Roberto Luksch

Expression of integrins in human bone marrow

Expression of integrins, a superfamily of glycoprotein α/β heterodimers which integrate the cytoskeleton with the extracellular matrix and/or mediate cell‐cell adhesive interactions, was examined on normal and leukaemic bone marrow cells by immunohistochemistry and immunotransmission electron microscopy (immuno‐TEM). Among the β1/VLA molecules studied, VLA‐2 and 6 were expressed on megakaryocytes and platelets, while VLA‐4 was present on 40% of haemopoietic cells, including monocytes, erythroblasts and immature cells; this molecule was typically localized at sites of intercellular contact, as seen by immuno‐TEM, suggesting it may be involved in interactions among haemopoietic cells during differentiation. In human longterm bone marrow cultures (LTBMC), VLA‐1 and 3 were present respectively on 35% and 40% of the adherent cells which included flbroblasts and endothelial cells, as shown by double‐labelling experiments; VLA‐2 was expressed only on a subpopulation of flbroblasts. β2/LeuCAM molecules were absent from platelets, megakaryocytes and HLA‐DR+/myelo‐peroxidase− early myeloid precursors, and appeared progressively during maturation in both lymphoid and myeloid cells. Expression of β3/cytoadhesin molecules was restricted to megakaryocytes and platelets and, in the adherent layer of LTBMC, to endothelial cells. The regulated expression and specific localization of integrins in the bone marrow suggest that these molecules may have a role in normal haemopoiesis.

Myelodysplastic syndrome with increased marrow fibrosis: a distinct clinico-pathological entity

Summary Seventeen cases of myelodysplastic syndrome (10 primary and seven secondary to previous radio‐chemotherapy), characterized by trilineage dysplasia, severe bone marrow fibrosis and a high number of megakaryocytes, are described. All of these patients had similar clinical and prognostic features consisting of pancytopenia, modest or absent visceral enlargement and poor survival. The use of CD61 antibodies, which recognize megakaryocytic cells at all stages of maturation, confirmed that these patients had a higher number of these cells than either normal subjects or patients affected by myelodysplastic syndrome (MDS) without fibrosis. Furthermore, primary and secondary MDS with fibrosis, although clinically and histopathologically similar, differed in terms of the number of megakaryoblasts which were significantly higher in primary forms (P<0·02). We conclude that MDS with fibrosis may represent a clinico‐pathological entity which needs to be distinguished from other MDS subtypes as well as from idiopathic myelofibrosis or malignant myelosclerosis.

Clouds of Oxygen: Adolescents With Cancer Tell Their Story in Music

Andrea Ferrari, Michela Casanova, Stefano Chiaravalli, Chiara Magni, Roberto Luksch, Monica Terenziani, Filippo Spreafico, Daniela Polastri, Cristina Meazza, Serena Catania, Elisabetta Schiavello, Veronica Biassoni, Marta Podda, Luca Bergamaschi, Nadia Puma, Carla Moscheo, Giacomo Gotti, Maura Massimino, Fondazione IRCCS Istituto Nazionale Tumori; Laura Veneroni, Carlo Alfredo Clerici, University of Milan, Milan, Italy.

Incidence and histological features of bone marrow involvement in malignant lymphomas

SummaryBone marrow biopsy (BMB) is a routine investigation in the diagnosis and staging of Hodgkins disease (HD) and non-Hodgkins lymphoma (NHL), and there is evidence supporting its prognostic importance in some histological varieties. The histological characteristics of BMB in 433 NHL and 155 HD patients were reviewed for clinicopathological correlations; 36 of these cases were also studied by means of immunohistochemistry. BM infiltrates were discovered in 171 NHL patients. In 36 cases, the diagnosis of NHL was directly established by BMB; a discordance between lymph node and BM histology was observed in 38 of the other 135 cases. BM-positive centroblastic and immunoblastic NHL were significantly associated with larger infiltrates, BM fibrosis, and megakaryocytic hyperplasia. Leukemization at diagnosis was more frequent in low-malignancy NHL. No correlation was found between histology and prognosis, although immunohistochemistry revealed a B-cell phenotype in all but two cases. BMB was positive in 18 of the 155 HD patients and directly diagnostic in two; Reed-Sternberg and Hodgkin cells were CD-30 positive and surrounded by T-cell infiltration. The concordance between BM and lymph node histology was fairly satisfactory, although the relationships between BM infiltration and other histological parameters may reflect peculiar interactions with BM microenvironmental factors. The usefulness of BMB in the diagnosis of malignant lymphomas has been demonstrated, and further progress can be expected from the availability of reliable immunohistochemical markers of clonality reacting on paraffin-embedded BM sections.

The Sooner the Better? How Symptom Interval Correlates With Outcome in Children and Adolescents With Solid Tumors: Regression Tree Analysis of the Findings of a Prospective Study

The potential impact of diagnostic delays on patients’ outcomes is a debated issue in pediatric oncology and discordant results have been published so far. We attempted to tackle this issue by analyzing a prospective series of 351 consecutive children and adolescents with solid malignancies using innovative statistical tools.

A cystic partially differentiated nephroblastoma producing α-fetoprotein

: A case of cystic partially differentiated nephroblastoma with immunohistochemical and serological demonstration of alpha-fetoprotein (AFP) production is described. To our knowledge, this is the first such case reported. The morphological heterogeneity of this rare tumor led us to describe the criteria of its nosological classification and of its differential diagnosis with intrarenal teratoma. AFP, besides being a marker of germline-derived tumor, was associated to this rare variant of Wilms tumor. Although the tumor did not show regression either on clinical or pathologic assessments, serum AFP levels decreased after preoperative chemotherapy and returned to normal limits after nephrectomy.

Neuroblastoma (Peripheral neuroblastic tumours)

Peripheral neuroblastic tumours (PNTs), a family of tumours arising in the embryonal remnants of the sympathetic nervous system, account for 7-10% of all tumours in children. In two-thirds of cases, PNTs originate in the adrenal glands or the retroperitoneal ganglia. At least one third present metastases at onset, with bone and bone marrow being the most frequent metastatic sites. Disease extension, MYCN oncogene status and age are the most relevant prognostic factors, and their influence on outcome have been considered in the design of the recent treatment protocols. Consequently, the probability of cure has increased significantly in the last two decades. In children with localised operable disease, surgical resection alone is usually a sufficient treatment, with 3-year event-free survival (EFS) being greater than 85%. For locally advanced disease, primary chemotherapy followed by surgery and/or radiotherapy yields an EFS of around 75%. The greatest problem is posed by children with metastatic disease or amplified MYCN gene, who continue to do badly despite intensive treatments. Ongoing trials are exploring the efficacy of new drugs and novel immunological approaches in order to save a greater number of these patients.

Measuring the efficacy of a project for adolescents and young adults with cancer: A study from the Milan Youth Project

Various projects dedicated specifically to adolescents and young adults (AYA) with cancer have been developed in recent years. A critical aspect of such programs is the ability to demonstrate its value, and therefore how to measure desired outcomes.

Allogeneic stem cell transplantation in therapy-related acute myeloid leukemia and myelodysplastic syndromes: Impact of patient characteristics and timing of transplant

Abstract Patients with therapy-related acute myeloid leukemia (t-AML) and myelodysplastic syndromes (t-MDS) have poor survival and high non-relapse mortality (NRM) after allogeneic stem cell transplantation. This retrospective study assessed the transplant outcomes of 29 consecutive patients with t-AML (83%) or t-MDS (17%) treated with allogeneic transplantation. The median age of patients was 51 years. Donors were mostly matched unrelated (52%), and 59% of patients received myeloablative conditioning. Two-year overall survival, event-free survival and relapse incidence were 37%, 34% and 33%; NRM was 17% at 100 days, and 32% at 2 years. Event-free survival was reduced in patients with high-risk cytogenetics (p = 0.02), Karnofsky performance status ≤ 80% (p = 0.001) and disease after induction ± consolidation (p = 0.006). NRM was higher in patients receiving > 2 therapy lines for previous cancer (p = 0.01) and in those allografted > 6 months from diagnosis (p = 0.03). In conclusion, allogeneic transplantation should be proposed timely to these patients after an accurate analysis of patient history.

Efficacy of topotecan plus vincristine and doxorubicin in children with recurrent/refractory rhabdomyosarcoma

Background This study investigates the efficacy and the feasibility of a chemotherapy regimen with topotecan plus vincristine and doxorubicin (TVD) given on an individually tailored basis to patients with refractory/recurrent rhabdomyosarcoma (RMS). Patients and methods Nine patients received TVD therapy at relapse, and six were assessable for response. Results All the six patients experienced objective response after two cycles of chemotherapy: one minor response, four partial response, and one complete response. Conclusions The value of our study is severely limited by the small number of cases, the single-institutional setting and the individually tailored treatment, but we nonetheless confirmed the feasibility and tolerability of topotecan-based chemotherapy in RMS.