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.

Real-World Clinical Outcomes and Adverse Events in Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib: A Single-Center Retrospective Study.

Background and Objectives: The treatment of chronic lymphocytic leukemia (CLL) has acquired new targeted therapies. In clinical trials, ibrutinib improved outcomes safely. Real-world data called for a reappraisal of ibrutinib strategies. We report on a single center's experience with ibrutinib monotherapy, aiming to explore the outcomes, tolerability, and prognosis of CLL patients in routine clinical practice. Materials and Methods: Data were collected from all CLL patients treated with ibrutinib at Fundeni Clinical Institute, Bucharest, Romania, between January 2016 and June 2021. Results: A total of one hundred twenty-three CLL adult patients were treated with ibrutinib. Of the patients, 87% had relapsed/refractory CLL. The median age at ibrutinib initiation was 65 years; 44.7% of patients were staged Rai III/IV. At 32-month median follow-up, the median progression-free survival (PFS) was 50 months, the overall survival (OS) was not reached, and the overall response rate (ORR) was 86.2%. The age or number of previous therapies did not impact outcomes or tolerability. An Eastern Cooperative Oncology Group performance status (ECOG PS) score ≥ 2 and shorter time from initiation of last therapy (TILT) before ibrutinib predicted inferior PFS. Baseline characteristics had no impact on the OS except for TILT in R/R CLL patients. Drug-related adverse events (AEs) of any grade and grade ≥ 3 AEs were reported in 82.1% and 30.9% of the patients, respectively. Infections were the most common AEs (29.3%). Drug discontinuation was permanent in 43.9% of patients, mainly due to disease progression (17.1%) and toxicity (8.9%). Patients with a Cumulative Illness Rating Scale (CIRS) score ≥ 6 had a higher risk for toxicity-related discontinuation. An ECOG PS ≥ 2 predicted an increased rate of permanent discontinuation and grade ≥ 3 AEs. Conclusions: The outcomes of this study align with the results from ibrutinib clinical trials. Our study demonstrated that poor patient fitness, early relapse before ibrutinib, and permanent ibrutinib discontinuation are essential outcome determinants. Patient comorbidity burden and fitness were significant predictors for ibrutinib intolerance.

Allogeneic Stem Cell Transplantation for Adult T-Cell Leukemia/Lymphoma-Romanian Experience.

Adult T-cell leukemia/lymphoma (ATLL) is a rare and aggressive mature T-cell malignancy caused by the human T lymphoma virus I (HTLV-I) affecting 3-5% of HTLV-1 carriers and is usually diagnosed in endemic regions. Romania is a region with high prevalence of HTLV-1 infection and ATLL and with low median age at diagnosis for aggressive types. We performed a retrospective analysis of post-transplant outcome in the first Romanian patients with ATLL receiving hematopoietic stem cell allotransplant. The study population included eight patients (three males, five females), with median age of 39.5 (range 26-57), with acute (one case) and lymphoma type (seven cases) that received peripheral stem cells (PBSC) from matched related (MRD) and unrelated donors (MUD) after reduced intensity conditioning. Graft versus host disease (GVHD) developed in six patients. Relapse occurred in four cases (50%) at a median time of 5-months post-transplant. Six patients died: four cases with disease-related deaths and two patients with GVHD-related deaths. The median survival post-transplant was 19.5 months (range 2.3-44.2 months). The post-transplant survival at 1-year was 62.5%, at 2-years 50%, and at 3-years 37.5%. In our opinion allogeneic transplant improves outcome in aggressive type ATLL.

Breast myeloid sarcoma after allogeneic stem cell transplantation for acute myelomonocytic leukemia - case report.

Defined as a rare extramedullary tumor, myeloid sarcoma (MS) is in the attention of specialists, although the information in the literature is represented especially through case reports. MS can precede acute myeloid leukemia (AML), appear simultaneous and can be the only manifestation of leukemia relapse after allogeneic stem cell transplantation (allo-SCT). We present the case of a 30-year-old female diagnosed with acute myelomonocytic leukemia (AML M4), with complete remission (CR) after chemotherapy, followed by allo-SCT for consolidation. After five months, the patient presented right breast tumors. Ultrasound-guided biopsy of the breast lesion displayed diffuse infiltration of undifferentiated tumor cells, with blastic granulocytic features, strongly immunopositive for cluster of differentiation (CD) 45, CD99, CD34 and myeloperoxidase (MPO) and negative for all epithelial markers [MNF116, cytokeratin 7 (CK7), estrogen receptor (ER), progesterone receptor (PR), E-cadherin]. The final diagnosis was AML relapse with breast MS. After multiple leukemia relapses with breast MS, the patient died with cerebral bleeding secondary to severe thrombocytopenia.

Haploidentical Donors: Can Faster Transplantation Be Life-Saving for Patients with Advanced Disease?

Haploidentical stem cell transplantation is a therapeutic option for patients without an HLA-matched donor. It is increasingly being used worldwide due to the application of posttransplantation cyclophosphamide and is associated with lower incidence of graft-versus-host disease and treatment-related mortality. Haploidentical donors are generally available for most patients and stem cells can be rapidly obtained. Delays in transplantation while waiting for unrelated donor cells can be potentially problematic for patients with advanced disease at risk for progression; thus, the use of haploidentical donors, especially in this setting, can be life-saving. Here we reviewed the literature on haploidentical stem cell transplantation performed with posttransplantation cyclophosphamide.

The occurrence of chronic lymphocytic leukemia after chronic phase of chronic myeloid leukemia: case report and literature review.

The occurrence of chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL) in the same patient is a rare event. In published literature, CML diagnosis follows CLL diagnosis or both leukemias are diagnosed simultaneously or rarely, CLL diagnosis follows CML diagnosis. We report the case of one patient with renal adenocarcinoma who was diagnosed with CLL 60 months after CML diagnosis. At that time, the patient was in complete cytogenetic response (CCyR) and major molecular response (MMR) of CML clone according to European LeukemiaNet (ELN) recommendations and presented clinical and hematological signs of progressive CLL clone. After 24 months of regular monitoring, the patient presented signs of CLL clone expansion. The FISH (fluorescence in situ hybridization) analysis for CLL prognostic factors, performed before treatment, was positive for tumor protein p53 (TP53) and 13q14.3 mutations. The Li-Fraumeni syndrome (LFS) was considered but TP53 mutation was considered acquired and patient's reduced overall, progression free and disease free survival might sustained that hypothesis. Imatinib (IM) was stopped and patient received chemotherapy until obtained a stable partial response. Twelve months after last cycle of chemotherapy, the patient received second line treatment due CLL clone progression signs but died due to neutropenia related complications. This article is the first Romanian report of CLL occurrence after CML diagnosis and as far as we know the fourth case report of such association in published literature.