Biomedical subjects

D Soligo

Publications and source records attributed to D Soligo.

At least 37 records · Page 2Linked to original sources

PubMed1999

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.

Adolescent↗

PubMed1999

Angiogenesis in myelodysplastic syndromes.

It is now well established that solid tumour growth depends on angiogenesis. However, less is known about the generation of new vessels in haematological malignancies and, in particular, in preleukaemic-myelodysplastic syndromes (MDS). In this study, bone marrow microvessel density (MVD) was assessed by immunohistochemistry and compared in trephine biopsies from 14 controls, five infectious disease (ID), 82 MDS, 15 acute myeloid leukaemia (AML) and 14 myeloproliferative disorder (MPD) patients. Statistical analysis (P < 0.001) demonstrated that MDS MVD was higher than in controls and ID (21 +/- 9 vs 6 +/- 2 and 10 +/- 8 respectively) but lower than AML (30 +/- 12) and MPD (40 +/- 12). Among MDS-FAB subtypes, MVD was significantly higher in RAEB-t, CMML and fibrosis subsets compared to RA, RARS and RAEB subsets (P= 0.008). To further investigate angiogenesis machinery, the expression of vascular endothelial growth factor (VEGF) was evaluated by means of immunohistochemistry in control, MDS, AML and MPD biopsies. Even though VEGF mRNA expression was reported in the past in AML cell cultures and cell lines, in our samples VEGF expression was found to be particularly strong in most of the megakaryocytes but significantly less prominent in other cell populations including blasts. Since our findings suggest a correlation between angiogenesis and progression to leukaemia, additional work is now warranted to determine what regulates the generation of new vessels in MDS and leukaemia.

Antigens, CD34↗

PubMed1998

G-CSF after autologous hemopoietic stem cell transplantation in malignant lymphoma.

Forty-eight autografted patients were studied after treatment with granulocyte-colony stimulating factor (G-CSF) and were compared with a historical series of 24 patients autografted with bone marrow (BM) without G-CSF. When the patients were divided on the basis of G-CSF administration, type of lymphoma and the source of hemopoietic stem cells, no significant difference was found in the median number of infused BM cells, duration of febrile episodes, platelet and hemoglobin recovery, or in the number of transfusions. The patients receiving peripheral blood (PB) + G-CSF had significantly shorter median durations of antibiotic therapy, hospital stay and polymorphonucleate (PMN) recovery. When the Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL) cases were considered separately, a significant difference between those receiving and those not receiving G-CSF was observed only in the HD group. The advantage offered by PB + G-CSF over BM + G-CSF was far more evident in the NHL group than in HD. It can be concluded that G-CSF improves the outcome of BM transplant in HD, and that the use of PB + G-CSF adds a further advantage; conversely, in NHL, PB + G-CSF is strikingly superior to BM + G-CSF, but the addition of G-CSF adds little advantage.

Adolescent↗

PubMed1998

Expansion of dendritic cells derived from human CD34+ cells in static and continuous perfusion cultures.

We examined the effects of different cytokine combinations and culture conditions on the expansion and modulation of cell surface antigens of CD34+ derived dendritic cells (DCs), the most efficient antigen-presenting cells capable of stimulating resting T cells in the primary immune response. Cells with a dendritic morphology and expressing HLA-DR, CD1a, S100 and CD83 were maximally expanded under serum-free conditions with the addition of SCF, GM-CSF, TNF-alpha, TGF-beta and Flt-3 ligand (fold increase of CD1a+ cells = 102 +/- 32 after 2 weeks of culture). CD34+ cells were also grown under continuous flow conditions in an artificial capillary system: after 14d of culture, the expansion in the total cell number was lower than that of the static cultures (3.3 +/- 2 v 18.9 +/- 4) but the percentage of CD1a+/CD83+/ CD80+ cells was considerably higher, whereas the CD14+ cells were significantly reduced (8.9 +/- 2 v 26 +/- 13). In continuous perfusion cultures, low levels of DC precursors and of LTC-IC were still present up to day 14. The DCs generated under flow conditions stimulated the mixed leucocyte reaction (MLR) more than the cells grown in static cultures. By electron microscopy, cells grown in the continuous flow system showed an increased number of large cells with numerous dendritic processes and abundant multilamellar complexes. The cells expanded under these conditions were sorted on the basis of their light-scatter properties into two fractions: one containing a predominance of CD1a+/S100+/ CD8 3+/CD80+/CD14- 'large cells' with great internal complexity (mature DCs); the second including 'small cells' either CD33+/CD14+, CD33+/CD15+ or CD33+/CD13-/CD14. The DCs generated and selected with this method are therefore particularly well suited for immunotherapeutic protocols.

Antigens, CD34↗

PubMed1998

Unrelated donor marrow transplantation for chronic myelogenous leukaemia.

Between January 1989 and July 1995 the search for an unrelated donor (UD) was started for 379 consecutive Italian patients with Philadelphia positive (Ph+) chronic myelogenous leukaemia (CML). 89 (23%) were transplanted. The overall probability of transplant before and after December 1991 was 16% and 49%, respectively (P=0.0001), and average interval between search activation and graft was 23 months and 13 months, respectively (P=0.0001). Disease-free survival (DFS) following 60 consecutive transplants performed before February 1996 was 41.5% at 48 months and was 64% for patients grafted after January 1993. In univariate analysis, five variables had a favourable effect on DFS: year of bone marrow transplantation (BMT) after 1993 (P=0.0002), HLA-DRB1 donor/recipient (D/R) match (P=0.0006), total body irradiation (TBI) containing regimen (P=0.0006), graft-versus-host disease (GvHD) prophylaxis including 'early' cyclosporin before the transplant, and a marrow cell dose > 3 x 10(8)/kg of recipient body weight (P=0.04). Multivariate analysis confirmed that HLA identity (P=0.006), TBI-containing regimen (P=0.0001) and 'early cyclosporin' (P=0.04) were associated with higher DFS. Transplant-related mortality (TRM) was 67% in patients grafted before January 1993 and 30% in patients grafted subsequently (P=0.002). Multivariate analysis confirmed DRB1 identity (P=0.03) and TBI-containing regimen (P=0.0005) to be independent factors predictive of low TRM. This suggests that the outcome of patients transplanted from an HLA DRB1 matched donor, after a TBI-containing preparative regimen, is similar to results recently reported in patients transplanted from geno-identical siblings. These results indicate that the search should be initiated at diagnosis for patients < 45 years of age and UD BMT should be considered early in the disease course for those with an available DRB1-matched unrelated donor.

Adolescent↗

PubMed1998

The diagnostic and prognostic value of bone marrow immunostaining in myelodysplastic syndromes.

Immunohistochemistry has been introduced as a means of increasing the diagnostic accuracy of bone marrow biopsy (BMB) in myelodysplastic syndromes (MDS); more recently the possibility of coupling immunostaining with other investigational techniques has broadened the spectrum of applications to the biology and physiopathology of MDS. Using panels of monoclonal antibodies (MoAbs), various histological classifications of MDS have been proposed as an alternative to the FAB criteria. The use of lineage-specific MoAbs has allowed a deeper insight into the dysplastic features of early hematopoietic precursors. The study of various gene products involved in the regulation of cell growth, proliferation and sensitivity to antineoplastic drugs, has revealed significant differences between MDS and morphologically-related disorders, particularly acute myelogenous leukemias (AML); these can be considered markers of a biological difference between the two groups of disorders and deserve consideration when designing therapeutic strategies for MDS. Both an increase in the percentage of cell positivity for the CD34 glycoprotein and a tendency of positive cells towards forming aggregates have been shown to be reliable predictors of leukemic transformation and survival, irrespective of the FAB subtype; furthermore, CD34 positivity has also proved to be a better prognostic factor than the presence of the abnormal localization of immature precursors (ALIP) on BMB. Finally, the simultaneous occurrence of "large" and CD34 positive aggregates can be proposed as a means of recognizing MDS patients with an exceedingly unfavourable prognosis, and who are therefore suitable for early aggressive therapy.

Biopsy↗

PubMed1998

In vitro effect of clozapine on hemopoietic progenitor cells.

BACKGROUND AND OBJECTIVE: Clozapine is a diabenzodiazepine derivative characterized by a high therapeutic index in schizophrenic patients resistant to traditional neuroleptic drugs, because of the rarity of any extrapyramidal side effects, and its particular hematologic toxicity. According to the international literature, clozapine-induced neutropenia occurs mainly during the first 4-6 months of treatment, and its incidence decreases considerably over time. This neutropenic effect is not dose-dependent and normally clears up after drug discontinuation, although it may evolve into agranulocytosis. The aim of this study is to evaluate the in vitro toxic effect of clozapine and N-desmethylclozapine on both committed and immature human hematopoietic progenitor cells. DESIGN AND METHODS: Cytotoxic assays were performed in vitro on normal human bone marrow samples treated with clozapine or with its metabolite N-desmethylclozapine. The clonogenic potential after treatment with both compounds was assessed on low density mononuclear cells (LD-MNC), purified CD34+ cells, cytokine driven liquid cultures and long term culture initiating cell (LTC-IC). RESULTS: Clozapine and N-desmethylclozapine had a dose-dependent inhibitory effect on in vitro growth of CFU-GM and BFU-E from normal bone marrow. The two drugs had toxic effects on purified CD34+ progenitor cells but no significant effect on LTI-IC. INTERPRETATIONS AND CONCLUSIONS: Our data indicate a cytotoxic effect, which is more pronounced with N-desmethylclozapine and at high doses, on the committed progenitor cell compartment but not on primitive hematopoietic cells. Furthermore, our data show that clozapine and N-desmethylclozapine have a direct effect on treated cells and do not induce apoptotic death.

Antipsychotic Agents↗

PubMed1997

Megakaryocytic progenitors can be generated ex vivo and safely administered to autologous peripheral blood progenitor cell transplant recipients.

We evaluated different culture conditions to obtain a lineage-selected proliferation of clonogenic megakaryocytic progenitors (MP). In low-density (LD) or CD34+ cell cultures, the best results were obtained in serum-free medium in the presence of megakaryocyte growth and development factor, stem cell factor, interleukin-3 (IL-3), IL-6, IL-11, FLT-ligand, and macrophage inflammatory protein-1alpha. In paired studies, expansion of LD cells was less effective than expansion of CD34+ cells, and pre-enrichment of CD34+ cells using negative depletion of lineage-positive cells produced significantly larger quantities of MP than pre-enrichment using positive selection. MP proliferation peaked on day 7 in culture, and an 8- +/- 5-fold expansion of CD34+/CD61+ cells, a 17- +/- 5-fold expansion of colony-forming units-megakaryocytes, and a 58- +/- 14-fold expansion of the total number of CD61+ cells was obtained. In a feasibility clinical study, 10 cancer patients (8 with breast cancer and 2 with non-Hodgkin's lymphoma) undergoing autologous peripheral blood progenitor cell (PBPC) transplant received MP generated ex vivo (range, 1 to 21 x 10(5)/kg CD61 cells) together with unmanipulated PBPC. Eight patients received a single allogeneic platelet transfusion, whereas platelet transfusion support was not needed in 2 of the 4 patients receiving the highest doses of cultured MP. This result compares favorably with a retrospective control group of 14 patients, all requiring platelet transfusion support. Adverse reactions or bacterial contamination of cell cultures have not been observed. In conclusion, MP can be expanded ex vivo and safely administered to autologous transplant recipients. Further clinical trials will indicate the reinfusion schedule able to consistently abrogate the need for allogeneic platelet transfusion support in autologous transplantation.

Cells, Cultured↗

PubMed1997

Multiple autoimmune events after autologous bone marrow transplantation.

A 36-year-old woman with RAEB-t and severe bone marrow fibrosis undergoing autologous BMT, developed a histologically documented GVHD-like skin rash. Thereafter, autoimmune thyroiditis, autoimmune thrombocytopenic purpura and autoimmune hemolytic anemia and a lupus anti-coagulant (LAC) were diagnosed. The patient is still alive, symptom-free and in first complete remission (CR); however, all of the autoantibodies are still detectable, with the exception being the anti-erythrocyte antibody. The most outstanding feature of the present case is the polymorphism of the autoimmune events, in the absence of a coexisting systemic autoimmune disease. This patient has achieved long-term disease-free survival (DFS) in first CR despite high-risk MDS and the repeated immunosuppressant therapy required because of the complications described above; a GVL reaction somewhat similar to the autoimmune events may have contributed towards maintaining disease control.

Adult↗

PubMed1997

A severe transfusion-dependent congenital dyserythropoietic anaemia presenting as hydrops fetalis.

We describe a case of congenital dyserythropoietic anaemia (CDA) presenting at week 20 of pregnancy with hydrops fetalis and very severe anaemia. Fetal blood examination showed marked erythroblastosis with morphologic alterations while the basic haematological and biochemical tests were in the normal range. The fetus received intravascular red blood cells transfusion at 20 and 25 weeks of gestation. After a caesarean section at week 33 the child became transfusion dependent. Haematological investigations demonstrated that the child is affected by a CDA-like picture which, although morphologically similar to CDA II, is Ham test negative and does not show the typical membrane proteins alterations.

Adult↗

PubMed1997

Autologous bone marrow transplantation in advanced Hodgkin's disease.

Autologous bone marrow transplantation (ABMT) has been proposed as an alternative treatment of resistant/refractory Hodgkin's disease (HD). Thirty-seven patients in various phases of HD underwent autografting in our Center: fourteen received a CBV conditioning regimen, the others BCNU or VP16 followed by cyclophosphamide and TBI. Three patients died before engraftment, 28 (75.67%) achieved CR and 6 showed persistent disease. As of March 1996, 18 patients had died and 13 were in continuous CR. The median event-free survival (EFS) and 3-year EFS chances were respectively 9 months and 31.3% in the series as a whole, 14 months and 40% in primary resistant disease, 9 months and 28.4% in responsive relapse, and 3 months and 22.2% in resistant relapse. As many of these patients had failed to respond to third-line therapies, their EFS figures are primarily attributable to the therapeutic efficacy of ABMT. Furthermore, since the EFS curves are better in patients seemingly characterized by a lower chance of chemoresistance, our data favour the use of ABMT in the earlier phases of HD.

Adolescent↗

PubMed1997

"Stem cell candidates" purified by liquid culture in the presence of Steel factor, IL-3, and 5FU are strictly stroma-dependent and have myeloid, lymphoid, and megakaryocytic potential.

Berardi et al. (Science 1995; 267:105) reported recently that combined cytokine stimulation and antimetabolite treatment were able to isolate cells with characteristics of hemopoietic stem cells. Bone marrow (BM) low-density cells were cultured for 1 week in the presence of Steel factor (SF), IL-3, and the antimetabolite 5-FU. Following this approach one in 10(5) BM cells were purified. These cells showed no clonogenic potential in soft gel assays but presented a striking myeloid-lymphoid potential as long-term culture-initiating cells (LTC-ICs). We investigated this new "stem cell candidate." following a similar approach we purified one in 55,000/130,000 cells from cord blood and peripheral blood in mobilized cancer patients. These cells displayed no clonogenic potential in methylcellulose assays in the presence of different cytokine combinations and generated very few or no clonogenic progenitors in liquid cultures in the presence of cytokines. When seeded on layers derived from the murine BM stromal cell line M2-10B4, 38-86% of the cells purified using this approach generated multilineage progenitors acting as LTC-lCs. In a different series of studies, after 5-week culture on human BM stromal cell line L87/4 layers, cells were forced to selected lineage differentiation by culture in the presence of low concentrations of SF and high concentrations of lineage-specific cytokines such as Flt3-ligand (myeloid and pre-B cell differentiation), Tpo (megakaryocytic differentiation). IL-7, and IL-2 (pre-B and NK differentiation). After 12-day culture under these conditions, generation of myeloid, pre-B, megakaryocytic, and NK progenitors was assessed by immunohistochemistry, flow cytometry, and mRNA expression of CD7, 14, 19, 41b, S6, and 61. We conclude that this procedure for multilineage progenitor cell purification is simple and effective and could have major implications for gene transfer and stem cell transplantation.

Cell Lineage↗

PubMed1996

Engineered stromal layers and continuous flow culture enhance multidrug resistance gene transfer in hematopoietic progenitors.

We recently reported that in stroma-free cultures 11-33% of clonogenic cells derived from a bulk long-term culture [long-term culture-clonogenic cells (LTC-CC)] could be transduced by supernatant exposure or coculture of human CD34+ progenitors with MDR retroviral producer line A12M1. We reasoned that a stromal cell layer may generate niches in which LTC-CC could enter in the S-phase, thus becoming a more accessible target for gene delivery. In static culture studies in flasks, human engineered stromal cell line L87/4 or stromal murine M2-10B4 cells were used as feeder after irradiation, and CD34+ cells from either cord blood or peripheral blood of mobilized cancer patients were exposed to MDR supernatant for 7 consecutive days before 5-week culture for LTC-CC evaluation. In continuous flow perfusion culture studies, CD34+ cells were seeded over irradiated stromal murine M2-1OB4 cells and exposed to MDR supernatant for 7 days before LTC-CC evaluation. In mock-transduced controls, <5% of LTC-CC were found to he viable after exposure to 10 ng/ml Taxol. In cells exposed to MDR supernatant in static stroma cultures, 68 +/- 4% of seeded LTC-CC were found to be drug resistant and express MDR mRNA as evaluated by reverse transcription-PCR analysis of single colonies. The addition of cytokines did not further enhance transfer efficiency. After MDR retroviral exposure in continuous flow cultures, 88 +/- 5% of LTC-CC were found to be drug resistant (P < 0.01 versus static stroma culture). P-glycoprotein expression in CD34+ cells was evaluated using flow cytometry and found to he higher after continuous flow versus static cultures. Finally, very high levels of P-glycoprotein expression after MDR supernatant exposure in the presence of stroma were confirmed by APAAP staining of cultured cells. We conclude that engineered stromal cell layers and continuous flow culture conditions can significantly enhance retroviral-mediated gene transfer into human hematopoietic progenitor cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1996

Functional and morphological characterization of immunomagnetically selected CD34+ hematopoietic progenitor cells.

We evaluated the potential of immunomagnetically selected (miniMACS) progenitor cells to give rise to colony-forming cells and their precursors, detected as long-term culture-initiating cells (LTC-IC), as well as their capacity to expand in liquid cultures. A 90% mean purity, a 43.2% yield and a 55.8-fold enrichment were achieved from normal bone marrow. When corrected for enrichment, the mean number of committed progenitor cells and the frequency of LTC-IC (evaluated by means of limiting dilution assay [LDA]) were not statistically different in low density mononuclear cells or in the CD34-enriched fractions. In five cases CD34+ selected cells grown in a stroma-free long-term bone marrow culture system with the addition of stem cell factor, interleukin 3, interleukin 6 and GM-CSF every 48 h, showed a 15 (+/- 15) and 31 (+/- 21) mean colony forming unit-granulocyte/macrophage fold increase on cultures at days 7 and 14. However, when corrected for enrichment, the expansion capability of these cells was significantly lower than that of the unseparated fraction, particularly after the first week. Immediately after separation, electron microscopy revealed that the CD34+ selected fraction contained more than 45% of well-differentiated myeloid cells (MPO+), with iron beads preferentially clustered at one pole of the cell surface and sometimes already endocytosed in pinocytic vesicles. After 24 h and 48 h incubation at 37 degrees C, the majority of the cells showed no iron particles, but about 30% of the cells were iron-labeled phagocytic cells. The percentage of apoptotic cells with internalized iron was negligible. These data show that immunomagnetically separated CD34+ cells may have a slightly impaired short-term expansion capability, but give rise to both committed and more primitive progenitor cells. During the separation, the iron beads are internalized, rapidly processed in the cytoplasm and do not seem to interfere with in vitro growth.

Adult↗

PubMed1996

Bone marrow histology and CD34 immunostaining in the prognostic evaluation of primary myelodysplastic syndromes.

The prognostic impact of bone marrow biopsy (BMB) histology and CD34 immunoreactivity was compared with that of the more conventional parameters (the FAB diagnosis, peripheral blood values, percentage of BM blasts and some common prognostic scores) in 100 MDS patients. Statistical correlations among the cytological, haematological, histological and immunohistochemical parameters and their relationship with clinical outcome were searched for. At univariate analysis, FAB classification (P < 0.001), pattern of blastic infiltration at BMB (P < 0.005), presence of CD34+ aggregates (P < 0.0005), percentage of blasts in BM aspirate (P < 0.0001) and percentage of CD34 positivity (P < 0.0001) proved to be linked to leukaemic transformation and, except for FAB classification, retained a high degree of prognostic significance in terms of survival. Leukaemic transformation occurred in 16/18 patients simultaneously presenting 'large' blastic infiltrates at BMB and CD34+ aggregates (P < 0.00001); 9/17 evaluable patients died within 12 months of diagnosis (P < 0.001)> Discriminant functions for leukaemic transformation and survival did not offer any advantage over univariate analysis in the prognostic work-up. The results indicate that the size of blastic aggregates and CD34 positivity allowed patients with a worse prognosis to be identified irrespective of their FAB subtype, but the prognostic impact is considerably greater when both parameters are simultaneously taken into account, as testified by the restricted and homogeneous subgroup of patients with both 'large' and CD34-positive aggregates.

Antigens, CD34↗

PubMed1996

Gene transfer-mediated generation of drug-resistant hemopoiesis.

Autologous- or allogeneic-bone marrow transplantation are increasingly used to overcome the myelosuppressive effects of high dose chemotherapy administered to cancer patients. Transfer of the multidrug resistance (MDR) gene in hemopoietic progenitors has been proposed as a tool to administer higher and possibly more curative doses of chemotherapy. Murine models have demonstrated that retrovirus-mediated MDR transfer in bone marrow cells can render animals resistant to myeloablative doses of Taxol, and in vitro studies have shown that MDR-transduced human CD34+ cells can generate drug-resistant multipotential hemopoietic progenitors such as long term culture-initiating cells. Given these results, phase I clinical trials are currently under way to evaluate feasibility and treatment-related toxicity of MDR gene transfer in cancer patients by means of safe retroviral vectors. Finally, Taxol treatment of MDR transduced mice and human CD34+ cells have indicated that MDR is a dominant selectable marker in vitro and in vivo, and vectors carrying both MDR and non selectable genes such as beta-globin or glucocerebrosidase could be used in the next future for gene therapy of inherited disorders like thalassemia or Gaucher disease.

Animals↗

PubMed1996

Unrelated donor marrow transplantation: initial experience of the Italian bone marrow transplant group (GITMO).

From 1 September 1988 to 30 September 1993, a search for an unrelated donor (URD) was started for 633 Italian patients. Eighty-five of them (13%) were transplanted. Despite the introduction of more strict criteria for the selection of compatible donors, the percentage of patients who reached transplant increased significantly after December 1992. For patients who started a search before and after January 1993, respectively the probability of transplant by 8 and 16 months from search activation was 4 and 10%, compared to 22 and 37% (P = 0.0001). The average intervals between search activation and graft were 15 and 8 months respectively, for the first and second group (P = 0.0001). Data of 75 consecutive transplants performed up to March 1994 were analyzed. Actuarial 2-year survival was 15% for patients grafted before 1992 and 40% for those grafted after January 1992. In this latter period, survival of patients with malignant and non-malignant disorders was 32 and 67%, respectively. In univariate analysis, patients younger than 16 years (P = 0.01), patients grafted after 1992 (P = 0.01) and patients receiving the marrow from a 6-antigen matched donor (P = 0.01) showed a higher survival probability. Multivariate analysis did not show any difference, probably due to the low number of patients and to short follow-up. The adoption of stricter and more accurate HLA-matching criteria and the consequent reduction of deaths related to acute GVHD were the main reasons for the improvement of survival observed in patients grafted after 1992.

Adolescent↗

PubMed1996

In vitro effects of IL-2 on NK-activity, clonogenic potential, blast cell proliferation and cytokine release of MDS bone marrow patients.

To evaluate the clinical usefulness of IL-2 in myelodysplastic syndromes (MDS) the in vitro effects of interleukin-2 (IL-2) on blast cell proliferation, clonogenic activity, cytokine release and cell mediated cytotoxicity were examined in 49 MDS patients. Morphological analyses of bone marrow (BM) cytospin preparations showed a significant decrease in the number of blast cells in MDS after incubation with IL-2. Incubation of bone marrow mononuclear cells (BMMNCs) with IL-2 induced a significant increase in the number of CFU-GM in comparison with untreated controls. gamma-IFN and GM-CSF, but not alpha-TNF were found to be released in significant amounts by the BMMNCs cultured with IL-2. No significant differences in the surface phenotypes of fresh lymphocytes were observed between the normal and MDS subjects. After incubation with IL-2, we observed a significant increase in the number of CD3-/CD56+ cells in both normal and MDS subjects. Peripheral blood (PB) and BM NK activity against K562 was significantly greater in MDS after stimulation with IL-2. These data suggest the clinical usefulness of IL-2 in a large subgroup of patients as it may reduce the percentage of blasts and increase clonogenic capacity and cell-mediated cytotoxicity.

Adult↗