Publications by authors named "Jonathan Canaani"

Venetoclax (Ven) plus hypomethylating agents are considered standard-of-care for patients with acute myeloid leukemia (AML) judged ineligible for intensive chemotherapy (IC). Real-world studies complement clinical trials, since patterns of patient selection, treatment-exposure and post-remission management may vary. This prospective observational multi-center study included 209 newly diagnosed IC-ineligible patients with a median age 75 years (interquartile range, 71-81 years).

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Outcomes for acute myeloid leukemia have improved significantly in the last decade with the approval of novel therapeutics targeting diverse vulnerabilities of leukemic cells, expanded access to stem cell transplantation, and improved safety of transplantation. While attainment of initial remission is now an expected outcome in most AML patients receiving intensive or non-intensive induction regimens, maintaining long-term remission and decreasing the risk of relapse remain critical challenges. Maintenance approaches employing assorted agents have yielded variable success and only recently have been integrated to the standard of care.

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Introduction: In recent years, fedratinib, a selective JAK2 inhibitor, has emerged as a potential therapeutic option for patients who have failed or are intolerant to ruxolitinib. Despite the promising results observed in clinical studies, real-world evidence from the USA and Europe suggests that the efficacy of fedratinib may be less conclusive. We report the characteristics, treatment patterns, and clinical outcomes of patients with myelofibrosis (MF) treated with fedratinib following ruxolitinib failure in Israel's clinical practice.

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Patients with FLT3-mutated acute myeloid leukaemia (AML) that relapse or are refractory (R/R) to intensive induction have poor outcomes. Gilteritinib has recently become standard-of-care for patients with R/R FLT3-mutated AML. We investigated whether adding venetoclax to gilteritinib (gilt-ven) improves outcomes as compared with gilteritinib monotherapy.

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Introduction: Blood product transfusion retains a critical role in the supportive care of patients with acute myeloid leukemia (AML). Whereas previous studies have shown increased transfusion dependency to portend inferior outcome, predictive factors of an increased transfusion burden and the prognostic impact of transfusion support have not been assessed recently.

Methods/patients: We performed a retrospective analysis on a recent cohort of patients given intensive induction chemotherapy in 2014-2022.

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Objectives: Dysregulation of BCL-2 family members has been reported in acute lymphocytic leukemia (ALL), with various BH3-dependencies of the leukemic clone. We conducted a multicenter retrospective cohort of patients with relapsed/refractory B or T ALL, with ven-chemotherapy or ven-navitoclax combinations, to assess efficacy and safety.

Methods: Seventeen patients were included in the analysis, median age was 32 years, with 6 B-ALL and 11 T-ALL patients.

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Venous thromboembolism (VTE) is frequently seen in acute myeloid leukemia (AML) patients and presents a significant clinical challenge. The association of VTE during intensive chemotherapy with risk models such as the Medical Research Council (MRC) cytogenetic-based assessment and the European LeukemiaNet (ELN) 2017 molecular risk model have not been rigorously evaluated. Additionally, there is a paucity of data pertaining to the long-term prognostic impact of VTE in AML patients.

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Second allogeneic hematopoietic stem-cell transplantation (HSCT2) is a therapeutic option for patients with acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) relapsing after a first transplant (HSCT1). However, patients allocated to HSCT2 may be a selected group with better prognosis and the added efficacy of HSCT2 is not well established. We retrospectively analyzed 407 consecutive patients with relapsed AML/MDS after HSCT1.

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Objectives: Define clinical and laboratory attributes of acute myeloid leukemia (AML) patients with long-term survival exceeding five years and compare them with AML patients succumbing to disease within 2 years of diagnosis.

Methods: A retrospective analysis of AML patients alive at least five years from the time of initial diagnosis. Baseline clinical data were compared with patients who died within 2 years of diagnosis.

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Baseline cytogenetics and disease status are key factors predicting the outcomes of allogeneic hematopoietic cell transplantation (HCT) in patients with acute myeloid leukemia (AML). The importance of cytogenetic risk in patients with primary refractory or relapsed (R/R) AML undergoing haploidentical (Haplo) HCT is unknown. We studied the impact of cytogenetic risk in patients with R/R de novo AML with active disease who underwent non-T-cell-depleted Haplo-HCT with post-transplantation cyclophosphamide from 2010 to 2020.

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Patients with FLT3-mutated relapsed or refractory (R/R) acute myeloid leukemia (AML) have a dismal prognosis. Gilteritinib is a FLT3 tyrosine kinase inhibitor (TKI) recently approved for patients with R/R AML. We aimed to characterize real-world data regarding gilteritinib treatment in FLT3-mutated R/R AML and to compare outcomes with matched FLT3-mutated R/R AML patients treated with chemotherapy-based salvage regimens.

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The clinical yield and benefit of performing bone marrow cultures for various clinical indications has been challenged and their clinical necessity remains debatable. We sought to assess the clinical yield and benefit of performing routine bone marrow cultures and determine whether various clinical, laboratory, and imaging parameters were predictive of a diagnostic bone marrow culture. This was a single center retrospective analysis of all patients who underwent a bone marrow study comprising bone marrow cultures from January 1, 2012, through March 1, 2018.

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There are no data indicating whether the number of induction courses needed to achieve first complete remission (CR1) is of prognostic significance in Haploidentical transplantation (HaploSCT). We compared transplantation outcomes of adults with AML that underwent HaploSCT in CR1, achieved following one or two induction courses. A total of 635 patients were included: 469 (74%) with 1 and 166 (26%) with two induction chemotherapy courses.

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Chemotherapy-based approaches still constitute an essential feature in the treatment paradigm of adult acute lymphoblastic leukemia (ALL). The German Multicenter Study Group (GMALL) is a well-established protocol for ALL. In this study, we assessed our recent experience with the GMALL 07/2003 protocol reviewing all adult ALL patients who were treated with GMALL in three major centers in Israel during 2007-2020.

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Early mortality remains a challenging therapeutic facet of the initial induction phase of intensive chemotherapy in patients with acute myeloid leukemia (AML). The impact of standard molecular evaluation and risk category of the European LeukemiaNet (ELN) 2017 classification model on early mortality has not been rigorously evaluated thus far. We reviewed the medical records of 320 consecutive adult patients with newly diagnosed AML treated with intensive induction chemotherapy in our center from 2007 to 2021.

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FMS-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutational status is a pivotal prognosticator in acute myeloid leukemia (AML) patients and significantly increases the risk of disease relapse. However, it remains unclear whether in FLT3-ITD patients referred for allogeneic stem cell transplantation (allo-SCT), baseline cytogenetics significantly impacts clinical outcome. Using the European Society of Blood and Marrow Transplantation registry, we performed a retrospective analysis of 1631 FLT3-ITD AML patients who underwent allo-SCT with the aim of determining the influence of cytogenetic risk category on patient outcomes.

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Cyclosporine A (CSA) and methotrexate (MTX) is the standard graft-versus-host disease (GVHD) prophylaxis regimen for matched sibling donor (MSD) allogeneic hematopoietic cell transplantation (allo-HCT). Recently, post-transplantation cyclophosphamide (PTCy) has been shown to be effective in GVHD prevention. In this registry-based study, we compared outcomes of 118 patients treated with PTCy and 1202 patients with CSA/MTX who underwent MSD allo-HCT for acute myelogenous leukemia.

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Background: Achievement of initial remission remains the most important clinical factor predicting long term survival in acute myeloid leukemia (AML) patients treated with intensive chemotherapy. Yet, whether the patient subset in need of a second cycle of intensive induction chemotherapy to reach remission experiences inferior outcomes compared to patients reaching remission after a single cycle of therapy, remains uncertain.

Patients And Methods: Retrospective analysis of 302 consecutive AML patients treated with intensive induction chemotherapy in our institution in 2007-2020.

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Importance: Previous studies have shown that uniform pathologic review of all splenectomy surgical specimens reveals new clinically actionable diagnoses only in a minority of cases.

Objective: To examine whether the aggregate of clinical, laboratory, imaging, and pathologic preoperative data is associated with a clinically beneficial pathologic study for routine splenectomy surgical specimens.

Design, Setting, And Participants: This single-center retrospective cohort study included all patients who underwent splenectomy from January 1, 2013, through December 31, 2018, at a single center.

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Introduction: Achievement of an initial complete remission (CR) following induction chemotherapy is tightly correlated with survival in acute myeloid leukemia (AML) patients, yet patients in CR with incomplete hematologic recovery (CRi) still experience improved outcomes compared with nonresponding patients. Whether CRi predicts prognosis in patients referred to an allogeneic stem cell transplantation (allo-SCT) is incompletely defined. In this analysis, we evaluated whether clinical outcomes of transplanted AML patients in CR and CRi were significantly different.

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Combinations of the BCL-2 inhibitor, venetoclax, with either hypomethylating agents (HMA) or low dose cytarabine (LDAC), have shown promising results in clinical trials of AML patients unfit for intensive therapy. We report on the efficacy and safety of venetoclax combinations in AML patients treated outside of clinical trials. Complete remission (CR) + CR with incomplete count recovery (CRi) were achieved in 61% of patients, with similar CR+CRi rates in with secondary AML, and in patients who were previously treated with HMA (61% and 43%, respectively).

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Background: Non-T-cell depleted haploidentical hematopoietic stem cell transplantation (HaploSCT) is being increasingly used in acute lymphoblastic leukemia (ALL) with improving patient outcomes. We have recently reported that outcomes of adult patients (pts) with ALL in complete remission (CR) receiving HaploSCT are comparable to unrelated donor transplants. We now compared HaploSCT and matched sibling donor (MSD) transplants in pts with ALL.

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Background: The use of haploidentical hematopoietic cell transplantation (haplo-HCT) with posttransplantation cyclophosphamide prophylaxis is gaining traction in patients with acute lymphoblastic leukemia (ALL).

Methods: The Acute Leukemia Working Party/European Society for Blood and Marrow Transplantation registry was used to evaluate the outcomes of adult patients with ALL who underwent haplo-HCT during 2011 through 2015 and compared them with the outcomes of those who underwent transplantation during 2016 through 2018.

Results: The analysis consisted of 195 patients, including 79 who underwent transplantation during 2011 through 2015 and 116 who underwent transplantation during 2016 through 2018.

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