E. Tagliaferri

Haematopoietic abnormalities after autologous stem cell transplantation in lymphoma patients.

Haematopoietic reconstitution after autologous stem cell transplantation (ASCT) was evaluated at different times in 26 lymphoma patients. All of the patients showed a significant decrease in the number of both committed (CFU-C) and more primitive progenitor cells (LTC-IC). The expansion of bone marrow progenitor cells in a ‘stroma-free’ long-term liquid culture system supplemented with SCF, IL-3, IL-6 and GM-CSF from 19 transplanted patients was significantly reduced compared to normal controls. The stromal cell compartment, evaluated by means of a CFU-F assay, was also greatly reduced. The number of haematopoietic and stromal cell progenitors was, nevertheless, very similar to their pre-transplant values. Bone marrow histology, which was evaluated at different times after transplant, showed an increase in reticulin fibres, the dilatation of parenchymal sinusoids and some morphological evidence of trilineage dysplasia in 11 patients; however, the same abnormalities were seen in the majority of pre-transplant samples. No cytogenetic abnormalities were observed in 15 patients before transplant, but four subsequently developed persistent clonal karyotypic alterations and five showed non-clonal abnormalities that generally disappeared over time. Our data suggest that both the stromal and the haematopoietic compartments are somehow damaged after ASCT for lymphoma; however, these defects generally pre-exist the transplant conditioning regimen and seem to become less pronounced over time.

Cytogenetic and myelodysplastic alterations after autologous hemopoietic stem cell transplantation.

Secondary myelodysplastic syndrome/acute myelogenous leukemia (MDS/AML) are today considered a primary complication of autologous hematopoietic stem cell transplantation. In our Center, 83 autografted patients underwent bone marrow (BM) biopsy and cytogenetic analysis at fixed intervals. Twelve patients developed non-clonal cytogenetic abnormalities and 10 patients clonal abnormalities, five of whom (three - 7, one - 5 and one t(9;11)) developed secondary MDS/AML. MDS was also diagnosed in two patients with a normal karyotype. In brief, seven patients (three males, four females; median age 36 years) developed MDS/AML 12-48 months (median 14) after autografting. The FAB diagnosis was AML-M2 in one, chronic myelomonocytic leukemia in two and refractory anemia with excess of blasts in transformation in four cases. Two patients presented a BM biopsy picture of MDS with fibrosis; none of them experienced leukemic transformation. Four MDS patients died, three of leukemic transformation and one of BM insufficiency; the two remaining patients are still living and untransformed. Our data underline the leukemogenic role of previous treatments, even if it is not possible to exclude that underlying disease and/or conditioning therapy may be involved.

HD-Ara-C in the Conditioning Regimen for BMT in Acute Leukemias

The choice of the most appropriate BMT conditioning regimen depends on whether the BMT is autologous or allogeneic BMT, the characteristics of the underlying disease, its susceptibility to antineoplastic agents, the entity of the expected GVL effect, the risk of GVHD, and the desired level of immunosuppression. Furthermore, there is still no unequivocal evidence concerning the superiority of either of the treatment schedules used in BMT Units (Mineishi et al 1999, Jilella et al 1999).

Autologous Bone Marrow Transplantation in Relapsing Acute Leukemias

Second complete remission (CR) can be achieved in more than 50% of relapsing patients with acute myelogenous (AML) and lymphoblastic leukemia (ALL); however, in spite of this relatively favourable CR rate, only a scant proportion of these patients experience long-term disease-free survival [1,2]. Various strategies have been designed in order to improve the above figure. Allogeneic (BMT) and autologous bone marrow transplantation (ABMT) appear to be therapeutic choices which could offer a significant advantage in terms of event free survival (EFS) [3,4].