Acute Promyelocytic Leukemia: Review of Complications Related to All-Trans Retinoic Acid and Arsenic Trioxide Therapy.

The hallmark of acute promyelocytic leukemia (APL) is the presence of the characteristic fusion transcript of the promyelocytic leukemia gene with the retinoic acid receptor α gene (PML::RARA). The PML::RARA fusion is a molecular target for all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Therapies based on ATRA plus ATO have excellent outcomes in terms of complete remission rates, overall survival, and achievement of deep and durable molecular responses with a very low incidence of relapse. However, although the combination of ATRA and ATO has lower hematologic toxicity than standard chemotherapy, its use is associated with a spectrum of distinctive toxicities, such as differentiation syndrome, liver toxicity, QT interval prolongation, and neurotoxicity. Rigorous monitoring of patients' clinical evolution is indispensable for identifying and addressing each complication. The objective is to maintain an equilibrium between treatment-induced adverse events and therapeutic efficacy. This paper focused on non-hematologic complications associated with the combination of ATRA and ATO. Additionally, we discuss late-onset complications of this therapy. In summary, the majority of treatment-related adverse events are manageable, self-limiting, and reversible. More so, there seems to be a lower incidence rate of secondary neoplasms compared to standard chemotherapy. However, further research is required to assess how the ATRA plus ATO regimen affects the emergence of additional comorbidities.

Invasive fusariosis in acute leukaemia patients-An outbreak in the haematology ward.

Fusarium, a common fungus, emerges as a pathogen in severely immunocompromised patients. We present a series of patients who developed invasive fusariosis (IF) during admission to an acute leukaemia ward: an outbreak of 12 cases in June and July 2018, followed by four sporadic cases until 2021. No case was reported earlier. All patients were clustered in the same location with indoor air and water installations found to be contaminated with Fusarium spp. thus a nosocomial outbreak was assumed. Following the water installation replacement, the number of Fusarium cases dramatically dropped to one or two isolated instances per year in the same location. All 16 patients had acute leukaemia and developed IF during severe neutropenia following induction therapy. IF diagnosis was based on positive blood cultures (14 patients) and/or on tissue biopsies (3 patients). The median time from admission to the IF onset was 20 days, and from the first day of severe neutropenia (≤500/mm3) was 11.5 days. All patients were febrile, eight had moderate-to-severe myalgias, eight had respiratory involvements: lung lesions and/or sinusitis and seven had characteristic skin lesions. Follow-up: 12 out of 16 (75%) were alive on Day 90; nine out of 15 (60%) were alive on Month 6. All with intractable neutropenia died. In severely neutropenic febrile patients, the triad of respiratory involvement/skin lesions/severe myalgia may suggest Fusarium aetiology. The ability to recover from neutropenia is critical to surmount IF. The indoor environment in immunocompromised dedicated settings must be constantly controlled.

Case report: High-risk acute promyelocytic leukemia and COVID-19-related myocarditis one patient, two cytokine storms.

Acute promyelocytic leukemia (APL) is a unique, highly curable subtype of acute myeloid leukemia, owing to the therapeutic advances of the last decades which led to high complete remission rates and excellent long-term survival. Nevertheless, it remains associated with high early mortality rates. Early death is the major cause of treatment failure in APL and is mainly attributed to coagulopathy, differentiation syndrome, and less commonly, infectious events. Timely recognition of each complication plays a crucial role in the management of patients diagnosed with APL. Coronavirus Infectious Disease 2019 (COVID-19) has shown great heterogeneity in patient presentation. Clinical manifestations range from asymptomatic disease to severe forms, mainly characterized by a hyperinflammatory syndrome leading to acute respiratory distress and multiorgan failure. Patients with acute leukemia and concomitant COVID-19-related hyperinflammatory syndrome have particularly poor outcomes. We hereby report the case of a 28-year-old male patient who was diagnosed with high-risk APL, with severe associated coagulopathy at presentation. He was treated with chemotherapy according to the AIDA regimen. The first week of induction therapy was complicated by a differentiation syndrome manifesting as fever not attributable to infection and respiratory distress with pulmonary infiltrates, resolved after ATRA discontinuation and corticotherapy. On the fourth week of treatment, he tested positive for acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with minor pulmonary involvement. Clinical manifestations over the following days included tachycardia and hypotension, associated with elevated inflammatory markers and cardiac biomarkers (troponin I x58 upper NV). Cardiovascular magnetic resonance imaging was consistent with myocarditis. COVID-19-associated myocarditis was successfully treated with methylprednisolone, intravenous immunoglobulins and Anakinra. Differentiation syndrome and COVID-19-associated myocarditis are two life-threatening complications that adversely impact survival. However, early recognition and prompt treatment initiation can improve clinical outcomes, as was the case of our patient.

Successful treatment of pulmonary haemorrhage and acute respiratory distress syndrome caused by fulminant Stenotrophomonas maltophilia respiratory infection in a patient with acute lymphoblastic leukaemia - case report.

BACKGROUND: Stenotrophomonas maltophilia-induced pulmonary haemorrhage is considered a fatal infection among haematological patients. The outcome can be explained by the patients' immunity status and late diagnosis and treatment. CASE PRESENTATION: We present the rare case of successful outcome in a 61-year-old female who developed alveolar haemorrhage and acute respiratory distress syndrome 8 days after a chemotherapy session for her acute lymphoblastic leukaemia, in the context of secondary bone marrow aplasia. Stenotrophomonas maltophilia was isolated in sputum culture. The patient benefitted from early empirical treatment with colistin followed by trimethoprim/sulfamethoxazole, according to the antibiogram. Despite a severe initial clinical presentation in need of mechanical ventilation, neuromuscular blocking agents infusion, and ventilation in prone position, the patient had a favourable outcome and was discharged from intensive care after 26 days. CONCLUSIONS: Stenotrophomonas maltophilia severe pneumonia complicated with pulmonary haemorrhage is not always fatal in haematological patients. Empirical treatment of multidrug-resistant Stenotrophomonas maltophilia in an immunocompromised haematological patient presenting with hemoptysis should be taken into consideration.

Let's Talk About BiTEs and Other Drugs in the Real-Life Setting for B-Cell Acute Lymphoblastic Leukemia.

Background: Therapy for acute lymphoblastic leukemia (ALL) are currently initially efficient, but even if a high percentage of patients have an initial complete remission (CR), most of them relapse. Recent data shows that immunotherapy with either bispecific T-cell engagers (BiTEs) of chimeric antigen receptor (CAR) T cells can eliminate residual chemotherapy-resistant B-ALL cells. Objective: The objective of the manuscript is to present improvements in the clinical outcome for chemotherapy-resistant ALL in the real-life setting, by describing Romania's experience with bispecific antibodies for B-cell ALL. Methods: We present the role of novel therapies for relapsed B-cell ALL, including the drugs under investigation in phase I-III clinical trials, as a potential bridge to transplant. Blinatumomab is presented in a critical review, presenting both the advantages of this drug, as well as its limitations. Results: Bispecific antibodies are discussed, describing the clinical trials that resulted in its approval by the FDA and EMA. The real-life setting for relapsed B-cell ALL is described and we present the patients treated with blinatumomab in Romania. Conclusion: In the current manuscript, we present blinatumomab as a therapeutic alternative in the bridge-to-transplant setting for refractory or relapsed ALL, to gain a better understanding of the available therapies and evidence-based data for these patients in 2019.