Andrea Messerotti

Mucorales-Specific T Cells in Patients with Hematologic Malignancies

Background Invasive mucormycosis (IM) is an emerging life-threatening fungal infection. It is difficult to obtain a definite diagnosis and to initiate timely intervention. Mucorales-specific T cells occur during the course of IM and are involved in the clearance of the infection. We have evaluated the feasibility of detecting Mucorales-specific T cells in hematological patients at risk for IM, and have correlated the detection of such cells with the clinical conditions of the patients. Methods and Findings By using an enzyme linked immunospot assay, the presence of Mucorales-specific T cells in peripheral blood (PB) samples has been investigated at three time points during high-dose chemotherapy for hematologic malignancies. Mucorales-specific T cells producing interferon-γ, interleukin-10 and interleukin-4 were analysed in order to detect a correlation between the immune response and the clinical picture. Twenty-one (10.3%) of 204 patients, accounting for 32 (5.3%) of 598 PB samples, tested positive for Mucorales-specific T cells. Two groups could be identified. Group 1, including 15 patients without signs or symptoms of invasive fungal diseases (IFD), showed a predominance of Mucorales-specific T cells producing interferon-gamma. Group 2 included 6 patients with a clinical picture consistent with invasive fungal disease (IFD): 2 cases of proven IM and 4 cases of possible IFD. The proven patients had significantly higher number of Mucorales-specific T cells producing interleukin-10 and interleukin-4 and higher rates of positive samples by using derived diagnostic cut-offs when compared with the 15 patients without IFD. Conclusions Mucorales-specific T cells can be detected and monitored in patients with hematologic malignancies at risk for IM. Mucorales-specific T cells polarized to the production of T helper type 2 cytokines are associated with proven IM and may be evaluated as a surrogate diagnostic marker for IM.

Long-term molecular remission with persistence of BCR-ABL1-specific cytotoxic T cells following imatinib withdrawal in an elderly patient with Philadelphia-positive ALL.

least 2 weeks thereafter. Treatment with bendamustine and alemtuzumab was not to be interrupted for CMV viraemia, but was to be held if there was evidence of CMV infection (i.e. fever) until such evidence resolved. Summary treatment outcomes and baseline characteristics of the nine patients enrolled are shown in Table I. Three subjects were enrolled in each cohort, at which point the trial was terminated due to slow accrual. One case (Patient 9) was not evaluable for response. Evaluable responses included one case of progressive disease, four cases of stable disease and three partial responses. Adverse events are summarized in Table II. There were five serious adverse events (myelosuppression, hypotension, infection and two cases of rash). A DLT of prolonged neutropenia occurred in one patient in the highest dosing cohort (C). In summary, this phase I dose escalation study demonstrates that patients with high risk CLL can be safely treated with bendamustine in combination with alemtuzumab without excessive toxicity or CMV reactivation. More data are needed to determine the efficacy of this combination in less heavily pre-treated patients.

NPM1 mutations may reveal acute myeloid leukemia in cases otherwise morphologically diagnosed as myelodysplastic syndromes or myelodysplastic/myeloproliferative neoplasms.

Nucleophosmin 1 (NPM1) gene mutations, resulting in aberrant cytoplasmic delocalization of NPM1 (NPMc+), are detected in about 30% of all de novo acute myeloid leukemia (AML) cases, and in 50–60% o...

Immunophenotypic profile and clinical outcome of monoclonal B-cell lymphocytosis in kidney transplantation

Monoclonal B‐cell lymphocytosis (MBL) is a lymphoproliferative disorder characterized by clonal expansion of a B‐cell population in peripheral blood of otherwise healthy subjects. MBL is divided into CLL (chronic lymphocytic leukemia)‐like, atypical CLL‐like and non‐CLL MBL. The aim of this study was to evaluate immunophenotypic characteristics and clinical outcomes of MBL in kidney transplant (KT) recipients. We retrospectively evaluated 593 kidney transplant (KT) recipients in follow‐up at our center. Among them, 157 patients underwent peripheral blood flow cytometry for different clinical indications. A 6‐color panel flow cytometry was used to diagnose MBL. This condition was detected in 5 of 157 KT recipients. Immunophenotypic characterization of MBL showed four cases of non‐CLL MBL and one case of CLL‐like MBL. At presentation, median age was 65 years (range 61‐73). After a median follow‐up of 3.1 years (95%CI; 1.1‐5) from diagnosis, patients did not progress either to CLL or to lymphoma. The disorder did not increase the risk of malignancy, severe infections, graft loss and mortality among our KT recipients. Surprisingly, all cases were also affected by concomitant monoclonal gammopathy of undetermined significance, which did not progress to multiple myeloma during follow‐up. In conclusion, our data suggest that MBL is an age‐related disorder, with non‐CLL MBL being the most common subtype among KT recipients.

Safety profile of Erwinia asparaginase treatment in adults with newly diagnosed acute lymphoblastic leukemia: a retrospective monocenter study

DISCLAIMER: The ideas and opinions expressed in the journal’s Just Accepted articles do not necessarily reflect those of Informa Healthcare (the Publisher), the Editors or the journal. The Publisher does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of the material contained in these articles. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosages, the method and duration of administration, and contraindications. It is the responsibility of the treating physician or other health care professional, relying on his or her independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Just Accepted articles have undergone full scientific review but none of the additional editorial preparation, such as copyediting, typesetting, and proofreading, as have articles published in the traditional manner. There may, therefore, be errors in Just Accepted articles that will be corrected in the final print and final online version of the article. Any use of the Just Accepted articles is subject to the express understanding that the papers have not yet gone through the full quality control process prior to publication. Just Accepted by Leukemia & Lymphoma

An unusual case of splenomegaly and increased lactate dehydrogenase heralding acute myeloid leukemia with eosinophilia and RUNX1-MECOM fusion transcripts.

We report the first case of acute myeloid leukemia (AML) with RUNX1–MECOM fusion transcripts, showing marked eosinophilia. A 63-year old man admitted in August 2013, had previously been observed in April 2013, because of persisting homogeneous splenomegaly and increased LDH, which were initially attributed to both minor β-thalassemia and previous acute myocardial infarction. However, based upon the retrospective analysis of clinical features combined with the documentation of both JAK2 V617F and c-KIT D816V mutations at AML diagnosis, an aggressive leukemic transformation with eosinophilia of a previously unrecognized myeloproliferative neoplasm, rather than the occurrence of de novo AML, may be hypothesized.

Effectiveness of originator (Neupogen) and biosimilar (Zarzio) filgrastim in autologous peripheral blood stem cell mobilization in adults with acute myeloid leukemia: a single-center retrospective study

Vincenzo Nasillo , Ambra Paolini , Giovanni Riva, Monica Morselli, Leonardo Potenza, Valeria Coluccio, Monica Maccaferri, Elisabetta Colaci, Valeria Fantuzzi, Andrea Messerotti, Laura Arletti, Valeria Pioli, Elisabetta Lugli, Andrea Gilioli, Chiara Quadrelli, Patrizia Zucchini, Daniela Vallerini, Ivana Lagreca, Patrizia Barozzi, Angela Cuoghi, Paola Bresciani, Roberto Marasca, Maria Teresa Mariano, Giovanni Ceccherelli, Patrizia Comoli, Daniele Campioli, Tommaso Trenti, Franco Narni, Mario Luppi and Fabio Forghieri Department of Medical and Surgical Sciences, Section of Hematology, University of Modena and Reggio Emilia, Azienda OspedalieroUniversitaria Policlinico, Modena, Italy; Immuno-Transfusional Medicine Unit, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy; Pediatric Hematology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo, Pavia, Italy; Department of Laboratory Medicine and Pathology, Unit a Sanitaria Locale (USL), Modena, Italy

Monoclonal Gammopathy of Undetermined Significance After Kidney Transplantation: Single-Center Experience

Background Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant plasma cell disorder. Prevalence and clinical outcomes of MGUS in kidney transplant (KT) recipients have been previously reported in few studies with conflicting results. Methods We conducted a retrospective study in a population of 548 KT recipients transplanted between 1998 and 2015. Results Thirty-nine (8.1%) subjects developed MGUS after KT. At diagnosis of MGUS, the average age was 52 ± 9.2 years, and 23% of the patients were younger than 50 years. Occurrence of MGUS was not influenced by age and sex. After a mean follow-up of 7.8 years, only 1 (2.5%) patient progressed to multiple myeloma. We found no differences in the incidence of solid and hematological malignancies, serious infections, graft failure, and mortality between KT patients with MGUS and a matched cohort of KT recipients without MGUS. The MGUS group had a significantly higher prevalence of monoclonal B cell lymphocytosis, premalignant condition poorly described in KT recipients. Prior history of glomerulonephritis or interstitial nephritis, as cause of renal failure, represented the only predictive factor for MGUS development. Conclusions MGUS is a premalignant disorder frequently encountered in KT recipients. We found no differences in clinical outcomes between MGUS patients and KT controls.

Epidemiology and clinical outcome of lower respiratory tract infections by respiratory syncytial virus or parainfluenza virus type 3 in adults receiving treatment for either acute leukemia or severe aplastic anemia: a retrospective single center study

Sara Bigliardi & Monica Morselli & Leonardo Potenza & Giovanni Riva & Valeria Coluccio & Monica Maccaferri & Ambra Paolini & Elisabetta Colaci & Valeria Fantuzzi & Francesco Soci & Vincenzo Nasillo & Andrea Messerotti & Laura Arletti & Valeria Pioli & Elisabetta Lugli & Andrea Gilioli & Chiara Quadrelli & Daniela Vallerini & Patrizia Barozzi & Ivana Lagreca & Roberto Marasca & Franco Narni & Erica Franceschini & Mauro Codeluppi & Cristina Mussini & Mario Luppi & Fabio Forghieri

An unusual case of B-ALL occurring in a patient with acute promyelocytic leukemia in remission after two hematopoietic SCTs: whose are the leukemic cells?

An unusual case of B-ALL occurring in a patient with acute promyelocytic leukemia in remission after two hematopoietic SCTs: whose are the leukemic cells?