Sabrina Giammarco

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.

Bone marrow transplantation versus immunosuppressive therapy in patients with acquired severe aplastic anemia

Standard front-line treatment for acquired aplastic anemia (AA) for patients is either immunosuppressive therapy (IST) or bone marrow transplantation (BMT), usually from an HLA identical sibling. Whereas long-term survival is comparable with either treatment, important differences remain: IST patients may have incomplete or no recovery, are exposed to late clonal disorders and relapse of the original disease. Transplantation is a curative treatment, but patients are exposed to transplant-related complications both acute and chronic, such as chronic graft versus host disease (cGvHD). In the year 2000, a study by the European Group for Blood and Marrow Transplantation (EBMT), looked at failure free survival (FFS), in patients receiving first-line BMT from an HLA identical sibling, or the first-line IST. Young patients with low neutrophil counts benefited of the first-line BMT; the opposite was true for older patients with higher neutrophil counts; and a third intermediate group of patients had comparable survival irrespective of the first-line therapy. We have now studied a more recent cohort of patients to assess whether things have changed over the years. We have found similar results, although overall survival has improved, as a consequence of changes in the IST and BMT protocols.

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.

Transplant outcome for patients with acquired aplastic anemia over the age of 40: has the outcome improved?

TO THE EDITOR: Age is known to be a strong negative predictor of survival in patients undergoing an allogeneic hematopoietic stem cell transplantation (HSCT) for severe acquired aplastic anemia (SAA), with higher mortality in patients >40 years of age,[1][1] and this has been confirmed in several

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.

Fecal but not serum calprotectin is a potential marker of GVHD after stem cell transplantation

Gastrointestinal graft-versus-host disease (GvHD) represents a life-threatening complication after stem cell transplantation. Differential diagnosis between gut GvHD and other causes of diarrhea after HSCT is still subjected to endoscopy and histological findings. The research for a reliable biomarker for gut GvHD might allow an early diagnosis of this condition and a consequent prompt treatment that could reduce unfavorable outcomes. Recently, fecal calprotectin was reported as reliable marker of gut involvement. We would evaluate if serum instead of fecal calprotectin could be considered a possible biomarker of gut GvHD. Serum calprotectin was measured in a cohort of 54 patients submitted to allogeneic stem cell transplantation using ELISA assay. For a subset of 21 patients, calprotectin serum levels were compared with fecal calprotectin detection. Contrary to fecal calprotectin, we found only a trend to high level of serum calprotectin for GvHD development and gut involvement, but statistical difference was not reached. Fecal but not serum calprotectin could be considered as possible biomarker for gut GvHD.