Elena Trabacchi

Ospedale Guglielmo da Saliceto, Caronno Pertusella, Lombardy, Italy

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Publications (25)157.32 Total impact

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    ABSTRACT: Nilotinib is a second-generation tyrosine kinase inhibitors that has been approved for the first-line treatment of chronic phase chronic myeloid leukemia, based on the results of a prospective randomized study of nilotinib vs. imatinib (ENESTnd). Apart from this registration study, very few data are currently available on nilotinib first-line. We report here the long-term, 6-year, results of the first investigator-sponsored, GIMEMA multicenter phase II, single-arm, trial with nilotinib 400 mg twice daily as first-line treatment in 73 chronic-phase chronic myeloid leukemia patients. Six-year overall survival and progression-free survival were 96%, with one death after progression to blast phase. At 6 years, 75% of the patients were still on nilotinib. The cumulative incidence of major molecular response was 98%; only one patient had a confirmed loss of major molecular response. The cumulative incidence of deep molecular response (MR 4.0) was 76%. Deep molecular response was stable (≥ 2 years) in 34% of these patients. Cardiovascular adverse events, mainly due to arterial thrombosis, occurred in 11/73 patients (15%), after 24 to 76 months of therapy. They were more frequent in elderly patients, and in those with baseline cardiovascular risk factors. None was fatal, although there was a relevant morbidity. This is the study with the longest follow-up of a high dose nilotinib (400 mg twice daily), highlighting the high efficacy and the cardiovascular toxicity of the drug (CTG.NCT.00481052). Copyright © 2015, Ferrata Storti Foundation.
    Haematologica 06/2015; DOI:10.3324/haematol.2015.129221 · 5.87 Impact Factor
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    ABSTRACT: Abstract: P230 Background: In the ENESTnd trial, nilotinib (NIL) showed superior efficacy compared to imatinib (IM); based on these results, NIL has been approved for frontline treatment of chronic myeloid leukemia (CML). The treatment-free remission (TFR) is an emerging treatment goal in CML and a sustained deep molecular response (DMR, MR4 or better) is a pre-requisite to achieve TFR. The 5-year update from the ENESTnd trial showed a superiority of NIL over IM in terms of achievement of DMR, but differences concerning the stability of DMR have not been reported yet. Independent studies are extremely relevant to confirm and to extend the results of company-sponsored trials. Aims: To assess the efficacy of NIL as first-line treatment in terms of achievement of DMR and stability of DMR Methods: A phase 3b study was conducted by the GIMEMA CML WP (CML0811; NCT01535391). The primary endpoint was the rate of MR4 at 24 months. Key secondary objectives: evaluation of the kinetics of molecular response and stability of DMR, assessment of the safety profile, evaluation of the outcome. The starting NIL dose was 300 mg BID, with dose escalation to 400 mg BID (in absence of safety issues) in case of suboptimal response or failure (ELN 2009 criteria), with the exception of progression to ABP or BCR-ABL mutations insensitive to NIL. The molecular response was assessed in GIMEMA standardized molecular laboratories (Labnet network). The MR4 was defined as either detectable disease ≤ 0.01% BCR-ABL or undetectable disease with ≥ 10.000 ABL copies; the MR4.5 was defined as either detectable disease ≤ 0.0032% BCR-ABL or undetectable disease with ≥ 32.000 ABL copies. Sustained MR4 or MR4.5: MR4 or MR4.5 for at least 1 year a, with at least 3 evaluable analysis. A prospective evaluation of glucose metabolism and serum lipids was performed. All the analysis were performed according to the ITT principle. Results: 130 CML patients in early chronic phase have been enrolled in 32 italian hematologic centers; median age, 50 years (range 18-85); high risk patients, 22%, 6% and 8% according to Sokal, Euro and EUTOS scores, respectively; clonal chromosomal abnormalities in Ph+ cells at baseline, 5%; e13a2 BCR-ABL transcript, 34%. The median follow-up is 29 months (24-37 months). At the last contact, the patients still on treatment with NIL were 100/130, 77% (86 with 600 mg, 9 with 300 mg or less, 5 with 800 mg daily), while 30/130 patients, 23%, permanently interrupted the study drug for the following reasons: 3% progression to ABP, 5% failure or suboptimal response (dose escalation not feasible or not effective), 8% adverse events, 1% TFR, 5% other reasons (including consent withdrawal and pregnancy). At 3 months, 80% of patients had BCR-ABL transcript levels < 10%; at 6 months, 78% of patients had BCR-ABL transcript levels < 1%. The major molecular response rates at 12 and 24 months were 57% and 65%, respectively. The rates of MR4 at 6, 12, 18 and 24 months were 12%, 28, 31% and 46%, respectively. Seventy-six patients (58%) achieved a MR4 at least once; the patients with a sustained MR4 were 39/76 (51%, or 30% of the total). The rates of MR4.5 at 6, 12, 18 and 24 months were 2%, 7%, 11% and 17%, respectively. Eleven patients achieved a sustained MR4.5. A significant increase of glycosylated hemoglobin was not observed. The total cholesterol, and both LDL and HDL cholesterol fractions significantly increased during treatment. Triglicerid concentrations had not significant variations. Six patients (5%) had a cardiovascular event, including myocardial infarction and arterial thrombosis. All the patients are still alive. Summary: The molecular response rates seem to be superior to the historical data of IM. NIL 300 mg BID as frontline treatment of BCR-ABL+ CML, with dose optimization in case of non optimal response, may improve the proportion of patients able to discontinue TKI treatment. Due to the metabolic effects, a baseline selection is important to maximize the therapeutic benefit and to minimize the cardiovascular risks.
    20 EHA congress, Wien; 06/2015
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    ABSTRACT: Filgrastim biosimilars have recently been introduced into clinical practice. To date biosimilars have demonstrated comparable efficacy and safety as the originator in chemotherapy-induced neutropenia. Published experience in engraftment after autologous stem cell transplantation (ASCT) is limited and concerns relatively few patients. With the aim of assessing the efficacy and the safety of filgrastim biosimilars in post-ASCT bone marrow recovery, we conducted a single institution, retrospective study in 56 lymphoma and myeloma patients who received filgrastim biosimilars (Tevagrastim(®) and Zarzio(®)) at standard doses from day 5. We compared our results with recently published data on the originator. A cost analysis of each biosimilar was performed. Neutrophil counts recovered in 55 patients. The median number of filgrastim biosimilar vials injected was seven per patient. The median time to neutrophil and platelet recovery was 10 and 12 days, respectively. Twenty-six patients had febrile neutropenia, in half of whom the agent involved was identified. In the cost analysis, the use of Tevagrastim(®) and Zarzio(®) was associated with cost reductions of 56% and of 86%, respectively. Despite differences in CD34+ cell counts and time of starting filgrastim, our results in terms of time to engraftment and median number of vials injected are similar to published data. Comparing our results by single conditioning regimen to recent literature data, the time to engraftment and duration of hospitalisation were equivalent. Significant differences were observed in the incidence of febrile neutropenia, perhaps due to different preventive and prophylactic protocols for infections. Although prospective studies should be performed to confirm our results, filgrastim biosimilars were found to be effective and safe in engraftment after ASCT.
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    ABSTRACT: Interferon α (IFNα) prolongs survival of CML patients achieving CCyR and potentially synergizes with TKIs. We report on the molecular status and long term outcome of 121 patients who were treated in Italy between 1986 and 2000 with IFNα based therapy and who obtained CCyR. After a median follow up of 16.5 years, 74 (61%) patients were switched to standard imatinib: 48 (65%) lost the CCyR on IFNα, and 36 (75%) are alive and in CCyR; 26 (35%) were switched to imatinib when they were still in CCyR on IFNα, and all 26 are alive and in CCyR. Forty-seven patients (39%) were never switched to imatinib: 24 (51%) continued and 23 (49%) discontinued IFNα, respectively, and 39/47 (83%) are alive and in CCyR. At last follow-up, the BCR-ABL transcripts level was available in 96/101 living patients (95%) The BCR-ABL:ABL ratio was between 0.1 and 0.01% (MR(3.0) ) in 17%, and less than 0.01% (MR(4.0) ) in 81% of patients. No patient was completely molecular negative (MR(4.5) or MR(5.0) ). The OS at 10 and 20 years is 92% and 84%, respectively. This study confirms that CCyR achieved with IFNα and maintained with or without imatinib or any other therapy significantly correlates with long term survival in CML patients who mostly have MR(4.0) . Complete molecular response (MR(4.5) or MR(5.0) ) seems to be unecessary for such a long survival. This study further supports development of studies testing the clinical effect of the combinations of TKIs with IFNα.
    American Journal of Hematology 10/2013; DOI:10.1002/ajh.23593 · 3.48 Impact Factor
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    ABSTRACT: A patient undergoing chemotherapy for multiple myeloma had a sudden onset of heart failure. Cardiac magnetic resonance was performed after echocardiography to rule out myocardial late enhancement, which was not detected. In- terestingly, the inversion time of the T1-weighted inversion recovery late enhancement sequence needed to be significantly increased (from the usual 250-300 to 490 ms) to obtain diagnostic images. This report presents the clinical case of this patient, and discusses potential implications.
    Diagnostic and interventional radiology (Ankara, Turkey) 11/2012; 18(6):552-4. DOI:10.4261/1305-3825.DIR.5923-12.2 · 1.43 Impact Factor
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    ABSTRACT: As it has been shown that α-interferon (αIFN) 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 αIFN treatment between 1989 and 1991. The Sokal score system was used as a reference. The new Euro score predicted the response to αIFN 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 αIFN. 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.
    British Journal of Haematology 11/2008; 111(2):587-595. DOI:10.1111/j.1365-2141.2000.02366.x · 4.96 Impact Factor
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    ABSTRACT: Imatinib mesylate is a tyrosine kinase inhibitor used as first line treatment in chronic myeloid leukemia and gastrointestinal stromal tumor patients. Although several in vitro and animal studies demonstrated that imatinib affects immune response, few immune alterations are described in humans. We retrospectively studied hematologic and immunological parameters in 72 chronic myeloid leukemia and 15 gastrointestinal stromal tumor patients treated with imatinib at standard dosage and in 20 chronic myeloid leukemia patients treated before the introduction of imatinib in clinical practice. Both chronic myeloid leukemia and gastrointestinal stromal tumor patients developed a significant reduction of gammaglobulin and immunoglobulin serum levels. No significant hypogammaglobulinemia was observed in chronic myeloid leukemia patients in the pre-imatinib era. These data demonstrate that imatinib treatment induces hypogammaglobulinemia that can reach a severe entity in 10% of cases, both in chronic myeloid leukemia and in gastrointestinal stromal tumor patients. Prospective studies are needed to evaluate immune humoral alterations and to define the real incidence of infectious events, including viral reactivations.
    Haematologica 08/2008; 93(8):1252-5. DOI:10.3324/haematol.12642 · 5.87 Impact Factor
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    American Journal of Hematology 07/2006; 81(7):557. DOI:10.1002/ajh.20586 · 3.48 Impact Factor
  • American journal of clinical oncology 01/2006; 28(6):636-7. DOI:10.1097/01.coc.0000159561.56846.08 · 2.61 Impact Factor
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    ABSTRACT: Point mutations within the ABL kinase domain of the BCR-ABL gene have been associated with clinical resistance to imatinib mesylate in chronic myeloid leukemia (CML) patients. To shed further light on the frequency, distribution, and prognostic significance of ABL mutations, we retrospectively analyzed a homogeneous cohort of late chronic phase CML patients who showed primary cytogenetic resistance to imatinib. Using denaturing high-performance liquid chromatography (D-HPLC) and sequencing, we screened for ABL mutations in a total of 178 bone marrow and/or peripheral blood samples from 40 late chronic phase CML patients homogeneously treated with imatinib 400 mg/d, who did not reach a major cytogenetic response at 12 months. Mutations were found in 19 of 40 patients (48%). Mutations were already detectable by D-HPLC at a median of 3 months from the onset of therapy. The presence of a missense mutation was significantly associated with a greater likelihood of subsequent progression to accelerated phase/blast crisis (P = .0002) and shorter survival (P = .001). Patients carrying mutations falling within the P-loop seemed to have a particularly poor outcome in terms of time to progression (P = .032) and survival (P = .045). Our results show that, irrespective of the hematologic response, monitoring for emerging mutations in the first months of therapy may play a role in detecting patients with worse prognosis, for whom a revision of the therapeutic strategy should be considered.
    Journal of Clinical Oncology 07/2005; 23(18):4100-9. DOI:10.1200/JCO.2005.05.531 · 18.43 Impact Factor
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    ABSTRACT: Primary pancreatic lymphoma (PPL) is a very rare disease. We report five cases of PPL (4 men and 1 woman, mean age 65 years) diagnosed and treated at our Institution from 1987 to 1997. None of these patients had evidence of extrapancreatic disease and they were categorized as PPL involving pancreas only (stage IE, 3 patients) or pancreas and peripancreatic lymph nodes (stage IIE, 2 patients). The most common presenting symptoms were abdominal pain and weight loss. Imaging techniques showed a mass of the pancreatic head in all cases. The histological diagnosis (3 diffuse-large cell non-Hodgkin's lymphoma and 2 lymphoplasmacytic lymphoma/immunocytoma) was made by ultrasound-guided fine needle aspiration biopsy and tissue core fine-needle biopsy in three patients and by surgery in the remaining two patients. The three patients diagnosed by percutaneous biopsy were treated with chemotherapy as front-line therapy and two of them received also local radiotherapy; one of these patients is still alive in complete remission at 69 months, one died of an unrelated disease at 67 months and one died of lymphoma relapse at 88 months. Two patients underwent pancreaticoduodenectomy plus adjuvant chemotherapy; one of them died of recurrent cholangitis 8 months after surgery while the other one is still alive in complete remission after 160 months. This study shows that: 1) imaging techniques can suggest the suspicion of PPL but are unable to distinguish PPL from pancreatic adenocarcinoma; 2) histological diagnosis can be easily obtained by percutaneous US-guided tissue core biopsy; 3) surgery can be avoided both for diagnosis and therapy but the treatment of choice of PPL may only be evaluated on a larger series of patients.
    Haematologica 03/2005; 90(2):ECR09. · 5.87 Impact Factor
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    ABSTRACT: Hepatitis C virus (HCV) is endemic in some areas of Northwestern Europe and the United States. HCV has been shown to play a role in the development of both hepatocellular carcinoma and B-cell non-Hodgkin's lymphoma (B-NHL). The biologic mechanisms underlying the lymphomagenic activity of the virus so far are under investigation. In this study, the role of antiviral (anti-HCV) treatment in B-NHL associated with HCV infection is evaluated. Thirteen patients with histologically proven low-grade B-NHL characterized by an indolent course (ie, doubling time no less than 1 year, no bulky disease) and carrying HCV infection were enrolled on the study. All patients underwent antiviral treatment alone with pegilated interferon and ribavirin. Response assessment took place at 6 and 12 months. Of the twelve assessable patients, seven (58%) achieved complete response and two (16%) partial hematologic response at 14.1 +/- 9.7 months (range, 2 to 24 months, median follow-up, 14 months), while two had stable disease with only one patient experiencing progression of disease. Hematologic responses (complete and partial, 75%) were highly significantly associated to clearance or decrease in serum HCV viral load following treatment (P = .005). Virologic response was more likely to be seen in HCV genotype 2 (P = .035), while hematologic response did not correlate with the viral genotype. Treatment-related toxicity did not cause discontinuation of therapy in all but two patients, one of whom, however, achieved complete response. This experience strongly provides a role for antiviral treatment in patients affected by HCV-related, low-grade, B-cell NHL.
    Journal of Clinical Oncology 02/2005; 23(3):468-73. DOI:10.1200/JCO.2005.06.008 · 18.43 Impact Factor
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    Haematologica 02/2005; 90(1):ECR09. · 5.87 Impact Factor
  • Daniele Vallisa · Elena Trabacchi · Luigi Cavanna
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    ABSTRACT: Lymphoproliferative disorders affecting the lung are infrequent. Therefore the diagnosis is often not easy, specially when the lung is primary affected. Moreover, new clinical-pathological entities are responsible of primary lung lymphoma that require specific treatment. It is important to keep in mind the chance that lung may be involved by lymphoproliferative disorders so to avoid the mistake of the misdiagnosis of this curable diseases since sometimes they have a good prognosis and a very different management from epithelial neoplasia of the lung.
    Current Drug Targets - Inflammation & Allergy 01/2005; 3(4):469-71. DOI:10.2174/1568010042634550
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    ABSTRACT: Since interferon-alpha and imatinib (IM; STI571, Glivec, Gleevec) are effective for the treatment of chronic myeloid leukemia (CML), and their mechanisms of action are different, we designed an exploratory study investigating the effects of a standard IM dose (400 mg/d) and a variable pegylated interferon-alpha (PegIFN) dose (50 microg/wk, 100 microg/wk, and 150 microg/wk). The criteria for dose adjustment were designed so as to ensure the delivery of the IM dose and to protect life quality. There were 76 patients with previously untreated Philadelphia (Ph)-positive CML enrolled in the study. There were 3 patients who discontinued IM and 45 patients who discontinued PegIFN. The severity of adverse events increased with increasing PegIFN dose. The IM dose could be administered to the patients who were assigned to receive 50 microg/wk or 100 microg/wk PegIFN but not to those who were assigned to receive 150 microg/wk. The median administered dose of PegIFN ranged between 32 microg/wk and 36 microg/wk. The cytogenetic response was 70% complete (Ph-neg 100%) and 83% major (Ph-neg > 65%). The BCR/ABL transcript was reduced by at least 3 logs in 68% of complete cytogenetic responders. These data of toxicity, compliance, and efficacy may assist in the design and preparation of prospective studies.
    Blood 12/2004; 104(13):4245-51. DOI:10.1182/blood-2004-03-0826 · 10.43 Impact Factor
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    ABSTRACT: Imatinib is a tyrosine-kinase inhibitor that binds to ABL proteins and induces cytogenetic remissions in patients with chronic myeloid leukemia (CML). In these patients measuring response by molecular techniques is clearly required. We determined the cytogenetic and molecular response (CgR, MR) to imatinib in 191 patients with late chronic-phase Philadelphia-positive (Ph+) CML, previously treated with interferon alpha. MR was assessed with real-time quantitative (TaqMan) reverse transcription-polymerase chain reaction and was expressed as the ratio between BCR/ABL and beta 2-microglobulin x 100, the lowest level of detectability of the method being 0.00001. A complete CgR (CCgR) was achieved in 85 (44%) of 191 patients and was maintained for 2 years in 67 (79%) of 85 patients. A reduction of the transcript level of more than 2 logs was achieved in all but 9 patients with CCgR versus none of 23 with partial CgR. In the CCgRs the median value of the MR was 0.0008 after 12 months and 0.0001 after 24 months, with the transcript level undetectable in 22 cases. We conclude that in CCgRs the degree of MR may vary from 2 to more than 4 logs, and that there is a progressive decrease of transcript level by time. Only 1 of 22 negative cases has had a relapse as yet.
    Blood 04/2004; 103(6):2284-90. DOI:10.1182/blood-2003-07-2575 · 10.43 Impact Factor
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    ABSTRACT: Recently, a fusion gene, FIP1-like 1 (FIP1L1)-PDGFR-α, has been found to be involved in some patients with idiopathic hypereosinophilic syndrome (HES) responsive to imatinib therapy. We report a new case of a patient with FIP1L1-PDGFR-α positive HES, treated with imatinib mesylate for more than 17 months, who obtained a complete molecular response.
    Haematologica 03/2004; 89(2):236-7. · 5.87 Impact Factor
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    ABSTRACT: We compared the early cytogenetic response (CgR) to a combination of imatinib mesylate (Glivec, Novartis Pharma, Basel, Switzerland) and a pegylated form of human recombinant interferon-alpha2b (pegIFN-alpha2b, PegIntron, Schering Plough, Kenilworth, New Jersey, USA) with the relative risk, either according to Sokal's or Euro scoring systems. Seventy-seven patients with early chronic phase, previously untreated, Ph-positive chronic myeloid leukemia (CML) received a combination of imatinib mesylate (400 mg/day) and pegIFN-alpha2b (3 consecutive cohorts treated with 50, 100 or 150 mg/weekly). Fifty-seven patients have completed the first 6 months of treatment and are evaluable for CgR. After 6 months of treatment, the overall major CgR rate was 89% and 90% in low risk patients (Sokal's and Euro, respectively), 76 and 59% in intermediate risk and 23% and 17% in high risk patients. These differences were significant (p=0.0001 for Sokal and 0.001 for e). For the first time, these data suggest that the early CgR rate to a imatinib mesylate-based regimen is significantly risk-related.
    Haematologica 04/2003; 88(3):256-9. · 5.87 Impact Factor
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    ABSTRACT: YNK01 (Starasid) is a prodrug that is adsorbed in the gut and is transformed in the liver in arabinosyl cytosine (AC). Low-dose AC (LDAC) is useful for the treatment of Philadelphia positive (Ph+) chronic myeloid leukemia (CML), especially in combination with alpha-interferon (alphaIFN). The use of YNK01 can avoid the daily s.c. injection of conventional AC. To assess the safety and the efficacy of alphaIFN and YNK01, we enrolled 86 consecutive previously untreated chronic phase Ph+ CML patients in a phase II study of alphaIFN (Intron-A) 5 MIU/m(2) daily and YNK01 600 mg daily 14 days a month. The 6-month complete hematologic response and the 12-month major cytogenetic response rates were 78 and 28%, respectively. In a prior study of alphaIFN and conventional LDAC, they were 62 and 22%, respectively. However, the compliance to the treatment was poor, with 25% of cases discontinuing the treatment within the first year. This was not because of the severity of the side effects but because of the frequency, duration and repetition of the side effects, for an overall frequency of 13.17 adverse events, mostly grade 1 and 2, per patient per year. Therefore, the study of this effective combination is being pursued, testing lower doses of alphaIFN and YNK01.
    Leukemia 04/2003; 17(3):554-9. DOI:10.1038/sj.leu.2402850 · 9.38 Impact Factor
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    ABSTRACT: Achieving a complete cytogenetic response (CCgR) is a major target in the treatment of chronic myeloid leukemia (CML) with interferon-alpha (IFN-alpha), but CCgRs are rare. The mean CCgR rate is 13%, in a range of 5% to 33%. A collaborative study of 9 European Union countries has led to the collection of data on 317 patients who were first seen between 1983 and 1997 and achieved CCgRs with IFN-alpha alone or in combination with hydroxyurea. The median time to first CCgR was 19 months (95% CI, 17-21; range, 3-84 months). At last contact, 212 patients were still alive and in continuous CCgR; 105 patients had lost CCgR, but 53% of them were still alive and in chronic phase. IFN-alpha treatment was discontinued permanently in 23 cases for response loss, in 36 cases for chronic toxicity (15 are still in unmaintained continuous CCgR), and in 8 cases because it was believed that treatment was no longer necessary (7 of these 8 patients are still in unmaintained continuous CCgR). The 10-year survival rate from first CCgR is 72% (95% CI, 62%-82%) and is related to the risk profile. High-risk patients lost CCgR more frequently and more rapidly and none survived more than 10 years. Low-risk patients survived much longer (10-year survival probability 89% for Sokal low risk and 81% for Euro low risk). These data point out that a substantial long-term survival in CCgRs is restricted mainly to low-risk and possibly intermediate-risk patients and occurs significantly less often in high-risk patients.
    Blood 12/2001; 98(10):3074-81. DOI:10.1182/blood.V98.10.3074 · 10.43 Impact Factor

Publication Stats

930 Citations
157.32 Total Impact Points

Institutions

  • 2005–2015
    • Ospedale Guglielmo da Saliceto
      Caronno Pertusella, Lombardy, Italy
  • 2000–2008
    • University of Bologna
      • Department of Experimental, Diagnostic and Specialty Medicine DIMES
      Bolonia, Emilia-Romagna, Italy