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C Skert,
D Damiani,
A Michelutti,
F Patriarca,
M Arpinati,
C Filì,
P Lucchi,
M Malagola,
C Bergonzi,
A Roccaro,
A Peli,
D Ricotta,
L Caimi,
R Fanin,
M Baccarani,
D Russo
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ABSTRACT: The role of different cytokines and cells of immune system in the pathogenesis of chronic GVHD (cGVHD) is still controversial. Earlier studies, which were either retrospective or analysed one or a few factors, did not show unequivocal results. We prospectively evaluated cytokine levels and lymphocyte subsets in 30 patients who underwent Allo-SCT to investigate their possible correlation with cGVHD. Levels of IL-4, IL-6, IL-10, IFN-gamma, tumour necrosis factor-alpha (TNF-alpha) and its soluble receptors were assessed by ELISA in 30 patients at different times after SCT. Lymphocyte subsets were evaluated by flow cytometry in peripheral blood at the same times as cytokines. A multivariate analysis was performed using principal component analysis and multi-factor ANOVA (analysis of variance). Eighteen patients developed cGVHD at a median time of 6 months (range, 5-9) after SCT. In multivariate analysis, we observed a correlation between cGVHD and clusters of cytokines and lymphocyte subsets from the third to the sixth month after SCT. These clusters changed their composition over time, but they constantly included natural killer (NK) and CD152+ T cells as negative predictors of cGVHD. TNF-alpha prevailed among other cytokines before the onset of cGVHD. This prevalence could be related partly to the defect of immunoregulatory cells.
Bone marrow transplantation 05/2009; 44(11):729-37. · 3.00 Impact Factor
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Bone Marrow Transplantation 04/2005; 35(5):523-4. · 3.75 Impact Factor
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F Patriarca, C Skert,
A Sperotto,
D Damiani,
M Cerno,
A Geromin,
F Zaja,
R Stocchi,
S Prosdocimo,
C Fili,
R Fanin
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ABSTRACT: We evaluated the incidence, the risk factors, and the outcome of late-onset noninfectious pulmonary complications (LONIPCs) among 50 patients who underwent allogeneic stem cell transplantation from unrelated donors. Of the 39 patients surviving at least 3 months, 10 (26%) fulfilled the diagnostic criteria of LONIPCs and were further subclassified as having bronchiolitis obliterans (four patients), bronchiolitis obliterans with organizing pneumonia (four patients), and interstitial pneumonia (two patients). Two patients had a durable partial remission after treatment with prednisone and cyclosporine; the remaining eight patients did not respond to treatment and five of them died of respiratory failure. Advanced stage of disease at transplant and chronic extensive graft-versus-host disease (GVHD) were significantly associated with the development of LONIPCs. Pulmonary function test (PFT) results before transplantation were similar in all patients, but patients with LONIPCs had a significant decrease in PFT indexes at the third month after BMT compared with controls. Moreover, the rate of cyclosporine taper during the fourth and fifth months after BMT was significantly more rapid in patients with LONIPCs than in controls, suggesting that the risk of LONIPCs may be influenced by a faster reduction of GVHD prophylaxis.
Bone Marrow Transplantation 05/2004; 33(7):751-8. · 3.75 Impact Factor
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[show abstract]
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ABSTRACT: Large-scale CD34+ enrichment has been demonstrated a safe method in autologous transplantation for multiple myeloma. However, the high CD34+ enrichment and the consequent plasma cell purging result in concomitant T-cell and dendritic-cell (DC) depletion, theoretically increasing the risk of life-threatening infections.
We evaluated immunological and dendritic reconstitution in 72 myeloma patients who had undergone CD34+-selected (n = 45) and unmanipulated (n = 27) stem cell transplant, and its correlation with infections.
Haematological recovery occurred promptly in all patients. Only a slight delay in platelet recovery to >50 x 10(9)/l was observed in patients receiving CD34+-enriched graft. Natural killer (NK) cell count recovered in all patients within 2 months and B-cell count had recovered by 6 months post-transplant in both groups. CD3 cells remained lower than normal in both groups. CD8 cells increased above the normal level, reaching a peak at day 90, and lowered to normal level within 1 year post-transplant. CD4 lymphocytes remained <50% of normal, especially in selected patients. In both groups, both DC1 and DC2 counts were already significantly lower than in normal individuals before conditioning therapy. Pre-conditioning levels of DC1 were reached in unmanipulated patients at day 30 and became normal at 6 months. In selected patients, DC1 pre-transplant level was observed at day 60 and was maintained thereafter. DC2 recovery showed a similar trend. In unselected patients, DC2 count increased to pre-conditioning level at haematological recovery and was normal after 1 year. In selected transplants, DC2 increased more slowly than DC1 in the same patients: pre-transplant level was detected at day 90 but was still significantly lower than normal 1 year after transplant. The incidence of infection was similar in both groups. Sepsis had Gram+ aetiology in the majority of cases. After engraftment only viral infections were recorded, mostly due to herpes reactivation, with no difference between groups.
In spite of a delay in immune recovery, CD34 enrichment is not associated with a significant increase of complications due to infection. Relatively fast NK cell recovery to pre-transplant levels and the presence of functionally efficient DCs can justify the low incidence of infections.
Annals of Oncology 04/2003; 14(3):475-80. · 6.43 Impact Factor
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D Damiani,
R Stocchi,
P Masolini,
A Michelutti,
A Sperotto,
A Geromin, C Skert,
M Cerno,
M Michieli,
M Baccarani,
R Fanin
[show abstract]
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ABSTRACT: There is persistent immunosuppression not only in allogeneic but also in autologous stem cell transplantation because humoral and cellular immunity may take a year or more to return to normal, with increased risk of infectious complications. This immune defect may also involve antigen presentation, in particular dendritic cell (DC) function. We evaluated DC subset reconstitution in 58 patients who underwent bone marrow (BM) or peripheral blood (PB) autologous haematopoietic stem cell transplantation (HSCT). In all patients DC type 1 (DC1) and DC type 2 (DC2) were already significantly lower than in normal individuals before conditioning therapy (DC1/microl 3.1 +/- 1.0, DC2/microl 3.0 +/- 1.1). On day 0 and day +7 the mean DC1 and DC2 numbers were very low in both groups. Patients who received unmanipulated marrow or peripheral blood stem cells reached pre-conditioning levels of DC1 and DC2 cells on day +20. In patients receiving selected CD34 cells, DC increased slowly and pre-transplant counts were observed only on day +60. Nearly 'normal' levels of DC1 and DC2 could be observed in the first group from day +180, and were maintained thereafter; in CD34(+) selected patients DC1 and DC2 counts remained lower than normal. Our data emphasise that circulating antigen presenting cells (APC) recover quickly. It remains to be determined if DC frequency in PB reflects their tissue function. The relatively low incidence of infections in patients undergoing autologous transplantation, despite defective lymphocyte reconstitution, could be related to functionally efficient DC.
Bone Marrow Transplantation 10/2002; 30(5):261-6. · 3.75 Impact Factor
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Haematologica 11/1999; 84(10):949-50. · 6.42 Impact Factor
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D Damiani,
S Grimaz,
L Infanti,
A Sperotto,
F Silvestri,
A Geromin,
M Cerno,
C Savignano,
M Michieli, C Skert,
R Fanin,
M Baccarani
[show abstract]
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ABSTRACT: This study compares harvest and hematological recovery data of 100 lymphoma patients who underwent BM harvest either after a short course of G-CSF (16 microg/kg for 3 days) (n = 57) or in steady-state conditions (n = 43). G-CSF allowed the attainment of a significantly higher median number of total nucleated cells x 10(8)/kg (4.4, range 1.4-17, vs 2.1, range 0.6-4.2; P < 0.0001), mononuclear cells x 10(8)/kg (0.55, range 0.20-1.4, vs 0.41, range 0.15-0.76, P < 0.0001) and CFU-GM/ml (310, range 10-5500, vs 80, range 10-3800, P = 0.008), with lower volumes of blood collected (17.5 ml/kg, range 8-31 vs 21.0, range 15-30, P = 0.0001). Hematological recovery was faster in patients who received pre-treated BM (median time to PMN >0.5 x 10(9)/l and to platelets >20 x 10(9)/l was 12, range 10-14, and 13, range 10-18, days, respectively) than in those autotransplanted with steady-state BM (median time to PMN >0.5 x 10(9)/l and to platelets >20 x 10(9)/l 13, range 10-18 and 14, range 10-20 days, respectively, P = 0.004 and P = 0.01). Transfusional requirement was significantly different and patients of the G-CSF group needed shorter hospitalization (17 days, range 12-24, vs 20 days, range 14-32; P = 0.02). These data suggest that treating patients with G-CSF before BM harvest improves the quality of the harvest and accelerates engraftment and hematological recovery.
Bone Marrow Transplantation 11/1999; 24(7):757-61. · 3.75 Impact Factor
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Haematologica 04/1999; 84(3):283-4. · 6.42 Impact Factor
