Publications by authors named "Angela Melpignano"

20 Publications

  • Page 1 of 1

A multicenter total therapy strategy for de novo adult Philadelphia chromosome positive acute lymphoblastic leukemia patients. Final results of the GIMEMA LAL1509 protocol.

Haematologica 2021 Feb 4. Epub 2021 Feb 4.

Hematology, Department of Translational and Precision Medicine, Sapienza University.

The GIMEMA LAL1509 protocol, designed for adult (≥18-60 years) de novo Ph+ acute lymphoblastic leukemia patients, was based on a dasatinib plus steroids induction - with central nervous system prophylaxis - followed by dasatinib alone in patients in complete molecular response or chemotherapy and/or allogeneic transplantation in patients not reaching a complete molecular response. Sixty patients (median age 41.9 years) were enrolled: 33 were p190+, 18 p210+ and 9 p190/p210+. At the end of induction (day +85), 58 patients (97%) achieved a complete hematologic remission. No deaths in induction were recorded. Eleven patients (18.3%) obtained a complete molecular response. Among non-complete molecular responders (n=47), 22 underwent an allogeneic transplant. Seventeen hematologic relapses occurred (median 7 months, range 3-40.1), 13 during consolidation and 4 post-transplant. ABL1 mutations (5 T315I, 3 V299L, 1 E281K and 1 G254E) were found in 10/13 relapsed cases. With a median follow-up of 57.4 months (range: 4.2-75.6), overall survival and disease-free survival are 56.3% and 47.2%. A better diseasefree survival was observed in patients who obtained a molecular response at day +85 compared to cases who did not. The presence of additional copy number aberrations - IKZF1 plus CDKN2A/B and/or PAX5 deletions - was the most important unfavorable prognostic factor on overall and disease-free survival (p=0.005 and p=0.0008). This study shows that in adult Ph+ ALL long-term survivals can be achieved with a total-therapy strategy based on a chemo-free induction and, in complete molecular responders, also without further systemic chemotherapy. Finally, the screening of additional copy number aberrations should be included in the diagnostic work-up. EudraCT 2010-019119-39.
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http://dx.doi.org/10.3324/haematol.2020.260935DOI Listing
February 2021

Managing chronic myeloid leukemia for treatment-free remission: a proposal from the GIMEMA CML WP.

Blood Adv 2019 12;3(24):4280-4290

Università di Bologna, Bologna, Italy.

Several papers authored by international experts have proposed recommendations on the management of BCR-ABL1+ chronic myeloid leukemia (CML). Following these recommendations, survival of CML patients has become very close to normal. The next, ambitious, step is to bring as many patients as possible into a condition of treatment-free remission (TFR). The Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA; Italian Group for Hematologic Diseases of the Adult) CML Working Party (WP) has developed a project aimed at selecting the treatment policies that may increase the probability of TFR, taking into account 4 variables: the need for TFR, the tyrosine kinase inhibitors (TKIs), the characteristics of leukemia, and the patient. A Delphi-like method was used to reach a consensus among the representatives of 50 centers of the CML WP. A consensus was reached on the assessment of disease risk (EUTOS Long Term Survival [ELTS] score), on the definition of the most appropriate age boundaries for the choice of first-line treatment, on the choice of the TKI for first-line treatment, and on the definition of the responses that do not require a change of the TKI (BCR-ABL1 ≤10% at 3 months, ≤1% at 6 months, ≤0.1% at 12 months, ≤0.01% at 24 months), and of the responses that require a change of the TKI, when the goal is TFR (BCR-ABL1 >10% at 3 and 6 months, >1% at 12 months, and >0.1% at 24 months). These suggestions may help optimize the treatment strategy for TFR.
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http://dx.doi.org/10.1182/bloodadvances.2019000865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929396PMC
December 2019

Luspatercept improves hemoglobin levels and blood transfusion requirements in a study of patients with β-thalassemia.

Blood 2019 03 7;133(12):1279-1289. Epub 2019 Jan 7.

Acceleron Pharma, Cambridge, MA; and.

β-thalassemia is a hereditary disorder with limited approved treatment options; patients experience anemia and its complications, including iron overload. The study aim was to determine whether luspatercept could improve anemia and disease complications in patients with β-thalassemia. This open-label, nonrandomized, uncontrolled study consisted of a 24-week dose-finding and expansion stage (initial stage) and a 5-year extension stage, currently ongoing. Sixty-four patients were enrolled; 33 were non-transfusion dependent (mean hemoglobin, <10.0 g/dL; <4 red blood cell [RBC] units transfused per 8 weeks), and 31 were transfusion dependent (≥4 RBC units per 8 weeks). Patients received 0.2 to 1.25 mg/kg luspatercept subcutaneously every 21 days for ≥5 cycles (dose-finding stage) and 0.8 to 1.25 mg/kg (expansion cohort and 5-year extension). The primary end point was erythroid response, defined as hemoglobin increase of ≥1.5 g/dL from baseline for ≥14 consecutive days (without RBC transfusions) for non-transfusion-dependent patients or RBC transfusion burden reduction ≥20% over a 12-week period vs the 12 weeks before treatment for transfusion-dependent patients. Eighteen non-transfusion-dependent patients (58%) receiving higher dose levels of luspatercept (0.6-1.25 mg/kg) achieved mean hemoglobin increase ≥1.5 g/dL over ≥14 days vs baseline. Twenty-six (81%) transfusion-dependent patients achieved ≥20% reduction in RBC transfusion burden. The most common grade 1 to 2 adverse events were bone pain, headache, and myalgia. As of the cutoff, 33 patients remain on study. In this study, a high percentage of β-thalassemia patients receiving luspatercept had hemoglobin or transfusion burden improvements. These findings support a randomized clinical trial to assess efficacy and safety. This study was registered at www.clinicaltrials.gov as #NCT01749540 and #NCT02268409.
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http://dx.doi.org/10.1182/blood-2018-10-879247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6440118PMC
March 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

Autologous stem cell transplantation for primary mediastinal B-cell lymphoma: long-term outcome and role of post-transplant radiotherapy. A report of the European Society for Blood and Marrow Transplantation.

Bone Marrow Transplant 2018 08 20;53(8):1001-1009. Epub 2018 Feb 20.

EBMT Lymphoma Working Party, Paris, France.

The purpose of this retrospective registry study was to investigate the outcome of autoSCT for primary mediastinal B-cell lymphoma (PMBCL) in the rituximab era, including the effects of eventual post-transplant radiotherapy (RT) consolidation. Patients with PMBCL aged between 18 and 70 years who were treated with a first autoSCT between 2000 and 2012 and registered with the EBMT were eligible. Eighty-six patients with confirmed PMBCL and the full data set required for this analysis were evaluable. Sixteen patients underwent autoSCT in remission after first-line therapy (CR/PR1), 44 patients were transplanted with chemosensitive relapsed or primary refractory disease (CR/PR >1), and 24 patients were chemorefractory at the time of autoSCT. With a median follow-up of 5 years, 3-year estimates of relapse incidence, progression-free survival, and overall survival were 6%, 94%, and 100% for CR/PR1; 31%, 64%, and 85% for CR/PR >1; and 52%, 39%, and 41% for REF, respectively. Whilst there was no significant benefit of post-transplant RT in the CR/PR >1 group, RT could completely prevent disease recurrence post d100 in the refractory group. In conclusion, autoSCT with or without consolidating RT is associated with excellent outcome in chemoimmunotherapy-sensitive PMBCL, whereas its benefits seem to be limited in chemoimmunotherapy-refractory disease.
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http://dx.doi.org/10.1038/s41409-017-0063-7DOI Listing
August 2018

Response to pomalidomide plus fixed low-dose dexamethasone in a case of secondary plasma cell leukaemia.

Leuk Res 2016 Jan 25;40:30-2. Epub 2015 Nov 25.

Haematology and BMT Unit-"Antonio Perrino" Hospital, 72100 Brindisi, Italy.

This is, to our knowledge, the first reported case of secondary Plasma Cell Leukemia that was successfully by pomalidomide plus fixed low-dose dexamethasone. Pomalidomide at a dosage of 4 mg orally on days 1-21 of repeated 28-day cycles associated with fixed low-dose dexamethasone (40 mg on days 1, 8, 15 and 22 of each 28-day cycle), outside of the clinical trials, was started as a final attempt. After the fourth course, the patient achieved an interesting response that included a significant reduction of circulating plasma cells from the peripheral blood, a very important decrease of the M-component, and normalization of haematological value. The toxicities were acceptable. The time to best response was 4 months.
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http://dx.doi.org/10.1016/j.leukres.2015.11.009DOI Listing
January 2016

The use of thrombopoietin-receptor agonists (TPO-RAs) in immune thrombocytopenia (ITP): a "real life" retrospective multicenter experience of the Rete Ematologica Pugliese (REP).

Ann Hematol 2016 Jan 24;95(2):239-44. Epub 2015 Nov 24.

Unit of Hematology with BMT, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.

Immune thrombocytopenia (ITP) is a disease which sees one-third of patients failing first and subsequent therapeutic approaches, including splenectomy. Thrombopoietin-receptor agonists (TPO-RAs) are recommended for adults who relapse after splenectomy or who have contraindications for splenectomy. In this multicenter study, a total of 124 patients were retrospectively evaluated: 55 (44.3 %) were treated by romiplostim and 69 (55.6 %) by eltrombopag. Mean age, number of young patients (<60 years), time from primary diagnosis of ITP to TPO-RA treatment, and previous lines of therapy were similar in both groups. The overall response rate was 80 % (44/55) for romiplostim and 94.2 % (65/69) for eltrombopag; the duration of response and the time to response were similar (p = NS). The response rate to both drugs in non-splenectomized patients was higher than that of splenectomized patients (p < 0.05). The mean duration of response was 30 months for romiplostim and 15 months for eltrombopag, due to later commercialization of eltrombopag. Failure was the most frequent cause of discontinuation. Thrombotic events were the most consistent adverse events and were recorded in 2 and 3 % of patients treated by romiplostim and eltrombopag, respectively. In conclusion, romiplostim and eltrombopag are effective in the majority of patients with chronic ITP who failed several lines of therapy; whether TPO-RAs could substitute splenectomy is under discussion and studies are warranted.
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http://dx.doi.org/10.1007/s00277-015-2556-zDOI Listing
January 2016

Azacitidine in the treatment of older patients affected by acute myeloid leukemia: A report by the Rete Ematologica Pugliese (REP).

Leuk Res 2015 Aug 20. Epub 2015 Aug 20.

Hematology and Bone Marrow Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy.

The optimal treatment of older patients (>65 years) with acute myeloid leukemia (AML) remains challenging in daily clinical practice; a choice has to be made between intensive chemotherapy and best supportive care. To guide physicians, several prognostic factors have been identified and risk scores developed. Recently, the DNA methyltransferase inhibitor azacitidine has become available for use in MDS and AML patients with up to 30% bone marrow blasts. However, limited data are available on the outcome of older unfit AML patients, regardless of their bone marrow blast count. We retrospectively analyzed the outcome of 90 newly diagnosed older unfit AML patients in 9 Institutions from the Apulia Region (REP). Responder patients (evaluation performed after 4 cycles of treatment even in cases of primary failure) showed a better overall survival than non responders (23 vs 6 months, p<.001). ECOG PS≥2 seems to be correlated with OS in multivariate analysis, while neither primary treatment failure (documented after 2 cycles) nor bone marrow blast count were correlated with a worse overall survival either at univariate (22 vs 29 months, p=.ns; 16 vs 19 months, p=.ns) or multivariate analysis. Overall, the results of our retrospective analysis seem to confirm the efficacy of AZA treatment for this unfit AML patients setting, in terms of both CR and OS, regardless of the bone marrow blasts count, while primary treatment failure should not lead to a discontinuation of treatment.
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http://dx.doi.org/10.1016/j.leukres.2015.08.005DOI Listing
August 2015

Paralytic ileus following "subcutaneous bortezomib" therapy: focus on the clinical emergency-report of two cases.

Clin Exp Med 2016 Feb 20;16(1):99-101. Epub 2015 Jan 20.

Haematology and BMT Unit, "Antonio Perrino" Hospital, SS 7 per Mesagne, 72100, Brindisi, Italy.

We retrospectively analyzed the medical history of 19 elderly myeloma patients treated with the "novel subcutaneous formulation of bortezomib." In our experience, two patients (10 %) discontinued treatment for paralytic ileus. The exact pathogenetic mechanisms of toxic megacolon and paralytic ileus due to "novel subcutaneous formulation of bortezomib" are unclear. Probably, it may be related to possible damage of the autonomic nerve fibers that control organ functions. Adequate prevention and management of the gastrointestinal (GI) toxicities with the use of fluid intake and prokinetic and laxative drugs (at least two types of agents in a suboptimal dose) especially in patients with risk factors for GI side effects (anti-myeloma novel agents, opioids or antiemetics, iron supplements, spinal and cord compression, immobility, history of constipation) can decrease the possibility of interruption of administration of drug and increase adherence to treatment. Clearly this complication must be borne in mind whenever a patient develops acute abdominal pain and distension.
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http://dx.doi.org/10.1007/s10238-015-0337-6DOI Listing
February 2016

Azacitidine in the front-line treatment of therapy-related myeloid neoplasms: a multicenter case series.

Anticancer Res 2015 Jan;35(1):461-6

Haematology Unit, IRCCS National Cancer Research Centre "Giovanni Paolo II", Bari, Italy.

Background/aim: A continued increase in the incidence of therapy-related myeloid neoplasms (t-MN) is expected due to the improvement of chemotherapeutic treatments for solid and haematological malignancies. The use of 5-azacytidine (AZA) is emerging in these patients. We, therefore, analyzed the outcome of patients with t-MN ineligible for intensive chemotherapy treated in the front-line with AZA.

Patients And Methods: We retrospectively collected clinical data from consecutive patients with t-MN treated in the front-line with AZA at five Haematology Centers. Response to therapy, overall survival (OS) and safety were considered.

Results: The overall response rate was of 35.7% with a median OS of 9.6 months. Patients who were heavily pre-treated for their primary malignancy (more than 3 lines of chemotherapy) presented a significant inferior OS (4.9 months). The principal reported toxicity was haematological with severe infections occurring in a minority of patients. Fatigue was the most common extra-haematological toxicity.

Conclusion: New aspects emerged on the management of t-MN. AZA may represent a reasonable choice for patients ineligible for intensive treatment, with the exception of heavily pre-treated patients who presented -anyway- a worse outcome.
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January 2015

Optimal time-points for minimal residual disease monitoring change on the basis of the method used in patients with acute myeloid leukemia who underwent allogeneic stem cell transplantation: a comparison between multiparameter flow cytometry and Wilms' tumor 1 expression.

Leuk Res 2015 Feb 29;39(2):138-43. Epub 2014 Nov 29.

Department of Hematology and Stem Cell Transplant Unit, IRCCS "Casa Sollievo della Sofferenza" Hospital, 71013 San Giovanni Rotondo, Italy.

Minimal residual disease (MRD) of 30 adult AML patients was monitored by multiparameter flow cytometry (MFC) and WT1 expression before and after allogeneic stem cell transplantation (allo-SCT). Diagnostic performance of pre-transplant MRD measured by MFC was higher than that obtained by WT1 expression. Comparable results were displayed at day +30 post-transplant, while better values by WT1 compared to MFC were found at day +90. Positive MRD by MFC predicted a shorter disease free survival (DFS) before and 1 month after transplant (p=0.006 and p=0.005), while only high WT1 levels at 1 month from the transplant significantly impacted on DFS (p=0.010). Our results support the idea that MRD monitoring by MFC should be suggested before and 30 days after the transplant, while WT1 expression should be preferred after this procedure. The assessment of MRD at day +30 from allo-SCT is recommended as post transplant check-point for the predictive role displayed, independently of the method used.
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http://dx.doi.org/10.1016/j.leukres.2014.11.011DOI Listing
February 2015

Bendamustine plus rituximab for relapsed or refractory diffuse large B cell lymphoma: a retrospective analysis.

Leuk Res 2014 Dec 22;38(12):1446-50. Epub 2014 Oct 22.

Hematology and Bone Marrow Transplantation Unit, Antonio Perrino Hospital, Brindisi, Italy.

For patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) who are not eligible for intensive chemotherapy because of comorbidities, advanced age, or relapse after heavy salvage regimens, treatment options are very limited and prognosis is poor. We retrospectively analyzed 29 patients with relapsed/refractory DLBCL treated with combination bendamustine plus rituximab (BR) between July 2010 and January 2014 to evaluate overall response rate (ORR), progression-free survival (PFS), duration of response (DOR) and treatment safety. Twenty-eight patients were available for this analysis. ORR was 50% (14 patients), with 39.3% CR (11 patients), and 10.7% PR (3 patients). SD was reported in 2 patients (7.2%) and PD in 12 patients (42.8%). At the median follow up of 8 months (range 1-37.4 months), the median PFS was 8 months for all patients (95% CI 5.5-26.6). The median DOR was 24.7 months (95% CI 3.2-24.7). Grade 3/4 toxicity observed included hematologic events: lymphopenia (42.8%), neutropenia (32.1%), anemia (17.2%), and thrombocytopenia (14.2%). BR can be considered to have a role in the treatment of patients with relapsed/refractory DLBCL with limited therapeutic options, in that it can induce long-term remission in some patients with an acceptable toxicity profile.
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http://dx.doi.org/10.1016/j.leukres.2014.10.001DOI Listing
December 2014

Small-Sized Clone of T Cells in Multiple Myeloma Patient after Auto-SCT: T-LGL Leukemia Type or Clonal T-Cell Aberration?

Case Rep Hematol 2013 21;2013:417353. Epub 2013 Apr 21.

Haematology Division and BMT Unit, Antonio Perrino Hospital, 72100 Brindisi, Italy.

Second cancers and particularly postransplant lymphoproliferative disorders (PTLDs) are extremely rare in patients undergoing autologous peripheral blood stem cell transplantation (auto-SCT). We report the case of clonally rearranged T-cell expansion which occurred after auto-SCT for Multiple Myeloma (MM). Does asymptomatic clonal T-cell large granular lymphocytic proliferation, in our experience, represent either a secondary cancer after auto-SCT or clonal T cell aberration or derive from expansion of coexisting undetected small-sized clone of T cells?
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http://dx.doi.org/10.1155/2013/417353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3652047PMC
May 2013

Clinical management of cardiovascular complications in patients with thalassaemia major: a large observational multicenter study.

Eur J Echocardiogr 2011 Mar 28;12(3):242-6. Epub 2011 Jan 28.

Cardiology, Galliera Hospital, Genoa, Italy.

Aims: To determine the clinical management of cardiovascular complications, and the extent of cardiac left ventricular (LV) involvement, in a large cohort of homogenously treated patients with thalassaemia major.

Methods And Results: Participants were ≥ 16 years of age and diagnosed with thalassaemia major requiring regular blood transfusions since the age of 2. Patient characteristics, clinical and echocardiography data for 524 patients were extracted from Webthal®, an Internet-shared database. Patients were considered to have evidence of cardiovascular disease if at least one cardiovascular drug was recorded in their file. The majority of patients (422 of 524; 80.5%) had not taken any cardiovascular drug. Among those who had angiotensin-converting enzyme-inhibitors were the most commonly used (81 patients) and these were used by significantly more males than females (P < 0.01). Patients in whom cardiovascular drugs were prescribed showed evidence of cardiac structural and/or functional abnormalities, inasmuch as fractional shortening and ejection fraction were significantly lower (31.3 vs. 35% and 54.4 vs. 60.6; both P < 0.001) and LV end-diastolic diameter index was significantly higher (32.9 vs. 31.8; P = 0.004). Interestingly, when compared with patients in whom cardiovascular drug therapy was not deemed necessary, transfusion period was longer in treated patients (26.2 vs. 24.5 years; P= 0.002).

Conclusion: Approximately 19% of regularly transfused and chelated thalassaemia major patients need cardiovascular drug therapy. This subgroup is characterized by a dilated and mildly hypokinetic left ventricle when compared with the majority of thalassaemia major patients, who do not need any cardioactive drug. These data underscore the importance of careful evaluation of cardiac functional status in patients with thalassaemia major. Moreover, this database may serve as a clinically useful reference grid for echocardiograph values in this patient population.
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http://dx.doi.org/10.1093/ejechocard/jeq190DOI Listing
March 2011

Myocardial iron overload assessed by magnetic resonance imaging (MRI)T2* in multi-transfused patients with thalassemia and acquired anemias.

Eur J Intern Med 2011 Feb 24;22(1):62-5. Epub 2010 Nov 24.

Unità Semplice di Ematologia, Ospedale Madonna delle Grazie, Matera, Italy.

Background: Cardiac complications secondary to iron overload remain a significant matter in patients with transfusion dependent anemias.

Patients And Methods: To evaluate cardiac siderosis, Magnetic resonance imaging T2* (MRI T2*) was performed in 3 cohorts of transfusion dependent patients: 99 with thalassemia major (TM), 20 with thalassemia intermedia (TI), and 10 with acquired anemias (AA). Serum ferritin was measured and all patients underwent echocardiographic evaluation.

Results: In TM patients cardiac T2* pathologic values (below 20 ms) were found in 37 patients. Serum ferritin was negatively associated with age (r=-0.32, p=0.001) and weakly with T2* values (r=-0.19, p=0.057). A positive correlation was found between T2* and LVEF (r=0.27, p=0.006). Out of 37 patients with T2*<20 ms, 18 (48%) had serum ferritin values<1000 ng/ml. In TI cohort, 3 patients had cardiac T2* pathologic values. In AA cohort, pathologic T2* values were found in 2 patients, who received 234 and 199 PRBC units, respectively, and were both on chelation therapy (in one patient ferritin value was 399 ng/ml). T2* values were negatively associated, but not significantly, with the number of PRBC transfused (r=-0.53, p=0.07).

Conclusion: In our experience, 37% of TM patients had a myocardial iron overload assessed by MRI T2*; this value is higher than in TI patients. Serum ferritin measurement was a poor predictor of myocardial siderosis. In patients with AA, more than 200 PRBC units transfused were required to induce cardiac hemosiderosis, in spite of chelation therapy and, in one patient, of normal ferritin values.
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http://dx.doi.org/10.1016/j.ejim.2010.10.005DOI Listing
February 2011

Retrospective case series of three patients with plasma cell leukemia treated with bortezomib-based regimens.

Clin Ther 2010 May;32(5):915-9

Clinical Division of Haematology and Bone Marrow Transplantation Unit, Antonio Perrino Hospital, Brindisi, Italy.

Background: Data from the literature have suggested that bortezomib is the only effective agent in the treatment of plasma cell leukemia (PCL), a type of plasma cell dyscrasia characterized by poor prognosis despite conventional chemotherapy including autologous and allogeneic transplantation.

Objective: This case series examined the antineoplastic activity of the bortezomib-based regimens in a small cohort of patients with PCL.

Case Summaries: We describe a retrospective review of the 3 cases of PCL diagnosed at Antonio Perrino Hospital, Brindisi, Italy, between July 2004 and October 2006 (2 women and 1 man, all white, ages 71, 64, and 42 years; 2 with primary PCL and 1 with secondary PCL). These patients were treated with bortezomib variously combined with other drugs outside of clinical trials. Patients 1 and 2 received bortezomib-based regimens (bortezomib 1.3 mg/m2 i.v. once daily on days 1, 4, 8, and 11; dexamethasone 20 mg i.v. once daily on days 1-4 and 8-11; oral cyclophosphamide 50 mg once daily on days 1-21, every 28 days) after 2 previous chemotherapeutic treatments. Patient 3 received a bortezomib-based regimen (bortezomib 1.3 mg/m2 i.v. once daily on days 1, 4, 8, and 11; doxorubicin 9 mg/m2 i.v. once daily on days 1-4; and dexamethasone 40 mg i.v. once daily on days 1-4, 8-11, and 15-18 during cycle 1 and days 1-4 during subsequent cycles) after one previous chemotherapeutic regimen. In all 3 patients, circulating plasma cells persisted. Patients 1 and 2 were not considered candidates for autologous peripheral blood stem cell transplantation (PBSCT) because of their nonresponse to the bortezomib-based regimens and severe deterioration of their clinical conditions (kidney and liver failure) due to disease progression. The overall survivals after administration of the bortezomib- based regimens were 4 months in patient 1 and 1 month in patient 2. After further treatment according to the modified protocol for patients with acute lymphatic leukemia (cyclophosphamide 800 mg/m2 i.v. on day 1 and 200 mg/m2 i.v. on days 2-5; vincristine 1.5 mg/m2 i.v. once daily on days 1, 8, and 15; doxorubicin 40 mg/m2 i.v. on day 1; methotrexate 1200 mg/m2/h i.v. + 240 mg/m2/h i.v. for 23 hours [modified CODOX-M protocol]) due to the unavailability of a human leukocyte antigen-identical donor, patient 3 received high-dose (200 mg/m2) melphalan with autologous PBSCT, obtaining partial remission lasting 9 months. The patient died 5 months later because of disease progression.

Conclusion: These 3 patients with primary or secondary PCL who received a bortezomib-based regimen as rescue medication did not respond to treatment.
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http://dx.doi.org/10.1016/j.clinthera.2010.05.008DOI Listing
May 2010

Pregnancy and beta-thalassemia: an Italian multicenter experience.

Haematologica 2010 Mar 10;95(3):376-81. Epub 2009 Nov 10.

Ospedale Regionale Microcitemie, ASL Cagliari, Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, Via Jenner s/n, 09121 Cagliari, Italy.

Background: Recent advances in the management of thalassemia have significantly improved life expectancy and quality of life of patients with this hemoglobinopathy, with a consequent increase in their reproductive potential and desire to have children.

Design And Methods: We describe the methods of conception and delivery, as well as the course and outcome of pregnancy including transfusions, iron overload and chelation in 46 women with thalassemia major (58 pregnancies) and in 11 women with thalassemia intermedia (17 pregnancies). Conception was achieved after gonadotrophin-induced ovulation in 33 of the women with thalassemia major and spontaneously in all of those with thalassemia intermedia.

Results: Among the women with thalassemia major, 91% of the pregnancies resulted in successful delivery of 45 singleton live-born neonates, five sets of twins and one set of triplets. No secondary complications of iron overload developed or worsened during pregnancy. When considering only the singleton pregnancies, the proportion of babies with intrauterine growth retardation did not differ from that reported in the general Italian population. The high prevalence of pre-term births (32.7%) was mostly related to multiple pregnancies and precautionary reasons. Pregnancy was safe in most women with thalassemia major or intermedia. However, women with thalassemia intermedia who had never previously been transfused or who had received only minimal transfusion therapy were at risk of severe alloimmune anemia if blood transfusions were required during pregnancy.

Conclusions: Provided that a multidisciplinary team is available, pregnancy is possible, safe and usually has a favorable outcome in patients with thalassemia. In women with hypogonadotropic hypogonadism, gonadal function is usually intact and fertility is usually retrievable.
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http://dx.doi.org/10.3324/haematol.2009.012393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2833066PMC
March 2010

What is the best salvage therapy for treatment of isolated CNS relapse in elderly patients with imatinib-responsive Ph(+) ALL?

Leuk Res 2007 Oct 25;31(10):1445-7. Epub 2007 Apr 25.

Clinical Division of Haematology and BMT Unit, "Antonio Perrino" Hospital, Brindisi, Italy.

We report the case of an elderly patient affected by Philadelphia positive Acute Lymphoblastic Leukaemia (Ph(+) ALL) who developed meningeal leukaemia during imatinib monotherapy, despite bone marrow molecular remission. Aggressive central nervous system (CNS)-directed therapy in combination with continued imatinib treatment might be, at the moment, the most effective salvage therapy for imatinib-responsive elderly patients with isolated CNS relapse. In view of the inefficacy of imatinib at preventing meningeal leukaemia for its poor penetration into the CNS, CNS prophylactic therapy should always be an integral part of any imatinib-based treatment strategy for Ph(+) ALL.
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http://dx.doi.org/10.1016/j.leukres.2007.03.018DOI Listing
October 2007