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Allogenic peripheral stem cell transplantation (HSCT), a procedure that is widely used in the treatment of a large number of malignant and nonmalignant hematological diseases, is still associated with a wide range of complications, one of the most important of which is graft-versus-host disease (GVHD). The patients undergoing allogeneic HSCT are at high risk of developing secondary neoplasms, particularly leukemias and lymphomas. Solid tumors are less frequent, but their incidence seems to be higher in the patients who develop GVHD; the most frequent solid tumors are squamous cell carcinomas. We here describe the clinical course and histopathologic aspects of a squamous cell carcinoma arising on GVHD-induced oral lesions in a 53-year-old woman with non-Hodgkin''s lymphoma undergoing allogeneic HSCT. Immediately after the transplantation, the patient developed GVHD involving the gastroenteric tract, skin, joints, and oral cavity, which was treated with cyclosporin, prednisone, azathioprine, colchicine, and photophereses. In addition to the sporadic reports of similar pictures published in the literature (16 cases of squamous cell carcinoma owing to oral GVHD in patients undergoing allogeneic HSCT), our case underlines the susceptibility of HSCT patients with oral GVHD to carcinoma of the oral cavity. All patients treated with allogeneic HSCT (particularly those who have developed GVHD) should therefore undergo a careful examination of the oral mucosa and be closely followed up over the long term with the aim of identifying the onset of secondary tumors as early as possible. [Copyright &y& Elsevier]

: ObjectiveMesenchymal stem cells (MSCs) are a population of multipotent cells that can proliferate and differentiate into multiple mesodermal tissues. We previously reported that monoclonal antibodies to the low-affinity nerve growth factor receptor (α-LNGFR) stain bone marrow (BM) mesenchymal cells. We now show that LNGFR antibodies label primitive MSCs with high specificity and purity in adult BM, and compare these cells to those isolated by plastic adherence (PA) and CD45−anti-glycophorin A− selection.: Materials and MethodsLow-density mononuclear cells (LD-MNCs) from normal BM were separated by PA or immunomagnetic selection for NGFR+ or CD45−α-glycophorin A− cells. The three fractions were grown in Iscove''s modified Dulbecco medium + 20% fetal bovine serum ± basic fibroblast growth factor (bFGF) in order to assess their proliferative capacity and evaluate their phenotype during culture. The clonogenic potential of the MSCs was assessed using a colony-forming unit fibroblast (CFU-F) assay, whereas multipotential differentiation was determined after culture in adipocytic and osteoblastic conditioned media.: ResultsThe NGFR+ mesenchymal cells grown without growth factors showed persistent NGFR expression (rapidly down-regulated after the addition of bFGF) and persistent CFU-F activity. The NGFR+ fractions were rich in clonogenic precursors: CFU-F median frequency was 1584/1 × 106 cells (range 325–13,793) in the NGFR+ cells and 35/1 × 106 cells (range 27–112) in the LD-MNCs. The NGFR− fraction never showed any residual CFU-F activity. Compared with the other two fractions, the NGFR+ cells (± bFGF) showed a 1 to 3 log greater expansion in the number of fibroblastic cells and a greater capacity to give rise to adipocyte colonies and induce osteoblastic differentiation, and they had similar effects in supporting the growth of hematopoietic precursors.: ConclusionThe data suggest that positive selection using low-affinity NGFR antibodies makes it possible to obtain homogeneous multipotent MSCs. [Copyright &y& Elsevier]

The CD11/CD18 family of leukocyte adhesion-promoting proteins sis compared or three members, each composed of a shared beta subunit (CD18) noncovalently associated with unique alpha subunit (CD18) noncovalently associated with unique alpha subunits (CD11 a, CD11b and CD11c respectiveley), Such three heterodimers, named LFA-1 (CD11a/CD18), H-Mac-1 (CD18) and gp150,95 (CD11c/CD18), are involved in mediating leukocyte adhesion in virtually all phases of the immune responses. Since Langerhans cells are regarded as cutaneous leukocytes, we investigated the expression of the members of the CD11/CD18 family on Langerhans cells. A vast series of immunostaining procedures was carried out , using monoclonal antibodies anti-CD11b,-CD11c, and -CD18. Normal skin frozen sections and epidermal sheets were investigated by immunohistology and immunofluorescence; suspended freshly isolated epidermal cells were processed using immunogold techniques, performed in both transmission and scanning electron microscopy, including double labeling procedures and semiquantitative analysis of the labeled cells. The results demonstrated the expression on the membrane of the CD11b, CD11c and CD18 antigens, thus indicating that at least the H-Mac-1 (CD-11b/CD18) and the gp 150,95 (CD11c/CD18) members of the CD11/CD18 family are detectable on the cell surface of human resting Langerhans cells. Since both such moieties serve as adhesion molecules in (a) cell-cell interactions and in (b) leukocyte migrtion and localization, the present results suggest that H-Mac-1 and gp150,95 might display a key role (a) in promoting interactions between Langerhans cells and other cells, and (b) in guiding the migration and localization of Langerhans cells. [ABSTRACT FROM AUTHOR]

The transplantation of two cord blood (CB) units obtained from unrelated donors (double CBT) is an effective strategy for adult patients with hematologic malignancies. Sustained hematopoiesis after double CBT is usually derived from a single donor, and only a few transplantation recipients displaying a stable mixed donor–donor chimerism have been reported. We investigated the mechanisms underlying single-donor predominance in double CBT by studying in vitro the role of the graft-versus-graft cell-mediated immune effect in two-way mixed-lymphocyte culture, along with the contribution of differential hematopoietic progenitor (HP) potency in HP mixed cultures. Results for the two-way mixed-lymphocyte culture showed that despite the weak and variable alloantigen-specific cytotoxic potential displayed by CB mononuclear cells, an immune-mediated dominance for one of the two CB units was detected in the majority of experiments. Alloantigen-induced cytotoxic activity was directed toward both CB-HP and phytohemagglutinin (PHA)-activated T lymphoblastoid cells. The CB unit with the higher fold expansion of CD34+ cells in single-expansion culture was prevalent in the HP mixed-expansion culture, as shown by DNA chimerism evaluation. Based on these data, we hypothesize that the dominant CB unit is able to develop prevalent cytotoxic activity toward activated lymphocytes of the other CB unit, thereby preventing them from exerting alloantigen-specific cytotoxic potential against both activated lymphocytes and HPs of the dominant unit. In accordance with this hypothesis, we propose the evaluation of alloantigen-induced cytotoxic activity generated in two-way mixed-lymphocyte culture and directed toward PHA-activated T lymphoblastoid cells as a tool to identify the potentially predominant CB unit before double CBT. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to assess the role of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with poor-risk Hodgkin''s disease (HD) compared to chemotherapy. A donor was identified in 26 patients (14 HLA identical siblings and 10 alternative donors), and 24 received a transplant (Allo group). Twenty patients without a donor received different chemotherapy regimens and radiotherapy (CHEMO group). After a median follow-up of 28 months (range: 1-110), the 2-year overall survival (OS) was 71% in the ALLO group compared to 50% in the CHEMO group (P = .031). In the Allo group, the 2-year progression-free survival (PFS) was 47%. The 1-year nonrelapse mortality (NRM) in the ALLO group was 8% versus 0% in the CHEMO group. This study, suggests that allogeneic transplantation may prolong the survival in patients with a poor-risk HD. [Copyright &y& Elsevier]

Summary: Allogenic hematopoietic stem cell transplantation (HSCT), a procedure that is widely used in the treatment of a large number of malignant and non-malignant hematological diseases, is still associated with a wide range of complications, one of the most important of which is graft versus host disease (GVHD). The patients undergoing allogenic HSCT are also at high risk of developing secondary neoplasms, particularly leukemias and lymphomas. Solid tumors are less frequent, and the incidence appears to increase over time; the most frequent solid tumors are squamous cell carcinomas. We found that almost all studies of solid cancers occurring after transplantation are based on relatively small numbers of cases which have been monitored for short periods, and little information is available on individual cancers. In particular, reports of oral cancers in HSCT are very few. Potential risk factors associated with the development of secondary solid cancers after HSCT have been well described. They include graft versus host disease (GVHD), preoperative regimens, with either radio-chemotherapy or chemotherapy alone, conditioning regimes, immunosuppressive GVHD prophylaxis, viral infection and chronic stimulation as a result of viral antigens, antigenic stimulation from histocompatibility differences between recipient and donor, primary diagnosis, interaction of any of these factors with genetic predisposition, and other factors such as sex and age. All patients treated with HSCT should therefore be closely followed over the long term with the aim of identifying the onset of secondary tumors as early as possible. [Copyright &y& Elsevier]

The detection of circulating cancer cells in the bone marrow (BM) and peripheral blood (PB) of patients with solid tumors may be useful for disease staging. To this aim, we evaluated the expression of the mammaglobin gene by reverse transcriptase polymerase chain reaction (RT-PCR) in 60 patients with breast cancer. Moreover, several controls were examined to test the specificity of this marker. The positive cases included 23.6% of the patients with and 9% of those without metastasis. Only 4/60 negative controls analyzed were positive by PCR. Our results show high specificity and a good correlation with disease status. [Copyright &y& Elsevier]

The first case of primary γ/δ cutaneous T-cell lymphoma (CTCL) with a fatal outcome is reported. The patient had the clinical and histopathologic features of disseminated page-toid reticulosis, a rare form of CTCL characterized by a strong epidermotropic lymphoid infiltrate. Extensive immuno-cytochemical studies showed that the neoplastic cells were almost exclusively localized in the epidermis, expressed the ͏/δ variant of the T-cell receptor (CD3+, TCR-δ-1+) and were CD5+, CD7+, CD27+, CD29+, CD43+, CD44+, CD45+, CD45RA+, CD54+, CD69+, but βF1-, Ti&gama;a-, BB3-, A13-, CD2-, CD4-, CD8-, CD11a-, CD49d-, CD25-, CD30-, and HLA-DR-. A comparison of our results with those of the literature, which have not included γ/δ T-cell receptor analysis, suggests that some reported cases of pagetoid reticulosis, may have phenotypes similar to our case, Electron microscopy studies demonstrated that the γ/δ T lymphocytes were villous, containing dense and multivesicular bodies, and formed close contacts with the surrounding keratinocytes, suggesting that these cells should have a role in the skin-associated lymphoid tissue. The proliferating cells in our case might represent, the neoplastic counterpart of the our case might represent the neop1astic counterpart of the recently reported CD2- subset of normal human peripheral blood &#947/δ T lymphocytes. [ABSTRACT FROM AUTHOR]