bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of infection on health-related quality of life (HRQoL) in patients with Philadelphia negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (Ph- R/R BCP ALL) in a randomized, open-label, phase 3 study (TOWER).
Authors: Schuh Andre C. , Li Yan , Topp Max S. , Zhang Xinke , Cannell Paul , Dombret Herve , Maertens Johan , Stein Anthony Selwyn , Franklin Janet 
Published: March 2020

e18511 Background: In the phase 3 TOWER study (NCT02013167), blinatumomab (BLIN) significantly improved overall survival in adults with Ph- R/R BCP ALL, and these patients (pts) also reported better HRQoL (EORTC QLQ-C30 measures) compared with standard of care (SOC) chemotherapy. This analysis assessed the impact of grade 3+ infection, which was reported in 34.1% of BLIN pts vs 52.3% of SOC pts, on HRQoL in TOWER. Methods: Pts were stratified into two groups: those with infection vs those without infection, between baseline and Day 8, Day 15, and Day 29. A difference-in-difference (DID) model investigated the impact of infection on HRQoL. A 5-point change is considered the minimum clinically important difference in the EORTC QLQ-C30 for between group comparisons (King et al. 1996). Results: In total, 342 pts (n = 247 BLIN; n = 95 SOC) had a non-missing baseline and ≥1 post-baseline HRQoL score for any scale. Grade 3+ infection was reported in 15 (4.5%) pts before Day 8, 49 (14.5%) pts before Day 15, and 76 (22.6%) pts before Day 29. Pts with grade 3+ infection reported clinical meaningful deterioration in global health status (GHS) score and in almost all functional subscales across timepoints assessed (Table). At Day 29, grade 3+ infection was associated with statistically significant and clinically meaningful deterioration in GHS and most functional scales (Table). Similar but smaller effects were also observed for symptom scales/items (data not shown). Conclusions: Grade 3+ infection in pts with Ph- R/R BCP ALL was associated with clinically meaningful deterioration in HRQoL. The lower incidence of infection in pts treated with BLIN vs SOC may have contributed to the improved HRQoL for pts treated with BLIN. Clinical trial information: NCT02013167. [Table: see text]
Venetoclax (VEN) and tyrosine kinase inhibitor (TKI) combinations in Philadelphia chromosome-positive (Ph+) acute myeloid leukemia (AML) and chronic myeloid leukemia myeloid blast phase (CML MBP).
Authors: Maiti Abhishek , Ravandi Farhad , Cortes Jorge E. , Jabbour Elias , Marx Kayleigh , Daver Naval Guastad , Garcia-Manero Guillermo , Konopleva Marina , Benton Christopher Brent , Masarova Lucia , Dinardo Courtney Denton , Bose Prithviraj , Naqvi Kiran , Pierce Sherry A. , Kantarjian Hagop M. , Short Nicholas James 
Published: March 2020

e18515 Background: Ph+ AML and CML MBP have poor outcomes. VEN synergizes with BCR-ABL TKIs in vitro and may eradicate Ph+ leukemic stem cells. However, the clinical activity of VEN+TKI regimens is unknown. Methods: We conducted a retrospective study on patients (pts) with Ph+ AML and CML MBP who received regimens with VEN+TKI at our institution. Results: We identified 6 pts with relapsed/refractory (R/R) Ph+ AML and 7 with CML MBP (2 transformed from chronic phase, 5 R/R). 10 pts (77%) were refractory to prior therapy and 3 (23%) had relapsed disease. Pt characteristics are shown in the Table. 5 AML pts (83%) had complex cytogenetics. Pts with CML MBP had received a median of 2 prior TKIs (range 1-3). 7 pts received decitabine-based combinations and 6 pts received intensive chemotherapy in combination with VEN+TKI. TKIs included ponatinib (n=7), dasatinib (n=4), bosutinib (n=1) and nilotinib (n=1). Among 12 evaluable pts, the overall response rate (CR + CRi + MLFS) was 50% (Table). In addition, 1 pt with AML developed aplastic marrow, underwent stem cell transplantation, and is still alive. Pts with CR/CRi vs. those without CR/CRi had higher median number of Ph+ metaphases (100% vs. 32%, p<0.01) and higher baseline BCR-ABL1 PCR (100% vs. 0.5% p=0.01). The only AML pt who achieved CR/CRi had 100% Ph+ metaphases. After a median follow-up of 10.9 months (mo), 5 pts are alive (1 AML, 4 CML MBP). The median overall survival for pts with AML and CML MBP were 2 mo and not reached, respectively. The median relapse-free survival was 8.2 mo. Conclusions: VEN+TKI combinations show encouraging activity in pre-treated, advanced Ph+ leukemias, particularly CML MBP. Clonal burden of Ph+ cells correlated with response. Prospective trials are needed to evaluate VEN+TKI combinations in Ph+ leukemias. Pt characteristics and outcomes (n/N [%] / median [range]). [Table: see text]
Real-world treatment patterns in adult patients (pts) with B-cell precursor acute lymphoblastic leukemia (BCP ALL) in first hematologic complete remission (CR1) with and without minimal residual disease (MRD).
Authors: Shah Shweta , Rose Darya , Cong Ze , Tibrewala Shruti , Chawla Anita , Zaman Faraz 
Published: March 2020

e18517 Background: B-cell precursor acute lymphoblastic leukemia (BCP ALL) is a rare and debilitating hematologic cancer. Among patients (pts) in complete remission (CR), minimal residual disease (MRD) is a strong prognostic factor for worse survival outcomes. Limited real-world data is available from the United States to characterize treatment patterns in BCP ALL pts. Methods: A chart review was conducted to assess treatment patterns among adult BCP ALL pts with and without MRD in first hematologic CR (CR1) across National Cancer Institute designated cancer centers, academic and community hospitals, and integrated delivery systems. The study period was the date of CR1 until 12 months post-CR1, relapse, or death. Eligible pts were ≥18 years of age with BCP ALL in CR1 between 4/2015 and 3/2017, with no other cancer diagnoses. Results: Overall, 65 (52%) of the 125 pts included in the study received drug therapy for ALL. Of the 79 total unique treatment regimens, the most frequently administered were intensification/consolidation regimens (46.8%), followed by long-term maintenance (36.7%), and preparation for hematopoietic stem cell transplantation (16.5%). Common regimens among Philadelphia chromosome-negative pts included hyper-CVAD (50%), monthly vincristine/prednisone, weekly methotrexate, and daily 6-mercaptopurine (31%), and CALGB 8811 (16.7%). The proportion of pts receiving drug therapy among community hospitals and academic settings were considerably similar (52% vs 48.3%).The majority of physicians selected hyper-CVAD as the standard of care for pts with MRD+ in CR1 (70.3%), with 48.4% of physicians selecting CALGB 8811, 32.8% selecting multiagent chemotherapy, and 29.7% selecting Linker-4, and 23.4% selecting monthly vincristine/prednisone, weekly methotrexate, daily 6-mercaptopurin. Conclusions: Nearly 50% of pts included in this study did not receive drug therapy for ALL (mean age: 47.8 years). The real-world treatment regimens among treated pts observed in this study are consistent with the NCCN guidelines although there is substantial heterogeneity in the management of BCP ALL.
Intensive minimal residual disease monitoring to drive early intervention after allogeneic hematopoietic stem cell transplant for pediatric acute leukemia.
Authors: Pincez Thomas , Santiago Raoul , Bittencourt Henrique , Louis Isabelle , Teira Pierre , Richer Johanne , Cellot Sonia , Duval Michel 
Published: March 2020

e18531 Background: Relapse of acute leukemia (AL) remains the main cause of death after allogeneic stem cell transplantation (HSCT) in children. Minimal residual disease (MRD) allows to detect leukemia cells in the bone marrow at low level. The impact of post-HSCT MRD monitoring to detect early leukemia recurrence, to guide therapeutic intervention, and to prevent overt relapse is unknown. We report our experience of systematic MRD monitoring after pediatric HSCT. Methods: All patients who underwent HSCT from January 2012 to December 2017 for an AL had bone marrow MRD performed for 2 years (months 1, 2, 3, 5, 7, 9, 12, 15, 18, 21 and 24). MRD was assessed by flow-cytometry (FC) and, when a molecular alteration was present, by nested RT-PCR. Results: Seventy-one HSCT were performed for AL of myeloid (n=38), lymphoid (n=31) or mixed (n=2) lineage in 59 patients at a median (range) age of 6.5 (0.7-18.4) years. Nine cases did not engraft or had a refractory disease at month+1 evaluation. In all other cases (n=62) MRD was monitored using FC (n=58) and/or RT-PCR (n=34). Thirty-three cases had a MRD detection and/or an overt relapse (≥5% blasts). In 23/33 cases (70%), MRD was detected without simultaneous overt relapse. In the 10 others, an overt relapse occurred without prior MRD detection. Among the cases monitored with RT-PCR, only one relapse occurred without a prior MRD detection. The follow-up protocol was not respected in this particular case. On early MRD detection, 20/23 cases underwent therapeutic intervention, the most frequent being the discontinuation of immunosuppressive drugs (n=13), with subsequent undetectable MRD in 6. Other interventions included chemotherapy (n=8), donor lymphocyte infusion (n=6) and/or interferon ± interleukine 2 (n=3), leading to an undetectable MRD in 3 cases. Overall after first MRD detection, 9/23 (39%) cases never experienced a subsequent overt relapse. Conclusions: Intensified MRD monitoring detected 70% of leukemia recurrences before overt relapse. Therapeutic intervention were taken in most of the cases and 39% never experienced overt leukemia relapse. More efficient immunotherapies may improve the impact of preemptive interventions.
CMV reactivation in allogeneic hematopoietic stem cell transplant patients receiving post-transplant cyclophosphamide.
Authors: Markowski Paul , Schaar Dale G. , Wei Catherine , Tyno Anne 
Published: March 2020

e18533 Background: Post transplant cyclophosphamide (PTCY) has been shown to be an effective treatment for prevention of graft versus host disease (GVHD). However, this increased immune suppression rates may increase the risk of CMV reactivation. There is limited published data addressing CMV reactivation in this patient population. Additionally there is no data on the efficacy of prophylactic letermovir in the patients who have received PTCY. In this study we analyzed the incidence of CMV reactivation in patients treated with PTCY and those not treated with PTCY, as well as the efficacy of letermovir in preventing CMV reactivation in the PTCY population. Methods: We conducted a retrospective review of MUD, MRD, and haploidentical stem cell transplant patients at our institution from 1/1/2014 until 12/10/2018. We analyzed the incidence of CMV reactivation (PCR > 137 DNA IU/ml), peak of CMV PCR titer and time to reactivation within the first 100 days post-transplant. Results: There were 150 patients with at least 60 days of follow-up that were included in this study. These patients were split into three groups: No post-transplant cyclophosphamide (NPTCY) (N = 64), received post-transplant cyclophosphamide (PTCY) (N = 70), and received PTCY and letermovir prophylaxis. (L-PTCY) (N = 15). The incidence of CMV reactivation was increased in the PTCY patients when compared to the NPTCY (44% vs 29%). In the NPTCY patients the donor (D) serostatus increased the risk of CMV reactivation (Recipient (R)+ D+ 73% vs R+D-36%) conversely in the PTCY group the donor CMV status did not influence reactivation rates (R+D+ 52% vs R+D- 81%). The CMV reactivation rate in the L-PTCY patients was lower when compared to the PTCY patients (21% vs 44%), additionally the L-PTCY patients had much lower peak CMV titers compared to PTCY group (445 vs 2112 IU/ml). Conclusions: This study demonstrates that there is an increased incidence of CMV reactivation in patients who receive PTCY. Additionally, the donor CMV serostatus does not appear to influence the incidence of CMV reactivation in patients receiving post-transplant CY. Although the number of patients in the L-PTCY group is small, it does appear to be an effective prophylactic treatment in patients receiving PTCY.
Healthcare implications of Clodtridium difficile infection after bone marrow transplant: Nationwide Readmission Database review.
Authors: Hegazi Mohamed , Elsabbagh Eman 
Published: March 2020

e18538 Background: Clostridium difficile infection (CDI) is a common complication following hematopoietic stem cell transplant in adults and is associated with substantial morbidity, and mortality. Despite this association, the first 90 days readmission rates and characteristics are poorly characterized. Objective: Utilizing the Nationwide Readmission Database (HCUP-NRD); we intended to analyze rates, predictors and hospitalization cost of CDI readmission after Hematopoietic Stem Cell Transplant (HSCT) in adults. Methods: Adult patients admitted after HSCT with at least 3 months of follow-up were included for analysis using administrative claim codes for CDI in the 2014 Nationwide Readmission Database. According to HSCT type, patients were stratified to either Umbilical Cord Blood Transplant (UCBT) or Bone Marrow Transplant (BMT) (autologous and allogenic). We subsequently evaluated for CDI readmission by day 90. Results: A total of 17,412 adult patients met the inclusion criteria, including 1.3 % that received UCBT, 98.7% that received BMT. All-causes readmission rate was 32.7% (5695/17412) and CDI readmission rate was 7.9% (450/5695). The median age was 60 years, 56.2% were male, median length of stay was 8 days and the median time lapsed after transplant discharge and CDI readmission was 28 days. The most common payer was private insurance at 57.6%. The median cost per CDI admission was $62,125 with net total cost $15.3 million. Conclusions: (1) CDI 90-day readmission rate among adult patients treated with HSCT is a significant morbidity and associated with considerable cost. (2) Further studies are warranted to evaluate factors that can contribute to decreased rate of CDI readmissions following HSCT.
CML patients presenting with priapism: Is there any disparity in outcome?
Authors: Jandial Aditya , Mishra Kundan , Sandal Rajeev , Lad Deepesh , Prakash Gaurav , Khadwal Alka , Varma Neelam , Malhotra Pankaj 
Published: March 2020

e18545 Background: Priapism, a urological emergency that needs prompt treatment, is an uncommon presenting feature of chronic myeloid leukemia (CML). CML frequently occurs in younger males and adolescents in developing countries. Occurrence of erectile dysfunction (ED) in this particular age group can severely decrease the quality of life. It is known that immediate treatment of priapism preserves erectile function. The data on the outcome of priapism in CML patients from developing world is limited. Methods: We analysed the CML patients treated at PGIMER Chandigarh from January 2003 to December 2018. Baseline spleen and liver size, hematological parameters, Sokal and Hasford score were documented. Duration of priapism, treatment received by the patients, and response to Imatinib were recorded. The severity of ED was assessed by SHIM (Sexual Health Inventory for Men) score. Results: Twenty-three patients (1.7%) out of total 1350 male CML-CP patients had priapism at diagnosis. The median age was 24 years (range 13 – 50 years); 60.8% patients belonged to 21 – 40 years age group. Median duration of priapism was 8 days (range 2 – 25 days). Splenomegaly and hepatomegaly were found in 91.3% and 56.5% patients, respectively. Baseline median hemoglobin was 9.9 g/dL; TLC was 283000/mm3 and platelet count was 352000/mm3. Based on Sokal score, 4/23, 16/23 and 3/23 patients belonged to low, intermediate and high risk categories, respectively. According to Hasford score, 7/23, 14/23 and 2/23 patients belonged to low, intermediate and high risk categories, respectively. All patients received cytoreductive therapy [hydroxyurea and Imatinib]; 21 patients underwent penile aspiration, 13 patients underwent therapeutic leucapheresis and 8 patients underwent distal penile shunt surgery. Majority of the patients (78.2%) achieved CHR at 6 weeks and 21 patients achieved MMR at 12 months. ED could be assessed in 14 patients on follow up. As per SHIM score, 2/14 and 12/14 patients had moderate and severe ED, respectively. The occurrence and severity of ED was unaffected by leucapheresis or shunt surgery. Conclusions: We found severe ED on follow up among majority of CML-CP patients with priapism at presentation. Despite favourable response to Imatinib, long duration of symptoms and hyperleucocytosis probably contributed to ischemic priapism and severe ED in the study cohort. We conclude that prolonged and untreated priapism in CML-CP patients is a major risk factor for ED. There is a need to sensitise the primary care physicians and surgeons in the developing world regarding this grave complication in CML patients.
LILRB4 expression in CMML and MDS based on response to hypomethylating agents.
Authors: Chien Kelly Sharon , Class Caleb A. , Montalban-Bravo Guillermo , Sasaki Koji , Naqvi Kiran , Ganan Gomez Irene , Wei Yue , Yang Hui , Kanagal-Shamanna Rashmi , Kantarjian Hagop M. , Garcia-Manero Guillermo 
Published: March 2020

e18550 Background: Leukocyte immunoglobulin-like receptor B4 (LILRB4) is expressed on M4 and M5 monocytic acute myeloid leukemia (AML) cells and leads to negative regulation of immune cell activation via T cell suppression. Its expression and role in chronic myelomonocytic leukemia (CMML) and myelodysplastic syndrome (MDS) are unknown. We investigated LILRB4 expression in patients with CMML and MDS and correlated it with response to hypomethylating agent (HMA) therapy. Methods: We evaluated bone marrow samples from 19 patients with CMML and 27 patients with MDS from 2008-2014. Transcriptomic and splicing analysis by RNA sequencing were performed on CD34-positive cells in CMML and MDS patient samples in addition to AML or MDS cell lines (n = 6). Gene set enrichment analysis was used to identify pathways associated with increased LILRB4 expression. Results: By the WHO 2016 classification for CMML, there were 8 CMML-0, 5 CMML-1, and 6 CMML-2 patients, and there were 2 low-risk, 8 intermediate-1-risk, 12 intermediate-2-risk, and 5 high-risk MDS patients by IPSS. A total of 12 CMML patients and 27 MDS patients received HMA, with 6 and 12 showing response, respectively. RNA expression of LILRB4 was increased in CMML patients when compared to MDS patients and healthy controls (q < 0.1) with no difference in expression based on risk groups. Pathway analysis revealed upregulation of PD-1 signaling (p = 0.004), CTLA-4 signaling (p = 0.004), and inflammatory response (p = 0.004), and gene correlates revealed a positive association with CTLA-4 expression (p = 0.05). LILRB4 expression was slightly increased in CMML patients who responded to HMAs (q > 0.1). In cell lines, LILRB4 was expressed in MOLM13 (AML M5), SKM1 (AML M5), and U937 (histiocytic lymphoma), with an increase in HMA-sensitive MOLM13 cells compared to HMA-resistant MOLM13 cells (q < 0.01) and no difference based on HMAs seen in other cell lines. Conclusions: LILRB4 expression is increased in CMML, with further increase in those exhibiting response to HMA therapy. It is positively correlated with immune checkpoint signaling pathways, particularly CTLA-4 expression. This may set the basis for exploring the possibility of anti-LILRB4 and anti-CTLA-4 combinations.
The role of frailty and comorbidity in treatment (tx) of elderly patients with Hodgkin lymphoma (HL).
Authors: Rodday Angie Mae , Hahn Theresa , Lindenauer Peter K , Friedberg Jonathan W. , Evens Andrew M. , Parsons Susan K. 
Published: March 2020

e19011 Background: While HL is highly curable in younger patients, older patients have higher rates of tx failure and death, which may reflect age-related factors, tx decisions, or disease biology. We described first-line tx in elderly patients with HL by frailty, comorbidity, and age. Methods: We analyzed Surveillance, Epidemiology and End Results (SEER)-Medicare data from 1999-2014. Patients with incident classical HL and Medicare Part A and B fee for service were included. First-line tx within 4 months of diagnosis (dx) was determined from inpatient, outpatient, and physician/supplier claims using chemotherapy J-codes, HCPCS codes, and DRG codes and was categorized as standard regimen, any other tx, and no tx. Pre-existing frailty and comorbidity ≤6 months prior to dx were separately defined using validated claims-based algorithms. Multinomial logistic regression estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI) to identify whether frailty, comorbidity, or age at dx were associated with first-line tx; their 3- and 2-way interactions were tested and removed if p < 0.1. We adjusted for race/ethnicity, Medicaid dual enrollment, population density, histology, stage, B symptoms, year (yr) of dx, and SEER registry. Results: Analyses included 2789 patients: median age was 76 yrs. 65% were frail, 79% of patients had ≥1 comorbidity, and 61% were frail and had comorbidity. 41% received a standard regimen, 32% received other tx, and 27% received no tx. No interactions were significant. Frailty, comorbidity, and older age were associated more use of other tx or no tx then standard regimens (Table). Conclusions: Frailty, comorbidity, and age were associated with first-line tx in elderly patients with HL. This may reflect physician tx decision, end-of-life care, or unique disease biology in older patients. Future research will study the relationships between first-line tx and outcomes. [Table: see text]
Activity of thymidine kinase as a prognostic marker of malignant proliferation in adolescents with lymphadenopathy.
Authors: Dmitrieva Viktoria V. , Frantsiyants Elena M. , Lysenko Irina B. , Pak Elena E. , Kozyuk Olga V. , Nikolaeva Nadezhda V. , Kapuza Elena A. , Shatokhina Olga N. , Shashkina Larisa Yu. , Kuznetsov Sergei A. , Mkrtchyan Gulnara A. , Starzhetskaya Maria V. , Bespalova Aleksandra I. , Yurchenko Darya Yu. , Popovyan Olga P. , Kutsevalova Olga Yu. 
Published: March 2020

e19013 Background: Lymphadenopathy presents an important differential diagnostic problem. Thymidine kinase (TK) is an intracellular enzyme catalyzing the conversion of thymidine to thymidine monophosphate in the presence of adenosine triphosphate. TK is the product of certain genes for the progression from G1 through S phase. Determination of serum levels of the first TK isoenzyme is considered to have prognostic significance in malignant proliferation. TK increases significantly in the direct contact of malignant cells with biological fluids such as blood, lymph, or serous effusions, therefore its level changes most significantly in systemic blood diseases. Elevated serum TK has prognostic information and determines a high risk of tumor progression. The purpose of the study was to improve the accuracy of diagnosis of Hodgkin's lymphoma in adolescents, with its differentiation from lymphadenitis. Methods: The study included 34 patients: 13 – lymphadenitis, 21 – Hodgkin's lymphoma. Healthy donors served as a control group. Activity of TK1 (U/L) was determined in the blood serum by radioenzymatic method (in vitro) using a standard test system (Immunotech, BeckmanCoulter, Czech Republic). When TK1 activity was within 10.6-14.8 U/L, adenopathy of unclear etiology was considered lymphadenitis, and in 39.6-45 U/L – Hodgkin's lymphoma. Results: Activity of TK in the blood serum of patients with lymphadenitis (U/L) is shown in Table. Conclusions: Activity of thymidine kinase 1 can be measured as an objective marker for the proliferation of malignant cells, increasing the accuracy of Hodgkin's lymphoma diagnosis in adolescents.[Table: see text]