Daniela Renzi

High density of CD68+/CD163+ tumour‐associated macrophages (M2‐TAM) at diagnosis is significantly correlated to unfavorable prognostic factors and to poor clinical outcomes in patients with diffuse large B‐cell lymphoma

To the Editor Tumour-Associated Macrophages (TAM) may have both anti-tumoural and tumour-promoting functions, depending on their acquired immunophenotype (M1 or M2). Recent studies have shown that TAM expression was related with prognosis in hematologic malignancies, particularly in Hodgkin’s lymphoma [1]. However, the role of microenvironment in diffuse large B-cell lymphoma (DLBCL) has been less studied in the last years, and contrasting results about the role of TAM concentration on prognosis were obtained. Hasselblom et al. demonstrated that it is not possible to predict worse clinical outcomes in terms of disease-free survival (DFS) and overall survival (OS) in DLBCL patients just evaluating CD68+ TAM concentration [2], whereas other studies showed that high TAM density was significantly related to poor prognosis [3] and worse therapy-response [4]. More recently, Nam et al. suggested that an increase ofM2-TAM predicts poor outcome in DBLCL patients treated with R-CHOP regimen [5]. The aim of this study is to quantify TAM concentration making use of a double immunofluorescence in DLBCL patients at diagnosis and to evaluate the presence of a significant correlation between the prevalent subtype of macrophages, clinical and biological disease features and clinical outcomes in terms of therapy response, DFS and OS. Sixty-one patients diagnosed with de novo DLBCL were enrolled in our study. Fifty-seven patients were treated with R-CHOP regimen (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone), whereas the remaining four received R-CHOP-like regimens (with liposomal Doxorubicin). Every patient gave an informed written consent to authorize sensitive data processing for scientific purposes; this study has been approved by a local Ethical Committee. Treatment responses were evaluated according to Cheson’s criteria [6]. Different subtypes of macrophage infiltration were identified by a double indirect immunofluorescence for CD68/CD163 (M2) and CD68/HLA-DR (M1). Antibodies against CD68 were used as primary antibodies to recognise CD68+ cells. Then we used a secondary antibody (Ab) binding the Fc fragment of the primary Ab. The secondary Ab was marked with Alexa Fluor 488 fluorochrome (Life

Cytomegalovirus reactivation after autologous stem cell transplantation in myeloma and lymphoma patients: A single-center study

AIM To determine the incidence of and the risk factors for cytomegalovirus (CMV) symptomatic infection and end-organ disease after autologous stem cell transplantation (ASCT). METHODS A total of 327 consecutive non CD34(+) selected autografts performed from the Hematology and Stem Cell Transplantation Unit of Regina Elena National Cancer Institute of Rome (Italy) in the period comprised between January 2003 to January 2015, were reviewed. Over the 327 autografts, 201 were performed in patients with multiple myeloma, whereas the remaining 126 in patients affected by non-Hodgkins lymphoma and Hodgkins lymphoma. The patients who underwent an ASCT for an acute leukemia (n = 20) in the same period were excluded from this analysis. CMV DNA load in the blood has been determined by polymerase-chain reaction in the case of a clinical suspicion of reactivation, therefore, no routine monitoring strategy was adopted. In the presence of signs and symptoms of CMV reactivation an antiviral treatment was performed. RESULTS Overall, 36 patients (11%) required a specific antiviral treatment for a symptomatic CMV reactivation (n = 32) or an end-organ disease (n = 4). We observed 20 and 16 cases of CMV reactivation among lymphoma (16%) and myeloma patients (8%), respectively. Among cases of end-organ disease, 3 were diagnosed as interstitial pneumonia and one remaining case as hemorrhagic enteritis. All cases of CMV reactivation were observed in IgG seropositive patients, with no documented cases of primary CMV infection. All patients were treated with a specific antiviral therapy, with a global rate of hospitalization of 55%; four patients received intravenous immunoglobulins. Transplant-related mortality was significantly higher in patients who experienced a CMV reactivation (8.4% ± 4.7% vs 1.7% ± 0.8%; P = 0.047). In univariate analysis, a pre-transplant HBcIgG seropositivity, a diagnosis of T-cell non-Hodgkins lymphoma and higher median age at transplant were significantly associated with the risk of developing a clinically relevant CMV infection requiring specific antiviral therapy (P < 0.001, P = 0.042 and P = 0.004, respectively). In multivariate analysis, only a pre-transplant HBcIgG seropositivity (OR = 8.928, 95%CI: 1.991-33.321; P = 0.023) and a diagnosis of T-cell non-Hodgkins lymphoma (OR = 4.739, 95%CI: 1.511-11.112; P = 0.042) proved to be independent predictors of a post-transplant clinically relevant CMV reactivation. CONCLUSION A symptomatic CMV infection can occur in about 11% of adult patients with lymphoma or myeloma undergoing ASCT. A pre-transplant HBcIgG seropositivity and a diagnosis of T-cell non-Hodgkins lymphoma should be considered as independent predictor factors of CMV reactivation.

Cryotherapy reduces oral mucositis and febrile episodes in myeloma patients treated with high-dose melphalan and autologous stem cell transplant: a prospective, randomized study

Cryotherapy reduces oral mucositis and febrile episodes in myeloma patients treated with high-dose melphalan and autologous stem cell transplant: a prospective, randomized study

Biosimilar filgrastim (Zarzio(®)) vs. lenograstim (Myelostim(®)) for peripheral blood stem cell mobilization in adult patients with lymphoma and myeloma: a single center experience.

1 Hematology and Stem Cell Transplantation Unit, Regina Elena National Cancer Institute, 2 Immuno-Transfusional Medicine, Leukapheresis and Cellular Therapy Unit, S. Camillo-Forlanini Hospital, 3 Immuno-Transfusional Medicine Unit, Regina Elena National Cancer Institute, 4 Scientifi c Direction, Regina Elena National Cancer Institute, and 5 Intensive Care and Pain Therapy Unit, Regina Elena National Cancer Institute, Rome, Italy

Ponatinib Induces a Persistent Molecular Response and Graft-versus-Host Disease/Graft-versus-Leukemia Effect in a Patient with Philadelphia-Positive Acute Lymphoblastic Leukemia with a T315I Mutation following Early Relapse after Allogeneic Transplant

We describe the case of a patient with a Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with dasatinib plus steroids as the first-line therapy who achieved a molecular complete remission and then underwent a matched, unrelated donor allogeneic transplant. Five months after the transplant, he experienced a disease relapse with an T315I mutation, which was resistant to salvage chemotherapy. Once the details of the T315I mutation were acquired, we initiated ponatinib treatment at a standard dosage and observed a rapid decrease of minimal residual disease (MRD) at molecular assessment. The bone marrow evaluation after 2, 3, 6, 10 and 13 months was negative for MRD. After starting ponatinib, the patient experienced a skin graft-versus-host disease (GVHD), whereas no occurrence of GVHD was observed after transplant, suggesting that the efficacy of ponatinib could be related not only to the direct antileukemic effect, but also to its ability to promote an indirect graft-versus-leukemia effect. Ponatinib was well tolerated but a thyroid dysfunction mimicking a cardiovascular toxicity was observed and solved with hormonal substitutive treatment.

The predictive value of Aspergillus PCR testing on bronchoalveolar lavage fluid for early diagnosis of invasive pulmonary aspergillosis in hematologic patients

Francesco Marchesi, Antonio Spadea, Fulvia Pimpinelli, Grazia Prignano, Maria Grazia Paglia, Daniele Forcella, Svitlana Gumenyuk, Daniela Renzi, Francesca Palombi, Antonella Vulcano, Francesco Pisani, Atelda Romano, Elena Papa, Francesco Facciolo, Fabrizio Ensoli, Corrado Girmenia and Andrea Mengarelli Hematology and Stem Cell Transplant Unit, Regina Elena National Cancer Institute, Rome, Italy; Molecular Virology, Pathology and Microbiology Laboratory, San Gallicano Dermatological Institute, Italy; Microbiology and Infectious Diseases Biorepository Laboratory, National Institute of Infectious Diseases “L. Spallanzani”, Italy; Thoracic Surgery Unit, Regina Elena National Cancer Institute, Rome, Italy; Hematology, “Sapienza” University, Rome, Italy

Lenograstim 5 µg/kg is not superior to biosimilar filgrastim 10 µg/kg in lymphoma patients undergoing peripheral blood stem cell mobilization after chemotherapy: preliminary results from a prospective randomized study: LENO VS BIOSIMILAR FIL FOR MOBILIZATION

Randomized trials comparing chemomobilization efficiency between lenograstim and biosimilar filgrastim are lacking. Our previous retrospective study suggested that lenograstim could be more effective than biosimilar filgrastim when used at the same conventional dosage (5 µg/kg) only in lymphoma patients undergoing peripheral blood stem cell mobilization. We planned a prospective randomized study comparing lenograstim 5 µg/kg with biosimilar filgrastim 10 µg/kg to verify the hypothesis of lenograstim superiority even at half the dosage (stress test). Herein we report data after enrolling 60% of planned patients.

Prevention of Bortezomib-Related Peripheral Neuropathy With Docosahexaenoic Acid and α-Lipoic Acid in Patients With Multiple Myeloma: Preliminary Data

Background and Aims: Peripheral neuropathy is a common complication of chemotherapy that can induce marked disability that negatively affects the quality of life in patients with multiple myeloma (MM). The aim of this study was to prevent the onset or the worsening of peripheral neuropathy in MM patients treated with bortezomib (BTZ), using a new nutritional neuroprotective compound. We report preliminary results of 18 out of 33 patients who completed the study. Methods: We administered a tablet of Neuronorm to patients, containing docosahexaenoic acid 400 mg, α-lipoic acid 600 mg, vitamin C 60 mg, and vitamin E 10 mg bid for the whole follow-up period. Neurological visit assessment, electroneurography, and evaluation scales were performed at baseline and after 6 months. Results: At 6 months, 8 patients had no chemotherapy-induced peripheral neuropathy, while 10 patients experienced chemotherapy-induced peripheral neuropathy of grade 1 according to the Common Terminology Criteria for Adverse Events, one of them with pain. Seventeen patients did not report painful symptoms; no limitation of functional autonomy and stability in quality of life domains explored was observed. Conclusions: Our results seem to indicate that early introduction of a neuroprotective agent in our patients with MM treated with BTZ could prevent the onset or the worsening of neuropathic pain, avoiding the interruption of the therapy with BTZ, and maintaining a good functional autonomy to allow normal daily activities. Despite the limitations due to the fact that this is a preliminary study, in a small population, with short follow-up, our data seem to indicate that the nutraceutical may have some potential to be considered for a future trial.