Infectious complications of induction treatment for acute myeloid leukaemia using the "7 + 3" protocol without antibiotic prophylaxis - 15 years of experience of one clinical site.

BACKGROUND: Infectious complications during induction chemotherapy of acute myeloid leukaemia are very common. Prophylactic use of antibiotics however is an ongoing challenge in this situation due to bacterial multi-drug resistance. The aim of this study was to provide a comprehensive overview of the incidence of infectious complications in patients with AML undergoing induction therapy using the "7+3" protocol without routine antibiotic prophylaxis at one clinical site providing specialised haematological care in the Czech Republic, over a period of 15 years. The study also evaluates the aetiological spectrum of causative agents and the development of antibiotic resistance in the context of the use of the various classes of antibiotics. The analysis includes evaluation of the importance of risk factors for infectious complications and their impact on treatment of the underlying disease. The data are compared with published figures for similar cohorts of patients. PATIENTS AND METHODS: This study presents a retrospective analysis of infectious complications in 242 patients with acute myeloid leukaemia undergoing the first cycle of induction therapy without routine antibiotic prophylaxis in one clinical site in Czech Republic during years 2006-2020. RESULTS: A total of 363 febrile episodes (FE) were recorded. At least 1 FE during the induction was detected in 229 (94.6%) patients. Clinically defined infection was the cause in 96 (26.4%) FEs and blood stream infection in 69 (19.0%) FEs. Both complications occurred simultaneously in 29 (8.0%) FEs. 169 (46.6%) FEs were evaluated as fever of unknown origin (FUO). The achievement of complete remission had a significant effect on the duration of the FE (6 vs. 9 days, P=0.0005) and on the overall survival duration (79.3 vs. 6.5 months, P<0.0001). Patients diagnosed with infection or FUO at diagnosis were significantly more likely to suffer from colonisation by multi-drug resistant bacterial strains at discharge (29.2% vs. 16.3%, P=0.022). This group of patients used antibiotic therapy for a significantly longer time (35 vs. 23 days, P<0.0001). Infection was a contributing cause of death in 18 (7.4%) patients. Mortality was significantly related to the failure to achieve complete remission (P<0.0001). CONCLUSION: Infectious mortality during induction treatment without routine antibiotic prophylaxis was comparable to the published cohorts with prophylaxis. Regular microbiology surveillance with adequate initial antibiotic treatment can compensate routine antibiotic prophylaxis with slower development of antibiotic resistance.

Precursor T-lymphoblastic lymphoma as a secondary malignancy in a young patient after successful treatment of acute promyelocytic leukemia.

BACKGROUND: Acute promyelocytic leukemia (APL) is a relatively rare subtype of acute myeloid leukemia. It has become the best curable subtype of acute leukemias in adults due to the inclusion of all-trans-retinoic acid (ATRA) in the treatment. Despite the efficacy of ATRA, chemotherapy must be added in APL patients in order to maintain durable complete remission. However, chemotherapy administration is inevitably related to many complications, including the risk of secondary malignancies. T-lymphoblastic lymphoma (T-LBL) is an infrequent disease that belongs to the group of highly aggressive lymphomas. CASE REPORT: The authors describe the case of a 25-year-old woman who was treated for APL in 2002 and developed precursor T-LBL 5 years later. CONCLUSION: Several cases of secondary acute lymphoblastic leukemias in 'cured' APL patients have been described, but probably no patient with secondary precursor T-LBL. Secondary malignancy has become one of the topics discussed (not only) in APL patients. It is apparently related to the excellent treatment outcomes and long-term survival. Better tailored treatment based on relevant prognostic factors allowing chemotherapy reduction or omission in some patients is needed.

Granulocyte transfusions collected after steroid priming for severe infections during neutropenia: A single center experience.

BACKGROUND: There is no universally accepted opinion on the use of granulocyte transfusions collected using apheresis (GTA) in neutropenic patients and severe infection. PATIENTS AND METHODS: The efficacy and safety of GTAs transfused at a single center over 10 years were analyzed retrospectively. GTAs were harvested from voluntary unrelated donors after priming with methylprednisolone using continuous apheresis and hydroxyethylstarch as sedimentation agent. RESULTS: 41 patients with neutropenia and hematologic malignancy (15 females and 26 males aged 22-69 (median 45.5)) were given a median 3.5 GTAs per patient (range: 1-17) containing a median 1.39×1010 granulocyte/GTA (range: 0.65-2.81). The indications for GTA use were soft tissue inflammation, sepsis, and pneumonia in 30, 22, and 14 cases, respectively. After GTA complete (30 patients: 73.2%) or partial (6 patients: 14.6%) healing of the infection was achieved. The success rate was 91.7% in soft tissue infections, 66.7% in invasive fungal infections, and 68% in sepsis. Septic shock (documented in 12 cases) was associated with a poor response (P<0.03; Chi-square test). Clinical worsening was observed in six cases (14.6%); four patients died. No significant short-term side effects of GTA treatment were recorded. CONCLUSIONS: In our study GTAs collected after steroid priming and used for the treatment of infection during severe neutropenia have shown comparable efficacy with several previously reported trials. However retrospective fashion of our study and inhomogeneous group of patients do not allow any firm conclusions. Prospective studies (including patients' registries) are needed for the better clarification of the role and the dose of GTAs necessary for the successful infection management during neutropenia.

Sources and pathways of spread of vancomycin-resistant enterococci in hemato-oncological patients.

The presented study aims at analyzing an increasing prevalence of vancomycin-resistant enterococci (VRE) isolated from various kinds of clinical material obtained from patients in the Department of Hemato-oncology (DHO), University Hospital in Olomouc, Czech Republic. Between January 1 and March 31, 2005, enterococci were isolated by standard microbiological procedures using both clinical material obtained from hospitalized patients and samples from the department environment. Resistance to vancomycin and teicoplanin was determined by a standardized microdilution method. Phenotype determination of resistance to vancomycin was verified by PCR detection of vanA and vanB genes. In VanA Enterococcus faecium, macrorestriction analysis was performed by pulsed-field gel electrophoresis. During the monitored period, a total of 128 Enterococcus sp. strains were isolated, of which 38 (30 %) isolates from 22 different patients were determined as VRE. Dominating were Enterococcus faecium VanA (63 %) and Enterococcus casseliflavus VanC (16 %) strains. At the same time, one Enterococcus faecium VanA strain was acquired from a bed-side table used by a patient in whom a similar strain had been isolated repeatedly from various clinical materials including a rectal swab taken in 2004. Based on the macrorestriction analysis of genome DNA in 24 vancomycin-resistant Enterococcus faecium VanA strains isolated from the patients' clinical material, one strain from the bed-side table surface and one strain isolated from stools in 2004, 8 unique restriction profiles with similarity ranging from 90 % to 100 % were identified, which could be classified into 3 clonal types. Thus, we can assume not only the endogenous origin of the VRE in hemato-oncological patients and their potential selection caused by therapy with broad-spectrum antibiotics but also the ability of the strains to survive in a hospital setting and, subsequently, to be spread clonally by various vectors.

Long-term remission of therapy-related acute myeloid leukemia with a new t(11;18)(q23;q21.2) translocation and KMT2A-ME2 (MLL-ME2) fusion gene.

We describe a unique case of a woman with acute myeloid leukemia with a new, previously undescribed translocation, t(11;18)(q23;q21.2), affecting the KMT2A (MLL) gene and resulting in an KMT2A(MLL)-ME2 fusion. This disease occurred secondarily following chemotherapy for a different acute myeloid leukemia with the recurrent genetic abnormality inv(16)(p13.1;q22). The secondary leukemia was treated with intensive chemotherapy without allogeneic hematopoietic cell transplantation. Complete remission lasting more than 10 years has been achieved with concurrent and sustained remission of the primary leukemia.

Spontaneous splenic rupture in a patient with acute promyelocytic leukaemia during induction chemotherapy.

BACKGROUND: Acute promyelocytic leukaemia (APL) is a subtype of acute myeloid leukaemia with high curability rates. However, it is often accompanied by severe coagulopathy and bleeding risk and thus represents a potentially fatal haematological emergency requiring immediate treatment. Spontaneous splenic rupture is a rare event in all haematological malignancies. Only two clinical cases have been described so far in a setting of APL. CASE REPORT: We report a patient with APL without preceding splenomegaly who underwent urgent splenectomy for spontaneously occurring splenic rupture during induction chemotherapy. After surgery the patient completed induction chemotherapy and achieved complete remission. CONCLUSION: This is the second case of spontaneous splenic rupture without preceding splenomegaly in a patient with APL during induction chemotherapy described so far. Our case demonstrates that emergent splenectomy can be lifesaving even in the unfavourable condition of patient with severe immune deficiency.

Procedure for granulocyte collection performed at the Blood Centre of the Faculty Hospital Ostrava.

BACKGROUND: Granulocyte apheresis is a safe and effective method for granulocyte collection. We present a five year experience (2006-2010) of the Blood Center, Faculty Hospital Ostrava, Czech Republic. Donor granulocyte transfusion is one treatment option for haemato-oncology patients with severe neutropenia complicated by bacterial/fungal infections unresponsive to standard antibiotic/antifungal treatment. In this study, we describe the experiences of the Blood Centre at the Faculty Hospital in Ostrava of granulocyte apheresis. METHODS AND RESULTS: A total of 149 granulocyte units were collected for 33 patients from the Department of Haemato-oncology, University Hospital Olomouc, over a 5-year period (2006-2010). Information on donor selection, laboratory screening, mobilization regimen and granulocyte yield was obtained and analyzed. All mandatory screening tests for infection markers, AB0 and Rh and abnormal erythrocyte antibodies were performed. The cytomegalovirus status of the donors was not investigated. Steroids were the only mobilization regimen used, and were generally well accepted. The mean granulocyte yield was 12.6×10(9)/per transfusion unit (range 5.4-30.3). All granulocyte concentrates were irradiated and transfused according to AB0 Rh compatibility within 24 h after collection. CONCLUSION: Based on our experience, granulocytapheresis is a safe and effective method for obtaining granulocytes but the yield can be significantly influenced by other variables. From the recipients' perspective, the use of donor granulocytes supports an effective therapeutic modality.

Comparison of new flu-bu12-tg conditioning with the standard bu-cy myeloablative regimen in patients undergoing allogeneic stem cell transplantation for acute myeloid leukemia.

AIMS: This study compares the outcomes of patients with high-risk acute myeloid leukemia (AML) who underwent allogeneic stem cell transplantation (SCT) after conditioning combining busulfan (16 mg/kg orally) and cyclophosphamide (120 mg/kg intravenously) (BU-CY) with those allografted after administration of fludarabine (150 mg/m(2) intravenously), busulfan (12 mg/kg orally) and thymoglobulin (6 mg/kg intravenously) (FLU-BU12-TG). MATERIAL AND METHODS: SCT after BU-CY and FLU-BU12-TG was performed in 21 and 10 AML patients. There were no significant differences between groups in number of patients treated in complete disease remission, gender, age, donors, CD34+, mononuclear cell (MNC) count in the graft and follow-up period. However, significantly more SCTs from unrelated (90% vs. 19%; p=0.00018) and HLA-mismatched donors (50% vs. 0%; p=0.0004) were performed in the FLU-BU12-TG group. The Cox proportional hazards model was used to assess the risk of post-transplant AML relapse and non-relapse mortality (NRM). The probability of post-transplant 2-year event-free survival (EFS) and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: No significant differences were found between the FLU-BU12-TG and BU-CY groups in risk of AML relapse (HR=1.036; 95% CI [0.102 - 10.47]; p=0.9), post-transplant NRM (HR=0.25; 95% CI [0.031 - 1.96]; p=0.18), 2-year EFS (89% vs. 43%; p=0.19) or OS (79% vs. 57%; p=0.23). CONCLUSION: These pilot results demonstrate the efficacy of the new FLU-BU12-TG conditioning regimen in patients allografted for high-risk AML. This conditioning might become an alternative approach in patients at high risk of severe post-transplant complications after the standard BU-CY myeloablative regimen.

Unusual manifestation of multiple myeloma: focal affection of central nervous system in a patient with chronic lymphocytic leukaemia.

INTRODUCTION: Involvement of the central nervous system as the first manifestation of multiple myeloma is very rare. AIM: To present an unusual case of the primomanifestation of a multiple myeloma in the form of a focal affection of the central nervous system in a patient with chronic lymphocytic leukaemia. METHODS AND RESULTS: A female patient diagnosed with chronic B-lymphocytic leukaemia with gradually increasing right-sided cerebellar symptomatology. The CT examination revealed expansion of the cranial vault with significant compression of brain structures. The tumour was extirpated and the histological examination led to a diagnosis of a plasmocytic myeloma. A thorough examination confirmed the diagnosis of multiple myeloma with significant osteolytic involvement of the skeleton. A combined chemo- and radiotherapy resulted in adjustment in the focal neurological finding, and a partial remission of the multiple myeloma was achieved. CONCLUSION: The above presented case describes two very unusual states: the primomanifestation of a multiple myeloma in form of a focal affection of the central nervous system, and the coincidence of a multiple myeloma as the second haematological malignancy in a patient with chronic B-lymphocytic leukaemia.