scholarly journals ETV6-NTRK3 is Associated With Trisomy 8 and Sensitive to TRK Inhibitor in Hematologic Malignancy: Case Report of a Refractory AML and Review of the Literature

2021 ◽  
Author(s):  
Ling Zhang ◽  
Lijun Wen ◽  
Zheng Wang ◽  
Zhao Zeng ◽  
Yi Xu ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Hematologic Malignancy ◽  
Low Frequency ◽  
Chromosomal Translocation ◽  
Fusion Transcript ◽  
Hematologic Malignancies ◽  
Tumor Type ◽  
Trisomy 8 ◽  
Genetic Features ◽  
Genetic Aberration

Abstract Background: The ETV6-NTRK3 fusion transcript has been found to recurrently identified in both solid tumors and leukemias. It has attracted a lot of interest for the clinical targeted therapy and genetic features in ETV6-NTRK3 positive solid tumors. While the t(12;15)(p13;q25)/ETV6-NTRK3 is a rare genetic aberration in hematologic malignancies at a low frequency of ≤1%. An accumulation of reported cases would be needed to discuss clinical and cytogenetic characteristics of the important entity. Therefore, it is useful to report every case for clinical implication of prognosis or therapy. Case presentation: We report the case of a previously healthy 30-year-old female, who was diagnosed as acute myeloid leukemia (AML) and presented with chemoresistance and short survival. The patient was treated with four cycles of chemotherapy but failed to achieve remission. Then the patient underwent a salvage haploidentical stem cell transplantation. Unfortunately, she worsened within 1 month and died of the refractory leukemia 35 days after transplantation. ETV6-NTRK3 rearrangement was revealed by RNA sequencing but the chromosomal translocation t(12;15)(p13;q25) was cryptic by conventional karyotype analysis. We review the literature and find that the ETV6-NTRK3 fusion transcript is associated with cryptic karyotype, trisomy 8, aggressive and poor prognosis in hematologic malignancy. The clinical and laboratory characteristics of ETV6-NTRK3 positive hematologic malignancies are different from those of solid tumors. Nevertheless, tropomyosin receptor kinase (TRK) inhibitor has powerful anti-tumor activity in patients with TRK fusion–driven cancers, regardless of the tumor type. Conclusions: We demonstrated that TRK inhibitor larotrectinib is an effective treatment on the primary bone marrow (BM) cells derived from the patient described here with ETV6-NTRK3 positive AML. Our report stresses the importance of screening for ETV6-NTRK3 fusion transcript in newly diagnosed leukemias and clinical treatment of TRK inhibitor in hematologic malignancies.

Effectiveness of Darbepoetin alfa Administered Every 3 Weeks on Clinical Outcomes in Patients with Hematologic Malignancies and Chemotherapy-Induced Anemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3767-3767 ◽  
Author(s):  
Ralph Vincent Boccia ◽  
Peter T. Silberstein ◽  
Simon Tchekmedyian ◽  
Dianne Tomita ◽  
Greg Rossi ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Darbepoetin Alfa ◽  
Hematologic Malignancy ◽  
Hematologic Malignancies ◽  
Target Range ◽  
Tumor Type ◽  
Open Label ◽  
Serious Adverse Events ◽  
The Mean ◽  
Tumor Types

Abstract Patients (pts) with cancer receiving chemotherapy commonly have chemotherapy-induced anemia (CIA), often resulting in reduced quality of life. The primary objective of this analysis was to summarize the effectiveness of darbepoetin alfa (DA) administered at 300mcg every 3 weeks (Q3W), in achieving and maintaining a hemoglobin (Hb) target range of 11–13g/dL in pts with hematologic malignancies and CIA, versus pts with solid tumors and CIA. Data for all 1493 pts enrolled in this multicenter, open-label, 16-week study who received at least one dose of DA are included in this exploratory analysis stratified by tumor type. Pts ≥18 years of age receiving multicycle chemotherapy and with Hb <11g/dL were eligible for this study. Hb-based endpoints were adjusted for red blood cell transfusions and analyzed with and without imputing missing Hb values. Pt-reported outcomes were assessed using the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) scale. Most pts were white (79%), 61% were female, and the median age was 64 years (range, 19 to 97). At baseline (BL), 31% of pts had Hb <10g/dL and 61% had Hb ≥10g/dL; the mean (SD) was 10.1 (0.7)g/dL. Hematologic malignancy (14%) was the third most common tumor type after breast (29%) and gastrointestinal (24%); 45% of the hematologic malignancies were non-Hodgkin’s lymphoma (NHL) pts. Hb, transfusion, and FACT-F endpoints are shown in the table. A slightly lower percent of NHL pts achieved the Hb target range recommended by current guidelines (11–13g/dL), compared to pts with other hematologic malignancies or with solid tumors. Similar proportions of pts with hematologic malignancies or solid tumors maintained Hb within the target range. The proportion of pts receiving RBC transfusions from week 5 to the end of study (EOS) was similar for pts with hematologic malignancies and for pts with solid tumors. Improvements in FACT-F scores were seen in all groups, although the mean change was lower in NHL pts compared with other tumor types. Serious adverse events were as expected for this patient population. DA Q3W appears to be effective in achieving and maintaining Hb between 11 to 13g/dL in pts with CIA and hematologic malignancies. Since chemotherapy is often administered Q3W, synchronizing DA treatment with pts’ chemotherapy schedules may simplify the treatment of CIA in these pts. Hematologic - NHL N=98 Hematologic - non-NHL N=118 Solid N=1277 All Tumor Types N=1493 *For pts who achieved target. **For pts available at day 29. K-M=Kaplan Meier. CL=confidence limits Mean (95%CL) BL Hb (g/dL) 10.1 (9.9, 10.2) 10.0 (9.8, 10.1) 10.1 (10.1, 10.2) 10.1 (10.1, 10.2) Pts who achieved ≥ Hb 11g/dL. Crude % (95% CL) 74 (66, 83) 82 (75, 89) 79 (77, 81) 79 (77, 81) Proportion of pts maintaining Hb between 11 and 13g/dL after achieving target - n (%)* 51 (70) 68 (70) 739 (73) 858 (73) Time to target Hb (weeks). K-M Median (95% CL) 7 (6, 8) 6 (4, 7) 4 (4, 5) 4 (4, 5) Transfusions from week 5 to EOS. Crude % (95% CL)** 21 (13, 30) 20 (13, 27) 18 (16, 20) 18 (16, 20) Mean change in FACT-F from BL to week 16 (95% CL) 2.8 (−0.9, 6.5) 5.2 (1.8, 8.6) 4.8 (3.9, 5.7) 4.7 (3.9, 5.6)

Acquired α-thalassemia in association with myelodysplastic syndrome and other hematologic malignancies

Blood ◽  
2005 ◽  
Vol 105 (2) ◽  
pp. 443-452 ◽  
Author(s):  
David P. Steensma ◽  
Richard J. Gibbons ◽  
Douglas R. Higgs
Keyword(s):  
Gene Expression ◽  
Myelodysplastic Syndrome ◽  
Molecular Mechanisms ◽  
Hematologic Malignancy ◽  
Globin Gene ◽  
Molecular Genetic ◽  
Hematologic Malignancies ◽  
Genetic Features ◽  
Diagnostic Confusion ◽  
Hematologic Neoplasia

AbstractAbnormalities of hemoglobin synthesis are usually inherited but may also arise as a secondary manifestation of another disease, most commonly hematologic neoplasia. Acquired hemoglobin disorders can be seen in any population and are not restricted to areas of the world with high incidences of inherited hemoglobinopathies. In fact, the acquired hemoglobinopathies may be more readily recognized where inherited hemoglobin abnormalities are rare and less likely to cause diagnostic confusion. Acquired α-thalassemia is the best characterized of the acquired red blood cell disorders in patients with hematologic malignancy, and it is almost always associated with a myelodysplastic syndrome (MDS). At least 2 molecular mechanisms for acquired α-thalassemia are now recognized: acquired deletion of the α-globin gene cluster limited to the neoplastic clone and, more commonly, inactivating somatic mutations of the trans-acting chromatin-associated factor ATRX, which cause dramatic down-regulation of α-globin gene expression. Here we review the clinical, hematologic, and molecular genetic features of α-thalassemia arising in a clonal myeloid disorder, and we discuss howATRX might affect gene expression in normal and abnormal hematopoiesis through epigenetic mechanisms.

scholarly journals Venous Thromboembolism (VTE) in Hematological and Non-Hematological Cancers: A Nationwide Analysis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3563-3563
Author(s):  
Manoj P Rai ◽  
Prabhjot Singh Bedi ◽  
Justin D. Kaner ◽  
Samanjit Kaur Kandola ◽  
Konchok Norgais ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Solid Tumors ◽  
Upper Extremity ◽  
Multivariate Regression ◽  
Research Funding ◽  
Hematologic Malignancy ◽  
Tumor Type ◽  
Advisory Committees ◽  
Lower Odds ◽  
Hematological Cancers

Abstract Introduction: Cancer patients tend to have a higher incidence of venous thromboembolism (VTE) - pulmonary embolism (PE) and deep venous thrombosis (DVT). There is conflicting data in the literature about the incidence of VTE in solid tumors versus hematological cancers. The purpose of this study was to analyze the prevalence of PE, DVT, and VTE in hospitalized patients with solid and hematologic malignancies using the National Inpatient Sample database. Methods: We performed a retrospective cohort analysis of the National Inpatient Sample 2014 Database (HCUP-NIS). Patients were included in the study if they had a principal diagnosis of DVT, PE, or both (VTE); primary or secondary diagnosis of solid tumors or hematological malignancy; and age 18 years or older. We performed univariate and multivariate regression to analyze the association of PE, DVT, and VTE with solid versus hematologic cancers. We performed univariate and multivariate regression to determine their statistical significance. We also performed univariate analysis for tumor type and saddle PE and upper extremity DVT. All analyses applied the HCUP-NIS weights. Results: We identified 27,410 patients with isolated DVT; 41,645 with isolated PE; and 69,055 with both DVT and PE (VTE). On multivariate analysis, hematologic malignancy had lower odds of DVT (OR 0.82, 95% CI 0.75-0.89), isolated PE (OR 0.65, 95% CI 0.60 - 0.71) and VTE (OR 0.72, 95% CI 0.67-0.76). Female sex and Charlson index were associated with modest increased odds of DVT, PE and VTE (OR <1.10 for all), while Asian/Pacific Islander race was associated with lower odds for each (OR 0.48-0.55). In contrast, black race was associated with greater odds of DVT (OR 1.49, 95% CI 1.37-1.62) and VTE (OR 1.27, 95% CI 1.2-1.34), but lower odds of isolated PE (OR 0.48, 95% CI 0.38-0.59). Native American and other race had lower odds of VTE (OR 1.27, 95% CI 1.2-1.34 and OR 0.82, 95% CI 0.71-0.95, respectively). Hispanic ethnicity had lower odds of PE (OR 0.66, 95% CI 0.59-0.73) and VTE (OR 0.76, 95% CI 0.70-0.82). Although, 91.1% of patients with malignancy and saddle PE had solid tumors, tumor type (solid versus hematological) was not statistically significant on univariate regression analysis (OR 0.83, 95% CI 0.58-1.18). Hematologic malignancy was associated with less upper extremity DVT (OR 0.69, 95% CI 0.54-0.88). Discussion: Based on the above data, patients with solid tumors are more likely to develop isolated DVT, PE, VTE, and upper extremity DVT. The analysis was likely underpowered to identify a difference for saddle PE, a relatively rare event with high mortality. Race appears to be associated in complex ways. In particular, it is unclear why black patients have increased odds of developing DVT or VTE, but lower odds for isolated PE. Two possible explanations are differences in health seeking behavior or increased outpatient mortality for isolated PE. As with saddle PE, it's likely the sample was too small to find differences for isolated DVT or PE for Native Americans and others. Additional studies to examine the reasons for differences by tumor type and race/ethnicity are needed. Table. Table. Disclosures Bussel: Rigel: Consultancy, Research Funding; Amgen Inc.: Consultancy, Research Funding; Protalex: Consultancy; Novartis: Consultancy, Research Funding; Momenta: Consultancy; Uptodate: Honoraria; Prophylix: Consultancy, Research Funding. Marks:Seattle Genetics: Equity Ownership; Heron: Membership on an entity's Board of Directors or advisory committees; Lilly: Membership on an entity's Board of Directors or advisory committees; Odonate: Membership on an entity's Board of Directors or advisory committees; UPMC: Employment.

scholarly journals Prevalence of Multiple Primary Hematologic Malignancies Seen at a Tertiary Care Center

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5017-5017
Author(s):  
Kathrine A Cooper ◽  
Jonathan Lattell ◽  
Beverly Gonzalez ◽  
Stephanie Kliethermes ◽  
Sucha Nand
Keyword(s):  
Hepatitis B ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Solid Tumors ◽  
Myeloid Leukemia ◽  
Cell Lymphoma ◽  
Hematologic Malignancy ◽  
B Cell Lymphoma ◽  
Hematologic Malignancies ◽  
Large B Cell Lymphoma

Abstract Background: There is a paucity of data regarding patients who develop multiple unrelated hematologic malignancies. This study aims to determine the prevalence of two or more hematologic malignancies in the same patient at Loyola University Medical Center (LUMC) over a period of 7 years and to explore associations with certain clinical risk factors. Methods: After obtaining IRB approval, the electronic medical record was queried for various hematologic malignancies according to ICD-9 codes from 2007-2014. Chemotherapy-associated and transformed malignancies were excluded. In addition, the following data were collected: age at first and second diagnoses, gender, ethnicity, HIV, EBV, CMV, hepatitis B or C, JAK2 mutation, or autoimmune disorders. Survival outcomes and presence of coexisting solid tumors were assessed. Results: Of 5902 patients diagnosed with any hematologic malignancy, 27 were found to have more than one. Two patients had three hematologic malignancies (Hodgkin lymphoma, cutaneous t-cell lymphoma, diffuse large B-cell lymphoma; chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), MALT lymphoma, diffuse large B-cell lymphoma). The most common first hematologic malignancy was CLL/SLL (10) followed by chronic myeloid leukemia (CML) (5) and Hodgkin lymphoma (4). The most common second primary hematologic malignancy was Hodgkin lymphoma (5), followed by multiple myeloma or plasmacytoma (4), acute myeloid leukemia (3) and CLL or monoclonal B-cell lymphocytosis (3). Thirty-seven of all malignancies were lymphoid, 16 myeloid and one Kaposi's sarcoma. Fifteen had both a myeloid and lymphoid malignancy; the remaining 12 patients had either two myeloid or two lymphoid malignancies. Seven cases were diagnosed synchronously and 20 metachronously. The median interval between the first and second diagnosis was 3 years (range: 0.19 - 6.26). The average age at diagnosis of the first and second disease was 62.4 and 67.2 years. Although not tested for statistical differences, the median survival after first and second diagnosis was 4.9 and 0.8 years, respectively. Seven patients also had at least one solid tumor malignancy; three had two different solid tumors. One patient had rheumatoid arthritis and hypothyroidism (SLL followed by Hodgkin lymphoma). Two patients had hypothyroidism, and four had type two diabetes. One patient had hepatitis B, and another had hepatitis B and C. Males were five times more likely to die after the first malignancy diagnosis compared to females, irrespective of the type of malignancy (p=0.04). No association was seen between survival and type of first malignancy or whether the second diagnosis was of lymphoid or myeloid lineage. Conclusion: These data show that in patients presenting with a hematologic malignancy, the risk of developing a second hematologic malignancy over a 7 year period was low at 0.005% (27 out of 5902). In about half (15 out of 27) the second hematologic malignancy belonged to a separate lineage and about a quarter (7/27) developed solid tumors. About one fourth of the patients (7/27) had an autoimmune disorder. Males in this cohort had a five-fold increased risk of death compared to females. The second hematologic malignancy was an ominous development and was associated with a median survival of 0.8 years. These observations should be confirmed in a prospective study. Disclosures No relevant conflicts of interest to declare.

Adoptive Cell Therapy for Gastrointestinal Cancers

2020 ◽  
Vol 04 (04) ◽  
pp. 345-350
Author(s):  
Ryan J. Slovak ◽  
Hyun S. Kim
Keyword(s):  
Cell Therapy ◽  
Clinical Research ◽  
Solid Tumors ◽  
Immune Cells ◽  
Ex Vivo ◽  
Adoptive Cell Therapy ◽  
Hematologic Malignancies ◽  
Gastrointestinal Cancers ◽  
Gastrointestinal Malignancies ◽  
Specific Antigens

AbstractThe reinfusion of autologous or allogeneic immune cells that have been educated and/or engineered ex vivo to respond to tumor-specific antigens is termed “adoptive cell therapy.” While adoptive cell therapy has made tremendous strides in the treatment of hematologic malignancies, its utilization for solid tumors has lagged somewhat behind. The purpose of this article is to concisely review the clinical research that has been done to investigate adoptive cell therapy as a treatment for gastrointestinal malignancies.

scholarly journals CAR-T cells and BiTEs in solid tumors: challenges and perspectives

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Julien Edeline ◽  
Roch Houot ◽  
Aurélien Marabelle ◽  
Marion Alcantara
Keyword(s):  
T Cells ◽  
Solid Tumors ◽  
Specific Antigen ◽  
Hematologic Malignancies ◽  
Antibody Fragments ◽  
New Drugs ◽  
Car T Cells ◽  
Cell Specificity ◽  
Car T ◽  
Early Phase Clinical Trials

AbstractChimeric antigen receptor (CAR)-modified T cells and BiTEs are both immunotherapies which redirect T cell specificity against a tumor-specific antigen through the use of antibody fragments. They demonstrated remarkable efficacy in B cell hematologic malignancies, thus paving the way for their development in solid tumors. Nonetheless, the use of such new drugs to treat solid tumors is not straightforward. So far, the results from early phase clinical trials are not as impressive as expected but many improvements are under way. In this review we present an overview of the clinical development of CAR-T cells and BiTEs targeting the main antigens expressed by solid tumors. We emphasize the most frequent hurdles encountered by either CAR-T cells or BiTEs, or both, and summarize the strategies that have been proposed to overcome these obstacles.

scholarly journals Extrapolation of pharmacokinetics and pharmacodynamics of sunitinib in children with gastrointestinal stromal tumors

2021 ◽  
Author(s):  
Reza Khosravan ◽  
Steven G. DuBois ◽  
Katherine Janeway ◽  
Erjian Wang
Keyword(s):  
Body Size ◽  
Solid Tumors ◽  
Gastrointestinal Stromal Tumors ◽  
Drug Exposure ◽  
Tumor Type ◽  
Plasma Drug ◽  
Safety And Efficacy ◽  
Stromal Tumors ◽  
Mixed Effects Modeling ◽  
Starting Dose

Abstract Purpose The starting dose of sunitinib in children with gastrointestinal stromal tumors (GIST) was extrapolated based on data in adults with GIST or solid tumors and children with solid tumors. Methods Integrated population pharmacokinetics (PK), PK/pharmacodynamics (PD), and exposure–response analyses using nonlinear mixed-effects modeling approaches were performed to extrapolate PK and PD of sunitinib in children with GIST at projected dose(s) with plasma drug exposures comparable to 50-mg/day in adults with GIST. The analysis datasets included PK/PD data in adults with GIST and adults and children with solid tumors. The effect of covariates on PK and safety/efficacy endpoints were explored. Results Two-compartment models with lag time were successfully used to describe the PK of sunitinib and its active metabolite SU012662. PK/PD models were successfully built to describe key continuous safety and efficacy endpoints. The effect of age on sunitinib apparent clearance (CL/F) and body surface area on SU012662 CL/F was statistically significant (P ≤ 0.001): children who were younger or of smaller body size had lower CL/F; however, age and body size did not appear to negatively affect safety or efficacy response to plasma drug exposure. Conclusion Based on PK, safety, and efficacy trial simulations, a sunitinib starting dose of ~ 25 mg/m2/day was predicted to provide comparable plasma drug exposures in children with GIST as in adults with GIST treated with 50 mg/day. However, in the absence of a tumor type effect of sunitinib on CL/F in children, the projected equivalent dose for this population would be ~ 20 mg/m2/day.

scholarly journals Predicting Responses to Checkpoint Inhibitors in Lymphoma: Are We Up to the Standards of Solid Tumors?

2020 ◽  
Vol 14 ◽  
pp. 117955492097636
Author(s):  
Ah-Reum Jeong ◽  
Edward D Ball ◽  
Aaron Michael Goodman
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
B Cell ◽  
Solid Tumors ◽  
Cell Lymphoma ◽  
Checkpoint Inhibitors ◽  
B Cell Lymphoma ◽  
Hematologic Malignancies ◽  
Checkpoint Blockade ◽  
Programmed Cell Death 1

Treatment of cancer has transformed with the introduction of checkpoint inhibitors. However, the majority of solid tumor patients do not respond to checkpoint blockade. In contrast, the response rate to programmed cell death 1 (PD-1) blockade in relapsed/refractory classical Hodgkin lymphoma (cHL) is 65% to 84% which is the highest among all cancers. Currently, checkpoint inhibitors are only approved for cHL and primary mediastinal B-cell lymphoma as the responses to single-agent checkpoint blockade in other hematologic malignancies is disappointingly low. Various established biomarkers such as programmed cell death 1 ligand 1 (PD-L1) protein surface expression, mismatch repair (MMR) status, and tumor mutational burden (TMB) are routinely used in clinical decision-making in solid tumors. In this review, we will explore these biomarkers in the context of hematologic malignancies. We review characteristic 9p24.1 structural alteration in cHL and primary mediastinal B-cell lymphoma (PMBCL) as a basis for response to PD-1 inhibition, as well as the role of antigen presentation pathways. We also explore the reported frequencies of MMR deficiency in various hematologic malignancies and investigate TMB as a predictive marker.

scholarly journals Transplantation of allogeneic CD34+ peripheral blood stem cells in patients with advanced hematologic malignancy

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4132-4138 ◽  
Author(s):  
WI Bensinger ◽  
CD Buckner ◽  
K Shannon-Dorcy ◽  
S Rowley ◽  
FR Appelbaum ◽  
...  
Keyword(s):  
Stem Cells ◽  
Body Weight ◽  
Peripheral Blood ◽  
Hematologic Malignancy ◽  
Chronic Gvhd ◽  
Allogeneic Transplantation ◽  
Hematologic Malignancies ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Sixteen patients with advanced hematologic malignancies were transplanted with HLA-identical allogeneic peripheral blood stem cells (PBSCs) that were selected for CD34+ cells by an avidin-biotin immunoadsorption technique. The median age of patients was 48 years (range, 37 to 67). Patients received 12.0 or 13.2 Gy of total body irradiation followed by 120 mg/kg of cyclophosphamide. Normal donors received 16 mg/kg of granulocyte-colony stimulating factor on days 1 to 6 followed by PBSC harvests on days 4 to 7. PBSC harvests were processed each day on a single avidin-blotin column containing an antibody to the CD34 antigen and processed cells were infused without cryopreservation daily for 4 consecutive days. Prophylaxis against graft-versus-host disease (GVHD) consisted of cyclosporine alone for 5 patients and CSA plus methotrexate for 11 patients. A median of 18.64 (6.74 to 34.97) x 10(8) CD34+ cells/kg patient body weight were collected from each donor. A median of 8.96 (2.62 to 17.34) x 10(8) CD34+ cells/kg patient body weight were recovered after avidin-biotin adsorption which represented a median CD34+ cell yield of 53% (18% to 77%) with a median purity of 62% (34% to 82%). There was a reduction in CD3+ cells from a median of 557.26 (227.73 to 677.77) x 106/kg to 0.73 x 10(4)/kg (0.40 to 3.65), in CD4+ cells from 351.72 (194.47 to 520.11) x 10(6)/kg to 0.40 (0.15 to 1.03) x 10(4)/kg and in CD8+ cells from 169.74 (53.34 to 325.83) x 10(6)/ kg to 0.32 (0.12 to 2.71) x 10(4)/kg representing a median 2.8 (2.19 to 3.14) log reduction in T cells. One patient died of infection on day 3 posttransplant and was unevaluable for recovery of neutrophils. The median day to recovery of 500 neutrophils/mL was 15 (8 to 26) in the remaining 15 patients. Six of 16 patients falled to achieve a platelet count of 20,000/mL before death on days 3 to 97 of transplant-related complications. The median day to achieving platelets of 20,000 mL in the remaining 10 patients was 11 (7 to 31). Eight of 16 patients (50%) died between 3 and 97 days posttransplant, 7 of transplant-related causes, and 1 of progressive disease. Grade 2–4 acute GVHD occurred in 12 out of 14 (86%) and grades 3–4 in 6 out of 14 (43%) evaluable patients. Six of 8 evaluable patients developed clinical chronic GVHD and 1 developed subclinical chronic GVHD. Bone marrow and/or peripheral blood chimerism studies in 12 evaluable patients showed 97% to 100% donor type in 11 patients with 1 patient in relapse showing 40% donor cells 60 to 90 days posttransplant. Four of 16 patients (25%) are alive and disease-free 312 to 576 days after transplant. There were no episodes of graft failure or rejection. This study shows that allogeneic transplantation using CD34+ selected PBSC results in prompt and sustained engraftment. CD34+ selection, as employed in this preliminary study, however, resulted in an apparently higher rate of acute and chronic GVHD. However, The sample size is quite small and precludes a more definitive conclusion regarding GVHD.

Suboptimal clinician awareness of appropriate NTRK fusion testing and TRK inhibitor use in solid tumors.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 229-229
Author(s):  
Ryan P. Topping ◽  
Krista Marcello ◽  
Terrence Fagan ◽  
Timothy A. Quill ◽  
Todd Michael Bauer ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Progressive Disease ◽  
Inhibitor Therapy ◽  
Tumor Type ◽  
Advanced Solid Tumors ◽  
Educational Activities ◽  
Time Period ◽  
Trk Inhibitors ◽  
Therapeutic Alternatives ◽  
Selection Of

229 Background: Since late 2018, 2 TRK inhibitors—larotrectinib and entrectinib—have been approved by the EMA and FDA for treating patients with advanced solid tumors harboring an NTRK fusion and progressive disease or no therapeutic alternatives. It is recommended that testing for NTRK fusions occur as early as possible after a diagnosis of advanced disease in patients with solid tumors to inform potential use of TRK inhibitors. Methods: Between April 2018 and April 2021, we conducted multiple live and online educational activities for oncology healthcare professionals (HCPs) on NTRK fusion testing and/or TRK inhibitor treatment for varied solid tumors. Each activity included polling questions designed to assess HCP knowledge and practice patterns. In this analysis, we assessed HCP responses to these questions to evaluate awareness of expert recommendations on NTRK fusion testing and the selection of TRK inhibitor therapy for appropriate patients. Results: In 6 live and online activities with data from April 2018 to April 2021, 29% of HCPs (n = 844) indicated that they ordered molecular profiling to test for NTRK fusions in all solid tumors in their current practice. Of note, low rates of testing were reported in TRK inhibitor/ NTRK testing-focused activities throughout this time period, with no significant increase over time. In assessing different patient cases across 8 activities where experts recommended TRK inhibitor therapy as optimal, many HCPs did not select a TRK inhibitor, with considerable variance by tumor type (Table). *For all cases, experts selected larotrectinib and/or entrectinib as optimal treatment. †HCP respondents. GBM, glioblastoma; GI, gastrointestinal; MSI-H, microsatellite instability-high; PD, progressive disease; PTC, papillary thyroid cancer.Conclusions: The rate of broad testing for NTRK fusions across patients with solid tumors remains low, and many HCPs lack awareness of when to consider a TRK inhibitor. Educational activities designed to address these deficiencies would be of clear benefit to HCPs treating patients with advanced solid tumors. A detailed analysis of HCP trends will be presented.[Table: see text]

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