San Martino dall'Argine, Italy
San Martino dall'Argine, Italy

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Della Chiesa M.,University of Genoa | Falco M.,Instituto Giannina Gaslini Genoa Quarto | Podesta M.,Centro Cellule Staminali e Terapia Cellulare | Locatelli F.,University of Pavia | And 3 more authors.
Blood | Year: 2012

Natural killer (NK) cells play a crucial role in early immunity after hematopoietic stem cell transplantation because they are the first lymphocyte subset recovering after the allograft. In this study, we analyzed the development of NK cells after intrabone umbilical cord blood (CB) transplantation in 18 adult patients with hematologic malignancies. Our data indicate that, also in this transplantation setting, NK cells are the first lymphoid population detectable in peripheral blood. However, different patterns of NK-cell development could be identified. Indeed, in a group of patients, a relevant fraction of NK cells expressed a mature phenotype characterized by the KIR +NKG2A - signature 3-6 months after transplantation. In other patients, most NK cells maintained an immature phenotype even after 12 months. A possible role for cytomegalovirus in the promotion of NK-cell development was suggested by the observation that a more rapid NK-cell maturation together with expansion of NKG2C +NK cells was confined to patients experiencing cytomegalovirus reactivation. In a fraction of these patients, an aberrant and hyporesponsive CD56 -CD16 +p75/AIRM1 -NK-cell subset (mostly KIR +NKG2A -) reminiscent of that described in patients with viremic HIV was detected. Our data support the concept that cytomegalovirus infection may drive NK-cell development after umbilical CB transplantation. © 2012 by The American Society of Hematology.

Rosti V.,Unit of Clinical Epidemiology and Center for the Study of Myelofibrosis | Bonetti E.,Unit of Clinical Epidemiology and Center for the Study of Myelofibrosis | Bergamaschi G.,Foundation Medicine | Campanelli R.,Unit of Clinical Epidemiology and Center for the Study of Myelofibrosis | And 11 more authors.
PLoS ONE | Year: 2010

Increased mobilization of circulating endothelial progenitor cells may represent a new biological hallmark of myeloproliferative neoplasms. We measured circulating endothelial colony forming cells (ECFCs) in 106 patients with primary myelofibrosis, fibrotic stage, 49 with prefibrotic myelofibrosis, 59 with essential thrombocythemia or polycythemia vera, and 43 normal controls. Levels of ECFC frequency for patient's characteristics were estimated by using logistic regression in univariate and multivariate setting. The sensitivity, specificity, likelihood ratios, and positive predictive value of increased ECFC frequency were calculated for the significantly associated characteristics. Increased frequency of ECFCs resulted independently associated with history of splanchnic vein thrombosis (adjusted odds ratio = 6.61, 95% CI = 2.54- 17.16), and a summary measure of non-active disease, i.e. hemoglobin of 13.8 g/dL or lower, white blood cells count of 7.8x10 9/L or lower, and platelet count of 400x10 9/L or lower (adjusted odds ratio = 4.43, 95% CI = 1.45-13.49) Thirteen patients with splanchnic vein thrombosis non associated with myeloproliferative neoplasms were recruited as controls. We excluded a causal role of splanchnic vein thrombosis in ECFCs increase, since no control had elevated ECFCs. We concluded that increased frequency of ECFCs represents the biological hallmark of a non-active myeloproliferative neoplasm with high risk of splanchnic vein thrombosis. The recognition of this disease category copes with the phenotypic mimicry of myeloproliferative neoplasms. Due to inherent performance limitations of ECFCs assay, there is an urgent need to arrive to an acceptable standardization of ECFC assessment. © 2010 Rosti et al.

Frassoni F.,Centro Cellule Staminali e Terapia Cellulare | Frassoni F.,Advanced Biotechnology Center | Varaldo R.,Centro Cellule Staminali e Terapia Cellulare | Gualandi F.,Divisione Ematologia | And 6 more authors.
Best Practice and Research: Clinical Haematology | Year: 2010

Cord blood transplant (CBT) in adult patients is scarcely utilized because of the risk of graft failure or very delayed platelet recovery. To improve the capacity and the speed to engraft, we have developed an intra-bone (IB) cord blood transplant technique. 75 patients with hematological malignancies, categorized by disease phase as early (18%), intermediate (20%) and advanced (62%), were transplanted. The median cell dose (TNC) infused was: 2.6 (1.35-5.4) × 107/kg; the HLA disparity was: 12 cases = 5/6, 62 cases = 4/6 and 1 case = 3/6 matched antigens. 72/75 patients engrafted (96%); median day of recovery of neutrophils (PMN) >500 × 109/L and platelets (PLT) >20 000 × 109/L was: 23 (14-44) and 35 (16-70) days respectively. The outcomes at 2 years according to Kaplan-Meier are: OS = 46% ± 5; RI = 18% ± 2; NRM = 39% ± 5. Acute GVHD incidence/severity was: grade 0-I = 64%, II = 14%, III-IV = 0%. The incidence of Chronic GVHD was globally low but in 3 cases was very severe. Intra-bone CBT is associated with high rate of engraftment, early and robust platelet recovery, low incidence of acute GVHD. A very promising aspect is that the relapse rate is low considering the advanced phase of the disease in two/thirds of patients. A suitable CBU was found for nearly every patient searching for a CBU. Therefore, IB CBT extends the possibility to transplant any patient for whom this approach represents the sole possibility of long-term survival. © 2010 Elsevier Ltd. All rights reserved.

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