Fuad El Rassi

Predicting early blast transformation in chronic-phase chronic myeloid leukemia: is immunophenotyping the missing link?

Flow cytometry (FC) is a commonly requested test in the workup of leukocytosis in community practices. The role of FC in chronic‐phase chronic myeloid leukemia (CP‐CML) is unknown. We hypothesized that finding aberrant cells with FC in CP‐CML may predict early blast‐phase (BP) transformation.

Sensitivity and specificity of cerebrospinal fluid flow cytometry for the diagnosis of leukemic meningitis in acute lymphoblastic leukemia/lymphoma

Abstract The presence of leukemic blasts detected by light microscopy in cerebrospinal fluid (CSF) establishes the diagnosis of leukemic meningitis in acute lymphoblastic leukemia/lymphoma (ALL). Flow cytometry immunophenotyping (FCI) is a very sensitive method that detects a minute number of aberrant cells, and is increasingly performed on CSF samples. We sought to determine the sensitivity and specificity of CSF FCI for the diagnosis of leukemic meningitis in ALL. Between November 2007 and August 2011, 800 CSF samples from 80 patients with ALL were available from diagnostic lumbar punctures (LPs; n = 80), follow-up LPs (n = 687) and at the time of relapse (n = 33). FCI was performed on 267 samples, and only identified aberrant cells in cytologically confirmed cases of leukemic meningitis. A blinded review of all cases with detectable CSF nucleated cells confirmed these findings. We conclude that CSF FCI has a 100% sensitivity and specificity for the detection of lymphoblasts. However, additional studies are needed to define the role this procedure plays in the diagnosis of leukemic meningitis.

Epsilon aminocaproic acid prevents bleeding in severely thrombocytopenic patients with hematological malignancies

Despite prophylactic platelet transfusions, bleeding remains a significant problem in thrombocytopenic patients.

Bosutinib: a SRC–ABL tyrosine kinase inhibitor for treatment of chronic myeloid leukemia

Bosutinib is one of five tyrosine kinase inhibitors commercially available in the United States for the treatment of chronic myeloid leukemia. This review of bosutinib summarizes the mode of action, pharmacokinetics, efficacy and safety data, as well as the patient-focused perspective through quality-of-life data. Bosutinib has shown considerable and sustained efficacy in chronic myeloid leukemia, especially in the chronic phase, with resistance or intolerance to prior tyrosine kinase inhibitors. Bosutinib has distinct but manageable adverse events. In the absence of T315I and V299L mutations, there are no absolute contraindications for the use of bosutinib in this patient population.

Update on Optimal Management of Acute Myeloid Leukemia

Acute myeloid leukemia (AML) represents a malignant accumulation of immature myeloid cells in the marrow, presenting with impaired hematopoiesis and its attendant complications, including bleeding, infection, and organ infiltration. Chromosomal abnormalities remain the most powerful predictors of AML prognosis and help to identify a subgroup with favorable prognosis. However, the majority of AML patients who are not in the favorable category succumb to the disease. Therefore, better efforts to identify those patients who may benefit from more aggressive and investigational therapeutic approaches are needed. Newer molecular markers aim at better characterizing the large group of intermediate-risk patients and to identify newer targets for therapy. A group that has seen little improvement over the years is the older AML group, usually defined as age ≥ 60. Efforts to develop less intensive but equally efficacious therapy for this vulnerable population are underway.

Clinical monitoring and management of complications related to chelation therapy in patients with β-thalassemia

ABSTRACT Iron chelating agents – deferoxamine (DFO), deferiprone (DFP), and deferasirox (DFX) – are used to treat chronic iron overload in patients with β-thalassemia in an attempt to reduce morbidity and mortality related to siderosis. Each of the approved iron chelating agents has its own advantages over the others and also has its own risks, whether related to over-chelation or not. In this review, we briefly discuss the methods to monitor the efficacy of iron chelation therapy (ICT) and the evidence behind the use of each iron chelating agent. We also portray the risks and complications associated with each iron chelating agent and recommend strategies to manage adverse events.

Venous access catheter-related thrombosis in patients with cancer

Abstract Patients with cancer are at high risk for developing venous thromboembolism (VTE), and the presence of a central venous catheter (CVC) further increases this risk. CVC-related VTE has serious implications related to the loss of vascular access, development of pulmonary embolism, recurrent VTE, infections and post-thrombotic syndrome. The pathogenesis of CVC-related VTE is complex and multifactorial, with risk factors associated with the catheter, the vessel selected for insertion and the underlying cancer as well as the anti-cancer therapy. Clinical presentation of CVC-related VTEs is often non-specific, and ultrasonography is the most commonly used radiological diagnostic test. Management of CVC-related VTE in patients with cancer requires a balance between the need for venous access, the risk of VTE recurrence and the risk of bleeding from treatment-induced thrombocytopenia. Effective VTE prophylaxis methods have yet to be defined. Ongoing studies are evaluating the role of newer oral antithrombotic agents and alternative interventional strategies for the prevention and treatment of CVC-related VTE in patients with cancer.

Early Diagnosis of Acute Myeloid Leukemia by Computed Tomography Scan

Introduction Acute leukemia is diagnosed in asymptomatic patients after the identification of abnormal peripheral blood counts; however, recent reports have described abnormal bone marrow signals on magnetic resonance imaging (MRI) in patients with previously undiagnosed leukemia. The diffusion-weighted imaging reflects the random motion of water protons and allows for measurement of the tissue microstructure, which permits differentiation between benign marrow edema and tumorous involvement of the bone marrow. The unique soft tissue contrast of MRI enables precise assessment of bone marrow infiltration early and before osteolytic changes become visible by conventional radiology imaging or computed tomography (CT) scans. CT machines were the first imaging devices to provide a detailed two-dimensional visualization of the internal anatomy. The use of a CT scan is the method of choice for the assessment of bone stability and allows for the evaluation of fracture risk and is, therefore, less sensitive than MRI in the detection of marrow processes. Nevertheless, CT scan imaging can differentiate tissue densities on the basis of differences in Hounsefield units. We present a case of acute leukemia first suspected when new marrow signal changes were detected on an annual CT scan 1 month before blood abnormalities.

Outcomes of Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia Following an Elective Switch From Second-Generation Tyrosine Kinase Inhibitor to Imatinib

Abstract The second‐generation tyrosine kinase inhibitors (TKIs) (2G‐TKIs) dasatinib (DAS) and nilotinib (NIL) yield faster responses in newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML) as compared with imatinib (IM); however, long‐term safety of these agents is a growing concern. We identified 20 patients with CP‐CML diagnosed between August 2013 and October 2016 who initiated 2G‐TKIs and were then switched after optimal response at 3 months to IM. Second‐generation TKIs initiated were DAS (n = 15), NIL (n = 3), or both sequentially due to intolerance (n = 1). One other patient initiated therapy with ponatinib on trial. Response was assessed by quantitative reverse‐transcriptase polymerase chain reaction (qRT‐PCR) for BCR‐ABL1 levels every 3 months and in patients with qRT‐PCR values less than 10% at 3 months, IM was started at 400 mg/d. IM was well tolerated except in 2 patients who required dose‐reduction and discontinuation due to grade 2 skin rash (1) and grade 2 anxiety (1). After initiation of IM therapy, the BCR‐ABL1 qRT‐PCR levels trended down as expected. At 12 months 16 (84.2%) of 19 evaluable patients showed a 3 log (major molecular remission) or better reduction in their PCR levels. In conclusion, this retrospective analysis shows that IM can be safely and effectively administered following optimal response to 2G‐TKIs. A prospective trial exploring this approach is currently enrolling and will be needed to confirm the safety and efficacy of this therapeutic approach.

Transfusion-transmitted malaria masquerading as sickle cell crisis with multisystem organ failure.

Fever accompanying vaso‐occlusive crisis is a common presentation in patients with sickle cell disease (SCD) and carries a broad differential diagnosis. Here, we report a case of transfusion‐transmitted malaria in a patient with SCD presenting with acute vaso‐occlusive crisis and rapidly decompensating to multisystem organ failure (MSOF).