Publications by authors named "Mariagrazia Michieli"

35 Publications

Prognostic impact of early-versus-late responses to different induction regimens in patients with myeloma undergoing autologous hematopoietic cell transplantation: Results from the CALM study by the CMWP of the EBMT.

Eur J Haematol 2021 May 27;106(5):708-715. Epub 2021 Feb 27.

University Hospital of Lille, Inserm, CHU Lille, INSERM, Infinite, Lille, France.

Background: In autologous stem cell transplant (ASCT)-eligible myeloma patients, prolonged induction does not necessarily improve the depth of response.

Method: We analyzed 1222 ASCT patients who were classified based on (a) the interval between induction and stem cell collection, (b) the type of induction regimen: BID (Bortezomib, IMiDs, and Dexamethasone), Bortezomib-based, or CTD (Cyclophosphamide, Thalidomide, and Dexamethasone), and (c) the time to best response (Early ie, best response within 4 or 5 months, depending on the regimen vs Late; Good ie, VGPR or better vs Poor).

Results: The length of induction treatment required to achieve a Good response did not affect PFS (P = .65) or OS (P = .61) post-ASCT. The three types of regimen resulted in similar outcomes: median PFS 31, 27.7 and 30.8 months (P = .31), and median OS 81.7, 92.7, and 77.4 months, respectively (P = .83). On multivariate analysis, neither the type nor the duration of the induction regimen affected OS and PFS, except for Early Good Responders who had a better PFS compared to Early Poor Responders (HR = 1.21, P-value = .02). However, achieving a Good response at induction was associated with a better response (≥VGPR) post-transplant.

Conclusion: The kinetics of response did not affect outcomes.
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http://dx.doi.org/10.1111/ejh.13602DOI Listing
May 2021

Real-world experience with decitabine as a first-line treatment in 306 elderly acute myeloid leukaemia patients unfit for intensive chemotherapy.

Hematol Oncol 2019 Oct 20;37(4):447-455. Epub 2019 Aug 20.

UO Ematologia e Trapianto Midollo Osseo, IRCCS Istituto Scientifico Universitario San Raffaele, Milan, Italy.

Despite widespread use of decitabine to treat acute myeloid leukaemia (AML), data on its effectiveness and safety in the real-world setting are scanty. Thus, to analyze the performance of decitabine in clinical practice, we pooled together patient-level data of three multicentric observational studies conducted since 2013 throughout Italy, including 306 elderly AML patients (median age 75 years), unfit for intensive chemotherapy, treated with first-line decitabine therapy at the registered schedule of 20 mg/m /iv daily for 5 days every 4 weeks. Overall response rate (ORR), overall survival (OS) curves, and multivariate hazard ratios (HRs) of all-cause mortality were computed. Overall, 1940 cycles of therapy were administered (median, 5 cycles/patient). A total of 148 subjects were responders and, therefore, ORR was 48.4%. Seventy-one patients (23.2%) had complete remission, 32 (10.5%) had partial remission, and 45 (14.7%) had haematologic improvement. Median OS was 11.6 months for patients with favourable-intermediate cytogenetic risk and 7.9 months for those with adverse cytogenetic risk. Median relapse-free survival after CR was 10.9 months (95% confidence interval [CI]: 8.7-16.0). In multivariate analysis, mortality was higher in patients with adverse cytogenetic risk (HR=1.58; 95% CI: 1.13-2.21) and increased continuously with white blood cell (WBC) count (HR=1.12; 95% CI: 1.06-1.18). A total of 183 infectious adverse events occurred in 136 patients mainly (>90%) within the first five cycles of therapy. This pooled analysis of clinical care studies confirmed, outside of clinical trials, the effectiveness of decitabine as first-line therapy for AML in elderly patients unfit for intensive chemotherapy. An adverse cytogenetic profile and a higher WBC count at diagnosis were, in this real life setting, unfavourable predictors of survival.
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http://dx.doi.org/10.1002/hon.2663DOI Listing
October 2019

Autologous stem cell transplantation for HIV-associated lymphoma in the antiretroviral and rituximab era: a retrospective study by the EBMT Lymphoma Working Party.

Bone Marrow Transplant 2019 10 25;54(10):1625-1631. Epub 2019 Feb 25.

University Hospital of Heidelberg, Heidelberg, Germany.

The present study aimed at describing the outcome of patients with HIV-associated lymphomas following autologous hematopoietic stem cell transplantation (autoHCT) in the rituximab and combined antiretroviral therapy (cART) era. Eligible for this retrospective study were HIV-positive patients with lymphoma who received autoHCT between 2007 and 2013. A total of 118 patients were included with a median age of 45 years (range 24-66). Underlying diagnoses were diffuse large B cell lymphoma in 47%, Hodgkin lymphoma in 24%, Burkitt lymphoma in 18%, and plasmablastic lymphoma in 7% of patients. Disease status at autoHCT was complete remission in 44%, partial remission (PR) in 38%, and less than PR in 18% of the patients. With a median follow-up of 4 years, 3-year non-relapse mortality, incidence of relapse, progression-free survival (PFS) and overall survival (OS) were 10%, 27%, 63% and 66%, respectively. By multivariate analysis, disease status less than PR but not CD4+ cell count at the time of autoHCT was a significant predictor of unfavorable PFS and OS. In conclusion, in the era of cART and chemoimmunotherapy, the outcome of autoHCT for HIV-related lymphoma is driven by lymphoma-dependent risk factors rather than by characteristics of the HIV infection.
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http://dx.doi.org/10.1038/s41409-019-0480-xDOI Listing
October 2019

Low-dose radiotherapy in diffuse large B-cell lymphoma.

Hematol Oncol 2017 Dec 25;35(4):472-479. Epub 2016 Oct 25.

Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico (CRO), National Cancer Institute, Aviano, Italy.

Low-dose radiotherapy (LDRT) given in 2 × 2 Gy is a highly effective and safe treatment for palliation of indolent lymphomas. Otherwise, very little regarding the use of LDRT for diffuse large B-cell lymphoma (DLBCL) has been investigated. We designed a phase 2 trial of LDRT in patients with DLBCL with indication for palliative radiation. Low-dose radiotherapy was administered on symptomatic areas only. Clinical response was assessed 21 days after LDRT and defined as reduction >50% of maximum diameter of the radiated lesions. Quality of life was scored by the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. Tumor subtype (germinal center B-cell type versus activated B-cell type) and the presence of TP53 mutations in pathologic specimens of the target lesion were also evaluated. Twenty-three of twenty-five radiated patients were evaluable for response, and 2 died of disease before the visit at 21 days. The overall response rate was 70% (16 of 23 patients), with 7 complete responses and 9 partial responses (mean duration of response, 6 months; range, 1-39 months). Fifteen patients answered to the QLQ-C30 questionnaires, and an improved quality of life was documented in 9 cases. TP53 mutations were detected in 2 of 6 (33%) nonresponders and in none of the responders (P = .12). Germinal center B-cell type responded better than activated B-cell type (response rate was 83% and 29%, respectively, P = .01). These findings indicate that LDRT is effective for palliation in patients with DLBCL.
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http://dx.doi.org/10.1002/hon.2368DOI Listing
December 2017

"Twistin' the night away": Fertility preservation in young adult female cancer survivors.

Cancer 2017 02 11;123(4):707-708. Epub 2016 Oct 11.

Division of Medical Oncology A CRO Aviano National Cancer Institute, Aviano, Italy.

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http://dx.doi.org/10.1002/cncr.30394DOI Listing
February 2017

Salvage High-Dose Chemotherapy for Relapsed Pure Seminoma in the Last 10 Years: Results From the European Society for Blood and Marrow Transplantation Series 2002-2012.

Clin Genitourin Cancer 2017 02 27;15(1):163-167. Epub 2016 Jun 27.

Istituti Ospitalieri di Cremona, Cremona, Italy.

Background: The optimal management of advanced seminoma that relapses after chemotherapy remains unknown. We retrospectively analyzed outcomes with the use of high-dose chemotherapy (HDCT).

Patients And Methods: Eligibility included adult male patients with pure seminomatous histology and treatment with salvage HDCT. Data of patients who received HDCT from 13 European Society for Blood and Marrow Transplantation (EBMT) centers were used. Multivariable Cox analyses evaluated the association of prespecified factors (line of treatment, prior radiotherapy, and chemosensitivity according to standard definition), with progression-free (PFS) and overall survival (OS). The prognostic ability of the model was assessed through the concordance statistic.

Results: From December 2002 to December 2012, 46 cases were identified. Median age was 38 years (interquartile range, 35-46 years). HDCT was provided as second-line therapy (n = 14, 30.4%) and in third-line or beyond third-line therapy (n = 20, 43.5%; 12 had missing information). Sixteen patients (34.8%) received paraortic and/or iliac radiotherapy, and 10 (21.7%) had disease that was cisplatin refractory or absolutely refractory. Median follow-up was 22 months (interquartile range, 8-56). On multivariable Cox analysis, refractory disease was a significantly negative prognostic factor for both PFS (hazard ratio, 6.04; 95% confidence interval, 1.86-19.64) and OS (hazard ratio, 3.93; 95% confidence interval, 1.07-14.45), while prior radiotherapy trended to significance for both. The c index was 0.74 and 0.66 for PFS and OS, respectively. The small numbers and the lack of any comparison with conventional-dose chemotherapy are major study limitations.

Conclusion: Despite our small sample size, this retrospective analysis suggested that HDCT may represent a valuable therapeutic option for patients with a pure seminoma after standard-dose chemotherapy failure. Our observation requires validation through a prospective study.
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http://dx.doi.org/10.1016/j.clgc.2016.06.013DOI Listing
February 2017

Autologous stem cell transplantation in HIV-positive patients affected by relapsed/partially responding lymphoma: let it be.

Expert Rev Hematol 2016 07 16;9(7):617-9. Epub 2016 Jun 16.

b Division of Medical Oncology A , CRO National Cancer Institute , Aviano , Italy.

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http://dx.doi.org/10.1080/17474086.2016.1194751DOI Listing
July 2016

Postautologous stem cell transplantation long-term outcomes in 26 HIV-positive patients affected by relapsed/refractory lymphoma.

AIDS 2015 Nov;29(17):2303-8

aUnit of Cell Therapy and High Dose Chemotherapy bUnit of Epidemiology and Biostatistics cUnit of Stem Cells Collection and Processing dUnit of Microbiology-Immunology and Virology eScientific Directorate fDivision of Medical Oncology A, CRO Aviano National Cancer Institute, Aviano, Italy.

Objectives: To describe survival data, CD4 T-cell long-term dynamics and the correlation between dynamics and events occurrence in 26 HIV-positive patients with refractory lymphoma in complete response after autologous stem cell transplantation (ASCT).

Design: Retrospective single-centre study.

Methods: Lymphoma relapse, second cancers and opportunistic infections were considered after ASCT. Group A included patients experiencing events after ASCT and group B the remaining patients. Overall survival, progression-free survival and event-free survival probabilities were estimated by Kaplan-Meier method. The comparison of median CD4 T-cell count at cancer diagnosis with matched values was investigated by Wilcoxon signed-rank test and between group A and B by Mann-Whitney U test.

Results: With a median of 6-year follow-up, the overall survival, the progression-free survival and the event-free survival at 10 years were 91, 86 and 36%. Compared with CD4 T-cell count at cancer diagnosis a higher amount was maintained over time after ASCT. Two patients experienced a lymphoma relapse at 4.3 and 3.1 years; five patients had secondary malignancies and nine patients opportunistic infections at a median time of 2.2 and 0.4 years from ASCT. At 6 and 12 months after ASCT, a significant difference in CD4 T-cell count was found between group A and B.

Conclusion: ASCT has a dramatic impact on survival of HIV-positive patients with refractory lymphoma. We support surveillance of opportunistic infections early after ASCT and of second cancers or lymphoma relapses later from ASCT. Both opportunistic infections and second malignancies were successfully managed and the only long-term death occurred due to lymphoma relapse. ASCT seems to contribute to immune recovery.
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http://dx.doi.org/10.1097/QAD.0000000000000851DOI Listing
November 2015

The long and winding road in cancer survivorship care.

Cancer 2015 Oct 2;121(20):3748-9. Epub 2015 Jul 2.

Division of Medical Oncology A, Centro di Riferimento Oncologico (CRO) Aviano National Cancer Institute, Aviano, Italy.

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http://dx.doi.org/10.1002/cncr.29545DOI Listing
October 2015

γ-Herpesvirus load as surrogate marker of early death in HIV-1 lymphoma patients submitted to high dose chemotherapy and autologous peripheral blood stem cell transplantation.

PLoS One 2015 10;10(2):e0116887. Epub 2015 Feb 10.

Scientific Directorate; CRO National Cancer Institute, IRCCS, Aviano, Pordenone, Italy.

Autologous stem cell transplantation (ASCT) is a feasible procedure for human immunodeficiency virus-1 (HIV-1) lymphoma patients, whose underlying disease and intrinsic HIV-1- and ASCT-associated immunodeficiency might increase the risk for γ-herpesvirus load persistence and/or reactivation. We evaluated this hypothesis by investigating the levels of Epstein-Barr virus (EBV)- and Kaposi sarcoma-associated herpesvirus (KSHV)-DNA levels in the peripheral blood of 22 HIV-1-associated lymphoma patients during ASCT, highlighting their relationship with γ-herpesvirus lymphoma status, immunological parameters, and clinical events. EBV-DNA was detected in the pre-treatment plasma and peripheral blood mononuclear cells (PBMCs) of 12 (median 12,135 copies/mL) and 18 patients (median 417 copies/10(6) PBMCs), respectively; the values in the two compartments were correlated (r = 0.77, p = 0.0001). Only EBV-positive lymphomas showed detectable levels of plasma EBV-DNA. After debulking chemotherapy, plasma EBV-DNA was associated with lymphoma chemosensitivity (p = 0.03) and a significant higher mortality risk by multivariate Cox analysis adjusted for EBV-lymphoma status (HR, 10.46, 95% CI, 1.11-98.32, p = 0.04). After infusion, EBV-DNA was detectable in five EBV-positive lymphoma patients who died within six months. KSHV-DNA load was positive in only one patient, who died from primary effusion lymphoma. Fluctuations in levels of KSHV-DNA reflected the patient's therapy and evolution of his underlying lymphoma. Other γ-herpesvirus-associated malignancies, such as multicentric Castleman disease and Kaposi sarcoma, or end-organ complications after salvage treatment were not found. Overall, these findings suggest a prognostic and predictive value of EBV-DNA and KSHV-DNA, the monitoring of which could be a simple, complementary tool for the management of γ-herpesvirus-positive lymphomas in HIV-1 patients submitted to ASCT.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0116887PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323102PMC
December 2015

Autograft HIV-DNA load predicts HIV-1 peripheral reservoir after stem cell transplantation for AIDS-related lymphoma patients.

AIDS Res Hum Retroviruses 2015 Jan;31(1):150-9

1 Microbiology, Immunology, and Virology Unit, CRO National Cancer Institute , Aviano, Italy .

Autologous stem cell transplantation (ASCT) is a widely used procedure for AIDS-related lymphomas, and it represents an opportunity to evaluate strategies curing HIV-1 infection. The association of autograft HIV-DNA load with peripheral blood HIV-1 reservoir before ASCT and its contribution in predicting HIV-1 reservoir size and stability during combination antiretroviral therapy (cART) after transplantation are unknown. Aiming to obtain information suggesting new functional cure strategies by ASCT, we retrospectively evaluated HIV-DNA load in autograft and in peripheral blood before and after transplantation in 13 cART-treated HIV-1 relapse/refractoring lymphoma patients. Among them seven discontinued cART after autograft infusion. HIV-DNA was evaluated by a sensitive quantitative real-time polymerase chain reaction (PCR). After debulking chemotherapy/mobilization, the autograft HIV-1 reservoir was higher than and not associated with the peripheral HIV-1 reservoir at baseline [median 215 HIV-DNA copies/10(6) autograft mononuclear cells, range 13-706 vs. 82 HIV-DNA copies/10(6) peripheral blood mononuclear cells (PBMCs), range 13-479, p = 0.03]. After high dose chemotherapy and autograft infusion, HIV-DNA levels reached a plateau between month 6 and 12 of follow-up. No association was found between peripheral HIV-DNA levels at baseline and after infusion in both cART interrupting and not interrupting patients. Only in the last subgroup, a stable significant linear association between autograft and peripheral blood HIV-1 reservoir emerged from month 1 (R(2) = 0.84, p = 0.01) to month 12 follow-up (R(2) = 0.99, p = 0.0005). In summary, autograft HIV-1 reservoir size could be influenced by the mobilization phase and predicts posttransplant peripheral HIV-1 reservoir size in patients on continuous cART. These findings could promote new research on strategies reducing the HIV-1 reservoir by using the ASCT procedure.
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http://dx.doi.org/10.1089/aid.2014.0157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287109PMC
January 2015

Survivorship care plans: a change of perspective or a failure.

J Clin Oncol 2014 Dec 22;32(34):3904. Epub 2014 Sep 22.

Centro di Riferimento Oncologico Aviano National Cancer Institute, Aviano, Italy.

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http://dx.doi.org/10.1200/JCO.2014.58.0621DOI Listing
December 2014

Reply to long-term survivorship clinics led by primary care physicians within the cancer center may be a good option for coordinated survivorship care.

Cancer 2014 Dec 24;120(23):3753-4. Epub 2014 Jul 24.

Unit of Cell Therapy and High Dose Chemotherapy, Centro di Riferimento Oncologico (CRO) Aviano National Cancer Institute, Aviano, Italy.

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http://dx.doi.org/10.1002/cncr.28941DOI Listing
December 2014

Which tools may help physicians in female fertility prediction after autologous bone marrow transplantation for lymphoma? A pilot study.

J Chemother 2014 Oct 21;26(5):293-9. Epub 2014 Jan 21.

Objective(s): The report of our experience on fertility preservation and the validation of some tools useful to predict fertility in young females who underwent haematopoietic cell transplantation for their lymphoma.

Study Design: A retrospective study involving 17 consecutive women of child-bearing age affected by lymphoma and submitted to haematopoietic cell transplantation in our centre.

Results: We described a high rate of parenthood in our patient series: 5 out of 17 (29%) patients became pregnant and 1 out of 5 had two pregnancies. It is suggestive that only patients who received gonadotropin-releasing hormone (GnRH) analogues co-treatment conceaved. Antral follicles number or ovarian volume, ascertained through transvaginal ultrasound before starting treatment, more than anti-Mullerian hormone (AMH) value, are tools that may help physicians to better predict fertility in young females of child-bearing age affected by lymphoma who desire to get pregnant after cancer cares.

Conclusion(s): The high rate of maternity we recorded may lead to comfort the young women who hope to become pregnant after cancer cares because pregnancy is possible in a certain percentage of cases even after highly toxic treatments to the ovaries. A higher ovarian volume or a higher number of antral follicles, before treatment start, ensures a greater chance of successful pregnancies. AMH value in lymphoma survivors is not sufficient to guide physicians in fertility predictions.
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http://dx.doi.org/10.1179/1973947813Y.0000000162DOI Listing
October 2014

Cancer survivorship: Is there a role for cancer survivor clinics?

Cancer 2014 Jun 11;120(12):1908-9. Epub 2014 Mar 11.

Unit of Cell Therapy and High Dose Chemotherapy, Centro di Riferimento Oncologico (CRO) Aviano National Cancer Institute, Aviano, Italy.

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http://dx.doi.org/10.1002/cncr.28658DOI Listing
June 2014

Hematopoietic growth factors support in the elderly cancer patients treated with antiblastic chemotherapy.

Anticancer Agents Med Chem 2013 Nov;13(9):1438-43

Department of Medical Oncology, National Cancer Institute of Aviano, Via Franco Gallini 2, 33081 Aviano (PN), Italy.

The 60% of tumors affected patients >65years of age and the future previsions are considering an amount of 70% after 2030. Elderly Patients presents multiple comorbidity, polipharmacy, and disability. Geriatric assessment helps physicians to take the best therapeutic decisions. Clinical conditions influence efficacy and tolerability of chemotherapy. Prophylactic use of G-CSF after chemotherapy lowers the rate and length of severe neutropenia , and decreases the episodes of febrile neutropenia. Anemia is a hematologic condition associated with ageing , but is frequently associated to concomitant chronic disease. Stem cells display increasing resistance to erythropoietin in the elderly patients and this is connected with the onset of pro-inflammatory cytokines characteristic of this age . Anemia is a common adverse event in cancer patients receiving chemotherapy. Several of the symptoms associated with anemia, such as fatigue, syncope, palpitations and dyspnea, reduce patient activity and have a profound effect on the quality of life [QOL]. Considering the unfit or frail status of elderly patient the at home use of peg-filgrastim and weekly or three weekly erythropoietin administration could be preferred for this setting of patients that lack of specialized nursing care or facilities. Further studies, considering the several differences in health organizations in vary countries, could be held to state the real impact of the biosimilars in comparison to the long acting originators in the reduction of costs in this group of patients.
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http://dx.doi.org/10.2174/18715206113136660352DOI Listing
November 2013

Autologus stem cell transplatation as a care option in elderly patients. A review.

Anticancer Agents Med Chem 2013 Nov;13(9):1419-29

Division of Medical Oncology A, National Cancer Institute, Via Franco Gallini 2, 33081 Aviano (PN), Italy.

The ageing population and the increase in life expectancy have put new social and health questions into the public health agenda of western countries. Hematological cancer incidence peaks in older population as a logical consequence of a longer lifespan promoting prolonged exposure to carcinogens and accumulation of genetic alterations. Hematological cancer represents a major cause of mortality in this age group despite recent progress observed in the management of cancer in the general population. Autologous stem cell transplantation (ASCT) represents a therapeutic option in the treatment of a large proportion of lymphomas and multiple myeloma, but their role in the onco-geriatric setting remains an open question, due to the presence of chronic disease. Ageing is characterized by progressive decrements in physiologic reserves and abilities to compensate for physical and/or functional limitations, which increase the risk of developing morbidity and disability. These events explains the extreme diversity of ageing individuals in terms of clinical and functional status. As a consequence, life expectancy in the elderly is influenced not only by the neoplastic diseases itself but also by the various co-morbidities common to this age group. The management of elderly people with hematological diseases potentially curative, should therefore combine both geriatric and tumor assessments. Among the elderly patients identified as being candidates for AHSCT, after the mobilization of progenitor cells from the bone marrow into the peripheral blood, the aphaeresis procedure is the most common method for collecting an adequate number of stem cells. The proper selection of patients may greatly improve the results and the toxicity related to cancer treatment in the elderly. We recommend the adoption of some form of geriatric assessment in the evaluation of any patient who is 70 years and older, this review intends to offer an overview of the state of art in ASCT in elderly patients.
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http://dx.doi.org/10.2174/18715206113136660357DOI Listing
November 2013

Stem cell mobilization in HIV seropositive patients with lymphoma.

Haematologica 2013 Nov 23;98(11):1762-8. Epub 2013 Aug 23.

High-dose chemotherapy with autologous peripheral blood stem cell rescue has been reported as feasible and effective in HIV-associated lymphoma. Although a sufficient number of stem cells seems achievable in most patients, there are cases of stem cell harvest failure. The aim of this study was to describe the mobilization policies used in HIV-associated lymphoma, evaluate the failure rate and identify factors influencing mobilization results. We analyzed 155 patients who underwent attempted stem cell mobilization at 10 European centers from 2000-2012. One hundred and twenty patients had non-Hodgkin lymphoma and 35 Hodgkin lymphoma; 31% had complete remission, 57% chemosensitive disease, 10% refractory disease, 2% untested relapse. Patients were mobilized with chemotherapy + G-CSF (86%) or G-CSF alone (14%); 73% of patients collected >2 and 48% >5 × 10(6) CD34(+) cells/kg. Low CD4+ count and refractory disease were associated with mobilization failure. Low CD4(+) count, low platelet count and mobilization with G-CSF correlated with lower probability to achieve >5 × 10(6) CD34(+) cells/kg, whereas cyclophosphamide ≥ 3 g/m(2) + G-CSF predicted higher collections. Circulating CD34(+) cells and CD34/WBC ratio were strongly associated with collection result. HIV infection alone should not preclude an attempt to obtain stem cells in candidates for autologous transplant as the results are comparable to the HIV-negative population.
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http://dx.doi.org/10.3324/haematol.2013.089052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3815178PMC
November 2013

Efficacy and tolerability of repeated cycles of a once-weekly regimen of bortezomib in lupus.

Rheumatology (Oxford) 2014 Feb 20;53(2):381-2. Epub 2013 Aug 20.

Rheumatology Clinic, Department of Medical and Biological Sciences, University Hospital Santa Maria della Misericordia, Piazzale S. Maria della Misericordia 15, 33100 Udine, Italy.

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http://dx.doi.org/10.1093/rheumatology/ket284DOI Listing
February 2014

Nutrition in oncologic patients during antiblastic treatment.

Front Biosci (Landmark Ed) 2013 Jan 1;18:120-32. Epub 2013 Jan 1.

Department of Medical Oncology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Via Franco Gallini 2, 33081 Aviano (PN), Italy.

Cancer may induce weight loss and cachexia, and cancer treatment may contribute to nutritional impairment. Here, we review the literature on the mechanisms of cancer cachexia and the pharmacological interventions both in use in clinical practice and currently under development. Based on this analysis, several nutritional proposals for cancer patients are suggested and the importance of good nutritional status in candidates for hematopoietic stem cell transplantation is highlighted.
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http://dx.doi.org/10.2741/4091DOI Listing
January 2013

Stem cell transplantation for lymphoma patients with HIV infection.

Cell Transplant 2011 27;20(3):351-70. Epub 2010 Sep 27.

Cell Therapy and High Dose Chemotherapy Unit, Centro di Riferimento Oncologico, CRO IRCCS, Via F. Gallini 2, Aviano, PN, Italy.

The advent of Highly Active Antiretroviral Therapy (HAART) has radically changed incidence characteristics and prognosis of HIV-positive patients affected by lymphomas. At this time there is consensus in the literature that, in first line, HIV-positive patients should always be treated with curative intent preferentially following the same approach used in the HIV-negative counterpart. On the contrary, an approach of salvage therapy in HIV-positive lymphomas is still a matter of debate given that for a wide range of relapsed or resistant HIV-negative Hodgkin's disease (HD) and non-Hodgkin lymphoma (NHL) patients, autologous peripheral or allogeneic stem cell transplantation are among the established options. In the pre-HAART era, therapeutic options derived from pioneering experiences gave only anecdotal success, either when transplantation was used to cure lymphomas or to improve HIV infection itself. Concerns relating to the entity, quality, and kinetics of early and late immune reconstitutions and the possible worsening of underlying viroimmunological conditions were additional obstacles. Currently, around 100 relapsed or resistant HIV-positive lymphomas have been treated with an autologous peripheral stem cell transplantation (APSCT) in the HAART era. Published data compared favorably with any previous salvage attempt showing a percentage of complete remission ranging from 48% to 90%, and overall survival ranging from 36% to 85% at median follow-up approaching 3 years. However, experiences are still limited and have given somewhat confounding indications, especially concerning timing and patients' selection for APSCT and feasibility and outcome for allogeneic stem cell transplant. Moreover, little data exist on the kinetics of immunological reconstitution after APSCT or relevant to the outcome of HIV infection. The aim of this review is to discuss current knowledge of the role of allogeneic and autologous stem cell transplantation as a modality in the cure of HIV and hemopoietic cancer patients. Several topics dealing with practical aspects concerning the management of APSCT in HIV-positive patients, including patient selection, timing of transplant, conditioning regimen, and relapse or nonrelapse mortality, are discussed. Data relating to the effects of mobilization and transplantation on virological parameters and pre- and posttransplant immune reconstitution are reviewed. Finally, in this review, we examine several ethical and legal issues relative to banking infected or potentially infected peripheral blood stem cells and we describe our experience and strategies to protect positive and negative donors/recipients and the health of caretakers.
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http://dx.doi.org/10.3727/096368910X528076DOI Listing
August 2011

Immune recovery after autologous stem cell transplantation is not different for HIV-infected versus HIV-uninfected patients with relapsed or refractory lymphoma.

Clin Infect Dis 2010 Jun;50(12):1672-9

Division of Medical Oncology A, National Cancer Institute, Aviano, Italy.

Background: High-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) are feasible and effective salvage treatments for human immunodeficiency virus (HIV)-related relapse or refractory lymphoma. Among the main concerns with ASCT in HIV-infected persons is the additional immune depletion caused by treatment, which could amplify the preexisting immune deficit. The aims of our study were to assess the impact of conventional chemotherapy before salvage treatment was administered, in this population, and to evaluate immune reconstitution dynamics during ASCT.

Methods: All 33 HIV-infected and HIV-uninfected patients who underwent comparable ASCT protocols at the National Cancer Institute (Aviano, Italy) who underwent 1 month of follow-up after transplantation were included in a prospective immunological study. Demographic, clinical, and immunovirological data were obtained before administration of induction therapy, during transplantation, and at 24 months of follow-up.

Results: Before HDC, no significant differences were observed in CD4(+) cell subsets and signal joint T cell receptor excision circles (sjTRECs), although HIV-infected persons had inverted ratios of CD4(+) cells to CD8(+) cells because they had higher CD8(+) T cell counts, compared with HIV-uninfected persons. After ASCT, this inversion was also observed in HIV-uninfected patients up to 24 months. CD4(+) cell subsets had similar recoveries, with a temporary setback in HIV-infected persons 3 months after reinfusion, together with an increase in infections. sjTRECs demonstrated similar dynamics in both populations and serve as a useful predictive marker of recovery of CD4(+) cell subsets. No significant changes emerged in HIV DNA levels during the follow-up period, with values at 24 months significantly lower than those at baseline.

Conclusions: Our study demonstrated that ASCT in HIV-infected persons with lymphoma does not worsen the initial immune impairment and does not enhance viral replication or the peripheral HIV reservoir in the long term.
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http://dx.doi.org/10.1086/652866DOI Listing
June 2010

High-dose therapy and autologous peripheral blood stem cell transplantation as salvage treatment for AIDS-related lymphoma: long-term results of the Italian Cooperative Group on AIDS and Tumors (GICAT) study with analysis of prognostic factors.

Blood 2009 Aug 18;114(7):1306-13. Epub 2009 May 18.

Division of Hematology, Spedali Civili di Brescia, Brescia, Italy.

After the introduction of highly active antiretroviral therapy (HAART), intensive treatment, including high-dose therapy (HDT) and peripheral blood stem cell transplantation (PBSCT), has become feasible in HIV-positive patients with Hodgkin (HL) and non-Hodgkin (NHL) lymphoma. Herein, we report the long-term results, on an intention-to-treat basis, of a prospective study on HDT and PBSCT in 50 HIV-positive HAART-responding patients with refractory/relapsed lymphoma. After debulking therapy, 2 patients had early toxic deaths, 10 had chemoresistant disease, 6 failed stem cell mobilization, 1 refused collection, and 4 progressed soon after PBSC harvest. Twenty-seven actually received transplant. Twenty-one patients are alive and disease-free after a median follow-up of 44 months (OS, 74.6%; PFS, 75.9%). Only lymphoma response significantly affected OS after transplantation. In multivariate analyses both lymphoma stage and low CD4 count negatively influenced the possibility to receive transplant. Median OS of all 50 eligible patients was 33 months (OS, 49.8%; PFS, 48.9%). Low CD4 count, marrow involvement, and poor performance status independently affected survival. PBSCT is a highly effective salvage treatment for chemosensitive AIDS-related lymphoma. It seems rational to explore its use earlier during the course of lymphoma to increase the proportion of patients who can actually receive transplant.
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http://dx.doi.org/10.1182/blood-2009-02-202762DOI Listing
August 2009

Human immunodeficiency virus-associated precursor T-lymphoblastic leukemia/lymphoblastic lymphoma: report of a case and review of the literature.

Hum Pathol 2009 Jul 7;40(7):1045-9. Epub 2009 May 7.

Servizio di Onco-Ematologia Clinico-Sperimentale, Centro di Riferimento Oncologico, Istituto Nazionale Tumori, IRCCS, 33081 Aviano, Italy.

We describe a case of human immunodeficiency virus-associated T-lymphoblastic leukemia/lymphoblastic lymphoma in a 43-year-old Italian man with a history of human immunodeficiency virus infection lasting 9 years. Immunoperoxidase stains showed that neoplastic cells were positive for CD3, TdT, CD45, CD10, CD1a, CD2, CD7, CD5, and CD43 (focal). The proliferation rate was approximately 70%, assessed by Ki-67/MIB-1 staining. Flow cytometry of the marrow aspirate revealed an intermediate/cortical T-lymphoblastic phenotype: negative for surface CD3 and positive for cytoplasmic CD3, CD1a, TdT, CD2, CD7, CD5, and CD8, with partial coexpression of dimCD4. Analysis of T-cell receptor gamma polymerase chain reaction products showed clonality. T-lymphoblastic leukemia/lymphoblastic lymphoma is a very rare occurrence in the clinical setting of human immunodeficiency virus infection. It is not listed in the World Health Organization classification of lymphomas associated with human immunodeficiency virus infection. Only 4 cases of human immunodeficiency virus-associated T-lymphoblastic leukemia/lymphoblastic lymphoma are reported in the current medical literature.
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http://dx.doi.org/10.1016/j.humpath.2008.12.021DOI Listing
July 2009

Autologous stem-cell transplantation in patients with HIV-related lymphoma.

J Clin Oncol 2009 May 30;27(13):2192-8. Epub 2009 Mar 30.

Hospital General Universitario [corrected] Gregorio Marañón, Madrid, Spain.

Purpose: Peripheral-blood autologous stem-cell transplantation (ASCT) in patients with HIV-related lymphoma (HIV-Ly) has been reported as a safe and useful procedure. Herein we report the European Group for Blood and Marrow Transplantation experience on patients with HIV-Ly undergoing ASCT.

Patients And Methods: This was a retrospective, multicentric, registry-based analysis.

Results: Since 1999, 68 patients from 20 institutions (median age, 41 years; range, 29 to 62 years) were included, diagnosed with non-Hodgkin's lymphoma (NHL; n = 50) or Hodgkin's lymphoma (n = 18). At the time of ASCT, 16 patients were in first complete remission (CR1); 44 patients were in CR more than 1, partial remission, or chemotherapy-sensitive relapse (chemo-S); and eight patients had chemotherapy-resistant disease. The median number of CD34(+) cells infused was 4.5 x 10(6)/kg (range, 1.6 to 21.2 x 10(6)/kg). Median time to neutrophil and platelet engraftment were 11 days (range, 8 to 36 days) and 14 days (range, 6 to 455 days), respectively, with a cumulative incidence (CI) at 1 year of 95.6% and 87%, respectively. CI of nonrelapse mortality (NRM) was 7.5% at 12 months after ASCT, mainly because of bacterial infections. CI of relapse was 30.4% at 24 months, statistically related with not being in CR at ASCT (relative risk [RR] = 3.6), NHL histology other than diffuse large B-cell lymphoma (RR = 3.4), and use of more than two previous treatment lines (RR = 3). At a median follow-up of 32 months (range, 2 to 81 months), progression-free survival (PFS) was 56%. Patients not in CR or with refractory disease at ASCT had poorer PFS (RR = 2.4 and 4.8, respectively).

Conclusion: Similarly to HIV-negative patients with lymphoma, ASCT is a useful treatment for patients with HIV-Ly and is associated with low NRM, mainly when performed in early stages and chemo-S disease.
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http://dx.doi.org/10.1200/JCO.2008.18.2683DOI Listing
May 2009

Comparable survival between HIV+ and HIV- non-Hodgkin and Hodgkin lymphoma patients undergoing autologous peripheral blood stem cell transplantation.

Blood 2009 Jun 23;113(23):6011-4. Epub 2009 Mar 23.

Hematology Department, Hospital General Universitario Gregorio Marañon, Madrid, Spain.

Autologous stem cell transplantation (ASCT) has been successfully used in HIV-related lymphoma (HIV-Ly) patients on highly active antiretroviral therapy. We report the first comparative analysis between HIV-Ly and a matched cohort of HIV(-) lymphoma patients. This retrospective European Group for Blood and Marrow Transplantation study included 53 patients (66% non-Hodgkin and 34% Hodgkin lymphoma) within each cohort. Both groups were comparable except for the higher proportion of males, mixed-cellularity Hodgkin lymphoma and patients receiving granulocyte colony-stimulating factor before engraftment and a smaller proportion receiving total body irradiation-based conditioning within the HIV-Ly cohort. Incidence of relapse, overall survival, and progression-free survival were similar in both cohorts. A higher nonrelapse mortality within the first year after ASCT was observed in the HIV-Ly group (8% vs 2%), predominantly because of early bacterial infections, although this was not statistically significant and did not influence survival. Thus, within the highly active antiretroviral therapy era, HIV patients should be considered for ASCT according to the same criteria adopted for HIV(-) lymphoma patients.
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http://dx.doi.org/10.1182/blood-2008-12-195388DOI Listing
June 2009

Ifosfamide, gemcitabine, and vinorelbine: a new induction regimen for refractory and relapsed Hodgkin's lymphoma.

Haematologica 2007 Jan;92(1):35-41

Department of Medical Oncology and Hematology, Istituto Clinico Humanitas, via Manzoni 56, 20089 Rozzano, Milan, Italy.

Background And Objectives: Response to pre-transplant salvage chemotherapy remains the most important prognostic factor for outcome in refractory or relapsed Hodgkin's lymphoma. Results of a new induction regimen are reported in terms of response rates, toxicity, and stem cell mobilization.

Design And Methods: Ninety-one patients with refractory or relapsed Hodgkin's lymphoma were treated prospectively with a salvage regimen consisting of ifosfamide 2000 mg/m2 on days 1 to 4, gemcitabine 800 mg/m2 on days 1 and 4, vinorelbine 20 mg/m2 on day 1, and prednisolone 100 mg on days 1 to 4 (IGEV).

Results: Forty-nine patients (53.8%) achieved a complete remission and 25 (27.5%) a partial response for an overall response rate of 81.3%. In the multivariate analysis response to the last chemotherapy (p<0.0001) and involvement of > or =3 sites (p<0.049) were the most important prognostic factors for response. Adequate CD34+ cell collection was achieved in 78 out of 79 (98.7%) mobilized patients. So far, no treatment-related death has been documented. Thirteen (4.2%) and 27 (8.6%) out of 313 evaluated cycles had to be delayed or reduced, respectively, mainly because of neutropenia and thrombocytopenia. No grade 4 non-hematologic toxicity was observed, except for one episode of mucositis.

Interpretation And Conclusions: The high response rate, in particular the complete remission rate, the low toxicity profile, and the very high mobilizing potential of the IGEV regimen strongly suggest that patients with relapsed/refractory Hodgkin's lymphoma may benefit from the use of this salvage induction regimen.
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http://dx.doi.org/10.3324/haematol.10661DOI Listing
January 2007

Rituximab plus infusional cyclophosphamide, doxorubicin, and etoposide in HIV-associated non-Hodgkin lymphoma: pooled results from 3 phase 2 trials.

Blood 2005 Mar 18;105(5):1891-7. Epub 2004 Nov 18.

Division of Medical Oncology A, National Cancer Institute, Via Pedemontana Occidentale 12, 33081, Aviano (PN) Italy.

Evidence suggests that infusional therapy is a more effective means for administering cytotoxic therapy than intravenous bolus therapy for lymphoma and offers greater potential for therapeutic synergy with rituximab, which has a long half-life. We pooled the results of 3 prospective phase 2 trials evaluating rituximab in combination with 96-hour infusion of cyclophosphamide (187.5-200 mg/m2 per day), doxorubicin (12.5 mg/m2 per day), and etoposide (60 mg/m2 per day) (R-CDE) plus granulocyte-colony-stimulating factor (G-CSF) in 74 patients with HIV-associated, B-cell non-Hodgkin lymphoma, of whom 56 (76%) patients received concurrent highly active antiretroviral therapy (HAART). The complete remission (CR) rate was 70% (95% confidence interval [CI], 59%-81%), and the estimated 2-year failure-free survival and overall survival rates were 59% (95% CI, 47%-71%) and 64% (95% CI, 52%-76%), respectively. Ten (14%) patients had opportunistic infections during or within 3 months of the end of R-CDE, and 17 (23%) patients developed nonopportunistic infections after that time. Six (8%) patients died because of infection; 2 (3%) of those infections were bacterial sepsis during R-CDE, and 4 (5%) were opportunistic infections that occurred between 2 and 8 months after the completion of R-CDE. R-CDE produced a 70% CR rate and a 59% 2-year failure-free survival rate in patients with HIV-associated lymphoma. Consistent with other reports, adding rituximab to cytotoxic therapy in this population may increase the risk for life-threatening infection. Further studies evaluating rituximab in combination with infusional chemotherapy are warranted, but caution is advised.
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http://dx.doi.org/10.1182/blood-2004-08-3300DOI Listing
March 2005

Antibody binding capacity for evaluation of MDR-related proteins in acute promyelocytic leukemia: Onset versus relapse expression.

Cytometry B Clin Cytom 2004 May;59(1):40-5

Department of Medical and Morphological Research, Division of Hematology, University Hospital, Udine, Italy.

Background: Multidrug resistance (MDR) remains a major obstacle for successful treatment in cancer, in particular in acute leukemia. In acute promyelocytic leukemia (APL), the high sensitivity to anthracyclines appears to be attributable to the low frequency of MDR proteins overexpression at onset even if 30% of patients still relapse and become resistant to therapy. In attempt to explain different blast cell sensitivity, we studied the expression of PGP, MRP1, MRP2, and LRP in 45 cases of APL, comparing onset of disease with relapse.

Methods: PGP, LRP, and MRP on bone marrow or peripheral blood blast cells were evaluated by flow cytometry using the MRK-16, LRP-56, MRP-m6, and MRP2 antibodies and results expressed by the mean fluorescence index (MFI). The antibody binding capacity (ABC) for each MDR protein was also calculated.

Results: At diagnosis, only 2 of 45 patients overexpressed PGP and 1 overexpressed LRP. PGP and LRP overexpressing cases significantly grew up during disease progression and at second relapse mean PGP MFI and mean LRP MFI were significantly higher than at onset (P = 0.001 and P = 0.008, respectively). By analyzing ABC, the same trend was more evident because a significant increment of PGP and LRP was observed at second (P = 0.002 and P = 0.002, respectively), but even at first relapse (P = 0.018 and P = 0.002, respectively). No changes were demonstrated in MRP1 and MRP2 expression in any phase of disease considered.

Conclusions: Our data confirm the low expression at diagnosis of proteins related to development of drug resistance in APL. The evidence of a relative easy induction of PGP and LRP, but not of MRP, can be useful in choosing drugs to employ for consolidation or rescue therapy.
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http://dx.doi.org/10.1002/cyto.b.20006DOI Listing
May 2004