bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of cladribine, idarubicin, cytarabine (CLIA) plus gilteritinib in patients (pts) with FLT3 mutated acute myeloid leukemia (AML).
Authors: Abuasab Tareq , Kantarjian Hagop M. , Garcia-Manero Guillermo , Bravo Guillermo Montalban , Alvarado Valero Yesid , Daver Naval Guastad , Yilmaz Musa , Pemmaraju Naveen , Chien Kelly Sharon , Kornblau Steven Mitchell , Burger Jan Andreas , Jain Nitin , Islam Rabiul , Dinardo Courtney Denton , Borthakur Gautam , Jabbour Elias , Ravandi Farhad , Kadia Tapan M. 
Published: June 2022

e19036 Background: The addition of multi-kinase inhibitors of FLT3 such as midostaurin and sorafenib to chemotherapy have demonstrated improved outcomes in patients with newly diagnosed FLT3 mutated AML Gilteritinib (gilt) is a second generation FLT3 inhibitor approved for pts with relapsed/refractory (R/R) FLT3-mutated AML. We studied to the combination of gilt with the CLIA regimen in FLT3 mutated AML. Methods: Eligible pts were between 18-65 years (yrs) with FLT3-mutated AML. Induction was: Cladribine 5 mg/m2 IV on D1-5, Cytarabine 1.5-2.0 g/m2 IV on D1-5, Idarubicin 10 mg/m2 IV on D1-3 and gilt 120 mg on D1-14. Consolidation was cladribine 5 mg/m2 IV for 3d, Cytarabine 750 mg/m2 IV for 3 d, and idarubicin 8 mg/m2 IV for 2 d, with gilt 120 mg continuously during cycle two onward. A historical cohort combining sorafenib (400 mg PO BID) with idarubicin + cytarabine (1.5 g/m2) backbone was used as comparison. Results: Twenty-four pts were enrolled with a median age of 53 yrs (range, 28-63). 21 pts (88%) had FLT3-ITD, 6 pts (25%) had FLT3-D835, and 3 pts (13%) had both. Nineteen pts (79%) had diploid cytogenetics, and 4 pts (18%) had trisomy 8. The most commonly co-occurring mutations were: NPM1 (46%), ASXL1 (29%), DNMT3A (29%), TET2 (25%), and KDM6A (20%). 16 pts (67%) achieved complete remission (CR), 2 (8%) had CR with incomplete recovery (CRi), for a CR/CRi rate of 75%. 13 responding pts (54%) underwent to allogeneic SCT. The median overall survival for the entire cohort was not reached. We compared these outcomes to our historical cohort of 107 pts treated with sorafenib combined with high-dose cytarabine-based chemotherapy. Other than older age and greater anemia for the gilt, there was not significant difference in baseline characteristics between the two groups. The CR/CRi rate was similar (75% gilt vs. 71% sorafenib; P = > 0.999) between the 2 cohorts; while there was a trend, there was no significant difference in OS with CLIA + Gilt (median NR vs. 17.3 months for sorafenib; P = 0.533). Conclusions: The combination of the FLT3 inhibitor gilteritinib to CLIA produced high rates of complete remission in pts diagnosed with FLT3-mutated AML. These results were similar for Sorafenib when combined with intensive chemotherapy with OS rates favoring gilteritinib. Further study of intensive chemotherapy with different FLT3 inhibitors is warranted. Clinical trial information: NCT02115295.
Retrospective analysis of toxicities and clinical outcomes with BCR-ABL1 tyrosine kinase inhibitors in B-cell acute lymphoblastic leukemia.
Authors: Venn Chad Michael , Zacholski Kyle , Tran Valerie , Alnimer Yanal Mufeed , Ho Thuy , Maher Keri Renee , Bouligny Ian Michael 
Published: June 2022

e19039 Background: The rapid adoption of BCR-ABL1 TKIs in Ph+ B-ALL occurred despite a lack of comparative trials, leading to an absence of data regarding the additive toxicities of BCR-ABL1 TKIs with many standard chemotherapy regimens. BCR-ABL1 TKIs have been associated with severe adverse events and may significantly impact treatment-related morbidity and mortality. The objective of this study is to describe the cumulative toxicity imposed by BCR-ABL1 TKIs and chemotherapy regimens. Methods: A total of 48 patients with Ph+ B-ALL treated with a BCR-ABL1 TKI plus chemotherapy between January 2015 and October 2021 were eligible to assess treatment-related toxicity. High-intensity chemotherapy regimens included HyperCVAD, CALGB 10403, ECOG1910, and ECOG2993; low to moderate intensity regimens included EWALL-Ph-01, TKI + POMP, TKI + corticosteroids, and TKI monotherapy. Regimens containing blinatumomab and inotuzumab ozogamicin in combination with a TKI were assessed separately. The primary outcome was the occurrence of grade 3/4 toxicities, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The first occurrence of CTCAE toxicities was collected for each line of therapy patients received. Results: Among the 48 patients analyzed, 71 total lines of therapy were identified. Of these, 54.9% (n = 39) were classified as high-intensity, 29.6% (n = 21) were low-moderate intensity, 9.9% (n = 7) were blinatumomab, and 5.6% (n = 4) were inotuzumab ozogamicin. In high- and low-moderate intensity regimens, a mean of 10.1 and 6.9 grade 3/4 toxicities occurred with dasatinib and imatinib, respectively (p = 0.076). Among low-moderate intensity regimens with dasatinib (n = 11), 63.6% (n = 7) discontinued dasatinib, 9.1% (n = 1) decreased the dasatinib dose, and 36.4% (n = 4) decreased or discontinued dasatinib due to toxicity. High-intensity chemotherapy regimens with dasatinib demonstrated 51.6% (n = 16) discontinuation, 38.7% (n = 12) dasatinib dose reduction, and 62.1% (n = 18) decreased or discontinued dasatinib due to toxicity. Conversely, among low-moderate (n = 4) and high-intensity (n = 5) regimens in combination with imatinib, no discontinuations or dose reductions occurred. These data demonstrate a greater dose reduction and discontinuation rate with dasatinib compared to imatinib in high-intensity regimens (p = 0.011); differences in low-moderate intensity regimens were not observed (p = 0.174). A secondary analysis did not reveal an association with dasatinib discontinuation rate and CR rate (p = 0.829) or overall survival (p = 0.941). Conclusions: A greater incidence of grade 3/4 toxicity leading to dose changes or discontinuation occurred with dasatinib compared to imatinib. While differences in CR or OS due to TKI-related toxicity were not identified, their occurrence likely contributes to treatment-related morbidity.
Mucormycosis in hematopoetic stem cell transplant recipients: A systematic review.
Authors: Rehman Mohammad Ebad Ur , Saeed Sajeel , Franco Diana , Chattaraj Asmi , Basit Jawad , Khan Hamza , Fazal Faizan , Anwer Faiz 
Published: June 2022

e19043 Background: Mucormycosis is a life-threatening infection caused by opportunistic fungi belonging to the order Mucorales. High mortality is reported in hematopoietic stem cell transplant (HSCT) recipients who develop mucormycosis in the post-transplant immunosuppressed state. This study reviews the epidemiology, diagnosis, treatment and outcome of mucormycosis in HSCT recipients. Methods: A systematic literature search was conducted on PubMed and Embase from inception to 5 Jan, 2022 using MeSH terms for 'mucormycosis' and 'hematopoietic stem cell transplantation'. We included case reports, case series and observational studies reporting individual patient data. Summary statistics were calculated for patient characteristics by tabulation and percentages. Hazard ratios were calculated using unconditional Cox proportional hazard models. Data analysis was done using SPSS. Results: The initial search revealed 405 articles. After exclusion of duplicates, reviews and non-relevant articles, data was included from 122 articles (183 patients). The most common sites of infection were lung (36.6%) and rhinocerebrum (7.1%). Disseminated infection occurred in 34 (18.6%) cases. Diagnosis was confirmed using histology, culture or both in 27%, 13% and 34% of cases, respectively. Seven genera of zygomycetes were identified, of which Rhizopus was most common (37.2%). The most common antifungals used were liposomal amphotericin B (LAMB) (74%) and posaconazole (27%). Surgical debridement was employed in 64 (35%) cases. Overall survival was 32% with LAMB and 34% with surgical debridement. Sixteen patients did not receive any therapy; none survived. Mortality was reported in 121 patients (68.4%). Death was attributed to mucormycosis in 84 cases (45.9%). Death attributed to mucormycosis was more frequent in Rhizopus infections (56%) compared to other species (40%, HR = 1.89, 95% CI 1.13-3.15, p < 0.05). Patients who underwent HSCT due to chronic myeloid leukemia (CML) had greater mortality due to mucormycosis (72%) compared to those with other underlying diseases (43%, HR = 2.31, 95% CI 1.26-4.21, p < 0.05). Conclusions: Mucormycosis has high mortality in HSCT recipients. Surgery and LAMB therapy can significantly improve survival. Prospective studies need to be undertaken to identify risk factors for mortality and appropriate treatment strategies. [Table: see text]
Initiation of an eligibility screening protocol prior to tissue typing of potential stem cell donors resulted in substantial cost savings.
Authors: St. John Luke , Gregory Tara K. , Wagner Patricia , Meissner Sarah , Schade Henning , Bearman Scott Irvin , Nash Richard A. , Rotta Marcello , Matous Jeffrey V. , Eghtedar Alireza , Tees Michael Timothy , Maris Michael B. , Mountjoy Luke 
Published: June 2022

e19047 Background: Human Leukocyte Antigen (HLA) typing is a necessary but expensive process to identify suitable donors for allogeneic hematopoietic cell transplantation (HCT) for the treatment of bone marrow disorders and hematologic malignancies. The likelihood of a patient and sibling being fully HLA matched is 25%. An HLA-identical related donor remains the preferred source among HCT recipients due to superior outcomes when compared to unrelated, mismatched, haploidentical, or cord blood. Because of the high probability of finding an HLA matched donor among siblings, and the benefit of quick access to these donors, it had been standard procedure at our institute to test all siblings to identify potential matches. The estimated costs of HLA typing alone is approximately $300-$1000 and is contingent upon the lab utilized and resolution of typing. The costs of HLA typing, additional testing, and screening are significant to patients and health care systems. Methods: Our institution initiated a protocol to assess potential sibling donors prior to HLA typing as per the donor eligibility guidelines of the National Marrow Donor Program (NMDP). From 2018-2020 each sibling was given a questionnaire prior to HLA typing and screened for suitability. If a sibling was determined to be ineligible for donation based on the NMDP guidelines, HLA typing and work up for that sibling was not pursued. Results: Between 2018 and 2020 we identified 789 potential donors for HCT. All potential donors were sent eligibility questionnaires. Based on this screening, 568 potential donors were found to be eligible for donation whereas 221 were ineligible. HLA typing was pursued in all eligible donors. This resulted in and estimated cost savings of $66,000-$221,000 in HLA typing alone. This translated into a substantial health care cost savings for our institution as compared to our prior policy of typing all siblings. Conclusions: Identification and work up for potential HLA matched siblings is critical for identifying optimal donors for HCT. Our previous policy of universal sibling screening was found to be costly due to typing individuals who later were found to be ineligible to donate. We found that the initiation of a simple donor screening protocol that excluded ineligible sibling donors resulted in significant cost savings compared to our prior policy of HLA typing all potential sibling donors. Cost savings are a relevant consideration in all aspects of healthcare and this screening tool could be a practical component of the best practice guidelines for HLA matching and HCT.
The efficacy and safety of second allogeneic hematopoietic stem cell transplantation.
Authors: Toprak Selami Kocak , Kırcalı Ekin , Cengiz Seval Guldane , Civriz Bozdag Sinem , Yuksel Meltem Kurt , Topcuoglu Pervin , Arslan Onder , Ozcan Muhit , Demirer Taner , Gurman Gunhan , Beksac Meral , Ilhan Osman 
Published: June 2022

e19048 Background: Second allogeneic hematopoietic cell transplant (sAHCT) might be indicated following a graft failure or disease relapse after the first one; although it might emerge with high rates of morbidities and mortality. Currently, there is a limited number of publications on this matter in the literature, here we aimed to share our sAHCT experience from a single center. Methods: Data from 51 patients who were eligible for sAHCT between 2001 and 2021 was evaluated retrospectively. All data was obtained from the Ankara University Faculty of Medicine, Department of Hematology and Bone Marrow Transplant Unit. Results: 51 patients were included in the present study. Median age at sAHCT was 34 (18- 65) and female/ male ratio 19/ 32 (37.3% / 62.7%). The same donor from the first transplant was eligible for sAHCT for most patients (n= 46, 90.2 %). sAHCT indication was graft failure for 11 patients (21.6 %) whereas 40 (78.4 %) patient went on sAHCT for disease relapse. Patients’ diagnoses were as follows: acute myeloid leukemia (n= 26, 50.9 %), acute lymphoblastic leukemia (n=9, 17.6 %), myelodysplastic syndrome (n= 6, 11.8 %), aplastic anemia (n= 6, 11.8 %) and others (CMML, CML, biphenotypic leukemia). Median number of transplanted CD34+ hematopoietic cells was 5.77 x x106/ kg (1.11- 8.29). Stem cell source was either bone marrow (n= 5, 9.8%) or peripheral blood (n= 46, 90.2 %). Myeloablative conditioning regimens were used for most sAHCTs (n= 30, 58.8%). Median overall survival (OS) rates for graft failure and disease relapse groups were 12.8 and 18.7 months, respectively (p= 0.63). During early transplant phase, 20 patients (39.2 %) died due to bone marrow aplasia, transplant failure or other complications. 1 year OS of the entire cohort was 33.3 % whereas 2-y- OS was 21.6% (95% CI= 25-45). 2 patients (3.9 %) died due to COVID19 during transplant process. On univariate analysis, sex, time from the first transplant (<12 months/ ≥12 months), conditioning intensity, sAHCT indication did not statistically significantly influence OS. Multivariate analysis confirmed a lower ECOG score (<2) at sAHCT significantly increased OS (p= 0.001). Conclusions: Based on this single center study, sAHCT is an efficacious treatment modality especially for patients with lower ECOG scores. sAHCT may offer long term survival for both graft failure and disease relapse states.
Treatment with anti-spike monoclonal antibodies in allogeneic HCT and CAR T-cell recipients with mild to moderate COVID-19: The Mayo Clinic experience.
Authors: Mohty Razan , Thoendel Matthew , Swei Samuel , Bansal Radhika , Palmer Jeanne , Hogan William J. , Vergidis Paschalis , Munoz Javier , Iqbal Madiha , Yassine Farah , Bennani Nabila Nora , Hathcock Matthew , Murthy Hemant S. , Castro Januario E. , Lin Yi , Razonable Raymund R. , Kharfan-Dabaja Mohamed 
Published: June 2022

e19049 Background: Prognosis of COVID-19 is poor in the setting of immunosuppression. Casirivimab/imdevimab (REGEN-COV), bamlanivimab, and sotrovimab are investigational monoclonal antibodies (MoAbs) authorized for treatment of mild/moderate COVID-19 for patients (pts) 12 years or older and who are at high-risk for progression to severe COVID-19. These neutralizing antibodies, against SARS-CoV-2 spike proteins, have been shown to decrease risk of progression to severe disease. Recipients of allogeneic stem cell transplants (allo-SCT) or chimeric antigen T cell therapy (CAR T cell) represent a high risk population. However, treatment outcomes with these MoAbs in these pts are not well described. Methods: This retrospective study included 33 consecutive adult pts who developed mild/moderate COVID-19 and received anti-spike SARS-CoV-2 MoAbs between December 2020 and November 2021. Allo-SCT (N=27) or CAR T cell (N=6) recipients were included, and outcomes were analyzed separately. Pts received REGEN-COV (N=19), bamlanivimab (N=11), or sotrovimab (N=1), missing (N=2). Results: In the allo-SCT cohort (N=27), median age at time of COVID-19 was 55 (23-76) years. Median time from allo-SCT to COVID-19 was 31 (22-64) months. Two pts received CAR T-cell therapy prior to allo-SCT. Diagnoses included leukemia or myeloid diseases (82%), lymphoma (11%), or myeloma (7%). Transplant characteristics are summarized (Table). Thirteen pts were vaccinated against SARS-CoV-2 prior to breakthrough COVID-19. Events considered included hospitalization due to COVID-19, disease progression, or death from any cause. The 6-month event-free and overall survivals were 81% and 91%, respectively. In the CAR T cell recipients cohort (N=6), 4 pts received axicabtagene ciloleucel for diffuse large B-cell or follicular lymphoma and 2 received brexucabtagene autoleucel for mantle cell lymphoma. The median follow-up was 8 (1-11) months. Two pts received autologous SCT prior to COVID-19. Median time from CAR T cell therapy to COVID-19 was 10 (3-24) months. Three pts were vaccinated prior to COVID-19. Only 1 pt was hospitalized due to severe COVID-19 requiring mechanical ventilation leading to death. Conclusions: These results show a potential benefit of MoAbs in high-risk pts, namely allo-SCT or CAR T cell recipients. Future studies should evaluate the role of prophylactic use MoAbs in these populations. A comparative analysis with a matched control cohort (who did not receive MoAbs) will be provided at the meeting. [Table: see text]
Palliative care pilot initiative for transplant patients: The Westchester Medical Center experience.
Authors: Mowatt Kelley , Danyko Stephanie , Barrie Mariama-Seray , Gordon Sandra , Marcotte Kathy , Rotundo Erica , Schoenfarber Adam , Ahmed Tauseef , Liu Delong , Seiter Karen , Lugassy Mara , Steinberg Amir S. 
Published: June 2022

e19050 Background: It is well known HCT recipients experience multiple symptoms affecting quality of life. Emerging data supports the role palliative care can play in mitigating these issues. Our cellular therapy team collaborated with the Palliative Care team on a pilot project incorporating their expertise into the management of our new allogeneic transplant patients. We chose this group of patients given their increased needs relative to other cellular therapy recipients (i.e. autologous, CTL) and our institution’s available resources. Methods: Patients admitted to the HCT unit for allogenic stem cell transplant underwent palliative care consult during their conditioning regimen. During the initial palliative care visit, performed by a specialist palliative care nurse practitioner, patients underwent comprehensive assessment of physical symptoms, psychosocial distress, and overall quality of life. Patients were then followed during hospitalization by members of the palliative care team including Nurse Practitioner, Social Worker and Chaplain, to address identified needs and support both the patient and their family. The palliative care team provided daily communication and recommendations to our inpatient HCT team. Results: Patient one was a 61-year-old man with intermediate risk MDS who underwent a reduced intensity conditioning regimen of busulfan, fludarabine, and alemtuzumab. His transplant was complicated by delirium and anorexia. Patient two was a 63-year-old man with AML who underwent a reduced conditioning regimen of the same combination. His transplant was complicated by bone pain and insomnia. Patient three was a 70-year-old woman with AML who also underwent a reduced conditioning regimen. Her transplant was complicated by severe mucositis and gastric reflux. Conclusions: Allogeneic stem cell transplant patients experience a multitude of symptoms and psychosocial distress. With the help of a dedicated palliative care assessment, we can improve patients’ quality of life during their admission for the transplant. Considering the positive feedback from patients, we plan to conduct a formal prospective study evaluating the impact of palliative care on adult stem cell transplant patients at our institution. By addressing the patient’s whole person rather than just their disease, we also hope to decrease number of admissions as well as length of stay. Ultimately, we look forward to expanding this to other malignancies as well.
Ruxolitinib in chronic steroid-refractory graft-versus-host-disease.
Authors: Kovalenko Iuliia , Saleem Tabinda , Laek Babray , Ali Rimsha , Mirza Taaha Muddassir , Chattaraj Asmi , Wahab Ahsan , Tamez ud din Asma , Qurashi Hafiz , Golubykh Konstantin , Malik Maidah , Khan Rafiullah 
Published: June 2022

e19053 Background: Ruxolitinib, an elective Janus Kinase (JAK) 1/2 inhibitor, has been approved by FDA for the treatment of steroid-refractory chronic graft-versus-host-disease (SR cGVHD) after the failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older. However, it remains underutilized despite promising results in the treatment of SR cGVHD. Methods: We did a comprehensive literature search across various data sets, including PubMed, Cochrane, and Embase, and presented data in ASH and ASCO. A review of the most recent data is summarized in this abstract. Results: Two retrospective cohort studies and one pilot prospective study evaluated ruxolitinib in SR cGVHD. In a retrospective cohort study by Yang et al., 36 patients with SR cGVHD treated with ruxolitinib showed complete response (CR) in 27.8% of patients with complete disappearance of cGVHD symptoms and partial response (PR) with symptom relief of 52.7% at a dose of 2.5 to 10 mg two times daily with ruxolitinib tapering one week after symptoms improvement. In the pilot prospective study by Mozo et al., 12 pediatric patients with SR cGVHD received ruxolitinib at a dose of 2.5 to 10 mg two times daily and showed CR in 8.3% of patients and PR in 82.7% of patients. Morozova et al. conducted a prospective pilot study in 20 patients with primary or secondary myelofibrosis who were treated with pre-transplant ruxolitinib 45 mg/day from ruxolitinib (45 mg) starting from seven days before transplant to 2 days before the transplant, and 15 mg from day five after transplant to day 100 after transplant along with cyclophosphamide 50 mg/kg on days three and four after transplant. PR was observed in 47.1% of patients at 6 months with the incidence of cGVHD of 20%. In Phase III trial by Zeiser et al. reported CR of 6.7% and PR of 43% in 165 patients treated with ruxolitinib at a dose of 10 mg daily for 6 cycles (28 days/cycle). The most common all-grade adverse events are listed here. Conclusions: Ruxolitinib was recently approved by FDA for the treatment of SR GVHD and should be utilized more due to its high effectiveness and tolerable safety profile.[Table: see text]