Therapeutic Management of Patients with FLT3 + Acute Myeloid Leukemia: Case Reports and Focus on Gilteritinib Monotherapy.

Acute myeloid leukemia is a malignant disorder of the bone marrow, characterized by differentiation, clonal expansion, and uncontrolled proliferation of malignant myeloid progenitor cells and by several molecular and genetic abnormalities. A mutation of FMS-like tyrosine kinase 3 gene can be observed in about one-third of cases of acute myeloid leukemia. Two FLT3 inhibitors are actually approved for FLT3 mutated acute myeloid leukemia: midostaurin, a multikinase first generation inhibitor with lower affinity for FLT3 binding, and gilteritinib fumarate, a potent second-generation inhibitor of both FLT3-ITD and TKD. Gilteritinib is a new effective and well-tolerated drug for patients with relapsing or refractory FLT3-positive acute myeloid leukemia. Thanks to its efficacy, low toxicity, its good manageability (oral formulation), this drug is suitable for all the patients, including elderly frail patient with concomitant therapies or pre-existing or underlying diseases, and can be used also in the outpatient setting, reducing risks and costs related to the hospitalization. We report and discuss seven cases of different patients with FLT3 positive acute myeloid leukemia successfully managed with gilteritinib in the real clinical practice.

Lichen planopilaris-like eruption in chronic myeloid leukemia patient during treatment with nilotinib as second-line therapy.

INTRODUCTION: Chronic myeloid leukemia (CML) is a malignant clonal disorder of hematopoietic stem cells characterized by a translocation of genetic material between chromosomes 9 and 22 resulting in the BCR-ABL fusion oncogene expression. Nilotinib is a potent second-generation tyrosine kinase inhibitor available as first line treatment. Among side effects QTc interval prolongation, pancreatitis, metabolic disorders and skin reactions are the most commonly seen. CASE REPORT: Here we describe a rare case of lichen planopilaris eruption that developed during therapy with nilotinib. MANAGEMENT & OUTCOME: Nilotinib dosage was reduced together with introduction of hydroxychloroquine with progressive improvement of alopecia. DISCUSSION: Collaboration with dermatologist and nilotinib dose reduction allowed to continue the drug maintaining major molecular response and patient's quality of life.

Eltrombopag as second line treatment in patients with primary immune thrombocytopenia: A single center real life experience.

Glucocorticoid treatment is the standard initial therapy for patients with immune thrombocytopenia (ITP). Despite a rate of 60-80% of initial remissions, only 30 to 50% of adults have a sustained response after discontinuation. Second line options are splenectomy, thrombopoietin-receptor agonists (TPO-RAs), rituximab and intravenous immunoglobulin. Third line treatments include a mix of immunosuppressive drugs (e.g. azathioprine, ciclosporin, etc.). Recently international guidelines have proposed a treatment algorithm formalizing TPO-RAs and splenectomy as second and third line respectively, confirming splenectomy as second line choice only in emergency. Here we present a single center observational retrospective study of eltrombopag as second line treatment. We evaluated 48 adult primary chronic ITP patients since 2003. Forty-four out of 48 patients received a first line treatment with glucocorticoids. Twenty-two (61%) patients needed a second line treatment: 18 received eltrombopag, 3 a second course of steroid and one patient underwent splenectomy. Every patient before starting eltrombopag or receiving splenectomy underwent bone marrow examination. Overall response rate to eltrombopag was 94% with a CR rate of 76% and a PR of 23%; only one patient was non responder, underwent splenectomy and received subsequent treatment with rituximab, romiplostim and cyclosporin obtaining CR. One patient developed an autoimmune pancytopenia about a month after starting TPO-RA and in addition to eltrombopag received steroid and rituximab with blood count improvement. After a median follow up of 21,1 months (range 0,4-64,7 months) 16 patients (89%) are still on therapy maintaining response. As regards safety, gastrointestinal side effects were rare and low grade; only one patient discontinued eltrombopag after few weeks, because of dizziness. One patient had a relapse of deep venous thrombosis while no major bleeding complications were observed. Our real-life single center experience confirms efficacy and safety of eltrombopag as second line treatment in chronic ITP patients.

Clinical Course and Risk Factors for In-Hospital Mortality of 205 Patients with SARS-CoV-2 Pneumonia in Como, Lombardy Region, Italy.

The aim of this study is to explore risk factors for in-hospital mortality and describe the effectiveness of different treatment strategies of 205 laboratory-confirmed cases infected with SARS-CoV-2 during the Lombardy outbreak. All patients received the best supportive care and specific interventions that included the main drugs being tested for repurposing to treat COVID-19, such as hydroxychloroquine, anticoagulation and antiviral drugs, steroids, and interleukin-6 pathway inhibitors. Clinical, laboratory, and treatment characteristics were analyzed with univariate and multivariate logistic regression methods to explore their impact on in-hospital mortality. Univariate analyses showed prognostic significance for age greater than 70 years, the presence of two or more relevant comorbidities, a P/F ratio less than 200 at presentation, elevated LDH (lactate dehydrogenase) and CRP (C-reactive protein) values, intermediate- or therapeutic-dose anticoagulation, hydroxychloroquine, early antiviral therapy with lopinavir/ritonavir, short courses of steroids, and tocilizumab therapy. Multivariable regression confirmed increasing odds of in-hospital death associated with age older than 70 years (OR 3.26) and a reduction in mortality for patients treated with anticoagulant (-0.37), antiviral lopinavir/ritonavir (-1.22), or steroid (-0.59) therapy. In contrast, hydroxychloroquine and tocilizumab have not been confirmed to have a significant effect in the treatment of SARS-CoV-2 pneumonia. Results from this real-life single-center experience are in agreement and confirm actual literature data on SARS-CoV-2 pneumonia in terms of both clinical risk factors for in-hospital mortality and the effectiveness of the different therapies proposed for the management of COVID19 disease.

The first case of Mycobacterium vaccae sepsis in a non-Hodgkin lymphoma patient: biological understandings and clinical consequencies.

Mycobacterium vaccae is a rapidly growing nonpathogenic species of the Mycobacteriaceae family of bacteria that can cause pulmonary and disseminated disease in particular in immunocompromised individuals. Here we describe a first case of matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass-spectrometry (MS) identification of this pathogen in a patient with non-Hodgkin's lymphoma during chemoimmunotherapy salvage treatment, and its impact on clinical decision making.

Plerixafor: what we still have to learn.

Plerixafor, a hematopoietic stem cell mobilizer, is indicated in combination with G-CSF to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma. Current evidence suggests that the addition of plerixafor with chemotherapy plus G-CSF is safe and effective in the large majority of the patients with low blood CD34(+) cell count after mobilization and/or poor yield after the first collection. Nevertheless, there are several questions strongly debated, and in this paper, we would like to identify areas of possible future use and development of the drug.

R-ESHAP plus pegfilgrastim as an effective peripheral stem cell mobilization regimen for autologous stem-cell transplantation in patients with relapsed/refractory diffuse large B-cell lymphoma.

Stem cell (SC) mobilization is significantly influenced by the mobilization schedule in patients with lymphoma. We evaluated data from 30 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) undergoing SC mobilization. All received R-ESHAP plus a single dose of pegfilgrastim. All patients collected ⩾ 2 × 10(6) CD34+cells/kg, 80% of them at least 5 × 10(6) CD34+cells/kg. Adverse effects of the regimen included myelosuppression and neutropenic fever. Herein, our results suggest that R-ESHAP plus pegfilgrastim is a highly effective mobilization strategy in patients affected by DLBCL associated with a low incidence of adverse events.

Efficacy of photopheresis extracorporeal procedure as single treatment for severe chronic GVHD: a case report.

Allogeneic hematopoietic stem cell transplantation is the only potentially curative therapeutic option for many malignant and nonmalignant hematologic disorders. Despite this, several factors unfavorably affect the outcome of this procedure and in particular chronic graft-versus-host disease (cGVHD) remains the principal cause of morbidity after allogeneic transplantation. Here we present our experience regarding a patient affected by extensive chronic GVHD (cGVHD) treated only with extracorporeal photopheresis procedure (ECP) as first line treatment. The patient, presenting an high risk myelodysplastic syndrome (MDS), underwent an allogeneic peripheral stem cells transplantation. About 2 months after transplantation she experienced a hematological and clinical relapse of MDS. After reinduction therapy with azacitidine she obtained a second complete remission. Because of the risk of relapse related to a strong immunosuppressant therapy and the previous infectious complication, we decided to start a treatment with ECP alone for cGVHD. After six procedure the patient obtained a complete resolution of all signs and symptoms of the cGVHD. This experience may support the possibility to use only an immunomodulant treatment like ECP for the cGVHD, reducing the risk of complications of prolonged immunosuppressant treatment.