Publications by authors named "Anna Mele"

19 Publications

  • Page 1 of 1

Carfilzomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma patients: the real-life experience of Rete Ematologica Pugliese (REP).

Ann Hematol 2021 Feb 7;100(2):429-436. Epub 2020 Nov 7.

Department of Hematology and Bone Marrow Transplant, Hospital Card. G. Panico, Via San Pio X, 73039, Tricase (LE), Italy.

Carfilzomib, lenalidomide, and dexamethasone (KRd) have been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) based on ASPIRE clinical trial. However, its effectiveness and safety profile in real clinical practice should be further assessed. We retrospectively evaluated 130 consecutive RRMM patients treated with KRd between December 2015 and August 2018, in 9 Hematology Departments of Rete Ematologica Pugliese (REP). The overall response rate (ORR) was 79%, with 37% complete response (CR). Treatment with KRd led to an improvement in response regardless of age, refractory disease, and number and type of previous therapies. After a median follow-up of 18 months, median PFS was 24 months and 2y-PFS was 54%. PFS was longer in patients achieving a very good partial response (VGPR) with median PFS of 32.4 months. The relapses after prior autologous transplant (ASCT) positively impact median PFS. Several baseline disease characteristics, such as III ISS scoring or elevated LDH, and prior exposure to lenalidomide were found to negatively impact PFS. Primary refractory or relapsed myeloma patients have been treated with KRd as bridge to ASCT with a great benefit. Thirty-four (83%) reached at least a partial response after KRd and 21 (61%) performed ASCT. In transplanted patients, median PFS was not reached and 2y-PFS was 100%. The treatment discontinuation rate due to adverse events (AEs) was 18%, most commonly for lenalidomide (11%). Overall, in 10% of patients, a KRd dose reduction was necessary at least once (2.5% for carfilzomib and 8% for lenalidomide). The most frequent AE was neutropenia (44%) and anemia (41%). Infections occurred in 14% of patients. Cardiovascular events occurred in 11% of patients. Elderly patients have tolerated therapy very well, without additional side effects compared to younger patients, except for cardiac impairment. Our analysis confirmed that KRd is effective in RRMM patients. It is well tolerated and applicable to the majority of patients outside clinical trials. A longer PFS was shown in patients achieving VGPR, in those lenalidomide naïve and in patients relapsing after previous ASCT. Previous ASCT should not hamper the option for KRd therapy. Accordingly, KRd should be used as bridge regimen to ASCT with remarkable improvement in response and PFS rates. Further clinical studies are needed.
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http://dx.doi.org/10.1007/s00277-020-04329-3DOI Listing
February 2021

Brentuximab vedotin prior to allogeneic stem cell transplantation increases survival in chemorefractory Hodgkin's lymphoma patients.

Ann Hematol 2019 Jun 14;98(6):1449-1455. Epub 2019 Mar 14.

Haematology, "Policlinico" Hospital, Bari, Italy.

This study reports a retrospective multicenter experience by the Rete Ematologica Pugliese (REP) over the past 16 years, aiming to compare the patients characteristics and outcomes of 21 brentuximab vedotin (BV)-pre-treated patients to 51 patients who received reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT) without prior BV. In total, 72 patients with classical Hodgkin's lymphomas who received allogeneic SCT were retrospectively studied. Prior use of BV had no effect on either engraftment or the incidence and severity of acute graft versus host disease (GVHD). Indeed, a lower incidence of chronic GVHD was observed in the BV group, with a 43% cumulative incidence at 3 years versus 47% in the no BV group, although this was not statistically significant. Despite the low incidence of chronic GVHD, survival was not worse in the BV-treated group: 3-year progression-free survival (PFS) was 53%, 3-year overall survival (OS) was 62%, 3-year non-relapse mortality (NRM) was 24%. In the no BV group, the 3-year PFS was 33%, 3-year OS was 44%, and 3-year NRM was 14%. In chemorefractory patients at the time of transplant, we found a statistically significant difference in PFS between the BV and no BV groups (51% vs. 10%, p = 0.013).
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http://dx.doi.org/10.1007/s00277-019-03662-6DOI Listing
June 2019

Outcomes of Reduced Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation for Hodgkin Lymphomas: A Retrospective Multicenter Experience by the Rete Ematologica Pugliese (REP).

Clin Lymphoma Myeloma Leuk 2019 01 12;19(1):35-40. Epub 2018 Sep 12.

Haematology, "G.Panico" Hospital, Tricase (LE), Italy.

Background: Hodgkin lymphoma (HL) is a potentially curable disease, and modern therapy is expected to successfully cure more than 80% of the patients. However, patients progressing after intensive treatments, such as autologous stem cell transplantation (SCT), have a very poor outcome. Allogeneic SCT offers the only strategy with a curative potential for these patients. This study reports a retrospective multicenter experience of the Rete Ematologica Pugliese (REP) over the past 17 years, aiming to define the impact of each patient's disease and transplant-related characteristics on outcomes.

Patients And Methods: We retrospectively studied 72 patients with HL who received allogeneic SCT from 2000 to 2017. At the time of allogeneic SCT, 33 (46%) patients had chemosensitive disease, and 39 (54%) were chemo-refractory. All patients received reduced-intensity conditioning, 50% received grafts from a matched sibling donor, and 50% from a matched-unrelated donor.

Results: With a median follow-up of 48 months (range, 3-195 months), 30 patients are alive, and 42 have died. The Kaplan-Meier estimates of overall survival and progression-free survival at 5 years were 35% and 34%, respectively. Following transplantation, 12 (17%) patients died of non-relapse mortality at a median of 90 days (range, 1 day-20 months). The causes of death included infection (n = 7), graft-versus-host disease (n = 3), and multi-organ failure (n = 2).

Conclusions: Allogeneic SCT results extend survival in selected patients with relapsed/refractory HL, showing low treatment-related mortality. Patients with active disease at the time of allogeneic transplantation have poor outcomes. Allogeneic SCT may be an effective salvage strategy for patients who relapse after an autologous SCT.
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http://dx.doi.org/10.1016/j.clml.2018.08.012DOI Listing
January 2019

Brentuximab vedotin as salvage treatment in Hodgkin lymphoma naïve transplant patients or failing ASCT: the real life experience of Rete Ematologica Pugliese (REP).

Ann Hematol 2018 Oct 27;97(10):1817-1824. Epub 2018 Jul 27.

Department of Hematology, Hospital University Riuniti, Foggia, Italy.

Brentuximab vedotin (BV) shows a high overall response rate (ORR) in relapsed/refractory (R/R) Hodgkin lymphoma (HL) after autologous transplant (ASCT). The aim of this multicenter study, conducted in nine Hematology Departments of Rete Ematologica Pugliese, was to retrospectively evaluate the efficacy and safety of BV as salvage therapy and as bridge regimen to ASCT or allogeneic transplant (alloSCT) in R/R HL patients. Seventy patients received BV. Forty-five patients (64%) were treated with BV as bridge to transplant:16 (23%) patients as bridge to ASCT and 29 (41%) as bridge to alloSCT. Twenty-five patients (36%), not eligible for transplant, received BV as salvage treatment. The ORR was 59% (CR 26%). The ORR in transplant naïve patients was 75% (CR 31%). In patients treated with BV as bridge to alloSCT, the ORR was 62% (CR 24%). In a multivariate analysis, the ORR was lower in refractory patients (p < 0.005). The 2y-OS was 70%. The median PFS was 17 months. Ten of the 16 (63%) naïve-transplant patients received ASCT, with 50% in CR before ASCT. In the 29 patients treated with BV as bridge to alloSCT, 28 (97%) proceeded to alloSCT with 25% in CR prior to alloSCT. The most common adverse events were peripheral neuropathy (50%), neutropenia (29%) and anemia (12%). These data suggest that BV is well tolerated and very effective in R/R HL, producing a substantial level of CR. BV may also be a key therapeutic agent to achieve good disease control before transplant, improving post- transplant outcomes, also in refractory and heavily pretreated patients, without significant overlapping toxicities with prior therapies.
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http://dx.doi.org/10.1007/s00277-018-3379-5DOI Listing
October 2018

Improved outcome of patients with relapsed/refractory Hodgkin lymphoma with a new fotemustine-based high-dose chemotherapy regimen.

Br J Haematol 2016 Jan 12;172(1):111-21. Epub 2015 Oct 12.

Dipartimento di Ematologia, Istituto Nazionale Tumori, Fondazione 'G. Pascale', IRCCS, UOC di Ematologia Oncologica e Trapianto di Cellule Staminali, Napoli, Italy.

High-dose chemotherapy (HDT) with autologous stem cell transplantation is the standard of care for relapsed/refractory (RR) Hodgkin lymphoma (HL). Given that HDT may cure a sizeable proportion of patients refractory to first salvage, development of newer conditioning regimens remains a priority. We present the results of a novel HDT regimen in which carmustine was substituted by a third-generation chloroethylnitrosourea, fotemustine, with improved pharmacokinetics and safety (FEAM; fotemustine, etoposide, cytarabine, melphalan) in 122 patients with RR-HL accrued into a prospective registry-based study. Application of FEAM resulted in a 2-year progression-free survival (PFS) of 73·8% [95% confidence interval (CI), 0·64-0·81] with median PFS, overall survival and time to progression yet to be reached. The 2-year risk of progression adjusted for the competitive risk of death was 19·4% (95% CI, 0·12-0·27) for the entire patient population. Most previously established independent risk factors, except for fluorodeoxyglucose ((18) (F) FDG)-uptake, were unable to predict for disease progression and survival after FEAM. Although 32% of patients had (18) (F) FDG-positrin emission tomography-positive lesions before HDT, the 2-year risk of progression adjusted for competitive risk of death was 19·4% (95% CI; 0·12-0·27). No unusual acute toxicities or early/late pulmonary adverse events were registered. FEAM emerges as an ideal HDT regimen for RR-HL patients typically pre-exposed to lung-damaging treatments.
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http://dx.doi.org/10.1111/bjh.13803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053328PMC
January 2016

Thalidomide, dexamethasone, Doxil and Velcade (ThaDD-V) followed by consolidation/maintenance therapy in patients with relapsed-refractory multiple myeloma.

Ann Hematol 2011 Dec 25;90(12):1449-56. Epub 2011 Mar 25.

Clinica di Ematologia Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Ancona, Via Conca, 71, 60020, Ancona, Italy.

In newly diagnosed multiple myeloma (MM), three/four-drug combinations as induction therapy seem to be more effective compared with two-drug associations in terms of response rate and duration of remission. Moreover, there is an emergent body of evidences that consolidation/maintenance therapy improves the quality of response and remission duration. However, the impact of these strategies in relapsed/refractory MM (r-rMM) is still unknown. This phase II study explored the four-drug combination of thalidomide, dexamethasone, pegylated liposomal doxorubicin (pLD), and bortezomib (ThaDD-V) as induction followed by consolidation therapy based on bortezomib-dexamethasone and thalidomide-dexamethasone and maintenance therapy with thalidomide in r-rMM patients. The primary end points of this study were best response and toxicity of the planned therapy. Forty-six patients were enrolled. At the end of therapy, the best response was as follows: 37% complete response (CR), 34.5% VGPR, and 4.5% PR with an ORR of 76%. Patients receiving ≤ 2 prior regimens had a CR rate significantly higher than those heavily treated (41% vs 0%; p=0.010). With a median follow-up of 31 months, median time to progression (TTP) and OS were 18.5 months and 40 months, respectively. By a 6-month landmark analysis, patients who completed the protocol had a significantly longer TTP compared with those who did not because of toxicity (not reached vs 7 months; p<0.0001). After the dose intensity of bortezomib was reduced due to an excess of peripheral neuropathy (PN), grade 3 PN occurred in 7.5% of patients. ThaDD-V followed by consolidation-maintenance therapy seems to be very effective in patients with r-rMM provided that this procedure is used early on relapse when very deep responses seem to be the rule.
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http://dx.doi.org/10.1007/s00277-011-1217-0DOI Listing
December 2011

Infectious complications in patients with multiple myeloma treated with new drug combinations containing thalidomide.

Leuk Lymphoma 2011 May 21;52(5):776-85. Epub 2011 Feb 21.

Clinica di Ematologia Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Ancona, Ancona, Italy.

The literature provides scant data concerning infectious complications and their effect on the outcome of patients with multiple myeloma (MM) treated with new drug combinations. Despite no substantial myelotoxic effect, thalidomide increases the risk of severe infections in patients with MM. We studied 202 patients who received regimens containing thalidomide in order to assess the time, type, outcome, and factors affecting development of severe infections, role of antibiotic prophylaxis, and effect of severe infections on final outcome. Thirty-eight patients (19%) developed a severe infection early during induction therapy and most infections were pneumonia. Only one patient died due to septic shock during neutropenia. No significant differences were reported in terms of progression-free survival (PFS) and overall survival (OS) between patients developing a severe infection and those who did not. Multivariate analysis determined a monoclonal component >3 g/dL and platelets <130 ,000/μL as factors associated with increased risk of severe infection. Primary antibiotic prophylaxis significantly decreased the probability of severe infection only in patients having both the above risk factors. Patients with MM receiving thalidomide combinations with high tumor burden are at high risk of developing severe infections and require primary antibiotic prophylaxis, whereas in other patients it is questionable. However, patient final outcome was not affected by infection development.
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http://dx.doi.org/10.3109/10428194.2011.555027DOI Listing
May 2011

Melphalan, prednisone, and thalidomide versus thalidomide, dexamethasone, and pegylated liposomal doxorubicin regimen in very elderly patients with multiple myeloma: a case-match study.

Leuk Lymphoma 2010 Aug;51(8):1444-9

Clinica di Ematologia Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Ancona, Italy.

The outcome of patients with multiple myeloma (MM) aged over 75 years remains poor, and the best therapeutic approach has still to be defined. We compared the response, toxicity, and outcome of 34 very elderly patients with MM receiving thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) to those of 34 patients matched for age, International Staging System (ISS), and creatinine who received melphalan, prednisone, thalidomide (MPT). ThaDD resulted in a significantly higher response: > or =PR (87.5% vs. 61.5%, p = 0.009) and > or =VGPR (55.5% vs. 29.5%; p = 0.03). No statistical differences were detected in terms of median probability of progression-free survival (PFS) and overall survival (OS) between the two treatments. Patients treated with MPT had more neutropenia, neuropathy, and heart toxicity, whereas thromboembolism resulted more frequently in patients receiving ThaDD. Therapy discontinuation occurred in 9% and 14.5% of patients treated with ThaDD and MPT, respectively. ThaDD can be considered a therapeutic option in very elderly patients with MM since it induces a faster and deeper response than that obtained with MPT, having similar safety profile.
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http://dx.doi.org/10.3109/10428194.2010.486878DOI Listing
August 2010

Thalidomide-dexamethasone versus interferon-alpha-dexamethasone as maintenance treatment after ThaDD induction for multiple myeloma: a prospective, multicentre, randomised study.

Br J Haematol 2009 Mar 13;144(5):653-9. Epub 2008 Nov 13.

Clinica di Ematologia Azienda Ospedaliero-Universitaria, Ospedali Riuniti Ancona, Ancona, Italy.

Maintenance therapy was explored in multiple myeloma (MM) patients after conventional thalidomide, dexamethasone and pegylated liposomal doxorubicin (ThaDD). Patients with newly or relapsed MM obtaining at least minor response after 6 ThaDD courses, were randomised to receive alpha-interferon (IFN) 3 MU 3 times a week or thalidomide 100 mg daily until relapse. Both groups also received pulsed dexamethasone 20 mg 4 d a month. Fifty-one patients were randomized in the IFN-dexamethasone (ID) arm and 52 in the thalidomide-dexamethasone (TD) arm. The characteristics of two groups were similar. A significantly better 2-years progression-free survival (PFS; 63% vs. 32%; P = 0.024) and overall survival (84% vs. 68%; P = 0.030) was observed in the thalidomide arm. In high-risk patients and in those achieving less than very good partial response after induction, TD fared better in term of PFS. Main side effects were peripheral neuropathy and constipation in TD group, fatigue, anorexia and haematological toxicity in ID arm. There was a 21% probability of discontinuation at 3 years in the thalidomide arm and 44% in the IFN arm (P = 0.014). Low-dose thalidomide plus pulsed low-dose dexamethasone after conventional thalidomide combination-based therapy was also feasible in the long term, enabling significantly better residual disease control if compared with a standard maintenance therapy.
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http://dx.doi.org/10.1111/j.1365-2141.2008.07495.xDOI Listing
March 2009

Serum C-reactive protein at diagnosis and response to therapy is the most powerful factor predicting outcome of multiple myeloma treated with thalidomide/ anthracycline-based therapy.

Clin Lymphoma Myeloma 2008 Oct;8(5):294-9

Clinica di Ematologia Azienda Ospedaliero-Universitaria, Ospedali Riuniti Ancona, Italy.

Background: Few studies have focused on factors affecting outcome in patients with multiple myeloma (MM) treated with thalidomide-based therapy. We investigated factors affecting response, progression-free survival (PFS), and overall survival (OS) in patients with MM treated with the thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) regimen with the aim to select patients benefiting more from this therapy.

Patients And Methods: Sixty-six patients with MM were treated first line with the ThaDD regimen. We analyzed demographics and disease-related characteristics to search for factors affecting response (> or = very good partial remission [VGPR] vs. < VGPR], PFS, and OS.

Results: Overall, 45 patients (68%) showed response > or = VGPR; median TTP and OS were 23.5 months and 35.5 months, respectively. Multivariate analysis selected only serum C-reactive protein (sCRP) as a predictive factor for response (P < .0001). By multivariate analysis, normal sCRP level (P = .001) and response to treatment > or = VGPR (P = .007) were found to be associated with longer PFS. The factors that remained significantly associated with a longer OS when assessed by multivariate analysis were normal sCRP level (P = .005) and response to therapy > or = VGPR (P = .019).

Conclusion: Serum C-reactive protein before therapy and response after therapy are the only factors useful in identifying patients benefiting from anthracycline/thalidomide-based therapy.
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http://dx.doi.org/10.3816/CLM.2008.n.041DOI Listing
October 2008

Technetium-99m sestamibi scintigraphy is sensitive and specific for the staging and the follow-up of patients with multiple myeloma: a multicentre study on 397 scans.

Br J Haematol 2007 Mar;136(5):729-35

Department of Haematology, San Salvatore Hospital, Pesaro, Italy.

We evaluated the additional benefit of Technetium(99)-sestamibi (99mTc-MIBI) scanning in comparison with standard X-ray techniques for multiple myeloma patients either at diagnosis or during follow-up. Between February 2001 and January 2005, 397 whole body scans were acquired. On 229 scans performed at diagnosis, 146 (64%) were positive and 81 cases have discordant X-ray results. The sensitivity of 99mTc-MIBI and X-ray were 77% and 45% respectively. As a result of 99mTc-MIBI, 40% of asymptomatic myeloma patients were up-staged. The positivity of 99mTc-MIBI correlated significantly with all of the most relevant clinical and biological parameters. Multivariate analysis selected only high reactive C protein (P = 0.0005), bone marrow infiltration (P = 0.02) and bone pain (P = 0.002) as factors affecting 99mTc-MIBI pattern. In 22 patients with solitary myeloma, 99mTc-MIBI was positive in 86% of cases and detected more disease sites than X-ray. Among 168 scans performed during follow-up, 99mTc-MIBI presented high specificity in patients showing a complete response (CR; 86%), and correlated with myeloma activity and with response to therapy. At multivariate analysis, a positive pattern correlated with bone marrow infiltration (P = 0.002) and disease status other than CR (P = 0.03). We conclude that 99mTc-MIBI scanning is an additional diagnostic tool with a high specificity for the staging and the follow-up of multiple myeloma patients.
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http://dx.doi.org/10.1111/j.1365-2141.2006.06489.xDOI Listing
March 2007

An observational study of once weekly intravenous ganciclovir as CMV prophylaxis in heavily pre-treated chronic lymphocytic leukemia patients receiving subcutaneous alemtuzumab.

Leuk Lymphoma 2006 Dec;47(12):2542-6

Department of Hematology, San Salvatore Hospital, Pesaro, Italy.

Fifteen consecutive resistant/relapsed chronic lymphocytic leukemia (CLL) patients (median age: 65 years) received alemtuzumab for 16 consecutive weeks. All patients had negative CMV anti genemia at baseline. Five patients received oral acyclovir 800 mg twice a day for CMV prophylaxis and 10 patients got intravenous (iv) ganciclovir 7.5 mg/kg once a week. A total of five CMV reactivations occurred, four in the acyclovir and one in the ganciclovir prophylaxis group. Alemtuzumab was then discontinued and all patients were treated with iv ganciclovir 7.5 mg/kg per day. All patients achieved negative CMV anti genemia after a median of 15 days of therapy. Weekly iv ganciclovir prophylaxis and alemtuzumab treatment were then restarted without any further CMV reactivations. In conclusion, weekly iv ganciclovir appears feasible and effective in preventing CMV reactivation and disease in this setting of high-risk immunocompromised patients, allowing an easier management of a therapy otherwise difficult to be routinely used.
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http://dx.doi.org/10.1080/10428190600929311DOI Listing
December 2006

Pegfilgrastim effectively mobilizes PBSC in a poor mobilizer multiple myeloma patient.

Eur J Haematol 2006 May 15;76(5):436-9. Epub 2006 Feb 15.

Department of Haematology, San Salvatore Pesaro, Italy.

Studies performed on mice and healthy human volunteers have shown that a single dose of pegfilgrastim (Peg-GCSF) is effective in stimulating peripheral blood stem cells (PBSC) mobilization. This prompted us to try the stimulation with pegfilgrastim in a patient previously non-mobilizing with a combination of chemotherapy and filgrastim. In December 2003, a 65-yr-old man was diagnosed as having stage III A IgG/k multiple myeloma. He received three courses of polichemotherapy (DC-IE) obtaining a stable response. Afterwards, the patient was treated with high-dose cyclophosphamide (CPM; 7 g/sqm) plus daily 10 mcg/kg filgrastim in order to mobilize PBSC, without success. After 2 months off therapy, the disease progressed and the patient received alternate cycles VAD (vincristine, dexamethasone, adriblastine)/high-dose dexamethasone. A second attempt to mobilize PBSC, using daily 10 mcg/kg filgrastim after the second and third VAD cycle, failed. In a further attempt to mobilize PBSC, we administered a single dose of 12 mg pegfilgrastim on day 5 after a fourth VAD course. Daily evaluation of circulatory CD34+ cells was started from day 8 after the end of chemotherapy. On day +10 postchemotherapy the CD34+ cell count was 24/microL and two aphaeresis were performed, harvesting 1.6 x 10(6) and 0.89 x 10(6) CD34+ cells/kg respectively (total 2.49 x 10(6) cells/kg). The only side effect was moderate skeletal pain. The patient underwent successful transplantation. The median times necessary to recover 0.5 x 10(9) PMN/L and 20 x 10(9) platelets/L after PBSC reinfusion were 9 and 12 d respectively. The patient did not need red blood cell or platelet transfusions. He experienced a sustained engraftment and maintains complete remission 9 months after the reinfusion. In conclusion, a single dose of pegfilgrastim was able to mobilize a sufficient number of CD34+ in a multiple myeloma patient not responsive to two previous attempts with high or standard dose chemotherapy followed by filgrastim. This approach, if confirmed on larger series and other diseases, could open new opportunities in stem cell mobilization for poor or non-mobilizers.
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http://dx.doi.org/10.1111/j.1600-0609.2005.00627.xDOI Listing
May 2006

Mini-ICE effectively mobilises peripheral blood stem cells after fludarabine-based regimens in acute myeloid leukaemia.

Eur J Haematol 2005 Apr;74(4):277-81

Department of Haematology, Hospital San Salvatore, Pesaro, Italy.

Fludarabine-based cycles severely impair mobilisation and collection of peripheral blood stem cells (PBSC) in acute myeloid leukaemia (AML). In an effort of reversing this side-effect, we studied the action on mobilisation and collection of PBSC of a low-dose regimen: 5-d Mini-ICE (oral idarubicin and etoposide; subcutaneous cytosine arabinoside) administered after fludarabine-based regimens in seven adult AML patients. Leukapheresis were started when the CD34+ cell count was more than 10/microL. The median number of harvested CD34+ cells was 8.1 x 10(6)/kg (range 3.08-15.2). All the patients were successfully submitted to PBSC transplantation. Median times to neutrophil and platelet recovery were rapid with a normal transfusional support. We suggest that the Mini-ICE programme is feasible, well tolerated and effective in terms of PBSC mobilisation and collection in low-yield AML patients previously treated with fludarabine. It is well known that a negative effect on stem cell mobilisation and harvest is observed not only after fludarabine administration in AML or low-grade lymphomas, but also after cycles based on different agents, such as thalidomide in multiple myeloma. This preliminary experience, if confirmed on larger series and/or other haematological malignancies, could open new opportunities to perform autologous PBSC transplantation in heavily pretreated cases, allowing a full source of therapeutic options before the start of the mobilisation process.
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http://dx.doi.org/10.1111/j.1600-0609.2004.00383.xDOI Listing
April 2005

Thalidomide plus oral melphalan compared with thalidomide alone for advanced multiple myeloma.

Hematol J 2004 ;5(4):312-7

Clinic of Haematology, Polytechnic University of Marches, Ancona, Italy.

Thalidomide, the prototype of a new class of agents active against multiple myeloma (MM), exerts synergistic/additive effects when combined with other drugs. The aim of this study was to compare the toxicity and efficacy of thalidomide alone and in combination with oral melphalan. Patients with advanced MM received 100 mg/day oral thalidomide escalated weekly up to 600 mg/day (n=23; T group), alone or with 0.20 oral mg/kg/die melphalan administered monthly for four consecutive days (n=27; TM group). A>/=50% paraprotein reduction was observed in 59% of TM compared with 26% of T patients (P=0.009); three TM patients were found to have an absence of paraprotein by immunofixation. After a median follow-up of 13 months (range 6-32), progression-free survival (PFS) at 2 years was significantly longer in the TM group (61 versus 45%; P=0.0376), whereas overall survival did not differ significantly. Toxicity was not significantly greater with the combination therapy; although DVT was more frequent (11 versus 4%), as was grade 3 leukopenia (30 versus 13%; P=0.073), there were no cases of severe infection. Thalidomide administered with oral melphalan improved response rates and PFS in patients with advanced MM without significantly increasing severe toxicity.
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http://dx.doi.org/10.1038/sj.thj.6200401DOI Listing
February 2005

Common and rare side-effects of low-dose thalidomide in multiple myeloma: focus on the dose-minimizing peripheral neuropathy.

Eur J Haematol 2004 Jun;72(6):403-9

Clinica di Ematologia, University of Ancona, Ancona, Italy.

Objectives: Thalidomide has demonstrated a remarkable efficacy in the treatment of multiple myeloma but its use may cause several toxicities. We have investigated the common and rare side-effects, especially analysing peripheral neuropathy, in order to optimise the thalidomide dose for minimizing this harmful side-effect.

Methods: Fifty-nine patients were treated with thalidomide alone or combined with oral melphalan. The median age was 69 yr. The initial dose of thalidomide was 100 mg/day increasing weekly by 100 mg increments until a maximum dose of 400 mg was attained. Melphalan was administered at a dose of 0.20 mg/kg/d for 4 d every 28 d.

Results And Conclusions: Nearly one-fourth of patients discontinued thalidomide because of toxicity. Constipation (71%), somnolence (36%) and fatigue (20%) were the most common side-effects and they were not dose dependent. Peripheral neuropathy occurred in 39% of patients and a thalidomide median daily dose of more than 150 mg was significantly associated with higher frequency and actuarial risk of peripheral neuropathy without improving the response rate. Deep venous thrombosis was observed in 7% of patients and other side-effects were rare. In patients with advanced multiple myeloma we found that a thalidomide daily dose of 150 mg minimizes peripheral neuropathy without jeopardizing response and survival.
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http://dx.doi.org/10.1111/j.1600-0609.2004.00238.xDOI Listing
June 2004

High-dose daunorubicin as liposomal compound (Daunoxome) in elderly patients with acute lymphoblastic leukemia.

Hematol J 2003 ;4(1):47-53

Clinica di Ematologia, Università degli Studi di Ancona, Azienda Ospedaliera Umberto I, Italy.

Elderly acute lymphoblastic leukemia (ALL) is a rare condition associated with low complete remission (CR) rate and short survival. In order to improve these results, we evaluate the efficacy and toxicity of Daunoxome, a liposomal daunorubicin, exhibiting toxicity profile and pharmacokinetic indices better than standard daunorubicin. In total, 15 consecutive patients with nonmature ALL were enrolled on a prospective phase II study. No exclusion was made because of older age, poor performance status and organ dysfunctions. Median age was 69 years; performance status resulted >/=2 in nine patients (60%), six patients (40%) were bcr-abl positive and two-thirds of the patients had comorbidities. Induction therapy consisted of vincristine, Daunoxome and dexamethasone. Patients in CR received one or two consolidation cycles of cyclophosphamide, cytarabine and topotecan followed, in patients achieving CR, by a two-year rotating maintenance course including vincristine, Daunoxome, cyclophosphamide and prednisone. In all, 11 patients (73%) achieved CR, three patients (20%) died early during the induction phase and one patient (7%) had resistant disease. Five patients (33%) relapsed after 5-21 months. With a median follow-up of 20 months, disease free survival (DFS) and overall survival (OS) at 2 years were 36 and 38%, respectively. Major toxicity included myelosuppression and infection. Our experience demonstrates that a high dose of daunorubicin as liposomal compound can be safely administered in elderly ALL, exhibiting high antitumor activity. Our therapeutic program shows evidence of benefit in DFS and OS.
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http://dx.doi.org/10.1038/sj.thj.6200222DOI Listing
July 2003