Invasive fungal disease (IFD) is one of the most serious complications of therapy in patients with immune suppression. It particularly concerns patients treated for malignant hematological diseases, immune deficiencies, or undergoing hematopoietic cell transplantation (HCT). Development of IFD can abrogate the effect of previous therapy and contributes to dismal outcome of the underlying disease. The Working Group consisting of members of the Polish Society of Hematology and Blood Transfusion, the Polish Society of Pediatric Oncology and Hematology, and the Polish Adult Leukemia Study Group has prepared recommendations for the diagnostic and therapeutic management of IFD in adults and children. This paper presents the current recommendations for patients in immune suppression treated in Polish pediatric and adult hematology and HCT centers, based on the guidelines of the European Conference on Infections in Leukaemia (ECIL) 2015–2019. Levels of diagnosis of IFD (possible, probable, and proven) and antifungal management (prophylaxis, as well as empirical and targeted therapies) are declared according to updated international criteria of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG) 2019. Patients with primary diagnosis of acute lymphoblastic leukemia, acute myeloblastic leukemia, severe aplastic anemia, chronic granulomatous disease, and severe combined immunodeficiency, as well as patients after allogeneic HCT, are included in the high-risk groups for development of IFD. For these patients, antifungal prophylaxis based on azoles or micafungin is recommended. In empirical therapy, caspofungin or liposomal/lipid formulas of amphotericin B are recommended. The Working Group has discouraged the use of itraconazole in capsules and amphotericin deoxycholate. Detailed guidelines for first- and second-line targeted therapies for invasive candidiasis, aspergillosis, mucormycosis, fusariosis, and scedosporiosis, as well as the principles of the recommended dosing of antifungals, are presented in this paper.
Proton pump inhibitors (PPIs) are drugs commonly used for many diseases of the gastrointestinal tract, such as gastroesophageal reflux disease, erosive esophagitis, and peptic ulcers of the stomach and duodenum. Used for about 30 years, they are currently the most effective drugs that reduce the gastric secretion of hydrochloric acid. However, a dramatic increase in their consumption has been recently observed. Very often, they are used not in accordance with the guidelines. The consequences of the long-term use of PPIs may be various, with the most common side effects being bone fractures, cardiovascular events, recurrent infections, and vitamin and mineral deficiencies. Case report: An 82-year-old and a 58-year-old patients who had been taking omeprazole, a PPI for several years, developed vitamin B12 and iron deficiency anemia. Both patients were administered PPI orally for nonspecific dyspeptic symptoms. An evaluation of the gastrointestinal tract did not reveal the evident causes of gastrointestinal blood loss. They were also screened negative for Helicobacter pylori infection. Conclusions: There are no definitive pieces of evidence that the long-term use of PPIs can induce anemia, but our cases strongly suggest this thesis. Physicians should be aware of this potential side effect and consider monitoring in high-risk patients.
Hemoglobin/red cell distribution width (RDW) ratio (HRR) and lymphocyte-to-monocyte ratio (LMR) are two novel bio-markers associated with overall survival (OS) and prognosis in several types of cancers. The aim of this study is to investigate the value of HRR and LMR in newly diagnosed multiple myeloma (MM) patients.
A total of 180 patients were included in this study. Patients diagnosed with MM between May 2013 and May 2019 at a single center were evaluated. HRR was calculated by dividing hemoglobin to RDW, both measured from the same sample. LMR was calculated by dividing absolute lymphocyte count (ALC) to absolute monocyte count (AMC).
The cutoff value for HRR was taken as 0.61, and the cutoff value for LMR was taken as 3.28. Patients were divided into low HRR, high HRR, low LMR, and high LMR groups. OS of the patients with low HRR was found lower compared with high HRR (36.7 months for low HRR and 53.2 months for high HRR, p < 0.001). Also, OS was found lower in the low LMR group (39.4 months for low LMR and 51.7 months for high LMR, p = 0.016). On multivariate analysis, low HRR and low LMR were predictive factors of OS (hazard ratio (HR) 2.08, 95% confidence intervals (CI) 1.31–3.03, and p = 0.002 for low HRR; HR 1.47, 95% CI 0.92–2.29, and p = 0.010 for low LMR).
Combining both HRR and LMR could be a prognostic biomarker and it reflects the status of the immune system in newly diagnosed MM patients.
Philadelphia-negative myeloproliferative neoplasms (Ph-neg MPNs) are characterized by clonal hematopoiesis derived from a mutated hematopoietic stem cell. Ph-neg MPNs rarely transforms into acute leukemia, and in most cases, the transformation leads to the development of acute myeloid leukemia (AML). The incidence of mixed-phenotype leukemia (MPAL) or acute lymphoblastic leukemia (ALL) with lineage switch is much rarer. The unidentified lineage of blast cells is due to the immaturity of their undifferentiated progenitors with co-expression of myeloid and lymphoid antigens. The prognosis of secondary acute leukemia transformed from Ph-neg MPN is very unfavorable, especially in MPAL or lineage switch from ALL to AML cases. Moreover, there are no therapeutic protocols for these specific leukemia subtypes. Therefore, we believe that all cases of MPAL or lineage switch leukemia should be reported. This article presents the case of a patient with JAK2-positive essential thrombocythemia (ET) transformed to MPAL, and a patient with triple-negative primary myelofibrosis (PMF) (negative for JAK2, CALR, and MPL) transformed to ALL with subsequent lineage switch to AML.
Myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal myeloid neoplasms. Allogeneic stem cell transplantation (allo-SCT) remains the curative method for MDS treatment. Little is known about the monitoring of minimal residual disease (MRD) in patients with MDS after allo-SCT.
We aimed to evaluate the significance of leukemia-associated immunophenotypes (LAIPs) identified in acute myeloid leukemia (AML) for MRD monitoring in patients with MDS after allo-SCT.
Material and methods
Seven males and 4 females with a median age of 55 years were included. The diagnosis of MDS was established according to 2016 World Health Organization (WHO) criteria. The significance of eight LAIPs in bone marrow samples using multiparameter flow cytometry (MFC) was evaluated for MRD.
Eight patients were positive for several LAIPs before allo-SCT. The identified LAIPs included the presence of aberrant lymphoid antigens on myeloblasts and lack of CD33 expression on myeloblasts. All studied MDS patients were negative for LAIPs at Day +30 after the procedure. This was followed by full-donor chimerism in all cases. The Ogata score after allo-SCT decreased in all patients in whom it was indicative for MDS before allo-SCT.
MFC could be useful in monitoring MRD in MDS patients after allo-SCT. Further studies in this field are needed.
Neurofibromatosis type 1 (NF1) is characterized by the occurrence of multisystem tumors. The objective of this study was to analyze the demographic and oncological profile of 830 NF1-individuals regarding prevalence, type, and spectrum of malignancy.
Patients and methods
The medical records of patients diagnosed with NF1 with a median age of 22.1 years (range: 0.8–81.6 years) who were followed up for malignancies from 1999 to 2018 were retrospectively reviewed.
The prevalence of malignancy occurring in patients diagnosed with NF1 was 34.8% (289/830). The most common types of neoplasia encompassed tumors strictly associated with NF1, including plexiform neurofibromas (PNF; 200/830; 24.1%) and optic pathway gliomas (91/830; 11%). The prevalence of PNFs-transforming to malignant peripheral nerve sheath tumors (MPNST) was 3.5% (7/200). The prevalence of other tumors was 4.8% (40/830). One patient was diagnosed with acute myeloid leukemia (AML), thus the risk of hematological malignancies among all patients with NF1 was 0.1% (1/830). In the population of patients with malignancies, 43/289 (14.9%) individuals were diagnosed with more than one malignancy.
The odds ratio (OR) of malignancy in a studied cohort of patients with NF1 was 23 (p < 0.001), while the OR of hematological malignancy was 5.1 (p = 0.1) in comparison with the general population.
Noninvasive T2* magnetic resonance imaging (MRI) assessment can stratify the risk of subsequent cardiac dysfunction in β-thalassemia major (TM) and β-thalassemia intermedia (TI) patients. The normal level of N-terminal pro B-type natriuretic peptides (NT-proBNP) can rule out acute heart failure.
We aim to investigate the relation of NT-proBNP level, T2* MRI, and echocardiographic findings in TM and TI patients.
Materials and methods
In this cross-sectional study, 41 TM patients, 41 TI patients, and 41 healthy individuals (HI) were enrolled. NT-proBNP level, T2* MRI, and two-dimensional echocardiography were assessed for all patients and controls.
There was statistically significant correlation between NT-proBNP levels and mitral inflow late diastolic velocity (r = −0.538; p = 0.006) in TM group. There was statistically significant correlation between NT-proBNP levels and tricuspid annulus systolic velocity (r = −0.438; p = 0.028), systolic velocity of septum (r = −0.472; p = 0.020), and mitral inflow early-to-late diastolic wave ratio (r = 0.592; p = 0.002) in TM group.
Early diagnosis and treatment of myocardial iron overload are likely to prevent the mortality in patients with established ventricular dysfunction. Since NT-proBNP levels were not significantly increased in documented left ventricular (LV) diastolic dysfunction, this factor may not be sensitive for the detection of latent LV diastolic dysfunction in the early stages of disease progression.
In patients with acute leukemia, lymphoma and chronic malignancies, donor and/or recipient Epstein-Barr virus (EBV) seropositive status increases the risk of development of chronic graft-versus-host disease (cGVHD) after allo-hematopoietic cell transplantation (allo-HCT), while it has no influence on other transplant outcomes. No data are available on the impact of EBV serostatus on transplant outcomes in patients with nonmalignant hematological disorders.
We analyzed the influence of the recipient's (R) and donor's (D) EBV serostatus on transplant outcomes (overall survival (OS); relapse-free survival (RFS); relapse incidence (RI); nonrelapse mortality (NRM); acute graft-versus-host disease (aGVHD); cGVHD) in patients with nonmalignant hematological disorders undergoing allo-HCT.
Patients and Methods
A total of 2,355 allo-HCTs performed between 1997 and 2016 for acquired bone marrow failure or hemoglobinopathies were included in this retrospective Registry megafile Infectious Diseases Working Party of the European Society of Blood and Marrow Transplantation (IDWP-EBMT) study.
Demographics: The median age of recipient was 17.7 years (range: 0–77), and 50.8% were children. 79.0% of recipients and 75.4% of donors were EBV-seropositive. 67.8% had HCT from a matched family donor, 4.6% from a mismatched family donor, and 27.6% from an unrelated donor (UD). T-cell depletion was performed in vivo and ex vivo in 82.2% and 6.6% of patients, respectively. Conditioning regimen was myeloablative in 63.7% and reduced intensity conditioning (RIC) in 36.3% of patients. The median follow-up was 4.7 years. Transplant outcomes: EBV-seropositive recipients in comparison with EBV-seronegative recipients had lower OS (85.4% vs. 88.4%, p = 0.035) and higher NRM (10.0% vs. 6.4%, p = 0.018). No other significant differences were found for: RI, RFS, and aGVHD or cGVHD with respect to EBV pretransplant serostatus donor and/or recipient. Multivariate analysis: A trend toward higher risk of development of cGVHD (HR = 1.31; p = 0.081) and better survival (HR = 0.78; p = 0.087) in allo-HCT from EBV-seropositive donors was found. Allo-HCT in EBV-seropositive recipients had a trend toward lower risk of development of cGVHD (HR = 0.75; p = 0.065). When four subgroups (R−/D−, R−/D+, R+/D−, R+/D+ EBV serology) were analyzed, the EBV serostatus had no significant impact on OS, RFS, RI, NRM and development of aGVHD or cGVHD.
Allo-HCT from EBV-seropositive versus EBV-seronegative donors are at 31% higher risk of cGVHD in patients with nonmalignant hematological disorders undergoing allo-HCT; however this difference is nonsignificant in multivariate analysis.