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G Rosti

Publications and source records attributed to G Rosti.

At least 55 records · Page 3Linked to original sources
PubMed2001

Real-time quantification of different types of bcr-abl transcript in chronic myeloid leukemia.

BACKGROUND AND OBJECTIVES: The most common translocation in chronic myeloid leukemia (CML) t(9;22) (q34;q22) produces the BCR/ABL fusion gene. We set up and evaluated a rapid and reliable real-time reverse-transcription-polymerase chain reaction (RT-PCR) approach using TaqMan technology for detection and quantification of bcr-abl transcripts in CML patients at diagnosis and during therapy. DESIGN AND METHODS: A pair of primers and probe complementary to ABL exon 2 were designed, enabling detection of the most frequent bcr-abl transcripts, and also of the normal ABL-Ia transcript as an internal control. Conditions were established to amplify less than 1(-10) target molecules/reaction and detect one CML cell in 10(6) cells from healthy donors. To determine the utility of the assay, we quantified the bcr-abl/ABL-Ia ratio in 59 bone marrow samples (45 samples with evidence of different Ph+ chromosome percentages and 14 samples in complete cytogenetic remission) from 48 CML patients, 34 of them at diagnosis and 14 in clinical remission (CR). In 14 cases, this ratio was compared with results obtained by a competitive-quantitative RT-PCR/capillary electrophoresis method from contemporary specimens. RESULTS: By real-time RT-PCR, the median value of bcr-abl/ABL-Ia ratio at diagnosis was 15.334 (range 3.3-28.81) and fell to 0.9 (range 0.003-26.1) in CR. The median value of bcr-abl/ABL-Ia ratio at cytogenetic remission was 0.7 (range 0.003-2.83). The real-time bcr-abl/ABL-Ia ratios correlated with those obtained by competitive RT-PCR (p < 0.0001) and the percentage of Ph+ metaphases (p < 0.0001). The high sensitivity and specificity of the real-time RT-PCR procedure was confirmed in all 14 patients with minimal residual disease. INTERPRETATION AND CONCLUSIONS. We conclude that this real-time RT-PCR procedure is a reliable and sensitive method of monitoring CML patients after therapy, and that the bcr-abl/ABL-Ia ratio correlates strongly with cytogenetic analysis.

Bone Marrow↗
PubMed2001

Neoadjuvant high dose chemotherapy plus peripheral blood progenitor cells in inflammatory breast cancer: a multicenter phase II pilot study.

BACKGROUND AND OBJECTIVES: With the introduction of combined modality therapy, approximately 30% of patients with inflammatory breast cancer (IBC) are alive and free of disease at 5 years, but the lack of control of systemic disease continues to be the main reason for treatment failure. The importance of the response to primary chemotherapy and, in particular, complete tumor regression after primary chemotherapy have previously been described to be among the most reliable prognostic factors along with the dose intensity of doxorubicin. DESIGN AND METHODS: To evaluate pathologic response rate and toxicity of neoadjuvant high dose chemotherapy (HDCT) with autologous peripheral blood progenitor cell (PBPC) support in patients affected by IBC, 21 patients were enrolled in a study in which it was planned that they would receive 4 courses of epirubicin 150 mg/m(2) plus granulocyte colony-stimulating factor (G-CSF) as induction and mobilizing chemotherapy. Patients with non-progressive disease were intended to receive 2 consecutive courses of a combination of high doses of mitoxantrone 40 mg/m(2) , thiotepa 500 mg/m(2) and cyclophosphamide 200 mg/kg as a conditioning regimen. RESULTS: PBPC collection was successful in 20/21 patients. Twelve patients received a single course of HDCT, whereas 7/20 patients underwent a double procedure. At a median follow up of 48 months, 20/21 patients were evaluable for toxicity and 19/21 for response. At surgery 4/19 patients (21%) had no evidence of viable tumor cells in the breast and in axillary nodes, while 4 (21%) and 11 patients (58%) had microscopic and macroscopic disease, respectively. Eight patients have relapsed (35%) so far at a median of 16 months (9-54) from diagnosis. Eleven patients remain alive without evidence of disease. Five out of 20 patients experienced severe cardiotoxicity with congestive heart failure (CHF) which was responsible for the only treatment-related death. INTERPRETATION AND CONCLUSIONS: This neoadjuvant HDCT regimen seems to be very effective in terms of objective responses, but we observed a high rate of cardiotoxicity and only a few patients were able to receive the two planned courses of high dose chemotherapy.

Adult↗
PubMed2000

Quantification of BCR-ABL transcripts in CML patients in cytogenetic remission after interferon-alpha-based therapy.

We measured using a competitive quantitative polymerase chain reaction-capillary electrophoresis (PCR-CE)-based assay, the levels of bcr-abl transcripts in 44 patients with chronic myeloid leukemia (CML) after interferon-alpha (IFN-alpha) therapy, who achieved a major (10 patients, MCR group) or complete (34 patients, CCR group) cytogenetic response. All 34 CCR patients had molecular evidence of residual disease detected in bone marrow samples at the time of best karyotypic response. The median number of bcr-abl transcripts of 34 evaluable patients in the CCR group at the time of complete cytogenetic remission was 4/microg RNA (range 3-4600), while the median number of bcr-abl transcripts of 10 patients in the MCR group at the time of best cytogenetic response was 4490/microg RNA (range 600-23 900) (P = 0.000024). In nine CCR and five MCR patients we were able to quantify the amount of bcr-abl transcript both at diagnosis and after interferon therapy: no statistical difference (P = 0.18) was found between the two groups at diagnosis (median bcr-abl transcripts/microg RNA was 30 000 vs. 39 650, respectively). During IFN-alpha therapy, the two groups were evaluable at the time of major karyotypic conversion: at this point, there was a statistical difference of expression of bcr-abl transcript between the CCR group (17 patients) (median 2700; range 76-40 000) and the MCR group (10 patients) (median 4490; range 600-23 900), respectively (P = 0.046). No differences of bcr-abl amount of transcript were found in patients with CCR obtained either by IFN-alpha therapy alone (20 patients) vs. IFN-alpha plus ABMT (13 patients) (P = 0.47). We firstly demonstrated that although the CCR and MCR groups were clinically, cytogenetically and molecularly indistinguishable at diagnosis, the two groups could be recognized successfully during interferon therapy based on the level of bcr-abl transcript.

Adolescent↗
PubMed2000

Second chronic phase before transplantation is crucial for improving survival of blastic phase chronic myeloid leukaemia.

Because successful outcome after transplantation seems to depend in acute myeloid leukaemia (AML) and in chronic phase chronic myeloid leukaemia (CML) on disease status at the time of transplantation, we investigated whether FLAN (fludarabine, cytosine arabinoside, mitoxantrone) induction before allogeneic stem cell transplantation (allo-SCT) may be useful in blastic phase (BP)-CML. Twenty patients with BP-CML were studied: 10 patients received FLAN induction chemotherapy before proceeding to early allo-SCT, whereas 10 patients were submitted to bone marrow transplantation (BMT) without remission induction. Eight out of 10 (80%) patients achieved second chronic phase after one course of therapy with FLAN and seven patients (six in second chronic phase and one with partial response) were then submitted to allo-SCT. Of the six patients transplanted in the second chronic phase, all achieved molecular remission, four are still in second chronic phase, with intervals ranging from 10 to 54 months, whereas one patient died from infection having relapsed 14 months after SCT and one died of transplant-related complications in the second chronic phase. Mean durations of second chronic phase and survival after allo-SCT were both significantly longer than in the group of 10 BP-CML patients submitted to allo-SCT without FLAN remission induction treatment [22.4 (range 1-61) vs. 3.5 months (range 1-10) with FLAN and 22.7 (range 2-61) vs. 6.4 (range 1-16) months without FLAN]. We conclude that FLAN induction therapy followed by early allo-SCT appears to be effective in the treatment of BP-CML and could provide a curative possibility for BP-CML patients.

Adult↗
PubMed2000

Testing Sokal's and the new prognostic score for chronic myeloid leukaemia treated with alpha-interferon. Italian Cooperative Study Group on Chronic Myeloid Leukaemia.

As it has been shown that alpha-interferon (alphaIFN) treatment modifies the survival of chronic myeloid leukaemia (CML) patients in comparison with conventional chemotherapy, a new prognostic score was devised with the aim of providing a treatment-adapted risk evaluation. We have tested the new prognostic score (the Euro score) in an independent series of 272 patients less than 56 years old with previously untreated, chronic phase, Philadelphia (Ph)-positive CML who had been assigned prospectively to alphaIFN treatment between 1989 and 1991. The Sokal score system was used as a reference. The new Euro score predicted the response to alphaIFN as the Sokal score. The median survival of low-risk, intermediate-risk and high-risk patients was similar using the Euro score (105, 65 and 45 months) and Sokal score (105, 76 and 45 months) but, by multivariate analysis, the Euro was more potent than Sokal for predicting survival time. The new Euro score identified more low-risk cases (59% vs. 48%) and fewer high-risk cases (9% vs. 23%) than the Sokal score. The main differences between the Euro and Sokal scores concerned age (it is more important in the Euro than in Sokal), spleen size and the percentage of myeloblasts in peripheral blood (more important in Sokal than in Euro). We conclude that the new Euro score marks an improvement in the prognostic evaluation of CML treated with alphaIFN. By comparison with the Sokal score, the Euro was more potent and identified more low-risk patients but left only a small number of cases in the high-risk group.

Adult↗
PubMed2000

Quantitative evaluation of BCR-ABL amount of transcript post mobilization with G-CSF of peripheral blood stem cells from chronic myeloid leukemia patients in cytogenetic response.

We studied nine patients affected by chronic myeloid leukemia (CML Ph+ and bcr-abl positive) and treated with alpha-interferon (alpha-INF) in order to: first, to evaluate the feasibility of a mobilization of peripheral blood stem cells induced by granulocyte-colony-stimulating factor (G-CSF) and the contamination by Ph+ cells and second, to quantify the amount of bcr-abl leukemia associated transcript by a quantitative assay during mobilization procedures, and post mobilization follow-up. Eight achieved a complete karyotypic remission before mobilization obtained with discontinuation of alpha-INF for few days and G-CSF at a dosage of 15 microg/kg/day for 5-7 consecutive days. By quantitative-competitive polymerase chain reaction (QC-PCR) assay, all the leukaphereses and bone marrow samples during post mobilization follow up were studied to determine the amount of bcr-abl transcript. Karyotypic and molecular analysis on evaluable leukapheresis showed that all the harvests were Ph negative and bcr-abl positive: in seven cases the levels of bcr-abl transcript were higher or equal to the pre-apheresis status. In three out of four patients, who underwent more than one leukapheresis procedure, we noticed a decreasing amount of bcr-abl contamination from the first to the last apheresis. Our results suggest that in patients who achieved a complete or major cytogenetic conversion with alpha-INF, it is possible to obtain a sufficient amount of PBSC for autografting by leukapheresis following priming G-CSF therapy and that the amount of neoplastic transcript does not seem to increase.

Adolescent↗
PubMed2000

Is there any difference in PBPC mobilization between cyclophosphamide plus G-CSF and G-CSF alone in patients with non-Hodgkin's Lymphoma?

We attempted to analyze whether the use of high-dose cyclophosphamide (CTX 7g/m2, group A) plus hematopoietic growth factor (G-CSF) or G-CSF alone (10 microg/Kg, group B) as a mobilizing regimen, could result in harvesting different numbers of CD34+ cells, committed progenitors and CD34+ cells subsets. The number of CD34+ cells considered as the target for each high-dose chemotherapy was > or = 2 x 10(6) /Kg/bw. Fifteen leukaphereses procedures were necessary in group A, while 16 procedures were performed in group B. We did not observe any difference between the two groups in terms of CD34+ cells/microl in the peripheral blood (117 vs 78; p = NS), whereas in the aphereses product we found a significant difference between the two groups of patients in terms of CD34+ cells (6.41 vs 2.89 x 10(6) /Kg/bw; p = .009), CFU-GM (82.5 vs 52.3 x 10(4) /Kg/bw; p = .04). Interestingly, we noted a different distribution of CD34+/33- cells between the 2 groups (mean value 39% vs 65%; p < .05), whereas we did not find any differences regarding CD34+/38-, CD34+/Thy1+, CD34+/HLADR-. The higher number of CFU-GM/Kg/bw collected in the former group did not translate into a superior plating efficiency (27.75 vs 30.29). Furthermore, we observed a strong correlation between CD34+ cells/microl in the peripheral blood and the total number of CD34+ cells in the leukaphereses product (r = 0.97), whereas this correlation was not found in group B (r = 0.15). In both groups of patients the number of CD34+ cells collected correlated well with CFU-GM (r = 0.93; r = 0.94), but definitely we did not observe any correlation between CD34+ cells/microl and CFU-GM in patients mobilized with G-CSF alone and this did not allow us to predict the harvest accurately. Finally, we evaluated the engraftment kinetics and we did not observe any statistically significant difference between the two groups of patients.

Adult↗
PubMed2000

Relationships between total CD34+ cells reinfused, CD34+ subsets and engraftment kinetics in breast cancer patients.

BACKGROUND AND OBJECTIVE: The aim of the present study was to evaluate the correlation between the number of CD34+ cells transfused and the duration of hypoplasia, and the relationship between various CD34+ subsets (CD34+/33-; CD34+/38-; CD34+/ HLA-DR-; CD34+/Thy-1+) and engraftment kinetics in a series of patients with breast cancer treated with high doses of thiotepa and melphalan. DESIGN AND METHODS: We treated 42 consecutive patients: 19 in an adjuvant context (>= 4 positive axillary nodes) and 23 for metastatic disease. A combination of thiotepa 600 mg/m(2) and melphalan 140-160 mg/m(2) was administered as the conditioning regimen. All patients received peripheral blood progenitor cells (PBPC) and growth factors for hematopoietic rescue. RESULTS: In univariate analysis, we found a significant relationship between the number of CD34+ cells reinfused and the time to hematologic recovery and the duration of hospital stay. We observed an inverse correlation between the number of CD34+ cells reinfused and the units of platelets transfused. Cox multivariate analysis confirmed that the number of CD34+ cells reinfused is the most effective predictor of time to hematologic recovery. CFU-GM resulted to be a better predictor of the duration of hospitalization. INTERPRETATION AND CONCLUSIONS: We found a significant relationship between the number of PBPC reinfused and the time to hematologic recovery after high doses of thiotepa and melphalan. In our experience, the numbers of subsets of CD34+ cells infused did not give compared additional information to that provided by the total number of CD34+ cells infused.

Adult↗
PubMed2000

Clinical value of quantitative long-term assessment of bcr-abl chimeric transcript in chronic myelogenous leukemia patients after allogeneic bone marrow transplantation.

BACKGROUND AND OBJECTIVE: For purposes of therapeutic decision making, we used quantitative polymerase chain reaction (PCR) for molecular follow-up of 55 patients with chronic myeloid leukemia (CML) in complete remission (CR) after allogeneic bone marrow transplantation (BMT) from HLA compatible donors. DESIGN AND METHODS: A total of 402 bone marrow samples from 40 patients transplanted in chronic phase (group 1) and 15 in accelerated/blastic phase (group 2) were analyzed by qualitative and quantitative PCR. RESULTS: Regarding clinical outcome, 34/40 (85%) group 1 vs. 8/15 (54%) group 2 patients are alive. Only 1/40 (2.5%) group 1 patient relapsed, as against 6/15 (40%) in group 2 (p = 0. 0002). At qualitative PCR, 8/40 (19%) group 1 vs. 9/15 (60%) group 2 patients were positive, with a significantly greater total number of positive samples in group 2 (33/129, 27% vs. 16/273, 5%; p<0.001). The probability of qualitative PCR positivity >1 year after BMT was significantly lower in group 1 patients (4/40 pts, 10% vs. 9/15 pts, 60%; p = 0.01). At quantitative PCR, 4/8 (50%) group 1 patients were positive only once (< 400 transcripts/microg RNA). In group 2, 9/15 (60%) patients had 3 or more positive samples (always with >4,000 copies/mg RNA); therapeutic interventions (cyclosporin A discontinuation, temporary a-interferon or donor lymphocyte infusion) restored molecular remission in 4/9 (44%) cases. INTERPRETATION AND CONCLUSIONS: This study indicates that quantitative PCR could provide practical indications capable of directing therapeutic interventions for transplanted CML patients, especially those transplanted in accelerated/blastic phase, for whom intensive monitoring is required.

Adolescent↗
PubMed2000

Patient management strategies and transplantation techniques in european stem cell transplantation centers offering breast cancer patients high-dose chemotherapy with peripheral blood stem cell support: a joint report from the EORTC and EBMT.

BACKGROUND AND OBJECTIVES: It is increasingly being realized that there are very considerable variations in individual hospitals' strategies for managing a particular group of patients, even if using similar therapeutic regimens. Such variations make it impossible to generalize estimations of treatment costs from one setting to others. The objective of this study is to examine the extent of variation in the current approaches in Europe to peripheral blood stem cell transplantation (PBSCT) in breast carcinoma. DESIGN AND METHODS: A questionnaire was developed and sent to the EBMT member institutions. The questionnaire comprised 85 questions covering the technical and clinical issues involved and the strategies followed for the management of the patients. This paper reports the results of the survey primarily by means of descriptive, univariate frequency distributions. The results of a more analytical approach, aiming at explaining patterns in the variations observed are also presented. RESULTS: A completed questionnaire was returned by 162 centers; 60% university hospitals, 14% cancer centers and the rest general hospitals. Considerable variations are observed between the centers with respect to all aspects of patient management and technical procedures investigated. In many respects, general hospitals follow different routines from university hospitals and dedicated cancer centers. INTERPRETATION AND CONCLUSIONS: Variability to the extent observed indicates an important scope for optimization of the procedures and a large potential for reduction of costs and perhaps for improvement of outcomes. Economic evaluations, for instance comparing PBSCT with autologous BMT as support for high dose chemotherapy, can not be generalized from one setting to another without careful examination of the procedures and strategies followed in each setting. European hospitals treating breast cancer patients with high dose chemotherapy supported by transplantation of peripheral blood stem cells use very different technical procedures for mobilization, harvest and re-implantation of stem cells. In addition, there are also wide variations in the way they manage the patients, e.g. with regard to the criteria for discharge from hospital after re-implantation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Prognostic and predictive value of intratumoral microvessels density in operable non-small-cell lung cancer.

Experimental evidence suggests that tumor growth and progression depend on angiogenesis. In a retrospective study we evaluated the relationship between tumor angiogenesis and survival in patients with NSCLC treated with potentially curative surgery between 1992 and 1997. The study population consisted of 76 patients. An anti-CD34 monoclonal antibody was used to measure angiogenesis in tumor samples. Angiogenesis was quantified in terms of microvessel count (MVC): in each sample the three most intense regions of neovascularization were identified under low microscopic power. A x250 field in each of the three areas was then counted and the highest count of the three fields was recorded. Disease free (DFS) and overall survival (OS) during follow up were evaluated. Gender, age, stage, histologic type and KI-67 were the other factors considered for analysis. The median MVC in our series was 41.5. Among the clinicopathologic parameters examined the microvessel count was the only one to show a significant association with disease free survival in univariate analysis (P = 0.04). MVC value is a new indicator of tumor aggressiveness in patients with NSCLC who underwent potentially curative surgery and should be taken into consideration in selecting patients for adjuvant treatment.

Aged↗
PubMed1999

Peripheral blood progenitor cell (PBPC) mobilization in heavily pretreated patients with germ cell tumors: a report of 34 cases.

The aim of the study was to evaluate peripheral blood progenitor cell mobilization by disease-specific chemotherapy in heavily pretreated patients with germ cell tumor (GCT), scheduled for high-dose chemotherapy. Thirty-four consecutive patients, 29 males and five females, with advanced GCT referred to our department for high-dose chemotherapy were evaluated retrospectively. Sixteen patients were mobilized by vinblastine 0.11 mg/kg on days 1 and 2, ifosfamide 1200 mg/m2 days 1-5 and cisplatin 20 mg/m2 days 1-5 (VeIP). In 10 patients, etoposide 75 mg/m2 days 1-5 was used instead of vinblastine (VIP), while in eight patients the mobilization was attempted by administering 7 g/m2 of cyclophosphamide. The choice of either etoposide or vinblastine was predicated upon which of these two drugs was associated with best results during premobilization chemotherapy. Cyclophosphamide was selected in patients refractory to previous cisplatin-based salvage chemotherapy. Twenty-five out of 34 patients underwent a successful PBPC collection. In 17 of them one leukapheresis procedure was sufficient to collect the target number of CD34+ cells, while in eight patients a double procedure was necessary. Altogether 33 aphereses were performed in 25 patients. In nine patients leukapheresis was not attempted. This was due to the fact that the chemotherapy failed to mobilize the target number of CD34+ cells in eight of them, treated with the VeIP mobilizing regimen, while one patient treated with high-dose cyclophosphamide rapidly progressed during therapy and for this reason leukapheresis was not undertaken. In conclusion, in heavily pretreated patients with GCT, PBPC mobilization is feasible by a further course of salvage chemotherapy. The choice of either etoposide (VIP) or vinblastine (VeIP) can be predicated upon which of these two drugs was associated with best results during premobilization chemotherapy. In our hands, VeIP seems to be less satisfactory as mobilizing treatment than VIP, possibly due to a superior number of premobilization courses of chemo therapy in some patients. Moreover, high-dose cyclophosphamide remains a good alternative for mobilizing patients refractory to salvage chemotherapy.

Adolescent↗
PubMed1999

Multiple courses of high-dose ifosfamide, carboplatin, and etoposide with peripheral-blood progenitor cells and filgrastim for small-cell lung cancer: A feasibility study by the European Group for Blood and Marrow Transplantation.

PURPOSE: To determine the feasibility and safety of multiple sequential courses of high-dose chemotherapy and peripheral-blood progenitor cells (PBPCs) administered in a multicenter setting to patients with small-cell lung cancer. PATIENTS AND METHODS: Sixty-nine patients (limited disease, n = 30; extensive disease, n = 39) treated at 15 European centers were scheduled to receive three courses of high-dose chemotherapy with ifosfamide 10 g/m(2), carboplatin 1200 mg/m(2), and etoposide 1200 mg/m(2) (ICE) divided over 4 days at 28-day intervals. PBPCs were harvested before treatment and mobilized with epirubicin 150 mg/m(2) administered via an intravenous bolus divided over 2 days and filgrastim 5 microg/kg/d administered subcutaneously. RESULTS: The performed leukaphereses (one to five per patient) yielded a median of 16.6 x 10(6)/kg (range, 1.0 to 96.6 x 10(6)/kg) CD34(+) cells, which was sufficient for three reinfusions. Fifty patients (72%) completed the treatment according to schedule. Nine patients completed two courses, and six patients completed one course of treatment. The increase in dose-intensity was 290% that of a standard ICE regimen. The median duration of myelosuppression was similar between courses, namely 4 days (range, 1 to 12 days) for leukocytes less than 0.5 x 10(9)/L and 4 days (range, 0 to 22 days) for thrombocytes less than 20 x 10(9)/L. Febrile neutropenia developed in 66% of courses, severe diarrhea in 14%, mucositis in 10%, and nausea and vomiting in 21% of courses. There were six cases of toxic death (9%), most of which occurred in the first year of accrual and thus were attributable to the learning curve. The antitumor effect of the regimen was reflected in an 86% remission rate (95% confidence interval [CI], 74% to 93%), with 51% of patients achieving a complete response (95% CI, 38% to 63%). Median overall survival was 18 months for patients with limited disease and 11 months for patients with extensive disease. CONCLUSION: This multiple sequential high-dose ICE regimen could be safely administered on a multicenter basis to patients with small-cell lung cancer. The dose-intensity could be increased to 290% that of standard ICE regimen. The benefit of this approach is currently being tested in a randomized trial that aims to double the long-term rate of survival for patients with small-cell lung cancer.

Adult↗
PubMed1999

A prospective study of alpha-interferon and autologous bone marrow transplantation in chronic myeloid leukemia. The Italian Co-operative Study Group on Chronic Myeloid Leukemia.

BACKGROUND AND OBJECTIVE: Alpha-interferon (alphaIFN) can induce cytogenetic remissions in chronic myeloid leukemia (CML). Hemopoietic progenitors can be collected from the marrow in remission and utilized for autologous repopulation after high dose chemotherapy. This study was designed with the purpose of evaluating the feasibility of a combined treatment policy of alphaIFN followed by autologous bone marrow transplantation (autoBMT). DESIGN AND METHODS: A prospective study of alphaIFN and autoBMT was begun in 1989. Two hundred and seventy-two consecutive previously untreated non-blastic Ph positive chronic myeloid leukemia (CML) patients, who were less than 56 years old, were enrolled over a 3-year period (1989-1991) and were assigned to receive human recombinant alphaIFN 2a (Roferon-A) at a dose of 9 MIU daily for at least one year. If they achieved a cytogenetic response consisting in a percentage of Ph neg metaphases of more than 25%, they were eligible for marrow harvesting and subsequent autografting after high dose busulfan (16 mg/kg) and melphalan (60 mg/m(2)). RESULTS: Seventy-six patients (28%) were eligible for a marrow harvest but the marrow was harvested in only 37 cases (14%), and only twenty-three patients (8%) were actually autografted. One patient died of infection nine days after autoBMT. The other patients recovered and did not suffer any late adverse events. Five patients progressed to blastic phase, six are alive in complete hematologic remission and eleven are alive in complete hematologic and cytogenetic remission. AlphaIFN treatment was reinstituted after autoBMT in 18 of 22 cases, but four patients who are in continuous complete cytogenetic remission were not given alphaIFN anymore. The progression-free survival of the autografted patients is 65% 8 years after registration. INTERPRETATION AND CONCLUSIONS: This study shows that bone marrow hemopoietic progenitors (Ph neg and Ph pos) can be collected from patients who respond to alphaIFN and can be used to rescue hemopoietic activity after high dose chemotherapy. Though some complete and durable cytogenetic remissions were obtained, the treatment could be applied only to a small group of good risk patients, highlighting that selection is very important and results cannot be extrapolated to the average patient.

Adult↗
PubMed1999

Treatment of small cell lung cancer.

Small cell lung cancer represents approximately 25% of all lung cancers. During the 1980s enormous efforts have been made to try to create a breakthrough in this peculiar disease but, despite the excellent results obtained in the early 1980s with multidrug chemotherapy, no significant improvements have been achieved in the 1990s. Overall response rates are in the range of 60-90% for patients with limited disease and 40-70% for those with extended disease, with pathological remissions in the range of 20-50%. Nevertheless, the majority of patients with small cell lung cancer continues to relapse and ultimately dies of the disease. New strategies under clinical evaluation are the multimodality approach, such as concurrent chemoradiation, and the use of dose-intensive regimes or even high-dose chemotherapy supported by autologous haemopoietic rescue. In the near future other strategies will be possible, owing to the tremendous increase in the knowledge of biological properties of this disease. This article aims to summarize the research so far, the current strategies and the probable future of the treatment of small cell lung cancer.

Carcinoma, Small Cell↗