bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of bortezomib added to standard daunorubicin and cytarabine during induction therapy and to intermediate-dose cytarabine (Int-DAC) for consolidation in patients with previously untreated acute myeloid leukemia (AML) age 60-75 years: CALGB study 10502.
Authors: Attar Eyal C. , Johnson Jeffrey L. , Amrein Philip C. , Lozanski Gerard , Wadleigh Martha , DeAngelo Daniel J. , Kolitz Jonathan E. , Powell Bayard L. , Voorhees Peter Michael , Wang Eunice S. , Blum William G. , Marcucci Guido , Bloomfield Clara D. , Moser Barry K , Stone Richard M. , Larson Richard A. ,   CALGB
Published: March 2020

6526 Background: We conducted a clinical trial to determine the complete remission (CR) rate in older AML patients treated with bortezomib (Bz) plus daunorubicin and cytarabine induction therapy and the maximal tolerated dose (MTD) of Bz when added to Int-DAC consolidation therapy. Methods: Ninety-five adults (60-75 yrs old; median, 67) with previously untreated AML (including therapy-related and prior MDS) received Bz 1.3 mg/m2 IV on days 1, 4, 8 and 11 with daunorubicin 60 mg/m2 on days 1-3 and cytarabine 100 mg/m2 by continuous IV infusion on days 1-7. Patients who achieved a CR received 2 courses of consolidation chemotherapy with cytarabine 2 gm/m2 over 3 hours on days 1-5 (Int-DAC) with Bz administered on days 1, 4, 8 and 11. Three cohorts with escalating dose levels of Bz were tested (0.7, 1.0, and 1.3 mg/m2). Dose limiting toxicities were assessed during the first cycle of consolidation. Predictors of response, including CD74 expression, were assessed. Results: The CR frequency was 65% (62/95). An additional 4% (4/95) achieved CR with incomplete platelet recovery. The CR rate according to ELN Genetic Groups was 90% (9/10) for favorable, 71% (12/17) for Int-I, 52% (17/33) for Int-II, and 46% (5/11) for adverse. Six patients had grade 3 sensory neuropathy. There were 6 treatment-related deaths during cycle 1 of induction and 2 during cycle 2. Bz plus Int-DAC proved tolerable at the highest dose tested. The median disease-free (DFS) and overall survivals (OS) for patients on this study were 8.2 and 12.1 months, respectively. Lower CD74 expression was associated with CR/CRp (p=.04) but not with DFS or OS. Conclusions: The addition of Bz 1.3 mg/m2 IV on days 1, 4, 8, and 11 to standard “3 + 7” daunorubicin and cytarabine induction chemotherapy for AML is well tolerated and results in a remission rate at least as high as would be expected with ”3+7” alone in older patients. The maximum tested dose of Bz given in combination with Int-DAC for remission consolidation was 1.3 mg/m2 and proved to be tolerable. Further testing of this regimen in a phase III study is planned.
Immune-reconstitution after combined haploidentical and umbilical cord blood transplantation.
Authors: van Besien Koen , Jain Nitin , Schouten Viviane , Liu Hongtao , Ulaszek Jodie , Wickrema Amittha , Artz Andrew S. 
Published: March 2020

6535^ Background: Umbilical cord blood (UCB) stem cells are frequently employed for allogeneic stem cell transplantation. However, delayed myeloid and lymphoid immune-reconstitution with UCB transplantation leads to increased risk of infections. We recently reported a pilot study combining UCB with a HLA haploidentical donor (Liu et al. Blood. 2011). Here, we report the immune reconstitution after the haploidentical-cord blood transplantation. Methods: Pts received reduced-intensity conditioning with fludarabine/melphalan/rATG and were assessed for lymphocyte subsets, serological response to pneumococcal vaccination, Cylex Immuknow assay which measures amount of ATP secreted by CD4 lymphocytes on stimulation by PHA, and T-cell spectratyping. Results: 45 pts, enrolled between 01/2007 and 04/2011, are included in this analysis. The median absolute lymphocyte subset counts at serial time-points are shown in the Table. The median absolute values of CD3, CD4 and CD8 counts remained below the normal range throughout the 1st year post-transplant. The NK-cells and B-cells reached normal range by day 30 and day 100, respectively. Serological response to pneumococcal vaccination was seen in 7/17 (defined as seroconversion or >3 fold rise in titers of serotype 14, 19F and 23F) evaluable pts at a median 74 days after vaccination. Immuknow assay showed that 6/6 pts tested within first 30 days of transplant had low values whereas 5/8 tested >1yr had normal/high values. Of the 9 pts who were assessed for T-cell receptor repertoire by T-cell spectratyping, 7 had a polyclonal, complex T cell repertoire similar to healthy controls. CMV viremia requiring treatment occurred in 14 patients. EBV reactivation occurred in 18 pts and 5 developed PTLD 68 to 314 days after transplant. Conclusions: Haploidentical cord blood transplantation leads to rapid myeloid recovery and recovery of B-cell and NK cell numbers. T-cell recovery is more delayed, but at 1-year most pts have a polyclonal T cell repertoire and robust T-cell responses. [Table: see text]
Low day 100 transplant-related mortality (TRM) and relapse rate following clofarabine (CLO) in combination with cytarabine, total body irradiation (TBI), and allogeneic stem cell transplantation (AlloSCT) in children, adolescents, and young adults (CAYA) with poor-risk acute leukemia.
Authors: Radhakrishnan Kavita , Ricci Angela M , Geyer Mark B , Harrison Lauren , Duffy Deirdre , Ozkaynak Mehmet Fevzi , Satwani Prakash , Cheerva Alexandra C , Talano Julie , Moore Theodore , Gillio Alfred P , Wada Randal K. , Baxter-Lowe Lee Ann , Cairo Mitchell S. 
Published: March 2020

6537 Background: CAYA with ALL or AML in third complete remission (CR3), refractory relapse (RR) or induction failure (IF) have an extremely poor prognosis, <20% EFS (Gaynon, BJH, 2005;Wells, JCO, 2003). CLO, an inhibitor of DNA polymerase and ribonucleotide reductase, has significant activity in CAYA with relapsed ALL/AML (Jeha, JCO 2006,2009) and synergy with cytarabine (Faderl, Blood, 2005). We sought to determine safety, day-100 TRM, and overall survival (OS) associated with CLO, cytarabine and TBI followed by AlloSCT in CAYA with poor-risk ALL/AML. Methods: This is a multi-center phase I/II trial of a novel conditioning regimen of CLO (dose escalation: 40mg/m2 [n=3], 46 mg/m2 [n=3], 52 mg/m2 [n=19]) x5d, sequential (4 hrs later) cytarabine 1000 mg/m2 x6d and TBI (1200cGy) followed by AlloSCT from matched related or unrelated donors in CAYA with ALL/AML in CR3, RR or IF. Patients with unrelated donors received R-ATG. GVHD prophylaxis consisted of tacrolimus and MMF (Bhatia/Cairo, BBMT, 2009). Kaplan-Meier method was used to determine the probabilities of engraftment, GVHD, TRM and OS. Results: 25 pts, median age: 11.3 yrs (1.5-20.7); M:F: 19:6, ALL/AML: 22:3 (10 CR3, 3 RR, 12 IF), 10 related donors, 15 unrelated donors (9 BM/PBSCs, 6 UCB). Median TNC and CD34 dose was 4.47x108/kg and 4.84x106/kg for BM/PBSCs and 4.0x107/kg and 2.8x105/kg for UCB, respectively. Probabilities of neutrophil, platelet engraftment and grade II-IV aGVHD were 100%, 92.9% and 47.5%, respectively. CLO dose was tolerable at 52mg/m2/d x5d without dose limiting toxicity. Probability of Day 100 TRM was only 4.3%. Probability of 1-yr PFS and OS were 51% (CI95: 28-71%), and 43% (CI95: 22-63%) respectively. Conclusions: Preliminary results suggest this novel regimen followed by AlloSCT is safe and well tolerated in CAYA with poor-risk ALL/ AML with CLO dose 52 mg/m2. Results are encouraging with respect to low risk of day 100 TRM and leukemic relapse associated with this conditioning regimen in this poor-risk population.
Single center experience treating adults with FLT3-mutated acute myeloid leukemia (AML).
Authors: Halpern Anna B. , Kunnavakkum Rangesh , Joseph Loren , Stock Wendy , Odenike Olatoyosi , Godley Lucy A. , Thirman Michael J. , Artz Andrew S. , Sipkins Dorothy , Liu Hongtao , Raca Gordana , Le Beau Michelle M. , Larson Richard A. 
Published: March 2020

6562 Background: Activating mutations of the fms-like tyrosine kinase-3 (FLT3) gene are common in AML. Depending upon the allele mutation fraction, these mutations have been associated with poor outcomes in prospective multi-center trials. Methods: We studied a consecutive series of adults with FLT3-mutated leukemia at our institution since we began testing in 2006 through Sept 2011. Clinical characteristics and patient (pt) outcomes were extracted through a retrospective chart review and analyzed using logistic regression and Cox proportional hazard models. Results: We identified 73 pts with a FLT3 mutation (71 with AML and 2 with myelodysplasia with <20% blasts). 62 (85%) presented to our institution at initial diagnosis; 11 (15%) were diagnosed elsewhere and seen by us only at relapse. 44 (60%) were men and 51 (70%) were white. Median age was 62 yrs (range, 19-90); 48% were <60 yrs old. 63 (86%) had an internal tandem duplication (ITD) mutation, 9 (12%) had the D835 point mutation (TKD), and 1 had both. An NPM1 mutation was also present in 26 (36%). Median white blood cell count at diagnosis was 53 x 103/µL (range, 0.8 - 466). 34 (47%) had monocytic morphology (M4 or M5). 8 (11%) pts had favorable karyotypes; 50 (68%) had normal karyotypes; 13 (18%) had unfavorable karyotypes. 58 (79%) received standard induction therapy (anthracycline + cytarabine for most; ATRA + arsenic trioxide for 3 with APL); 46/58 (79%) achieved a complete remission (CR). Including the 15 pts who received only low intensity therapies, 40/64 (63%) with an ITD and 6/9 (67%) with a TKD mutation achieved CR. 31 (42%) pts received an allogeneic transplant, 21 in first CR (CR1) and 10 after relapse. Median overall survival (OS) for the whole group was 417 days (95% CI: 291-780); it was 684 days for those diagnosed at our institution and 285 days for those seen only after relapse. Median disease-free survival (DFS) in CR1 was 417 days. Median OS for pts transplanted in CR1 was 1262 days from initial diagnosis and 416 days for those transplanted after relapse. DFS did not differ with or without a transplant (median, 526 vs 305 days; p=.64). Conclusions: FLT3-mutated AML is heterogeneous. Our single center experience is similar to that reported from multi-center trials.
Mitoxantrone and etoposide for acute myeloid leukemia in first relapse.
Authors: Im Annie P. , McLaughlin Brian Thomas , Lin Yan , Raptis Anastasios , Agha Mounzer E. , Hou Jing-Zhou , Redner Robert , Boyiadzis Michael 
Published: March 2020

6563 Background: Achievement of complete remission (CR) for relapsed acute myeloid leukemia (AML) is crucial for improving prognosis and survival. However, there are no established standard therapies for AML in first relapse. Our purpose was to evaluate the efficacy and toxicity of a regimen of mitoxantrone and etoposide for relapsed AML and assess factors that may be predictive of response. Methods: Patients were identified from a database of patients with AML treated at the University of Pittsburgh Cancer Institute from 1999-2011. Subjects were patients with AML in first relapse treated with mitoxantrone 10mg/m2 and etoposide 100mg/m2 daily on days 1-5. An exploratory analysis was performed to determine CR rate, overall survival, toxicities, and predictive factors. Results: The study cohort consisted of 66 patients with AML in first relapse, median age 56.5 years (range 21-75). At time of relapse, 12 were classified as having poor cytogenetics, 39 had intermediate cytogenetics, and 5 had favorable cytogenetics (9 patients did not have karyotype analysis). 34.8% (23/66) of patients achieved CR, and 16 went on to have allogeneic hematopoietic cell transplantation. Patients with favorable, intermediate, and poor cytogenetics had CR rates of 60% (3/5), 35.9% (14/39) and 50% (6/12), respectively. Median survival was 8.1 months (95% CI 5.1-11.9). Patients who achieved CR had significantly improved survival compared to those who did not (20.0 months vs. 5.2 months, p<0.0001). Median days to neutrophil and platelet recovery were 37.5 (range 19-81) and 40 (range 21-81), respectively. There were no grade 3/4 hepatic toxicities. The 4-week and 8-week mortality rates were 4.5% and 13.6%, respectively. Duration of first remission greater than 12 months was predictive of CR (p<0.001), whereas age, cytogenetics, bone marrow blast percentage, and white blood cell count at relapse were not. Conclusions: In an unselected heterogeneous patient population with relapsed AML, mitoxantrone and etoposide was an effective regimen with acceptable toxicity, and those who achieved CR had significantly improved overall survival. Duration of first remission greater than 12 months was the only predictive factor, and response was seen among all cytogenetic risk groups.
Incidence of second and secondary malignancies in patients with CLL: A single institution experience.
Authors: Dalia Samir , Chavez Julio C. , Domingo Gelenis , Carballido Estrella M. , Aguayo-Hiraldo Paibel I. , Sweet Kendra Lynn , Crescentini Robert M. , Sokol Lubosh , Bello Celeste M. , Cultrera Jennifer L. , Shah Bijal D. , Lancet Jeffrey E. , Komrokji Rami S. , Sotomayor Eduardo M. , Pinilla-Ibarz Javier 
Published: March 2020

6568 Background: Patients with chronic lymphocytic leukemia (CLL) have a higher incidence of second malignancies than the general population with one study showing the risk at 2.2 times the general popualtion. The increased incidence is thought to be due to immunosupression which results in decreased cell surveillance and proliferation of malignant cells. Our study aims to present the rate of second malignancies by cancer type in patients with CLL at our institution. Methods: The Moffitt Cancer Center Total Cancer Care (TCC) database was used to identify patients who had a diagnosis of CLL between January 1993-December 2009. Individual charts were reviewed to confirm the diagnosis of CLL, collect demographic data, and to assess for the presence of a second malignancy under an IRB approved protocol. A second malignancy was defined as another malignancy or transformation of CLL reported in the medical record. Second malignancy data was placed in three categories; skin cancers, solid tumor malignancy, and hematologic malignancy. Results: 546 CLL patients were included in the study. Median age was 62.5 years. 84 (43%) were Stage 0 and 62 (32%) were Stage 1 RAI at diagnosis indicating earlier disease. 266 (49%) patients had a second or secondary malignancy. A total of 304 cancers were identified. 14% of patients had more than one malignancy. Melanoma was identified in 44 (16.5%) patients and non-melanoma skin cancer was identified in 54 (20%). Lung cancer was identified as the most frequent solid tumor malignancy with 36 (13.5%) cases, followed by prostate (35), breast (21), colorectal (15), and bladder (14). 10 patients had a Richter’s transformation of their CLL. 26 patients developed either myelodysplastic syndrome or acute myelogenous leukemia. Conclusions: Second malignancies are frequent in CLL patients. Immunosupression, increased UV light exposure, longer life expectancy in low risk CLL, and tertiary cancer center referral bias are likely reasons for these increased rates. Further research is needed to identify the precise mechanism which cause patients with CLL to have higher rates of second malignancies and to identify if there is an increased risk of a specific type of malignancy in patients with CLL.
Induction chemotherapy with high-dose cytarabine and mitoxantrone in elderly acute myeloid leukemia (AML) patients.
Authors: Ramanathan Muthalagu , Cerny Jan , Raffel Glen , Walsh William Vincent , Woda Bruce , Miron Patricia , Nath Rajneesh 
Published: March 2020

6569 Background: Induction chemotherapy is often not used in elderly patients with AML due to poor prognosis and inferior outcomes. We present here our experience in treating 20 patients age>70yrs with an induction regimen consisting of high dose cytarabine and mitoxantrone (HiDAC/MITO). Methods: We analyzed all patients age > 70 years who underwent induction with HiDAC/MITO at our institution from January 2009 to December 2011. 20 patients received HiDAC at 3 g/m2 daily on days 1-5 and mitoxantrone 80mg/m2* once on day 2(*one patient received 60mg/m2). The end points analyzed were complete remission (CR) and induction mortality at day 30, overall survival and progression free survival. Results: Median age was 75 years (70-83). 11 (55%) patients were male and 9 (45%) patients were female. Median duration of follow up of 10 (50%) patients who are still alive at the time of this analysis is 439 days (38-1095). High risk cytogenetics was noted in 11 (55%) patients including two patients with FLT3 mutated cytogenetics. Intermediate risk cytogenetics was noted in 9 (45%) patients including 2 patients with NPM1 mutated FLT 3 WT AML. 12 (60%) patients had secondary AML. The age unadjusted charlson comorbidity index (CCI) was 3 (2-9). 15 (75%) patients attained CR and 3 (15%) patients attained a CR with incomplete platelet recovery (CRp). CR +CRp rate was 90%. Two (10%) patients were refractory to induction and 5 (25%) patients relapsed at a later time point after induction. Median duration of hospital stay was 28 days (22-60). Median time to ANC >1K was 23.5 days (18-29), excluding 2 patients who had refractory disease. Median time to platelet recovery >100K was 25 days (20-44), excluding 2 patients with refractory disease and 3 patients with CRp. Regimen related toxicity included cardiac toxicity in 4 patients and bacteremia in 11 patients. Five (25%) patients were consolidated with stem cell transplant. Median overall survival (OS) was 151 days (38-1095) and progression free survival (PFS) was 131 days (38-1049). Conclusions: HiDAC/MITO induction is well tolerated by elderly patients with AML and demonstrates an overall response (CR+CRp) rate of 90% coupled with no induction deaths.
A simple but effective model to decrease early deaths in acute promyelocytic leukemia (APL).
Authors: Jillella Anand P. , Sadek Ibrahim , Morrison Devi , Natrajan Kavita , Awan Farrukh Tauseef , Kolhe Ravindra , Kota Vamsi 
Published: March 2020

6573 Background: Recent reports suggest that approximately 30% of patients with APL die during induction. This has been confirmed in large population-based studies in Sweden and the US. A recent analysis of SEER data from 13 population-based cancer registries with 1400 APL patients in the US showed that 17% of all patients and 24% of patients greater than 55 years of age die within one month of diagnosis. The most common causes of death are bleeding, infection, differentiation syndrome and multi-organ failure. Patients who survive induction have an excellent cure rate with few late relapses. Hence, decreasing early deaths is a high priority both at experienced as well as smaller centers with limited leukemia treatment experience in this highly curable disease. Methods: At Georgia Health Sciences University, between 7/2005 and 6/2009, 19 patients were diagnosed with APL. Seven patients (5 high-risk and 2 low-risk) died during induction resulting in an unusually high mortality rate of 37%. All patients who survived induction are still in remission at present. The high early death rate prompted us to develop a simple, 2 page treatment algorithm that focuses on quick diagnosis, prompt initiation of therapy, and proactive and aggressive management of all the major causes of death during induction. We also made our treatment protocol available to smaller treatment centers and helped the treating oncologists manage the patient during the first few days after diagnosis. Results: From 11/2010 to 12/2011, we treated 4 patients at GHSU and helped manage 4 patients at 2 outreach sites. The age range was 30 to 60; two patients were high-risk, 5 intermediate- and one low-risk. There were no deaths during induction and all eight patients proceeded to consolidation treatment. Conclusions: While we recognize that this is a small cohort, our own experience and a similar approach pioneered by investigators in Brazil clearly shows this to be an effective intervention to decrease early deaths in APL. We believe our experience warrants large scale implementation of our protocol in an attempt to reduce early APL mortality.
Cancer testicular antigens as a prognostic markers of chronic lymphocytic leukemia.
Authors: Chavez Julio C. , Domingo Gelenis , Dalia Samir , Dubovsky Jason A. , Berchmans Emmanuel , Powers John Joseph , Sweet Kendra Lynn , Crescentini Robert M. , Sotomayor Eduardo M. , Komrokji Rami S. , Pinilla-Ibarz Javier 
Published: March 2020

6575 Background: CLL is the most common leukemia in adults and has a variable course and prognosis. Clinical staging systems and the use of biomarkers such as cytogenetics and the IGVH mutational status remain the gold standard for stratification. Cancer testis antigens (CTAs) expression analyses have shown prognostic impact in other hematological malignancies such as acute leukemias and multiple myeloma. With the analysis of CTAs we aim to discover additional molecular markers that can help us predict the clinical course and outcome in CLL patients. Methods: We analyzed the expression by RT-PCR of 39 known CTAs including members of the MAGE, GAGE, MAD-CT and SSX CTAs families in a group of 59 CLL patients seen at our institution. The Moffitt Cancer Center Total Cancer Care (TCC) database was used to correlated these findings with relevant clinical and molecular markers such as Rai stage, demographic data, initial WBC count, IGVH mutational status, CD38 expression, cytogenetics by FISH analysis and treatment outcomes. Overall survival (OS) and progression free survival (PFS) were calculated using Kaplan Meier curves with a SPSS statistical software Results: Deletion 13q was the most common gene abnormality in 35/59 (59.3%). 29/59 (49.1%) required at least one line of treatment. MAGE family CTAs were present in 53/59 (83.9%), MAD-CT in 24/59 (40.7%), SSX in 14/59 (23.7%) and GAGE in 12/59(20.3%). 35/59 (59.3%) CLL patients expressed 2 or more MAGE family CTAs. No differences were noted in the Rai staging, initial white blood cell count, B symptoms, extranodal disease, presence of CD38, or unmutated IVGH. The OS was not significantly different among all CTAs families with a tendency towards a better OS those expressing the SSX family (p=0.63). Additionally, CLL patients with single expression of MAD-CT1 (p=0.05) and MAGE-B2 (p=0.038) antigens correlated with improved survival. Conclusions: Patients with SSX family have a trend towards improved survival. When analyzed by individual antigen, MAD-CT1 and MAGE-B2 expression was associated with improved survival. Further studies with a larger number of patients are needed to assess the real value of the expression of CTAs in CLL.