It is an exciting era in leukemia owing to the development of novel targeted therapies and advances in genomics, pathophysiology, prognostication, and monitoring (e.g., highly sensitive measurable residual disease assays). Currently, most leukemias are effectively treated with immunotherapies (highly effective monoclonal antibodies targeting CD19 [blinatumomab], or CD22 [inotuzumab ozogamicin]), BCR::ABL1 tyrosine kinase inhibitors (TKIs; e.g., dasatinib, ponatinib), Bruton TKIs (e.g., ibrutinib, acalabrutinib), BCL-2 inhibitors (venetoclax), IDH1/2 inhibitors (ivosidenib, olutasidenib, and enasidenib), FLT3 inhibitors (e.g., midostaurin, quizartinib, and gilteritinib), menin inhibitors (revumenib, ziftomenib), and chimeric antigen receptor T-cell therapies. These novel agents and their judicious use in combination strategies have transformed the treatment landscape across all leukemias, significantly increased survival and quality of life for patients, and attenuated the need for intensive chemotherapy and hematopoietic stem cell transplantation. Leukemia subtypes, such as Philadelphia-positive acute lymphoblastic leukemia (incurable before 2000) and chronic lymphocytic leukemia (previously considered incurable) with historically dire prognoses were recently transformed to favorable leukemias with 5- and 10-year survival rates of 80+% and 90+%, respectively. The BCR::ABL1 TKIs resulted in normal life expectancy in chronic myeloid leukemia. Notable advances have also been made in AML with targeted therapies, although some subsets (older/unfit patients for intensive chemotherapy, complex karyotype, TP53-mutated, KMT2A-rearranged, and treated secondary AML) still have unfavorable outcomes. Herein, we provide a high-level overview of prominent clinical developments across all leukemias. In contemporary times, harnessing the benefits of novel targeted therapies and the evolving treatment landscape bolster the optimistic view that most, if not all, leukemias are curable.

BACKGROUND: The prognosis is poor for patients who have relapsed-refractory acute myelogenous leukemia (AML). Most published reports analyzed results from therapies in first-salvage AML or in studies that were conducted before 2000. Several novel agents and strategies are being tested for potential approval as treatment for patients with relapsed-refractory AML in second salvage. Therefore, it is important to establish the historic results of anti-AML therapies in this setting in the modern era. The objective of the current study was to analyze the results from second salvage therapies in patients with AML since 2000 with regard to response and survival. METHODS: In total, 673 patients who received second salvage therapies for AML since 2000 were analyzed. Their median age was 60 years (range, 18-89 years). Salvage therapy consisted of cytarabine-based regimens in 267 patients, noncytarabine combinations in 37, hypomethylating agent-based regimens in 136, and phase 1 and 2 single agents in 233. RESULTS: Eighty-six of the 673 patients (13%) achieved a complete response (CR) or a CR with low platelet count (CRp). The median duration of CR-CRp was 7.2 months. The median survival was 4.4 months (95% confidence interval, 4.0-4.8 months), and the 1-year survival rate was 16% (95% confidence interval, 14%-19%). Multivariate analysis identified the following as independent adverse factors for achievement of CR-CRp: platelets <50 x 10(9)/L (P<.001), complex karyotype with >= 3 chromosomal abnormalities (P=.02), regimens that did not include cytarabine or hypomethylating agents (P=.014), and no prior CR lasting >= 12 months with frontline or salvage 1 therapies (P<.001). The independent adverse factors associated with worse survival were age >= 60 years (P=.01), platelets <50 x 10(9)/L (P=.02), peripheral blasts >= 20% (P=.03), albumin <= 3g/dL (P=.04), and complex karyotype (P=.003). The authors also applied and validated, in the current population, the 2 multivariate-derived prognostic models for CR and survival developed in their previous study of 594 patients who received treatment for second salvage AML from the previous 2 decades. CONCLUSIONS: This large-scale analysis establishes the modern historic results of second salvage therapy in AML and validates the prognostic models associated with outcome. These data could be used to analyze the differential benefits of current or future investigational strategies under evaluation in this setting and for the purpose of potential approval of new agents in the United States and the world. (C) 2018 American Cancer Society.

Historically, progress in leukemia research has been slow, but it has accelerated recently as a result of understanding the pathophysiology of leukemias and implementing more effective and targeted therapies. This review summarizes the progress across leukemia subsets and projects the potential cure of most leukemias in the next decade.

Background: Granulocyte transfusions (GTX) in neutropenic patients (pts) have been used in an effort to treat infections not responding to antimicrobial therapy, but the efficacy and safety of GTX remains controversial. The objective of this study is to describe the outcome of pts with perirectal and perineal infections who received unirradiated GTX.

Background: Patients with Acute Myeloid Leukemia (AML) experience profound neutropenia; infections remain the leading cause of morbidity and mortality. Transfusion of functional non-irradiated allogeneic granulocytes may treat or prevent infections in AML patients, and may also have anti-leukemic benefits. Study Design: Patients free of infection, with a diagnosis of AML or high-risk myelodysplastic syndrome undergoing induction or first-salvage therapy were eligible. Allogeneic Granulocyte Transfusions (GTs) were administered to neutropenic (<0.5 × 109/L) patients every 3-4 days until sustained ANC recovery, initiation of new therapy, or completion of 6 weeks on study. Results: 45 patients enrolled with a median age of 67 years (range 23-83); 27 (60%) were male. Five patients (11%) never received a GT, due to donor screening failure and/or donor unavailability. 119 donors donated 156 granulocyte concentrates to the remaining 40 patients. The median number of GTs transfused per patient was 3 (range 1-9). All patients experienced >1 neutropenic fever, with an average of one infectious episode per patient. Other adverse reactions were urticaria/pruritis (n=1), rash (n=1), and hypotension (n=1). Response to leukemiadirected therapy included complete remission in 50%, overall response rate of 70%, and 8-week mortality of 8%. Median overall survival was 15 months, with 51% 1-year survival. Conclusion: Administration of non-irradiated functional allogeneic GTs to neutropenic MDS/AML patients is safe and feasible. No transfusion-associated graft-versus-host-disease (TA-GVHD) was reported and no increased toxicity was described, including among the 10% receiving subsequent allogeneic stem cell transplant. The favorable patient outcomes within this diverse group of primarily elderly AML are notable.

Abstract Background: A retrospective analysis was performed to evaluate the collection efficiency of two apheresis devices for granulocytes using the Spectra Optia (TerumoBCT) vs. the Cobe Spectra (Cobe: TerumoBCT) which served as control. Study Design and Methods: A total of 410 granulocyte collections (GCs) were collected from volunteer healthy blood donors (<4%) and family and friends of severely neutropenic oncology patients requiring GCs from July 2014 to November 2015. All healthy male and females donors eligible to donate blood with peripheral venous access were allowed to donate granulocytes after first undergoing Platelet Apheresis with very few exceptions. This was performed to evaluate the donor's ability to undergo a lengthy apheresis procedure. All first time donors were mobilized with G-CSF (600/480 mcg) and/or Dexamethasone 8 mg 12 hours prior to the apheresis. Both instruments were primed with acid citrate-dextrose (ACD-A) and then changed to a coagulation buffer of a 500 mL bag of 6% hydroxyethyl starch (HES) to which 40 mL of trisodium citrate 46.7% was added. The maximum allowed time for the apheresis procedures on both devices was 3 hours. 186 consecutive GCs were performed using the Spectra Optia from March to November 2015 vs. 224 consecutive GCs using the Cobe Spectra device from July 2014 to March 2015 and served as control. The GCs were transfused to both adult and pediatric patients. GC products greater than 500 mL were divided into double/triple or quadruple units based on the total white count of the unit. Hematopoietic stem cell transplant and pediatric patients received irradiated GCs whereas leukemia patients received non-irradiated GCs. Statustical Method: All statistical analysis were performed using R version 3.3.0. The Wilcoxon rank-sum test was used to compare continuous variables between the Spectra Optia and Cobe Spectra. All statistical tests used a significance level of 5%. No adjustments for multiple donations were made. The table summarizes characteristics by group [ Cobe Spectra (COBE) vs. Spectra Optia (SPECTRA)]. The table presents for each variable, by group, the number of patients, the minimum ("Min") and maximum ("Max") values, the quartiles ("q1" and "q2"), the median, mean and the standard deviation ("SD"), along with the number of missing values ("#NA"), if any. For each parameter, there is also a p-value corresponding to a Wilcoxson rank-sum test. Results: From a total of 186 Spectra Optia granulocytapheresis we were able to process and obtain 433 GC units (21 single, 90 double, 72 triple and 4 quadruple units) as compared to the Cobe Spectra where 224 granulocytapheresis yielded 393 GC units (single 85, double 109 and 30 triple units). All of the split/unspilt GCs from both apheresis devices had a minimum wbc count > 1.0 x 10e10. We found the following parameters - total blood volume processed, totall WBC collected, run time, bag wbc, absolute neutrophil count, absolute lymphocyte count, granulocyte collection efficiency, post-stimulation platelet count, absolute platelet count, MPV and number of GCs split were significantly higher ( p = <0.0001) using the fully automated Spectra Optia while volume collected, hematocrit, bag platelets and platelet collection efficiency were significantly higher ( p=<0.0001) using the Cobe Spectra. The age of the Cobe Spectra patients were older on average (p=0.00015) (Table) The weight, height, pre- and post stimulation WBC and pre-stimulation platelet counts of the donors were of no significance. (Table) Conclusion: The ability to achieve higher granulocyte counts per liter of blood processed with a higher granulocyte CE using the fully automated Spectra Optia has allowed us to process and split Granulocyte Units leading to the availability of multiple units thus easing some of the Granulocyte shortages that our severely neutropenic oncology patients currently experience. ReferenceCancelas JA, Padmanabhan A, Le T et al. Spectra Optia granulocyte apheresis collections results in higher collection efficiency of viable, functional neutrophils in a randomized crossover, multicenter trial. Transfusion; 2015; 55: 751-55Leitner GC, Kolovratova K, Horvath M et al. Granulocyte collection using a novel apheresis system eases the procedure and provides concentrates of high quality. Transfusion 2015; 55: 991-5 Table Characteristics by Group Table. Characteristics by Group Disclosures No relevant conflicts of interest to declare.

Background: The incorporation of intensive chemotherapy, hematopoietic stem cell transplantation (HSCT), targeted therapies including rituximab and tyrosine kinase inhibitors contributes substantial improvement in the outcome of patients with ALL over decades. VAD was changed to hyper-CVAD in 1992; rituximab was added to hyper-CVAD for CD20 positive ALL in 1999/2000; inotuzumab ozogamicin in combination with low-intensity chemotherapy was offered to elderly patients starting in 2011. The aim of this study is to describe the outcome of patients with ALL over decades by age groups.

Red blood cells undergo biochemical and morphologic changes during storage and the time-dependent changes known as “storage lesions” are well documented. It is assumed the longer the RBCs are stored the less effective are the transfusion outcomes.

The high prices of cancer drugs are affecting the care of patients with cancer and our health care system.1 In the United States, the average price of new cancer drugs increased 5- to 10-fold over 15 years, to more than $100,000 per year in 2012. A study by Howard et al2 documented the escalation in cancer drug prices by an average of $8500 a year over the past 15 years. The cost of drugs for each additional year lived (after adjusting for inflation) has increased from $54,000 in 1995 to $207,000 in 2013.

Accurate identification of patients likely to achieve long-progression-free survival (PFS) after chemoimmunotherapy is essential given the availability of less toxic alternatives, such as ibrutinib. Fludarabine, cyclophosphamide, and rituximab (FCR) achieved a high response rate, but continued relapses were seen in initial reports. We reviewed the original 300 patient phase 2 FCR study to identify long-term disease-free survivors. Minimal residual disease (MRD) was assessed posttreatment by a polymerase chain reaction-based ligase chain reaction assay (sensitivity 0.01%). At the median follow-up of 12.8 years, PFS was 30.9% (median PFS, 6.4 years). The 12.8-year PFS was 53.9% for patients with mutated immunoglobulin heavy chain variable (IGHV) gene (IGHV-M) and 8.7% for patients with unmutated IGHV (IGHV-UM). 50.7% of patients with IGHV-M achieved MRD-negativity posttreatment; of these, PFS was 79.8% at 12.8 years. A plateau was seen on the PFS curve in patients with IGHV-M, with no relapses beyond 10.4 years in 42 patients (total follow-up 105.4 patient-years). On multivariable analysis, IGHV-UM (hazard ratio, 3.37 [2.18-5.21]; P < .001) and del(17p) by conventional karyotyping (hazard ratio, 7.96 [1.02-61.92]; P = .048) were significantly associated with inferior PFS. Fifteen patients with IGHV-M had 4-color MRD flow cytometry (sensitivity 0.01%) performed in peripheral blood, at a median of 12.8 years posttreatment (range, 9.5-14.7). All were MRD-negative. The high rate of very long-term PFS in patients with IGHV-M after FCR argues for the continued use of chemoimmunotherapy in this patient subgroup outside clinical trials; alternative strategies may be preferred in patients with IGHV-UM, to limit long-term toxicity.

At the 8th meeting of the International Hematological Malignancies Conference held in 2012, a new Society of Hematologic Oncology (SOHO) was organized. At the 2012 meeting, over 750 people became members of SOHO. Over the next year, an additional 500 people joined. The Society now has a membership of 1,239 individuals. The first formal meeting of SOHO was held in 2013 at the Westin Galleria in Houston, Texas, September 18–21. The meeting was 3½ days in duration and there were 127 scientific presentations. There were also 11 meet-the-professor presentations and 69 posters that were presented complete with abstracts. Also at the meeting in 2013, the leadership organized three standing committees of The Society. The first would be a Steering Committee, which had 21 members, the second an Education Committee which had 29 members, and the third would be a Scientific Committee which had 23 members. The three founding members of the Society became the Board of Directors. In addition, we enrolled 12 members into an Ambassador Program, representing 12 countries, from Central America, South America, and Europe. The meeting in 2013 was sufficiently successful to assure that SOHO will be an important scientific meeting and make an important contribution to progress into the control of the hematological malignancies.

Studies of the leukemias in the laboratory and in the clinic have generated many new concepts and therapies that will undoubtedly continue to be rapidly applied to the other forms of systemic cancer, particularly the concept of narrowly targeted personalized therapy that has proven so effective in CML. It seems likely that other subtypes of leukemia will eventually approach the success achieved with APL, CML, and pediatric ALL.

Abstract Patients with acute myeloid leukemia (AML) experience sustained and profound neutropenia during induction chemotherapy; infections remain the leading cause of morbidity and mortality in myelosuppressed leukemia patients. The current standard of care is to provide patients with broad-spectrum antibiotic, antifungal and antiviral therapy; however resistance to available anti-infective agents is increasing. Transfusion of functional non-irradiated allogeneic granulocytes to neutropenic leukemia patients may treat, delay or prevent infections in patients with leukemia, and importantly may also have anti-leukemia benefits. Patients treated at MD Anderson Cancer Center with a diagnosis of AML undergoing front-line AML therapy were eligible. Patients were required to be free of signs and symptoms of infection at the time of study entry, and have sufficient volunteer donors to administer prophylactic white cell transfusions approximately twice a week for six weeks. Allogeneic white cell transfusions (≥ 4 x 10¹⁰ cells per transfusion) were administered every 3-4 days during the induction chemotherapy cycle, so long as patients remained neutropenic with an absolute neutrophil count < 500. Prophylactic transfusions continued until the time of sustained ANC recovery, initiation of a new treatment regimen, or after the completion of 6 weeks on protocol. Herein we provide the results of the first 21 patients. Median age was 67 (range 23-78); 12 patients were male and 9 were female. All patients were enrolled at the time of initiation of AML induction therapy. Seven patients had a diagnosis of therapy-related AML (6 with an antecedent hematologic disorder and 1 with prior solid malignancy). Various treatment regimens were administered and are displayed in Table 1, along with cytogenetic and MD Anderson prognostic model classification. Patients received a median of 5 transfusions (range 0 – 11). Of 21 patients, 1 withdrew consent prior to the first transfusion, and 3 patients discontinued transfusions prior to the end of study (due to a diagnosis of pneumonia in one with potential concern for increased pulmonary toxicity with continued transfusions, and two at patient requests due to fevers and myalgias post transfusions). Median time to ANC recovery was 38 days (range 14 – 137) and platelet recovery 29 days (range 12 – 160), consistent with the elderly population and the allotted treatment regimens. All patients experienced at least one neutropenic fever, often within 48 hours of white cell administration. Documented infections included 2 instances of bacteremia (1 streptococcal and 1 E. coli), 2 urinary tract infections (both coagulase negative staphylococci), 8 cases of pneumonia (1 documented E. coli, 7 culture-negative and presumed fungal pneumonia per imaging). There was one patient with neutropenic colitis per imaging. There were no induction-related deaths. 8-week mortality was 5% (n=1) and 12-week mortality was 20% (n=4). With a median follow-up time on study of 20.3 weeks, overall survival is 67% with a median survival which has not yet been reached (Figure 1). Overall response to initial induction chemotherapy was 67% (9 CR, 1 CRi, 4 PR). A total of 15 patients (71%) ultimately attained a CR (after the first cycle or with additional cycles of therapy), and 4 patients received a stem cell transplant at the time of CR/CRi. In conclusion, prophylactic transfusion of allogeneic non-irradiated white blood cells for newly diagnosed AML patients during induction chemotherapy was associated with a decreased incidence of life-threatening infections, decreased induction mortality (6-week OS of 100%), and may also lead to improved remission rates and overall survival. This feasibility study has been expanded to enroll a total of 50 patients, with updated results to be provided at the annual meeting. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Red blood cells (RBC) undergo biochemical and morphologic changes during storage and the changes known as “storage lesion” have raised concerns that RBCs stored for lengthy periods could increase mortality risks in patients receiving transfusions.We sought to analyze the association between aged RBCs and intensive care unit admissions, short-term and long-term survivals of patients undergoing hematopoietic stem cell transplantation (HSCT) and the association between overall survival and the number of RBCs transfused up to 100 days after HSCT. We reviewed the data from the Blood Bank database files from November 2008 to December 2009 for 334HSCT patientswho were alive 100 days after HSCT at the University of Texas MD Anderson Cancer Center. The patients were categorized into ICU vs. non-ICU patients after HSCT. We compared the age of RBCs, units of RBCs transfused and patients admitted to the ICU vs. non-ICU patients after HSCT. We found that the number of RBCs transfused correlated with overall survival and not with the age of the red cells transfused before and after HSCT.For both categories of patients: ICU vs. non-ICU patients, our retrospective analysis noted that those who received the most RBC transfusions had the worst survival. Received: 27 October, 2017; Accepted: 09 November, 2017; Published: 29 December, 2017 *Corresponding author: Fleur M Aung, Department of Laboratory Medicine, Unit 0800, 1515 Holcombe Blvd, Houston, Texas 75088, USA, Tel: (713) 792-8630, Fax: (713) 792-2634; E-mail: fmaung@mdanderson.org Symbiosis www.symbiosisonline.org www.symbiosisonlinepublishing.com Symbiosis Group * Corresponding author email: fmaung@mdanderson.org Introduction Red blood cells (RBCs) undergo well-documented biochemical and morphologic changes during storage. These “storage lesions,” 1-14and have raised concerns that stored older RBCs could increase mortality risk in patients receiving RBC transfusion. Donor RBCs contain a mixed population of cells ranging from newly formed reticulocytes to 120-day-old RBCs at the time of donation, and it has not been established with certainty whetherstorage lesions affect different stages of maturity equally.9Prolong storage of RBCs results in increased oxygen affinity after 14 days of storage due to progressive consumption of the high-energy phosphate (2,3-diphophoglycerate 2,3-DPG), decreased activity of most enzymes involved in energy metabolism (metabolic dysregulation), accumulation of reactive oxygen species (ROS), protein fragmentation and impairment of the band 3 transport metabolon, preferential loss of certain lipids and enrichment of others in the membrane fraction with exacerbation of membrane loss (vesiculation). There is uncertainty to the actual effectiveness and damage that allogeneic blood can cause to the transfused patient.13, 14Theprimary aim of blood storage in the United States has been to extend the storage life of a preciousand perishable product with the use of additive storage solutions (AS-1, AS-3, AS-5 or AS-7) to maximize its availability such as the using the oldest stored blood first to avoid wasting the blood. However, the clinical consequences of transfusion of aged RBCs remain unclear for patients undergoing hematopoietic stem cell transplantation (HSCT). Objectives The primary objective of the current study was to analyze the association between the age of RBCs transfused before and after HSCT and intensive care unit (ICU) admission as well as short-term (100 days after transplant) and long-term (>100 days after transplant) overall survival rates after HSCT. The secondary objective was to analyze the association between overallsurvival ratesand the number of RBC units transfused up to 100 days after HSCT. Methods Study Design The retrospective study design was approved by The University of TexasMD Anderson Cancer Center Institutional Review Board. Data were collected from the Blood Bank and Stem Cell and Cellular Therapy data-basesof our institution as well as patients’ electronic medical records.The 2008-2009 Blood Bank records were reviewed for adult and pediatric patients who had undergone HSCT. All data onRBCs transfused at MD AndersonCancer Center before (D-100 to D-1) and after (D0 to D+100) were included. Patients who had received a mixture of newer and agedRBCs were included in the study. For our analysis, the age of RBCs transfused was grouped using three cutoff points:

Allogeneic granulocyte transfusion has evolved into a viable therapeutic option for immunocompromised severely neutropenic leukemic patients and those with hematopoietic stem cell transplant with life-threatening bacterial and fungal infections. The collection of larger cell doses of granulocyte concentrates (GCs) has been facilitated by the stimulation of donors with granulocyte colony stimulating factor (G-CSF) and dexamethasone. The synergistic effect of G-CSF and dexamethasone has allowed the collection of larger cell doses of GCs and its use has increased steadily. This has allowed us to split the high-yield GC products and facilitated distribution of the split GC products to a second or third patient who needs GCs but lacks donors. The main objective of this article was to present our rationale for splitting GC products and how the split GC units were transfused to multiple patients. We believe that split GCs are as equally effective as unsplit GCs and that multiple patients benefit from splitting GCs.