bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of lenalidomide induction therapy on peripheral blood stem cell collection in patients undergoing autologous stem cell transplant for multiple myeloma.
Authors: Bhutani Divaya , Zonder Jeffrey A. , Abrams Judith , Ratanatharathorn Voravit , Uberti Joseph P. , Abidi Muneer Hyder 
Published: March 2020

6549 Background: Autologous stem cell transplant (ASCT) remains part of standard therapy for Multiple Myeloma (MM). Lenalidomide (LEN) is a newer, effective therapy for MM. It has been suggested that prior LEN therapy is associated with an increased risk of stem cell collection failure, particularly when only G-CSF is used for mobilization. Methods: We conducted a retrospective chart review of 310 consecutive MM pts who underwent pheresis to collect stem cells for first ASCT between July 1, 2007 and June 30, 2011 at the Karmanos Cancer Institute. We compared differences in quantity of CD34 cells collected, days needed to collect the target number of cells (> 2.5 x 10*6 CD34+ cells/kg), days to platelet and neutrophil engraftment. We also evaluated the association between CD34+ cells collected and the number of cycles of LEN therapy. Results: Of 310 patients, 90% were mobilized with only G-CSF initially. Patients were analyzed as two groups: LEN exposed (LEN(+); n = 128) and LEN naive(LEN(-); n = 182). Median age in both groups was 58 years. No differences in race, sex and MM stage distribution were observed between the two groups. The median number of stem cells collected in the LEN(+) group was significantly less than the LEN(-) group (6.46 vs. 7.56 x 10*6 CD34 cells/kg; p= 0.0004). In addition, the median number of pheresis sessions required for adequate stem cell collection were significantly more in the LEN(+)group as compared to LEN(-) group (2 vs.1 sessions; p=0.002). In the LEN(+) group, there was a negative correlation between CD34+ cells collected and the prior number of cycles of LEN (p=0.0001). There was no statistically significant excess in the number of stem cell collection failures with G-CSF in the LEN(+) group (7% vs. 4% p=0.31). All pts who failed collection after G-CSF were successfully collected with Cytoxan or Plerixafor priming. LEN exposure had no effect on post-ASCT neutrophil or platelet recovery. Conclusions: Although Lenalidomide exposure is associated with a slightly lower CD34+ stem cell yield and on average an extra session of pheresis when G-CSF is used for mobilization, collection failure is uncommon and post-ASCT engraftment is normal.
Secondary neutropenia (SN) after autologous hematopoietic stem cell transplantation (AHSCT) in patients (pts) with lymphoma.
Authors: Nathan Sunita , Maciejewski John Joseph , Rich Elizabeth Shima , Venugopal Parameswaran , Christopherson Kent W. , Gregory Stephanie A. , Fung Henry C. 
Published: March 2020

6552 Background: Plerixafor for mobilization of autologous stem cells (ASC) has increased the yield of transplanted ASC and is evolving as an important option for mobilization. A prior study reported a 10% incidence of SN after AHSCT (BMT 2009 Aug; 44(3): 175-83). Incidence and outcome of SN in the setting of Plerixafor/G-CSF (P/G), is unknown. We report the incidence and possible etiology for the development of SN in pts undergoing AHSCT for lymphoma at our institution. Methods: Data from 80 consecutive AHSCT pts over a 2 year period were reviewed. All pts were mobilized using P/G. Demographics, AHSCT indication, prior therapies (Rx), conditioning regimen (CR), engraftment and post-transplant complications were identified and collected. SN was defined as ANC <1000 after initial engraftment. Results: 80 pts underwent an AHSCT for lymphoma from 2009-11. 70 pts had evaluable data. 37 (52.86%) pts (average age 55.4 yrs) were male and 33 (47.14%) pts (average age 48.3 yrs) female. 25 (35.7%) pts had ≥2 comorbidities. Indications included relapsed/ refractory B-NHL, T-NHL and HL. 47 (67%) pts had Stage IV ds, 48.9% with BM involvement. 17 (24.3%) pts had >2 Rx, 18 (25.7%) with loco-regional XRT and 3 (4.3%) with RIT. CR included BEAM, BEC and Benda-EAM +/- Rituxan. # of CD34+ cells given ranged; 1.77-19.99 x 10^6/kg. Neutrophil engraftment occurred at a median of 11 days. 26 (37.14%) pts developed SN possibly from PCP prophylactic antibiotics and infections. Prior BM involvement, Rx or XRT had no role. 5 (45.4%) pts with Benda-EAM CR had SN. Associated morbidity/mortality were not noted. Conclusions: We conclude that secondary neutropenia is common after autologous stem cell transplant using the Plerixafor/GCSF combination for mobilization and is higher than reported in the literature (37% vs 10%). Patients who received this combination for mobilization should be followed up closely in the post-transplant period for secondary neutropenia. About half the patients who received the Benda-EAM conditioning regimen developed secondary neutropenia warranting its use with caution outside of a clinical trial.
Post hoc analysis of relationship between baseline white blood cell count and survival outcome in a randomized phase III trial of decitabine in older patients with newly diagnosed acute myeloid leukemia.
Authors: Arthur Chris , Cermak Jaroslav , Delaunay Jacques , Mayer Jiri , Mazur Grzegorz , Thomas Xavier G. , Wierzbowska Agnieszka , Jones Mark M. , Tarassoff Peter G. , Kantarjian Hagop 
Published: March 2020

6559 Background: In a large phase III trial (N=485), patients (pts) ≥65y with newly diagnosed acute myeloid leukemia (AML) received 1-h IV infusion of decitabine (DAC) 20 mg/m2 for 5 consecutive days every 4 wk or treatment choice (TC) with supportive care or cytarabine 20 mg/m2 subcutaneous injection for 10 consecutive days every 4 wk (NCT00260832; Kantarjian et al. JCO, in press). Enrolled pts had white blood cell (WBC) count <40 x109/L; baseline WBC counts were relatively low (median [range] DAC: 3.1 x109/L [0.3-127.0]; TC: 3.7 x109/L [0.5-80.9]). This post hoc analysis assessed baseline WBC count and survival outcome. Methods: Overall survival (OS) and progression-free survival (PFS) were summarized by baseline WBC subgroups (<1, 1-5, >5 x109/L). Results: Mature survival data (2010) were based on intent-to-treat (ITT) population (446 deaths: TC, n=227; DAC, n=219). OS was 5.0 mo for TC vs 7.7 mo for DAC (nominal P=.037). For each WBC subgroup, differences in OS for TC vs DAC were not significant (NS), but hazard ratios (HR) favored DAC for all subgroups (Table). There was a significant difference in PFS in favor of DAC for patients with baseline WBC 1–5 x109/L (P=.005; HR=0.67) and >5 x109/L (P=.027; HR=0.71). Conclusions: These data are consistent with overall results, with a trend toward improved outcome with DAC regardless of baseline WBC count in older pts with newly diagnosed AML. Further analyses are warranted. [Table: see text]
Increased risk of MDS/AML post radiation treatment for breast cancer: Analysis of SEER data 2001-2008.
Authors: Kaplan Henry G. , Malmgren Judith April , DeRoos Anneclaire 
Published: March 2020

6560 Background: Ionizing radiation is a known cause of myeloid leukemia, but it is not known whether therapeutic doses for breast cancer (BC) pose risk. We hypothesized that BC radiation treatment is associated with increased risk of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML)) as seen in a previously conducted institutional cohort study. Methods: We used 2001-2008 Surveillance, Epidemiology and End Results (SEER) database records to identify a cohort of first primary BC patients treated with radiation who were unlikely to be treated with chemotherapy (stage 0 and estrogen receptor positive (ER+) stage I). We identified subsequent MDS/AML diagnoses in the BC cohort, using SEER to query appropriate ICD-O-3 codes. We compared observed MDS/AML rates in the BC cohort to expected rates, estimated for first primary MDS/AML in the entire population, and calculated observed/expected rate ratios with 95% confidence intervals (CI). Results: We estimated an increased overall risk of MDS/AML in the breast cancer cases treated with radiation compared to the general population (RR=4.23, 95% CI 3.41, 5.18). The relative risk was higher for stage I ER+ breast cancer cases <65 years of age (RR=7.75, 95% CI 5.18, 11.05) than for stage 0 cases <65 years of age (RR=3.65, 95% CI 1.57, 7.05). Among women 65 years and older, there was a more modest increased risk, only seen for stage 1 ER+ breast cancer cases (RR=1.52) (table). Conclusions: Our results suggest that radiation treatment for breast cancer is associated with increased risk of MDS/AML. The effect appears to be age-dependent. [Table: see text]
Mevalonate pathway inhibitors in the treatment of B-cell chronic lymphocytic leukemia.
Authors: Bobba Ravi Kiran , Benakanakere Indira , Bearelly Smitha , Arya Monica , Sleigtholm Richard , Freter Carl 
Published: March 2020

6561 Background: B-cell chronic lymphocytic leukemia (CLL) cells are arrested in G0/G1 phase of the cell cycle and are resistant to programmed cell death, hypothesized to contribute to the resistance of CLL cells to standard chemotherapy with curative intent. Methods: Mec-2 cells and Wac-3 cells are CLL cells that have been shown to be resistant to fludarabine and rituximab. We tested a novel enzyme inhibitor’s ability to render CLL cells sensitive to fludarabine and rituximab. Results: BIBB515, a lanosterol synthase inhibitor, at a concentration of 10μM, was able to reduce the cell viability from 82% in controls to 65% after 72 hours. Fludarabine 10μM alone did not reduce the cell viability, 82 % in controls compared to 80%. BIBB515+ fludarabine treatment for 72 hours, at the dose of 10μM each decreased the cell viability to 37%. Cell proliferation by MTT assay was 0.66±0.010 in control compared to 0.37±0.01 in BIBB515+fludarbine and 0.21±0.01 in BIBB515+ fludarabine+ rituximab. There is a 68% down-regulation of cell proliferation using this treatment. There was a two fold induction of CD 20 with combination treatment, and BIBB515 treatment. The mechanism of cell death in the combination treatment of BIBB515 and fludarabine may be due to the up regulation of cell surface marker CD-20. WAC-3 is another CLL cell line that is sensitive to fludarabine, and resistant to rituximab. BIBB515 sensitizes WAC-3 cells to CD 20 antibody rituximab. There is a 68.7% decrease in cell proliferation with combination treatment of BIBB515 and rituximab. Proliferation of Mec-2 cells were inhibited by 60µM and 30µM terbinafine. Ro-48-8071, showed dose-dependent activity, alone or in combination to fludarabine was seen to induce cell death in Mec-2 cells. Fludarabine alone did not have any effect on these cells. Conclusions: Inhibitors of the mevalonate pathway make resistant CLL cells sensitive to current chemotherapeutic agents. Exploiting this mechanism could alter the current treatment regimens, leading to control of the disease in advanced stages by either inducing the leukemic cells to be static or to regress. This strategy may also limit the toxicities involved with chemotherapy.
Overall and cancer-specific survival of breast, colon, and lung cancer in patients with and without chronic lymphocytic leukemia: A SEER population-based study of over 1 million patients.
Authors: Solomon Benjamin Maurice , Rabe Kari G. , Slager Susan L , Brewer Jerry D , Cerhan James R. , Shanafelt Tait D. 
Published: March 2020

6571 Background: Chronic lymphocytic leukemia (CLL) is associated with an increased risk of developing second cancers. However, it is unknown whether CLL alters the natural history of these cancers once they occur. Methods: All patients with breast (n=583,838), colon (n=412,932), prostate (n=632,922), lung (n=489,290), kidney (n=95,902), pancreas (n=82,121) and ovarian (n=61,958) cancer reported to the Surveillance, Epidemiology, and End Results (SEER) Program from 1990 to 2007 were identified. Overall survival (OS; death due to any cause) and cancer-specific survival (death due to cancer site of interest) were examined, comparing patients with or without pre-existing CLL. Age- and sex-adjusted hazard ratios (HRs) were calculated. Results: OS for patients with pre-existing CLL was inferior for patients with breast (HR=1.61; p<0.001), colon (HR=1.65; p<0.001), kidney (HR=1.41; p<0.001), prostate (HR=1.75; p<0.001), and lung (HR=1.22; p<0.001) cancer after adjusting for age and sex. After excluding CLL-related deaths, OS remained shorter among patients with breast (p<0.001), colon (p<0.001), kidney (p=0.03), prostate (p<0.001), and lung (p<0.001) cancer. Cancer-specific survival was inferior for patients with breast (HR=1.29; p=0.03), colon (HR=1.75; p<0.001), and lung cancer (HR=1.17; p<0.001) who had pre-existing CLL after adjusting for age and sex. Conclusions: Several common cancers, including breast, colon, and lung, have inferior overall and cancer-specific survival when there is coexistent CLL. [Table: see text]
L-arginine depletion by PEG-arginase I, a new potential therapy for acute lymphoblastic leukemia.
Authors: Crombet Ramos Ofelia , Hernandez Claudia , Morrow Kevin , Cole John T. , Rodriguez Paulo 
Published: March 2020

6580 Background: Advances in therapies have resulted in an overall complete remission rate of approximately 85% for childhood acute lymphoblastic leukemia (ALL). In contrast, the overall remission rate of adults with leukemia continues to be poor, only about 40% in cases of T cell-ALL (T-ALL). Therefore, it is imperative to generate new therapies that alone or in combination with other treatments could potentially increase the percentages of complete responders or be used to treat the refractory ALL population. Our published results show that a pegylated form of human arginase I (peg-Arg I) prevented T-ALL cell proliferation in vitro and in vivo through the induction of tumor cell apoptosis. Interestingly, the anti-leukemic effects induced by peg-Arg I did not affect the anti-tumor activity of normal T cells, suggesting an anti-tumor specific effect. Our hypothesis states that peg-Arg I has an anti-tumoral effect on B-ALL and T-ALL cells in vitro and that the sensitivity of ALL cells to peg-Arg I depends on their expression of argininosuccinate synthase (ASS) and their ability to produce L-arginine de novo from citrulline. Methods: Malignant T cell proliferation was tested using nonradioactive cell proliferation yellow tretrazolium salt kit. Apoptosis studies were based on the expression of annexin V. Western blot assays were conducted to determine enzymatic expression in different cell lines. Results: The results of our in vitro experiments showed that peg-Arg I had a pro-apoptotic and anti-proliferattive effect on B-ALL cells similar to the one previously seen on T-ALL cells. These effects can be overcome in cell lines able that express ASS and therefore to produce L-arginine de novo. Conclusions: Our results suggest the role of ASS in the ALL-apoptosis induced by peg-Arg-I. Our next steps include: _Understand why ASS-expressing ALL cells do not undergo apoptosis when cultured with peg-Arg-I_Determine the role of ASS in the anti-leukemic effect induced by peg-Arg-I in vivo. Completion of this research is expected to lead to a better understanding of how peg-Arg-I kills ALL cells and could provide the foundation for a novel therapy for ALL patients.
Prognostic and predictive significance of smudge cell percentage on routine blood smear in chronic lymphocytic leukemia patients: A single center study from northern India.
Authors: Gogia Ajay , Raina Vinod , Sharma Atul , Kumar Lalit , Gupta Ritu , Vishnubhatla Sreeniwas , Gajendra Smeeta 
Published: March 2020

6593 Background: Smudge cells are ruptured lymphocytes seen on routine blood smears of chronic lymphocytic leukemia (CLL) patients. We evaluated prognostic and predictive significance of smudge cells percentage on a blood smear in CLL patients. Methods: We calculated smudge cell percentages (ratio of smudged to intact cells plus smudged lymphocyte) on archived blood smears of 185 untreated CLL patients registered at I.R.C.H, AIIMS, New Delhi over a period of 11 years. Results: There were 135 males and 50 females. The median age was 60 years (28-89). Median absolute lymphocyte count was 42 X109/L. Clinical Rai stage distribution was: stage 0 - 10%, stage I - 15%, stage II - 40%, stage III -15 % and stage IV - 20%. The median smudge cells percentage was 27% (4% to 76%). There was no correlation of proportion of smudge cells with age, sex, lymphocyte count, organomegaly, ZAP 70 + or CD 38 + CLL patients, but there was significant correlation with stage of disease. Median smudge cell percentage in stage 0 & I -33% (12-76), stage II- 31% (12-61) and stage III&IV-21% (4-51) [ p=<0.001]. One third of early stage (0, I &II) patients required treatment during follow up, at the end of 5 years of follow up 55% required treatment with smudge cell < 30%, against 24% patients requiring treatment with smudge cells > 30% [p=0.01]. The percentage of smudge cells as a continuous variable correlated with OS [HR 0.96, p< 0.001]. The 5-year survival rate was 51% for patients with 30% or less smudge cells compared with 81% for patients with more than 30% of smudge cells. Thirty percent of patients died during follow up. Median OS was 5 years with median follow up period of 3.9 years. Smudge cells percentage (<30% vs. >30%) had significant association with OS [HR 0.47, 95%CI (0.32-0.71), p=0.001)]. Conclusions: Simple and inexpensive detection of smudge cells on blood smears on routine diagnostic test useful in predicting progression free and OS in CLL patients and may be beneficial in countries with limited recourses.
Omacetaxine mepesuccinate in chronic-phase chronic myeloid leukemia (CML) in patients resistant, intolerant, or both to two or more tyrosine-kinase inhibitors (TKIs).
Authors: Akard Luke Paul , Kantarjian Hagop , Nicolini Franck E. , Wetzler Meir , Lipton Jeffrey Howard , Baccarani Michele , Craig Adam , Nanda Nisha , Brown Peter D. , Cortes Jorge E. 
Published: March 2020

6596 Background: Omacetaxine mepesuccinate (“omacetaxine”) is a first-in-class, reversible, transient inhibitor of protein elongation that facilitates tumor cell death without depending on BCR-ABL signaling. Clinical activity was shown in two phase 2, open-label, multicenter studies of patients with treatment-resistant CML who had failed at least prior imatinib, many of whom were also resistant to or intolerant of dasatinib and/or nilotinib. Methods: A subset of data from the phase 2 studies included patients in chronic phase who were resistant/intolerant to ≥2 approved TKIs. Omacetaxine 1.25 mg/m2 was given subcutaneously twice daily: ≤14 consecutive days/28-day cycle for induction, ≤7 days/cycle as maintenance. Patients had never achieved or lost response to ≥2 TKIs (R group), were intolerant of ≥2 TKIs (I), or resistant to 1 and intolerant of another (R/I) were evaluated. Results: Of 81 patients (median age, 58 years), 69 were R, 7 I, and 5 R/I. Major cytogenetic response occurred in 13 (19%) in the R group (median duration not reached), 2 (29%) I (median duration 7.4 months), and 1 (20%) R/I (duration 17.7 months). For all patients, cycles of exposure and study duration were 7 cycles and 9.1 months (R); 4 cycles, 7.3 months (I); and 2 cycles, 2.3 months (R/I). Median overall survival in months were 33.9 (R), not reached (I), and 25.0 (R/I). Of 66 (81%) patients with treatment-related grade 3/4 adverse events (AEs), the most common were thrombocytopenia in 44 R, 6 I, and 4 R/I patients and neutropenia in 32 R, 4 I, and 1 R/I. Fifteen patients had an AE leading to discontinuation (10 R, 2 I, 3 R/I), primarily disease progression. There were 9 deaths (the most common were disease progression, sepsis), 8 I, 1 R/I; 2 were considered related to treatment (both sepsis). Conclusions: This subset analysis of patients with chronic-phase CML and prior therapy with ≥2 TKIs shows that omacetaxine provides efficacy and tolerability across TKI-R, I, and R/I groups. Interpretation of the I and the R/I group data was limited by small sample sizes. Support: Teva Pharmaceutical Industries Ltd.
Prospective evaluation of serial 2-hydroxyglutarate in acute myeloid leukemia (AML) to determine response to therapy and predict relapse.
Authors: Fathi Amir Tahmasb , Abdel-Wahab Omar Ibrahim , Sadrzadeh Hossein , Foster Julia , Burke Meghan , Borger Darrell R. , Iafrate A. John , Adamia Sophia , Liu Suiyang , Ballen Karen K. , Amrein Philip C. , Attar Eyal C. , Straley Kimberly , Yen Katharine , Schenkein David P. , Neuberg Donna S. , Levine Ross L. , Chen Yi-Bin Albert , Stone Richard M. 
Published: March 2020

6606 Background: Mutations in isocitrate dehydrogenase (IDH1 and IDH2) occur in 10-20% of AML patients and result in production of 2-hydroxyglutarate (2-HG). We hypothesize that serial 2-HG quantification may be used to monitor response and predict relapse in patients with AML. Methods: We are conducting a prospective study at MGH and DFCI to (1) assess changes in serum and urine 2-HG levels during treatment in patients with newly diagnosed AML, (2) compare 2-HG levels in serum, urine, and bone marrow and, (3) serially compare 2-HG levels with IDH1/2mutant allele burden. In those with elevated serum 2-HG (≥1000ng/ml), 2-HG is monitored serially or at relapse. Results: To date, 20 patients have been enrolled, 5 (25%) of whom had elevated baseline serum 2-HG. All 5 were found to have IDH1/2 mutations. The serum 2-HG for these patients was significantly higher than for those who were IDH-wt (median 1933 vs 87ng/mL; p<0.001). Urine 2-HG was also higher in IDH-mutant patients (median 30500 vs 4230ng/mL; p<0.021), as was bone marrow 2-HG (median 9870 vs 309ng/mL; p<0.005). Serum 2-HG levels strongly correlated with that in urine (R2 0.987). Serum 2-HG decreased in all IDH mutant patients on therapy, but more rapidly in those receiving induction chemotherapy (Table), all of whom achieved remission, than those receiving hypomethylatingagents. Conclusions: Patients with IDH-mutant AML have markedly elevated serum and urine 2-HG. 2-HG levels decreased with therapy and there is a strong correlation between serum and urine 2-HG. Data on the sensitivity of serial 2-HG monitoring as well as comparison with mutant IDH1/2allele burden will be presented. This data suggests that serial 2-HG quantification may be a valuable non-invasive biomarker in this genetically defined subset of AML. [Table: see text]