bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low risk for symptomatic venous thromboembolic events (vte) during cytokine administration for peripheral blood stem cell mobilization
Authors: Naina H. V. , Pruthi R. K. , Litzow M. R. , Ansell S. M. , Dispenzieri A. , Hogan W. J. , Gertz M. A. , Elliott M. A. , Gastineau D. A. , Kumar S. K. 
Published: August 2020

7039 Background: Erythropoiesis-stimulating agents are known to increase the risk for VTE events, especially in patients with underlying malignancies. However, there is a paucity of information on other hematopoietic growth factors such as granulocyte colony-stimulating factor (GSCF) granulocyte-macrophage colony stimulating factor (GM-CSF) AMD 3001 and risk for VTE. Methods: Between January 2000 and October 2008, a total of 631 patients underwent peripheral blood stem cell mobilization (PBSCM) using either GCSF, GMCSF, cyclophosphamide, AMD 3100, or with any of the above combination. We included only patients with a diagnosis of AL amyloidosis (AL), multiple myeloma (MM) Hodgkin's lymphoma (HL) and non Hodgkin's lymphoma (NHL). Patients’ demographic details and diagnosis of VTE were collected from electronic medical records. Results: Of the 631 patients who underwent PBSCM the median age of the patients was 57 years (range 17–77). 448 patients (71%) received single agent GCSF, 82 (13%) received combination of GMCSF and cyclophosphamide, 52 (8%) received cyclophosphamide and GCSF, 30 patients received a combination of GMCSF and GCSF, 10 (1.5%) patients received GCSF and AMD 3100. Of the 631 patients, 278 (44%) MM, 209 (33%) NHL, 114 (18%) AL, and 20 (3%) had HL. We found 7 (1.1%) patients with symptomatic VTE occurring between administration of growth factors and stem cell transplant. The median duration from the administration of growth factors to detection of VTE was 5 days (range 1–30). Two AL,3 MM and 2 NHL. Of the 7 patients, 2 patients had pulmonary embolism and 1 patient developed deep vein thrombosis. Two patients with AL developed heparin induced thrombocytopenia (HIT). The remaining 4 patients developed symptomatic catheter related thrombosis. Only 1 patient had past history of VTE. Of the 7 patients, 5 received GCSF alone, 1 received GMCSF, and cyclophosphamide, 1 received GCSF and cyclophosphamide. Of the 4 patients who developed catheter related thrombosis, catheter was removed in 2 patients. None of the patients developed VTE related morality. Conclusions: The risk for symptomatic VTE during PBSCM is low. HIT should be considered as a possible cause for VTE in patients undergoing PBSCM. No significant financial relationships to disclose.
Outpatient versus inpatient autologous stem cell transplantation for malignant hematologic disorders
Authors: Ghavamzadeh A. , Allahyari A. , Alimoghaddam K. , Karimi A. , Shamshiri A. , Abolhasani R. , Manookian A. , Asadi M. , Khatami F. 
Published: August 2020

7042 Background: High-dose chemotherapy with autologous stem cell support is utilized for the treatment of a variety of malignancies including Hodgkin/non-Hodgkins lymphoma and acute leukemias. The aim of this study was to compare the time of engraftment and mortality rate and cost of neutropenic treatment in outpatient versus inpatient autologous stem cell transplantation (SCT). Methods: 9 outpatients (5 HL, 2 NHL, and 2 AML) were compared with 32 inpatients (15 HL, 8 NHL, and 9 AML; for whom the outpatient facilities were not ready) from May 2008 to December 2008. All patients were below 45 yrs; median age for outpatients and inpatients were 26 and 30 years respectively. Also all the patients were in complete remission and without significant organ failure. They received conditioning regimen (CEAM for NHL and HL, busulfan and etoposide for AML) and stem cell infusion in hospital. The day after SCT, outpatient group were discharged and followed by outpatient SCT team, and to be re-hospitalized in case of febrile neutropenia, after sepsis workup and performing chest x-ray, they were received the first dose of antibiotic in hospital and treatment continued in home. Results: For outpatients and inpatients, median time to WBC engraftment was 11 and 12 days (p = 0.03), time to PLT engraftment was 15 and 25 days (p = 0.20), number of transfused single donor PLT was 3 and 4.5 units (p = 0.21), duration of neutropenic fever was 6 and 9 days (p = 0.001), duration of hospitalization (after SCT) 0 and 16 (p < 0.001), respectively. All outpatients are alive and 3 patients from other group died between days +35 and +100 after SCT due to transplantation complications. For inpatient group the cost of drugs, just for neutropenic fever antibiotic therapy was six times than outpatient group. Conclusions: Results show that out-patient autologous SCT in malignant hematologic disorders is feasible and comparable with inpatient protocol. We are waiting for more patients and longer follow-up for future conclusions. No significant financial relationships to disclose.
Expression of different isoforms of the B-cell mutator activation-induced cytidine deaminase (AID) in BCR-ABL1-positive acute lymphoblastic leukemia (ALL) patients
Authors: Lonetti A. , Iacobucci I. , Ferrari A. , Messina M. , Cilloni D. , Soverini S. , Papayannidis C. , Baccarani M. , Foà R. , Martinelli G. 
Published: August 2020

7049 Since the activation-induced cytidine deaminase (AID) enzyme can target non-immunoglobulin (Ig) genes and may even act as a genome-wide mutator, we investigated AID expression in BCR-ABL1-positive ALL and in chronic myeloid leukemia (CML) at the time of progression to blast crisis. On the 61 de novo adult BCR-ABL1-positive ALL patients (pts), AID mRNA and protein were detected in 36 (59%); their expression correlated with BCR-ABL1 transcript levels and disappeared after treatment with tyrosine kinase inhibitors at the time of remission. AID expression was also found in lymphoid blast crisis CML (50%), but not in myeloid lineage or in chronic phase CML. Different isoforms of AID were identified: 13/61 (21%) pts expressed the full-length isoform; 19/61 (31%) co-expressed the wild-type and different AID splice variants with deaminase activity (AIDΔE4a, with a 30 bp deletion of exon 4; AIDΔE4, with the exon 4 deletion; AIDins3, with the retention of intron 3–4); 4/61 (7%) expressed the AIDΔE3-E4 isoform without deaminase activity (deletion of exons 2 and 3). To investigate whether AID introduces DNA-single strand breaks, we performed a genome wide analysis by 250K NspI single nucleotide polymorphism (SNP) array. Patients who expressed wild-type AID had a higher number of alterations compared to AID-negative (median copy number alteration of 14 versus 4. respectively, p < 0.03). Recurring copy number abnormalities were identified in genes with an established role in leukemogenesis, such as IKZF1, CDKN2A, CDKN2B, PAX5, MELK, BTG1, and MDS1. Our findings show that BCR-ABL1-positive ALL cells aberrantly express different isoforms of AID that can act as mutator outside the Ig gene loci in promoting genetic instability in leukemia cells. Supported by: European LeukemiaNet, AIL, AIRC, FIRB 2006, Fondazione del Monte di Bologna e Ravenna, Strategico di Ateneo, GIMEMA Onlus. No significant financial relationships to disclose.
A phase III study exploring various doses of imatinib (IM) or IM in combination for newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML) patients (pts): Results of an interim analysis of the SPIRIT trial of French CML group
Authors: Nicolini F. E. , Mahon F. X. , Guilhot J. , Buzyn A. , Tulliez M. , Berthou C. , Christian B. , Guyotat D. , Preudhomme C. , Guilhot F. 
Published: August 2020

7058 Background: IM 400 mg daily is the front-line treatment of CP CML, but provides only 50% major molecular responses (MMR) at 18 months (Mo). We designed a phase III randomized multicenter open-label prospective trial comparing IM 400 mg/d (n=159) with 3 experimental arms: IM 600 mg/d (n=160), IM 400 mg/d + s/c cytarabine (Ara-C), (20 mg/m2/d, d15–28 of 28-day cycles) (n=158) and IM 400 mg/d + s/c Peg-IFN2a (90 μg/wk) (n=159). Pts were allocated at a 1.1.1.1 ratio, stratified by Sokal risk groups. Molecular assessments were centralized and blinded. An interim analysis of 636 pts was planned based on an IS BCR-ABL/ABL ratio <0.01% (Optimal Molecular Response, OMR) at 1 year (α=0.85%, β=10%). Results: 636 pts were recruited between 9/2003 and 10/2007, median age 51 (18–78) yrs, 62% males, median follow-up for alive pts 36 (12–62) Mo. At 3 Mo, 88% of pts achieved complete hematologic response. Complete cytogenetic response (CCyR), MMR and OMR rates are presented (Table). MMR rates at 6 and 12 Mo were higher for IM-PegIFN as compared to IM-400 (p<10-3). At 18 Mo the cumulative OMR rates were 22% (IM-400), 28% (IM-600), 25% (IM-Ara-c), 43% (IM-PegIFN). Grade 3/4 neutropenia and/or thrombocytopenia occurred during the first year in 8% IM-400, 14% IM-600, 41% IM-Ara-C and 40% IM-PegIFN arms respectively. Grade 3/4 non-hematological toxicities occurred in 19% IM-400 (edemas, muscle cramps), 30% IM-600, 27% IM-Ara-C (diarrhea) and 31% IM-PegIFN pts (skin rashes, asthenia). Within the first 12 Mo, discontinuation of experimental treatment occurred in 8% IM-600, 39% Ara-C and 45% PegIFN pts. Conclusions: Although a significant number of pts reduced or stopped PegIFN within the first year, significant improvements in molecular response rates were observed in the IM-Peg IFN arm and may translate into survival benefit. [Table: see text] [Table: see text]
Phase I study results of nanomolecular liposomal annamycin in refractory ALL
Authors: Shepard R. C. , Talluto C. C. , Jacob G. 
Published: August 2020

7066 Background: There continues to be no effective second-line therapy for refractory AML or ALL and the cure rate with current therapy has not significantly improved in decades. The first-line therapy for adult AML has remained the same 7 + 3 that it was a generation ago. Annamycin was specifically synthesized to overcome MDR and to have little to no cardiac toxicity when given as a nanomolecular liposomal entity. Methods: We performed a phase I multi-center, open-label, MTD study of nanomolecular liposomal annamycin in patients with refractory ALL. The secondary objective was to study the MDR-1 encoded P-1u70 glycoprotein expression in correlation with CD34 expression and MDR-1 MRP mRNA levels in refractory ALL patients before and after receiving liposomal annamycin. Results: Thirty patients were enrolled on the study. The MTD was determined to be 150 mg/m2/day for 3 days. Eight of the patients completed 1 cycle of the 3 days of treatment. Of these 8 subjects, 5 (62%) had an efficacy signal. All 5 completely cleared circulating blasts. Three subjects also cleared bone marrow blasts. Of these 3, 1 went on to a successful bone marrow transplant. The other 2 had tumor lysis syndrome and unfortunately expired. Other than the tumor lysis syndromes, there was only 1 SAE definitely related to the study drug which was a grade 3 mucositis but there were also 3 other SAEs of grade 3 or 4 mucositis probably related to the study drug which comprised the MTD determination. There were no reports of cardiac toxicity. Conclusions: Nanomolecular liposomal annamycin appears to be effective through its innate resistance to MDR even as a single agent in refractory adult ALL. We are now testing it in a phase I study in children and young adults with refractory ALL or AML. [Table: see text]
Prevalence and therapeutic relationships of pericardial effusions in patients with leukemia
Authors: Sampat K. R. , Garcia-Gutierrez V. , Rossi A. , Pierce S. , Cortes J. , Kantarjian H. , Garcia-Manero G. 
Published: August 2020

7067 Background: Little is known regarding the prevalence and natural history of pericardial disease in patients with leukemia. Recently, there have been reports of an increased incidence of pericardial effusions (PEf) in patients receiving histone deacetylase inhibitors (HDACi) such as MGCD0103. Although a direct causal relationship has not been established yet, this complication may have a significant impact for the future development of this class of drugs. To study this issue, we retrospectively analyzed a large cohort of patients with leukemia, who were evaluated at MD Anderson Cancer Center (MDACC), to determine the prevalence, timing, and characteristics of PEf in leukemia. Methods: We reviewed 3,327 patients with acute myeloid leukemia (AML, N = 1,809, 54%), acute lymphocytic leukemia (ALL, N = 494, 15%), or myelodysplastic syndrome (MDS, N =1,024, 31%), who were seen at MDACC from August 2003 to July 2008. Of this group, 1,982 patients (60%) had an echocardiogram at some point during their care at MDACC. Data regarding diagnosis, timing, effusion size, and prior therapy was collected in the 401 patients (20.2%) that had echocardiographic evidence of PEf. Results: The overall prevalence of PEf was 21.7%, 21.1%, and 19.9% (p = 0.72) in patients with AML, ALL, and MDS, respectively. In the 401 total patients with PEf, 22.8%, 25.0%, and 18.4% (p = 0.33) of these effusions were found before treatment in the three disease categories, respectively. The rest occurred after some form of chemotherapy, accounting for 77.2%, 75.0%, and 81.6% (p = 0.73) of the total PEf by disease, respectively. Most PEf were of minimal size (67%) overall. No differences in effusion characteristics, including severity, were observed among different types of therapies including HDACi. Conclusions: PEf are relatively common in patients with leukemia at initial presentation and are usually asymptomatic. Their incidence increases with therapy administration although it appears that this is not a process related to specific classes of treatment or type of leukemia. No significant financial relationships to disclose.
The effects of sildenafil citrate on malignant B-cells in patients with chronic lymphocytic leukemia
Authors: McGregor B. A. , Gorrebeeck A. , Struble E. , Harroff A. 
Published: August 2020

7076 Background: Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the Western Hemisphere, with over 10,000 cases diagnosed annually in the United States. It is characterized by progressive accumulation of functionally incompetent long-lived lymphocytes, shown to be secondary to a defect in programmed cell death or apoptosis. The phosphodiesterase inhibitor sildenafil induces capsase dependent apoptosis of malignant B lymphocytes in vitro. This study will test the hypothesis that sildenafil reduces the expression of BCL-2 and increases the spontaneous apoptosis rate of malignant B-cells in patients with CLL. Methods: Thirteen patients with Rai Stage 0 CLL were enrolled. Nine of the patients were aged sixty-five years or older and received sildenafil 25 mg weekly; four patients were under the age of sixty-five and received sildenafil 25 mg weekly. All patients took the medication for a total of three months. Lymphocyte counts, BCL-2 expression, caspase 3 activity, and apoptosis rate were monitored on enrollment and monthly for duration of the study. Results: The median age of patients enrolled in the study was 74 with a median white blood cell count of 18 x103/mL. Twelve of the 13 patients completed three months of therapy. While one patient withdrew due to blehparitis, not felt to be a side effect of sildenafil, all other patients tolerated the medication well without any adverse effects. There was no significant decrease in white blood cell count or Bcl-2 expression; capsase 3 activity and apoptosis rates remained undetectable on presentation and throughout treatment. Conclusions: At a dose of 25 to 50 mg weekly, sildenafil does not appear to have any effects on the malignant B cells in CLL. While this dose may not produce a measurable clinical or cellular response, higher doses may still have an effect on the malignant B cells of CLL. The dose of sildenafil was based on a case series of patients with Viagra who had decreases in IgM levels while taking sildenafil 25–50 mg weekly. Subsequent studies in have shown a greater reduction in IgM in patients taking sildenafil 100 mg daily and patients did not report any significant side effects. A follow-up study using sildenafil 100 mg daily is warranted. No significant financial relationships to disclose.
Comorbidities and prognosis of myelodysplastic syndromes
Authors: Naqvi K. , Oh J. , Garcia-Manero G. , Pierce S. , Suarez-Almazor M. E. 
Published: August 2020

7086 Background: Cancer patients often experience comorbidities that may affect their therapeutic plan, prognosis, and outcome. Few studies have evaluated comorbidities in myelodysplastic syndromes (MDS). The aim of our study was to determine the effect of comorbidity on the survival of patients with MDS. Methods: We reviewed the medical records of consecutive adult MDS patients who presented to our comprehensive cancer center in 2002. The Adult Comorbidity Evaluation-27 (ACE-27), a validated 27-item comorbidity index for cancer patients, was used to assess the severity of comorbid conditions. For each patient, we obtained demographic data and specific staging information based on the International Prognostic Scoring System (IPSS). We also collected information on bone marrow transplantation (BMT), mortality and survival. Kaplan-Meier methods and log-rank tests were used to assess survival. Results: Of the 55 patients included in this preliminary report, 41 (74.5%) were male, and 47 (85.5%) were white; mean age was 66.4 years; mean follow-up 22.2 months. The three most common comorbidities were hypertension, diabetes mellitus, and coronary artery disease. A total of 90.9% of patients had an IPSS risk of intermediate or higher. The ACE-27 comorbidity scores were as follows: none, 18 patients (32.7%); mild, 17 (30.9%); moderate, 9 (16.4%); and severe, 11 (20.0%). Fifty patients (90.9%) died, whereas 9 (16.4%) underwent BMT. Median survival according to ACE-27 scores was: 22 months for patients with no comorbidity, 11 months for patients with mild or moderate comorbidity, and 8 months for those with severe comorbidity; this trend did not reach statistical significance (p = 0.42). A linear trend was observed between the severity of comorbidity and having received BMT: half of the patients with no comorbidities received BMT compared to none in the group with a severe score (p = 0.02). Conclusions: A small trend was observed between survival and comorbidity. Most of our patients had an advanced IPSS stage which may have decreased the strength of this association. Patients with comorbid conditions received BMT less often than those without comorbidity. Further studies are needed to evaluate the effects of comorbidities on the prognosis and therapeutic options of patients with early-stage MDS. No significant financial relationships to disclose.
Plerixafor (P) plus G-CSF (G) in previous peripheral blood progenitor cell (HPC) mobilization failures (MF)
Authors: Van Rhee F. , Panozzo S. , Anaissie E. , Pineda-Roman M. , Waheed S. , Alsayed Y. , Nair B. , Cottler-Fox M. , Barlogie B. 
Published: August 2020

7095 Background: Successful autologous stem cell transplantation (AT) requires harvesting sufficient HPC to ensure reliable engraftment, which cannot be accomplished in ∼10% of previously treated patients. Methods: MF was defined as the inability to collect at least 2 x106 CD34+ cells/kg with growth factor alone (GF) (n=38) or in combination with chemotherapy (GF-CT) (n=27). Of 65 patients reported here, 45 were enrolled in a compassionate use program and 20 were part of a clinical trial (AMD3100–2102); 55 had MM, 9 had lymphoma and 1 had primary amyloidosis. All patients had been treated previously and included prior AT in 26 patients, 15 of whom had 2 AT and 2 had ≥3 AT. The P+G regimen started with G (10 μg/kg) for 4 days, P (240 μg/kg) was added on the evening of day 4; both P and G were continued until completion of collection. In the case of MM, all collected products were analyzed for tumor contamination by DNA/cIg flow cytometry. Results: Of all 65 patients, 63 initiated apheresis which yielded a median 3.6x106 CD34/ kg (range, 0.3–17.8) during a median of 5 days (d) of collection (range, 2–7), with successive median daily CD34 yields of 1.1, 0.9, 0.6, 0.5, 0.3, 0.4 and 0.5 x106/kg. MM cells were mobilized in only 2/55 patients. Additional collection was undertaken in 25 patients, using GF or GF-CT in 19 (median, 3.2x106 CD34 cells; range, 0–8.5), further P+G in 5 (median, 1.7x106 CD34 cells/kg; range, 0.9–3.5), and 1 patient received P+G on a third occasion (2.2x106 CD34 cells /kg). Of 63 patients, 51 (81%) and 24 (38%), respectively, collected ≥2.0 and ≥5.0x106 CD34 /kg. AT was supported with P+G derived products in 43 patients including 7 who received 2 AT. With median infused CD34+cells of 3.6x106 / kg (range, 1.0–7.7), the median times to neutrophils > 500/μl and platelets >20,000/ μl were 14 d (range, 11–35) and 15 d (range, 9–253). Conclusions: P+G ensures collection of an adequate HPC product after MF in 81% that affords durable engraftment even though 40% had prior AT. [Table: see text]
BEAM or BuCyE high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin's lymphoma patients
Authors: Kim J. , Kim E. , Sohn B. , Yoon D. , Yoo C. , Kim S. , Lee D. , Kim S. , Lee J. , Suh C. 
Published: August 2020

7097 Background: The objective of this study was to compare the efficacy and toxicity of two high-dose regimens for autologous stem cell transplantation (ASCT) in patients with non-Hodgkin's lymphoma (NHL): BEAM (BCNU, etoposide, cytarabine, and melphalan) and BuCyE (busulfan, cyclophosphamide, and etoposide). Methods: We analysed 65 NHL patients, who underwent high-dose chemotherapy with BEAM (N=43) or BuCyE (N=22), followed by ASCT, at the Asan Medical Center. BEAM was used from February 2002 to October 2005, and BuCyE was used from November 2005 to April 2008. Results: Median age was 46 years (range: 15–68), and baseline characteristics, such as gender, International Prognostic Index (IPI), age adjusted IPI, stage and status of disease at ASCT, and median number of infused CD 34+cells/kg were well balanced between groups. The incidence of mucositis, nausea/vomiting, diarrhea and bleeding, and the number of events clinically important infections during ASCT did not differ between groups. Median follow-up for survivors was 49.3 months in the BEAM group and 21.5 months in the BuCyE group. Median overall survival (OS) was 30.6 months (95% confidence interval [CI], 8.19–53.0 months) and 22.6 months (95% CI, 12.1–33.1 months) and median event-free survival (EFS) was 16.1 months (95% CI, 0.0–53.6 months) and 11.2 months (95% CI, 0.0–22.5 months) in the BEAM and BuCyE group, respectively. There were no significant differences in OS (p=0.636) and EFS (p=0.575) between the two groups. Conclusions: In our analysis, BuCyE appeared to be not inferior to BEAM for survival. And we found that regimen-related toxicities did not differ significantly between the two groups. No significant financial relationships to disclose.