Elisabetta Metafuni

The role of HLA-G 14-bp polymorphism in allo-HSCT after short-term course MTX for GvHD prophylaxis.

HLA-G molecules are HLA class Ib antigens characterized by tolerogenic and immunoinhibitory functions. The HLA-G 14-bp insertion/deletion (ins/del) polymorphism controls protein expression and seems to be implicated in both MTX treatment response and SCT outcome. The aim of our study is to evaluate the role of HLA-G 14 bp polymorphism in subjects affected by hematological malignancies undergoing allo-SCT and receiving MTX therapy for GvHD prophylaxis. We performed a retrospective analysis of HLA-G 14 bp polymorphism using a specific PCR in 47 recipients and in their respective donors, and evaluated the correlation with the incidence of aGvHD, OS and disease-free survival (DFS) after allo-SCT. We did not observe any correlation between this polymorphism and the risk of aGvHD occurrence. On the contrary, we found that the recipients with a 14 bp ins/14 bp ins genotype were characterized by a lower OS and DFS in univariate and multivariate analysis (OS=OR: 3.235; DFS=OR: 3.302). These data indicate a role for recipient HLA-G 14 bp polymorphism in allo-SCT immunotolerance status and follow-up.

Prospective evaluation of epstein-barr virus reactivation after stem cell transplantation: association with monoclonal gammopathy.

Epstein–Barr Virus (EBV) reactivation and EBV-related post-transplant lymphoproliferative disease (PTLD) have emerged as a severe complication after stem cell transplantation (SCT). We prospectively evaluated 104 consecutive patients receiving SCT either autologous or allogeneic. Fifty-two patients (50%) presented EBV DNA-emia and five of them developed PTLD proven or probable. PTLD rate was 9.6% among patients with EBV DNA-emia. One patient developed PTLD without EBV DNA-emia (0.96%). Overall PTLD incidence was 5.7%. No PTLD developed after autologous SCT. EBV DNA-emia was significantly more frequent after allogeneic than autologous SCT (60.7% vs 17.4%, p = 0.0002). At EBV reactivation, serum protein electrophoresis and immunofixation were assessed. Global incidence of γ-peak after allogeneic SCT with EBV reactivation was 65.3% (32/49 patients) and monoclonal gammopathy (MG) was identified in 23/28 evaluable patients (82%). All patients with PTLD developed γ-peak and in five of them MG was identified. MG is consistently associated with EBV DNA-emia and may help identification of progression to PTLD after allogeneic SCT.

Sorafenib for refractory FMS-like tyrosine kinase receptor-3 (FLT3/ITD+) acute myeloid leukemia after allogenic stem cell transplantation

Mutations of FLT3 in AML is an entity characterized by a signifiantpoorprognosis andaredescribed inabout30%ofAML inadults. sually patients with this subtype of AML carrying either internal andem duplication (ITD) or mutation at codon 835 are referred or allogeneic stem cell transplantation (ASCT) but a proportion f them would eventually relapse. The introduction of targeted herapy against FLT3+AML is yielding conflicting results andmany rials are running with newmolecules. We used sorafenib, a multiargeted tyrosine kinase inhibitor FDA approved for the treatment f advanced renal cell and hepatocellular carcinoma, on a comassionate basis in two patients with FLT3+AML relapsing after SCT.

Role of fecal calprotectin as biomarker of gastrointestinal GVHD after allogeneic stem cell transplantation

To the editor: We read with interest the article of Rodriguez-Otero et al.[1][1] The authors studied the ability of fecal calprotectin (FC), α-1 antitrypsin, and elastase to diagnose acute gastrointestinal GVHD (GI-GVHD) after allogeneic stem cell transplantation (SCT). In their experience, FC and

Salivary Proteomic Analysis and Acute Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

Graft-versus-host disease (GVHD) is the major life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), developing in 35%-70% of all allo-HSCT recipients despite immunosuppressive prophylaxis. The recent application of proteomic tools that allow screening for differentially expressed or excreted proteins in body fluids could possibly identify specific biomarkers for GVHD. Whole saliva is highly attractive for noninvasive specimen collection. In the present study, we collected saliva specimens from 40 consecutives patients who underwent allo-HSCT between December 2008 and March 2011 at our institution. The specimens were analyzed by HPLC coupled to electrospray-ionization mass spectrometry. Variable expression of S100 protein family members (S100A8, S100A9, and S100A7) was detected. Fourteen of 23 patients with GVHD demonstrated the presence of S100A8, compared with only 2 patients without GVHD and 0 patients in the control group (P = .001). S100A7 was detectable in 11 of the 23 patients with GVHD but was absent in the other 2 groups (P = .0001). S100A9-short was detected in 20 patients with GVHD, in 9 patients without GVHD, and in 8 healthy volunteers (P = .01) Further studies are needed to clarify the role of these proteins as a marker of GVHD or as an index of mucosal inflammation.

Donor erythrocytosis induced by sorafenib treatment after allogeneic hematopoietic SCT in a patient with acute myeloid leukemia

Donor erythrocytosis induced by sorafenib treatment after allogeneic hematopoietic SCT in a patient with acute myeloid leukemia

Hyperleukocytosis and leukostasis: management of a medical emergency

ABSTRACT Introduction: Hyperleukocytosis is defined as a white blood cell count greater than 100,000/mL in patients affected by acute leukemia and often it is associated with increased morbidity and mortality, that can be up to 40% if unrecognized. Areas covered: Risk factors include younger age, myelomonocytic or monocytic/monoblastic morphology, microgranular variant of acute promyelocitic leukemia and T-cell ALL, and some cytogenetic abnormalities. Poor prognosis due to high early death rate secondary to leukostasis. The mechanisms at the origin of leukostasis are still poorly understood. The management of acute hyperleukocytosis and leukostasis involves supportive measures and reducing the number of circulating leukemic blast cells, with careful monitoring of fluid balance, control of uric acid production and control of urine pH to prevent tumour lysis syndrome. Expert commentary: Several studies have been performed to ameliorate the outcome of this setting of patients. The high number of leukocytes may cause 3 main complications: disseminated intravascular coagulation (DIC), tumor lysis syndrome (TLS), and leukostasis. Although hyperleukocytosis and tumour lysis syndrome are still a challenge for clinicians, a better prognosis for these conditions is emerging in the last years.

Cytokine profile of autologous platelet-derived eye drops in patients with ocular chronic graft-versus-host disease.

Ocular chronic GVHD is efficaciously treated with autologous platelet‐derived eye drops. We investigated the cytokine content of eye drops produced using a non‐gelified lysate obtained from autologous platelet‐rich plasma in six patients with ocular GVHD. In both the responding (n = 4) and the resistant (n = 2) patients, the eye drops were significantly enriched with various growth factors, in amounts proportional with the platelet counts. In contrast, chemokine ligand and interleukin levels were similar to those of plasma. The non‐responding patients showed the highest levels of chemokine (C‐X‐C motif) ligand (CXCL)10. These findings provide possible explanations for beneficial or detrimental effects of eye drops.

Role of flow-cytometric immunophenotyping in prediction of BCR/ABL1 gene rearrangement in adult B-cell acute lymphoblastic leukemia: FLOW-CYTOMETRY IN BCR/ABL1 ADULT B-ALL

We performed a retrospective analysis of 88 adult patients with B‐ALL diagnosed in our center by a flow‐cytometric assessment. Immunophenotypic expression of leukemic cells was explored by simultaneous evaluation of positivity, percentage of expressing cells and median fluorescence intensity (MFI). BCR/ABL1 fusion transcripts were assessed by RT‐PCR analysis and were identified in 36 patients (40.9%). CD10 and CD34 were positive in the totality of BCR/ABL1‐positive cases. Patients with gene rearrangement had a greater frequency of CD66c, CD13 and CD33 positivity compared with BCR/ABL1‐negative cases. Moreover, BCR/ABL1‐positive cases exhibited a greater median percentage and MFI values of CD13, CD33, CD66c, CD10, CD34 and CD25 expressions, but a lower median percentage and MFI values of CD38 and CD22 expressions than patients without gene rearrangement. Multivariate logistic regression analysis showed that CD10, CD38 and CD13 expressions were independent predictors for the presence of BCR/ABL1 rearrangement. Predictive probabilities of molecular occurrence based on these markers are proposed.

Changes in protein serum levels during stem cell transplantation

GvHD is one of the major complication after stem cell transplantation affecting transplant‐related mortality. Throughout the last years, many serum proteins were been proposed as possible biomarkers for GvHD.