Haematopoietic abnormalities after autologous stem cell transplantation in lymphoma patients

Abstract

Summary: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 pretransplant 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. Keywords: bone marrow transplantation; cytogenetics; haematopoietic stem cells; stromal cells High-dose chemo-radiotherapy followed by the infusion of cryo-preserved autologous bone marrow or peripheral blood stem cells has been increasingly used for the treatment of a variety of malignant haematopoietic diseases. 1After the pancytopenic period, the majority of patients recover normal peripheral blood counts and tend to maintain them for many years after the transplant.2,3 However,

Chromosomal abnormalities in women with breast cancer after autologous stem cell transplantation are infrequent and may not predict development of therapy-related leukemia or myelodysplastic syndrome

“…25 To our knowledge, only one case with a single trisomy X has been described as a secondary MDS (refractory anemia subtype), which developed 4 months after ASCT in a patient with Hodgkin's lymphoma. 30,31 Unlike our cases, the patient died 2 months after the onset of MDS. Nevertheless, this case may be similar to ours with trisomy X.…”

In vitro assessment of bone marrow endothelial colonies (CFU-En) in non-Hodgkin's lymphoma patients undergoing peripheral blood stem cell transplantation

“…These data are in agreement with previous reports, showing a damage of the marrow microenvironment after bone marrow transplantation or the administration of cytostatic drugs. [25][26][27] Based on these data it can be said that in remission phase of NHL patients perturbations and physiological stress such as those that may occur in the BM after chemotherapy do not prevent the growth of endothelial cells in contrast to what happened to the fibroblast component of the BM. The persistence of ECs may contribute to the bone marrow hematopoietic reconstitution by producing potent stimulating factors such as b-FGF, which, under acidosis conditions, has been shown to stimulate EC proliferation and protection from apoptosis, 28 or VEGF that can be produced in larger amounts by repopulating progenitors, which can ultimately stimulate (by a paracrine loop) the proliferation of both immature (angioblasts) and differentiated endothelial cells.…”

Diagnosis of secondary myelodysplastic syndromes (MDS) following autologous transplantation should not be based only on morphological criteria used for diagnosis of de novo MDS

“…Investigation of dyserythropoietic and dysthrombopoietic atypias has been previously restricted to the early post-transplant period (first 12 weeks) after transplantation. [19][20][21] Transient dyserythropoiesis has been reported to be present in all cases 60 days following transplantation. 20 We have found that dyserythropoietic changes persist in some cases for a long time after autografting, although usually only a minority of erythroblasts are affected.…”

“…Information about the influence of transplantation on bone marrow cellularity is scanty. [21][22][23][24] We have observed that the transplant process induces hematopoietic damage, increasing the number of cases with decreased cellularity and thrombopoiesis 6 months after the procedure. However, this damage is transitory since these parameters return to normal in most patients 1 year after transplantation.…”