Preclinical activity and a pilot phase I study of pacritinib, an oral JAK2/FLT3 inhibitor, and chemotherapy in FLT3 -ITD-positve AML

In conclusion, pacritinib, an inhibitor ofFLT3-ITD and resistant-conferring TKD mutations, was well tolerated and demonstrated preliminary anti-leukemic activity in combination with chemotherapy in patients withFLT3 mutations.
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research

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Conclusion: Decitabine in combination with chemotherapy or molecular therapy has shown efficacious properties in refractory or relapsed AML patients. PMID: 31242832 [PubMed - in process]
Source: Hematology - Category: Hematology Tags: Hematology Source Type: research
Discussion This case demonstrates successful cure of pre-B-ALL complicating XLA by alloSCT with restoration of B-cell development and functional antibody response. We are aware of only one previous case of pre-B-ALL in an XLA patient (21), which suggests that human BTK deficiency in itself does not predispose to pre-B-ALL. However, there are data to suggest that BTK may act as a tumor suppressor, and BTK deficiency may predispose to tumor development following a “second hit.” Mice with a genetic deficiency in Slp65, a gene encoding an adaptor protein that functions together with BTK, have a block in progenito...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
The prevention of relapse is the major therapeutic challenge in older patients with acute myeloid leukemia (AML) who have obtained a complete remission (CR) on intensive chemotherapy. In this randomized phase 3 study (HOVON97) in older patients (≥60 years) with AML or myelodysplastic syndrome with refractory anemia with excess of blasts, in CR/CR with incomplete hematologic recovery (CRi) after at least 2 cycles of intensive chemotherapy, we assessed the value of azacitidine as postremission therapy with respect to disease-free survival (DFS; primary end point) and overall survival (OS; secondary end point). In total, 1...
Source: Blood - Category: Hematology Authors: Tags: Myeloid Neoplasia, Clinical Trials and Observations Source Type: research
Abstract Normal hematopoiesis can be disrupted by the leukemic bone marrow microenvironment, which leads to cytopenia-associated symptoms including anemia, hemorrhage and infection. Among them, thrombocytopenia is a major and fatal complication in patients with acute leukemia. However, the mechanisms underlying defective thrombopoiesis in leukemia have not been fully elucidated. In steady state, thrombocytes are continuously produced by megakaryocytes. Using the MLL-AF9 induced acute myeloid leukemia mouse model, we have demonstrated a preserved number and proportion of megakaryocyte-primed hematopoietic stem cell...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
Acute myeloid leukemia (AML) is a heterogeneous malignant disease characterized by the accumulation of immature myeloid progenitor cells, which leads to anemia, thrombocytopenia and impaired immunity. Treatment with intensive chemotherapy regimens of adult AML patients who are 60 years of age or younger results in hematologic remission in about 70-90% of patients, but at least 30% of these patients will experience a relapse [1]. Remaining cells in the bone marrow after chemotherapy treatment are thought to be responsible for the relapse.
Source: Leukemia Research - Category: Hematology Authors: Tags: Research paper Source Type: research
Conclusion: These findings indicate that with the baseline covariates evaluated, we have a poor ability to predict commonly occurring grade 3 and higher toxicities that occur during the first cycle of 7+3 induction therapy for AML. These findings support the claim that randomization is necessary to compare toxicities between standard and investigational regimens. Moreover, assuming that trial eligibility criteria are often stringent in an attempt to minimize the occurrence of treatment toxicities in study participants, the lack of strong association between individual baseline characteristics and toxicities could be used t...
Source: Blood - Category: Hematology Authors: Tags: 613. Acute Myeloid Leukemia: Clinical Studies: Poster I Source Type: research
ConclusionOur first-in-human clinical trial demonstrates promising efficacy of cCAR therapy in treating patients with relapsed/ refractory AML. cCAR is able to eradicate leukemia blasts and leukemia stem cells, exerting a profound tumor killing effect that is superior to single target CAR T cell therapies. cCAR is also shown to induce total myeloid ablation in bone marrow, suggesting that it may act as a safer alternative to avoid the severe toxicities caused by standard bone marrow ablation regimens without sacrificing the anti-tumor efficacy. This strategy will likely benefit patients who are unable to tolerate total bod...
Source: Blood - Category: Hematology Authors: Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Immunotherapy Source Type: research
Introduction: Hyperleukocytosis, defined as a white blood cell count (WBC) of>50 x 109/L or>100 x 109/L, is seen in newly diagnosed AML and often results in leukostasis, increased risk of complications, and potentially early death. Those pts often require urgent evaluation and therapy. Leukapheresis is also sometimes used despite limited evidence supporting its use. There is limited data regarding the impact of time (day/night) and day (weekday/weekend) of admission and time to initiation of IC on outcomes in pts with hyperleukocytosis.Methods: Data were collected from 12 centers in USA and Europe (EU). Eligible pts ...
Source: Blood - Category: Hematology Authors: Tags: 615. Acute Myeloid Leukemia: Commercially Available Therapy, excluding Transplantation: Poster I Source Type: research
Conclusions:Decitabine combined chemotherapy could improve the inductive remission rate on MDS-like AML patients under 60 years old in the first course.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - Category: Hematology Authors: Tags: 615. Acute Myeloid Leukemia: Commercially Available Therapy, excluding Transplantation: Poster II Source Type: research
Conclusions: Gilteritinib and AZA were generally well tolerated with no unexpected AEs. This combination therapy induced antileukemic responses in newly diagnosed FLT3mut+ AML pts unfit to receive standard induction chemotherapy. Based on these results, pts are being enrolled into the randomized portion of the study with a dose of 120 mg gilteritinib for the combination treatment arm.DisclosuresWang: Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Speakers Bureau; Jazz: Speakers Bureau; Amgen: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or a...
Source: Blood - Category: Hematology Authors: Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster II Source Type: research
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