bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracranial hemorrhage (ICH) in acute leukemia (AL): A single-center study from a general hospital with two cases managed with middle meningeal artery (MMA) embolization.
Authors: Yohannan Binoy , Cervoni-Curet Frances Natalia , Martinez Gutierrez Juan Carlos , Chen Peng Roc , Rios Adan 
Published: June 2023

e19033 Background: ICH is a devastating and potentially fatal complication in patients with AL. Contributing factors for ICH include thrombocytopenia, hyperleukocytosis, and coagulopathy. Acute promyelocytic leukemia (APL) has a higher risk of disseminated intravascular coagulation (DIC) and fatal ICH, contributing to early deaths from the disease. At our institution, we have incorporated MMA embolization into traditional methods of observation and surgery for the management of ICH in AL patients. Methods: We performed a single-center retrospective study of adult AL patients with ICH at Memorial Hermann Hospital Texas Medical Center from January 1, 2013, to December 31, 2022. Data collected included: age at diagnosis, type of AL, white blood cell count (WBC), platelet count, coagulation profile, Glasgow Coma Scale score at presentation, response to platelet transfusion, need for surgical, minimally invasive intervention, and mortality rates at 72 hours and 30 days. Descriptive statistics were used to analyze the data. Results: Among 160 consecutive AL patients, we identified 22 (13.75%) with ICH at presentation (APL = 11, AML = 6, B-ALL = 3, Burkitt leukemia = 1, myeloid sarcoma = 1). All were newly diagnosed except for one (an intracranial relapse of AML). Median age was 54 (range, 20–82) years; 60% were women. Subject races included white (n = 10), Asian (n = 5), Hispanic (n = 2), African American (n = 2), and others (n = 3). Median WBC count at admission was 23 (range, 0.2–400) × 109/L. Thrombocytopenia (platelet levels < 50,000/μL) was present in 16 patients (72%), and 3 had platelet counts < 10,000/μL. Twelve patients (54%) had evidence of DIC. Sites of ICH included intraparenchymal (n = 8), subarachnoid (n = 3), subdural (n = 10), cerebellum (n = 1). In 3 patients, ICH extended into the ventricles. Three patients had ≥2 types of ICH. Three patients had middle cerebral artery ischemic stroke in addition to ICH. One patient with myelofibrosis and myeloid sarcoma had bilateral subdural hematomas (SDHs) on admission and developed a fatal basal ganglia ICH during induction chemotherapy. All APL patients were promptly started on all-trans retinoic acid. Two patients had refractory thrombocytopenia. Five patients required craniotomy, with 2 deaths from recurrent ICH. Two patients with SDH underwent MMA embolization with favorable outcomes. Four patients (18%) died within 72 hours of admission (APL = 3, AML = 1). The 30-day mortality rate among patients presenting with ICH was 31% (n = 7). Conclusions: ICH in AL continues to be a major cause of mortality and morbidity. Early diagnosis, transfusion support, correction of coagulopathy, and neurosurgical expertise are critical in improving outcomes in AL-associated ICH. MMA embolization is a new, minimally invasive strategy for the management of SDH in these critically ill patients.
Outcomes of different therapies in acute myeloid leukemia patients with core-binding factor.
Authors: Zhou Yile , Wang Huafeng , Jin Jie 
Published: June 2023

e19036 Background: Acute myeloid leukemia (AML) with RUNX1:RUNXT1 fusion or CBFB:MYH11 fusion is defined as core-binding factor AML (CBF-AML) and has been considered to show favorable prognosis. Methods: We conducted a retrospective analysis on previously untreated CBF-AML patients who received standard-dose induction therapies between Jan 2018 and Dec 2020 in our medical center. Patients were classified into 5 groups based on the induction regimens: VA, DA, IA, HAA, and DAV. The dosage of these regimens were determined as follows: VA, venetoclax 100mg d1,200mg d2, 400mg d3-28, Azacytidine 75mg/m2 d1-7; DA, daunorubicin 60mg/m2 d1-3, cytarabine 100mg/m2 d1-7; idarubicin 8-10mg/m2 d1-3, cytarabine 100mg/m2 d1-7; HAA, homoharringtonine 2mg/m2 d1-7, cytarabine 100mg/m2 d1-7, aclarubicin 12mg/m2 d1-7; DAV, daunorubicin 60mg/m2 d1-3, cytarabine 100mg/m2 d1-7, venetoclax 100mg d4, 200mg d5, 400mg d6-11. The response rate and survival data were analysed between these groups. Results: There’s a total of 106 CBF-AML patients involved, 85(80.2%) with RUNX1:RUNXT1 fusion and 21(19.8%) with CBFB:MYH11 fusion. The most common concomitant mutation was KIT (33%), and the most frequent hotspot mutation site was D816V in exon 17. The median age was 46 years ranging from 7 to 78, and 46.2% of the patients were male.Patients were classified into 5 groups based on the induction regimens, and there were 9 in VA group, 21 in HAA group, 23 in DA group, 38 in IA group, and 15 in DAV group. The CR rate of each group was 55.6%(VA), 87.0%(DA), 65.8%(IA), 90.4%(HAA), and 100%(DAV) respectively. Among the patients who received CR, patients in DAV group showed more pronounced decreasing of fusion gene levels (median 1450 fold) than other groups, while VA group had the slightest (median 8.9 fold). As to the survival, the median follow-up time was 15.2 months, and the median overall survival (OS) were not reached in all the groups. In the RUNX1:RUNXT1 fusion subgroup, DAV group showed significantly improved OS and event-free survival (EFS) than other groups, while VA groups was the worst. The median EFS were as follows: 3.5months(VA), not reached(HAA), 10.9months(DA), 7.9months(IA), and not reached(DAV) respectively. Conclusions: Our study demonstrated a promising therapeutic results of DAV regimen, and an unsatisfactory therapeutic results of VA regimen in CBF-AML. CBF-AML patients showed significantly improved CR rate, elimination of fusion genes, OS, and EFS when received intense chemotherapy, especially DAV and HAA regimen, than VA regimen. These results indicated that intense chemotherapy may be an optimal choice for CBF-AML.
Phase II trial of mini-hyper-CVD-inotuzumab (InO) followed by blinatumomab (blina) consolidation in patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL).
Authors: Nasnas Cedric Christophe , Jabbour Elias , Haddad Fadi , Short Nicholas James , Macaron Walid , Zoghbi Marianne , Nasr Lewis Fady , Jain Nitin , Almanza Emmanuel , Sasaki Koji , Ravandi Farhad , Kebriaei Partow , Huang Xuelin , Garcia-Manero Guillermo , Kadia Tapan M. , Wang Sa A , Jacob Jovitta , Garris Rebecca , O'Brien Susan M. , Kantarjian Hagop M. 
Published: June 2023

e19037 Background: Promising results were seen with low intensity chemotherapy mini-Hyper-CVD (mini-HCVD) in combination with InO in R/R ALL. Adding blina may further improve outcomes. Methods: Pts with R/R Philadelphia-negative B-ALL were treated with mini-HCVD (Cycles 1, 3, 5, 7) and methotrexate/cytarabine (Cycles 2, 4, 6, 8) for 8 cycles. Initially, InO was given on Day (D) 3 of the first 4 cycles at the dose of 1.8-1.3 mg/m2 in Cycle (C) 1, followed by 1.3-1.0 mg/m2 in subsequent cycles. POMP maintenance was for a total of 3 yrs. Protocol was amended after pt #67 to add 4 cycles of blina after 4 cycles of mini-HCVD+InO. InO was given on D2 and 8 at the dose of 0.6 and 0.3 mg/m2 in C1, and then on D2 and 8 at the dose of 0.3 mg/m2 in subsequent cycles; blina was given at standard dose in C5-8. Maintenance was reduced to 12 cycles of POMP with 1 cycle of blina after each 3 cycles of POMP for a total of 4 cycles. Rituximab was given for CD20+ disease. All pts received 8 doses of intrathecal chemotherapy. Results: Between 2/2013 and 7/2021, 110 pts were treated. Patient characteristics are shown in the table. 79 (72%) pts were treated in Salvage (S) 1, and 31 (28%) in S2+. 21 (19%) pts had received prior ASCT. 91 (83%) pts responded (complete remission, 63%). The overall response rate was 93% in S1, 59% in S2, and 57% in S3+. The rates of MRD negativity by flow were higher in S1 vs S2+ (89% vs 67%; P=0.047). 53 (48%) pts underwent ASCT. After a median follow-up of 48 months (mo) (range, 9-115), the median OS and RFS were 17 mo (4-yr, 36%) and 13 mo (4-yr, 37%), respectively. Pts in S1 had better OS compared with S2+ (4-yr OS, 43% vs 18%; P<0.001). The 4-yr RFS was 38% in S1 and 27% in S2+ ( P=0.14). In S1, 41 pts were treated before the amendment and 38 after the amendment; their 4-yr OS was 41% and 48% ( P=0.99), and their 4-yr RFS was 39% and 36%, respectively ( P=0.95). A landmark analysis of pts who achieved remission showed no survival difference between pts who did or did not undergo ASCT, with 4-yr OS of 49% and 48% ( P=0.98), and 4-yr RFS of 46% and 37% ( P=0.68), respectively. Sinusoidal obstruction syndrome (SOS) was noted in 10 (9%) pts, and its incidence decreased from 13% with single dose of InO to 2% with lower and fractionated doses of InO ( P=0.056). Conclusions: The combination of mini-HCVD and reduced-dose InO with sequential blina improved the outcomes of pts with R/R ALL. The new treatment schedule resulted in a lower rate of SOS compared to the original schedule. Clinical trial information: NCT01371630 . [Table: see text]
Gilteritinib or venetoclax in relapsed or refractory FLT3mut acute myeloid leukemia.
Authors: Murray Graeme , Bouligny Ian Michael , Patel Tilak , Doyel Michael , Boron Josh , Tran Valerie , Gor Juhi , Hang Yiwei , Ho Thuy , Zacholski Kyle , Venn Chad Michael , Alnimer Yanal Mufeed , Wages Nolan , Grant Steven , Maher Keri Renee ,   LCRT
Published: June 2023

e19046 Background: FLT3 mutations in AML are associated with high relapse rates and shorter survival compared to FLT3 wild-type. After intensive chemotherapy (IC) failure, clinicians can choose between several salvage regimens; however, the optimal therapy sequence remains unclear. This study compares two salvage therapies: gilteritinib or venetoclax and a hypomethylating agent (HMA; decitabine or azacitidine). Methods: We retrospectively analyzed 129 patients with AML and mutated FLT3-ITD or FLT3-TKD. We identified those that failed first-line IC (CPX-351 or conventional 7+3 with or without midostaurin) and received salvage. We compared patients treated with gilteritinib or venetoclax + HMA as the next line of therapy from January 1, 2018 to January 1, 2022 at VCU Massey Cancer Center. To reduce confounding, no patient in the venetoclax group received gilteritinib in a subsequent line of therapy. We recorded baseline disease characteristics, genetic risk by ELN 2022, induction regimens, response, and survival. We used Fisher’s exact test for nominal data and Mann-Whitney for ordinal data. We analyzed survival by the Kaplan-Meier method and compared groups with the log-rank test. Results: We identified 129 patients with FLT3-ITD or FLT3-TKD mutated AML and analyzed them over 228 treatment phases. In the front-line setting, 89 (68.9%) patients received IC; 55 (61.8%) received salvage therapy for relapsed or refractory disease, and 16 received either gilteritnib (N=6) or venetoclax-based (N=10) salvage. The median age of the gilteritinib cohort was significantly younger ( p = 0.007), but there were no differences between groups with respect to ELN 2022 adverse risk ( p = 0.633) or between ECOG ( p = 0.700) or Charlson Comorbidity Index scores ( p = 0.104). The composite complete remission (CCR; CR + CRi) rate of the gilteritinib cohort was 20.0%, compared to 60.0% for the venetoclax cohort ( p = 0.282). No patient in the gilteritinib cohort achieved MRD negativity. Among responders in the venetoclax cohort, MRD negativity was 75.0% ( p = 0.400). The median overall survival in the gilteritinib cohort was 3.9 months — significantly shorter than 7.8 months for the venetoclax cohort ( p = 0.048). Conclusions: Venetoclax + HMA appears superior to gilteritinib for subsequent therapy after IC failure in FLT3mut AML, despite the gilteritinib cohort being significantly younger. The limitations of this study include its retrospective nature — prospective trials are needed to confirm these findings. [Table: see text]
FLAG-IDA or venetoclax in previously treated TP53mut acute myeloid leukemia.
Authors: Tran Valerie , Bouligny Ian Michael , Murray Graeme , Patel Tilak , Doyel Michael , Boron Josh , Gor Juhi , Hang Yiwei , Ho Thuy , Zacholski Kyle , Venn Chad Michael , Alnimer Yanal Mufeed , Wages Nolan , Grant Steven , Maher Keri Renee ,   LCRT
Published: June 2023

e19047 Background: Patients with del17p or TP53mut acute myeloid leukemia (AML) have short durations of remission and dismal overall survival. The benefit of fludarabine-based intensive chemotherapy (IC), such as FLAG-IDA or FLAG, remains unclear. Additionally, while venetoclax has revolutionized the treatment of AML, the comparative efficacy of venetoclax with a hypomethylating agent (HMA; decitabine or azacitidine) remains unknown in patients with del17p or TP53mut AML. We aimed to compare FLAG-based regimens to venetoclax + HMA in this subgroup of disease while controlling for IC candidacy. Methods: We retrospectively analyzed 79 patients with AML and TP53mut or del17p. Of these, 25 met study inclusion criteria: age 70 or younger, treated with front-line IC, and treated with either fludarabine-based therapy (with or without idarubicin, N = 15) or venetoclax + HMA (N = 10) in the subsequent line. To further reduce confounding effects, no patients in the FLAG group received venetoclax + HMA, and no patients in the venetoclax group received FLAG. We recorded baseline patient and disease characteristics, cytogenetic risk, response, and survival. We used Fisher’s exact test for nominal data and Mann-Whitney for ordinal data. We analyzed survival by the Kaplan-Meier method and compared groups with the Mantel-Cox test. Results: We analyzed 25 patients with TP53mut or del17p AML initially treated with IC and subsequently underwent salvage therapy with FLAG or venetoclax + HMA. The salvage regimen in each cohort was initiated after a median of one line of therapy, with no difference between groups ( p = 0.089). Patients in the FLAG cohort were significantly younger than the venetoclax cohort (54 y. vs 62 y., p = 0.046), but there were no significant differences in the Charlson Comorbidity Index scores (4 vs 4, p = 0.127) or ECOG scores (1 vs 2, p = 0.053) at salvage. There were also no differences in the median TP53 variant allele frequency (VAF) between the cohorts ( p = 0.095). The composite complete remission (CRR: CR + CRi) rate was 28.6% in the venetoclax cohort, compared to 46.7% in the FLAG cohort ( p = 0.648). Patients that received FLAG had significantly prolonged median overall survival compared to venetoclax + HMA (13.1 m. vs 4.5 m., p = 0.004). Conclusions: In patients with del17p or TP53mut AML, FLAG-based salvage appears to offer a significant improvement in overall survival following IC failure. Prospective trial designs are needed to confirm these findings. [Table: see text]
A National Cancer database study on the demographic factors associated with mast cell leukemia.
Authors: Voth Caitlyn , Wu Xinxin , Keirns Darby , Luker Andrew , Silberstein Peter T. , Hsia Beau 
Published: June 2023

e19049 Background: Mast cell leukemia (MCL) is a rare form of malignant mastocytosis that involves a multi-system organ spread of mast cells. One study reported the 5-year overall survival rate as 16.6%. The median age of diagnosis in another study was 56 years, with a higher incidence in female patients compared to males. The rarity of MCL makes it difficult to fully understand its epidemiology, but analyzing database trends could provide valuable insight into the socioeconomic and demographic associations with MCL. Demographic data from the National Cancer Database (NCDB) was examined to assess trends in patients diagnosed with MCL. Methods: A retrospective cohort analysis utilizing the NCDB from 2004 – 2020 examined patients with a histologic diagnosis of MCL (N = 96). Descriptive statistics was used to investigate demographic factors, including: age, sex, race, Hispanic status, educational level, Charlson-Deyo score, household income, insurance type, treatment facility type, type of community, and distance from facility. The incidence trend over time was interpreted via regression analysis. Results: The NCDB had 96 patients with a confirmed diagnosis of MCL between the years 2004 – 2020. The incidence of patients diagnosed per year trended upward (R2 = 0.573). The average age of diagnosis was 60.2 years old and the median age was 63 (SD = 17.5, range = 13 – 88 years). There were more males (53.1%) than females (46.9%) diagnosed. Patients were more likely to be White (87.5%) and non-Hispanic (91.7%). 16.9% of patients were located in an area where 15.3% or more of adults do not have a high school diploma. Most individuals (71.9%) had Charlson-Deyo comorbidity scores of 0, followed by 1 (22.9%). More patients had household incomes in the highest quartile (42.9%). The most common insurance was Medicare (41.7%), followed closely by private insurance (39.6%). An academic/research facility (59.5%) was the most common place for treatment. The vast majority of patients resided in metropolitan counties (85.1%). The average distance of residence from the treatment facility was 54.2 miles (SD = 141.4, range = 0.4 – 1151.1). Conclusions: The information obtained in this NCDB analysis can be used to better understand the demographic factors associated with MCL diagnosis. The median age of diagnosis in the NCDB was 63 years with a predominance of males to females, which differs from the prior literature. Data trends show that patients were most likely White, non-Hispanic, upper quartile income earners, residing in metropolitan counties, and treated at an academic facility. Interestingly, patients were most commonly under Medicare insurance, which is reserved for those over the age of 65 or those with qualifying disabilities. Further studies are needed to understand the discrepancy between this analysis and prior literature, along with the impact this has on patterns of diagnosis, treatment, and overall survival with MCL.
Acute myeloid leukemia (AML) outcomes in the era of novel therapies: A 9-year single-institution experience.
Authors: Gera Kriti , Martir Daniela , Zhang Zhongyue , Adams Carolyn Brooke , Richards Ashley , Hsu Jack , Hiemenz John W. , Brown Randy , Dean Erin , Farhadfar Nosha , Wingard John R. , Al-Mansour Zeina 
Published: June 2023

e19053 Background: Recent advances and approval of multiple targeted and non-targeted agents have significantly transformed care for Acute Myeloid Leukemia (AML) over the past 5 years, particularly for older/unfit patients. While this has provided clinicians with several treatment options in both upfront and relapsed/refractory setting, it has also increased the complexity of clinical decision making. Although several trials have shown immense promise of these therapies, the real-world outcomes have not been reported. The primary aim of this study is to compare survival outcomes in newly diagnosed and relapsed AML before and after the introduction of the novel AML treatments that were granted FDA approval over the past 5 years. Methods: We performed a retrospective single-center analysis on adult patients (≥ 18 years) with newly diagnosed and relapsed AML treated at University of Florida Cancer Hospital between January 2012 and December 2020. Patients were stratified according to the time of diagnosis and Overall survival (OS) was estimated using Kaplan Meier method. Survival between groups was compared using log-rank test. Results: A total of 1617 patients were included in this analysis. Median age was 61 years (range 18-83) and 54.4% of patients were men. 71.4% patients were of white race. Median OS was 71.5 months with 1-year OS of 67.4%. Women had significantly better survival than men (1-year OS: 72% vs 63.6%, p=0.0043). 1-year OS for patients diagnosed in 2012-14, 2015-17 and 2018-20 was 73.5%, 67.6% and 58.1% respectively (p < 0.0001). There were no significant differences in survival based on race. 21.4% (n=347) patients had relapse of AML. Median OS for AML relapse was 9.8 months with 1-year survival of 45.1%. There were no significant differences in survival of patients based on race, sex and year of diagnosis. Conclusions: Our study reports decline in 1-year survival of patients with AML in the modern era despite introduction of several novel therapies in recent years. Additionally, relapsed AML continues to have dismal outcomes despite the availability of multiple novel agents for R/R AML. These results are surprising given the reported good efficacy of these agents in clinical trials. Possible explanations include under-representation of real-life patients in clinical trials, poor tolerability of these therapies by the average patient, and/or barriers to access to these novel therapies in healthcare due to prohibitive high cost, inadequate insurance coverage, or limited availability. Larger-scale real-life population-based studies are needed to further investigate the validity of these findings. [Table: see text]
Impact of body mass index (BMI) and weight changes on hematopoietic stem cell transplant (HSCT) outcomes in the elderly population.
Authors: Hemrajani Anshu , Ismail Zahra , Elms Destry James , Moore Mary , Smith Scott E. , Hagen Patrick , Stiff Patrick J. , Tsai Stephanie 
Published: June 2023

e19058 Background: HSCT remains the only curative treatment for high-risk hematologic malignancies. Reduced intensity conditioning (RIC) has increasingly allowed transplant of elderly patients. However, maximizing outcomes in this population remains a challenge. We examine the influence of BMI and weight changes on HSCT outcomes in the elderly. Methods: This was a retrospective review of 216 patients ≥60 years of age who underwent first HSCT at the Loyola University Medical Center between 8/30/2000-6/15/2017. Pearson Chi-square tests for independence evaluated the associations between categorical variables and timing of recurrence. Fisher’s exact test were used where expected frequencies were <5. Independent two-sample t-tests and ANOVA assessed differences in numerical variables. Results: BMI at time of transplant, defined as underweight (BMI<18), normal weight (BMI 18-25), overweight (BMI 25-30), and morbidly obese (BMI>30), did not impact incidence of cardiac dysfunction, pulmonary complications (Cx’s), renal Cx’s, graft versus host disease (GVHD), paraenteral nutrition (TPN) use, changes in albumin, or mortality. However, there was a trend towards increased disease relapse in those who were not normal weight (p=.08). Normal weight (BMI 18-25) at Day 100 was associated with decreased cardiac dysfunction (p=.02), days of hospitalization (p = .03), and mortality (p = .02) compared to non-normal BMI (BMI < 18 or BMI > 25). But there appeared no difference in rates of renal Cx's, GVHD, TPN use, or relapse. Having >10% weight change at discharge from transplant admission was associated with increased renal Cx’s (p = .007), infectious Cx’s (p = .03), use of TPN (p = .006), length of hospital stay (p = .0002), and mortality (p = .009). However, it was not associated with cardiac dysfunction, pulmonary Cx’s, readmissions by 6 months, GVHD, or relapse. Having >10% weight change at Day 100 was associated with increased risk of acute (p = .01) and chronic GVHD (p = .002) and readmissions by 6 months (p = .01), but not with other Cx’s, relapse, or mortality. Conclusions: Patients who were underweight or overweight at key timepoints may impact complications and HSCT outcomes. Furthermore, maintaining a stable weight during transplant admission and the first 100 days was associated with decreased rates of complications and adverse HSCT outcomes. These findings warrant further evaluation into age-related weight and nutritional targets to improve understanding and optimize HSCT outcomes in this vulnerable population. [Table: see text]