where the most vulnerable population is treated. To date, disparities in outcomes of BMT between patients in public and private health systems have not been widely studied. Objectives Primary: to determine the impact of access to private healthcare in BMT recipients by comparing the outcomes of patients treated in two centers that are led by a single team. Secondary objectives were to determine differences in the overall treatment population and transplantation strategies in each context. Patients and Methods We performed a retrospective analysis of consecutive patients aged 15 and older who underwent BMT regardless of diagnosis form 2015-2021 in two Institutions: 1) A private hematology practice treating insured patients in conventional BMT units similar to those in high-income countries (Private) and 2) A public academic institution where an outpatient transplant strategy is common in the context of significant limitations in access to quality supportive care and high-cost medications (Public). Both programs are led by the same team of hematologists following similar transplant strategies with the salient features being the frequent use of peripheral blood stem cells, chemotherapy-based conditioning regimens, and the preferred use of haploidentical donors vs. matched unrelated donors. We excluded second transplants from this analysis and patients who received them were censored at the time of infusion. We compared baseline characteristics, overall survival (OS), event free survival (EFS), non-relapse mortality (NRM), and the incidence of GVHD in the two different treatment systems. Results A total of 219 patients underwent BMT from January 2015 to June 2021, n=166 (76%) were performed in the Public setting, and n=53 (24%) in the Private setting. Patients in the Private group were older, with a higher proportion of high/very high disease risk index (DRI), hematopoietic cell comorbidity index (HCT-CI) and more frequent use of myeloablative conditioning (Table 1). A similar proportion haploidentical donor grafts were performed (61 vs 57%) with a single matched unrelated donor transplant in the Private center. Median follow-up was 9.7 (0.2-71), and 10.3 (0.7-67.6) months, for Public and Private centers respectively (p=0.38). Median time to neutrophil and platelet engraftment were similar. Seventy patients (42%) in Public, and 15 patients (28%) in Private groups relapsed (p=0.049), with a median time to relapse of 17.5 vs. 47.6 months (p Conclusion Patients who undergo BMT in the public health system are at risk for significantly worse outcomes when compared to patients cared for in private systems even if a similar strategy is followed and are led by the same team. Figure 1 Figure 1. Disclosures González López: AMGEN: Honoraria; JANSSEN: Honoraria. Gomez-Almaguer: Janssen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Bristol-Myers-Squibb: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau. Gomez-De Leon: ASH: Research Funding; Abbvie: Honoraria; Sanofi: Honoraria; Novartis: Honoraria.

Introduction Pediatric inspired regimens can achieve good outcomes in adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL) by delivering intense non-myelosuppressive chemotherapy and are considered standard. Experience with the implementation of these regimens outside of academic centers in high-income countries is limited. Furthermore, Mexican patients (with "hispanic ethnicity") have increased risk for relapse and treatment related complications. Objectives Primary objective: to determine 2-year overall survival (OS) and event-free survival (EFS). Secondary objectives: to determine the impacts of treatment abandonment and measurable residual disease (MRD) on outcomes, and to compare treatment costs with a widely used standard regimen in the United States. Patients and Methods Consecutive patients 16-45 years diagnosed with Ph-negative B-cell acute lymphoblastic leukemia after 2016 were included. The salient features of our modified-BFM regimen include the use mitoxantrone, E. coli L-asparaginase, without systemic cytarabine or high dose methotrexate designed to be delivered entirely in an outpatient basis for maximum affordability (Table 1), given that we treat an uninsured population that must cover their own treatment costs out of pocket. Genetic risk assessment was limited to BCR/ABL. Thereafter, relapse risk assessment was based exclusively on "next generation" flow cytometry measurable residual disease (MRD) after consolidation, with a planned allogeneic transplant for MRD-positive patients (≥0.001%). Treatment abandonment was defined as a missed ≥14-day period during intensive treatment or ≥1 month during maintenance. Statistical analysis was performed as intent-to-treat. Lastly, drugs included in our protocol were compared to those of CALGB 10403 with current local pricing in USD. Results Ninety-one AYAs have been treated, 47 women and 44 men, with a median age of 21 years (range, 15-45), mostly with a good functional capacity and no comorbidities (ECOG≤2: 92.1%; HCT-Ci 0-1: 97.8%); 43.8% of patients had ≥30x10 9/L white blood cells at diagnosis and 31.7% had grade ≥1 obesity. Notable grade ≥3 adverse events during induction were infections/neutropenic fever (35.6%),hepatotoxicity (11%) and thrombosis/bleeding (8.1%) with 44.3% eventually requiring hospitalization. Induction related mortality was 11%. Only n=3 were refractory to induction and the remainder assessed achieved complete remission (n=63; 95.5%) with a median follow-up of 15 months (range, 0.9-50.1). N=29 received induction and consolidation entirely on an outpatient basis, ulterior hospitalizations during therapy were rare. Treatment abandonment was common (n=24; 26.4%) usually during induction (n=8; 32%) or consolidation (n=12; 48%) and mostly related to unaffordability. For the same reason, transfers to social security healthcare systems were also frequent (n=19; 20.9%). Most patients assessed were MRD negative (n=38; 74.5%) Early relapse incidence was 32.9%; 44.4% in MRD-positive and 27.5% in MRD-negative patients (p=0.43). OS at 24 months was 61.5% (95% CI 47-73%) and EFS 49.8% (95% CI 37-62%) with excellent outcomes for MRD-negative patients (Figure 1, Panels A and B). Treatment abandonment and MRD positivity were the only independent predictors of mortality in a multivariate analysis (HR 7.8 [95% CI 2.8-21.9] and HR 4.5 [95% CI 1.4-14], respectively). Lastly, the total cumulative price for medications included in our regimen was calculated at $16,750 vs. $36,061 USD in CALGB 10403, representing a cost reduction of 53.5%. Conclusions The treatment of Hispanic ALL patients with our regimen has shown promising outcomes at a reduced cost for patients. Genetic risk assessment, induction mortality, treatment abandonment and lack of access to novel therapies for MRD positive patients remain the main barriers for improving outcomes further. Figure 1 Figure 1. Disclosures Gomez-De Leon: Novartis: Honoraria; ASH: Research Funding; Sanofi: Honoraria; Abbvie: Honoraria. González López: JANSSEN: Honoraria; AMGEN: Honoraria. Gomez-Almaguer: Roche: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Bristol-Myers-Squibb: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau.

Background: Up to one-third of patients with Hodgkin lymphoma (HL) are not responsive to first-line therapy or eventually relapse. New drugs, including anti-PDL1 (i.e., nivolumab) and monoclonal antibodies (i.e., brentuximab vedotin (BV)), have changed the landscape in the treatment of HL. However, the financial toxicity associated with these new drugs is worrisome and are practically inaccessible to most patients living in low-middle income countries. The approved dose of nivolumab in refractory classical Hodgkin Lymphoma (HL) is 3 mg/kg, but lower doses have demonstrated efficacy. Objective: To assess the efficacy of low-dose nivolumab at a fixed dose of 40 mg, 100 mg, or 140 mg in combination with BV 1.8 mg/kg every three weeks in patients with relapsed or refractory (R/R) HL. Methods: We conducted a retrospective analysis of adults with R/R HL who received BV at 1.8 mg/kg and low-dose nivolumab at a fixed dose of 40 mg, 100 mg, or 140 mg IV every three weeks. Patients were routinely offered the highest dose possible that could be afforded for at least 4 cycles, as treatment costs were covered out of pocket. We calculated treatment responses, and overall survival (OS), and progression-free survival (PFS) with the Kaplan-Meier method. Results: A total of 10 patients (50% male, median of age 26.5 years (15-50)) with R/R HL were included; n=7 relapsed and n=3 refractory patients. Median follow-up was 11.5 months (range, 5-18) (antes o después del BV/nivo?). The median previous lines of treatment were three (range, 1-4) and regimens were ESHAP (2, 20%), IGEV (3, 30%)), CGEV (1, 10%), ICE (3, 30%), and allogenic transplantation (1, 10%). Six patients (60%) had received radiotherapy (median dose: 21.5 Gy, range: 20-25). Five patients (50%) received 40 mg of nivolumab, n=3 100 mg (30%) and n=2 140mg (20%). The median dose per cycle was 0.93 mg/kg (range, 0.48-1.9 mg/kg). After a median of 4 (range, 4-8) cycles of low-dose nivolumab + BV the overall response rate was 80% (n=8); five obtained a complete response (CR) (50%) and n=3 a partial response (30%) . One patient (10%) had stable disease, and the other progressed (10%). Grade 1 or 2 adverse events occurred in n=6 patients (60%), including neuropathy (n=2), grade 1 leucopenia (n=3), fever (n=1), and myalgia (n=1). No grade III or IV adverse events were reported. One-year OS and PFS was 83.3%. Transplant consolidation was conducted in six cases (60%) (three autologous and three haploidentical), three are awaiting transplantation and one relapsed after achieving CR before transplant conditioning. One patient died on day +21 after haploidentical transplantation in the context of progressive disease. Conclusion: A short course of low-dose nivolumab and BV showed remarkable efficacy, achieving response in most patients with minimal toxicity and allowed patients with R/R HL who could not afford standard doses to undergo transplantation. The real-world safety and efficacy of low-dose nivolumab and BV should be further addressed in more extensive prospective studies. Figure 1 Figure 1. Disclosures Gomez-De Leon: ASH: Research Funding; Sanofi: Honoraria; Novartis: Honoraria; Abbvie: Honoraria. Gomez-Almaguer: Janssen: Honoraria, Speakers Bureau; Bristol-Myers-Squibb: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau.

Background: Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder that results from accelerating platelet clearance, destruction, and production. Front-line therapy for newly diagnosed ITP includes corticosteroids, intravenous immune globulin, or anti-D immunoglobulin. However, after these single-agent therapies, relapses will occur in half of patients. We previously reported the safety, feasibility, and efficacy of the combination of dexamethasone, low-dose rituximab, and the thrombopoietin receptor agonist (TPO-Ra) eltrombopag as front-line treatment in newly diagnosed ITP. Romiplostim, another TPO-Ra is approved by the FDA for patients with chronic ITP. However, the safety, tolerability, and efficacy of romiplostim combined with low-dose rituximab, and high-dose dexamethasone in newly diagnosed ITP remain unknown. Objective: Our primary objectives were safety, and tolerability. Secondary objectives were initial response and relapse incidence. Methods: An open-label, single-arm study was performed in Hospital Universitario "Dr. José Eleuterio González" in Monterrey, Mexico (Clinical trials.gov NCT04588194). Eligible patients were newly diagnosed ITP patients, treatment-naïve, ≥18 years, with a platelet count ≤30×10 9/L. Patients were excluded if they had an active infection, pregnancy, or malignant disease. The treatment regimen was romiplostim (2 mcg/kg weekly, four doses), low-dose rituximab (100 mg weekly, four doses) and high-dose dexamethasone (40 mg PO, days 1-4). Dexamethasone was allowed up to 3 cycles. Partial (PR) and complete responses (CR) were defined as an increase in platelet counts ≥30×10 9/L (at least a doubling of the baseline count) and ≥100×10 9/L, respectively. Results: We included ten consecutive patients. The median age was 34.5 years (range, 17-63). Seven patients were men (70%). The median platelet account at diagnosis was 6x10 9/L (range 0-23), and median follow-up was 180 days (range 30-270). The median number of romiplostim doses was 3.5 (range 1-4), and three (30%) patients required dose adjustment due to thrombocytosis. All but one patient achieved response (CR or PR) at a median of 7 days (range 7-28). Five patients (50%) achieved CR at 28 days of treatment, and four patients (40%) PR. No significant adverse effects have occurred during treatment; one patient presented grade 1 myalgia and the other a grade 2 soft tissue infection. Five patients (50%) relapsed during follow-up. Recently, four (40%) patients remain in CR and three (30%) in PR. Conclusion: The combination of romiplostim, low-dose rituximab, and high-dose dexamethasone was safe and effective. This "total therapy" approach was associated with minimum side effects and rapid initial response. Prospective validation in a larger sample is needed. Figure 1 Figure 1. Disclosures Gomez-Almaguer: Janssen: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau; Bristol-Myers-Squibb: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. OffLabel Disclosure: Romiplostim in firs-line therapy for immune thrombocytopenia

Introduction One important aspect of quality assurance in transplantation relates to the maintenance of central venous access (CVA), especially in outpatient conditions in which patients have a higher degree of activity and manipulation of CVA tends to be more frequent. A comprehensive program oriented to prevent and control complications related to CVA insertion, maintenance and removal is thought to be a highly effective strategy to improve safety outcomes. Methods A retrospective study evaluating complications related to central venous access (CVA) in patients undergoing hematopoietic stem cell transplantation (HSCT) was conducted using electronic medical records (EMR) at our center. Laboratory and radiology reports were collected in order to identify complications related to CVA. Patients from May 2015 to July 2021 were included in the study. As per local protocol, insertion of Mahurkar catheter for cell collection is conducted by an experienced surgeon under general anesthesia on day -3 and after a short-stay (6 hours) in hospital patients are discharged. On day -2, cell collection is accomplished following all cautionary measures and removal of catheter is done on day -1. Maintenance and care of CVA is guided by standardized protocols related to cleaning, manipulation, blood sample collection and removal. All patients signed a consent to participate in the study and the study protocol was approved by Clínica Ruiz IRB. To be considered as statistically significant, results had to display a two-sided p value Results A total of 1088 patients recruited since May 2015 were included in the study. Main indication for auto-HSCT was multiple sclerosis with 1066 (98%), followed by chronic inflammatory demyelinating polyneuropathy with 16 (1.5%) and 5 (0.5%) patients with other autoimmune disorders. Median age of donors was 46 (40 - 54) years. Median dose of CD34 + cells x10 6/kg infused per patient was 7.0 (3.7 - 11.3) and the median of collection events per patient was 1 (1 - 2). Cell collection was accomplished via apheresis in (99.5%) of patients, of those CVA was used as collection site in 998 (92%) patients, while a change for peripheral venous access occurred in 85 (8%) patients, due to different reasons, most frequent being any type of CVA obstruction in 62 (83%) of donors. Pneumothorax occurred in 11 (1.1%) patients in whom CVA was used for collection. All cases were successful managed with pleural drainage and hospital admission longer than 24 hours was required for 3 (27%). Furthermore, catheter-related bloodstream infections were identified in 3 (0.3%) patients whom were admitted and treated with broad-spectrum antibiotics and discharged with no further events. There were no misplacement, thrombotic- nor hemorrhagic-related events in patients with CVA. A multifactorial analysis revealed that relevant factors such as, age, sex and type of disease were not correlated with any type of CVA-related complications. Conclusions We have shown that prevention and control of complications related to CVA at our campuses are highly effective. The proportion of patients experiencing a CVA-related complication was minimal in comparison with other experiences. Disclosures Gomez-Almaguer: Roche: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Bristol-Myers-Squibb: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau.

Introduction Several autoimmune disorders such as multiple sclerosis, Stiff man syndrome or chronic inflammatory demyelinating polyneuropathy (CIDP) can benefit from autologous hematopoietic stem cell transplantation (HSCT) due to its immunomodulatory effects at short- and long-term. Here we present the results from the conduction of an outpatient HSCT procedures in 16 patients with CIDP. Methods Prospective study of HSCT in persons with CIDP recruited since 2015. Patients with and without previous immunomodulatory therapy were enrolled and a 3-month wash-out period was recquired; previous or current use of walking support was not a contraindication. All patients signed a consent before starting the study and the study protocol was approved by Clínica Ruiz IRB. Before the conditioning, all participants underwent a comprehensive evaluation. On day -11 and -10, patients received cyclophosphamide (Cy) at 50 mg/kg, followed by a 7-day course of G-CSF previous to cell collection (day -2) through apheresis using a Mahurkar catheter. Then, on day -2 and -1 a second round of Cy at 50 mg/kg was given (Figure 1). Transfusions and antimicrobial prophylaxis were administered per local protocol. Upon hematological recovery (>500 ANC) all patients received a rituximab infusion at 1000 mg. Results Sixteen patients with CIDP underwent screening for transplantation clearance and all of them proceeded to HSCT. Of those, 8 (50%) patients were male. Median age at transplantation was found to be 44 years (SD 10.5). Walking support was employed at the time of HSCT by 7 (44%) patients and most frequent previous therapy was intravenous immunoglobulin in 4 (25%) patients. On average a mean 8.5x10 6/kg (SD 4.2) of CD34 + cells were infused. The mean nadir neutropenia was found to be 0.11x10 9/L (SD 0.13) and the median time of granulocytes recovery was 7.0 days (SD 2.9) while median time of platelet recovery was 5.5 days (SD 3.0). One (6%) patient was admitted to hospital due to febrile neutropenia and 4 (25%) patients required red-blood cell and platelet transfusion support. In 3 of 5 persons the need of walking support reverted. Conclusions Our experience suggests that people with CIDP may undergo HSCT with no major complications on an outpatient basis. Hospital admissions, hematological recovery, and infectious complications seem to be relatively low-severity complications that could be manage with standard protocols. Figure 1 Figure 1. Disclosures Gomez-Almaguer: Bristol-Myers-Squibb: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau.

Introduction: COVID-19 has transformed stem cell transplantation (HSCT) dynamics throughout the world. Bone Marrow Transplantation units are facing many challenges complicating admission; deferrals in transplant schedules and even temporary closure. Delay in treatment may have a negative impact in outcomes. Outpatient care has been an alternative to hospital care in patients undergoing HSCT since the 1990s. Potential advantages include improved patient independence and satisfaction, improved quality of life, and less hospital resource utilization, which is of particular importance during this epidemic. In this prospective cohort study, we investigated the impact of the pandemic in our outpatient HSCT program. Objective: To describe the outcomes of patients undergoing ambulatory HSCT during the COVID-19 pandemic. Methods: Adults and children with any hematological disease undergoing any type of HSCT with an outpatient intent from March to July 2020 were included. All were required to have a Karnofsky score >70%, serum creatinine Results: Since the beginning of COVID-19 pandemic in Mexico (February 28th 2020) 21 HSCT have been conducted with ambulatory intent. Fourteen allogeneic (allo-HSCT, 66.6%) (10 haploidentical, 4 matched related donors) and 7 autologous (auto-HSCT) (33.3%%) transplants have been performed. The median age was 27 years (range, 3-70) for allogeneic HSCT and 30 years for autologous (range, 2-63). Acute leukemia (5 lymphoblastic, 5 myeloblastic) was the most common indication for allo-HSCT, and multiple myeloma for auto-HSCT. PCR for SARS-Cov2 was tested only in 1 receptor before the transplant, due to prior test unavailability in asymptomatic persons. Engraftment was achieved in all patients. All received conditioning as outpatients. Twelve (57.4%) were never hospitalized (4/7 auto and 8/14 allo-HSCT) with a median age of 32.5 (range, 16-70). For allo-HSCT median length of stay (LOS) was 2 days (range, 0-21) while for auto-HSCT was 0 days (range, 0-9). The most common reason for hospitalization was febrile neutropenia (n=6, 46%). A median of 7 visits per patient (4-14) were required until day +100 or last follow-up in the outpatient clinic and complemented with 4 (1-18) telemedicine consults. No one died from transplant related mortality. No cases of COVID19 were documented. Conclusion: Outpatient transplantation is a feasible alternative for performing HSCT during the COVID-19 pandemic minimizing the risk of infection and providing a safe environment for patients, donors, and healthcare providers. Disclosures Gomez-Almaguer: Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

There is scarce information regarding the concentration of cytokines in cerebrospinal fluid (CSF) of children with acute lymphoblastic leukemia (ALL) and their clinical association with CNS status. A prospective analysis of 40 patients18years with newly diagnosed ALL was performed. Human cytokine magnetic bead panel assay values of IL-2, IL-4, IL-6, IL-8, IL-10, MCP-1, TNF-α in CSF at diagnosis, end of induction to remission, and 6months after diagnosis were determined. IL-6 and MCP-1 values showed a significant increment at the end of induction. From the whole group 4 (10.0%), patients relapsed to the CNS at a median of 11.48months. A significantly higher value of TNF-α at third determination in these CNS-relapsed patients was documented, 7.48 vs. 2.86pg/mL in 36 children without relapse (p=0.024). TNF-α concentration increased at a median 5.48months before CNS relapse. By receiver-operating characteristic curve (ROC) analysis, the best cut-off point of TNF-α concentration that better predicted CNS relapse was ≥1.79pg/mL. In conclusion an increase in TNF-α concentration on CSF preceded CNS relapse in children with ALL. An increase in MCP-1 and IL-6 was not associated to CNS relapse and appears to result from an inflammatory response after IT injection of chemotherapy.

Introduction Acute myeloid leukemia (AML) with hyperleukocytosis is associated to high early mortality rates and needs aggressive treatment. Induction chemotherapy (ICH), leukapheresis and hydroxyurea (HU) are the most frequent used leukoreductive strategies. Delay in ICH is very common, leukapheresis is not widely available and hydroxyurea and leukapheresis do not modify early mortality rates. Therefore alternative strategies to leukoreduce patients with AML and hyperleukocytosis are needed. Vinblastine is widely available, cheap, with preclinical activity and promising results in relapsed AML. We explored the leukoreductive power of a single dose of vinblastine in patients with newly diagnosed AML and hyperleukocytosis. Patients and methods We conducted a prospective pilot study that included consecutive patients with newly diagnosed non-M3 AML, aged 16 to 60 years, and with a WBC ≥50,000/µL at time of presentation and in whom immediate ICH with 7+3 was not possible because of hospital limitations (i.e. delay in ICH drug availability). We excluded patients with PML/RAR-alfa rearrangement and/or t(15;17), poor performance status (ECOG >2), any preceding chemotherapy, organic dysfunction (defined as a modified Marshall score ≥2) or pregnancy. After diagnostic confirmation, a single dose of vinblastine at 6 mg/m2 i.v. was administered. We documented leukocytes (WBC) and number of blasts on the day of vinblastine administration (0h) and 48 hours later. We represented the achieved leukoreduction with boxplots and compared the absolute reduction in WBC (delta WBC) and blasts (delta blasts) after vinblastine administration. We compared the leukoreductive power of vinblastine to other leukoreductive strategies (HU, leukapheresis). We calculated toxicities (grade 4 neutropenia and thrombocytopenia), median length of hospitalization and parental antibiotics, and overall survival (OS). We documented cases of disseminated intravascular coagulation, leukostasis and tumor lysis syndrome. This study complies with the Declaration of Helsinki, and our local ethics committee. Results A total of 11 patients were enrolled in the study, seven were men (63.6%), with a median age of 48 (21-78) years. Median follow-up was 21 days (2-833 days). The most frequent morphologic subtype was M4 (3, 27.3%), M5 (2, 18.2%) and M2 (2, 18.2%). Cytogenetics were obtained in three cases (27.3%) and all of them were classified as intermediate risk. Forty eight hours after vinblastine administration the WBC lowered from 122x109/L (50.1-380) to 47.3x109/L (22.1-170) representing a 54% (26.7-84.2) decrese (p=0.0001) (figure 1) while blasts number lowered from 204 x 109/L (47.8-361) to 6.4 x 109/L (0-1.6) representing a 85.7% (75-100) decrease (p=0.005) (figure 1). In Table 1 we compare our results with other strategies. All patients experienced grade 4 neutropenia and thrombocytopenia. There were no cases of disseminated intravascular coagulation, leukostasis or tumor lysis syndrome. Severe infections (grade III-IV) occurred in 8 patients (two patients presented neutropenic colitis, five with severe pneumonia, and one SARS-COV2). Four patients presented septic shock and died during induction therapy. Median length of hospitalization and parental antibiotics were 19 days (2-30) and 7 days (range, 2-24), respectively. A CR was achieved in 4 patients (36.4%) after one induction cycle. One patient presented refractory disease and five died before response evaluation. One patient relapsed at 16 months of follow-up. Median OS was 11 months (0-31.8). Allogeneic stem cell transplantation was performed in 1 patient. Conclusion We documented a marked reduction in both WBC and blasts after 48 hours of vinblastine administration. Our study suggests that the leukoreductive power of a single dose of vinblastine is similar to HU and leukapheresis in patients with AML with hyperleukocytosis. Vinblastine is a widely available, cheap and myelotoxic drug that could extend the arsenal to treat newly diagnosed AML with hyperleukocytosis. Disclosures Gomez-Almaguer: AstraZeneca:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Roche:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Pfizer:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Celgene/BMS:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Amgen:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;AbbVie:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Janssen:Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Background Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for acute leukemia (AL) with the potential to achieve long-term remission. Nevertheless, relapse remains the main cause of mortality after allo-HSCT. Isolated extramedullary relapse (iEMR) is defined as the presence of clonal blasts in tissues other than the medullary compartment, in the absence of bone marrow relapse (BMR) and with full donor chimerism. Reports on its prevalence and risk factors are rare and its implications on prognosis and treatment continue to be an area of active study. Our aim was to describe the rates, clinical characteristics, and outcomes of patients with iEMR in the post-allo-HSCT setting. Methods Retrospective multicenter study that included patients ≥15-years-old diagnosed with AL who underwent allo-HSCT with chemotherapy-only conditioning regimens between 1999-2019. Patients referred to participating centers after HSCT and those with incomplete medical records were excluded. The Kaplan-Meier method was used to construct survival curves, differences between groups were analyzed using the log-rank test, and a standard Cox-regression was carried out for multivariate analysis. Results One hundred twenty-four patients were included with a median follow-up of 12 months (1-158) after allo-HSCT. The most common AL phenotype was lymphoblastic (ALL) in 66.1% (n=82). High-risk cytogenetics were present in 23.9% (n= 28). Twenty-three patients (18.5%) had a history of extramedullary disease (EMD) prior to allo-HSCT, CNS being the most common site in 52.2% (n=12). Additional baseline characteristics are presented in Table 1. Median overall survival (OS) for the cohort was 15 months (1-158). Factors related to decreased OS on univariate analysis are shown in Table 2. Independent risk factors for mortality were: belonging to the non-AYA group (HR 4.7,95%CI 1.6-13.3; p=0.004), grade III-IV acute GVHD (HR 3.9, 95%CI 1.6-9.8; p=0.003), and absence of chronic GHVD (HR 10.3, 95%CI 3.4-30.9; p Sixty-seven patients (54%) relapsed after allo-HSCT with a median time to relapse of 13 months (1-158). Of these, 19 (28.4%) had EM involvement, of which 16 (23.9%) had iEMR. All cases of iEMR occurred in patients with ALL. The most commonly involved EM sites were CNS in 47.3% (n=9), skin in 26.3% (n=5), and breast in 15.8% (n=3). Of patients with post-allo-HSCT CNS relapse, 85.7% (n=6) had prior history of pre-HSCT CNS EMD. Post-relapse therapy was administered to 76.1% (n=51), including a second allo-HSCT in 25.5% (n=13), the remaining patients transitioned to palliative care. Median relapse free survival (RFS) was 13 months (1-124). Factors demonstrating a protective role are described in Table 2. On multivariate analysis, early disease stage at time of HSCT (HR 0.35, 95% CI 0.18-0.71; p=0.003) and the development of chronic GVHD (HR 0.29, 95% CI 0.15-0.54; p The median OS after relapse was 4 months (2.6-5.3). Factors related to increased survival on univariate analysis are described in Table 2 and in Figure 1. On multivariate analysis, an iEMR (HR 0.13, 95% CI 0.026-0.67; p= 0.015), as compared to a relapse with a medullary component, and a complete remission after post-relapse therapy (HR 0.095, 95%CI 0.039-0.233; p Conclusion Isolated EMR was highly prevalent in our population as compared to historical cohorts. This reflects differences in Latin American AL epidemiologic distribution, with high representation of ALL, and our limited access to conditioning regimens based on total body irradiation. Patients that had an iEMR and achieved treatment response had improved survival outcomes which may reflect a more indolent biology allowing the clinician time to implement therapy intensification interventions. Additionally, in our setting, escalation of pre-HSTC therapy to achieve deeper responses and tailoring HSCT, in combination with post-HSCT CNS prophylaxis, are potential strategies that should be pursued further. Disclosures No relevant conflicts of interest to declare.

Introduction: Several studies published in recent years dealing with the detection of Central Nervous System (CNS) disease in Acute Lymphoblastic Leukemia (ALL) have demonstrated superiority in terms of sensitivity of Flow Cytometry (FCM) over standard cytology (Tawfik et al, 2018). However, whether CNS activity detected by FCM has an impact on the clinical outcome of ALL adult patients, is still a matter of debate. (Del Principe et al, 2019) Methodology: We analyzed a retrospective cohort of newly diagnosed ALL adult patients in an oncologic center in Mexico, who had a CNS analysis by FCM and conventional cytology, diagnosed between 2017 and 2019. The primary endpoint was to assess the impact on the survival of patients with CNS disease detected by FCM. We defined positive FCM (FCM+) when the patient had >10 phenotypically pathologic events and positive cytology (Cyt+) when the patent had confirmed CNS-2 or CNS-3 activity as defined by NCCN and ESMO; double-negative (DN) patients were considered when neither FCM nor cytology demonstrated disease as described above. Baseline characteristics were grouped in tables and summarized as medians and ranges for quantitative variables or frequencies in qualitative variables. Basal characteristics and different outcomes were compared by the chi-square test for binary variables, and the Mann-Whitney U test for quantitative variables. Overall Survival (OS) and Disease-Free Survival (DFS) analysis were made by Kaplan-Meier curves. A comparison between groups was performed using the log-rank test, with a significant P value less than 0.05 and a 95% confidence interval (CI). We performed a Cox regression model to obtain an HR with a 95% confidence interval for survival to identify risk associations. Results: Of the 92 evaluable patients, the median age was 28 years. 88% of all ALL were ALL-B. The median count of leucocytes was 11.65 x109/L (range 4.71-38.24 x109/L); median LDH was 758 UI/L (range 314-1242 UI/L). 63% of patients had an unfavorable karyotype (hypodiploidy, complex karyotype, or KMT2A). At diagnosis, 27 (28%) were positive by FCM and negative by cytology. The median of the analyzed events was 14,733 (5,025-50,000) with a viability of 38.5% (22-61.75). Only 6 patients were positive by both techniques. 45% of patients with CNS involvement had neurological symptoms (mainly headache). The most used treatment was BFM in 56.7% of patients, followed by HyperCVAD in 37.8%. Patients with documented CNS infiltration by FCM or cytology were treated with triple intrathecal chemotherapy two times per week. Three patients had no response after two weeks of treatment, one received radiotherapy without any response and the other two were dead for chemotherapy toxicity. We found gender as the only statistically significant variable associated with a higher FCM+ (77% males vs 23% females, p For the entire cohort, the complete remission (CR) after induction was 84% and 63% had a negative minimal residual disease (MRD) by FCM in the bone marrow. 15% of the patients were refractory. There were no differences between CR (73% versus 88%, p= 0.16), MRD negativity (46% versus 69%, p=0.11), refractory disease (26% versus 10%, p=0.13) or relapsed disease (50% versus 43%, p=0.65) between FCM(+) and ND groups. The OS for the entire cohort was 11.3 months. Patients with FCM+ had a lower survival of 5.6 months [CI95% (0.72-10.67)] compared with 11.8 months [CI95% (0.47-11.95)] in the DN group. The median DFS for the FCM+ patients was 4.6 months [CI95% (3.42-5.92)] versus 16.4 months [CI95% (6.21-26.75)] for DN group. In the Cox regression model, the HR for survival in patients with FCM+ was 1.85 (CI95% 1.004-3.421; p=0.04). Conclusions: Despite the retrospective nature of this study, the detection of CNS involvement was increased from 6% to 28% employing FCM compared with cytology. As mentioned previously, in other studies, FCM has greater sensitivity than cytology (Ranta et al. 2014). According to our results, the presence of CNS disease, detected by FCM has an adverse impact on OS in adult patients with newly diagnosed ALL. These results dictate consideration of FCM as a routine study in the diagnosis of ALL. Prospective studies are needed to evaluate more intensive treatment in these patients. Figure Disclosures No relevant conflicts of interest to declare.

Introduction: The proportion of Acute lymphoblastic T cell leukemia/lymphoma (T-ALL/LBL) in Latinamerica (LA) is about 13% [Quiroz, 2018], compared with 25% of other publications [Litzow,2015]. In the largest leukemia series of adult Mexican population, the incidence of T-ALL was merely 2.9% with a -SG. The main objective of this study was to describe the epidemiological characteristic and survival of T-ALL in 4 reference oncology centers in Mexico. Methods: Retrospective cohort study from 2014 to 2019 in all consecutive, newly diagnosed T-ALL patients defined by flow cytometry (FC). The primary end point was to assess the survival of T-ALL in a Hispanic population. Baseline characteristics were grouped in tables and summarized as medians and ranges. Sub-groups were compared using chi-square test for binary variables and Mann-Whitney U test for quantitative variables. The Overall Survival (OS) analysis was made using Kaplan-Meier curves and comparison between groups was performed using the log-rank test with a significant P value less than 0.05 with 95% confidence interval. Results: A total of 47 patients were identified, which represent 11.1% of all acute leukemia the median of age was 30 years. The 83.7% being identified in the adolescent young-adult (AYA) group. Counterintuitively a 44.9% had a previous comorbidity (diabetes, hypertension, dyslipidemia) considering the range of age. The 85% had a low risk of mortality using the modified Charlson index, the median count of leukocytes was 36 x 109 (range 6.78-117) and 28% presented with initial hyperleukocytosis, the median LDH was 605 UI/l (range 343-1451). Applying the European Group for the Immunological Classification of Leukemias criteria: 28% were cortical T, 41.7% were mature and approximately 30% were be classified as early. Applying the early T-P (ETP) definition a total of 10 cases were identified (22.2% prevalence). The use of hyperCVAD and pediatric inspired regimens shared the same rate (41.3%), strikingly there is still a 17.4% of patients that received other type of chemotherapy for diverse reasons (economic, shortage of treatment, patient or physician preference) being the CHOP-inspired schemes the most used. The rate of complete response (CR) at 4 weeks after induction was 68.2% with 54.2% having a negative minimal residual disease (MRD). After 8 weeks a total of 34 (77.3%) patients achieved CR, with 63.6% and 66.7 % maintaining negative MRD at 16 weeks and after consolidations, respectively. Only 38.3% were able to complete the full induction treatment without a dose adjustment due to toxicity. A total of 8 (19.5%) were refractory to initial frontline treatment and eventually 23 (60.5%) relapsed, with a total of 10 patients presenting with CNS infiltration at relapse. A total of 6 patients received an allogenic stem cell transplant (ASCT), with 4 of them being alive and in CR at the 100 days cutoff. The median OS was 16 months (CI 95% 11.4-21.09) and 38.8% of our population was alive at the 24 months cutoff. This time period was drastically reduced for the non-AYA population who had a OS of 7.69 months (CI 95% 0-21.24) and 21.9% a 24 months progression free survival (PFS), compared with 16.6 months (CI 7.41-25.81) and 41.6% 24 months PFS. In the univariate analysis refractoriness to induction (p 0.039) and higher number of cycles (p 0.02) were associated with worse outcome. Conclusions: The T-ALL predominantly affects AYA populations while its incidence in our country appears to be lower even in large oncologic concentration centers. The proportion of ETP was slightly higher than that reported in other studies. Lower CR rates with a low frequency of ASCT in comparison to those reported in high income countries was observed, probably associated with the delay in implementation of pediatric-inspired regimens and lack of access to ASCT. Disclosures No relevant conflicts of interest to declare.

Background Hematopoietic stem cell transplantation (HSCT) feasibility has increased in the last decades because of haplo-HSCT, changes in chemotherapy schedules, and the possibility of an outpatient-based HSCT. The main barriers remain in low-middle income countries. There is a lack of information regarding haplo-HSCT with a myeloablative (MAC) regimen on an outpatient basis. Objectives Our primary objective was to determine if outpatient haplo-HSCT was feasible. Study design Single center, retrospective cohort, n=60 adult patients undergoing Haplo-HSCT. Descriptive statistical analysis, univariate and multivariate comparison. Patients and method We analyzed 60 adult patients transplanted with an intended haplo-HSCT on an outpatient basis from 2015 to 2019 in our unit. A multivariate analysis was performed on risk factors for hospitalization. Results Median age was 27 years (15-64). All patients underwent conditioning as outpatients, and none required hospitalization before day 0. Thirteen patients (21.6%) were followed completely in the outpatient clinic and 47 (78.3%) required hospitalization in a median of 3 days after infusion (range, 1-14). The median length of stay (LOS) was 8 days (IQR, 3-17). Fever secondary to cytokine release syndrome (CRS) was the most common reason for hospitalization occurring in 43/47 (91.5%), 4 were related to infection and 36 were related to CRS. In the univariate analysis, CRS, slower engraftment, and female sex were associated with the need for hospitalization. In the multivariate analysis, only CRS remained significant (OR 9.14 [95%CI, 1.58-56.46]). The 2-year overall survival (OS) was 41.7% for ambulatory transplant vs. 38% for those requiring hospitalization (P = 0.12). The 2-year event-free survival (EFS) was 33% for outpatient patients and 16.7% for those hospitalized (log-rank, P=0.062). Conclusions We demonstrated the feasibility and safety of carrying out an outpatient haplo-HSCT, potentially resulting in cost savings and perhaps a higher quality of life.

Introduction. Hematopoietic stem cell donors (HSCD) frequently suffer from anxiety and feelings that are usually unnoticed by the physician o their relatives. The origin is multifactorial: fear of pain, fear of the procedure, adverse effects of growth factor, feelings of responsibility regarding the success of the transplant, family pressure, etc. HSCD could show ambivalence of feelings about the donation, which may be related to the moral obligation to help a sick relative and fear of the donation procedure, thus originating anxiety and moral distress (MD). We evaluated the incidence of MD, anxiety, and other symptoms in a group of HSCD regarding donor related allogeneic transplantation. Materials and methods. A prospective observational study was carried out through a survey applied to 60 consecutive HSCD from April, 2014 to January, 2017. Protocol was approved by Institutional Ethics Review Committee and was carried out according to the Declaration of Helsinki. HSCD completed 3 written self-answered questionnaires (Questionnaire to assess moral distress (MDQ) elaborated by the researcher, State Trait Anxiety Index (STAI®) and Edmonton Symptom Assessment System (ESAS)) in three stages: right before initiating stem cell mobilization, immediately before the apheresis procedure, and 24 hours after the donation. Cell mobilization was done with granulocyte colony-stimulating factor (G-CSF) 10 µg/kg/day/4 days while the apheresis collection was performed on the fifth day as an outpatient basis in all cases. Results. Sixty donors, 36 male and 24 female with a mean age of 38.2 years (SD = 13.6) were included. HSCD was a brother/sister of the patient in 39 cases (65%), and one parent in 21 cases. Regarding donor educational level, only 24 (40%) donors had university level. MDQ: Most donors felt happy to be the donor (97%), but 28% said they were not given the opportunity to accept or refuse being the donor, 10% would have preferred that another person had been the donor, and 5% mentioned that donation worsened their family relationship and they would not donate cells again if necessary. The number of donors with negative feelings regarding the donation decreased through the 3MD questionnaires (Table 1). STAI: In the first, second, and third questionnaire, the mean score for the state of anxiety was 12.1 (SD = 7.6), 10.3 (SD = 6.6), and 7.9 (SD = 5.7), respectively. In first STAI, mild to moderate anxiety was observed in 33% of the donors and severe anxiety was observed in 7%, observing a higher score in the first questionnaire, just before starting cell mobilization; however, that score gradually decreased in the following questionnaires. ESAS: In the first questionnaire, although no procedure was still performed, all donors had symptoms, including insomnia (33%), anxiety (33%), and tiredness (30%). In the second ESAS questionnaire, symptoms worsened, mainly pain (78%), tiredness (63%), and insomnia (55%), which was probably related to G-CSF. In the third ESAS questionnaire, there was a significant decrease in the symptoms: pain (60%), tiredness (50%), and discomfort (40%). The average global score for 10 symptoms evaluated was 10.5 (SD = 14.2), 20.1 (SD = 16.0), and 12.3 (SD = 14.4) for the first, second, and third ESAS questionnaires, respectively. According to the score given to each symptom, the most frequent disabling symptoms in each questionnaire were hyporexia (10%), pain (23%), and discomfort (15%) in ESAS questionnaire 1, 2, and 3, respectively. Higher scores for MD correlated with higher scores in STAI questionnaires as well as with lower levels of education (r=0.456, p< .005). Conclusions MD in the donor can manifest both clinically and socially through insomnia, fatigue, loss of appetite, anxiety, and ambivalence of feelings (happy to be the donor but feel morally obligated to donate) which may affect family relationships. Although there is no instrument to measure the MD before performing any procedure in the present study, the donors had different symptoms, such as negative feelings, anxiety, tiredness, difficulty to sleep, and even pain; all of them without an apparent physical reason. It is desirable that donors receive bioethical counseling and psychological guidance before the donation process in order to provide them with the necessary information regarding the experience they are about to endure. Disclosures Gomez-Almaguer: Amgen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau.

Introduction Cytokine release syndrome (CRS) is a common and potentially severe toxicity associated with haploidentical peripheral blood hematopoietic stem cell transplantation (Haplo-HSCT). CRS is characterized by immune activation and a high level of circulating inflammatory cytokines, particularly interleukin-6 (IL-6). While tocilizumab, an IL-6 receptor-targeted monoclonal antibody has been effectively used to treat CRS in the context of immunotherapy, it has not been evaluated during the acute Haplo-HSCT period. We hypothesized that prophylactic tocilizumab can prevent CRS after Haplo-HSCT. We report the results of a pilot trial to evaluate its use. Methods Patients ≥18 years undergoing Haplo-HSCT of peripheral blood in a single center with any underlying diagnosis were included. The conditioning was myeloablative and was administered as follows: cyclophosphamide 350 mg / m2 and fludarabine 25 mg / m2 (days -5-3) or rabbit antithymocyte globulin (2.5 mg / kg days -4, -3), plus melphalan 200 mg / m2 PO (days -2-1). Prophylaxis of graft versus host disease (GVHD) consisted of cyclophosphamide (50 mg / kg / day, days +3 and +4), cyclosporine and mycophenolate mofetil on day +5. The cells were infused on day 0. Tocilizumab was administered on day -1 in a single dose of 4 mg / kg IV. CRS was rated according to Lee et al. The primary outcome included the incidence and severity of CRS, the adverse effects associated with tocilizumab, hospitalization and graft rates and the incidence of GVHD. Results Ten patients have enrolled, with an average age of 26 years (range 19-32). The underlying diagnoses were acute lymphoblastic leukemia (n = 7), acute myeloid leukemia (n = 1) and non-Hodgkin lymphoma (n = 2). There were no infusion reactions associated with tocilizumab. Six patients (60%) developed CRS, all grades 1-2, with a median day of onset on day +2 (range 1-3) and a median fever duration of 2 days (range 2-3), often accompanied by nausea, diarrhea, dehydration and transaminitis. All patients were hospitalized; hospitalization was not related to CRS in three patients. 4 patients are alive without relapse (40%), 2 patients alive with relapse (20%), 3 patients died due to transplant-related mortality (30%), one patient dies from relapse (10%). No graft failure occurred and mixed chimerism was observed in a patient. Acute GVHD with steroid response has been diagnosed in 2 cases (20%, grade I / II). The median follow-up is 8.3 months (range 0-20). Conclusion What we observe about the prophylactic use of tocilizumab for Haplo-HSCT of peripheral blood is that its administration is feasible, Grades 1-2 CRS was observed in 60% of patients, grades 3-4 were not observed, however the use of tocilizumab did not prevent hospitalizations. More feasibility data is required before starting a definitive randomized trial to evaluate the use of tocilizumab for Haplo-HSCT peripheral blood. Disclosures Gomez-Almaguer: Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau. OffLabel Disclosure: Tocilizumab for Prophylaxis of Cytokine Release Syndrome

Introduction: Diffuse Large B-Cell Lymphoma (DLBCL) is the most frequent subtype of high-grade lymphoma in Latin American patients. The neutrophil-to-lymphocyte ratio (NLR) has shown to be prognostic in patients with DLBCL in Asia, Europe, and the United States. We previously reported that NLR ≥4 was an adverse prognostic factor for overall survival (OS) in DLBCL patients treated with chemoimmunotherapy. We aim to assess the prognostic and predictive role of NLR ≥4 in a learning cohort of DLBCL patients from South America and confirm the findings in a validation cohort of DLBCL patients from Mexico. Methods: The study period was from January 2002 through January 2018, and included patients with de novo DLBCL treated with standard chemoimmunotherapy with a curative intent. A cohort of patients from South America (Peru, Argentina, Venezuela, Chile and Colombia) was the learning cohort, a cohort of patients from Mexico was the validation cohort. Univariate and multivariate logistic regression analysis and Cox proportional-hazard regression models were fitted for complete response (CR) as well as for OS in the learning cohort and the validation cohort, separately. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Results: A total of 597 patients with a diagnosis of DLBCL were included. The learning cohort included 274 patients, and the validation cohort included 323 patients. In the learning cohort, CR rates for DLBCL patients with NLR ≥4 and NLR In the validation cohort, CR rates for DLBCL patients with NLR ≥4 and NLR Conclusion: This multi-institutional collaborative study identifies and validates an easy-to-use tool, NLR ≥4, as an independent factor predictive of lower rates of CR and prognostic of worse survival, independent of the IPI and the NCCN-IPI scores, in Latin-American patients with DLBCL treated with standard chemoimmunotherapy. Disclosures M: Roche-Mexico: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Merck-Sharp-Dome: Speakers Bureau. Peña:Novartis: Other: Congress inscription and flights; Tecnofarma: Other: Congress inscription and flights; Roche: Other: Congress inscription and flights; Biotoscana: Other: Congress inscription and flights; Janssen: Other: Congress inscription and flights; Pfizer: Membership on an entity's Board of Directors or advisory committees. Rojas:Pfizer: Membership on an entity's Board of Directors or advisory committees; ABBVIE: Membership on an entity's Board of Directors or advisory committees; NOVARTIS: Membership on an entity's Board of Directors or advisory committees; ROCHE: Membership on an entity's Board of Directors or advisory committees. Paredes:Tecnofarma: Honoraria. Ramirez-Ibarguen:Roche-Mexico: Consultancy, Speakers Bureau. Gomez-Almaguer:Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Castillo:Pharmacyclics: Consultancy, Research Funding; Abbvie: Research Funding; Beigene: Consultancy, Research Funding; TG Therapeutics: Research Funding; Janssen: Consultancy, Research Funding.

Background: Patients with lymphoma and myeloma undergoing autologous hematopoietic stem cell transplantation (ASCT) are at risk for mobilization failure, defined as the inability to harvest the minimum recommended 2x106/kg CD34+ cells prior to conditioning. This limitation can be surpassed by combining multiple apheresis sessions, cryopreservation and adding plerixafor to filgrastim. However, these strategies substantially increase transplant costs and are unaffordable for many patients in low and middle-income countries (LMIC). Furthermore, standard doses of plerixafor can lead to unnecessarily high CD34+ cell yields, leading to resource waste. We have previously shown that a reduced dose of plerixafor at 0.12 μg/kg is effective in a pilot trial. Consequently, we have incorporated RD-plerixafor to a mobilization algorithm using peripheral CD34+ cell analysis to be used in a setting with limited resources. Objective: To evaluate the efficacy of a decision-making mobilization algorithm in patients with lymphoma or myeloma defined by our ability to harvest at least 2x106Kg CD34+ cells in a single apheresis session. Methods: We performed a single-arm prospective study including consecutive adults diagnosed with lymphoma or myeloma undergoing ASCT in our institution. Patients received a mobilization regimen consisting of filgrastim 5 μg/kg BID for 4 days. On day 4 peripheral blood CD34+ cell flow cytometry analysis was performed. We designed a mobilization algorithm hypothesizing that if the day 4 CD34+ pre-count was 5-10 cells/μL, a single RD-plerixafor dose at 0.12 mg/kg (11 hours prior to apheresis) would be sufficient to achieve a successful harvest (≥2x106/kg CD34+) in one large-volume apheresis session based on a prior local study (Panel B). Patients with Results: Twenty-nine patients were included. Baseline characteristics and outcomes are shown in Table 1. Median day 4 CD34+ cell pre-count was 15 cells/μL (range, 1.4-88.7). Following our algorithm n=19 patients received filgrastim (65.5%), n=6 received RD-plerixafor (20.7%) and n=4 full-dose plerixafor (13.8%). Median day 5 peripheral blood CD34+ increased to 34.3 cells/μL (range, 10.8-107) (Wilcoxon signed ranked p Conclusion: Incorporating RD-plerixafor into a mobilization algorithm is a safe and effective strategy that increases access to transplantation in patients with lymphoma and myeloma at risk of harvesting failure. External validation of our decision-making algorithm is warranted. Disclosures Gomez-Almaguer: Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau.

Background. Establishing research capacity in low and middle-income countries (LMIC) is key for improving health systems and implementing actionable programs through evidence-based assessments. Few studies have analyzed hematology research capacity in LMICs. The American Society of Hematology (ASH) annual meeting is the largest hematology event where peer-reviewed contributions from researchers worldwide are selected for presentation based on scientific merit. Therefore, it can provide a useful snapshot of the current status of hematology research in a single point in time. For this reason, we analyzed abstracts presented at the 2018 ASH annual meeting (ASH18) with a focus on those from authors working in a LMIC. Objective. To describe the proportion of abstracts presented at ASH18 from an LMIC and analyze their characteristics as a surrogate for academic contributions to global hematology. Methods. We reviewed all abstracts presented at ASH18 in an oral presentation or poster form published online in the supplemental edition of Blood 2018;132 (Suppl 1). LMICs were selected according to the World Bank classification including countries or territories with a gross national income Results. A total of 4,871 abstracts presented at ASH 2018, with 1,026 oral presentations and 3,845 posters were available online. Among them, 510 abstracts (10.5%) had a contributing author from an institution in an LMIC, corresponding to 92 (9%) of all oral presentations and 418 (10.9%) of all posters (Figure 1). LMIC-only contributions represented 4.7% of all abstracts (n=229). The most common LMIC of origin for LMIC-only contributions was China with 133 (58.1%) (Figure 1). Most abstracts were clinical and multicentric in nature (62 and 70.2%, respectively), and in 42.5% of them a COI was reported. Clinical trials reflected 19% of all LMIC contributions. In 31.9% of cases the first author was affiliated to an institution in a HIC. Mixed LMIC/HIC contributions had significantly more COIs and industry sponsors than those from LMIC-only institutions (Table 1). When comparing between oral vs poster LMIC presentations, works selected for an oral presentation were significantly more clinical and multicentric, had a higher proportion of clinical trials, more COIs and identified industry sponsors (Table 2). Conclusions. LMICs, where more than 80% of the world population resides, were responsible for only a small fraction of contributions to ASH18, half of them representing a form of international collaboration, with a high number of COI disclosures. Disclosures Gomez-Almaguer: Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau.

Introduction: Allogeneic hematopoietic stem cell transplantation (alloHSCT) offers an effective, potentially life saving treatment for a broad range of malignant and nonmalignant hematologic disorders. To some degree, an adequate performance status, comorbidity and disease control, and an available donor must be present in order to be considered as a suitable candidate. In addition, sociodemographic factors such as insurance coverage, high out-of-pocket costs and transplant center availability might impair access to alloHCT, particularly in low and middle-income countries (LMIC). Currently, in the era of haploidentical grafts donor availability has been largely resolved and is no longer the biggest barrier for reaching transplantation in LMIC, becoming the most common form of alloHSCT in our center. On the other hand, most outcomes-based publications in the field of alloHSCT are focused only on the transplanted, not on an "intent-to-transplant" basis. The current reasons for not being transplanted once a patient is considered for the procedure are unknown. Therefore, as early adopters of haploidentical transplantation we aimed to evaluate patients that were not grafted. Objetive: To determine barriers to alloHSCT and patient outcomes by studying the population that was HLA typed and/or had a consult in our center, regardless of the event of transplantation Methods: All adult patients who were HLA-typed and considered potentially eligible for transplantation in our center were included. Since 2015 haploidentical donors have become the immediate next best option when a matched sibling donor is unavailable in our center, due to a lack of access and increased costs of unrelated donors and umbilical cord blood. Related alloHSCT have been largely subsidized by the government, reducing transplant costs to a minimum for uninsured patients. We performed a retrospective review of patient records from January 2016- December 2018, regardless of baseline diagnosis, donor source and conditioning regimen. We documented demographic variables, identified the reasons for not performing the alloHCT, and performed a landmark analysis from the time of HLA typing in comparison to patients that did reach transplantation. Univariate and multivariate analyses were performed to identify covariates associated to not reaching transplantation. Results: One hundred and thirty five patients were HLA-typed and considered eligible to proceed to alloHCT. Forty-seven (34.8%) were not transplanted. In six cases, alloHSCT was considered unnecessary. The proportion of patients who received transplantation was similar regardless of the availability of a MSD vs haploidentical donor (68.2 vs 66.7% repectively, p=0.53). Transplanted patients had a significantly lower disease risk index (DRI) and more frequently had private healthcare. Other baseline characteristics between transplanted and not transplanted cohorts are presented in Table 1. The reasons for not proceeding with transplantation were disease status (refractory disease or relapse prior to conditioning) in 15 patients (36.6%), followed by procedure rejection by patient/family and/or treatment abandonment in 12 (29.2%), 5 (12.2%) did not have a suitable donor, 4 (9.7%) due to economic difficulties, and 4 (9.7%) developed important comorbidities. A high DRI and lack of insurance coverage were associated with a higher risk for not getting a transplant in both univariate and multivariate analyses (Table 1). As expected, the outcome of patients that were not transplanted was dismal overall and particularly in high/very high DRI patients (Figure 1, Panel A-D). Conclusion: In the era of haploidentical transplantation, the biggest barrier in our limited-resource context is disease activity/relapse, followed by patient rejection/treatment abandonment, and not the availability of a donor. We must perform transplants promptly and increase education for patients and family in order to overcome these limitations. Disclosures Gomez-Almaguer: Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau.

Introduction. Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphomas (NHL). The use of chemoimmunotherapy (R-CHOP) in DLBCL has improved Overall Survival (OS). However, there are among 45-55% of patients who will die due to relapse, progression (refractoriness) or toxicity to treatment. Genomic classifications are difficult to use in clinical practice, especially in lain America, due to the need of trained personnel and cost. So, we continue using the International Prognostic Index (IPI) and its variations (e.g. revised-IPI, NCCN-IPI) for prognostic purposes. However, other biological variables have been reported to be prognostic, such as serum beta-2-microglobulin (B2M), lymphocyte/monocyte ratio (LMR), neutrophil/lymphocyte ratio (NLR), platelets/lymphocyte ratio (PLR) and serum albumin (SA). These factors have been associated with burden of disease, inflammation and nutritional status. Aim. Therefore, we performed a retrospective analysis of the databases of two Latin American groups to determine which biological variable is the most powerful factor prognostic of OS. Methods. A total of 1,250 patients were analyzed from two databases [(Grupo de Estudio para el Linfoma Mexicano (GELMEX) and the Grupo de Estudio para el Linfoma Latino Americano (GELL)], where 525 patients met the following inclusion criteria: DLBCL diagnosis by immunochemistry; complete data on absolute lymphocyte, absolute monocyte, absolute neutrophil and absolute platelet count, serum B2M and SA; and complete data on traditional variables for calculating risk groups for IPI, NCCN-IPI & R-IPI. The LMR, NLR and PLR was obtained. We evaluated the AUC of the biological variables and the differences among each one of them (including cut-off). Kaplan-Meier curves (KMC) were estimated and subsequently, the inference of OS was evaluated by Hazard Ratio (HR) Cox-regression in univariate/multivariate analyses by forward model. All variables with p Outcomes: Clinical characteristics of the cohort (n=525) were as follows: median follow-up time was 32 months (range: 0.2-132), 52% were male, 60% had more than 60 y/o (≥75 y/o, 21%), one third (32%) had a bad performance status (ECOG ≥2), 63% had advanced stage (III-IV), 49% had high serum lactate dehydrogenase (LDH; ratio 1.1-2.9, 41%; ratio ≥3, 8%), 21% had ≥2 extranodal sites involved (28%, NCCN-specific sites) and 43% had bulky disease. SA had the best AUC comparing with other variables (see figure 1). 5-y OS rates by SA (>3.2 mg/dL vs. ≤3.2 mg/dL) were 72% vs 34% (Log Rank p Conclusion: Low SA emerges as an easy-to-use, important biological factor prognostic of worse survival, independent of the IPI, R-IPI and NCCN-IPI scores, in Latin American patients with DLBCL treated with chemoimmunotherapy. Figure 1 Disclosures M: Roche-Mexico: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Merck-Sharp-Dome: Speakers Bureau. Ramirez-Ibarguen:Roche-Mexico: Consultancy, Speakers Bureau. Peña:Novartis: Other: Congress inscription and flights; Tecnofarma: Other: Congress inscription and flights; Roche: Other: Congress inscription and flights; Biotoscana: Other: Congress inscription and flights; Janssen: Other: Congress inscription and flights; Pfizer: Membership on an entity's Board of Directors or advisory committees. Paredes:Tecnofarma: Honoraria. Gomez-Almaguer:Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Abello:Takeda: Other: Participation in advisory board meeting. Tena:Roche-Mexico: Employment. Castillo:Abbvie: Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; TG Therapeutics: Research Funding.

Bone marrow (BM) aspiration plays an important role in hematologic malignancies diagnosis. Access and cost of diagnostic flow cytometry remains a problem in low and middle-income countries. In this context, morphological diagnosis by BM smear often represents the only means to rapidly diagnose our patients. Therefore, in this context obtaining the highest quality sample possible during the procedure is paramount. Despite being a well-known problem, evidence-based recommendations to improve BM aspirate quality are few, with studies evaluating factors associated with poor quality samples lacking. Objectives To determine factors associated with poor quality BM aspirates defined by an aspicular or hemodiluted sample in a hematology referral center. Materials and methods We conducted a retrospective study in our University Hospital and analyzed the BM smear samples stored in our center performed from October 2014 to December 2018. We collected and analyzed data based on diagnosis, age, gender, recent chemotherapy, and the variables of a complete blood count performed just before each BM aspiration. The quality of the BM smear was defined in any of the following: aspicular (without spicules), pauciaspicular (1-3 spicules), spicular (> 3 spicules), defining aspicular BM smear as non-diagnostic samples. Univariate analysis was performed looking for diferences between operators (in a 3-year residency program). In the other hand, in the multivariate analysis we seek to reveal the factors associated with obtaining hemodiluted (aspicular) bone marrow aspirate-smears. Results A total of 1,073 BM aspirates were evaluated. Hematology fellows performed 97% of BM aspirates; the remaining 3% were performed by attending physicians. In our analysis, 301 aspirates were aspicular, constituting 28.1% of the total number of aspirate smears. Most BM aspirates were performed for a diagnostic evaluation (66.3%) with the rest of the procedures for subsequent hematologic malignancy response assessments. In the univariate analysis, no differences were observed between operators. In a multivariate analysis the presence of an age >65 years (OR 3.1, 95% CI 2.3 to 4.1) and hemoglobin Conclusions We found no differences between operators, emphasizing that there are other factors to consider in addition to a correct BM aspiration technique or operator experience. We believe this is crucial to recognize, especially in developing countries where morphological diagnosis remains the only means for the diagnosis or response evaluation of our patients. BM aspirate sample quality is multifactorial, being age and hemoglobin important factors. In addition, obtaining aspicular or hemodiluted samples represents not only a diagnostic challenge, but also delays the treatment of our patients. Disclosures Gomez-Almaguer: Celgene: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Teva: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau.

Immune thrombocytopenia (ITP) results from platelet destruction and production suppression. Eltrombopag belongs to a new class of thrombopoietin-mimetic drugs that raise platelet counts in ITP patients. We performed a single-arm study to assess the response to a single course of dexamethasone (40 mg by mouth, days 1-4) in combination with eltrombopag (50 mg, days 5-32) in 12 adults with newly diagnosed ITP in an outpatient setting. Median follow-up was 12.5 months. After therapy (day 33), 100% of patients achieved at least ≥30 × 10(9)/L platelets. Four patients relapsed. Complete response at 6 months (platelets ≥100 × 10(9)/L) was achieved in 50% of patients and response at 6 months (platelets ≥30100 × 10(9)/L) was achieved in another 25%; relapse-free survival was 66.7% at 12 months (median response duration of 8.3 months). In conclusion, eltrombopag/dexamethasone is a feasible frontline therapy for ITP. This trial is registered at www.clinicaltrials.gov as NCT01652599.

Introduction: Our center has implemented an outpatient-based peripheral blood haploidentical HSCT (haplo-HSCT) program since 2012. Cytokine release syndrome (CRS) associated with T-cell replete haplo-HSCT is characterized by fever and high levels of inflammatory cytokines with symptom onset typically occurring early after cell infusion, coinciding with maximal in vivo T-cell expansion. In this study, we report our analysis of CRS development after T cell-replete haplo-HSCT after using prophylactic dexamethasone and focusing on the impact of CRS on hospitalization and transplant outcomes in our outpatient program. Methods: In this retrospective study, adult patients undergoing a T-cell replete haplo-HSCT at our transplant center between January 2016-2018 were included. CRS was defined and graded using the criteria described by Lee et. al. Conditioning was based on fludarabine 25 mg/m2/day (day -5 to -3), cyclophosphamide 350 mg/m2/day (day -5 to -3), and oral melphalan 50-100 mg/m2 (day -2 to -1). For graft-versus-host disease (GVHD) prophylaxis we used post-transplant cyclophosphamide (PTCy) 50 mg/kg on days +3 and +4 as well as mycophenolate mofetil and either cyclosporine or tacrolimus starting on day +5. All patients received dexamethasone 8 mg IV on day 0 to +2 as prophylaxis against CRS. Disease-risk index (DRI) and HCT-Comorbidity Index (HCT-CI) were calculated based on established definitions. The primary objective was to evaluate the incidence of CRS with dexamethasone prophylaxis during an outpatient-based peripheral blood haplo-HSCT. Secondary objectives were to describe factors associated with CRS and to determine the impact of CRS on transplant outcomes and hospitalizations. Results: There were 42 patients included; the median age was 32.5 years (range, 16-66). The median DRI score was 3 (range, 1-4). The most common underlying diagnosis was acute lymphoblastic leukemia (n=14, 33%), followed by acute myeloid leukemia (n=8, 19%), and lymphoma (n=7, 16.6%). Conditioning was myeloablative (n=33, 79%) or reduced-intensity (n=9, 21%). Thirty patients (71.4%) developed CRS. CRS severity was grade 1-2 in 28 patients (66.7%) and grade 3 in 2 patients (4.8%). Median day of onset occurred on day +2 (range 0-4) and usually resolved after PTCy on day +5 (range, 1-11). The incidence of CRS was not associated with recipient age, number of CD34+ cells infused, DRI score, baseline HCT-CI score, and conditioning intensity. Time to neutrophil and platelet engraftment was not different in patients with CRS compared with patients without. Hospitalization was required in 36 cases (87%) while 6 patients (13%) were followed in a fully-outpatient basis, including 2 patients with grade 1 CRS. The median length of hospitalization was 13 days (range, 0-50) for patients with CRS and 8 days for patients without CRS (range, 0-44). The most common signs and symptoms besides fever were gastrointestinal manifestations (36.6%), hypoxemia (30%), fluid-responsive hypotension (16%) while 2 patients required vasopressors. Conclusion: The completely ambulatory conduct of haplo-HSCT was limited by the development of CRS. However, even in patients who developed CRS median length of hospitalization was short. CRS was common despite dexamethasone prophylaxis although most CRS were of grade 1 or 2. None of the factors evaluated were associated with CRS development in this context, and CRS did not influence time to engraftment, cumulative incidence of acute or chronic GVHD. New strategies are required to prevent CRS and prevent hospitalizations associated with haplo-HSCT. Disclosures Gomez-Almaguer: AbbVie: Consultancy; Novartis: Consultancy.

Introduction: Numerous clinical trials have been conducted in order to reduce or prevent the appearance of mucositis in patients undergoing cancer treatment and some of these have appeared in the clinical guidelines as recommendations (Keefe,DM Cancer 2007). However, to date no molecule has been shown to prevent appearance of this kind of lesions. Selenium, a trace element in the organism, cofactor of multiple biological processes, has been used previously for mucositis chemoprevention in head and neck tumors. We conducted a study to know if selenium supplementation has an impact on the development of mucositis. Objective: We aim to know the impact of Selenium in patients undergoing hematopoietic stem cell transplantation, in the presentation and duration of mucositis comparing against placebo. Methods: We performed a double blind clinical trial in a single center pilot study approved by our ethics committee. All patients candidates for autologous or allogeneic HSCT above 18 years were submitted for our study previous informed consent by our institution. Patients were randomized into one of two arms: a) selenium methionine, b) placebo. Previously randomized, patients were administered supplementation with oral selenium methionine at a dose of 400mcg/day or placebo starting 7 days prior transplantion. We determined a baseline measurement of serum and urinary selenium. Subsequent measurements were made each week for a total of 28 days. Evaluations were made with validated SMAQ questionnaires which also included scales of mucositis severity, using the WHO mucositis scale. All of them performed by an observer blinded to what supplementation were being administered to each patient. Results: We have recruited a total of 31 patients, of whom 16 were allogeneic and 15 autologous. We observed that 38.7% developed some degree of mucositis, most of them on the allogeneic arm (10 patients). Selenium consumption arm was associated with a median decrease of 32% (1.9 vs 2.8) in the WHO scale in the severity of mucositis compared to the placebo arm (p=0.046), however we didn't find difference in mucositis resolution time between groups (p=0.162). On the other hand, selenium supplementation was associated with shorter platelet engraftment time (p=0.041), without any significant difference in neutrophil engraftment time. With a follow up of 112 days, there are no difference about mortality or other analized variables. Conclusions: Supplementation with selenium was associated with a slight decrease in the severity of mucositis in comparison with placebo. Without any relevant findings in relation to mortality or other variables analized. Disclosures Gomez-Almaguer: Novartis: Consultancy; AbbVie: Consultancy. Herrera-Rojas:Janssen: Employment.

Introduction: Pernicious anemia is the leading cause of vitamin B12 deficiency worldwide, caused by an autoimmune reaction against parietal cells in the gastric mucosa leading to B12 absorption impairment. The treatment of pernicious anemia is based on replacement of cobalamin, oral and sublingual routes have been described nevertheless its absorption is erratic. The recommended schedules for vitamin B12 replacement is an intramuscular injection of 1000μg every other day for 1 to 2 weeks followed by weekly injections for a month and then tapered to once a month indefinitely (Green.Blood 2017;129(19):2603-2611). Such an approach can limit treatment adherence for patients in a resource-poor setting and may be unnecessary. Furthermore, the toxicity of cobalamin is minimal, while the benefit of larger doses is unknown. Objective: We aim to demonstrate that a single mega-dose intramuscular (IM) injection of a multivitamin formulation is sufficient to achieve and maintain a complete hematologic response for a six-month period. Methods: We performed a single center pilot study approved by our ethics committee and registered in Clinicaltrials.gov (NCT03372447). All patients with newly diagnosed, untreated pernicious anemia ≥18 years were included after written informed consent was obtained. A single IM dose of a multivitamin formulation consisting on cobalamin 10,000 μg, thiamin 100 mg, and pyridoxine 50 mg was administered. Complete blood count (CBC) was performed at 15 and 30 days and monthly thereafter for a total of six months. Partial response (PR) was considered when Hb ≥10g/dl, Normal WBC, PLT ≥100x103/μL, Complete response (CR) was defined as Hb ≥12g/dl, normal WBC and PLT. Our primary outcome was normalization of CBC (CR) at 6 months. As secondary outcomes we evaluated safety and measured levels of methylmalonic acid (MMA), homocysteine (HCY) and B12 levels (B12L) at diagnosis, three and six months after treatment. Results: Eight patients have been enrolled (5 men and 3 women), median age was 58 years (range 25-77). None had neurological symptoms at presentation. Median laboratory values at diagnosis were Hb 5.9 g/dL (range 3.9-10.7), mean corpuscular volume 113.2 fL (range 94.6-122.9), WBC 2.68x103/μL (range 1.26-6.08), PLT 93x103/μL (range 9.75-156,000), lactic dehydrogenase 3082IU/L (range 439-9840), B12L 85 pg/ml (range 83-90), HCY 154.09 μmol/L (range 83.7-182.44), MMA 24435 nmol/L (range 5175-99500). By day 30 all patients achieved PR. At the end of the third month, 100% of patients reached a CR regarding Hb and WBC while 88% of patients reached a complete PLT response. Median Hb increment at 1 month and 3 months was 6.15g/dl (range 3.1-7.74) and 1.8g/dl (range 0.4-3.7) respectively. The difference between Hb concentration at all time-points was statistically significant (ANOVA; p=0.002) particularly in the first 15 days (p=0.025), while post hoc testing revealed that increments in Hb after the second-week post-treatment were not (p>0.05). Until now, 4/8 patients have completed the primary outcome and all of them have maintained CR and normal levels of HCY and B12L without further cobalamin doses, only one patient had an asymptomatic increase of MMA. No adverse events following the administration of multivitamin preparation were documented. Conclusions: A single dose of a 10,000μg B12 multivitamin was safe and tolerated. Thus far all patients have achieved and maintained a response for at least six months. This simplified single cobalamin administration is an effective option for the treatment of pernicious anemia. Disclosures Gomez-Almaguer: AbbVie: Consultancy; Novartis: Consultancy.

Background. High-dose cyclophosphamide and a haematopoietic cell autotransplant is an effective therapy of multiple sclerosis (MS). This is often done in an inpatient setting using frozen blood cells either blood or bone marrow cells. Objective. Determine if this procedure can be safely and effectively simplified. Methods. We developed an autotransplant protocol actionable in an outpatient setting using refrigerated blood cells collected after giving cyclophosphamide, 50 mg/kg/d x 2 d and filgrastim, 10 μg/kg/d. A 2nd identical dose of cyclophosphamide was given 9 d later followed by infusion of blood cells stored at 4º C for 1-4 d. Subjects received rituximab after bone marrow recovery, 100 mg, every 2 mo for 1 y or rituximab, 1 g in 1 dose based on the subject's residence country (Figure 1). The co-primary outcomes were rate of bone marrow recovery and therapy-related mortality (TRM). Secondary outcomes included MS relapse-free survival (MS-RFS) and survival. Cumulative dose of cyclophosphamide was 200 mg/Kg Results. We treated 426 consecutive subjects. Median age was 47 y (range, 21-68 y). 145 (34%) were male. 84 (20%) had primary progressive MS, 173 (41%), relapsing remitting MS and 169 (39%), secondary progressive MS. Median blood cell storage time was 1 d (range, 1-4 d). Median intervals to granulocytes >0.5 x10E+9/L was 8 d (range, 2-12) and to platelets >20 x10E+/L, 8 days (range, 1-12). 412 subjects (96%) were treated as outpatients. Median follow-up is 6 mo (range, 3-30 mo). There was 1 death from TRM. In 304 subjects (71%) with data from neurologic evaluations ≥3 posttransplant median MS RFS is 27 mo (95% confidence interval [CI], 24, 30 mo). Estimated 1 y MS RFS is 85% (80, 90%) with no significant difference between the 3 MS variants. Median survival will exceed 30 mo. An unusual aspect of our study was giving two 2-d blocks of cyclophosphamide 8 days apart rather than 4 d continuously done for 3 reasons: (1) use of cyclophosphamide to mobilize blood cells for the autograft; (2) facilitate using a refrigerated rather than frozen autograft; and (3) decrease toxicity. Our finding of rapid bone marrow recovery using refrigerated grafts is like our experience in persons with plasma cell myeloma and lymphomas receiving high-dose therapy and an autotransplant. Conclusion. The strategy we developed was actionable in an outpatient setting with rapid recovery of granulocytes and platelets and only 1 early death. Estimated MS-RFS and survival were good. MS variant type did not correlate with MS-RFS or survival. Disclosures Gomez-Almaguer: AbbVie: Consultancy; Novartis: Consultancy.

Introduction: Donor lymphocyte infusion (DLI) is a useful therapy for mixed chimerism (MC) or measurable residual disease (MRD) after allogeneic hematopoietic cell transplantation (HSCT) in patients with malignancies, while it is less effective for overt relapse and is limited by graft-versus-host disease (GVHD). Multiple DLI products can be obtained from a single leukoapheresis without granulocyte-colony-stimulating factor (G-CSF) priming, while cryopreserving surplus is an alternative for peripheral blood grafts. The ideal DLI CD3+ cell dose remains undefined ranging from 1-500x106/kg. However, leukoapheresis and cryopreservation are not risk-free, they are expensive and their costs prohibitive for many patients in developing countries. Furthermore, T-cell doses present in standard whole blood units can reach ≥1x106/kg in healthy donors which can be further increased after G-CSF exposure. For these reasons we have used G-CSF-primed whole blood units (WB-DLI) in HLA-matched and haploidentical (Haplo) transplant recipients and report our single-center experience. Methods: Patients ≥16 years of age who received WB-DLI at any time after HLA-matched related or Haplo peripheral blood HSCT due to relapse, MRD, MC or poor graft function were included from 2016-2018. Donors were stimulated with filgrastim 5 μg/kg every 24 hours for 3 days prior to donation. Standard pre-transfusion testing included major/minor crossmatch and flow cytometry analysis for lymphocyte subset quantification. The blood draw was performed on day 4 with the aim to collect 450 mL of whole blood in a standard collection bag. For patients with major and bidirectional ABO mismatch who had not undergone group switch or had a mixed population in solid-phase typing, a reactive major crossmatch was considered an absolute contraindication, while a reactive minor crossmatch was not. WB-DLI was infused fresh on the day of collection without manipulation in an outpatient basis. For relapsed patients, concurrent chemotherapy was administered on a case-by-case basis. Disease evaluation after relapse was performed on day +30 after treatment, while chimerism analysis was performed on day +60 through standard methods. GVHD prophylaxis was performed with oral cyclosporine A or tacrolimus and gradually tapered in a 60-day window. Results: Fourteen patients received a single dose of WB-DLI, median age was 32 years (16-67), 50% were female. Most common diagnoses were acute lymphoblastic leukemia, (n=5) and acute myeloid leukemia (n=5), followed by myelodysplastic syndrome (n=2), non-Hodgkin lymphoma (n=1) and chronic myeloid leukemia (n=1). Nine patients received Haplo grafts, while 5 were HLA-matched. Three patients had previous GVHD inactive at the time of WB-DLI. Indication for WB-DLI was relapse for 6 patients, 3 had MRD while 5 remained in remission; one patient received WB-DLI due to poor graft function. Median chimerism at the time of WB-DLI was 72% (range 38-100%). A single infusion was administered in all cases. Median mononuclear cell count obtained was 32x10x6/kg (range, 9-74), while median CD3+ cell count was 6.7x106/Kg (range 5.2-19). No immediate, severe adverse effects were observed. Febrile non-hemolytic transfusion reaction was documented in 4 cases after completing the procedure. No complications were observed in n=4 ABO mismatch cases including (n=2) major and bidirectional patients. Overall 50% of patients responded. Chimerism was improved in 50%, with a median increase of 28% (range 9-53%). Median post-DLI chimerism was 92.5% (range 20-100). Regarding patients treated for relapse or MRD, 3/9 patients responded (33%). Overall 8/14 patients eventually relapsed (57%) with a 12-month progression free survival of 27.5%, lower in relapsed/MRD positive patients (Figure I) (log rank test p=0.02 and 0.04, respectively). Overall survival at 12 months was 61.2%. Three patients developed acute GVHD, two of them grade III/IV in a median of 13 days (range 7-38). Four patients died due to relapse. Median follow-up after WB-DLI was 5 months (range 0.6-20.1 months). The cost of obtaining and administering WB-DLI was $350 USD per dose. Conclusions: DLI obtained from unmanipulated, GCSF-primed whole-blood is a safe and affordable adoptive cell therapy. It is effective and improves mixed chimerism after HSCT, while it was less effective for overt relapse. Disclosures Gomez-Almaguer: AbbVie: Consultancy; Novartis: Consultancy.

Background aims Cerebral palsy (CP) is related to severe perinatal hypoxia with permanent brain damage in nearly 50% of surviving preterm infants. Cell therapy is a potential therapeutic option for CP by several mechanisms, including immunomodulation through cytokine and growth factor secretion. Methods In this phase I open-label clinical trial, 18 pediatric patients with CP were included to assess the safety of autologous bone marrow–derived total nucleated cell (TNC) intrathecal and intravenous injection after stimulation with granulocyte colony-stimulating factor. Motor, cognitive, communication, personal-social and adaptive areas were evaluated at baseline and 1 and 6 months after the procedure through the use of the Battelle Developmental Inventory. Magnetic resonance imaging was performed at baseline and 6 months after therapy. This study was registered in ClinicaTrials.gov (NCT01019733). Results A median of 13.12 × 10 8 TNCs (range, 4.83–53.87) including 10.02 × 10 6 CD34+ cells (range, 1.02–29.9) in a volume of 7 mL (range, 4–10.5) was infused intrathecally. The remaining cells from the bone marrow aspirate were administered intravenously; 6.01 × 10 8 TNCs (range, 1.36–17.85), with 3.39 × 10 6 cells being CD34+. Early adverse effects included headache, vomiting, fever and stiff neck occurred in three patients. No serious complications were documented. An overall 4.7-month increase in developmental age according to the Battelle Developmental Inventory, including all areas of evaluation, was observed (±SD 2.63). No MRI changes at 6 months of follow-up were found. Conclusions Subarachnoid placement of autologous bone marrow–derived TNC in children with CP is a safe procedure. The results suggest a possible increase in neurological function.

Introduction: Immune thrombocytopenia (ITP) is an autoimmune disorder that results from platelet destruction and production suppression. Frontline-therapy includes corticosteroids, intravenous immune globulin or anti-D immunoglobulin. Single-agent treatments have not been successful in inducing prolonged remission, as relapse will occur in approximately 50% of patients. Low-dose rituximab (100 mg) has been used for the treatment of ITP, showing an activity almost similar to the 375 mg/m2 standard dose. We and others have reported sustained response rates ranging from 58% to 76% using rituximab plus dexamethasone as a frontline therapy. Eltrombopag is a thrombopoietin nonpeptide mimetic that has been shown to raise platelet count in chronic ITP, and we have previously reported eltrombopag/dexamethasone as a feasible frontline therapy for ITP reaching 100% response rates.The lack of sustained response in many adult patients with newly diagnosed acute ITP has stimulated the search for a treatment that modifies the natural course of the disease. Objetive: We aim to evaluate efficacy, safety, and response duration of low-dose weekly rituximab (100 mg weekly, four doses) plus high-dose dexamethasone (40 mg PO, days 1-4) in combination with eltrombopag (50 mg, days 1-28) as frontline therapy in newly diagnosed primary ITP in an ambulatory setting. Methods: This is an ongoing open-label, single-arm study performed in patients with newly diagnosed ITP from the Hospital Universitario Dr. Jose Eleuterio Gonzalez in Monterrey, Mexico (Clinical trials.gov NCT02834286). Eligible patients are 16 years or older, with bleeding manifestations and/or a platelet count ²30×109/L, without previous treatment. Patients are excluded if they had active infection, pregnancy, or a malignant disease. A complete blood count is performed at baseline, on days 3, 5, 7 and then weekly for 28 days, monthly until month 6, and every 3 months thereafter. Partial and complete responses are defined as an increase in platelet counts ³30×109/L and ³100×109/L, respectively. Results: Ten consecutive patients have been enrolled from March 2015 until July 2016. Median age was 37 years (16-61). Six patients were women (60%) and four were men (40%). Median platelet account at diagnosis was 7 « 109/L (range 1.2-28). Median follow-up has been 7 months (range 1-13). All patients achieved at least a partial response (PR) at a median of 4 days (range 3-14). Complete response (CR) was achieved in 9 patients in a median of 7 days (7-22); all of them were still in CR at the end of treatment (Day 28). One patient lost response at 28 days and received a second high-dexamethasone course maintaining CR. No significant adverse effects have occurred during treatment, only 1 patient reported mild myalgia. No relapses have been documented until now.Currently, 8 patients remain in CR and 2 in PR. Conclusion:This is the first trial evaluating the response of low-dose rituximab in combination with eltrombopag and high-dose dexamethasone in newly diagnosed patients with ITP.Low-dose rituximab in combination with eltrombopag and high dose dexamethasone is a feasible frontline therapy for ITP. This drug combination showed high response rates achieved very rapidly, with a low incidence of side effectsand might represent an attractive option in patients with ITP and substantial bleeding. Table Characteristics and follow-up of patients M: Male, F: Female, CR: Complete Response, PR: Partial Response Table. Characteristics and follow-up of patients. / M: Male, F: Female, CR: Complete Response, PR: Partial Response Disclosures Gomez-Almaguer: Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Introduction Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder that involves antibody and cell mediated destruction of platelets as well as suppression of their production. Prednisone is the initial standard therapy in adults1. High-dose dexamethasone as front-line therapy given as pulses of 40 mg per day for 4 consecutive days, was effective in 85% of patients, nevertheless, 50% relapsed within six months2. The prices of ITP drugs for 1 month of treatment in an adult range from prednisone; $16, eltrombopag; $5,934, intravenous immune globulin (IVIG) (80 g); $9,648, to rituximab (2 g); $15,5963. Only prednisone/dexamethasone and eltrombopag are available in oral presentation, for this reason, ambulatory treatment is an alternative for these patients. The trombopoietin receptor agonists are effective for the treatment of patients with chronic ITP, although response is dependent on continued administration. Eltrombopag is a small molecule agonist of the c-mpl (TpoR) receptor, which is the physiological target of thrombopoietin. This drug effectively raises the platelet count in adult patients (aged 18 years and over) as second/third line therapy, that is for patients refractory to corticosteroids and IVIG who have had their spleen removed or when splenectomy is not an option4. Our group, as well as others, has previously sought to improve response rates in these patients, particularly with the use of rituximab5, 6. To our knowledge neither eltrombopag nor romiplostim have been used as front line therapy in ITP, therefore the purpose of this study was to assess the efficacy of eltrombopag and dexamethasone in this setting. Patients and Methods This was a prospective, phase 2 study, using the combination of eltrombopag (50 mg PO once a day for 4 weeks) and high-dose dexamethasone (40 mg PO days 1,2,3,4) in untreated adult patients with immune thrombocytopenia or in patients with less than 7 days of treatment with corticosteroids. Complete response (CR) was defined as an increase in platelet count >100×109/L. Partial response (PR) was defined as an increase in the platelet count greater to 30 ×109/L according to standard criteria. Duration of response was considered from the day of initial administration to the first time of relapse (platelet count Results Twelve consecutive patients were enrolled from June 2012 to June 2013, 6 women and 6 men. The median age at diagnosis was 50 years (range, 20 - 80 years). The median platelet count at diagnosis was 7 x 109/L (range, 2 - 29 x 109/L). Patients were followed for a median of 2.5 months (range 1.1 - 13). After steroid treatment at day +5, ten patients had responded (83.3%), five had achieved CR (41.7%), and five PR. After completing treatment with eltrombopag at day +34, all patients responded (100%), nine patients achieved CR (75%) and three PR (25%). Two patients relapsed in a median time of 39.5 days (range, 30.1 - 49), both regaining CR after treatment with another high-dose dexamethasone course and low-dose rituximab (4 doses of 100 mg every week). At 3 months follow-up 66.7% remained in CR and 33.3% in PR (n=6). At 6 months follow-up two patients remained in CR and two in PR (n=4). Time to best response achieved was 34 days from diagnosis (range, 19 – 64.1). At the end of follow-up 9 patients (75%) remained in CR and 3 patients in PR (25%). Total treatment cost per patient was $1,640 approximately. Conclusion Currently the initial treatment of ITP patients is based on prednisone or high dose dexamethasone with or without IVIG. This approach is associated with high cost and high relapse rate. The results from our pilot study suggest that high dose dexamethasone and eltrombopag are very effective as first line treatment for acute ITP in adults. This treatment is ambulatory, affordable and well tolerated; however, we still don't know if this approach will have a favorable impact on the relapse rate of this disease. Disclosures: Off Label Use: Eltrombopag as first line treatment for ITP.